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European Resuscitation Council and European Society of Intensive Care Medicine Guidelines for Post-resuscitation Care 2015: Section 5 of the European Resuscitation Council Guidelines for Resuscitation 2015

Resuscitation, October 2015, Pages 202 - 222

Summary of changes since 2010 guidelines

In 2010, post-resuscitation care was incorporated into the Advanced Life Support section of the European Resuscitation Council (ERC) Guidelines. 1 The ERC and the European Society of Intensive Care Medicine (ESICM) have collaborated to produce these post-resuscitation care guidelines, which recognise the importance of high-quality post-resuscitation care as a vital link in the Chain of Survival. 2 These post-resuscitation care guidelines are being co-published in Resuscitation and Intensive Care Medicine.

The most important changes in post-resuscitation care since 2010 include:

  • There is a greater emphasis on the need for urgent coronary catheterisation and percutaneous coronary intervention (PCI) following out-of-hospital cardiac arrest of likely cardiac cause.
  • Targeted temperature management remains important but there is now an option to target a temperature of 36 °C instead of the previously recommended 32–34 °C.
  • Prognostication is now undertaken using a multimodal strategy and there is emphasis on allowing sufficient time for neurological recovery and to enable sedatives to be cleared.
  • A novel section has been added which addresses rehabilitation after survival from a cardiac arrest. Recommendations include the systematic organisation of follow-up care, which should include screening for potential cognitive and emotional impairments and provision of information.

The international consensus on cardiopulmonary resuscitation science and the guidelines process

The International Liaison Committee on Resuscitation (ILCOR, ) includes representatives from the American Heart Association (AHA), the European Resuscitation Council (ERC), the Heart and Stroke Foundation of Canada (HSFC), the Australian and New Zealand Committee on Resuscitation (ANZCOR), the Resuscitation Council of Southern Africa (RCSA), the Inter-American Heart Foundation (IAHF), and the Resuscitation Council of Asia (RCA). Since 2000, researchers from the ILCOR member councils have evaluated resuscitation science in 5-yearly cycles. The most recent International Consensus Conference was held in Dallas in February 2015 and the published conclusions and recommendations from this process form the basis of the ERC Guidelines 2015 and for these ERC-ESICM post-resuscitation care guidelines. During the three years leading up to this conference, 250 evidence reviewers from 39 countries reviewed thousands of relevant, peer-reviewed publications to address 169 specific resuscitation questions, each in the standard PICO (Population, Intervention, Comparison, Outcome) format. To assess the quality of the evidence and the strength of the recommendations, ILCOR adopted the GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. Each PICO question was reviewed by at least two evidence reviewers who drafted a science statement based on their interpretation of all relevant data on the specific topic and the relevant ILCOR task force added consensus draft treatment recommendations. Final wording of science statements and treatment recommendations was completed after further review by ILCOR member organisations and by the editorial board, and published in Resuscitation and Circulation as the 2015 Consensus on Science and Treatment Recommendations (CoSTR). These ERC-ESICM guidelines on post-resuscitation care are based on the 2015 CoSTR document and represent consensus among the writing group, which included representatives of the ERC and the ESICM.


Successful return of spontaneous circulation (ROSC) is the first step towards the goal of complete recovery from cardiac arrest. The complex pathophysiological processes that occur following whole body ischaemia during cardiac arrest and the subsequent reperfusion response during CPR and following successful resuscitation have been termed the post-cardiac arrest syndrome. 3 Depending on the cause of the arrest, and the severity of the post-cardiac arrest syndrome, many patients will require multiple organ support and the treatment they receive during this post-resuscitation period influences significantly the overall outcome and particularly the quality of neurological recovery.4, 5, 6, 7, 8, 9, 10, and 11 The post-resuscitation phase starts at the location where ROSC is achieved but, once stabilised, the patient is transferred to the most appropriate high-care area (e.g., emergency room, cardiac catheterisation laboratory or intensive care unit (ICU)) for continued diagnosis, monitoring and treatment. The post-resuscitation care algorithm ( Fig. 5.1 ) outlines some of the key interventions required to optimise outcome for these patients.


Fig. 5.1 Post-resuscitation care algorithm. SBP: systolic blood pressure; PCI: percutaneous coronary intervention; CTPA: computed tomography pulmonary angiogram; ICU: intensive care unit; MAP: mean arterial pressure; ScvO2: central venous oxygenation; CO/CI: cardiac output/cardiac index; EEG: electroencephalography; ICD: implanted cardioverter defibrillator.

Some patients do awake rapidly following cardiac arrest – in some reports it is as high as 15–46% of the out-of hospital cardiac arrest patients admitted to hospital.12, 13, and 14 Response times, rates of bystander CPR, times to defibrillation and the duration of CPR impact on these numbers. 14 Although we have no data, it is reasonable to recommend that if there is any doubt about the patient's neurological function, the patient's trachea should be intubated and treatment to optimise haemodynamic, respiratory and metabolic variables, together with targeted temperature management started, following the local standardised treatment plan.

Of those comatose patients admitted to ICUs after cardiac arrest, as many as 40–50% survive to be discharged from hospital depending on the cause of arrest, system and quality of care.7, 10, 13, 14, 15, 16, 17, 18, 19, and 20 Of the patients who survive to hospital discharge, the vast majority have a good neurological outcome although many with subtle cognitive impairment.21, 22, 23, and 24

Post-cardiac arrest syndrome

The post-cardiac arrest syndrome comprises post-cardiac arrest brain injury, post-cardiac arrest myocardial dysfunction, the systemic ischaemia/reperfusion response, and the persistent precipitating pathology.3, 25, and 26 The severity of this syndrome will vary with the duration and cause of cardiac arrest. It may not occur at all if the cardiac arrest is brief. Post-cardiac arrest brain injury manifests as coma, seizures, myoclonus, varying degrees of neurocognitive dysfunction and brain death. Among patients surviving to ICU admission but subsequently dying in-hospital, brain injury is the cause of death in approximately two thirds after out-of hospital cardiac arrest and approximately 25% after in-hospital cardiac arrest.27, 28, 29, and 30 Cardiovascular failure accounts for most deaths in the first three days, while brain injury accounts for most of the later deaths.27, 30, and 31 Withdrawal of life sustaining therapy (WLST) is the most frequent cause of death (approximately 50%) in patients with a prognosticated bad outcome,14 and 30 emphasising the importance of the prognostication plan (see below). Post-cardiac arrest brain injury may be exacerbated by microcirculatory failure, impaired autoregulation, hypotension, hypercarbia, hypoxaemia, hyperoxaemia, pyrexia, hypoglycaemia, hyperglycaemia and seizures. Significant myocardial dysfunction is common after cardiac arrest but typically starts to recover by 2–3 days, although full recovery may take significantly longer.32, 33, and 34 The whole body ischaemia/reperfusion of cardiac arrest activates immune and coagulation pathways contributing to multiple organ failure and increasing the risk of infection.35, 36, 37, 38, 39, 40, and 41 Thus, the post-cardiac arrest syndrome has many features in common with sepsis, including intravascular volume depletion, vasodilation, endothelial injury and abnormalities of the microcirculation.42, 43, 44, 45, 46, 47, and 48

Airway and breathing

Control of oxygenation

Patients who have had a brief period of cardiac arrest responding immediately to appropriate treatment may achieve an immediate return of normal cerebral function. These patients do not require tracheal intubation and ventilation but should be given with oxygen via a facemask if their arterial blood oxygen saturation is less than 94%. Hypoxaemia and hypercarbia both increase the likelihood of a further cardiac arrest and may contribute to secondary brain injury. Several animal studies indicate that hyperoxaemia early after ROSC causes oxidative stress and harms post-ischaemic neurones.49, 50, 51, 52, and 53 One animal study showed that adjusting the fractional inspired concentration (FiO2) to produce an arterial oxygen saturation of 94–96% in the first hour after ROSC (controlled reoxygenation) achieved better neurological outcomes than achieved with the delivery of 100% oxygen. 54 One clinical registry study that included more than 6000 patients supports the animal data and shows post-resuscitation hyperoxaemia in the first 24 h is associated with worse outcome, compared with both normoxaemia and hypoxaemia. 55 A further analysis by the same group showed that the association between hyperoxia and outcome was dose-dependent and that there was not a single threshold for harm. 56 An observational study that included only those patients treated with mild induced hypothermia also showed an association between hyperoxia and poor outcome. 57 In contrast, an observational study of over 12,000 post-cardiac arrest patients showed that after adjustment for the inspired oxygenation concentration and other relevant covariates (including sickness severity), hyperoxia was no longer associated with mortality. 58 A meta-analysis of 14 observational studies showed significant heterogeneity across studies. 59

The animal studies showing a relationship between hyperoxia and worse neurological outcome after cardiac arrest have generally evaluated the effect of hyperoxia in the first hour after ROSC. There are significant practical challenges with the titration of inspired oxygen concentration immediately after ROSC, particularly in the out-of hospital setting. The only prospective clinical study to compare oxygen titrated to a target range (in this case 90–94% oxygen saturation) versus giving 100% oxygen after out of hospital cardiac arrest was stopped after enrolling just 19 patients because it proved very difficult to obtain reliable arterial blood oxygen saturation values using pulse oximetry. 60 A recent study of air versus supplemental oxygen in ST-elevation myocardial infarction showed that supplemental oxygen therapy increased myocardial injury, recurrent myocardial infarction and major cardiac arrhythmia and was associated with larger infarct size at 6 months. 61

Given the evidence of harm after myocardial infarction and the possibility of increased neurological injury after cardiac arrest, as soon as arterial blood oxygen saturation can be monitored reliably (by blood gas analysis and/or pulse oximetry), titrate the inspired oxygen concentration to maintain the arterial blood oxygen saturation in the range of 94–98%. Avoid hypoxaemia, which is also harmful – ensure reliable measurement of arterial oxygen saturation before reducing the inspired oxygen concentration.

Control of ventilation

Consider tracheal intubation, sedation and controlled ventilation in any patient with obtunded cerebral function. Ensure the tracheal tube is positioned correctly, well above the carina. Hypocarbia causes cerebral vasoconstriction and a decreased cerebral blood flow. 62 After cardiac arrest, hypocapnia induced by hyperventilation causes cerebral ischaemia.63, 64, 65, 66, and 67 Observational studies using cardiac arrest registries document an association between hypocapnia and poor neurological outcome.68 and 69 Two observation studies have documented an association with mild hypercapnia and better neurological outcome among post-cardiac arrest patients in the ICU.69 and 70 Until prospective data are available, it is reasonable to adjust ventilation to achieve normocarbia and to monitor this using the end-tidal CO2 and arterial blood gas values. Lowering the body temperature decreases the metabolism and may increase the risk of hypocapnia during the temperature intervention. 71

Although protective lung ventilation strategies have not been studied specifically in post-cardiac arrest patients, given that these patients develop a marked inflammatory response, it seems rational to apply protective lung ventilation: tidal volume 6–8 ml kg−1 ideal body weight and positive end expiratory pressure 4–8 cm H2O.48 and 72

Insert a gastric tube to decompress the stomach; gastric distension caused by mouth-to-mouth or bag-mask ventilation will splint the diaphragm and impair ventilation. Give adequate doses of sedative, which will reduce oxygen consumption. A sedation protocol is highly recommended. Bolus doses of a neuromuscular blocking drug may be required, particularly if using targeted temperature management (TTM) (see below). Limited evidence shows that short-term infusion (≤48 h) of short-acting neuromuscular blocking drugs given to reduce patient-ventilator dysynchrony and risk of barotrauma in ARDS patients is not associated with an increased risk of ICU-acquired weakness and may improve outcome in these patients. 73 There are some data suggesting that continuous neuromuscular blockade is associated with decreased mortality in post-cardiac arrest patients 74 ; however, infusions of neuromuscular blocking drugs interfere with clinical examination and may mask seizures. Continuous electroencephalography (EEG) is recommended to detect seizures in these patients, especially when neuromuscular blockade is used. 75 Obtain a chest radiograph to check the position of the tracheal tube, gastric tube and central venous lines, assess for pulmonary oedema, and detect complications from CPR such as a pneumothorax associated with rib fractures.76 and 77


Coronary reperfusion

Acute coronary syndrome (ACS) is a frequent cause of out-of-hospital cardiac arrest (OHCA): in a recent meta-analysis, the prevalence of an acute coronary artery lesion ranged from 59% to 71% in OHCA patients without an obvious non-cardiac aetiology. 78 Since the publication of a pioneering study in 1997, 79 many observational studies have shown that emergent cardiac catheterisation laboratory evaluation, including early percutaneous coronary intervention (PCI), is feasible in patients with ROSC after cardiac arrest.80 and 81 The invasive management (i.e., early coronary angiography followed by immediate PCI if deemed necessary) of these patients, particularly those having prolonged resuscitation and nonspecific ECG changes, has been controversial because of the lack of specific evidence and significant implications on use of resources (including transfer of patients to PCI centres).

Percutaneous coronary intervention following ROSC with ST-elevation

In patients with ST segment elevation (STE) or left bundle branch block (LBBB) on the post-ROSC electrocardiogram (ECG) more than 80% will have an acute coronary lesion. 82 There are no randomised studies but given that many observational studies reported increased survival and neurologically favourable outcome, it is highly probable that early invasive management is beneficial in STE patients. 83 Based on available data, emergent cardiac catheterisation laboratory evaluation (and immediate PCI if required) should be performed in adult patients with ROSC after OHCA of suspected cardiac origin with STE on the ECG. This recommendation is based on low quality of evidence from selected populations. Observational studies also indicate that optimal outcomes after OHCA are achieved with a combination of TTM and PCI, which can be included in a standardised post-cardiac arrest protocol as part of an overall strategy to improve neurologically intact survival.81, 84, and 85

Percutaneous coronary intervention following ROSC without ST-elevation

In contrast to the usual presentation of ACS in non-cardiac arrest patients, the standard tools to assess coronary ischaemia in cardiac arrest patients are less accurate. The sensitivity and specificity of the usual clinical data, ECG and biomarkers to predict an acute coronary artery occlusion as the cause of OHCA are unclear.86, 87, 88, and 89 Several large observational series showed that absence of STE may also be associated with ACS in patients with ROSC following OHCA.90, 91, 92, and 93 In these non-STE patients, there are conflicting data from observational studies on the potential benefit of emergent cardiac catheterisation laboratory evaluation.92, 94, and 95 A recent consensus statement from the European Association for Percutaneous Cardiovascular Interventions (EAPCI) has emphasised that in OHCA patients, cardiac catheterisation should be performed immediately in the presence of ST-elevation and considered as soon as possible (less than 2 h) in other patients in the absence of an obvious non-coronary cause, particularly if they are haemodynamically unstable. 96 Currently, this approach in patients without STE remains controversial and is not accepted by all experts. However, it is reasonable to discuss and consider emergent cardiac catheterisation laboratory evaluation after ROSC in patients with the highest risk of a coronary cause for their cardiac arrest. Factors such as patient age, duration of CPR, haemodynamic instability, presenting cardiac rhythm, neurological status upon hospital arrival, and perceived likelihood of cardiac aetiology can influence the decision to undertake the intervention in the acute phase or to delay it until later on in the hospital stay.

Indications and timing of computed tomography (CT) scanning

Cardiac causes of OHCA have been extensively studied in the last few decades; conversely, little is known on non-cardiac causes. Early identification of a respiratory or neurological cause would enable transfer of the patient to a specialised ICU for optimal care. Improved knowledge of prognosis also enables discussion about the appropriateness of specific therapies, including TTM. Early identification of a respiratory or neurological cause can be achieved by performing a brain and chest CT-scan at hospital admission, before or after coronary angiography. In the absence of signs or symptoms suggesting a neurological or respiratory cause (e.g., headache, seizures or neurological deficits for neurological causes, shortness of breath or documented hypoxia in patients suffering from a known and worsening respiratory disease) or if there is clinical or ECG evidence of myocardial ischaemia, coronary angiography is undertaken first, followed by CT scan in the absence of causative lesions. Several case series showed that this strategy enables diagnosis of non-cardiac causes of arrest in a substantial proportion of patients.97 and 98 In those with cardiac arrest associated with trauma or haemorrhage a whole body CT scan may be indicated.99 and 100

Haemodynamic management

Post-resuscitation myocardial dysfunction causes haemodynamic instability, which manifests as hypotension, low cardiac index and arrhythmias.32 and 101 Perform early echocardiography in all patients in order to detect and quantify the degree of myocardial dysfunction.33 and 102 Post-resuscitation myocardial dysfunction often requires inotropic support, at least transiently. Based on experimental data, dobutamine is the most established treatment in this setting,103 and 104 but the systematic inflammatory response that occurs frequently in post-cardiac arrest patients may also cause vasoplegia and severe vasodilation. 32 Thus, noradrenaline, with or without dobutamine, and fluid is usually the most effective treatment. Infusion of relatively large volumes of fluid is tolerated remarkably well by patients with post-cardiac arrest syndrome.7, 8, and 32 If treatment with fluid resuscitation, inotropes and vasoactive drugs is insufficient to support the circulation, consider insertion of a mechanical circulatory assistance device (e.g., IMPELLA, Abiomed, USA).7 and 105

Treatment may be guided by blood pressure, heart rate, urine output, rate of plasma lactate clearance, and central venous oxygen saturation. Serial echocardiography may also be used, especially in haemodynamically unstable patients. In the ICU an arterial line for continuous blood pressure monitoring is essential. Cardiac output monitoring may help to guide treatment in haemodynamically unstable patients but there is no evidence that its use affects outcome. Some centres still advocate use of an intra aortic balloon pump (IABP) in patients with cardiogenic shock, although the IABP-SHOCK II Trial failed to show that use of the IABP improved 30-day mortality in patients with myocardial infarction and cardiogenic shock.106 and 107

Similarly to the early goal-directed therapy that is recommended in the treatment of sepsis, 108 although challenged by several recent studies,109, 110, and 111 a bundle of therapies, including a specific blood pressure target, has been proposed as a treatment strategy after cardiac arrest. 8 However its influence on clinical outcome is not firmly established and optimal targets for mean arterial pressure and/or systolic arterial pressure remain unknown.7, 8, 112, 113, and 114 One observational study of 151 post-cardiac arrest patients identified an association between a time-weighted average mean arterial pressure (measured every 15 min) of greater than 70 mmHg and good neurological outcome. 113 A recent study showed an inverse relationship between mean arterial pressure and mortality. 101 However, whether the use of vasoactive drugs to achieve such a blood pressure target achieves better neurological outcomes remains unknown. In the absence of definitive data, target the mean arterial blood pressure to achieve an adequate urine output (1 ml kg−1 h−1) and normal or decreasing plasma lactate values, taking into consideration the patient's normal blood pressure, the cause of the arrest and the severity of any myocardial dysfunction. 3 These targets may vary depending on individual physiology and co-morbid status. Importantly, hypothermia may increase urine output 115 and impair lactate clearance. 101

Tachycardia was associated with bad outcome in one retrospective study. 116 During mild induced hypothermia the normal physiological response is bradycardia. In animal models this has been shown to reduce the diastolic dysfunction that usually is present early after cardiac arrest. 117 Bradycardia was previously considered to be a side effect, especially below a rate of 40 min−1; however, recent retrospective studies have shown that bradycardia is associated with a good outcome.118 and 119 As long as blood pressure, lactate, SvO2 and urine output are sufficient, a bradycardia of ≤40 min−1 may be left untreated. Importantly, oxygen requirements during mild induced hypothermia are reduced.

Relative adrenal insufficiency occurs frequently after successful resuscitation from cardiac arrest and it appears to be associated with a poor prognosis when accompanied by post-resuscitation shock.120 and 121 Two randomised controlled trials involving 368 patients with IHCA showed improved ROSC with the use of methylprednisolone and vasopressin in addition to adrenaline, compared with the use of placebo and adrenaline alone: combined RR 1.34 (95% CI 1.21–1.43).122 and 123 No studies have assessed the effect of adding steroids alone to standard treatment for IHCA. These studies come from a single group of investigators and the population studied had very rapid advanced life support, a high incidence of asystolic cardiac arrest, and low baseline survival compared with other IHCA studies. Further confirmatory studies are awaited but, pending further data, do not give steroids routinely after IHCA. There is no clinical evidence for the routine use of steroids after OHCA.

Immediately after a cardiac arrest there is typically a period of hyperkalaemia. Subsequent endogenous catecholamine release and correction of metabolic and respiratory acidosis promotes intracellular transportation of potassium, causing hypokalaemia. Hypokalaemia may predispose to ventricular arrhythmias. Give potassium to maintain the serum potassium concentration between 4.0 and 4.5 mmol l−1.

Implantable cardioverter defibrillators

Insertion of an implantable cardioverter defibrillator (ICD) should be considered in ischaemic patients with significant left ventricular dysfunction, who have been resuscitated from a ventricular arrhythmia that occurred later than 24–48 h after a primary coronary event.124, 125, and 126 ICDs may also reduce mortality in cardiac arrest survivors at risk of sudden death from structural heart diseases or inherited cardiomyopathies.127 and 128 In all cases, a specialised electrophysiological evaluation should be performed before discharge for placement of an ICD for secondary prevention of sudden cardiac death.

