Post-Cardiac Arrest Care

Vasopressors for Post-Cardiac Arrest Shock

Last Full Review: ILCOR 2025

Arterial hypotension (systolic blood pressure less than 100 millimeters of mercury [mmHg]) after cardiac arrest is reported to occur in 65% of patients within the first 6 hours after return of spontaneous circulation (ROSC) and is an independent predictor of death (Kilgannon et al. 2008, 410). Post-ROSC hypotension is likely due to a combination of factors, including myocardial stunning from ischemia-reperfusion injury, systemic inflammatory response, and catecholamine-induced myocardial toxicity from epinephrine administered during resuscitation. The Red Cross guidelines suggest maintaining a mean arterial blood pressure of at least 60 millimeters of mercury (mmHg) to 65 mmHg in patients after cardiac arrest. However, the pharmacologic management of hypotension in this period has not undergone a previous systematic review by the International Liaison Committee on Resuscitation (ILCOR) or the American Red Cross Scientific Advisory Council.

 

Evidence Summary

A 2015 ILCOR systematic review and Consensus on Science with Treatment Recommendations (CoSTR) (Skrifvars et al. 2023; Drennan et al. 2025, S72) evaluated evidence for the use of a vasopressor or a combination of vasopressors provided intravenously as an infusion in adults with sustained ROSC after cardiac arrest and with a need for vasopressor infusion to manage low blood pressure. The review question compared this intervention with no vasopressor use, a different vasopressor or a different combination of vasopressors provided intravenously or as an infusion after ROSC. A total of eight studies were included in the review, allowing comparisons of norepinephrine versus epinephrine, norepinephrine versus dopamine, and  dopamine combined with either norepinephrine or epinephrine versus dopamine alone. Critical survival outcomes for each comparison are summarized here, while the full review is available online (Skrifvars et al. 2023).

For norepinephrine versus epinephrine, no difference was shown for survival at 30 days (one randomized controlled trial [RCT], 40 patients) (Pansiritanachot et al. 2024, 100551); for survival to hospital discharge (two studies, 451 and 1,893 patients respectively) (Smida et al. 2024, 110201; Wender et al. 2024, 453); or for good neurologic function at discharge (one study, 1,893 patients) (Wender et al. 2024, 453). Two studies (766 and 221 patients respectively) (Bougouin et al. 2022, 300; Normand et al. 2024, 72) showed the administration of epinephrine to be associated with higher in-hospital mortality (aOR, 2.6; 95% CI, 1.4–4.7; and aOR, 6.2; 95% CI, 2.4–16.3). One study (755 patients) (Bougouin et al. 2022, 300) reported higher likelihood of unfavorable neurologic outcome at discharge with epinephrine (aOR, 3.4; 95% CI, 2.4–5.0).

For norepinephrine versus dopamine, one study (1,011 patients) (Li et al. 2020, 7951025) found no difference in 30-day survival or favorable functional outcome.

For norepinephrine combined with dopamine versus dopamine alone, one study (Li et al. 2020, 7951025) found no difference in survival to 30 days, but norepinephrine combined with dopamine was associated with lower odds of favorable neurologic outcome at 30 days (aOR, 0.20; 95% CI, 0.04–0.78). A second study (310 patients) (Bro-Jeppesen et al. 2015, 318) found dopamine with norepinephrine or epinephrine was associated with higher 30-day mortality compared with dopamine alone.

The ILCOR CoSTR concluded that there is insufficient evidence to recommend a specific vasopressor to treat low blood pressure in patients after cardiac arrest (Skrifvars et al. 2023; Drennan et al. 2025, S72).

Insights and Implications

The decision by the ILCOR Advanced Life Support Task Force to not recommend a specific vasopressor to treat low blood pressure in patients after cardiac arrest was multifactorial. There was only one small RCT included in the systematic review, and all other observational studies were considered likely to be prone to confounding by indication (i.e., epinephrine is only used in the most critically and unstable patients), which makes it difficult to draw firm conclusions on the differences between the effect of epinephrine and norepinephrine on outcomes. A consistent benefit was not shown from either epinephrine or norepinephrine.

Currently, norepinephrine is the first line vasopressor recommended for septic shock by the Surviving Sepsis Campaign guidelines (Evans et al. 2021, e1063). The European Society of Cardiology guidelines for management of acute myocardial infarction patients presenting with ST-segment elevation recommend norepinephrine as a first line vasopressor for management of low blood pressure and other resuscitation organizations recommend this as well (Henry et al. 2021, e815; Ibanez, et al. 2018, 19; McDonagh et al. 2021, 3599). There are some observational studies (Levy et al. 2018, 173; Myburgh et al. 2008, 2226) of vasopressor use in cardiogenic shock or low blood pressure that suggest greater adverse effects with the use of epinephrine. The Red Cross guideline good practice statement to consider norepinephrine as a first-line vasopressor for post-ROSC hypotension (depending on the clinical situation) considers the indirect evidence for adverse effects seen with other vasopressors.

