Post-cardiac arrest care: An integrated approach to management after resuscitation

Abstract

Post-cardiac arrest care is key in determining neurological recovery and survival after return of spontaneous circulation (ROSC). Despite recent advances, post-arrest mortality remains high due to myocardial dysfunction, cerebral injury, and systemic inflammation. Guidelines recommend avoiding hypotension and using individualized hemodynamic targets with a mean arterial pressure ≥ 65 mmHg commonly used as an initial threshold, although higher targets may be considered in select patients with impaired cerebral autoregulation. Early coronary angiography and revascularization are indicated for ST-elevation myocardial infarction but have not demonstrated a mortality benefit in non-ST-elevation cohorts. Current evidence increasingly emphasizes strict fever prevention and individualized temperature management strategies, while uncertainty remains regarding which patient subgroups may benefit from deeper hypothermia. Post-ROSC ventilation strategies suggest avoiding both hypoxemia and severe hyperoxemia, targeting peripheral oxygen saturation of 92%-98% and normocapnia. Sedation with propofol or dexmedetomidine and analgesia with fentanyl/remifentanil, with appropriate shivering control, enhances targeted temperature management tolerance. Multimodal neuroprognostication incorporating neurological examination, electrophysiology, neuroimaging, and biomarkers (such as neuron-specific enolase and neurofilament light chain) should be performed. Early prognostic findings should be interpreted cautiously to minimize premature withdrawal of life-sustaining therapy. Future research should refine hemodynamic, temperature, and prognostic targets to optimize individualized post-resuscitation care for patients with cardiac arrest.

Key Words: Cardiac arrest; Post-resuscitation care; Targeted temperature management; Neuroprognostication; Hemodynamics; Oxygenation

Core Tip: Post-cardiac arrest syndrome remains associated with high mortality and poor neurological outcomes despite advances in resuscitation care. This review summarizes the current evidence on comprehensive post-resuscitation management, including hemodynamic optimization, coronary interventions, targeted temperature management, ventilation, metabolic support, sedation, and multimodal neuroprognostication. Current evidence increasingly favors strict fever prevention and individualized management strategies over uniform protocol-driven targets. Early multidisciplinary care and cautious delayed neuroprognostication remain critical to minimizing secondary neurologic injury and improving outcomes after cardiac arrest.

INTRODUCTION

Cardiac arrest remains one of the most devastating and life-altering events for patients and their families. Annually, 350000 people in the United States suffer an out-of-hospital cardiac arrest (OHCA) with short-term survival rates of approximately 6%[1,2]. Management priorities revolve around two major goals: Prevention of neurological injury and minimization of the risk of recurrence of cardiac or hemodynamic decompensation. Early restoration of perfusion and oxygenation has the potential to significantly alter the outcomes in these patients[3]. The initial efforts are heavily focused on achieving return of spontaneous circulation (ROSC), and once achieved, it becomes imperative to admit these patients swiftly to the intensive care unit (ICU). Due to progressive ischemic neurological injury, cardiac arrest is associated with considerably worse short- and long-term outcomes. Even after ROSC is achieved, patients tend to suffer from myocardial dysfunction, neurological insult, and systemic perfusion imbalances, leading to post-cardiac arrest syndrome (PCAS)[4,5].

A significant amount of effort has been invested in improving the chain of survival from the time of cardiac arrest until the patient reaches the hospital, involving high-quality cardiopulmonary resuscitation (CPR), early defibrillation, advanced life support, and airway management. Immediately post-arrest, ischemic depolarization of neurons initiates a cascade of neurological injury in these patients. Following ROSC, reperfusion injury further contributes to secondary neurologic damage[6]. Post-ischemic dysregulation follows this and lasts for several minutes to several days, while the return of synaptic plasticity takes several weeks to years, with post-resuscitation oxidative stress potentially accelerating brain dysfunction[7]. Interestingly, the 10-year survival rate exceeds 60% for patients who survive their initial acute hospital stay or at least 30 days after OHCA[8].