Disability (optimising neurological recovery)

Cerebral perfusion

Animal studies show that immediately after ROSC there is a short period of multifocal cerebral no-reflow followed by transient global cerebral hyperaemia lasting 15–30 min.129, 130, and 131 This is followed by up to 24 h of cerebral hypoperfusion while the cerebral metabolic rate of oxygen gradually recovers. After asphyxial cardiac arrest, brain oedema may occur transiently after ROSC but it is rarely associated with clinically relevant increases in intracranial pressure.132 and 133 In many patients, autoregulation of cerebral blood flow is impaired (absent or right-shifted) for some time after cardiac arrest, which means that cerebral perfusion varies with cerebral perfusion pressure instead of being linked to neuronal activity.134 and 135 In a study that used near-infrared spectroscopy to measure regional cerebral oxygenation, autoregulation was disturbed in 35% of post-cardiac arrest patients and the majority of these had been hypertensive before their cardiac arrest 136 ; this tends to support the recommendation made in the 2010 ERC Guidelines: after ROSC, maintain mean arterial pressure near the patient's normal level. 1 However, there is a significant gap in the knowledge about how temperature impacts the optimal blood pressure.


Although it has been common practice to sedate and ventilate patients for at least 24 h after ROSC, there are no high-level data to support a defined period of ventilation, sedation and neuromuscular blockade after cardiac arrest. Patients need to be sedated adequately during treatment with TTM, and the duration of sedation and ventilation is therefore influenced by this treatment. A meta-analysis of drugs used for sedation during mild induced hypothermia showed considerable variability among 68 ICUs in a variety of countries. 137 There are no data to indicate whether or not the choice of sedation influences outcome, but a combination of opioids and hypnotics is usually used. Short-acting drugs (e.g., propofol, alfentanil, remifentanil) will enable more reliable and earlier neurological assessment and prognostication (see Section 7). 138 Volatile anaesthetics have been used to sedate post cardiac arrest patients 139 but although there are some animal data suggesting myocardial and neurological benefits, 140 there are no clinical data showing an advantage with this strategy. Adequate sedation will reduce oxygen consumption. During hypothermia, optimal sedation can reduce or prevent shivering, which enables the target temperature to be achieved more rapidly. Use of published sedation scales for monitoring these patients (e.g., the Richmond or Ramsay Scales) may be helpful.141 and 142

Control of seizures

Seizures are common after cardiac arrest and occur in approximately one-third of patients who remain comatose after ROSC. Myoclonus is most common and occurs in 18–25%, the remainder having focal or generalised tonic–clonic seizures or a combination of seizure types.31, 143, 144, and 145 Clinical seizures, including myoclonus may or may not be of epileptic origin. Other motor manifestations could be mistaken for seizures 146 and there are several types of myoclonus 147 the majority being non-epileptic. Use intermittent electroencephalography (EEG) to detect epileptic activity in patients with clinical seizure manifestations. Consider continuous EEG to monitor patients with a diagnosed status epilepticus and effects of treatment.

In comatose cardiac arrest patients, EEG commonly detects epileptiform activity. Unequivocal seizure activity according to strict EEG-terminology 148 is less common but post-anoxic status epilepticus was detected in 23–31% of patients using continuous EEG-monitoring and more inclusive EEG-criteria.75, 149, and 150 Patients with electrographic status epilepticus may or may not have clinically detectable seizure manifestations that may be masked by sedation. Whether systematic detection and treatment of electrographic epileptic activity improves patient outcome is not known.

Seizures may increase the cerebral metabolic rate 151 and have the potential to exacerbate brain injury caused by cardiac arrest: treat with sodium valproate, levetiracetam, phenytoin, benzodiazepines, propofol, or a barbiturate. Myoclonus can be particularly difficult to treat; phenytoin is often ineffective. Propofol is effective to suppress post-anoxic myoclonus. 152 Clonazepam, sodium valproate and levetiracetam are antimyoclonic drugs that may be effective in post-anoxic myoclonus. 147 After the first event, start maintenance therapy once potential precipitating causes (e.g., intracranial haemorrhage, electrolyte imbalance) are excluded.

The use of prophylactic anticonvulsant drugs after cardiac arrest in adults has been insufficiently studied.153 and 154 Routine seizure prophylaxis in post-cardiac arrest patients is not recommended because of the risk of adverse effects and the poor response to anti-epileptic agents among patients with clinical and electrographic seizures.

Myoclonus and electrographic seizure activity, including status epilepticus, are related to a poor prognosis but individual patients may survive with good outcome (see Section 7).145 and 155 Prolonged observation may be necessary after treatment of seizures with sedatives, which will decrease the reliability of a clinical examination. 156

Glucose control

There is a strong association between high blood glucose after resuscitation from cardiac arrest and poor neurological outcome.13, 15, 20, 157, 158, 159, 160, 161, 162, and 163 Although one randomised controlled trial in a cardiac surgical intensive care unit showed that tight control of blood glucose (4.4–6.1 mmol l−1 or 80–110 mg dl−1) using insulin reduced hospital mortality in critically ill adults, 164 a second study by the same group in medical ICU patients showed no mortality benefit from tight glucose control. 165 In one randomised trial of patients resuscitated from OHCA with ventricular fibrillation, strict glucose control (72–108 mg dl−1, 4–6 mmol l−1) gave no survival benefit compared with moderate glucose control (108–144 mg dl−1, 6–8 mmol l−1) and there were more episodes of hypoglycaemia in the strict glucose control group. 166 A large randomised trial of intensive glucose control (81 mg dl−1 – 108 mg dl−1, 4.5–6.0 mmol l−1) versus conventional glucose control (180 mg dl−1, 10 mmol l−1 or less) in general ICU patients reported increased 90-day mortality in patients treated with intensive glucose control.167 and 168 Severe hypoglycaemia is associated with increased mortality in critically ill patients, 169 and comatose patients are at particular risk from unrecognised hypoglycaemia. Irrespective of the target range, variability in glucose values is associated with mortality. 170 Compared with normothermia, mild induced hypothermia is associated with higher blood glucose values, increased blood glucose variability and greater insulin requirements. 171 Increased blood glucose variability is associated with increased mortality and unfavourable neurological outcome after cardiac arrest.157 and 171

Based on the available data, following ROSC maintain the blood glucose at ≤10 mmol l−1 (180 mg dl−1) and avoid hypoglycaemia. 172 Do not implement strict glucose control in adult patients with ROSC after cardiac arrest because it increases the risk of hypoglycaemia.

Temperature control

Treatment of hyperpyrexia

A period of hyperthermia (hyperpyrexia) is common in the first 48 h after cardiac arrest.13, 173, 174, 175, and 176 Several studies document an association between post-cardiac arrest pyrexia and poor outcomes.13, 173, 175, 176, 177, and 178 The development of hyperthermia after a period of mild induced hypothermia (rebound hyperthermia) is associated with increased mortality and worse neurological outcome.179, 180, 181, and 182 There are no randomised controlled trials evaluating the effect of treatment of pyrexia (defined as ≥37.6 °C) compared to no temperature control in patients after cardiac arrest and the elevated temperature may only be an effect of a more severely injured brain. Although the effect of elevated temperature on outcome is not proven, it seems reasonable to treat hyperthermia occurring after cardiac arrest with antipyretics and to consider active cooling in unconscious patients.

Targeted temperature management

Animal and human data indicate that mild induced hypothermia is neuroprotective and improves outcome after a period of global cerebral hypoxia-ischaemia.183 and 184 Cooling suppresses many of the pathways leading to delayed cell death, including apoptosis (programmed cell death). Hypothermia decreases the cerebral metabolic rate for oxygen (CMRO2) by about 6% for each 1 °C reduction in core temperature and this may reduce the release of excitatory amino acids and free radicals.183 and 185 Hypothermia blocks the intracellular consequences of excitotoxin exposure (high calcium and glutamate concentrations) and reduces the inflammatory response associated with the post-cardiac arrest syndrome. However, in the temperature range 33–36 °C, there is no difference in the inflammatory cytokine response in adult patients according to a recent study. 186

All studies of post-cardiac arrest mild induced hypothermia have included only patients in coma. One randomised trial and a pseudo-randomised trial demonstrated improved neurological outcome at hospital discharge or at 6 months in comatose patients after out-of-hospital VF cardiac arrest.187 and 188 Cooling was initiated within minutes to hours after ROSC and a temperature range of 32–34 °C was maintained for 12–24 h.

Three cohort studies including a total of 1034 patients, have compared mild induced hypothermia (32–34 °C) to no temperature management in OHCA and found no difference in neurological outcome (adjusted pooled odds ratio (OR), 0.90 [95% CI 0.45–1.82].189, 190, and 191 One additional retrospective registry study of 1830 patients documented an increase in poor neurological outcome among those with nonshockable OHCA treated with mild induced hypothermia (adjusted OR 1.44 [95% CI 1.039–2.006]). 192

There are numerous before and after studies on the implementation of temperature control after in hospital cardiac arrest but these data are extremely difficult to interpret because of other changes in post cardiac arrest care that occurred simultaneously. One retrospective cohort study of 8316 in-hospital cardiac arrest (IHCA) patients of any initial rhythm showed no difference in survival to hospital discharge among those who were treated with mild induced hypothermia compared with no active temperature management (OR 0.9, 95% CI 0.65–1.23) but relatively few patients were treated with mild induced hypothermia. 193

In the Targeted Temperature Management (TTM) trial, 950 all-rhythm OHCA patients were randomised to 36 h of temperature control (comprising 28 h at the target temperature followed by slow rewarm) at either 33 °C or 36 °C. 31 Strict protocols were followed for assessing prognosis and for withdrawal of life-sustaining treatment (WLST). There was no difference in the primary outcome – all cause mortality, and neurological outcome at 6 months was also similar (hazard ratio (HR) for mortality at end of trial 1.06, 95% CI 0.89–1.28; relative risk (RR) for death or poor neurological outcome at 6 months 1.02, 95% CI 0.88–1.16). Detailed neurological outcome at 6 months was also similar.22 and 24 Importantly, patients in both arms of this trial had their temperature well controlled so that fever was prevented in both groups. TTM at 33 °C was associated with decreased heart rate, elevated lactate, the need for increased vasopressor support, and a higher extended cardiovascular SOFA score compared with TTM at 36 °C.101 and 194 Bradycardia during mild induced hypothermia may be beneficial – it is associated with good neurological outcome among comatose survivors of OHCA, presumably because autonomic function is preserved.118 and 119

The optimal duration for mild induced hypothermia and TTM is unknown although it is currently most commonly used for 24 h. Previous trials treated patients with 12–28 h of targeted temperature management.31, 187, and 188 Two observational trials found no difference in mortality or poor neurological outcome with 24 h compared with 72 h of hypothermia.195 and 196 The TTM trial provided strict normothermia (<37.5 °C) after hypothermia until 72 h after ROSC. 31

The term targeted temperature management or temperature control is now preferred over the previous term therapeutic hypothermia. The Advanced Life Support Task Force of the International Liaison Committee on Resuscitation made several treatment recommendations on targeted temperature management 128 and these are reflected in these ERC guidelines:

  • Maintain a constant, target temperature between 32 °C and 36 °C for those patients in whom temperature control is used (strong recommendation, moderate-quality evidence).
  • Whether certain subpopulations of cardiac arrest patients may benefit from lower (32–34 °C) or higher (36 °C) temperatures remains unknown, and further research may help elucidate this.
  • TTM is recommended for adults after OHCA with an initial shockable rhythm who remain unresponsive after ROSC (strong recommendation, low-quality evidence).
  • TTM is suggested for adults after OHCA with an initial nonshockable rhythm who remain unresponsive after ROSC (weak recommendation, very low-quality evidence).
  • TTM is suggested for adults after IHCA with any initial rhythm who remain unresponsive after ROSC (weak recommendation, very low-quality evidence).
  • If targeted temperature management is used, it is suggested that the duration is at least 24 h (as undertaken in the two largest previous RCTs31 and 187) (weak recommendation, very low-quality evidence).

It is clear that the optimal target temperature after cardiac arrest is not known and that more high-quality large trials are needed. 197

When to control temperature?

Whichever target temperature is selected, active temperature control is required to achieve and maintain the temperature in this range. Prior recommendations suggest that cooling should be initiated as soon as possible after ROSC, but this recommendation was based only on preclinical data and rational conjecture. 198 Animal data indicate that earlier cooling after ROSC produces better outcomes.199 and 200 Observational studies are confounded by the fact that there is an association between patients who cool faster spontaneously and worse neurological outcome.201, 202, and 203 It is hypothesised that those with the most severe neurological injury are more prone to losing their ability to control body temperature.

Five randomised controlled trials used cold intravenous fluids after ROSC to induce hypothermia,204, 205, 206, and 207 one trial used cold intravenous fluid during resuscitation, 208 and one trial used intra-arrest intranasal cooling. 209 The volume of cold fluid ranged from 20 to 30 ml kg−1 and up to 2 l, although some patients did not receive the full amount before arrival at hospital. All seven trials suffered from the unavoidable lack of blinding of the clinical team, and three also failed to blind the outcomes assessors. These trials showed no overall difference in mortality for patients treated with prehospital cooling (RR, 0.98; 95% CI 0.92–1.04) compared with those who did not receive prehospital cooling. No individual trial found an effect on either poor neurological outcome or mortality.

Four RCTs provided low quality evidence for an increased risk of re-arrest among subjects who received prehospital induced hypothermia (RR, 1.22; 95% CI 1.01–1.46),204, 205, and 207 although this result was driven by data from the largest trial. 207 Three trials reported no pulmonary oedema in any group, two small pilot trials found no difference in the incidence of pulmonary oedema between groups,204 and 208 and one trial showed an increase in pulmonary oedema in patients who received prehospital cooling (RR, 1.34; 95% CI 1.15–1.57). 207

Based on this evidence, prehospital cooling using a rapid infusion of large volumes of cold intravenous fluid immediately after ROSC is not recommended. It may still be reasonable to infuse cold intravenous fluid where patients are well monitored and a lower target temperature (e.g., 33 °C) is the goal. Early cooling strategies, other than rapid infusion of large volumes of cold intravenous fluid, and cooling during cardiopulmonary resuscitation in the prehospital setting have not been studied adequately. Whether certain patient populations (e.g., patients for whom transport time to a hospital is longer than average) might benefit from early cooling strategies remains unknown.

How to control temperature?

The practical application of TTM is divided into three phases: induction, maintenance and rewarming. 210 External and/or internal cooling techniques can be used to initiate and maintain TTM. If a target temperature of 36 °C is chosen, for the many post cardiac arrest patients who arrive in hospital with a temperature less than 36 °C, a practical approach is to let them rewarm spontaneously and to activate a TTM-device when they have reached 36 °C. The maintenance phase at 36 °C is the same as for other target temperatures; shivering, for example, does not differ between patients treated at 33 °C and 36 °C. 31 When using a target of 36 °C, the rewarming phase will be shorter.

If a lower target temperature, e.g., 33 °C is chosen, an infusion of 30 ml kg−1 of 4 °C saline or Hartmann's solution will decrease core temperature by approximately 1.0–1.5 °C.206, 207, and 211 However, in one prehospital randomised controlled trial this intervention was associated with increased pulmonary oedema (diagnosed on the initial chest radiograph) and an increased rate of re-arrest during transport to hospital. 207

Methods of inducing and/or maintaining TTM include:

  • Simple ice packs and/or wet towels are inexpensive; however, these methods may be more time consuming for nursing staff, may result in greater temperature fluctuations, and do not enable controlled rewarming.11, 19, 188, 212, 213, 214, 215, 216, 217, 218, and 219 Ice cold fluids alone cannot be used to maintain hypothermia, 220 but even the addition of simple ice packs may control the temperature adequately. 218
  • Cooling blankets or pads.221, 222, 223, 224, 225, 226, and 227
  • Water or air circulating blankets.7, 8, 10, 182, 226, 228, 229, 230, 231, 232, 233, and 234
  • Water circulating gel-coated pads.7, 224, 226, 233, 235, 236, 237, and 238
  • Transnasal evaporative cooling 209 – this technique enables cooling before ROSC and is undergoing further investigation in a large multicentre randomised controlled trial. 239
  • Intravascular heat exchanger, placed usually in the femoral or subclavian veins.7, 8, 215, 216, 226, 228, 232, 240, 241, 242, 243, 244, and 245
  • Extracorporeal circulation (e.g., cardiopulmonary bypass, ECMO).246 and 247

In most cases, it is easy to cool patients initially after ROSC because the temperature normally decreases within this first hour.13 and 176 Admission temperature after OHCA is usually between 35 °C and 36 °C and in a recent large trial the median temperature was 35.3 °C. 31 If a target temperature of 36 °C is chosen allow a slow passive rewarm to 36 °C. If a target temperature of 33 °C is chosen, initial cooling is facilitated by neuromuscular blockade and sedation, which will prevent shivering. 248 Magnesium sulphate, a naturally occurring NMDA receptor antagonist, that reduces the shivering threshold slightly, can also be given to reduce the shivering threshold.210 and 249

In the maintenance phase, a cooling method with effective temperature monitoring that avoids temperature fluctuations is preferred. This is best achieved with external or internal cooling devices that include continuous temperature feedback to achieve a set target temperature. 250 The temperature is typically monitored from a thermistor placed in the bladder and/or oesophagus.210, 251, and 252 As yet, there are no data indicating that any specific cooling technique increases survival when compared with any other cooling technique; however, internal devices enable more precise temperature control compared with external techniques.226 and 250

Plasma electrolyte concentrations, effective intravascular volume and metabolic rate can change rapidly during rewarming, as they do during cooling. Rebound hyperthermia is associated with worse neurological outcome.179 and 180 Thus, rewarming should be achieved slowly: the optimal rate is not known, but the consensus is currently about 0.25–0.5 °C of rewarming per hour. 228 Choosing a strategy of 36 °C will reduce this risk. 31

Physiological effects and side effects of hypothermia

The well-recognised physiological effects of hypothermia need to be managed carefully 210 :

  • Shivering will increase metabolic and heat production, thus reducing cooling rates – strategies to reduce shivering are discussed above. The occurrence of shivering in cardiac arrest survivors who undergo mild induced hypothermia is associated with a good neurological outcome253 and 254; it is a sign of a normal physiological response. Occurrence of shivering was similar at a target temperature of 33 °C and 36 °C. 31 A sedation protocol is required.
  • Mild induced hypothermia increases systemic vascular resistance and causes arrhythmias (usually bradycardia). 241 Importantly, the bradycardia caused by mild induced hypothermia may be beneficial (similar to the effect achieved by beta-blockers); it reduces diastolic dysfunction 117 and its occurrence has been associated with good neurological outcome.118 and 119
  • Mild induced hypothermia causes a diuresis and electrolyte abnormalities such as hypophosphataemia, hypokalaemia, hypomagnesaemia and hypocalcaemia.31, 210, and 255
  • Hypothermia decreases insulin sensitivity and insulin secretion, and causes hyperglycaemia, 188 which will need treatment with insulin (see glucose control).
  • Mild induced hypothermia impairs coagulation and may increase bleeding, although this effect seems to be negligible 256 and has not been confirmed in clinical studies.7, 31, and 187 In one registry study, an increased rate of minor bleeding occurred with the combination of coronary angiography and mild induced hypothermia, but this combination of interventions was the also the best predictor of good outcome. 20
  • Hypothermia can impair the immune system and increase infection rates.210, 217, and 222 Mild induced hypothermia is associated with an increased incidence of pneumonia257 and 258; however, this seems to have no impact on outcome. Although prophylactic antibiotic treatment has not been studied prospectively, in an observational study, use of prophylactic antibiotics was associated with a reduced incidence of pneumonia. 259 In another observational study of 138 patients admitted to ICU after OHCA, early use of antibiotics was associated with improved survival. 260
  • The serum amylase concentration is commonly increased during hypothermia but the significance of this unclear.
  • The clearance of sedative drugs and neuromuscular blockers is reduced by up to 30% at a core temperature of 34 °C. 261 Clearance of sedative and other drugs will be closer to normal at a temperature closer to 37.0 °C.
Contraindications to targeted temperature management

Generally recognised contraindications to TTM at 33 °C, but which are not applied universally, include: severe systemic infection and pre-existing medical coagulopathy (fibrinolytic therapy is not a contraindication to mild induced hypothermia). Two observational studies documented a positive inotropic effect from mild induced hypothermia in patients in cardiogenic shock,262 and 263 but in the TTM study there was no difference in mortality among patients with mild shock on admission who were treated with a target temperature of 33 °C compared with 36 °C. 194 Animal data also indicate improved contractile function with mild induced hypothermia probably because of increased Ca2+ sensititvity. 264

Other therapies

Neuroprotective drugs (Coenzyme Q10, 223 thiopental, 153 glucocorticoids,123 and 265 nimodipine,266 and 267 lidoflazine 268 or diazepam 154 ) used alone, or as an adjunct to mild induced hypothermia, have not been shown to increase neurologically intact survival when included in the post arrest treatment of cardiac arrest. The combination of xenon and mild induced hypothermia has been studied in a feasibility trial and is undergoing further clinical evaluation. 269


This section has been adapted from the Advisory Statement on Neurological Prognostication in comatose survivors of cardiac arrest, 270 written by members of the ERC ALS Working Group and of the Trauma and Emergency Medicine (TEM) Section of the European Society of Intensive Care Medicine (ESICM), in anticipation of the 2015 Guidelines.