Mechanical Circulatory Support After Return of Spontaneous Circulation Following Cardiac Arrest

Last Full Review: ILCOR 2025

Over the past decade, several mechanical circulatory support devices have been developed to assist patients with cardiogenic shock following the return of spontaneous circulation (ROSC) after cardiac arrest. Mechanical circulatory support devices aim to stabilize hemodynamics, improve organ perfusion, and serve as a bridge to recovery or further interventions. These devices are percutaneously inserted, catheter-based axial flow pumps for temporary left ventricular or right ventricular support that provide continuous (non-pulsatile) flow. A new systematic review on mechanical circulatory support devices was completed by the International Liaison Committee on Resuscitation (ILCOR) for 2025.

 

Evidence Summary

A 2025 systematic review and Consensus on Science with Treatment Recommendations (CoSTR) (Scquizzato et al. 2024; Drennan et al. 2025, S72) sought evidence in adults with cardiogenic shock after ROSC following cardiac arrest in any setting for management with a mechanical circulatory support device compared to management without a mechanical circulatory support device or usual post-resuscitation care. The review only included randomized controlled trials (RCTs) in humans where a mechanical circulatory support device was not initiated during ongoing CPR.

Multiple clinical outcomes were assessed this this review. Pooled analyses from up to 14 randomized trials found no difference between early routine treatment with a temporary mechanical circulatory support device and standard care in patients with cardiogenic shock, with or without prior cardiac arrest, for outcomes of survival at 30 days or hospital discharge, 6 months, 1 year and the longest available follow-up. In addition, no difference was found between treatment with a mechanical circulatory support device and standard care for outcomes at 30 days of stroke, hemolysis, sepsis, need for renal replacement therapy and for length of hospital stay. However, no RCTs were designed to assess a benefit in the population of interest (patients with ROSC after cardiac arrest), and apart from a single small study (Møller et al. 2024, 1382) from the inpatient setting, indirect data was used from patients with cardiogenic shock (Scquizzato et al. 2024; Drennan et al. 2025,S72).

The CoSTR authors commented on two studies (Scquizzato et al. 2024; Drennan et al. 2025, S72). One RCT (Møller et al. 2024, 1382) compared a microaxial flow pump with standard care alone in infarct-related cardiogenic shock and found improved survival at 180 days. Patients resuscitated from cardiac arrest who remained comatose (Glasgow Coma Scale less than or equal to 8) at hospital arrival were excluded. The second study, an individual patient data meta-analysis of nine RCTs, found a benefit with mechanical circulatory support devices in patients with ST-elevation myocardial infarction without resuscitation before arrival of emergency medical service, or with a duration of resuscitation less than 10 minutes, but not in the overall population of cardiac arrest patients (Thiele et al. 2024, 1019).

In terms of adverse effects or complications, findings from 12 RCTs and 1,738 patients with cardiogenic shock (59% resuscitated from cardiac arrest) showed a higher occurrence of moderate to severe bleeding at 30 days in patients receiving a mechanical circulatory support device compared to standard care (Scquizzato et al. 2024; Drennan et al. 2025, S72). In addition, data from 11 RCTs with 1,710 patients in cardiogenic shock (59% resuscitated from cardiac arrest) showed a higher occurrence of a peripheral ischemic vascular complication at 30 days in patients with a mechanical circulatory support device compared to standard care (Scquizzato et al. 2024; Drennan et al. 2025, S72).

The ILCOR treatment recommendations for this review include (Scquizzato et al. 2024; Drennan et al. 2025. S72):

• A weak recommendation suggests against the routine use of mechanical circulatory support devices in patients with cardiogenic shock after cardiac arrest and return of spontaneous circulation.
• A weak recommendation suggests considering mechanical circulatory support devices in highly selected patients with cardiogenic shock after cardiac arrest and return of spontaneous circulation, in settings where this can be implemented.
• A good practice statement suggests monitoring for adverse events and complications to allow rapid identification and treatment when a mechanical circulatory support device is used.

 

Insights and Implications

One of the ILCOR recommendations suggests consideration of mechanical circulatory support devices in highly selected patients with cardiogenic shock after cardiac arrest and ROSC in settings where this can be implemented (Scquizzato et al. 2024; Drennan et al. 2025, S72). This leads to the obvious question: What subgroup is a “highly-selected patient?” There was some evidence demonstrating improved survival at 180 days (Møller et al. 2024, 1382) in patients resuscitated from cardiac arrest with a Glasgow Coma Scale score of 8 or less at hospital arrival and who received a microaxial flow pump compared with standard care. Benefit was also shown with mechanical circulatory support devices in patients with ST-elevation myocardial infarction without resuscitation before arrival of emergency medical service or those with a duration of cardiac arrest of less than 10 minutes. However, there was not sufficient evidence to make a recommendation on selecting patients with cardiogenic shock after cardiac arrest and ROSC for mechanical circulatory support. The ILCOR review team emphasizes the need for caution when considering the use of mechanical circulatory support devices until further evidence becomes available (Scquizzato et al. 2024; Drennan et al. 2025, S72. Other considerations include significant cost of mechanical circulatory support devices, the need for specialized skills and resources, and risk of adverse effects or complications such as bleeding and limb ischemia.