Post-resuscitation care requires urgent stabilization of the airway and hemodynamics, rapid identification and reversal of the cause of arrest, temperature management, and multidisciplinary support for salvaging organs, including management of cerebral ischemia, myocardial dysfunction, and reperfusion injury (Figure 1). Early transfer of these patients to specialized cardiac arrest and shock centers may be crucial for their survival. Neuro-prognostication should be deferred for at least 72 hours, and premature withdrawal of care should be avoided even in comatose patients.

Figure 1 Framework for post-resuscitation care after cardiac arrest. Post return of spontaneous circulation management requires a multidisciplinary, individualized approach that integrates hemodynamic optimization, temperature management, respiratory support, neurologic monitoring, coronary evaluation, metabolic stabilization, and supportive critical care measures. Key domains include maintaining adequate cerebral and systemic perfusion, actively preventing fever with selective use of targeted temperature management, avoiding hypoxemia and severe hyperoxia, early identification of reversible coronary etiologies, structured neuroprognostication, and ongoing reassessment of goals of care. Management strategies should be tailored according to neurologic status, hemodynamic profile, arrest characteristics, and available institutional resources. ROSC: Return of spontaneous circulation; MAP: Mean arterial pressure; MCS: Mechanical circulatory support; TTM: Targeted temperature management; SpO₂: Peripheral oxygen saturation; PaCO₂: Arterial carbon dioxide tension; ECG: Electrocardiogram; EEG: Electroencephalogram; SSEP: Somatosensory evoked potential; NSE: Neuron-specific enolase; NfL: Neurofilament light chain; STEMI: ST-elevation myocardial infarction; OHCA: Out-of-hospital cardiac arrest. Figure created with BioRender (Supplementary material).

Our narrative review was developed through a structured review of major literature on adult post-cardiac arrest care. PubMed/MEDLINE, guideline statements from the American Heart Association, the European Resuscitation Council, and the Neurocritical Care Society, and major randomized controlled trials published between 2000 and 2026 were reviewed. Priority was given to landmark randomized trials, large observational studies, society guidelines, and consensus statements focusing on hemodynamic optimization, coronary interventions, targeted temperature management (TTM), ventilation strategies, sedation, and neuroprognostication after ROSC.

Recent bibliometric analyses of the global CPR literature have demonstrated increasing research focus on TTM, cardiogenic shock, extracorporeal support, and outcome-oriented post-resuscitation care, underscoring the need for reviews focused on post-cardiac arrest management[9]. In this review, we discuss the current clinical evidence, recent updates, global consensus, and factors involved in optimal post-resuscitation care in adults.

HEMODYNAMICS AND CORONARY INTERVENTIONS

Current guidelines generally recommend avoidance of hypotension and targeting a mean arterial pressure (MAP) of at least 65 mmHg in post-ROSC patients, although optimal hemodynamic targets may vary depending on baseline vascular physiology, chronic hypertension, and cerebral autoregulatory status[10]. Physiologically, a higher MAP is targeted to maintain adequate cerebral perfusion pressure in the presence of neurological injury (loss of cerebral autoregulation). However, a consistent clinical benefit of targeting MAP > 80 mmHg in most comatose post-ROSC patients has not been identified, although select patients with impaired cerebral autoregulation may physiologically benefit from higher pressures[11]. While avoidance of hypotension is strongly supported in post-ROSC care, evidence supporting routine targeting of higher MAP thresholds remains limited and inconsistent across randomized studies, with personalized hemodynamic strategies being an important area of ongoing investigation.