Hypoxic-ischaemic brain injury is common after resuscitation from cardiac arrest. 271 Two thirds of those dying after admission to ICU following out-of-hospital cardiac arrest die from neurological injury; this has been shown both before 28 and after27, 30, and 31 the implementation of target temperature management (TTM) for post-resuscitation care. Most of these deaths are due to active withdrawal of life sustaining treatment (WLST) based on prognostication of a poor neurological outcome.27 and 30 For this reason, when dealing with patients who are comatose after resuscitation from cardiac arrest minimising the risk of a falsely pessimistic prediction is essential. Ideally, when predicting a poor outcome the false positive rate (FPR) should be zero with the narrowest possible confidence interval (CI). However, most prognostication studies include so few patients that even if the FPR is 0%, the upper limit of the 95% CI is often high.272 and 273 Moreover, many studies are confounded by self-fulfilling prophecy, which is a bias occurring when the treating physicians are not blinded to the results of the outcome predictor and use it to make a decision on WLST.272 and 274 Finally, both TTM itself and sedatives or neuromuscular blocking drugs used to maintain it may potentially interfere with prognostication indices, especially those based on clinical examination. 156

Clinical examination

Bilateral absence of pupillary light reflex at 72 h from ROSC predicts poor outcome with close to 0% FPR, both in TTM-treated and in non-TTM-treated patients (FPR 1 [0–3] and 0 [0–8], respectively)156, 275, 276, 277, 278, 279, 280, 281, 282, 283, and 284 and a relatively low sensitivity (19% and 18%, respectively). Similar performance has been documented for bilaterally absent corneal reflex.272 and 273

In non-TTM-treated patients276 and 285 an absent or extensor motor response to pain at 72 h from ROSC has a high (74 [68–79]%) sensitivity for prediction of poor outcome, but the FPR is also high (27 [12–48]%). Similar results were observed in TTM-treated patients.156, 277, 278, 279, 280, 282, 283, 284, 286, 287, and 288 Nevertheless, the high sensitivity of this sign may enable it to be used to identify the population with poor neurological status needing prognostication. Like the corneal reflex, the motor response can be suppressed by sedatives or neuromuscular blocking drugs. 156 When interference from residual sedation or paralysis is suspected, prolonging observation of these clinical signs beyond 72 h from ROSC is recommended, in order to minimise the risk of obtaining false positive results.

Myoclonus is a clinical phenomenon consisting of sudden, brief, involuntary jerks caused by muscular contractions or inhibitions. A prolonged period of continuous and generalised myoclonic jerks is commonly described as status myoclonus. Although there is no definitive consensus on the duration or frequency of myoclonic jerks required to qualify as status myoclonus, in prognostication studies in comatose survivors of cardiac arrest the minimum reported duration is 30 min. The names and definitions used for status myoclonus vary among those studies.

While the presence of myoclonic jerks in comatose survivors of cardiac arrest is not consistently associated with poor outcome (FPR 9%),145 and 272 a status myoclonus starting within 48 h from ROSC was consistently associated with a poor outcome (FPR 0 [0–5]%; sensitivity 8%) in prognostication studies made in non-TTM-treated patients,276, 289, and 290 and is also highly predictive (FPR 0% [0–4]; sensitivity 16%) in TTM-treated patients.144, 156, and 291 However, several case reports of good neurological recovery despite an early-onset, prolonged and generalised myoclonus have been published. In some of these cases myoclonus persisted after awakening and evolved into a chronic action myoclonus (Lance–Adams syndrome).292, 293, 294, 295, 296, and 297 In others it disappeared with recovery of consciousness.298 and 299 The exact time when recovery of consciousness occurred in these cases may have been masked by the myoclonus itself and by ongoing sedation. Patients with post-arrest status myoclonus should be evaluated off sedation whenever possible; in those patients, EEG recording can be useful to identify EEG signs of awareness and reactivity and to reveal a coexistent epileptiform activity.

While predictors of poor outcome based on clinical examination are inexpensive and easy to use, they cannot be concealed from the treating team and therefore their results may potentially influence clinical management and cause a self-fulfilling prophecy. Clinical studies are needed to evaluate the reproducibility of clinical signs used to predict outcome in comatose post-arrest patients.


Short-latency somatosensory evoked potentials (SSEPs)

In non-TTM-treated post-arrest comatose patients, bilateral absence of the N20 SSEP wave predicts death or vegetative state (CPC 4–5) with 0 [0–3]% FPR as early as 24 h from ROSC,276, 300, and 301 and it remains predictive during the following 48 h with a consistent sensitivity (45–46%).276, 300, 302, 303, and 304 Among a total of 287 patients with absent N20 SSEP wave at ≤72 h from ROSC, there was only one false positive result (positive predictive value 99.7 [98–100]%). 305

In TTM-treated patients, bilateral absence of the N20 SSEP wave is also very accurate in predicting poor outcome both during mild induced hypothermia278, 279, 301, and 306 (FPR 2 [0–4]%) and after rewarming277, 278, 286, 288, and 304 (FPR 1 [0–3]%). The few cases of false reports observed in large patient cohorts were due mainly to artefacts.279 and 284 SSEP recording requires appropriate skills and experience, and utmost care should be taken to avoid electrical interference from muscle artefacts or from the ICU environment. Interobserver agreement for SSEPs in anoxic–ischaemic coma is moderate to good but is influenced by noise.307 and 308

In most prognostication studies bilateral absence of N20 SSEP has been used as a criterion for deciding on withdrawal of life-sustaining treatment (WLST), with a consequent risk of self-fulfilling prophecy. 272 SSEP results are more likely to influence physicians’ and families’ WLST decisions than those of clinical examination or EEG. 309

Absence of EEG reactivity

In TTM-treated patients, absence of EEG background reactivity predicts poor outcome with 2 [1–7]% FPR288, 310, and 311 during TH and with 0 [0–3]% FPR286, 288, and 310 after rewarming at 48–72 h from ROSC. However, in one prognostication study in posthypoxic myoclonus three patients with no EEG reactivity after TTM had a good outcome. 144 Most of the prognostication studies on absent EEG reactivity after cardiac arrest are from the same group of investigators. Limitations of EEG reactivity include lack of standardisation as concerns the stimulation modality and modest interrater agreement. 312

Status epilepticus

In TTM-treated patients, the presence of status epilepticus (SE), i.e., a prolonged epileptiform activity, during TH or immediately after rewarming150, 291, and 313 is almost invariably – but not always – followed by poor outcome (FPR from 0% to 6%), especially in presence of an unreactive150 and 314 or discontinuous EEG background. 75 All studies on SE included only a few patients. Definitions of SE were inconsistent among those studies.


Burst-suppression has recently been defined as more than 50% of the EEG record consisting of periods of EEG voltage <10 μV, with alternating bursts. 148 However, most of prognostication studies do not comply with this definition.

In comatose survivors of cardiac arrest, either TTM-treated or non-TH-treated, burst-suppression is usually a transient finding. During the first 24–48 h after ROSC 305 in non-TTM-treated patients or during hypothermia in TTM-treated patients288, 306, and 315 burst-suppression may be compatible with neurological recovery while at ≥72 h from ROSC75, 276, and 316 a persisting burst-suppression pattern is consistently associated with poor outcome. Limited data suggest that specific patterns like a pattern of identical bursts 317 or association with status epilepticus 75 have very high specificity for prediction of poor outcome.

Apart from its prognostic significance, recording of EEG – either continuous or intermittent – in comatose survivors of cardiac arrest both during TH and after rewarming is helpful to assess the level of consciousness – which may be masked by prolonged sedation, neuromuscular dysfunction or myoclonus – and to detect and treat non-convulsive seizures 318 which may occur in about one quarter of comatose survivors of cardiac arrest.75, 149, and 291


NSE and S-100B are protein biomarkers that are released following injury to neurons and glial cells, respectively. Their blood values after cardiac arrest are likely to correlate with the extent of anoxic–ischaemic neurological injury and, therefore, with the severity of neurological outcome. S-100B is less well documented than is NSE. 319 Advantages of biomarkers over both EEG and clinical examination include quantitative results and likely independence from the effects of sedatives. Their main limitation as prognosticators is that it is difficult to find a consistent threshold for identifying patients destined to a poor outcome with a high degree of certainty. In fact, serum concentrations of biomarkers are per se continuous variables, which limits their applicability for predicting a dichotomous outcome, especially when a threshold for 0% FPR is desirable.

Neuron-specific enolase (NSE)

In non-TTM-treated patients the NSE threshold for prediction of poor outcome with 0% FPR at days 24–72 from ROSC was 33 mcg l−1 or less in some studies.276, 320, and 321 However, in other studies this threshold was 47.6 mcg l−1 at 24 h, 65.0 mcg l−1 at 48 h and 90.9 mcg l−1 at 72 h. 302

In TTM-treated patients the threshold for 0% FPR varied between 49.6 mcg l−1 and 151.4 mcg l−1 at 24 h,313, 322, 323, 324, 325, and 326 between 25 mcg l−1 and 151.5 mcg l−1 at 48 h,279, 313, 322, 323, 324, 325, 326, 327, 328, and 329 and between 57.2 mcg l−1 and 78.9 mcg l−1 at 72 h.321, 324, and 327

The main reasons for the observed variability in NSE thresholds include the use of heterogeneous measurement techniques (variation between different analysers),330, 331, and 332 the presence of extra-neuronal sources of biomarkers (haemolysis and neuroendocrine tumours), 333 and the incomplete knowledge of the kinetics of its blood concentrations in the first few days after ROSC. Limited evidence suggests that the discriminative value of NSE levels at 48–72 h is higher than at 24 h.323, 325, and 334 Increasing NSE levels over time may have an additional value in predicting poor outcome.323, 324, and 334 In a secondary analysis of the TTM trial, NSE values were measured at 24, 48 and 72 h in 686 patients; an increase in NSE values between any two points was associated with a poor outcome. 335


Brain CT

The main CT finding of global anoxic–ischaemic cerebral insult following cardiac arrest is cerebral oedema, 133 which appears as a reduction in the depth of cerebral sulci (sulcal effacement) and an attenuation of the grey matter/white matter (GM/WM) interface, due to a decreased density of the GM, which has been quantitatively measured as the ratio (GWR) between the GM and the WM densities. The GWR threshold for prediction of poor outcome with 0% FPR in prognostication studies ranged between 1.10 and 1.22.281, 325, and 336 The methods for GWR calculation were inconsistent among studies.


MRI changes after global anoxic–ischaemic brain injury due to cardiac arrest appear as a hyperintensity in cortical areas or basal ganglia on diffusion weighted imaging (DWI) sequences. In two small studies,337 and 338 the presence of large multilobar changes on DWI or FLAIR MRI sequences performed within five days from ROSC was consistently associated with poor outcome while focal or small volume lesions were not. 329

Apparent diffusion coefficient (ADC) is a quantitative measure of ischaemic DWI changes. ADC values between 700 and 800 × 10−6 mm2 s−1 are considered to be normal. 339 Brain ADC measurements used for prognostication include whole-brain ADC, 340 the proportion of brain volume with low ADC 341 and the lowest ADC value in specific brain areas, such as the cortical occipital area and the putamen.322 and 342 The ADC thresholds associated with 0% FPR vary among studies. These methods depend partly on subjective human decision in identifying the region of interest to be studied and in the interpretation of results, although automated analysis has recently been proposed. 343

Advantages of MRI over brain CT include a better spatial definition and a high sensitivity for identifying ischaemic brain injury; however, its use can be problematic in the most clinically unstable patients. 339 MRI can reveal extensive changes when results of other predictors such as SSEP or ocular reflexes are normal.329 and 339

All studies on prognostication after cardiac arrest using imaging have a small sample size with a consequent low precision, and a very low quality of evidence. Most of those studies are retrospective, and brain CT or MRI had been requested at the discretion of the treating physician, which may have caused a selection bias and overestimated their performance.

Suggested prognostication strategy

A careful clinical neurological examination remains the foundation for prognostication of the comatose patient after cardiac arrest. 344 Perform a thorough clinical examination daily to detect signs of neurological recovery such as purposeful movements or to identify a clinical picture suggesting that brain death has occurred.

The process of brain recovery following global post-anoxic injury is completed within 72 h from arrest in most patients.290 and 345 However, in patients who have received sedatives ≤12 h before the 72 h post ROSC neurological assessment, the reliability of clinical examination may be reduced. 156 Before decisive assessment is performed, major confounders must be excluded346 and 347; apart from sedation and neuromuscular blockade, these include hypothermia, severe hypotension, hypoglycaemia, and metabolic and respiratory derangements. Suspend sedatives and neuromuscular blocking drugs for long enough to avoid interference with clinical examination. Short-acting drugs are preferred whenever possible. When residual sedation/paralysis is suspected, consider using antidotes to reverse the effects of these drugs.

The prognostication strategy algorithm ( Fig. 5.2 ) is applicable to all patients who remain comatose with an absent or extensor motor response to pain at ≥72 h from ROSC. Results of earlier prognostic tests are also considered at this time point.


Fig. 5.2 Prognostication strategy algorithm. EEG: electroencephalography; NSE: neuron-specific enolase; SSEP: somatosensory evoked potentials; ROSC: return of spontaneous circulation; FPR: false positive rate; CI: confidence interval.

Evaluate the most robust predictors first. These predictors have the highest specificity and precision (FPR <5% with 95% CIs <5% in patients treated with controlled temperature) and have been documented in >5 studies from at least three different groups of investigators. They include bilaterally absent pupillary reflexes at ≥72 h from ROSC and bilaterally absent SSEP N20 wave after rewarming (this last sign can be evaluated at ≥24 h from ROSC in patients who have not been treated with controlled temperature). Based on expert opinion, we suggest combining the absence of pupillary reflexes with those of corneal reflexes for predicting poor outcome at this time point. Ocular reflexes and SSEPs maintain their predictive value irrespective of target temperature.283 and 284

If none of the signs above is present to predict a poor outcome, a group of less accurate predictors can be evaluated, but the degree of confidence in their prediction will be lower. These have FPR <5% but wider 95% CIs than the previous predictors, and/or their definition/threshold is inconsistent in prognostication studies. These predictors include the presence of early status myoclonus (within 48 h from ROSC), high values of serum NSE at 48–72 h after ROSC, an unreactive malignant EEG pattern (burst-suppression, status epilepticus) after rewarming, the presence of a marked reduction of the GM/WM ratio or sulcal effacement on brain CT within 24 h after ROSC or the presence of diffuse ischaemic changes on brain MRI at 2–5 days after ROSC. Based on expert opinion, we suggest waiting at least 24 h after the first prognostication assessment and confirming unconsciousness with a Glasgow motor score of 1–2 before using this second set of predictors. We also suggest combining at least two of these predictors for prognostication.

No specific NSE threshold for prediction of poor outcome with 0% FPR can be recommended at present. Ideally, every hospital laboratory assessing NSE should create its own normal values and cut-off levels based on the test kit used. Sampling at multiple time-points is recommended to detect trends in NSE levels and to reduce the risk of false positive results. 335 Care should be taken to avoid haemolysis when sampling NSE.

Although the most robust predictors showed no false positives in most studies, none of them singularly predicts poor outcome with absolute certainty when the relevant comprehensive evidence is considered. Moreover, those predictors have often been used for WLST decisions, with the risk of a self-fulfilling prophecy. For this reason, we recommend that prognostication should be multimodal whenever possible, even in presence of one of these predictors. Apart from increasing safety, limited evidence also suggests that multimodal prognostication increases sensitivity.286, 311, 325, and 348

When prolonged sedation and/or paralysis is necessary, for example, because of the need to treat severe respiratory insufficiency, we recommend postponing prognostication until a reliable clinical examination can be performed. Biomarkers, SSEP and imaging studies may play a role in this context, since they are insensitive to drug interference.

When dealing with an uncertain outcome, clinicians should consider prolonged observation. Absence of clinical improvement over time suggests a worse outcome. Although awakening has been described as late as 25 days after arrest,291, 298, and 349 most survivors will recover consciousness within one week.31, 329, 350, 351, and 352 In a recent observational study, 351 94% of patients awoke within 4.5 days from rewarming and the remaining 6% awoke within ten days. Even those awakening late, can still have a good neurological outcome. 351


Although neurological outcome is considered to be good for the majority of cardiac arrest survivors, cognitive and emotional problems and fatigue are common.23, 24, 279, 353, 354, 355, and 356 Long-term cognitive impairments are present in half of survivors.22, 357, and 358 Memory is most frequently affected, followed by problems in attention and executive functioning (planning and organisation).23 and 359 The cognitive impairments can be severe, but are mostly mild. 22 In one study, of 796 OHCA survivors who had been employed before their cardiac arrest, 76.6% returned to work. 360 Mild cognitive problems are often not recognised by health care professionals and cannot be detected with standard outcome scales such as the Cerebral Performance Categories (CPC) or the Mini-Mental State Examination (MMSE).24 and 361 Emotional problems, including depression, anxiety and posttraumatic stress are also common.362 and 363 Depression is present in 14–45% of the survivors, anxiety in 13–61% and symptoms of posttraumatic stress occur in 19–27%. 355 Fatigue is also a complaint that is often reported after cardiac arrest. Even several years after a cardiac arrest, 56% of the survivors suffer severe fatigue. 356

It is not only the patients who experience problems; their partners and caregivers can feel highly burdened and often have emotional problems, including symptoms of posttraumatic stress.356 and 364 After hospital discharge both survivors and caregivers frequently experience a lack of information on important topics including physical and emotional challenges, implantable cardioverter defibrillators (ICD), regaining daily activities, partner relationships and dealing with health care providers. 365 A systematic review on coronary heart disease patients also showed the importance of active information supply and patient education. 366

Both cognitive and emotional problems have significant impact and can affect a patient's daily functioning, return to work and quality of life.356, 367, and 368 Therefore, follow-up care after hospital discharge is necessary. Although the evidence on the rehabilitation phase appears scarce, three randomised controlled trials have shown that the outcome after cardiac arrest can be improved.369, 370, and 371 First, an eleven-session nursing intervention reduced cardiovascular mortality and depressive symptoms. It did so by focussing on physiological relaxation, self-management, coping strategies and health education. 369 Another nursing intervention was found to improve physical symptoms, anxiety, self-confidence and disease knowledge.370 and 371 This intervention consisted of eight telephone sessions, a 24/7 nurse pager system and an information booklet and was directed at improving self-efficacy, outcome efficacy expectations and enhancing self-management behavioural skills. 372 A third intervention called ‘Stand still…, and move on’, improved overall emotional state, anxiety and quality of life, and also resulted in a faster return to work. 373 This intervention aimed to screen early for cognitive and emotional problems, to provide information and support, to promote self-management and to refer to specialised care, if needed.374 and 375 It generally consisted of only one or two consultations with a specialised nurse and included supply of a special information booklet.

The organisation of follow-up after cardiac arrest varies widely between hospitals and countries in Europe. Follow-up care should be organised systematically and can be provided by a physician or specialised nurse. It includes at least the following aspects:

Screening for cognitive impairments. There is currently no gold standard on how to perform such screening. A good first step would be to ask the patient and a relative or caregiver about cognitive complaints (for example problems with memory, attention, planning). If feasible, administer a structured interview or checklist, such as the Checklist Cognition and Emotion, 376 or a short cognitive screening instrument, such as the Montreal Cognitive Assessment (MoCA) (freely available in many languages at ). In cases where there are signs of cognitive impairments, refer to a neuropsychologist for neuropsychological assessment or to a specialist in rehabilitation medicine for a rehabilitation programme. 377

Screening for emotional problems. Ask whether the patient experiences any emotional problems, such as symptoms of depression, anxiety or posttraumatic stress. General measures that can be used include the Hospital Anxiety and Depression Scale (HADS) and the Impact of Event Scale.378 and 379 In case of emotional problems refer to a psychologist or psychiatrist for further examination and treatment. 355

Provision of information. Give active information on the potential non-cardiac consequences of a cardiac arrest including cognitive impairment, emotional problems and fatigue. Other topics that can be addressed include heart disease, ICDs, regaining daily activities, partner relationships and sexuality, dealing with health care providers and caregiver strain. 365 It is best to combine written information with the possibility for personal consultation. An example of an information booklet is available (in Dutch and English).373 and 374

Organ donation

Organ donation should be considered in those who have achieved ROSC and who fulfil criteria for death using neurological criteria. 380 In those comatose patients in whom a decision is made to withdraw life-sustaining therapy, organ donation should be considered after circulatory death occurs. Organ donation can also be considered in individuals where CPR is not successful in achieving ROSC. All decisions concerning organ donation must follow local legal and ethical requirements, as these vary in different settings.

Non-randomised studies have shown that graft survival at one year is similar from donors who have had CPR compared with donors who have not had CPR: adult hearts (3230 organs381, 382, 383, 384, 385, 386, and 387), adult lungs (1031 organs383, 385, and 388), adult kidneys (5000 organs381 and 383), adult livers (2911 organs381 and 383), and adult intestines (25 organs 383 ).

Non-randomised studies have also shown that graft survival at one year was similar when organs recovered from donors with ongoing CPR were compared to other types of donors for adult kidneys (199 organs389, 390, and 391) or adult livers (60 organs390, 392, and 393).

Solid organs have been successfully transplanted after circulatory death. This group of patients offers an opportunity to increase the organ donor pool. Organ retrieval from donation after circulatory death (DCD) donors is classified as controlled or uncontrolled.394 and 395 Controlled donation occurs after planned withdrawal of treatment following non-survivable injuries and illnesses. Uncontrolled donation describes donation from patients with unsuccessful CPR in whom a decision has been made that CPR should be stopped. Once death has been diagnosed, the assessment of which includes a pre-defined period of observation to ensure a spontaneous circulation does not return, 396 organ preservation and retrieval takes place. Aspects or uncontrolled organ donation are complex and controversial as some of the same techniques used during CPR to attempt to achieve ROSC are also used for organ preservation after death has been confirmed, e.g., mechanical chest compression and extracorporeal circulation. Locally agreed protocols must therefore be followed.