Oxygen and Carbon Dioxide Target Levels in Adults

Last Full Review: ILCOR 2025
Last Update: 2024

Following return of spontaneous circulation (ROSC), the post-cardiac arrest period is a time when patients often require mechanical ventilation and when hypoxemia and hyperoxemia may be associated with brain injury (Roberts et al. 2018, 2114). Similarly, because carbon dioxide is a major regulator of cerebral blood flow and thus intracranial pressure, the targeting of oxygen and carbon dioxide levels through a ventilation strategy in intubated patients with ROSC may have a role in mitigating post-arrest brain injury and improving neurological outcome.

The topic of oxygen and ventilation (carbon dioxide) targets during the post-cardiac arrest period was addressed in an updated systematic review and Consensus on Science with Treatment Recommendations (CoSTR) by the International Liaison Committee on Resuscitation (ILCOR) in 2024 (Holmberg et al. 2023; Greif et al. 2024, e580). Publication of a secondary analysis (Meyer et al. 2024, 20) of a previous randomized control trial (RCT) (Schmidt et al. 2022, 1467) led to another update for 2025.

 

Evidence Summary

A systematic review and Consensus on Science with Treatment Recommendations (CoSTR) (Holmberg et al. 2024; Drennan et al. 2025, S72) was updated by ILCOR in 2025. The review sought evidence of clinical outcomes for unresponsive adults with sustained ROSC after cardiac arrest in any setting who receive a ventilation strategy targeting specific peripheral oxygen saturation (SpO₂), partial pressure of oxygen in arterial blood (PaO₂), and/or partial pressure of carbon dioxide in arterial blood (PaCO₂) levels, compared with no specific targets or an alternate target. Only randomized controlled trials (RCTs) were included, as well as RCTs from the 2024 review. A single study was added to the 2024 review from the updated search (Meyer et al. 2024, 20), which included a secondary analysis of an RCT with 771 patients that found no difference between higher and lower oxygen targets in comatose survivors of cardiac arrest for the outcome of favorable neurologic outcome at 1 year.

The 2024 systematic review included seven RCTs from the 2020 review (Berg et al. 2020, S92) and five from 2024 (Holmberg et al. 2024, 106). A separate narrative literature review (Bray et al. 2023, 109899) provides an in-depth summary of data related to oxygen targets post-ROSC identified in recent RCTs, observational studies and animal studies. The RCTs included in the 2024 ILCOR systematic review used differing, specific oxygen and carbon dioxide strategies or goals.

In the prehospital setting, four RCTs evaluated a strategy of lower oxygen targets compared with higher oxygen targets. An oxygen “target” was defined as:

• A fraction of inspired oxygen (FiO₂) of 30% versus 100% (Kuisma et al. 2006, 199).
• Administration of 2 to 4 liters per minute (L/minute) versus greater than 10 L/minute oxygen (Bray et al. 2023, 109899).
• An oxygen saturation of 94% to 98% versus an FiO₂ of 100% (Thomas et al. 2019, 16).
• An oxygen saturation of 90% to 94% compared with 98% to 100% (EXACT trial) (Bernard et al. 2022, 1818).

 

The detailed results of this review can be found online in the CoSTR (Holmberg et al. 2024; Drennan et al. 2025, S72).

In summary, for critical outcomes of survival to hospital discharge (Bernard et al. 2022, 1818; Bray et al. 2023, 109899; Kuisma et al. 2006, 199; Thomas et al. 2019, 16) and survival with favorable neurological outcome at discharge (Bernard et al. 2022, 1818; Kuisma et al. 2006, 199), moderate certainty evidence did not find a benefit from lower oxygen targets than from higher oxygen targets. Individual RCTs that were reviewed did not show a benefit from lower oxygen targets compared with higher oxygen targets for other outcomes, such as survival to 3 months and 12 months. Of note, however, is the EXACT trial (Bernard et al. 2022, 1818) in which a higher proportion of patients randomized to the lower oxygen titration (intervention) group (oxygen saturation target, 90% to 94%) compared with the higher oxygen titration (standard care) group (oxygen saturation target, 98% to 100%) experienced hypoxemia and required an increase in oxygen to 100%. In addition, survival to hospital discharge was less in the lower oxygen titration group. Randomization for this trial did not occur until after the patient was hemodynamically stable and had an oxygen saturation greater than 94% on 100%, and in the case of the higher oxygen titration group, titration occurred via a ventilator once in the hospital.