The blood pressure and oxygenation targets in post resuscitation care trial, a double-blind randomized controlled trial involving patients with OHCA, showed no difference in survival or neurological outcomes in patients with greater MAP goals compared to those with lower MAP goals [77 mmHg vs 63 mmHg: Hazard ratio (HR), 1.08; 95%CI: 0.84-1.37; P value 0.56; n = 789] within 90 days, indicating that targeting higher MAP goals in comatose post-ROSC patients did not significantly improve outcomes[12]. Importantly, fixed MAP targets may not adequately account for interindividual variability in cerebral autoregulation following cardiac arrest. Patients with chronic hypertension or impaired autoregulatory mechanisms may require higher perfusion pressures to maintain adequate cerebral blood flow. Emerging approaches involving cerebral autoregulation monitoring, near-infrared spectroscopy, and individualized hemodynamic assessment may help refine personalized perfusion targets in future post-resuscitation care strategies, although robust outcome-based evidence remains limited.

Patients resuscitated after cardiac arrest are often in a state of hemodynamic compromise, with nearly 40%-70% of patients experiencing post-resuscitation shock[13,14]. In clinical practice, shock may often be multifactorial. Myocardial stunning, vasoplegia, and systemic inflammation further complicate the management of patients with PCAS, and early echocardiography may help elucidate the mechanisms contributing to hypotension and shock[15-18]. Furthermore, invasive hemodynamic assessment and mechanical circulatory support (MCS) may be considered in carefully selected patients with refractory cardiogenic shock despite optimized medical therapy. Early transfer to specialized cardiac arrest and shock centers may improve multidisciplinary access to advanced critical care, coronary intervention, and MCS strategies.

Vasopressor support is crucial for hypotensive patients with PCAS, with norepinephrine being the preferred agent due to its overall efficacy, safety, and the paucity of comparative clinical data among vasopressors in this setting[19]. Additional vasoactive agents may be added based on the predominant type of shock and the patient’s hemodynamic characteristics and electrical stability (heart rate, arrhythmias, and other comorbidities). No pharmacological support is typically recommended for patients with hemodynamically stable bradyarrhythmia. However, if it is accompanied by hemodynamic compromise, chronotropic pharmacologic support and temporary pacing should be considered.

Coronary angiography may be crucial in identifying the culprit lesion in subjects with cardiac arrest and suspected coronary ischemic etiology. However, the timing of angiography remains debatable. Most clinical trials conducted to date suggest that early or emergent coronary angiography may be beneficial in patients with ST-elevated myocardial infarction (STEMI), which is typically associated with a totally occluded infarct artery[20]. However, such benefits have not been shown in patients with non-STEMI (NSTEMI), which is usually related to suboptimal coronary flow and atherothrombosis[21-25]. Despite the lack of benefits in the outcomes, individualized decision-making should be encouraged, particularly in patients with ongoing cardiogenic shock or electrical instability, since these trials largely excluded unstable patients.

Overall, current evidence supports individualized hemodynamic management focused primarily on avoiding hypotension rather than a uniform escalation toward higher MAP targets. Although higher pressures may improve surrogate physiologic parameters in selected patients, robust evidence demonstrating improved neurological recovery or survival remains limited. Beyond hemodynamic stabilization and coronary reperfusion strategies, mitigation of secondary neurologic injury remains central to post-resuscitation care.

TARGETED TEMPERATURE MANAGEMENT

Hypothermia has been extensively studied in patients with cardiac arrest. However, the evidence has been modest (and variable) in adults, despite a strong physiological explanation and a considerably favorable effect in animal models [over 60% reduction in mortality; odds ratio (OR): 0.33; 95%CI: 0.24-0.45] and in the pediatric population[26,27]. The earliest clinical trials compared outcomes with temperature control at 33-36 °C for the first 24 hours, whereas newer trials emphasized avoiding fever [≤ 37.5 °C or ≤ 37.7 °C (European recommendation)]. The lack of consistent replication of preclinical hypothermia data in human clinical trials is likely multifactorial. Potential explanations include overestimating the translational impact of preclinical findings, delayed initiation of hypothermia in clinical settings, and limited high-quality evidence on the optimal depth and duration of cooling. In addition, the complex pathophysiology of PCAS and the potential adverse effects of hypothermia may further influence clinical outcomes.