Screening for inherited disorders

Many sudden death victims have silent structural heart disease, most often coronary artery disease, but also primary arrhythmia syndromes, cardiomyopathies, familial hypercholesterolaemia and premature ischaemic heart disease. Screening for inherited disorders is crucial for primary prevention in relatives as it may enable preventive antiarrhythmic treatment and medical follow-up.397, 398, and 399 This screening should be performed using clinical examination, electrophysiology and cardiac imaging. In selected cases, genetic mutations associated with inherited cardiac diseases should also be searched. 400

Cardiac arrest centres

There is wide variability in survival among hospitals caring for patients after resuscitation from cardiac arrest.9, 13, 16, 17, 401, 402, and 403 Many studies have reported an association between survival to hospital discharge and transport to a cardiac arrest centre but there is inconsistency in the hospital factors that are most related to patient outcome.4, 5, 9, 17, 401, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, and 416 There is also inconsistency in the services that together define a cardiac arrest centre. Most experts agree that such a centre must have a cardiac catheterisation laboratory that is immediately accessible 24/7 and the facility to provide targeted temperature management. The availability of a neurology service that can provide neuroelectrophysiological monitoring (electroencephalography (EEG)) and investigations (e.g., EEG and somatosensory evoked potentials (SSEPs)) is also essential.

There is some low-level evidence that ICUs admitting more than 50 post-cardiac arrest patients per year produce better survival rates than those admitting less than 20 cases per year 17 ; however, differences in case mix could account for these differences. An observational study showed that unadjusted survival to discharge was greater in hospitals that received ≥40 cardiac arrest patients/year compared with those that received <40 per year, but this difference disappeared after adjustment for patient factors. 417

Several studies with historic control groups have shown improved survival after implementation of a comprehensive package of post-resuscitation care that includes mild induced hypothermia and percutaneous coronary intervention.7, 10, 11, and 418 There is also evidence of improved survival after out-of-hospital cardiac arrest in large hospitals with cardiac catheter facilities compared with smaller hospitals with no cardiac catheter facilities. 9 In a study of 3981 patients arriving with a sustained pulse at one of 151 hospitals, the Resuscitation Outcome Consortium (ROC) investigators have shown that early coronary intervention and mild induced hypothermia were associated with a favourable outcome. 84 These interventions were more frequent in hospitals that treated higher number of OHCA patients per year.

Several studies of OHCA arrest failed to demonstrate any effect of transport interval from the scene to the receiving hospital on survival to hospital discharge if ROSC was achieved at the scene and transport intervals were short (3–11 min).406, 412, and 413 This implies that it may be safe to bypass local hospitals and transport the post-cardiac arrest patient to a regional cardiac arrest centre. There is indirect evidence that regional cardiac resuscitation systems of care improve outcome after ST elevation myocardial infarction (STEMI).407, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, and 442

The implication from all these data is that specialist cardiac arrest centres and systems of care may be effective.443, 444, 445, and 446 Despite the lack of high quality data to support implementation of cardiac arrest centres, it seems likely that regionalisation of post-cardiac arrest care will be adopted in most countries.

Conflicts of interest


Jerry P. Nolan Editor-in-Chief Resuscitation
Alain Cariou Speakers honorarium BARD-France
Bernd W. Böttiger No conflict of interest reported
Charles D. Deakin Director Prometheus Medical Ltd.
Claudio Sandroni No conflict of interest reported
Hans Friberg Speakers honorarium Bard Medical-Natus Inc.
Jasmeet Soar Editor Resuscitation
Kjetil Sunde No conflict of interest reported
Tobias Cronberg No conflict of interest reported
Veronique R.M. Moulaert No conflict of interest reported