Other RCTs evaluated various oxygen strategies after admission to the intensive care unit. For the meta-analysis of these studies, oxygen targets were defined as:

• A PaO₂ of 10 to 15 kilopascals (kPa) compared with 20 to 25 kPa (approximately 75 to 113 millimeters of mercury (mmHg) versus 150 mmHg to 188 mmHg) (Jakkula et al. 2018, 2112).
• An oxygen saturation of 90% to 97% compared with standard care (Young et al. 2020, 2411).
• A PaO₂ of 9 to 10 kPa compared with 13 to 15 kPa (approximately 68 mmHg to 75 mmHg versus 98 mmHg to 105 mmHg) (Schmidt et al. 2022, 1476).
• An oxygen saturation of 88% to 96% compared with 96% to 100% (Semler et al. 2022, 1759).
• A PaO₂of 60 mmHg compared with 90 mmHg (Crescioli et al. 2023, 109838).

 

Meta-analyses of these studies did not show a benefit from lower oxygen targets compared with higher oxygen targets.

For the RCTs evaluating ventilation targeting moderate hypercapnia compared with normocapnia or low normal PaCO₂ after ROSC, three RCTs were included from the prehospital setting. For this meta-analysis, targets were defined as a:

• PaCO₂ of 50 mmHg to 55 mmHg compared with 35 mmHg to 45 mmHg (Eastwood et al. 2023, 45; Eastwood et al. 2016, 108).
• PaCO₂ of approximately 44 mmHg to 45 mmHg compared with 34 mmHg to 35 mmHg (Jakkula et al. 2018, 2112).

 

The ILCOR review of these studies found no consistent evidence of benefit or harm from targeting moderate hypercapnia compared with normocapnia using the different strategies investigated.

The ILCOR treatment recommendations for oxygen and carbon dioxide targets are unchanged with the 2025 update to the CoSTR and include (Holmberg et al. 2024; Drennan et al. 2025, S72):

• A strong recommendation to use 100% inspired oxygen until the arterial oxygen saturation or the PaO₂can be measured reliably in adults with ROSC after cardiac arrest in both the prehospital setting and the in-hospital setting.
• A strong recommendation for avoiding hypoxemia in adults with ROSC after cardiac arrest in any setting.
• A weak recommendation to avoid hyperoxemia in adults with ROSC after cardiac arrest in any setting.
• Following reliable measurement of arterial oxygen levels, ILCOR suggests targeting an oxygen saturation of 94% to 98% or a PaO₂of 75 mmHg to 100 mmHg in adults with ROSC after cardiac arrest in any setting. (Good practice statement)
• When relying on pulse oximetry, healthcare professionals should be aware , t of the increased risk of inaccuracy that may conceal hypoxemia in patients with darker skin pigmentation. (Good practice statement)
• A revised ILCOR treatment recommendation for carbon dioxide targets suggests targeting normocapnia (a PaCO₂ of 35 mmHg to 45 mmHg) in adults with ROSC after cardiac arrest.

 

Insights and Implications

The 2024 ILCOR CoSTR (Holmberg et al. 2024; Drennan et al. 2025, S72) remarks that there was variability in oxygenation targets across both RCTs and observational studies, making it difficult to identify an evidence-based optimal range for oxygen saturation. While the 2025 ILCOR treatment recommendations are largely unchanged from 2020, a new good practice statement suggests setting a goal or target oxygen saturation of 94% to 98% in adults after ROSC in any setting. This good practice statement emphasizes the prerequisite that this target be set after reliable measurement of arterial oxygen levels, which may be obtained with a pulse oximeter or by measuring the PaO₂.

In the prehospital setting, arterial blood gas analysis is typically not available, and a pulse oximetry reading may be difficult to obtain or inconsistent (i.e., unreliable). Emergency medical services clinicians may be required to assist with ventilation via a bag-valve-mask device or through a supraglottic or endotracheal tube while attempting to monitor a pulse oximeter reading in a moving vehicle. Titrating down the FiO₂ following ROSC in the prehospital setting may be too soon, and titrating to an oxygen saturation target of 90% to 94% may be harmful. While additional studies are needed to confirm this finding, deferring titration of oxygen until soon after arrival at the emergency department—where an arterial oxygen saturation can be reliably measured—is reasonable.

A weak recommendation suggests targeting normocapnia (i.e., a PaCO₂ of 35 mmHg to 45 mmHg) in adults with ROSC after cardiac arrest. The evidence for a specific carbon dioxide (CO₂) target was inconsistent across all studies, while data from RCTs did not show any effect from different CO₂ targets.

 

Post-Cardiac Arrest Temperature Control

Last Full Review: American Red Cross Scientific Advisory Council 2021; ILCOR 2021
Last Update: 2024

The use of targeted temperature management (TTM) has been recommended in the past for adults with sustained return of spontaneous circulation (ROSC) following out-of-hospital cardiac arrest, and who remain unconscious, to reduce global oxygen demand and improve outcomes after cardiac arrest. Updated reviews by the International Liaison Committee on Resuscitation (ILCOR) (Granfeldt et al. 2021, 160) and the American Red Cross Scientific Advisory Council in 2021 (American Red Cross Scientific Advisory Council 2021) included a large clinical trial (Dankiewicz et al. 2021, 2283). Meta-analysis of data from six trials evaluating hypothermia at 32° C to 34° C for 12 to 24 hours did not show a statistically significant improvement when compared with normothermia for outcomes of survival or favorable neurological outcome. In addition, meta-analyses of other temperature targets (33° C versus 36° C, and 33° C versus 34° C) did not show a difference in outcomes (Granfeldt et al. 2021, 160).  