Despite the shortcomings and challenges, temperature management remains an important component of post-resuscitation care, although current evidence increasingly favors strict fever prevention and individualized patient selection over routine deep hypothermia. Data from relatively small clinical trials conducted nearly two decades ago showed that mild to moderate therapeutic hypothermia (32-34 °C) for 12-24 hours was associated with favorable neurologic outcomes at discharge and 6 months in patients successfully resuscitated after an out-of-hospital ventricular fibrillation arrest[28,29]. This led to a widespread and rather premature adoption of TTM in this population. Subsequent larger clinical trials expanded the studied populations to include non-shockable rhythms and compared hypothermia (≤ 33 °C) with higher temperature targets (34-36 °C or strict normothermia with fever prevention). The risk of mortality or poor neurologic outcome was noted to be similar in the hypothermia and control groups at 6 months [TTM trial: Relative risk (RR): 1.02; 95%CI: 0.88-1.16; P value = 0.78; n = 950; TTM-2 trial: RR: 1.04; 95%CI: 0.94-1.14; P value = 0.37; n = 1900; Moderate vs mild therapeutic hypothermia in comatose survivors of out-of-hospital cardiac arrest trial: RR: 1.07; 95%CI: 0.86-1.33; P value = 0.56; n = 389][30-32]. The results of these trials suggest that avoiding fever may be just as effective as therapeutic hypothermia, albeit accounting for the advancements in critical care management over the past several years (clinical trials summarized in Table 1).

Table 1 Completed and ongoing major clinical trials on targeted temperature management.

Trial	n	Rhythm	TTM strategy/goals	Primary endpoint	Primary endpoint event rates/effect sizes	Neurologic outcome(s)
HACA (2002)[28]	275	S	32-34 °C vs normothermia	Favorable neurologic outcome at 6 months	55% vs 39%; OR: 1.40 (95%CI: 1.08-1.81)a	Improved
Bernard et al[29], 2002	77	S	33 °C vs normothermia	Survival to discharge with good neurologic outcome	49% vs 26%b	Improved
TTM1 (2013)[30]	950	S/NS	33 °C vs 36 °C	All-cause mortality at end of trial	50% vs 48%; HR: 1.06 (95%CI: 0.89-1.28)	Similar
FROST-I (2018)[69]	291	S	32 °C vs 33 °C vs 34 °C	Favorable neurologic outcome at 6 months	46.4% vs 44.9% vs 42.3%c	Similar
HYPERION (2019)[33]	584	NS	33 °C vs normothermia	Favorable neurologic outcome at 90 days	10.2% vs 5.7%; absolute difference 4.5% (95%CI: 0.1-8.9)d	Improved
CAPITAL CHILL (2021)[32]	389	S	31 °C vs 34 °C	Survival with favorable neurologic outcome at 180 days	RR: 1.07; 95%CI: 0.86-1.33e	Similar
ISOCRATE (2021)[70]	120	S	Rewarming at 0.25 °C/hour vs 0.5 °C/hour	IL-6 levels at rewarming	No significant difference in IL-6 levels between groups	Similar
TTM2 (2021)[31]	1900	S/NS	33 °C vs normothermia (< 37.5 °C)	Death by 6 months	50% vs 48%; RR: 1.04 (95%CI: 0.94-1.14)f	No difference
ICE-CAP[71]	1800 (expected maximum)	S/NS	33 °C for 12 hours vs 24 hours vs 72 hours	Favorable neurologic outcome at 6 months	Pending	Ongoing
R-CAST OHCA[36]	380 (expected)	S/NS	34 °C vs normothermia (moderate-severe PCAS)	Favorable neurologic outcome at 30 days	Pending	Ongoing
STEPCARE (TEMPCARE part evaluates temperature)[68,72]	3500 (expected)	S/NS	Evaluating sedation, temperature, and hemodynamics	All-cause mortality at 6 months	Pending	Ongoing

^aP value < 0.01 vs normothermia.