  • 1 C.D. Deakin, J.P. Nolan, J. Soar, et al. European Resuscitation Council Guidelines for Resuscitation 2010. Section 4. Adult advanced life support. Resuscitation. 2010;81:1305-1352
  • 2 J. Nolan, J. Soar, H. Eikeland. The chain of survival. Resuscitation. 2006;71:270-271
  • 3 J.P. Nolan, R.W. Neumar, C. Adrie, et al. Post-cardiac arrest syndrome: epidemiology, pathophysiology, treatment, and prognostication. A Scientific Statement from the International Liaison Committee on Resuscitation; the American Heart Association Emergency Cardiovascular Care Committee; the Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiopulmonary, Perioperative, and Critical Care; the Council on Clinical Cardiology; the Council on Stroke. Resuscitation. 2008;79:350-379
  • 4 D.W. Spaite, B.J. Bobrow, U. Stolz, et al. Statewide regionalization of postarrest care for out-of-hospital cardiac arrest: association with survival and neurologic outcome. Ann Emerg Med. 2014;64 496–506e1
  • 5 H. Soholm, K. Wachtell, S.L. Nielsen, et al. Tertiary centres have improved survival compared to other hospitals in the Copenhagen area after out-of-hospital cardiac arrest. Resuscitation. 2013;84:162-167
  • 6 H. Kirves, M.B. Skrifvars, M. Vahakuopus, K. Ekstrom, M. Martikainen, M. Castren. Adherence to resuscitation guidelines during prehospital care of cardiac arrest patients. Eur J Emerg Med. 2007;14:75-81
  • 7 K. Sunde, M. Pytte, D. Jacobsen, et al. Implementation of a standardised treatment protocol for post resuscitation care after out-of-hospital cardiac arrest. Resuscitation. 2007;73:29-39
  • 8 D.F. Gaieski, R.A. Band, B.S. Abella, et al. Early goal-directed hemodynamic optimization combined with therapeutic hypothermia in comatose survivors of out-of-hospital cardiac arrest. Resuscitation. 2009;80:418-424
  • 9 B.G. Carr, M. Goyal, R.A. Band, et al. A national analysis of the relationship between hospital factors and post-cardiac arrest mortality. Intensive Care Med. 2009;35:505-511
  • 10 M. Oddo, M.D. Schaller, F. Feihl, V. Ribordy, L. Liaudet. From evidence to clinical practice: effective implementation of therapeutic hypothermia to improve patient outcome after cardiac arrest. Crit Care Med. 2006;34:1865-1873
  • 11 R. Knafelj, P. Radsel, T. Ploj, M. Noc. Primary percutaneous coronary intervention and mild induced hypothermia in comatose survivors of ventricular fibrillation with ST-elevation acute myocardial infarction. Resuscitation. 2007;74:227-234
  • 12 C.D. Deakin, R. Fothergill, F. Moore, L. Watson, M. Whitbread. Level of consciousness on admission to a Heart Attack Centre is a predictor of survival from out-of-hospital cardiac arrest. Resuscitation. 2014;85:905-909
  • 13 A. Langhelle, S.S. Tyvold, K. Lexow, S.A. Hapnes, K. Sunde, P.A. Steen. In-hospital factors associated with improved outcome after out-of-hospital cardiac arrest. A comparison between four regions in Norway. Resuscitation. 2003;56:247-263
  • 14 O. Tomte, G.O. Andersen, D. Jacobsen, T. Draegni, B. Auestad, K. Sunde. Strong and weak aspects of an established post-resuscitation treatment protocol – a five-year observational study. Resuscitation. 2011;82:1186-1193
  • 15 J.P. Nolan, S.R. Laver, C.A. Welch, D.A. Harrison, V. Gupta, K. Rowan. Outcome following admission to UK intensive care units after cardiac arrest: a secondary analysis of the ICNARC Case Mix Programme Database. Anaesthesia. 2007;62:1207-1216
  • 16 S.P. Keenan, P. Dodek, C. Martin, F. Priestap, M. Norena, H. Wong. Variation in length of intensive care unit stay after cardiac arrest: where you are is as important as who you are. Crit Care Med. 2007;35:836-841
  • 17 B.G. Carr, J.M. Kahn, R.M. Merchant, A.A. Kramer, R.W. Neumar. Inter-hospital variability in post-cardiac arrest mortality. Resuscitation. 2009;80:30-34
  • 18 M. Niskanen, M. Reinikainen, J. Kurola. Outcome from intensive care after cardiac arrest: comparison between two patient samples treated in 1986–87 and 1999–2001 in Finnish ICUs. Acta Anaesthesiol Scand. 2007;51:151-157
  • 19 J. Hovdenes, J.H. Laake, L. Aaberge, H. Haugaa, J.F. Bugge. Therapeutic hypothermia after out-of-hospital cardiac arrest: experiences with patients treated with percutaneous coronary intervention and cardiogenic shock. Acta Anaesthesiol Scand. 2007;51:137-142
  • 20 N. Nielsen, J. Hovdenes, F. Nilsson, et al. Outcome, timing and adverse events in therapeutic hypothermia after out-of-hospital cardiac arrest. Acta Anaesthesiol Scand. 2009;53:926-934
  • 21 P. Sulzgruber, A. Kliegel, C. Wandaller, et al. Survivors of cardiac arrest with good neurological outcome show considerable impairments of memory functioning. Resuscitation. 2015;88:120-125
  • 22 G. Lilja, N. Nielsen, H. Friberg, et al. cognitive function in survivors of out-of-hospital cardiac arrest after target temperature management at 33 degrees C versus 36 degrees C. Circulation. 2015;131:1340-1349
  • 23 V.R.M.P. Moulaert, J.A. Verbunt, C.M. van Heugten, D.T. Wade. Cognitive impairments in survivors of out-of-hospital cardiac arrest: a systematic review. Resuscitation. 2009;80:297-305
  • 24 T. Cronberg, G. Lilja, J. Horn, et al. Neurologic function and health-related quality of life in patients following targeted temperature management at 33 degrees C vs 36 degrees C after out-of-hospital cardiac arrest: a randomized clinical trial. JAMA Neurol. 2015;72:634-641
  • 25 N. Mongardon, F. Dumas, S. Ricome, et al. Postcardiac arrest syndrome: from immediate resuscitation to long-term outcome. Ann Intensive Care. 2011;1:45
  • 26 D. Stub, S. Bernard, S.J. Duffy, D.M. Kaye. Post cardiac arrest syndrome: a review of therapeutic strategies. Circulation. 2011;123:1428-1435
  • 27 V. Lemiale, F. Dumas, N. Mongardon, et al. Intensive care unit mortality after cardiac arrest: the relative contribution of shock and brain injury in a large cohort. Intensive Care Med. 2013;39:1972-1980
  • 28 S. Laver, C. Farrow, D. Turner, J. Nolan. Mode of death after admission to an intensive care unit following cardiac arrest. Intensive Care Med. 2004;30:2126-2128
  • 29 T.M. Olasveengen, K. Sunde, C. Brunborg, J. Thowsen, P.A. Steen, L. Wik. Intravenous drug administration during out-of-hospital cardiac arrest: a randomized trial. JAMA. 2009;302:2222-2229
  • 30 I. Dragancea, M. Rundgren, E. Englund, H. Friberg, T. Cronberg. The influence of induced hypothermia and delayed prognostication on the mode of death after cardiac arrest. Resuscitation. 2013;84:337-342
  • 31 N. Nielsen, J. Wetterslev, T. Cronberg, et al. Targeted temperature management at 33 degrees C versus 36 degrees C after cardiac arrest. N Engl J Med. 2013;369:2197-2206
  • 32 I. Laurent, M. Monchi, J.D. Chiche, et al. Reversible myocardial dysfunction in survivors of out-of-hospital cardiac arrest. J Am Coll Cardiol. 2002;40:2110-2116
  • 33 M. Ruiz-Bailen, E. Aguayo de Hoyos, S. Ruiz-Navarro, et al. Reversible myocardial dysfunction after cardiopulmonary resuscitation. Resuscitation. 2005;66:175-181
  • 34 A. Chalkias, T. Xanthos. Pathophysiology and pathogenesis of post-resuscitation myocardial stunning. Heart Fail Rev. 2012;17:117-128
  • 35 E.L. Cerchiari, P. Safar, E. Klein, W. Diven. Visceral, hematologic and bacteriologic changes and neurologic outcome after cardiac arrest in dogs. The visceral post-resuscitation syndrome. Resuscitation. 1993;25:119-136
  • 36 C. Adrie, M. Monchi, I. Laurent, et al. Coagulopathy after successful cardiopulmonary resuscitation following cardiac arrest: implication of the protein C anticoagulant pathway. J Am Coll Cardiol. 2005;46:21-28
  • 37 D. Grimaldi, E. Guivarch, N. Neveux, et al. Markers of intestinal injury are associated with endotoxemia in successfully resuscitated patients. Resuscitation. 2013;84:60-65
  • 38 B.W. Roberts, J.H. Kilgannon, M.E. Chansky, et al. Multiple organ dysfunction after return of spontaneous circulation in postcardiac arrest syndrome. Crit Care Med. 2013;41:1492-1501
  • 39 B.W. Bottiger, H. Bohrer, T. Boker, J. Motsch, M. Aulmann, E. Martin. Platelet factor 4 release in patients undergoing cardiopulmonary resuscitation – can reperfusion be impaired by platelet activation?. Acta Anaesthesiol Scand. 1996;40:631-635
  • 40 B.W. Bottiger, J. Motsch, V. Braun, E. Martin, M. Kirschfink. Marked activation of complement and leukocytes and an increase in the concentrations of soluble endothelial adhesion molecules during cardiopulmonary resuscitation and early reperfusion after cardiac arrest in humans. Crit Care Med. 2002;30:2473-2480
  • 41 B.W. Bottiger, J. Motsch, H. Bohrer, et al. Activation of blood coagulation after cardiac arrest is not balanced adequately by activation of endogenous fibrinolysis. Circulation. 1995;92:2572-2578
  • 42 C. Adrie, M. Adib-Conquy, I. Laurent, et al. Successful cardiopulmonary resuscitation after cardiac arrest as a “sepsis-like” syndrome. Circulation. 2002;106:562-568
  • 43 C. Adrie, I. Laurent, M. Monchi, A. Cariou, J.F. Dhainaou, C. Spaulding. Postresuscitation disease after cardiac arrest: a sepsis-like syndrome?. Curr Opin Crit Care. 2004;10:208-212
  • 44 O. Huet, L. Dupic, F. Batteux, et al. Postresuscitation syndrome: potential role of hydroxyl radical-induced endothelial cell damage. Crit Care Med. 2011;39:1712-1720
  • 45 K. Fink, M. Schwarz, L. Feldbrugge, et al. Severe endothelial injury and subsequent repair in patients after successful cardiopulmonary resuscitation. Crit Care. 2010;14:R104
  • 46 M.E. van Genderen, A. Lima, M. Akkerhuis, J. Bakker, J. van Bommel. Persistent peripheral and microcirculatory perfusion alterations after out-of-hospital cardiac arrest are associated with poor survival. Crit Care Med. 2012;40:2287-2294
  • 47 J. Bro-Jeppesen, J. Kjaergaard, M. Wanscher, et al. Systemic inflammatory response and potential prognostic implications after out-of-hospital cardiac arrest: a substudy of the target temperature management trial. Crit Care Med. 2015;43:1223-1232
  • 48 Y. Sutherasan, O. Penuelas, A. Muriel, et al. Management and outcome of mechanically ventilated patients after cardiac arrest. Crit Care. 2015;19:215
  • 49 J. Pilcher, M. Weatherall, P. Shirtcliffe, R. Bellomo, P. Young, R. Beasley. The effect of hyperoxia following cardiac arrest – a systematic review and meta-analysis of animal trials. Resuscitation. 2012;83:417-422
  • 50 C.F. Zwemer, S.E. Whitesall, L.G. D’Alecy. Cardiopulmonary-cerebral resuscitation with 100% oxygen exacerbates neurological dysfunction following nine minutes of normothermic cardiac arrest in dogs. Resuscitation. 1994;27:159-170
  • 51 E.M. Richards, G. Fiskum, R.E. Rosenthal, I. Hopkins, M.C. McKenna. Hyperoxic reperfusion after global ischemia decreases hippocampal energy metabolism. Stroke. 2007;38:1578-1584
  • 52 V. Vereczki, E. Martin, R.E. Rosenthal, P.R. Hof, G.E. Hoffman, G. Fiskum. Normoxic resuscitation after cardiac arrest protects against hippocampal oxidative stress, metabolic dysfunction, and neuronal death. J Cereb Blood Flow Metab. 2006;26:821-835
  • 53 Y. Liu, R.E. Rosenthal, Y. Haywood, M. Miljkovic-Lolic, J.Y. Vanderhoek, G. Fiskum. Normoxic ventilation after cardiac arrest reduces oxidation of brain lipids and improves neurological outcome. Stroke. 1998;29:1679-1686
  • 54 I.S. Balan, G. Fiskum, J. Hazelton, C. Cotto-Cumba, R.E. Rosenthal. Oximetry-guided reoxygenation improves neurological outcome after experimental cardiac arrest. Stroke. 2006;37:3008-3013
  • 55 J.H. Kilgannon, A.E. Jones, N.I. Shapiro, et al. Association between arterial hyperoxia following resuscitation from cardiac arrest and in-hospital mortality. JAMA. 2010;303:2165-2171
  • 56 J.H. Kilgannon, A.E. Jones, J.E. Parrillo, et al. Relationship between supranormal oxygen tension and outcome after resuscitation from cardiac arrest. Circulation. 2011;123:2717-2722
  • 57 D.R. Janz, R.D. Hollenbeck, J.S. Pollock, J.A. McPherson, T.W. Rice. Hyperoxia is associated with increased mortality in patients treated with mild therapeutic hypothermia after sudden cardiac arrest. Crit Care Med. 2012;40:3135-3139
  • 58 R. Bellomo, M. Bailey, G.M. Eastwood, et al. Arterial hyperoxia and in-hospital mortality after resuscitation from cardiac arrest. Crit Care. 2011;15:R90
  • 59 C.H. Wang, W.T. Chang, C.H. Huang, et al. The effect of hyperoxia on survival following adult cardiac arrest: a systematic review and meta-analysis of observational studies. Resuscitation. 2014;85:1142-1148
  • 60 P. Young, M. Bailey, R. Bellomo, et al. HyperOxic Therapy OR NormOxic Therapy after out-of-hospital cardiac arrest (HOT OR NOT): a randomised controlled feasibility trial. Resuscitation. 2014;85:1686-1691
  • 61 D. Stub, K. Smith, S. Bernard, et al. Air versus oxygen in ST-segment elevation myocardial infarction. Circulation. 2015;131:2143-2150
  • 62 D.K. Menon, J.P. Coles, A.K. Gupta, et al. Diffusion limited oxygen delivery following head injury. Crit Care Med. 2004;32:1384-1390
  • 63 P. Bouzat, T. Suys, N. Sala, M. Oddo. Effect of moderate hyperventilation and induced hypertension on cerebral tissue oxygenation after cardiac arrest and therapeutic hypothermia. Resuscitation. 2013;84:1540-1545
  • 64 G. Buunk, J.G. van der Hoeven, A.E. Meinders. Cerebrovascular reactivity in comatose patients resuscitated from a cardiac arrest. Stroke. 1997;28:1569-1573
  • 65 G. Buunk, J.G. van der Hoeven, A.E. Meinders. A comparison of near-infrared spectroscopy and jugular bulb oximetry in comatose patients resuscitated from a cardiac arrest. Anaesthesia. 1998;53:13-19
  • 66 R.O. Roine, J. Launes, P. Nikkinen, L. Lindroth, M. Kaste. Regional cerebral blood flow after human cardiac arrest. A hexamethylpropyleneamine oxime single photon emission computed tomographic study. Arch Neurol. 1991;48:625-629
  • 67 J.E. Beckstead, W.A. Tweed, J. Lee, W.L. MacKeen. Cerebral blood flow and metabolism in man following cardiac arrest. Stroke. 1978;9:569-573
  • 68 B.W. Roberts, J.H. Kilgannon, M.E. Chansky, N. Mittal, J. Wooden, S. Trzeciak. Association between postresuscitation partial pressure of arterial carbon dioxide and neurological outcome in patients with post-cardiac arrest syndrome. Circulation. 2013;127:2107-2113
  • 69 A.G. Schneider, G.M. Eastwood, R. Bellomo, et al. Arterial carbon dioxide tension and outcome in patients admitted to the intensive care unit after cardiac arrest. Resuscitation. 2013;84:927-934
  • 70 J. Vaahersalo, S. Bendel, M. Reinikainen, et al. Arterial blood gas tensions after resuscitation from out-of-hospital cardiac arrest: associations with long-term neurologic outcome. Crit Care Med. 2014;42:1463-1470
  • 71 P. Falkenbach, A. Kamarainen, A. Makela, et al. Incidence of iatrogenic dyscarbia during mild therapeutic hypothermia after successful resuscitation from out-of-hospital cardiac arrest. Resuscitation. 2009;80:990-993
  • 72 A.S. Slutsky, V.M. Ranieri. Ventilator-induced lung injury. N Engl J Med. 2013;369:2126-2136
  • 73 W. Alhazzani, M. Alshahrani, R. Jaeschke, et al. Neuromuscular blocking agents in acute respiratory distress syndrome: a systematic review and meta-analysis of randomized controlled trials. Crit Care. 2013;17:R43
  • 74 J.D. Salciccioli, M.N. Cocchi, J.C. Rittenberger, et al. Continuous neuromuscular blockade is associated with decreased mortality in post-cardiac arrest patients. Resuscitation. 2013;84:1728-1733
  • 75 M. Rundgren, E. Westhall, T. Cronberg, I. Rosen, H. Friberg. Continuous amplitude-integrated electroencephalogram predicts outcome in hypothermia-treated cardiac arrest patients. Crit Care Med. 2010;38:1838-1844
  • 76 A.C. Miller, S.F. Rosati, A.F. Suffredini, D.S. Schrump. A systematic review and pooled analysis of CPR-associated cardiovascular and thoracic injuries. Resuscitation. 2014;85:724-731
  • 77 Y. Kashiwagi, T. Sasakawa, A. Tampo, et al. Computed tomography findings of complications resulting from cardiopulmonary resuscitation. Resuscitation. 2015;88:86-91
  • 78 J.M. Larsen, J. Ravkilde. Acute coronary angiography in patients resuscitated from out-of-hospital cardiac arrest – a systematic review and meta-analysis. Resuscitation. 2012;83:1427-1433
  • 79 C.M. Spaulding, L.M. Joly, A. Rosenberg, et al. Immediate coronary angiography in survivors of out-of-hospital cardiac arrest. N Engl J Med. 1997;336:1629-1633
  • 80 A.C. Camuglia, V.K. Randhawa, S. Lavi, D.L. Walters. Cardiac catheterization is associated with superior outcomes for survivors of out of hospital cardiac arrest: review and meta-analysis. Resuscitation. 2014;85:1533-1540
  • 81 J.T. Grasner, P. Meybohm, A. Caliebe, et al. Postresuscitation care with mild therapeutic hypothermia and coronary intervention after out-of-hospital cardiopulmonary resuscitation: a prospective registry analysis. Crit Care. 2011;15:R61
  • 82 J. Garcia-Tejada, A. Jurado-Roman, J. Rodriguez, et al. Post-resuscitation electrocardiograms, acute coronary findings and in-hospital prognosis of survivors of out-of-hospital cardiac arrest. Resuscitation. 2014;85:1245-1250
  • 83 N.I. Nikolaou, H.R. Arntz, A. Bellou, F. Beygui, L.L. Bossaert, A. Cariou. European Resuscitation Council Guidelines for Resuscitation 2015. Section 8. Initial management of acute coronary syndromes resuscitation. Resuscitation. 2015;95:263-276
  • 84 C.W. Callaway, R.H. Schmicker, S.P. Brown, et al. Early coronary angiography and induced hypothermia are associated with survival and functional recovery after out-of-hospital cardiac arrest. Resuscitation. 2014;85:657-663
  • 85 F. Dumas, L. White, B.A. Stubbs, A. Cariou, T.D. Rea. Long-term prognosis following resuscitation from out of hospital cardiac arrest: role of percutaneous coronary intervention and therapeutic hypothermia. J Am Coll Cardiol. 2012;60:21-27
  • 86 D. Zanuttini, I. Armellini, G. Nucifora, et al. Predictive value of electrocardiogram in diagnosing acute coronary artery lesions among patients with out-of-hospital-cardiac-arrest. Resuscitation. 2013;84:1250-1254
  • 87 F. Dumas, S. Manzo-Silberman, J. Fichet, et al. Can early cardiac troponin I measurement help to predict recent coronary occlusion in out-of-hospital cardiac arrest survivors?. Crit Care Med. 2012;40:1777-1784
  • 88 G. Sideris, S. Voicu, J.G. Dillinger, et al. Value of post-resuscitation electrocardiogram in the diagnosis of acute myocardial infarction in out-of-hospital cardiac arrest patients. Resuscitation. 2011;82:1148-1153
  • 89 D. Muller, L. Schnitzer, J. Brandt, H.R. Arntz. The accuracy of an out-of-hospital 12-lead ECG for the detection of ST-elevation myocardial infarction immediately after resuscitation. Ann Emerg Med. 2008;52:658-664
  • 90 F. Dumas, A. Cariou, S. Manzo-Silberman, et al. Immediate percutaneous coronary intervention is associated with better survival after out-of-hospital cardiac arrest: insights from the PROCAT (Parisian Region Out of hospital Cardiac ArresT) registry. Circ Cardiovasc Interv. 2010;3:200-207
  • 91 P. Radsel, R. Knafelj, S. Kocjancic, M. Noc. Angiographic characteristics of coronary disease and postresuscitation electrocardiograms in patients with aborted cardiac arrest outside a hospital. Am J Cardiol. 2011;108:634-638
  • 92 R.D. Hollenbeck, J.A. McPherson, M.R. Mooney, et al. Early cardiac catheterization is associated with improved survival in comatose survivors of cardiac arrest without STEMI. Resuscitation. 2014;85:88-95
  • 93 B. Redfors, T. Ramunddal, O. Angeras, et al. Angiographic findings and survival in patients undergoing coronary angiography due to sudden cardiac arrest in Western Sweden. Resuscitation. 2015;90:13-20
  • 94 J. Bro-Jeppesen, J. Kjaergaard, M. Wanscher, et al. Emergency coronary angiography in comatose cardiac arrest patients: do real-life experiences support the guidelines?. Eur Heart J Acute Cardiovasc Care. 2012;1:291-301
  • 95 J. Dankiewicz, N. Nielsen, M. Annborn, et al. Survival in patients without acute ST elevation after cardiac arrest and association with early coronary angiography: a post hoc analysis from the TTM trial. Intensive Care Med. 2015;41:856-864
  • 96 M. Noc, J. Fajadet, J.F. Lassen, et al. Invasive coronary treatment strategies for out-of-hospital cardiac arrest: a consensus statement from the European association for percutaneous cardiovascular interventions (EAPCI)/stent for life (SFL) groups. EuroIntervention. 2014;10:31-37
  • 97 J. Chelly, N. Mongardon, F. Dumas, et al. Benefit of an early and systematic imaging procedure after cardiac arrest: insights from the PROCAT (Parisian Region Out of Hospital Cardiac Arrest) registry. Resuscitation. 2012;83:1444-1450
  • 98 M. Arnaout, N. Mongardon, N. Deye, et al. Out-of-hospital cardiac arrest from brain cause: epidemiology, clinical features, and outcome in a multicenter cohort. Crit Care Med. 2015;43:453-460
  • 99 N.D. Caputo, C. Stahmer, G. Lim, K. Shah. Whole-body computed tomographic scanning leads to better survival as opposed to selective scanning in trauma patients: a systematic review and meta-analysis. J Trauma Acute Care Surg. 2014;77:534-539
  • 100 A. Truhlar, C.D. Deakin, J. Soar, et al. European Resuscitation Council Guidelines for Resuscitation 2015. Section 4. Cardiac arrest in special circumstances. Resuscitation. 2015;95:147-200
  • 101 J. Bro-Jeppesen, M. Annborn, C. Hassager, et al. Hemodynamics and vasopressor support during targeted temperature management at 33 degrees C versus 36 degrees C after out-of-hospital cardiac arrest: a post hoc study of the target temperature management trial. Crit Care Med. 2015;43:318-327
  • 102 W.T. Chang, M.H. Ma, K.L. Chien, et al. Postresuscitation myocardial dysfunction: correlated factors and prognostic implications. Intensive Care Med. 2007;33:88-95
  • 103 K.B. Kern, R.W. Hilwig, R.A. Berg, et al. Postresuscitation left ventricular systolic and diastolic dysfunction: treatment with dobutamine. Circulation. 1997;95:2610-2613
  • 104 A. Vasquez, K.B. Kern, R.W. Hilwig, J. Heidenreich, R.A. Berg, G.A. Ewy. Optimal dosing of dobutamine for treating post-resuscitation left ventricular dysfunction. Resuscitation. 2004;61:199-207
  • 105 S. Manzo-Silberman, J. Fichet, A. Mathonnet, et al. Percutaneous left ventricular assistance in post cardiac arrest shock: comparison of intra aortic blood pump and IMPELLA Recover LP2.5. Resuscitation. 2013;84:609-615
  • 106 H. Thiele, U. Zeymer, F.J. Neumann, et al. Intraaortic balloon support for myocardial infarction with cardiogenic shock. N Engl J Med. 2012;367:1287-1296
  • 107 Y. Ahmad, S. Sen, M.J. Shun-Shin, et al. Intra-aortic balloon pump therapy for acute myocardial infarction: a meta-analysis. JAMA Intern Med. 2015;175:931-939
  • 108 R.P. Dellinger, M.M. Levy, A. Rhodes, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41:580-637