Recommendations by ILCOR in 2021 emphasized the need to actively prevent fever and maintain normothermia for cardiac arrest patients with ROSC and persistent unconsciousness, while hypothermic temperature control may be considered for certain subpopulations based on the clinical situation. Newly identified studies have led to an updated 2024 systematic review by ILCOR.

Coinciding with the 2021 ILCOR review of TTM (Granfeldt et al. 2021, 160) was the introduction of a change in terminology. Targeted temperature management has had different meanings and different definitions, creating difficulties when evaluating research. The term has been updated for clarity to temperature control, with the following specific definitions:

• Hypothermic temperature control is active temperature control with the target temperature below the normal range.
• Normothermic temperature control is active temperature control with the target temperature in the normal range.
• Fever prevention temperature control is monitoring temperature and actively preventing and treating temperature above the normal range.
• No temperature control is having no protocolized active temperature control strategy.

 

 

Evidence Summary

A 2024 updated ILCOR systematic review (Granfeldt et al. 2023, 109928) and Consensus on Science with Treatment Recommendations (CoSTR) (Granfeldt et al. 2023; Greif et al. 2024) sought evidence related to the use of temperature control in adults with ROSC following in-hospital cardiac arrest or out-of-hospital cardiac arrest (OHCA). Multiple specific interventions and comparisons were evaluated, including:

• Hypothermic temperature control (studies targeting 32° Cto 34° C) compared with no temperature control (studies targeting normothermia or fever prevention included in the review)
• Timing of temperature control, with induction before a specific time point, such as prehospital or intracardiac arrest before ROSC, compared with temperature control induction after that specific time point
• Temperature control at a specific temperature (e.g., 33° C) compared with temperature control at a different temperature
• Temperature control for a specific duration (e.g., 48 hours) compared with a different specific duration (e.g., 24 hours)
• Temperature control with a specific method, such as external, compared with temperature control with a different specific method, such as internal
• Temperature control with a specific rewarming rate compared with a different specific rewarming rate or no specific rewarming rate

 

The updated systematic review included six new trials that were added to the 21 trials identified in the previous 2021 review for meta-analyses. The full CoSTR, (Granfeldt et al. 2023; Greif et al. 2024) with detailed results of each comparison and meta-analyses, is available online. 

In summary, a difference was not shown between hypothermic temperature control and normothermic temperature control or between other specific temperatures studies, different durations or methods of temperature control. Temperature comparisons included 32° C to 34° C versus normothermia or fever prevention, 33° C versus 36° C, 32° C versus 34° C, 33° C versus 34 ° C, 33° C versus 32° C and 31° C versus 34° C. Several of these comparisons were based on a single study. For duration of cooling, specific comparisons included 12 to 24 hours of temperature control versus 36 hours of temperature control, 48 hours of hypothermic temperature control and 24 hours of hypothermic temperature control. Methods of temperature control included endovascular cooling versus surface cooling. Rewarming studies compared rewarming at 0.25° C/hour versus 0.50° C/hour. 

The updated treatment recommendations stemming from the ILCOR CoSTR (Granfeldt et al. 2023; Greif et al. 2024) include:

• A suggestion of actively preventing fever by targeting a temperature of 37.5° C or less for those patients who remain comatose after ROSC from cardiac arrest (weak recommendation, low certainty evidence)
• Subpopulations of cardiac arrest patients who may benefit from targeting hypothermia at 32° C  to 34° C remains uncertain 
• Comatose patients with mild hypothermia after ROSC should not be actively warmed to achieve normothermia (Good practice statement)
• A recommendation against the routine use of prehospital cooling with rapid infusion of large volumes of cold intravenous fluid immediately after ROSC (strong recommendation, moderate certainty evidence)
• A suggestion for surface or endovascular temperature control techniques when temperature control is used in comatose patients after ROSC (weak recommendation, low certainty of evidence)
• When a cooling device is used, a suggestion of using a temperature control device that includes a feedback system based on continuous temperature monitoring to maintain the target temperature (Good practice statement)
• A suggestion for active prevention of fever for 36 to 72 hours in post-cardiac arrest patients who remain comatose (Good practice statement)

 

Insights and Implications

The primary change in the ILCOR good practice statement and Red Cross guidelines between 2021 and 2024 is a modification in the suggested duration of active fever prevention—from at least 72 hours to 36 to 72 hours. The available evidence is too limited to make a more specific guideline recommendation, but the ongoing Influence of the Cooling duration on Efficacy in Cardiac Arrest Patients (ICECAP) trial (Meurer et al. 2024, 502) may help delineate the optimal duration of hypothermic temperature control for neuroprotection following OHCA. 