^bP value < 0.05 vs normothermia.

^cP value = 0.83 for three-group comparison.

^dP value = 0.04 vs normothermia.

^eP value = 0.56 vs 34 °C.

^fP value = 0.37 vs normothermia.

Major completed and ongoing randomized clinical trials evaluating targeted temperature management (TTM) after cardiac arrest. Early landmark trials, including hypothermia after cardiac arrest and Bernard et al[29], demonstrated improved neurologic outcomes with hypothermia compared with normothermia in patients with shockable rhythms. Subsequent larger clinical trials, such as TTM1 and TTM2, reported no significant differences in mortality or neurologic outcomes between lower-temperature targets and active normothermia/fever-prevention strategies. More recent and ongoing studies are evaluating alternative temperature targets, duration of cooling, rewarming strategies, and multimodal post-cardiac arrest care approaches to refine patient selection and optimize neurologic recovery. n: Sample size during statistical analysis; Rhythm: Initial rhythm during cardiac arrest; TTM: Targeted temperature management; HACA: Hypothermia after cardiac arrest; S: Shockable; OR: Odds ratio; CI: Confidence interval; TTM1: Targeted temperature management-1 trial; NS: Non-shockable; HR: Hazard ratio; FROST-I: Finding the optimal cooling temperature after out-of-hospital cardiac arrest trial; HYPERION: Therapeutic hypothermia after cardiac arrest in nonshockable rhythm trial; CAPITAL CHILL: Moderate vs mild therapeutic hypothermia in comatose survivors of out-of-hospital cardiac arrest trial; RR: Relative risk or risk ratio; ISOCRATE: Impact of speed of rewarming after cardiac arrest and therapeutic hypothermia; IL-6: Interleukin 6; TTM2: Targeted temperature management-2 trial; ICE-CAP: Influence of cooling duration on efficacy in cardiac arrest patients; R-CAST OHCA: Neurological outcomes with hypothermia vs normothermia in patients with moderate initial illness severity following resuscitation from out-of-hospital cardiac arrest trial; PCAS: Post-cardiac arrest syndrome; STEPCARE: Sedation, temperature and pressure after cardiac arrest and resuscitation trial.

Interestingly, the therapeutic hypothermia after cardiac arrest in nonshockable rhythm trial evaluated targeted hypothermia in non-shockable rhythms in both out-of-hospital and in-hospital cardiac arrest and discovered a beneficial impact of hypothermia on neurologic outcome at 90-day (determined by a cerebral performance category score of 1 or 2) (10.2% vs 5.7%; absolute difference 4.5%; 95%CI: 0.1-8.9; P value = 0.04; n = 584) compared to normothermia[33]. However, no difference was observed in the 90-day mortality rate (81.3% vs 83.2%; difference: -1.9%; 95%CI: -8.0 to 4.3). Additionally, the trial’s robustness was marginal, with a fragility index of 1, meaning that a change in even one subject’s outcome would render the differences statistically insignificant.

Currently, the American Heart Association recommends fever prevention (≤ 37.5 °C) for at least 24 hours, after which patients may be rewarmed at rates of 0.25 °C/hour to 0.5 °C/hour[34]. Similarly, a comparable rewarming rate should be considered for hypothermic patients at baseline. Shivering should be avoided using scheduled acetaminophen doses, appropriate sedation, and, in some cases, neuromuscular blockade. There is considerable heterogeneity in post-ROSC patients, which makes it challenging to objectively evaluate the therapeutic efficacy of hypothermia. While some patients are critically ill to begin with, others are too stable to influence the outcomes solely due to temperature management. A major challenge remains identifying patients most likely to benefit from targeted interventions. Therefore, attempts have been made to develop a scoring system to identify patients who would benefit most from these interventions.