  • 109 C.I. Pro, D.M. Yealy, J.A. Kellum, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014;370:1683-1693
  • 110 ARISE Investigators, ANZICS Clinical Trials Group, S.L. Peake, A. Delaney, M. Beiley, et al. Goal-directed resuscitation for patients with early septic shock. N Engl J Med. 2014;371:1496-1506
  • 111 P.R. Mouncey, T.M. Osborn, G.S. Power, et al. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med. 2015;372:1301-1311
  • 112 M.E. Beylin, S.M. Perman, B.S. Abella, et al. Higher mean arterial pressure with or without vasoactive agents is associated with increased survival and better neurological outcomes in comatose survivors of cardiac arrest. Intensive Care Med. 2013;39:1981-1988
  • 113 J.H. Kilgannon, B.W. Roberts, A.E. Jones, et al. Arterial blood pressure and neurologic outcome after resuscitation from cardiac arrest. Crit Care Med. 2014;42:2083-2091
  • 114 E.L. Walters, K. Morawski, I. Dorotta, et al. Implementation of a post-cardiac arrest care bundle including therapeutic hypothermia and hemodynamic optimization in comatose patients with return of spontaneous circulation after out-of-hospital cardiac arrest: a feasibility study. Shock. 2011;35:360-366
  • 115 A. Zeiner, G. Sunder-Plassmann, F. Sterz, et al. The effect of mild therapeutic hypothermia on renal function after cardiopulmonary resuscitation in men. Resuscitation. 2004;60:253-261
  • 116 C. Torgersen, J. Meichtry, C.A. Schmittinger, et al. Haemodynamic variables and functional outcome in hypothermic patients following out-of-hospital cardiac arrest. Resuscitation. 2013;84:798-804
  • 117 H. Post, J.D. Schmitto, P. Steendijk, et al. Cardiac function during mild hypothermia in pigs: increased inotropy at the expense of diastolic dysfunction. Acta Physiol (Oxf). 2010;199:43-52
  • 118 H. Staer-Jensen, K. Sunde, T.M. Olasveengen, et al. Bradycardia during therapeutic hypothermia is associated with good neurologic outcome in comatose survivors of out-of-hospital cardiac arrest. Crit Care Med. 2014;42:2401-2408
  • 119 J.H. Thomsen, C. Hassager, J. Bro-Jeppesen, et al. Sinus bradycardia during hypothermia in comatose survivors of out-of-hospital cardiac arrest – a new early marker of favorable outcome?. Resuscitation. 2015;89:36-42
  • 120 F. Pene, H. Hyvernat, V. Mallet, et al. Prognostic value of relative adrenal insufficiency after out-of-hospital cardiac arrest. Intensive Care Med. 2005;31:627-633
  • 121 G. Hekimian, T. Baugnon, M. Thuong, et al. Cortisol levels and adrenal reserve after successful cardiac arrest resuscitation. Shock. 2004;22:116-119
  • 122 S.D. Mentzelopoulos, S. Malachias, C. Chamos, et al. Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest: a randomized clinical trial. JAMA. 2013;310:270-279
  • 123 S.D. Mentzelopoulos, S.G. Zakynthinos, M. Tzoufi, et al. Vasopressin, epinephrine, and corticosteroids for in-hospital cardiac arrest. Arch Intern Med. 2009;169:15-24
  • 124 D.S. Lee, L.D. Green, P.P. Liu, et al. Effectiveness of implantable defibrillators for preventing arrhythmic events and death: a meta-analysis. J Am Coll Cardiol. 2003;41:1573-1582
  • 125 P.E. Vardas, A. Auricchio, J.J. Blanc, et al. Guidelines for cardiac pacing and cardiac resynchronization therapy: The Task Force for Cardiac Pacing and Cardiac Resynchronization Therapy of the European Society of Cardiology. Developed in collaboration with the European Heart Rhythm Association. Eur Heart J. 2007;28:2256-2295
  • 126 P.G. Steg, S.K. James, D. Atar, et al. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J. 2012;33:2569-2619
  • 127 R.M. John, U.B. Tedrow, B.A. Koplan, et al. Ventricular arrhythmias and sudden cardiac death. Lancet. 2012;380:1520-1529
  • 128 J. Soar, C.W. Callaway, M. Aibiki, et al. Part 4: advanced life support: 2015 International consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations. Resuscitation. 2015;95:e71-e122
  • 129 G. Buunk, J.G. van der Hoeven, A.E. Meinders. Cerebral blood flow after cardiac arrest. Neth J Med. 2000;57:106-112
  • 130 M.G. Angelos, K.R. Ward, J. Hobson, P.D. Beckley. Organ blood flow following cardiac arrest in a swine low-flow cardiopulmonary bypass model. Resuscitation. 1994;27:245-254
  • 131 M. Fischer, B.W. Bottiger, S. Popov-Cenic, K.A. Hossmann. Thrombolysis using plasminogen activator and heparin reduces cerebral no-reflow after resuscitation from cardiac arrest: an experimental study in the cat. Intensive Care Med. 1996;22:1214-1223
  • 132 T. Sakabe, A. Tateishi, Y. Miyauchi, et al. Intracranial pressure following cardiopulmonary resuscitation. Intensive Care Med. 1987;13:256-259
  • 133 Y. Morimoto, O. Kemmotsu, K. Kitami, I. Matsubara, I. Tedo. Acute brain swelling after out-of-hospital cardiac arrest: pathogenesis and outcome. Crit Care Med. 1993;21:104-110
  • 134 H. Nishizawa, I. Kudoh. Cerebral autoregulation is impaired in patients resuscitated after cardiac arrest. Acta Anaesthesiol Scand. 1996;40:1149-1153
  • 135 C. Sundgreen, F.S. Larsen, T.M. Herzog, G.M. Knudsen, S. Boesgaard, J. Aldershvile. Autoregulation of cerebral blood flow in patients resuscitated from cardiac arrest. Stroke. 2001;32:128-132
  • 136 K. Ameloot, C. Genbrugge, I. Meex, et al. An observational near-infrared spectroscopy study on cerebral autoregulation in post-cardiac arrest patients: time to drop ‘one-size-fits-all’ hemodynamic targets?. Resuscitation. 2015;90:121-126
  • 137 C. Chamorro, J.M. Borrallo, M.A. Romera, J.A. Silva, B. Balandin. Anesthesia and analgesia protocol during therapeutic hypothermia after cardiac arrest: a systematic review. Anesth Analg. 2010;110:1328-1335
  • 138 T.W. Bjelland, O. Dale, K. Kaisen, et al. Propofol and remifentanil versus midazolam and fentanyl for sedation during therapeutic hypothermia after cardiac arrest: a randomised trial. Intensive Care Med. 2012;38:959-967
  • 139 J. Hellstrom, A. Owall, C.R. Martling, P.V. Sackey. Inhaled isoflurane sedation during therapeutic hypothermia after cardiac arrest: a case series. Crit Care Med. 2014;42:e161-e166
  • 140 J. Knapp, G. Bergmann, T. Bruckner, N. Russ, B.W. Bottiger, E. Popp. Pre- and postconditioning effect of Sevoflurane on myocardial dysfunction after cardiopulmonary resuscitation in rats. Resuscitation. 2013;84:1450-1455
  • 141 E.W. Ely, B. Truman, A. Shintani, et al. Monitoring sedation status over time in ICU patients: reliability and validity of the Richmond Agitation-Sedation Scale (RASS). JAMA. 2003;289:2983-2991
  • 142 B. De Jonghe, D. Cook, C. Appere-De-Vecchi, G. Guyatt, M. Meade, H. Outin. Using and understanding sedation scoring systems: a systematic review. Intensive Care Med. 2000;26:275-285
  • 143 B.D. Snyder, W.A. Hauser, R.B. Loewenson, I.E. Leppik, M. Ramirez-Lassepas, R.J. Gumnit. Neurologic prognosis after cardiopulmonary arrest, III: seizure activity. Neurology. 1980;30:1292-1297
  • 144 A. Bouwes, D. van Poppelen, J.H. Koelman, et al. Acute posthypoxic myoclonus after cardiopulmonary resuscitation. BMC Neurol. 2012;12:63
  • 145 D.B. Seder, K. Sunde, S. Rubertsson, et al. Neurologic outcomes and postresuscitation care of patients with myoclonus following cardiac arrest. Crit Care Med. 2015;43:965-972
  • 146 S.R. Benbadis, S. Chen, M. Melo. What's shaking in the ICU? The differential diagnosis of seizures in the intensive care setting. Epilepsia. 2010;51:2338-2340
  • 147 J.N. Caviness, P. Brown. Myoclonus: current concepts and recent advances. Lancet Neurol. 2004;3:598-607
  • 148 L.J. Hirsch, S.M. LaRoche, N. Gaspard, et al. American Clinical Neurophysiology Society's standardized critical care EEG terminology: 2012 version. J Clin Neurophysiol. 2013;30:1-27
  • 149 R. Mani, S.E. Schmitt, M. Mazer, M.E. Putt, D.F. Gaieski. The frequency and timing of epileptiform activity on continuous electroencephalogram in comatose post-cardiac arrest syndrome patients treated with therapeutic hypothermia. Resuscitation. 2012;83:840-847
  • 150 S. Legriel, J. Hilly-Ginoux, M. Resche-Rigon, et al. Prognostic value of electrographic postanoxic status epilepticus in comatose cardiac-arrest survivors in the therapeutic hypothermia era. Resuscitation. 2013;84:343-350
  • 151 M. Ingvar. Cerebral blood flow and metabolic rate during seizures. Relationship to epileptic brain damage. Ann NY Acad Sci. 1986;462:194-206
  • 152 F. Thomke, S.L. Weilemann. Poor prognosis despite successful treatment of postanoxic generalized myoclonus. Neurology. 2010;74:1392-1394
  • 153 Randomized Clinical Study of Thiopental Loading in Comatose Survivors of Cardiac Arrest. Brain Resuscitation Clinical Trial I Study Group. N Engl J Med. 1986;314:397-403
  • 154 W.T. Longstreth Jr., C.E. Fahrenbruch, M. Olsufka, T.R. Walsh, M.K. Copass, L.A. Cobb. Randomized clinical trial of magnesium, diazepam, or both after out-of-hospital cardiac arrest. Neurology. 2002;59:506-514
  • 155 E. Amorim, J.C. Rittenberger, M.E. Baldwin, C.W. Callaway, A. Popescu, Post Cardiac Arrest Service. Malignant EEG patterns in cardiac arrest patients treated with targeted temperature management who survive to hospital discharge. Resuscitation. 2015;90:127-132
  • 156 E.A. Samaniego, M. Mlynash, A.F. Caulfield, I. Eyngorn, C.A. Wijman. Sedation confounds outcome prediction in cardiac arrest survivors treated with hypothermia. Neurocrit Care. 2011;15:113-119
  • 157 F. Daviaud, F. Dumas, N. Demars, et al. Blood glucose level and outcome after cardiac arrest: insights from a large registry in the hypothermia era. Intensive Care Med. 2014;40:855-862
  • 158 H. Losert, F. Sterz, R.O. Roine, et al. Strict normoglycaemic blood glucose levels in the therapeutic management of patients within 12 h after cardiac arrest might not be necessary. Resuscitation. 2007;76:214-220
  • 159 M.B. Skrifvars, K. Saarinen, K. Ikola, M. Kuisma. Improved survival after in-hospital cardiac arrest outside critical care areas. Acta Anaesthesiol Scand. 2005;49:1534-1539
  • 160 M. Mullner, F. Sterz, M. Binder, W. Schreiber, A. Deimel, A.N. Laggner. Blood glucose concentration after cardiopulmonary resuscitation influences functional neurological recovery in human cardiac arrest survivors. J Cereb Blood Flow Metab. 1997;17:430-436
  • 161 P.A. Calle, W.A. Buylaert, O.A. Vanhaute. Glycemia in the post-resuscitation period. The Cerebral Resuscitation Study Group. Resuscitation. 1989;17 Suppl:S181-188 discussion S99-206
  • 162 W.T. Longstreth Jr., P. Diehr, T.S. Inui. Prediction of awakening after out-of-hospital cardiac arrest. N Engl J Med. 1983;308:1378-1382
  • 163 W.T. Longstreth Jr., T.S. Inui. High blood glucose level on hospital admission and poor neurological recovery after cardiac arrest. Ann Neurol. 1984;15:59-63
  • 164 G. van den Berghe, P. Wouters, F. Weekers, et al. Intensive insulin therapy in the critically ill patients. N Engl J Med. 2001;345:1359-1367
  • 165 G. Van den Berghe, A. Wilmer, G. Hermans, et al. Intensive insulin therapy in the medical ICU. N Engl J Med. 2006;354:449-461
  • 166 T. Oksanen, M.B. Skrifvars, T. Varpula, et al. Strict versus moderate glucose control after resuscitation from ventricular fibrillation. Intensive Care Med. 2007;33:2093-2100
  • 167 S. Finfer, D.R. Chittock, S.Y. Su, et al. Intensive versus conventional glucose control in critically ill patients. N Engl J Med. 2009;360:1283-1297
  • 168 N.-S.S. Investigators, S. Finfer, B. Liu, et al. Hypoglycemia and risk of death in critically ill patients. N Engl J Med. 2012;367:1108-1118
  • 169 J.S. Krinsley, A. Grover. Severe hypoglycemia in critically ill patients: risk factors and outcomes. Crit Care Med. 2007;35:2262-2267
  • 170 G. Meyfroidt, D.M. Keenan, X. Wang, P.J. Wouters, J.D. Veldhuis, G. Van den Berghe. Dynamic characteristics of blood glucose time series during the course of critical illness: effects of intensive insulin therapy and relative association with mortality. Crit Care Med. 2010;38:1021-1029
  • 171 N. Cueni-Villoz, A. Devigili, F. Delodder, et al. Increased blood glucose variability during therapeutic hypothermia and outcome after cardiac arrest. Crit Care Med. 2011;39:2225-2231
  • 172 A. Padkin. Glucose control after cardiac arrest. Resuscitation. 2009;80:611-612
  • 173 M. Takino, Y. Okada. Hyperthermia following cardiopulmonary resuscitation. Intensive Care Med. 1991;17:419-420
  • 174 R.W. Hickey, P.M. Kochanek, H. Ferimer, H.L. Alexander, R.H. Garman, S.H. Graham. Induced hyperthermia exacerbates neurologic neuronal histologic damage after asphyxial cardiac arrest in rats. Crit Care Med. 2003;31:531-535
  • 175 A. Takasu, D. Saitoh, N. Kaneko, T. Sakamoto, Y. Okada. Hyperthermia: is it an ominous sign after cardiac arrest?. Resuscitation. 2001;49:273-277
  • 176 A. Zeiner, M. Holzer, F. Sterz, et al. Hyperthermia after cardiac arrest is associated with an unfavorable neurologic outcome. Arch Intern Med. 2001;161:2007-2012
  • 177 R.W. Hickey, P.M. Kochanek, H. Ferimer, S.H. Graham, P. Safar. Hypothermia and hyperthermia in children after resuscitation from cardiac arrest. Pediatrics. 2000;106:118-122
  • 178 M.N. Diringer, N.L. Reaven, S.E. Funk, G.C. Uman. Elevated body temperature independently contributes to increased length of stay in neurologic intensive care unit patients. Crit Care Med. 2004;32:1489-1495
  • 179 S.A. Winters, K.H. Wolf, S.A. Kettinger, E.K. Seif, J.S. Jones, T. Bacon-Baguley. Assessment of risk factors for post-rewarming “rebound hyperthermia” in cardiac arrest patients undergoing therapeutic hypothermia. Resuscitation. 2013;84:1245-1249
  • 180 J. Bro-Jeppesen, C. Hassager, M. Wanscher, et al. Post-hypothermia fever is associated with increased mortality after out-of-hospital cardiac arrest. Resuscitation. 2013;84:1734-1740
  • 181 M. Leary, A.V. Grossestreuer, S. Iannacone, et al. Pyrexia and neurologic outcomes after therapeutic hypothermia for cardiac arrest. Resuscitation. 2013;84:1056-1061
  • 182 J. Bro-Jeppesen, J. Kjaergaard, T.I. Horsted, et al. The impact of therapeutic hypothermia on neurological function and quality of life after cardiac arrest. Resuscitation. 2009;80:171-176
  • 183 A.J. Gunn, M. Thoresen. Hypothermic neuroprotection. NeuroRx. 2006;3:154-169
  • 184 M.T. Froehler, R.G. Geocadin. Hypothermia for neuroprotection after cardiac arrest: mechanisms, clinical trials and patient care. J Neurol Sci. 2007;261:118-126
  • 185 J.N. McCullough, N. Zhang, D.L. Reich, et al. Cerebral metabolic suppression during hypothermic circulatory arrest in humans. Ann Thorac Surg. 1999;67:1895-1899 discussion 919-21
  • 186 J. Bro-Jeppesen, J. Kjaergaard, M. Wanscher, et al. The inflammatory response after out-of-hospital cardiac arrest is not modified by targeted temperature management at 33 degrees C or 36 degrees C. Resuscitation. 2014;85:1480-1487
  • 187 Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002;346:549-556
  • 188 S.A. Bernard, T.W. Gray, M.D. Buist, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med. 2002;346:557-563
  • 189 F. Dumas, D. Grimaldi, B. Zuber, et al. Is hypothermia after cardiac arrest effective in both shockable and nonshockable patients?: insights from a large registry. Circulation. 2011;123:877-886
  • 190 C. Testori, F. Sterz, W. Behringer, et al. Mild therapeutic hypothermia is associated with favourable outcome in patients after cardiac arrest with non-shockable rhythms. Resuscitation. 2011;82:1162-1167
  • 191 J. Vaahersalo, P. Hiltunen, M. Tiainen, et al. Therapeutic hypothermia after out-of-hospital cardiac arrest in Finnish intensive care units: the FINNRESUSCI study. Intensive Care Med. 2013;39:826-837
  • 192 T.J. Mader, B.H. Nathanson, W.E. Soares 3rd, R.A. Coute, B.F. McNally. Comparative effectiveness of therapeutic hypothermia after out-of-hospital cardiac arrest: insight from a large data registry. Therap Hypothermia Temp Manage. 2014;4:21-31
  • 193 G. Nichol, E. Huszti, F. Kim, et al. Does induction of hypothermia improve outcomes after in-hospital cardiac arrest?. Resuscitation. 2013;84:620-625
  • 194 M. Annborn, J. Bro-Jeppesen, N. Nielsen, et al. The association of targeted temperature management at 33 and 36 degrees C with outcome in patients with moderate shock on admission after out-of-hospital cardiac arrest: a post hoc analysis of the Target Temperature Management trial. Intensive Care Med. 2014;40:1210-1219
  • 195 H. Yokoyama, K. Nagao, M. Hase, et al. Impact of therapeutic hypothermia in the treatment of patients with out-of-hospital cardiac arrest from the J-PULSE-HYPO study registry. Circ J. 2011;75:1063-1070
  • 196 B.K. Lee, S.J. Lee, K.W. Jeung, H.Y. Lee, T. Heo, Y.I. Min. Outcome and adverse events with 72-hour cooling at 32 degrees C as compared to 24-hour cooling at 33 degrees C in comatose asphyxial arrest survivors. Am J Emerg Med. 2014;32:297-301
  • 197 N. Nielsen, H. Friberg. Temperature management after cardiac arrest. Curr Opin Crit Care. 2015;21:202-208
  • 198 J.P. Nolan, P.T. Morley, T.L. Vanden Hoek, R.W. Hickey. Therapeutic hypothermia after cardiac arrest. An advisory statement by the Advancement Life support Task Force of the International Liaison committee on Resuscitation. Resuscitation. 2003;57:231-235
  • 199 K. Kuboyama, P. Safar, A. Radovsky, et al. Delay in cooling negates the beneficial effect of mild resuscitative cerebral hypothermia after cardiac arrest in dogs: a prospective, randomized study. Crit Care Med. 1993;21:1348-1358
  • 200 F. Colbourne, D. Corbett. Delayed postischemic hypothermia: a six month survival study using behavioral and histological assessments of neuroprotection. J Neurosci. 1995;15:7250-7260
  • 201 M. Haugk, C. Testori, F. Sterz, et al. Relationship between time to target temperature and outcome in patients treated with therapeutic hypothermia after cardiac arrest. Crit Care. 2011;15:R101
  • 202 J. Benz-Woerner, F. Delodder, R. Benz, et al. Body temperature regulation and outcome after cardiac arrest and therapeutic hypothermia. Resuscitation. 2012;83:338-342
  • 203 S.M. Perman, J.H. Ellenberg, A.V. Grossestreuer, et al. Shorter time to target temperature is associated with poor neurologic outcome in post-arrest patients treated with targeted temperature management. Resuscitation. 2015;88:114-119
  • 204 F. Kim, M. Olsufka, W.T. Longstreth Jr., et al. Pilot randomized clinical trial of prehospital induction of mild hypothermia in out-of-hospital cardiac arrest patients with a rapid infusion of 4 degrees C normal saline. Circulation. 2007;115:3064-3070
  • 205 A. Kamarainen, I. Virkkunen, J. Tenhunen, A. Yli-Hankala, T. Silfvast. Prehospital therapeutic hypothermia for comatose survivors of cardiac arrest: a randomized controlled trial. Acta Anaesthesiol Scand. 2009;53:900-907
  • 206 S.A. Bernard, K. Smith, P. Cameron, et al. Induction of therapeutic hypothermia by paramedics after resuscitation from out-of-hospital ventricular fibrillation cardiac arrest: a randomized controlled trial. Circulation. 2010;122:737-742
  • 207 F. Kim, G. Nichol, C. Maynard, et al. Effect of prehospital induction of mild hypothermia on survival and neurological status among adults with cardiac arrest: a randomized clinical trial. JAMA. 2014;311:45-52
  • 208 G. Debaty, M. Maignan, D. Savary, et al. Impact of intra-arrest therapeutic hypothermia in outcomes of prehospital cardiac arrest: a randomized controlled trial. Intensive Care Med. 2014;40:1832-1842
  • 209 M. Castren, P. Nordberg, L. Svensson, et al. Intra-arrest transnasal evaporative cooling: a randomized, prehospital, multicenter study (PRINCE: Pre-ROSC IntraNasal Cooling Effectiveness). Circulation. 2010;122:729-736
  • 210 K.H. Polderman, I. Herold. Therapeutic hypothermia and controlled normothermia in the intensive care unit: practical considerations, side effects, and cooling methods. Crit Care Med. 2009;37:1101-1120
  • 211 S.A. Bernard, K. Smith, P. Cameron, et al. Induction of prehospital therapeutic hypothermia after resuscitation from nonventricular fibrillation cardiac arrest. Crit Care Med. 2012;40:747-753
  • 212 S.A. Bernard, B.M. Jones, M.K. Horne. Clinical trial of induced hypothermia in comatose survivors of out-of-hospital cardiac arrest. Ann Emerg Med. 1997;30:146-153
  • 213 M. Busch, E. Soreide, H.M. Lossius, K. Lexow, K. Dickstein. Rapid implementation of therapeutic hypothermia in comatose out-of-hospital cardiac arrest survivors. Acta Anaesthesiol Scand. 2006;50:1277-1283
  • 214 G. Belliard, E. Catez, C. Charron, et al. Efficacy of therapeutic hypothermia after out-of-hospital cardiac arrest due to ventricular fibrillation. Resuscitation. 2007;75:252-259
  • 215 J. Aberle, S. Kluge, J. Prohl, et al. Hypothermia after CPR through conduction and convection – initial experience on an ICU. Intensivmed Notfallmed. 2006;43:37-43
  • 216 A. Feuchtl, et al. Endovascular cooling improves neurological short-term outcome after prehospital cardiac arrest. Intensivmed. 2007;44:37-42
  • 217 M. Fries, C. Stoppe, D. Brucken, R. Rossaint, R. Kuhlen. Influence of mild therapeutic hypothermia on the inflammatory response after successful resuscitation from cardiac arrest. J Crit Care. 2009;24:453-457
  • 218 I.M. Larsson, E. Wallin, S. Rubertsson. Cold saline infusion and ice packs alone are effective in inducing and maintaining therapeutic hypothermia after cardiac arrest. Resuscitation. 2010;81:15-19
  • 219 R. Skulec, T. Kovarnik, G. Dostalova, J. Kolar, A. Linhart. Induction of mild hypothermia in cardiac arrest survivors presenting with cardiogenic shock syndrome. Acta Anaesthesiol Scand. 2008;52:188-194
  • 220 A. Kliegel, A. Janata, C. Wandaller, et al. Cold infusions alone are effective for induction of therapeutic hypothermia but do not keep patients cool after cardiac arrest. Resuscitation. 2007;73:46-53
  • 221 D.W. Benson, G.R. Williams Jr., F.C. Spencer, A.J. Yates. The use of hypothermia after cardiac arrest. Anesth Analg. 1959;38:423-428
  • 222 Y. Yanagawa, S. Ishihara, H. Norio, et al. Preliminary clinical outcome study of mild resuscitative hypothermia after out-of-hospital cardiopulmonary arrest. Resuscitation. 1998;39:61-66
  • 223 M.S. Damian, D. Ellenberg, R. Gildemeister, et al. Coenzyme Q10 combined with mild hypothermia after cardiac arrest: a preliminary study. Circulation. 2004;110:3011-3016
  • 224 A.W. Hay, D.G. Swann, K. Bell, T.S. Walsh, B. Cook. Therapeutic hypothermia in comatose patients after out-of-hospital cardiac arrest. Anaesthesia. 2008;63:15-19
  • 225 A. Zeiner, M. Holzer, F. Sterz, et al. Mild resuscitative hypothermia to improve neurological outcome after cardiac arrest. A clinical feasibility trial. Hypothermia After Cardiac Arrest (HACA) Study Group. Stroke. 2000;31:86-94