In a detailed discussion by the ILCOR task force, it was noted that although evidence is limited, active temperature control continues to be recommended in post-cardiac arrest patients (Granfeldt et al. 2023; Greif et al. 2024). Fever prevention temperature control was favored by the majority of the ILCOR task force as opposed to hypothermic temperature control, based on the findings of the systematic review—including fewer side effects than with hypothermic temperature control and the need for fewer resources. Hypothermic temperature control can be resource-intensive and require the coordination of endovascular or other cooling, ongoing cardiac care, neurological monitoring and additional post-arrest care. Hospitals and medical centers that provide post-cardiac arrest care typically have protocols for active temperature control.

No difference was found in the 2024 ILCOR systematic review in overall outcomes between patients treated with hypothermia, normothermia, or with fever prevention. Notably, there was no evidence of worse outcomes with hypothermic temperature control. One trial (Lascarrou et al. 2019, 2327) showed better survival with favorable functional outcome in the hypothermic temperature control group among nonshockable cardiac arrest patients. However, 90-day survival was not significantly different. It is important to recognize that the large trials of hypothermic temperature control have primarily included a population of cardiac arrest patients with an initial shockable rhythm and a primary cardiac cause. In the U.S., the initial rhythm seen in cardiac arrest is more often nonshockable, as may be seen in noncardiac, respiratory events (e.g., drug overdose, drowning, sepsis and respiratory failure) (Tsao et al. 2023, e93). Additional studies are needed to determine if the subgroup of patients with an initial nonshockable rhythm, or patients with cardiac arrest not due to a primary cardiac cause, may benefit from hypothermic temperature control.

 

Mean Arterial Blood Pressure Goal in Adults

Last Full Review: ILCOR 2015
Last Update: 2024

Is there an optimal mean arterial pressure (MAP) to maintain for patients with return of spontaneous circulation (ROSC) post-cardiac arrest? A systematic review (Callaway et al. 2015, S84) by the International Liaison Committee on Resuscitation (ILCOR) in 2015 found insufficient evidence to recommend a specific hemodynamic target for patients with ROSC following cardiac arrest. Additional studies on hemodynamic goals post-ROSC have since been published, including a systematic review (Niemelä 2023, 109862).

The ILCOR systematic review (Niemelä 2023, 109862) used an individual patient data meta-analysis to determine outcomes by targeting an MAP higher or lower than 70 mmHg in patients post-ROSC. This review was used by ILCOR in an adolopment process (Schünemann et al. 2017, 101), which is a process designed to guide the adaptation of an existing published systematic review, following strict methodology, including an updated search of the literature and incorporation of relevant new studies. The adolopment process can result in the formation of Consensus on Science with Treatment Recommendations (CoSTR) by ILCOR.

 

Evidence Summary

A 2023 ILCOR systematic review (Niemelä et al. 2023, 109862) using the adolopment process included randomized controlled trials (RCTs) evaluating a MAP of 71 mmHg or higher in adults with sustained ROSC after cardiac arrest, compared with a MAP of 70 mmHg or lower. Four RCTs (Jakkula et al. 2018, 2091; Ameloot et al. 2019, 1804; Grand 2020, S100; Kjaergaard et al. 2022, 1456) of 1065 patients treated after out-of-hospital cardiac arrest compared lower and higher MAP targets following ROSC. For the lower MAP target, actual MAPs in the studies varied from 63 mmHg to 70 mmHg. Mean arterial pressures in the higher MAP studies ranged from 71 mmHg to 100 mmHg. A continuous infusion of norepinephrine was used in most studies to obtain the targeted MAP.

For the critical outcome of mortality at 180 days, a difference was not shown when targeting a higher MAP compared with a lower MAP (RR, 1.08, 95% CI, 0.92–1.26). No difference was shown for other outcomes, including good functional outcome at 180 days, intensive care unit mortality and new arrhythmia resulting in hemodynamic compromise or cardiac arrest when targeting a higher MAP compared with a lower MAP.

The accompanying ILCOR CoSTR (Skrifvars et al. 2023; Greif et al. 2024) concludes that while the four studies included since the 2015 review provide significant new evidence, an optimal blood pressure strategy post-ROSC has still not been identified. An updated ILCOR treatment recommendation states that there is insufficient evidence to recommend a specific blood pressure goal after cardiac arrest. Therefore, they suggest a MAP goal of at least 60 mmHg to 65 mmHg in patients after out-of-hospital and in-hospital cardiac arrest.

Insights and Implications

The suggested MAP threshold of 65 mmHg was agreed upon by the ILCOR task force leading this review, as it is the accepted standard in other forms of critical evidence and there is no evidence to deviate from this standard in post-cardiac arrest patients. Targeting a higher MAP was not found to have a statistically significant benefit or harm, but an upper limit for MAP is unknown. Indirect evidence from a retrospective analysis (Walsh et al. 2013, 507) of perioperative data from 33,330 noncardiac surgeries found an association between an intraoperative MAP less than 55 mmHg and adverse cardiac and renal-related outcomes. Although this study involves a different patient population, it points out the potential harms from hypotension while the optimal strategy for achieving a target MAP is one of several identified knowledge gaps described in need of future research.