The revised PCAS for therapeutic hypothermia (R-CAST) score was designed to quantify the initial severity of PCAS with five components: Initial rhythm (shockable/non-shockable), total downtime until ROSC, pH and lactate within 30 minutes of ROSC, and the motor component of the Glasgow Coma Score[35]. The neurological outcomes with hypothermia vs normothermia in patients with moderate initial illness severity following resuscitation from out-of-hospital cardiac arrest trial is an ongoing multicenter study that utilizes this score to study the effects of hypothermia on favorable neurological outcomes at 30 days in patients with moderately severe PCAS after OHCA[36]. Furthermore, clinical trials have primarily studied post-resuscitation dynamics in patients with underlying cardiac disease. This limits the generalizability of these results due to the lack of quality clinical evidence related to other causes of cardiac arrest, such as substance overdose, respiratory insufficiency, and septic shock.

The TTM2 trial substantially shifted post-resuscitation care paradigms away from routine deep hypothermia toward active fever prevention and targeted normothermia[31]. These findings have redirected attention toward the practical challenges of maintaining sustained normothermia and preventing rebound pyrexia after rewarming, which may contribute to secondary neurologic injury[37]. Current evidence supports strict fever prevention and maintenance of normothermia as the default strategy in most comatose post-ROSC patients, while deeper hypothermia may remain reasonable in carefully selected subgroups, particularly those with non-shockable rhythms or severe anoxic injury.

METABOLIC DERANGEMENTS

Early post-ROSC metabolic acidosis and lactate levels reflect tissue hypoperfusion and cellular metabolic demand[38]. Elevated lactate levels within the first hour after ROSC independently predict higher mortality and poor neurological outcomes, whereas rapid lactate clearance within 24 hours predicts improved survival[39-41]. Severe metabolic acidosis is noted exceedingly commonly in resuscitated patients, contributes to refractory shock, and is associated with mortality in the ICU[42]. The Society for Cardiovascular Angiography and Intervention recommends serial lactate measurements every 2-3 hours with normalization to < 2 mmol/L within 24 hours of shock recognition as part of a ‘door to lactate clearance’ initiative for early shock identification and optimization of support[43].

Early blood pH is an independent predictor of neurological prognosis, with a lower pH reflecting greater systemic derangement[44]. A pH > 7.2 is recommended for post-ROSC patients[45]. Moreover, a multimodal framework involving factors such as age, initial shockable rhythm, downtime, and early laboratory markers such as lactate, C-reactive protein, and glomerular filtration rate holds strong predictive value for survival [area under the curve (AUC): 0.86, 95%CI: 0.82-0.89] and favorable neurological outcome (AUC: 0.84, 95%CI: 0.80-0.88)[46].

VENTILATION

Appropriate oxygenation remains critical to avoid the propagation of hypoxic ischemic injury and mitochondrial dysfunction in comatose patients after ROSC. While hypoxia is intuitively concerning in ongoing hypoxic brain injury, hyperoxia may also be deleterious to the brain due to reactive oxygen species-mediated oxidative stress and resultant tissue damage[47]. Animal studies suggest that hyperoxia during the reperfusion phase may worsen brain injury[48]. However, these results have not translated meaningfully into clinical outcomes in human clinical trials. The Reduction of Oxygen After Cardiac Arrest trial evaluated the impact of conservative and liberal oxygen saturation in patients revived after an OHCA, primarily in the early stages of post-resuscitation care[49]. Patients were randomized into two groups based on peripheral oxygen saturation (SpO₂) targets: 90%-94% vs ≥ 98% during transport and initial ICU admission. No difference was noted in survival to hospital discharge (conservative vs liberal oxygenation groups: OR: 0.68; 95%CI: 0.46-1, P value = 0.05; sensitivity analysis: OR: 0.71; 95%CI: 0.48-1.06; P value = 0.09). However, those with a conservative oxygen saturation goal fared worse in avoiding pre-ICU hypoxia (OR of hypoxemic episode prior to ICU admission, 2.37; 95%CI: 1.49-3.79; P < 0.001).