  • 226 C.W. Hoedemaekers, M. Ezzahti, A. Gerritsen, J.G. van der Hoeven. Comparison of cooling methods to induce and maintain normo- and hypothermia in intensive care unit patients: a prospective intervention study. Crit Care. 2007;11:R91
  • 227 T. Uray, R. Malzer. Out-of-hospital surface cooling to induce mild hypothermia in human cardiac arrest: a feasibility trial. Resuscitation. 2008;77:331-338
  • 228 J. Arrich. Clinical application of mild therapeutic hypothermia after cardiac arrest. Crit Care Med. 2007;35:1041-1047
  • 229 S. Castrejon, M. Cortes, M.L. Salto, et al. Improved prognosis after using mild hypothermia to treat cardiorespiratory arrest due to a cardiac cause: comparison with a control group. Rev Esp Cardiol. 2009;62:733-741
  • 230 C.W. Don, W.T. Longstreth Jr., C. Maynard, et al. Active surface cooling protocol to induce mild therapeutic hypothermia after out-of-hospital cardiac arrest: a retrospective before-and-after comparison in a single hospital. Crit Care Med. 2009;37:3062-3069
  • 231 R.A. Felberg, D.W. Krieger, R. Chuang, et al. Hypothermia after cardiac arrest: feasibility and safety of an external cooling protocol. Circulation. 2001;104:1799-1804
  • 232 A.C. Flint, J.C. Hemphill, D.C. Bonovich. Therapeutic hypothermia after cardiac arrest: performance characteristics and safety of surface cooling with or without endovascular cooling. Neurocrit Care. 2007;7:109-118
  • 233 K.J. Heard, M.A. Peberdy, M.R. Sayre, et al. A randomized controlled trial comparing the Arctic Sun to standard cooling for induction of hypothermia after cardiac arrest. Resuscitation. 2010;81:9-14
  • 234 R.M. Merchant, B.S. Abella, M.A. Peberdy, et al. Therapeutic hypothermia after cardiac arrest: unintentional overcooling is common using ice packs and conventional cooling blankets. Crit Care Med. 2006;34:S490-S494
  • 235 M. Haugk, F. Sterz, M. Grassberger, et al. Feasibility and efficacy of a new non-invasive surface cooling device in post-resuscitation intensive care medicine. Resuscitation. 2007;75:76-81
  • 236 J.H. Kilgannon, B.W. Roberts, M. Stauss, et al. Use of a standardized order set for achieving target temperature in the implementation of therapeutic hypothermia after cardiac arrest: a feasibility study. Acad Emerg Med. 2008;15:499-505 official journal of the Society for Academic Emergency Medicine
  • 237 B.D. Scott, T. Hogue, M.S. Fixley, P.B. Adamson. Induced hypothermia following out-of-hospital cardiac arrest: initial experience in a community hospital. Clin Cardiol. 2006;29:525-529
  • 238 C. Storm, I. Steffen, J.C. Schefold, et al. Mild therapeutic hypothermia shortens intensive care unit stay of survivors after out-of-hospital cardiac arrest compared to historical controls. Crit Care. 2008;12:R78
  • 239 P. Nordberg, F.S. Taccone, M. Castren, et al. Design of the PRINCESS trial: pre-hospital resuscitation intra-nasal cooling effectiveness survival study (PRINCESS). BMC Emerg Med. 2013;13:21
  • 240 F.M. Al-Senani, C. Graffagnino, J.C. Grotta, et al. A prospective, multicenter pilot study to evaluate the feasibility and safety of using the CoolGard System and Icy catheter following cardiac arrest. Resuscitation. 2004;62:143-150
  • 241 M. Holzer, M. Mullner, F. Sterz, et al. Efficacy and safety of endovascular cooling after cardiac arrest: cohort study and Bayesian approach. Stroke. 2006;37:1792-1797
  • 242 A. Kliegel, H. Losert, F. Sterz, et al. Cold simple intravenous infusions preceding special endovascular cooling for faster induction of mild hypothermia after cardiac arrest – a feasibility study. Resuscitation. 2005;64:347-351
  • 243 N. Pichon, J.B. Amiel, B. Francois, A. Dugard, C. Etchecopar, P. Vignon. Efficacy of and tolerance to mild induced hypothermia after out-of-hospital cardiac arrest using an endovascular cooling system. Crit Care. 2007;11:R71
  • 244 A.O. Spiel, A. Kliegel, A. Janata, et al. Hemostasis in cardiac arrest patients treated with mild hypothermia initiated by cold fluids. Resuscitation. 2009;80:762-765
  • 245 B. Wolff, K. Machill, D. Schumacher, I. Schulzki, D. Werner. Early achievement of mild therapeutic hypothermia and the neurologic outcome after cardiac arrest. Int J Cardiol. 2009;133:223-228
  • 246 K. Nagao, K. Kikushima, K. Watanabe, et al. Early induction of hypothermia during cardiac arrest improves neurological outcomes in patients with out-of-hospital cardiac arrest who undergo emergency cardiopulmonary bypass and percutaneous coronary intervention. Circ J. 2010;74:77-85
  • 247 D. Stub, S. Bernard, V. Pellegrino, et al. Refractory cardiac arrest treated with mechanical CPR, hypothermia, ECMO and early reperfusion (the CHEER trial). Resuscitation. 2015;86:88-94
  • 248 M.A. Mahmood, R.M. Zweifler. Progress in shivering control. J Neurol Sci. 2007;261:47-54
  • 249 A. Wadhwa, P. Sengupta, J. Durrani, et al. Magnesium sulphate only slightly reduces the shivering threshold in humans. Br J Anaesth. 2005;94:756-762
  • 250 M.A. Gillies, R. Pratt, C. Whiteley, J. Borg, R.J. Beale, S.M. Tibby. Therapeutic hypothermia after cardiac arrest: a retrospective comparison of surface and endovascular cooling techniques. Resuscitation. 2010;81:1117-1122
  • 251 P. Knapik, W. Rychlik, D. Duda, R. Golyszny, D. Borowik, D. Ciesla. Relationship between blood, nasopharyngeal and urinary bladder temperature during intravascular cooling for therapeutic hypothermia after cardiac arrest. Resuscitation. 2012;83:208-212
  • 252 J. Shin, J. Kim, K. Song, Y. Kwak. Core temperature measurement in therapeutic hypothermia according to different phases: comparison of bladder, rectal, and tympanic versus pulmonary artery methods. Resuscitation. 2013;84:810-817
  • 253 O. Tomte, T. Draegni, A. Mangschau, D. Jacobsen, B. Auestad, K. Sunde. A comparison of intravascular and surface cooling techniques in comatose cardiac arrest survivors. Crit Care Med. 2011;39:443-449
  • 254 S.U. Nair, J.B. Lundbye. The occurrence of shivering in cardiac arrest survivors undergoing therapeutic hypothermia is associated with a good neurologic outcome. Resuscitation. 2013;84:626-629
  • 255 K.H. Polderman, S.M. Peerdeman, A.R. Girbes. Hypophosphatemia and hypomagnesemia induced by cooling in patients with severe head injury. J Neurosurg. 2001;94:697-705
  • 256 A.C. Brinkman, B.L. Ten Tusscher, M.C. de Waard, F.R. de Man, A.R. Girbes, A. Beishuizen. Minimal effects on ex vivo coagulation during mild therapeutic hypothermia in post cardiac arrest patients. Resuscitation. 2014;85:1359-1363
  • 257 S. Perbet, N. Mongardon, F. Dumas, et al. Early-onset pneumonia after cardiac arrest: characteristics, risk factors and influence on prognosis. Am J Respir Crit Care Med. 2011;184:1048-1054
  • 258 N. Mongardon, S. Perbet, V. Lemiale, et al. Infectious complications in out-of-hospital cardiac arrest patients in the therapeutic hypothermia era. Crit Care Med. 2011;39:1359-1364
  • 259 D.J. Gagnon, N. Nielsen, G.L. Fraser, et al. Prophylactic antibiotics are associated with a lower incidence of pneumonia in cardiac arrest survivors treated with targeted temperature management. Resuscitation. 2015;92:154-159
  • 260 K.J. Davies, J.H. Walters, I.M. Kerslake, R. Greenwood, M.J. Thomas. Early antibiotics improve survival following out-of hospital cardiac arrest. Resuscitation. 2013;84:616-619
  • 261 M.A. Tortorici, P.M. Kochanek, S.M. Poloyac. Effects of hypothermia on drug disposition, metabolism, and response: a focus of hypothermia-mediated alterations on the cytochrome P450 enzyme system. Crit Care Med. 2007;35:2196-2204
  • 262 S. Schmidt-Schweda, A. Ohler, H. Post, B. Pieske. Moderate hypothermia for severe cardiogenic shock (COOL Shock Study I & II). Resuscitation. 2013;84:319-325
  • 263 C. Zobel, C. Adler, A. Kranz, et al. Mild therapeutic hypothermia in cardiogenic shock syndrome. Crit Care Med. 2012;40:1715-1723
  • 264 C. Jacobshagen, T. Pelster, A. Pax, et al. Effects of mild hypothermia on hemodynamics in cardiac arrest survivors and isolated failing human myocardium. Clin Res Cardiol. 2010;99:267-276
  • 265 S.T. Grafton, W.T. Longstreth Jr. Steroids after cardiac arrest: a retrospective study with concurrent, nonrandomized controls. Neurology. 1988;38:1315-1316
  • 266 P.Y. Gueugniaud, P. Gaussorgues, F. Garcia-Darennes, et al. Early effects of nimodipine on intracranial and cerebral perfusion pressures in cerebral anoxia after out-of-hospital cardiac arrest. Resuscitation. 1990;20:203-212
  • 267 R.O. Roine, M. Kaste, A. Kinnunen, P. Nikki, S. Sarna, S. Kajaste. Nimodipine after resuscitation from out-of-hospital ventricular fibrillation: a placebo-controlled, double-blind, randomized trial. JAMA. 1990;264:3171-3177
  • 268 Brain Resuscitation Clinical Trial II Study Group. A randomized clinical study of a calcium-entry blocker (lidoflazine) in the treatment of comatose survivors of cardiac arrest. N Engl J Med. 1991;324:1225-1231
  • 269 O.J. Arola, R.M. Laitio, R.O. Roine, et al. Feasibility and cardiac safety of inhaled xenon in combination with therapeutic hypothermia following out-of-hospital cardiac arrest. Crit Care Med. 2013;41:2116-2124
  • 270 C. Sandroni, A. Cariou, F. Cavallaro, et al. Prognostication in comatose survivors of cardiac arrest: an advisory statement from the European Resuscitation Council and the European Society of Intensive Care Medicine. Resuscitation. 2014;85:1779-1789
  • 271 I.G. Stiell, G. Nichol, B.G. Leroux, et al. Early versus later rhythm analysis in patients with out-of-hospital cardiac arrest. N Engl J Med. 2011;365:787-797
  • 272 C. Sandroni, F. Cavallaro, C.W. Callaway, et al. Predictors of poor neurological outcome in adult comatose survivors of cardiac arrest: a systematic review and meta-analysis. Part 2: patients treated with therapeutic hypothermia. Resuscitation. 2013;84:1324-1338
  • 273 C. Sandroni, F. Cavallaro, C.W. Callaway, et al. Predictors of poor neurological outcome in adult comatose survivors of cardiac arrest: a systematic review and meta-analysis. Part 1: patients not treated with therapeutic hypothermia. Resuscitation. 2013;84:1310-1323
  • 274 R.G. Geocadin, M.A. Peberdy, R.M. Lazar. Poor survival after cardiac arrest resuscitation: a self-fulfilling prophecy or biologic destiny?. Crit Care Med. 2012;40:979-980
  • 275 G. Bertini, M. Margheri, C. Giglioli, et al. Prognostic significance of early clinical manifestations in postanoxic coma: a retrospective study of 58 patients resuscitated after prehospital cardiac arrest. Crit Care Med. 1989;17:627-633
  • 276 E.G. Zandbergen, A. Hijdra, J.H. Koelman, et al. Prediction of poor outcome within the first 3 days of postanoxic coma. Neurology. 2006;66:62-68
  • 277 L.L. Bisschops, N. van Alfen, S. Bons, J.G. van der Hoeven, C.W. Hoedemaekers. Predictors of poor neurologic outcome in patients after cardiac arrest treated with hypothermia: a retrospective study. Resuscitation. 2011;82:696-701
  • 278 A. Bouwes, J.M. Binnekade, D.F. Zandstra, et al. Somatosensory evoked potentials during mild hypothermia after cardiopulmonary resuscitation. Neurology. 2009;73:1457-1461
  • 279 A. Bouwes, J.M. Binnekade, M.A. Kuiper, et al. Prognosis of coma after therapeutic hypothermia: a prospective cohort study. Ann Neurol. 2012;71:206-212
  • 280 J.E. Fugate, E.F. Wijdicks, J. Mandrekar, et al. Predictors of neurologic outcome in hypothermia after cardiac arrest. Ann Neurol. 2010;68:907-914
  • 281 S.P. Choi, C.S. Youn, K.N. Park, et al. Therapeutic hypothermia in adult cardiac arrest because of drowning. Acta Anaesthesiol Scand. 2012;56:116-123
  • 282 O.B. Wu, L.M. Lima, F.O. Vangel, M.G. Furie, K.L.D.M. Greer. Predicting clinical outcome in comatose cardiac arrest patients using early noncontrast computed tomography. Stroke. 2011;42:985-992
  • 283 D.M. Greer, J. Yang, P.D. Scripko, et al. Clinical examination for prognostication in comatose cardiac arrest patients. Resuscitation. 2013;84:1546-1551
  • 284 I. Dragancea, J. Horn, M. Kuiper, et al. Neurological prognostication after cardiac arrest and targeted temperature management 33 degrees C versus 36 degrees C: results from a randomised controlled clinical trial. Resuscitation. 2015;93:164-170
  • 285 M.A. Topcuoglu, K.K. Oguz, G. Buyukserbetci, E. Bulut. Prognostic value of magnetic resonance imaging in post-resuscitation encephalopathy. Int Med. 2009;48:1635-1645
  • 286 A.O. Rossetti, M. Oddo, G. Logroscino, P.W. Kaplan. Prognostication after cardiac arrest and hypothermia: a prospective study. Ann Neurol. 2010;67:301-307
  • 287 A.O. Rossetti, L.A. Urbano, F. Delodder, P.W. Kaplan, M. Oddo. Prognostic value of continuous EEG monitoring during therapeutic hypothermia after cardiac arrest. Crit Care. 2010;14:R173
  • 288 A.O. Rossetti, E. Carrera, M. Oddo. Early EEG correlates of neuronal injury after brain anoxia. Neurology. 2012;78:796-802
  • 289 A. Krumholz, B.J. Stern, H.D. Weiss. Outcome from coma after cardiopulmonary resuscitation: relation to seizures and myoclonus. Neurology. 1988;38:401-405
  • 290 E.F. Wijdicks, G.B. Young. Myoclonus status in comatose patients after cardiac arrest. Lancet. 1994;343:1642-1643
  • 291 J.C. Rittenberger, A. Popescu, R.P. Brenner, F.X. Guyette, C.W. Callaway. Frequency and timing of nonconvulsive status epilepticus in comatose post-cardiac arrest subjects treated with hypothermia. Neurocrit Care. 2012;16:114-122
  • 292 J. Accardo, D. De Lisi, P. Lazzerini, A. Primavera. Good functional outcome after prolonged postanoxic comatose myoclonic status epilepticus in a patient who had undergone bone marrow transplantation. Case Rep Neurol Med. 2013;2013:8721-8727
  • 293 E.P. Arnoldus, G.J. Lammers. Postanoxic coma: good recovery despite myoclonus status. Ann Neurol. 1995;38:697-698
  • 294 S. Datta, G.K. Hart, H. Opdam, G. Gutteridge, J. Archer. Post-hypoxic myoclonic status: the prognosis is not always hopeless. Crit Care Resusc. 2009;11:39-41
  • 295 W.A. English, N.J. Giffin, J.P. Nolan. Myoclonus after cardiac arrest: pitfalls in diagnosis and prognosis. Anaesthesia. 2009;64:908-911
  • 296 W.C. Goh, P.D. Heath, S.J. Ellis, P.A. Oakley. Neurological outcome prediction in a cardiorespiratory arrest survivor. Br J Anaesth. 2002;88:719-722
  • 297 H.R. Morris, R.S. Howard, P. Brown. Early myoclonic status and outcome after cardiorespiratory arrest. J Neurol Neurosurg Psychiatry. 1998;64:267-268
  • 298 D.M. Greer. Unexpected good recovery in a comatose post-cardiac arrest patient with poor prognostic features. Resuscitation. 2013;84:e81-e82
  • 299 J.M. Lucas, M.N. Cocchi, J. Salciccioli, et al. Neurologic recovery after therapeutic hypothermia in patients with post-cardiac arrest myoclonus. Resuscitation. 2012;83:265-269
  • 300 T. Stelzl, M.J. von Bose, B. Hogl, H.H. Fuchs, K.A. Flugel. A comparison of the prognostic value of neuron-specific enolase serum levels and somatosensory evoked potentials in 13 reanimated patients. Eur J Emerg Med. 1995;2:24-27
  • 301 M. Tiainen, T.T. Kovala, O.S. Takkunen, R.O. Roine. Somatosensory and brainstem auditory evoked potentials in cardiac arrest patients treated with hypothermia. Crit Care Med. 2005;33:1736-1740
  • 302 V.C. Zingler, B. Krumm, T. Bertsch, K. Fassbender, B. Pohlmann-Eden. Early prediction of neurological outcome after cardiopulmonary resuscitation: a multimodal approach combining neurobiochemical and electrophysiological investigations may provide high prognostic certainty in patients after cardiac arrest. Eur Neurol. 2003;49:79-84
  • 303 T.L. Rothstein. The role of evoked potentials in anoxic–ischemic coma and severe brain trauma. J Clin Neurophysiol. 2000;17:486-497
  • 304 P. Zanatta, S. Messerotti Benvenuti, F. Baldanzi, E. Bosco. Pain-related middle-latency somatosensory evoked potentials in the prognosis of post anoxic coma: a preliminary report. Minerva Anestesiol. 2012;78:749-756
  • 305 G.B. Young, G. Doig, A. Ragazzoni. Anoxic–ischemic encephalopathy: clinical and electrophysiological associations with outcome. Neurocrit Care. 2005;2:159-164
  • 306 M.C. Cloostermans, F.B. van Meulen, C.J. Eertman, H.W. Hom, M.J. van Putten. Continuous electroencephalography monitoring for early prediction of neurological outcome in postanoxic patients after cardiac arrest: a prospective cohort study. Crit Care Med. 2012;40:2867-2875
  • 307 E.G. Zandbergen, A. Hijdra, R.J. de Haan, et al. Interobserver variation in the interpretation of SSEPs in anoxic–ischaemic coma. Clin Neurophysiol. 2006;117:1529-1535
  • 308 R. Pfeifer, S. Weitzel, A. Gunther, et al. Investigation of the inter-observer variability effect on the prognostic value of somatosensory evoked potentials of the median nerve (SSEP) in cardiac arrest survivors using an SSEP classification. Resuscitation. 2013;84:1375-1381
  • 309 R.G. Geocadin, M.M. Buitrago, M.T. Torbey, N. Chandra-Strobos, M.A. Williams, P.W. Kaplan. Neurologic prognosis and withdrawal of life support after resuscitation from cardiac arrest. Neurology. 2006;67:105-108
  • 310 A.Z. Crepeau, A.A. Rabinstein, J.E. Fugate, et al. Continuous EEG in therapeutic hypothermia after cardiac arrest: prognostic and clinical value. Neurology. 2013;80:339-344
  • 311 M. Oddo, A.O. Rossetti. Early multimodal outcome prediction after cardiac arrest in patients treated with hypothermia. Crit Care Med. 2014;42:1340-1347
  • 312 E. Westhall, I. Rosen, A.O. Rossetti, et al. Interrater variability of EEG interpretation in comatose cardiac arrest patients. Clin Neurophysiol. 2015;
  • 313 J.E. Wennervirta, M.J. Ermes, S.M. Tiainen, et al. Hypothermia-treated cardiac arrest patients with good neurological outcome differ early in quantitative variables of EEG suppression and epileptiform activity. Crit Care Med. 2009;37:2427-2435
  • 314 A.O. Rossetti, M. Oddo, L. Liaudet, P.W. Kaplan. Predictors of awakening from postanoxic status epilepticus after therapeutic hypothermia. Neurology. 2009;72:744-749
  • 315 M. Kawai, U. Thapalia, A. Verma. Outcome from therapeutic hypothermia and EEG. J Clin Neurophysiol. 2011;28:483-488
  • 316 S.H. Oh, K.N. Park, Y.M. Kim, et al. The prognostic value of continuous amplitude-integrated electroencephalogram applied immediately after return of spontaneous circulation in therapeutic hypothermia-treated cardiac arrest patients. Resuscitation. 2012;84:200-205
  • 317 J. Hofmeijer, M.C. Tjepkema-Cloostermans, M.J. van Putten. Burst-suppression with identical bursts: a distinct EEG pattern with poor outcome in postanoxic coma. Clin Neurophysiol. 2014;125:947-954
  • 318 J. Claassen, F.S. Taccone, P. Horn, M. Holtkamp, N. Stocchetti, M. Oddo. Recommendations on the use of EEG monitoring in critically ill patients: consensus statement from the neurointensive care section of the ESICM. Intensive Care Med. 2013;39:1337-1351
  • 319 B.W. Bottiger, S. Mobes, R. Glatzer, et al. Astroglial protein S-100 is an early and sensitive marker of hypoxic brain damage and outcome after cardiac arrest in humans. Circulation. 2001;103:2694-2698
  • 320 H. Rosen, K.S. Sunnerhagen, J. Herlitz, C. Blomstrand, L. Rosengren. Serum levels of the brain-derived proteins S-100 and NSE predict long-term outcome after cardiac arrest. Resuscitation. 2001;49:183-191
  • 321 I.G. Steffen, D. Hasper, C.J. Ploner, et al. Mild therapeutic hypothermia alters neuron specific enolase as an outcome predictor after resuscitation: 97 prospective hypothermia patients compared to 133 historical non-hypothermia patients. Crit Care. 2010;14:R69
  • 322 J. Kim, B.S. Choi, K. Kim, et al. Prognostic performance of diffusion-weighted MRI combined with NSE in comatose cardiac arrest survivors treated with mild hypothermia. Neurocrit Care. 2012;17:412-420
  • 323 T. Oksanen, M. Tiainen, M.B. Skrifvars, et al. Predictive power of serum NSE and OHCA score regarding 6-month neurologic outcome after out-of-hospital ventricular fibrillation and therapeutic hypothermia. Resuscitation. 2009;80:165-170
  • 324 M. Rundgren, T. Karlsson, N. Nielsen, T. Cronberg, P. Johnsson, H. Friberg. Neuron specific enolase and S-100B as predictors of outcome after cardiac arrest and induced hypothermia. Resuscitation. 2009;80:784-789
  • 325 B.K. Lee, K.W. Jeung, H.Y. Lee, Y.H. Jung, D.H. Lee. Combining brain computed tomography and serum neuron specific enolase improves the prognostic performance compared to either alone in comatose cardiac arrest survivors treated with therapeutic hypothermia. Resuscitation. 2013;84:1387-1392
  • 326 T. Zellner, R. Gartner, J. Schopohl, M. Angstwurm. NSE and S-100B are not sufficiently predictive of neurologic outcome after therapeutic hypothermia for cardiac arrest. Resuscitation. 2013;84:1382-1386
  • 327 C. Storm, J. Nee, A. Jorres, C. Leithner, D. Hasper, C.J. Ploner. Serial measurement of neuron specific enolase improves prognostication in cardiac arrest patients treated with hypothermia: a prospective study. Scand J Trauma Resusc Emerg Med. 2012;20:6
  • 328 M. Tiainen, R.O. Roine, V. Pettila, O. Takkunen. Serum neuron-specific enolase and S-100B protein in cardiac arrest patients treated with hypothermia. Stroke. 2003;34:2881-2886
  • 329 T. Cronberg, M. Rundgren, E. Westhall, et al. Neuron-specific enolase correlates with other prognostic markers after cardiac arrest. Neurology. 2011;77:623-630
  • 330 S.M. Bloomfield, J. McKinney, L. Smith, J. Brisman. Reliability of S100B in predicting severity of central nervous system injury. Neurocrit Care. 2007;6:121-138
  • 331 P. Stern, V. Bartos, J. Uhrova, et al. Performance characteristics of seven neuron-specific enolase assays. Tumour Biol. 2007;28:84-92
  • 332 M. Rundgren, T. Cronberg, H. Friberg, A. Isaksson. Serum neuron specific enolase – impact of storage and measuring method. BMC Res Notes. 2014;7:726
  • 333 P. Johnsson, S. Blomquist, C. Luhrs, et al. Neuron-specific enolase increases in plasma during and immediately after extracorporeal circulation. Ann Thorac Surg. 2000;69:750-754
  • 334 M. Huntgeburth, C. Adler, S. Rosenkranz, et al. Changes in neuron-specific enolase are more suitable than its absolute serum levels for the prediction of neurologic outcome in hypothermia-treated patients with out-of-hospital cardiac arrest. Neurocrit Care. 2014;20:358-366
  • 335 P. Stammet, O. Collignon, C. Hassager, et al. Neuron-specific enolase as a predictor of death or poor neurological outcome after out-of-hospital cardiac arrest and targeted temperature management at 33 degrees C and 36 degrees C. J Am Coll Cardiol. 2015;65:2104-2114
  • 336 S.H. Kim, S.P. Choi, K.N. Park, C.S. Youn, S.H. Oh, S.M. Choi. Early brain computed tomography findings are associated with outcome in patients treated with therapeutic hypothermia after out-of-hospital cardiac arrest. Scand J Trauma Resusc Emerg Med. 2013;21:57
  • 337 T. Els, J. Kassubek, R. Kubalek, J. Klisch. Diffusion-weighted MRI during early global cerebral hypoxia: a predictor for clinical outcome?. Acta Neurol Scand. 2004;110:361-367