 

Post-Cardiac Arrest Coronary Angiography

Last Full Review: ILCOR 2021
Last Update: 2022

A 2021 systematic review (Nikolaou et al. 2021, 28) and Consensus on Science with Treatment Recommendations (CoSTR) (Wyckoff et al. 2022, e645; Drennan et al. 2021) by International Liaison Committee on Resuscitation (ILCOR) evaluated evidence to support early versus late coronary angiography following cardiac arrest of suspected cardiac etiology with return of spontaneous circulation (ROSC), with or without ST-elevation on electrocardiogram (ECG). Results of this review informed the 2021 Red Cross guidelines. A new randomized controlled trial (RCT) (Desch et al. 2021, 2544) on this topic has since been identified, and for 2022, the CoSTR (Nikolaou et al. 2021, 28)  and CoSTR (Wyckoff et al. 2022, e645; Drennan et al. 2022) has been updated with the search strategy restricted to RCTs published since the prior search was run.

 

Evidence Summary

A 2021 ILCOR systematic review (Drennan et al. 2021; Wyckoff et al. 2022, e645) of early versus late coronary angiography in comatose patients following cardiac arrest of suspected cardiac etiology with ROSC was updated (Wyckoff et al. 2022a, e483; Drennan et al. 2022) to include a single new RCT (Desch et al. 2021, 2544) allowing additional meta-analyses of some outcomes for patients without ST-segment elevation on post-ROSC ECG. The overall results of the revised meta-analyses are unchanged, and the ILCOR treatment recommendations are unchanged (Wyckoff et al. 2022a, e483; Drennan et al. 2022).

Insights and Implications

The Red Cross guideline wording reflects the finding that for post-cardiac arrest patients without ST-segment elevation on ECG, regardless of a shockable or non-shockable presenting cardiac arrest rhythm, there was insufficient evidence to show improved outcomes with early coronary angiography. Early coronary angiography is an accepted standard of care for ST-elevation myocardial infarction without cardiac arrest. No evidence was found in the ILCOR systematic review to alter this strategy for patients with ST-segment elevation following cardiac arrest with ROSC.

 

Post-Cardiac Arrest Care Seizure Prophylaxis or Treatment

Last Full Review: ILCOR 2020
Last Update: 2024

Seizures or epileptiform activity on electroencephalograms (EEGs) occur in approximately 20% to 30% of comatose patients in the post-cardiac arrest period and are manifestations of post-cardiac arrest brain injury. A 2020 International Liaison Committee on Resuscitation (ILCOR) systematic review did not find evidence supporting the use of prophylactic anti-seizure medication in adults who are comatose following return of spontaneous circulation (ROSC) from cardiac arrest (Cronberg et al. 2020; Berg 2020, S92). This review has been updated following newly identified trials.

 

Evidence Summary

A 2024 ILCOR systematic review and Consensus on Science with Treatment Recommendations (CoSTR) (Nicholson et al. 2024; Greif et al. 2024) assessed the effect of prophylaxis and treatment of seizures on survival and neurological and functional outcomes for both adult and pediatric patients with cardiac arrest and ROSC. Findings from the pediatric arm of this review can be found in the American Red Cross Healthcare Guidelines, Pediatric Advanced Life Support: EEG Monitoring and Seizure Management. 

For the review of prophylactic anti-seizure medication, two prospective randomized controlled trials (RCTs) were included (Brain Resuscitation Clinical Trial Group 1986, 397; Longstreth et al. 2002, 506). No benefit was shown from prophylactic anti-seizure medication (thiopentone versus standard care) in 262 patients for good neurological outcome at 12 months (Brain Resuscitation Clinical Trial Group 1986, 397). A second RCT found no difference from treatment with magnesium, diazepam or combined treatment with magnesium and diazepam versus placebo for an outcome of survival with good neurological outcome at 3 months (Longstreth et al. 2002, 506). A nonrandomized prospective trial with historic controls reported no improvement in neurological outcome at hospital discharge with thiopentone compared with standard care (Monsalve et al. 1987, 244).

Evidence identified for the treatment of seizures in comatose post-cardiac arrest patients was limited to a single RCT (Ruijter et al. 2022, 724) that included 172 patients. This trial compared standard care plus administration of anti-seizure medications versus standard care alone for suppressing rhythmic and generalized periodic EEG activity detected on continuous EEG monitoring for at least 48 consecutive hours. Standard care included active temperature control in both groups. Complete suppression of rhythmic and periodic EEG activity for 48 consecutive hours occurred in 49/88 patients (56%) in the anti-seizure medication group and in 2/83 patients (2%) in the standard care group. However, no benefit was found in this trial for outcomes of survival with favorable neurological outcome at 3 months. 

No RCTs were identified that assessed clinical outcomes following treatment of clinical seizures post-cardiac arrest compared with no seizure treatment.