Furthermore, other clinical trials did not provide convincing evidence that moderate hyperoxia is deleterious to these patients in terms of clinical outcomes. One randomized controlled trial suggested that the use of 100% fraction of inspired oxygen (FiO₂) may be linked to greater serum levels of neuron-specific enolase (NSE), a surrogate marker for neurologic injury, at 24 hours, when compared to a lower FiO₂ with backup support to avoid hypoxemia (SpO₂ < 95%)[50]. The clinical goal should remain the avoidance of both hypoxemia and unnecessary hyperoxemia, with oxygen titration guided by arterial blood gas assessment when feasible, since pulse oximeters may provide inconsistent measurements, especially in subjects with chronic lung disease[51]. Current guideline recommendations favor maintaining SpO₂ between 92% and 98%, emphasizing cautious oxygen supplementation rather than liberal oxygen exposure[45].

There is a physiologic rationale supporting mild hypercapnia in comatose patients after resuscitation. Carbon dioxide produces cerebral vasodilation, which may increase cerebral blood flow and exert potential anti-inflammatory effects. However, excessive hypercapnia may worsen cerebral edema and, therefore, should be avoided[52]. Similar to oxygenation, this effect has not been effectively translated into human trials. A large trial suggested that targeted mild hypercapnia (PaCO₂ 50-55 mmHg) did not affect neurological outcomes at six months when compared to targeted normocapnia (PaCO₂ 35-45 mmHg) (adjusted RR: 0.98; 95%CI: 0.87-1.11; P value = 0.76)[53]. Therefore, although mild hypercapnia appears physiologically tolerable in some patients with challenging acid-base balance, current evidence remains insufficient to support routine therapeutic hypercapnia.

SEDATION, ANALGESIA, AND NEUROMUSCULAR BLOCKADE

Sedation and analgesia facilitate cessation of shivering, reduce metabolic demand, and optimize comfort in patients undergoing cooling with TTM. Propofol and fentanyl/remifentanil are the agents of choice for sedation and analgesia, respectively[45]. Propofol should be used with caution in patients with refractory hypotension because it may worsen hypotension[54]. Alternatively, dexmedetomidine may be used in hypotensive patients, but caution must be exercised in bradycardic patients[55]. Benzodiazepine infusions should typically be avoided because of the greater probability of delirium associated with their use[56]. If indicated, shorter-acting agents (such as midazolam) should be preferred. Neuromuscular blocking agents may be reserved for patients in whom shivering is challenging to control despite adequate sedation[57]. Following stabilization of systemic physiology, accurate neurologic assessment and prognostication become major priorities in post-resuscitation care.

NEUROMONITORING AND NEUROPROGNOSTICATION OF ANOXIC ENCEPHALOPATHY

Diagnosing anoxic encephalopathy necessitates exclusion of confounding factors such as metabolic disturbances (hypernatremia, hyponatremia, and hypoglycemia), vascular processes (intracranial bleed, ischemic stroke), infections (sepsis, intracranial infections), toxin exposures (drug overdose, alcohol intoxication, ingestion of toxic substances), and pharmacological effects of sedatives or neuromuscular blockers[58,59]. Other neurological conditions, such as locked-in syndrome, Lance-Adams syndrome, akinetic mutism, and advanced dementia, should also be excluded before neuroprognostication of anoxic encephalopathy[60-62]. Initially, anoxic encephalopathy often presents as a coma, marked by a lack of self-awareness and disrupted sleep-wake cycles. Over 2-4 weeks, patients may either show signs of recovery or progress to a persistent vegetative state or brain death[63,64].