  • 338 M. Mlynash, D.M. Campbell, E.M. Leproust, et al. Temporal and spatial profile of brain diffusion-weighted MRI after cardiac arrest. Stroke. 2010;41:1665-1672
  • 339 E.F. Wijdicks, N.G. Campeau, G.M. Miller. MR imaging in comatose survivors of cardiac resuscitation. AJNR Am J Neuroradiol. 2001;22:1561-1565
  • 340 O. Wu, A.G. Sorensen, T. Benner, A.B. Singhal, K.L. Furie, D.M. Greer. Comatose patients with cardiac arrest: predicting clinical outcome with diffusion-weighted MR imaging. Radiology. 2009;252:173-181
  • 341 C.A. Wijman, M. Mlynash, A.F. Caulfield, et al. Prognostic value of brain diffusion-weighted imaging after cardiac arrest. Ann Neurol. 2009;65:394-402
  • 342 S.P. Choi, K.N. Park, H.K. Park, et al. Diffusion-weighted magnetic resonance imaging for predicting the clinical outcome of comatose survivors after cardiac arrest: a cohort study. Crit Care. 2010;14:R17
  • 343 J. Kim, K. Kim, S. Hong, et al. Low apparent diffusion coefficient cluster-based analysis of diffusion-weighted MRI for prognostication of out-of-hospital cardiac arrest survivors. Resuscitation. 2013;84:1393-1399
  • 344 T. Sharshar, G. Citerio, P.J. Andrews, et al. Neurological examination of critically ill patients: a pragmatic approach. Report of an ESICM expert panel. Intensive Care Med. 2014;40:484-495
  • 345 E.O. Jorgensen, S. Holm. The natural course of neurological recovery following cardiopulmonary resuscitation. Resuscitation. 1998;36:111-122
  • 346 T. Cronberg, M. Brizzi, L.J. Liedholm, et al. Neurological prognostication after cardiac arrest – recommendations from the Swedish Resuscitation Council. Resuscitation. 2013;84:867-872
  • 347 F.S. Taccone, T. Cronberg, H. Friberg, et al. How to assess prognosis after cardiac arrest and therapeutic hypothermia. Crit Care. 2014;18:202
  • 348 P. Stammet, D.R. Wagner, G. Gilson, Y. Devaux. Modeling serum level of s100beta and bispectral index to predict outcome after cardiac arrest. J Am Coll Cardiol. 2013;62:851-858
  • 349 E. Al Thenayan, M. Savard, M. Sharpe, L. Norton, B. Young. Predictors of poor neurologic outcome after induced mild hypothermia following cardiac arrest. Neurology. 2008;71:1535-1537
  • 350 A.V. Grossestreuer, B.S. Abella, M. Leary, et al. Time to awakening and neurologic outcome in therapeutic hypothermia-treated cardiac arrest patients. Resuscitation. 2013;84:1741-1746
  • 351 B. Gold, L. Puertas, S.P. Davis, et al. Awakening after cardiac arrest and post resuscitation hypothermia: are we pulling the plug too early?. Resuscitation. 2014;85:211-214
  • 352 J.J. Krumnikl, B.W. Bottiger, H.J. Strittmatter, J. Motsch. Complete recovery after 2 h of cardiopulmonary resuscitation following high-dose prostaglandin treatment for atonic uterine haemorrhage. Acta Anaesthesiol Scand. 2002;46:1168-1170
  • 353 K. Smith, E. Andrew, M. Lijovic, Z. Nehme, S. Bernard. Quality of life and functional outcomes 12 months after out-of-hospital cardiac arrest. Circulation. 2015;131:174-181
  • 354 R. Phelps, F. Dumas, C. Maynard, J. Silver, T. Rea. Cerebral performance category and long-term prognosis following out-of-hospital cardiac arrest. Crit Care Med. 2013;41:1252-1257
  • 355 K.P. Wilder Schaaf, L.K. Artman, M.A. Peberdy, et al. Anxiety, depression, and PTSD following cardiac arrest: a systematic review of the literature. Resuscitation. 2013;84:873-877
  • 356 E.M. Wachelder, V.R. Moulaert, C. van Heugten, J.A. Verbunt, S.C. Bekkers, D.T. Wade. Life after survival: long-term daily functioning and quality of life after an out-of-hospital cardiac arrest. Resuscitation. 2009;80:517-522
  • 357 T. Cronberg, G. Lilja, M. Rundgren, H. Friberg, H. Widner. Long-term neurological outcome after cardiac arrest and therapeutic hypothermia. Resuscitation. 2009;80:1119-1123
  • 358 J. Torgersen, K. Strand, T.W. Bjelland, et al. Cognitive dysfunction and health-related quality of life after a cardiac arrest and therapeutic hypothermia. Acta Anaesthesiol Scand. 2010;54:721-728
  • 359 F.J. Mateen, K.A. Josephs, M.R. Trenerry, et al. Long-term cognitive outcomes following out-of-hospital cardiac arrest: a population-based study. Neurology. 2011;77:1438-1445
  • 360 K. Kragholm, M. Wissenberg, R.N. Mortensen, et al. Return to work in out-of-hospital cardiac arrest survivors: a nationwide register-based follow-up study. Circulation. 2015;131:1682-1690
  • 361 S.M. Cobbe, K. Dalziel, I. Ford, A.K. Marsden. Survival of 1476 patients initially resuscitated from out of hospital cardiac arrest. BMJ. 1996;312:1633-1637
  • 362 H.C. Kamphuis, J.R. De Leeuw, R. Derksen, R. Hauer, J.A. Winnubst. A 12-month quality of life assessment of cardiac arrest survivors treated with or without an implantable cardioverter defibrillator. Europace. 2002;4:417-425
  • 363 G. Gamper, M. Willeit, F. Sterz, et al. Life after death: posttraumatic stress disorder in survivors of cardiac arrest – prevalence, associated factors, and the influence of sedation and analgesia. Crit Care Med. 2004;32:378-383
  • 364 G. Pusswald, E. Fertl, M. Faltl, E. Auff. Neurological rehabilitation of severely disabled cardiac arrest survivors. Part II. Life situation of patients and families after treatment. Resuscitation. 2000;47:241-248
  • 365 C.M. Dougherty, J.Q. Benoliel, C. Bellin. Domains of nursing intervention after sudden cardiac arrest and automatic internal cardioverter defibrillator implantation. Heart Lung: J Crit Care. 2000;29:79-86
  • 366 J.P. Brown, A.M. Clark, H. Dalal, K. Welch, R.S. Taylor. Patient education in the management of coronary heart disease. Cochrane Database Syst Rev. 2011;:CD008895
  • 367 A. Lundgren-Nilsson, H. Rosen, C. Hofgren, K.S. Sunnerhagen. The first year after successful cardiac resuscitation: function, activity, participation and quality of life. Resuscitation. 2005;66:285-289
  • 368 V.R. Moulaert, E.M. Wachelder, J.A. Verbunt, D.T. Wade, C.M. van Heugten. Determinants of quality of life in survivors of cardiac arrest. J Rehabil Med. 2010;42:553-558
  • 369 M.J. Cowan, K.C. Pike, H.K. Budzynski. Psychosocial nursing therapy following sudden cardiac arrest: impact on two-year survival. Nurs Res. 2001;50:68-76
  • 370 C.M. Dougherty, F.M. Lewis, E.A. Thompson, J.D. Baer, W. Kim. Short-term efficacy of a telephone intervention by expert nurses after an implantable cardioverter defibrillator. Pacing Clin Electrophysiol. 2004;27:1594-1602
  • 371 C.M. Dougherty, E.A. Thompson, F.M. Lewis. Long-term outcomes of a telephone intervention after an ICD. Pacing Clin Electrophysiol. 2005;28:1157-1167
  • 372 C.M. Dougherty, G.P. Pyper, H.A. Frasz. Description of a nursing intervention program after an implantable cardioverter defibrillator. Heart Lung: J Crit Care. 2004;33:183-190
  • 373 V.R. Moulaert, C.M. van Heugten, B. Winkens, et al. Early neurologically-focused follow-up after cardiac arrest improves quality of life at one year: a randomised controlled trial. Int J Cardiol. 2015;193:8-16
  • 374 V.R. Moulaert, J.A. Verbunt, W.G. Bakx, et al. ‘Stand still…, and move on’, a new early intervention service for cardiac arrest survivors and their caregivers: rationale and description of the intervention. Clin Rehabil. 2011;25:867-879
  • 375 V.R. Moulaert, J.C. van Haastregt, D.T. Wade, C.M. van Heugten, J.A. Verbunt. ‘Stand still…, and move on’, an early neurologically-focused follow-up for cardiac arrest survivors and their caregivers: a process evaluation. BMC Health Serv Res. 2014;14:34
  • 376 C. van Heugten, S. Rasquin, I. Winkens, G. Beusmans, F. Verhey. Checklist for cognitive and emotional consequences following stroke (CLCE-24): development, usability and quality of the self-report version. Clin Neurol Neurosurg. 2007;109:257-262
  • 377 K.D. Cicerone, D.M. Langenbahn, C. Braden, et al. Evidence-based cognitive rehabilitation: updated review of the literature from 2003 through 2008. Arch Phys Med Rehabil. 2011;92:519-530
  • 378 P. Spinhoven, J. Ormel, P.P. Sloekers, G.I. Kempen, A.E. Speckens, A.M. Van Hemert. A validation study of the Hospital Anxiety and Depression Scale (HADS) in different groups of Dutch subjects. Psychol Med. 1997;27:363-370
  • 379 E. van der Ploeg, T.T. Mooren, R.J. Kleber, P.G. van der Velden, D. Brom. Construct validation of the Dutch version of the impact of event scale. Psychol Assess. 2004;16:16-26
  • 380 C. Sandroni, C. Adrie, F. Cavallaro, et al. Are patients brain-dead after successful resuscitation from cardiac arrest suitable as organ donors? A systematic review. Resuscitation. 2010;81:1609-1614
  • 381 C. Adrie, H. Haouache, M. Saleh, et al. An underrecognized source of organ donors: patients with brain death after successfully resuscitated cardiac arrest. Intensive Care Med. 2008;34:132-137
  • 382 A.A. Ali, E. Lim, M. Thanikachalam, et al. Cardiac arrest in the organ donor does not negatively influence recipient survival after heart transplantation. Eur J Cardiothorac Surg. 2007;31:929-933
  • 383 A. Orioles, W.E. Morrison, J.W. Rossano, et al. An under-recognized benefit of cardiopulmonary resuscitation: organ transplantation. Crit Care Med. 2013;41:2794-2799
  • 384 M.A. Quader, L.G. Wolfe, V. Kasirajan. Heart transplantation outcomes from cardiac arrest – resuscitated donors. J Heart Lung Transplant. 2013;32:1090-1095
  • 385 K. Pilarczyk, B.R. Osswald, N. Pizanis, et al. Use of donors who have suffered cardiopulmonary arrest and resuscitation in lung transplantation. Eur J Cardiothorac Surg. 2011;39:342-347
  • 386 I. Sánchez-Lázaro, L. Almenar-Bonet, L. Martínez-Dolz, et al. Can we accept donors who have suffered a resuscitated cardiac arrest? Transplantation proceedings. (Elsevier, Amsterdam, 2010) 3091-3092
  • 387 K.W. Southerland, A.W. Castleberry, J.B. Williams, M.A. Daneshmand, A.A. Ali, C.A. Milano. Impact of donor cardiac arrest on heart transplantation. Surgery. 2013;154:312-319
  • 388 A.W. Castleberry, M. Worni, A.A. Osho, et al. Use of lung allografts from brain-dead donors after cardiopulmonary arrest and resuscitation. Am J Respir Crit Care Med. 2013;188:466-473
  • 389 A. Alonso, C. Fernandez-Rivera, P. Villaverde, et al. Renal transplantation from non-heart-beating donors: a single-center 10-year experience. Transplant Proc. 2005;37:3658-3660
  • 390 A. Casavilla, C. Ramirez, R. Shapiro, et al. Experience with liver and kidney allografts from non-heart-beating donors. Transplantation. 1995;59:197-203
  • 391 M.L. Nicholson, M.S. Metcalfe, S.A. White, et al. A comparison of the results of renal transplantation from non-heart-beating, conventional cadaveric, and living donors. Kidney Int. 2000;58:2585-2591
  • 392 C. Fondevila, A.J. Hessheimer, E. Flores, et al. Applicability and results of Maastricht type 2 donation after cardiac death liver transplantation. Am J Transplant. 2012;12:162-170
  • 393 A. Otero, M. Gomez-Gutierrez, F. Suarez, et al. Liver transplantation from maastricht category 2 non-heart-beating donors: a source to increase the donor pool?. Transplant Proc. 2004;36:747-750
  • 394 G. Kootstra. Statement on non-heart-beating donor programs. Transplant Proc. 1995;27:2965
  • 395 A.R. Manara, P.G. Murphy, G. O’Callaghan. Donation after circulatory death. Br J Anaesth. 2012;108:i108-i121 Suppl 1
  • 396 A.R. Manara, I. Thomas. The use of circulatory criteria to diagnose death after unsuccessful cardiopulmonary resuscitation. Resuscitation. 2010;81:781-783
  • 397 M.F. Ranthe, B.G. Winkel, E.W. Andersen, et al. Risk of cardiovascular disease in family members of young sudden cardiac death victims. Eur Heart J. 2013;34:503-511
  • 398 J.R. Skinner. Investigation following resuscitated cardiac arrest. Arch Dis Child. 2013;98:66-71
  • 399 J.R. Skinner. Investigating sudden unexpected death in the young: a chance to prevent further deaths. Resuscitation. 2012;83:1185-1186
  • 400 E.R. Behr, C. Dalageorgou, M. Christiansen, et al. Sudden arrhythmic death syndrome: familial evaluation identifies inheritable heart disease in the majority of families. Eur Heart J. 2008;29:1670-1680
  • 401 J. Engdahl, P. Abrahamsson, A. Bang, J. Lindqvist, T. Karlsson, J. Herlitz. Is hospital care of major importance for outcome after out-of-hospital cardiac arrest? Experience acquired from patients with out-of-hospital cardiac arrest resuscitated by the same Emergency Medical Service and admitted to one of two hospitals over a 16-year period in the municipality of Goteborg. Resuscitation. 2000;43:201-211
  • 402 J.M. Liu, Q. Yang, R.G. Pirrallo, J.P. Klein, T.P. Aufderheide. Hospital variability of out-of-hospital cardiac arrest survival. Prehosp Emerg Care. 2008;12:339-346
  • 403 J. Herlitz, J. Engdahl, L. Svensson, K.A. Angquist, J. Silfverstolpe, S. Holmberg. Major differences in 1-month survival between hospitals in Sweden among initial survivors of out-of-hospital cardiac arrest. Resuscitation. 2006;70:404-409
  • 404 C.W. Callaway, R. Schmicker, M. Kampmeyer, et al. Receiving hospital characteristics associated with survival after out-of-hospital cardiac arrest. Resuscitation. 2010;81:524-529
  • 405 M.T. Cudnik, C. Sasson, T.D. Rea, et al. Increasing hospital volume is not associated with improved survival in out of hospital cardiac arrest of cardiac etiology. Resuscitation. 2012;83:862-868
  • 406 D.P. Davis, R. Fisher, S. Aguilar, et al. The feasibility of a regional cardiac arrest receiving system. Resuscitation. 2007;74:44-51
  • 407 R.T. Fothergill, L.R. Watson, G.K. Virdi, F.P. Moore, M. Whitbread. Survival of resuscitated cardiac arrest patients with ST-elevation myocardial infarction (STEMI) conveyed directly to a Heart Attack Centre by ambulance clinicians. Resuscitation. 2014;85:96-98
  • 408 M. Hansen, R. Fleischman, G. Meckler, C.D. Newgard. The association between hospital type and mortality among critically ill children in US EDs. Resuscitation. 2013;84:488-491
  • 409 A.C. Heffner, D.A. Pearson, M.L. Nussbaum, A.E. Jones. Regionalization of post-cardiac arrest care: implementation of a cardiac resuscitation center. Am Heart J. 2012;164:493-501e2
  • 410 I. Lund-Kordahl, T.M. Olasveengen, T. Lorem, M. Samdal, L. Wik, K. Sunde. Improving outcome after out-of-hospital cardiac arrest by strengthening weak links of the local chain of survival: quality of advanced life support and post-resuscitation care. Resuscitation. 2010;81:422-426
  • 411 M.R. Mooney, B.T. Unger, L.L. Boland, et al. Therapeutic hypothermia after out-of-hospital cardiac arrest: evaluation of a regional system to increase access to cooling. Circulation. 2011;124:206-214
  • 412 D.W. Spaite, B.J. Bobrow, T.F. Vadeboncoeur, et al. The impact of prehospital transport interval on survival in out-of-hospital cardiac arrest: implications for regionalization of post-resuscitation care. Resuscitation. 2008;79:61-66
  • 413 D.W. Spaite, I.G. Stiell, B.J. Bobrow, et al. Effect of transport interval on out-of-hospital cardiac arrest survival in the OPALS study: implications for triaging patients to specialized cardiac arrest centers. Ann Emerg Med. 2009;54:248-255
  • 414 D. Stub, K. Smith, J.E. Bray, S. Bernard, S.J. Duffy, D.M. Kaye. Hospital characteristics are associated with patient outcomes following out-of-hospital cardiac arrest. Heart. 2011;97:1489-1494
  • 415 T. Tagami, K. Hirata, T. Takeshige, et al. Implementation of the fifth link of the chain of survival concept for out-of-hospital cardiac arrest. Circulation. 2012;126:589-597
  • 416 N. Bosson, A.H. Kaji, J.T. Niemann, et al. Survival and neurologic outcome after out-of-hospital cardiac arrest: results one year after regionalization of post-cardiac arrest care in a large metropolitan area. Prehosp Emerg Care. 2014;18:217-223
  • 417 See ref. 404 .
  • 418 J. Wnent, S. Seewald, M. Heringlake, et al. Choice of hospital after out-of-hospital cardiac arrest – a decision with far-reaching consequences: a study in a large German city. Crit Care. 2012;16:R164
  • 419 J.L. Thomas, N. Bosson, A.H. Kaji, et al. Treatment and outcomes of ST segment elevation myocardial infarction and out-of-hospital cardiac arrest in a regionalized system of care based on presence or absence of initial shockable cardiac arrest rhythm. Am J Cardiol. 2014;114:968-971
  • 420 F. Vermeer, A.J. Oude Ophuis, E.J. vd Berg, et al. Prospective randomised comparison between thrombolysis, rescue PTCA, and primary PTCA in patients with extensive myocardial infarction admitted to a hospital without PTCA facilities: a safety and feasibility study. Heart. 1999;82:426-431
  • 421 P. Widimsky, L. Groch, M. Zelizko, M. Aschermann, F. Bednar, H. Suryapranata. Multicentre randomized trial comparing transport to primary angioplasty vs immediate thrombolysis vs combined strategy for patients with acute myocardial infarction presenting to a community hospital without a catheterization laboratory. The PRAGUE study. Eur Heart J. 2000;21:823-831
  • 422 P. Widimsky, T. Budesinsky, D. Vorac, et al. Long distance transport for primary angioplasty vs immediate thrombolysis in acute myocardial infarction. Final results of the randomized national multicentre trial – PRAGUE-2. Eur Heart J. 2003;24:94-104
  • 423 M.R. Le May, D.Y. So, R. Dionne, et al. A citywide protocol for primary PCI in ST-segment elevation myocardial infarction. N Engl J Med. 2008;358:231-240
  • 424 J.H. Abernathy 3rd, G. McGwin Jr., J.E. Acker 3rd, L.W. Rue 3rd. Impact of a voluntary trauma system on mortality, length of stay, and cost at a level I trauma center. Am Surg. 2002;68:182-192
  • 425 T.P. Clemmer, J.F. Orme Jr., F.O. Thomas, K.A. Brooks. Outcome of critically injured patients treated at Level I trauma centers versus full-service community hospitals. Crit Care Med. 1985;13:861-863
  • 426 D. Culica, L.A. Aday, J.E. Rohrer. Regionalized trauma care system in Texas: implications for redesigning trauma systems. Med Sci Monit. 2007;13:SR9-SR18
  • 427 E.L. Hannan, L.S. Farrell, A. Cooper, M. Henry, B. Simon, R. Simon. Physiologic trauma triage criteria in adult trauma patients: are they effective in saving lives by transporting patients to trauma centers?. J Am Coll Surg. 2005;200:584-592
  • 428 D.T. Harrington, M. Connolly, W.L. Biffl, S.D. Majercik, W.G. Cioffi. Transfer times to definitive care facilities are too long: a consequence of an immature trauma system. Ann Surg. 2005;241:961-966 discussion 6-8
  • 429 M. Liberman, D.S. Mulder, A. Lavoie, J.S. Sampalis. Implementation of a trauma care system: evolution through evaluation. J Trauma. 2004;56:1330-1335
  • 430 E.J. MacKenzie, F.P. Rivara, G.J. Jurkovich, et al. A national evaluation of the effect of trauma-center care on mortality. N Engl J Med. 2006;354:366-378
  • 431 N.C. Mann, R.M. Cahn, R.J. Mullins, D.M. Brand, G.J. Jurkovich. Survival among injured geriatric patients during construction of a statewide trauma system. J Trauma. 2001;50:1111-1116
  • 432 R.J. Mullins, J. Veum-Stone, J.R. Hedges, et al. Influence of a statewide trauma system on location of hospitalization and outcome of injured patients. J Trauma. 1996;40:536-545 discussion 45-6
  • 433 R.J. Mullins, N.C. Mann, J.R. Hedges, W. Worrall, G.J. Jurkovich. Preferential benefit of implementation of a statewide trauma system in one of two adjacent states. J Trauma. 1998;44:609-616 discussion 17
  • 434 R.J. Mullins, J. Veum-Stone, M. Helfand, et al. Outcome of hospitalized injured patients after institution of a trauma system in an urban area. JAMA. 1994;271:1919-1924
  • 435 R. Mullner, J. Goldberg. An evaluation of the Illinois trauma system. Med Care. 1978;16:140-151
  • 436 R. Mullner, J. Goldberg. Toward an outcome-oriented medical geography: an evaluation of the Illinois trauma/emergency medical services system. Soc Sci Med. 1978;12:103-110
  • 437 A.B. Nathens, G.J. Jurkovich, F.P. Rivara, R.V. Maier. Effectiveness of state trauma systems in reducing injury-related mortality: a national evaluation. J Trauma. 2000;48:25-30 discussion 1
  • 438 A.B. Nathens, R.V. Maier, S.I. Brundage, G.J. Jurkovich, D.C. Grossman. The effect of interfacility transfer on outcome in an urban trauma system. J Trauma. 2003;55:444-449
  • 439 J. Nicholl, J. Turner. Effectiveness of a regional trauma system in reducing mortality from major trauma: before and after study. BMJ. 1997;315:1349-1354
  • 440 D.A. Potoka, L.C. Schall, M.J. Gardner, P.W. Stafford, A.B. Peitzman, H.R. Ford. Impact of pediatric trauma centers on mortality in a statewide system. J Trauma. 2000;49:237-245
  • 441 J.S. Sampalis, A. Lavoie, S. Boukas, et al. Trauma center designation: initial impact on trauma-related mortality. J Trauma. 1995;39:232-237 discussion 7-9
  • 442 J.S. Sampalis, R. Denis, P. Frechette, R. Brown, D. Fleiszer, D. Mulder. Direct transport to tertiary trauma centers versus transfer from lower level facilities: impact on mortality and morbidity among patients with major trauma. J Trauma. 1997;43:288-295 discussion 95-96
  • 443 M.W. Donnino, J.C. Rittenberger, D. Gaieski, et al. The development and implementation of cardiac arrest centers. Resuscitation. 2011;82:974-978
  • 444 G. Nichol, T.P. Aufderheide, B. Eigel, et al. Regional systems of care for out-of-hospital cardiac arrest: a policy statement from the American Heart Association. Circulation. 2010;121:709-729
  • 445 G. Nichol, J. Soar. Regional cardiac resuscitation systems of care. Curr Opin Crit Care. 2010;16:223-230
  • 446 J. Soar, S. Packham. Cardiac arrest centres make sense. Resuscitation. 2010;81:507-508


a Department of Anaesthesia and Intensive Care Medicine, Royal United Hospital, Bath, UK

b School of Clinical Sciences, University of Bristol, UK

c Anaesthesia and Intensive Care Medicine, Southmead Hospital, Bristol, UK

d Cochin University Hospital (APHP) and Paris Descartes University, Paris, France

e Department of Clinical Sciences, Division of Neurology, Lund University, Lund, Sweden

f Adelante, Centre of Expertise in Rehabilitation and Audiology, Hoensbroek, The Netherlands

g Cardiac Anaesthesia and Cardiac Intensive Care and NIHR Southampton Respiratory Biomedical Research Unit, University Hospital, Southampton, UK

h Department of Anaesthesiology and Intensive Care Medicine, University Hospital of Cologne, Cologne, Germany

i Department of Clinical Sciences, Division of Anesthesia and Intensive Care Medicine, Lund University, Lund, Sweden

j Department of Anaesthesiology, Division of Emergencies and Critical Care, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway

k Department of Anaesthesiology and Intensive Care, Catholic University School of Medicine, Rome, Italy

Corresponding author.

This article is being published simultaneously in Resuscitation and Intensive Care Medicine.