The ILCOR treatment recommendations based on this CoSTR statement contain minor revisions from 2020, primarily for clarity, including a good practice statement that suggests treatment of both clinically apparent and electrographic seizures in post-cardiac arrest adults. The International Liaison Committee on Resuscitation continues to suggest against the use of prophylactic anti-seizure medication in post-cardiac arrest adults who are comatose. There is a new recommendation that suggests treatment of rhythmic and periodic EEG patterns that are on the ictal-interictal continuum in comatose post-cardiac arrest adults.

Definitions

Terminology and definitions used in this review and in the Red Cross guidelines have been established by the American Clinical Neurophysiology Society (Hirsch et al. 2021, 1). The full CoSTR is available online for more details. Definitions include: 

• Electrographic seizure: Epileptiform discharges averaging greater than 2.5 Hz for 10 seconds or more (more than 25 discharges in 10 seconds), OR, any pattern with definite evolution as defined previously and lasting 10 or more seconds. 
• Electroclinical seizure: An EEG pattern with either definite clinical correlate time-locked to the pattern (or any duration), OR, EEG and clinical improvement with a parenteral anti-seizure medication.
• Ictal-interictal continuum: An EEG pattern that “does not qualify as an electrographic seizure or electrographic status epilepticus, but there is a reasonable chance that it may be contributing to impaired alertness, causing other clinical symptoms and/or contributing to neuronal injury.”

 

Insights and Implications

Red Cross Guidelines are informed by the 2024 ILCOR systematic review on post-cardiac arrest seizure prophylaxis and treatment (Nicholson et al. 2024; Greif et al. 2024). The guideline and recommendation against the use of prophylactic anti-seizure medication post-cardiac arrest is based on the lack of direct evidence that anti-seizure medication prevents seizures or improves important clinical outcomes, and the evidence that the medication is not associated with improved outcomes in adults with other forms of acute brain injury and can produce significant side effects. In addition, sedatives are commonly used in comatose post-cardiac arrest patients and are known to have anti-seizure effects.

The current Red Cross Guidelines provide a good practice statement that healthcare professionals may consider continuous EEG monitoring in comatose adults with ROSC post-cardiac arrest. The 2024 ILCOR systematic review did not specifically look at the relative benefit of continuous EEG monitoring compared with intermittent EEG monitoring, and notes that continuous EEG monitoring is labor-intensive and likely to add significant cost to patient care. Continuous EEG monitoring in comatose post-arrest patients may be associated with increased detection of rhythmic and periodic EEG activity and changes to anti-seizure medications. Expert consultation is suggested for EEG monitoring and interpretation. Further research is needed in the post-cardiac arrest population to identify optimal timing and technique for EEG monitoring.

 

Post-Cardiac Arrest Prophylactic Antibiotics

Last Full Review: ILCOR 2020

A 2020 International Liaison Committee on Resuscitation (ILCOR) systematic review and Consensus on Science with Treatment Recommendations evaluated the early prophylactic use of antibiotics compared with delayed, clinically driven administration of antibiotics in adults following ROSC from cardiac arrest in any setting (Berg et al. 2020, s92).

 

Evidence Summary

Outcomes reviewed included survival, survival with good neurological outcome, critical care length of stay, infective complications, and duration of mechanical ventilation or of antibiotic administration (Berg et al. 2020, s92).

Two randomized controlled trials (RCTs) included in the systematic review (François et al. 2019, 1831; Ribaric et al. 2017, 103) with 254 patients showed no benefit from use of prophylactic antibiotics compared with clinically driven administration of antibiotics (RR, 0.89; 95% CI, 0.71–1.12; P=0.31; RD, -0.06; 95% CI, -0.19–0.06) for outcomes of survival with good neurological outcome (up to day 30) at last recorded time point (Berg et al. 2020, s92). The same two RCTs did not show a benefit for survival up to day 30 with prophylactic antibiotics compared with clinically driven administration; conflicting results were reported for two observational studies. The RCTs (François et al. 2019, 1831; Ribaric et al. 2017, 103) included showed no benefit from prophylactic antibiotic use compared with standard care for the outcomes of infective complications (pneumonia), for critical care length of stay, or for duration of mechanical ventilation (Berg et al. 2020, s92).

A weak recommendation is made by ILCOR against the use of prophylactic antibiotics in patients following return of spontaneous circulation after cardiac arrest (Berg et al. 2020, s92).

Insights and Implications

In making this recommendation, the reviewers note that it does not cover situations where antibiotics are used for confirmed or suspected infections, and that both of the included RCTs enrolled only out-of-hospital cardiac arrest patients who were treated with targeted temperature management (32° C to 35° C [89.6° F to 95° F]) (Berg et al. 2020, s92). Another consideration noted is that pneumonia occurs in about 50% of intensive care unit patients after cardiac arrest, but it is unlikely to contribute to mortality as most deaths are attributed to neurological, cardiovascular or multi-organ failure (Berg et al. 2020, s92). Additionally, the incidence of pneumonia after cardiac arrest would mean using prophylactic antibiotics in large numbers of patients without specific benefit.