Once confounding factors are excluded, neuroprognostication should be performed using a multimodal approach that integrates neurological examination, electrophysiology [electroencephalogram (EEG) and somatosensory evoked potentials (SSEPs)], neuroimaging (computed tomography and magnetic resonance imaging), and blood biomarkers [such as NSE and neurofilament light chain (NfL)][64]. Elevated NfL levels predict poorer neuroprognosis at admission and 72 hours after cardiac arrest[65]. Neuroprognostication should be delayed to minimize the confounding effects of sedation or metabolic derangements[64]. Continuous EEG monitoring allows real-time assessment of cerebral activity, identification of electrographic status epilepticus (which may be noted in approximately 20% of patients post-ROSC), and early detection of malignant background patterns on EEG[66].

The persistent absence of brainstem reflexes, bilaterally absent N20 responses on SSEPs, highly malignant EEG patterns, and diffuse injury on neuroimaging are highly specific for poor neurological outcomes[67]. In contrast, improved motor responses, normal biomarkers, and the absence of cortical injury on imaging are predictive of better outcomes. Because individual tests may yield discordant results, combining modalities can increase prognostic accuracy.

In routine clinical practice, implementation of multimodal neuroprognostication is often limited by delayed sedation clearance, variable access to continuous EEG or SSEPs, and institutional differences in neurocritical care expertise. Modern multimodal monitoring techniques may provide important prognostic information earlier in the clinical course; however, early findings should be interpreted cautiously because premature pessimistic prognostication may contribute to a self-fulfilling prophecy through early withdrawal of life-sustaining therapy[10]. Moreover, access to continuous EEG monitoring, SSEPs, advanced neuroimaging, and specialized neurocritical care expertise may remain limited in many centers, creating practical challenges in implementing fully multimodal neuroprognostication strategies. Current guidelines, therefore, advise delaying definitive neuroprognostication until at least 72 hours after ROSC or rewarming.

CONCLUSION

Cardiac arrest is a life-altering event in a patient’s life and is associated with a remarkably poor prognosis. The current literature supports maintaining normothermia or strict fever prevention in comatose patients for 24-72 hours after ROSC. Early coronary intervention is indicated in patients with STEMI or in subjects with hemodynamic or electrical instability, but is not beneficial in hemodynamically stable NSTEMI patients. The initial management of these patients largely consists of maintaining normoxia and normocapnia, with prompt correction of electrolyte abnormalities and acidosis.

Neuromonitoring and prognostication remain challenging in patients with anoxic encephalopathy due to suboptimal prognostic tools and staff expertise. Exclusion of confounding factors is necessary before prognostication. An international clinical trial (STEP CARE) is currently underway to assess differences in temperature, sedation, and MAP goals in patients with ROSC[68].

Early multidisciplinary involvement and referral to higher cardiac arrest centers may be key to improving overall outcomes in these patients. However, our current understanding of this area is severely limited. Despite multiple studies on hypothermia, the groups that would benefit the most from hypothermia remain uncertain, and characterizing the patient phenotypes based on initial rhythm, total downtime, and illness severity who would benefit the most from it is an area of continued interest. Furthermore, the optimal duration and timing of TTM and their effects on long-term neurological recovery remain areas for further research. Future studies should further evaluate the optimal duration, intensity, and methods of fever prevention in the post-TTM2 era, including prolonged prophylactic normothermia strategies. Lastly, access to multimodal neuroprognostication tools (such as continuous EEG, SSEPs, biomarkers, and imaging) and neurocritical care experts would improve prognostic accuracy and guide appropriate discussions on goals of care.

Joint discussions and shared decisions with next of kin or health care proxies are required, bearing in mind the limited evidence base for most interventions and the limitations of early neuroprognostication. Future post-resuscitation care paradigms may increasingly shift toward precision resuscitation strategies that incorporate individualized hemodynamic, temperature, and neurophysiologic targets rather than uniform protocol-driven thresholds.