Care after return of spontaneous circulation (ROSC)

Post-resuscitation care

Victims of out-of-hospital cardiac arrest (OHCA) who achieve ROSC in the emergency room (ER) are transferred to the intensive care unit (ICU), coronary care unit (CCU), or catheterization laboratory. A 12-lead ECG must be obtained immediately after ROSC in order to identify cases with ST-segment elevations, which demand urgent coronary angiography with the intent to perform PCI. The decision to transfer the patient to the ICU or CCU depends on the system of care and patient status. The absolute majority of patients should be managed in the ICU. Post-resuscitation care requires expertise and resources to diagnose, monitor and manage neurological injuries, hemodynamic and respiratory instability, multiorgan failure, infections, seizures and temperature management. The ICU is the preferred level of care for the absolute majority. The CCU may be suitable for stable (hemodynamically and respiratory) and fully conscious patients who experienced a brief cardiac arrest.

Post-resuscitation care is an integral component of the chain of survival. It includes diagnosis of post-cardiac arrest syndrome (PCAS), optimization of ventilation, oxygenation, hemodynamics, antiischemic treatment, temperature treatment, treatment of seizures, and infections. However, the underlying evidence for many of the recommendations is based on few randomized trials and the evidence is often conflicting. Many recommendations are therefore based on observational data, expert opinion, or extrapolation from other fields (e.g. sepsis research) or physiological reasoning.

Cardiac arrest care is advanced and should preferably only be conducted in specialized centers. Patients who are not in specialized cardiac arrest centers should, if feasible, be transferred to such centers.

Post-cardiac arrest syndrome (PCAS)

Post-cardiac arrest syndrome (PCAS) emerges after ROSC or initiation of ECMO. The syndrome was first described by Negovsky, who identified four processes that defined the victim’s outcome:

1. Neurological injury
2. Myocardial dysfunction
3. Systemic response to reperfusion and ischemia
4. Effects of the underlying cause of cardiac arrest

Neurological injuries may cause coma, seizures (myoclonus), stroke, cognitive dysfunction, Parkinsonism, vegetative state, or brain death. The cause of brain injuries is anoxic cell death, continued dysfunction in cerebral blood flow (autoregulation) after ROSC and cerebral hypoperfusion.

Myocardial dysfunction is defined by stunning, which means that myocardial contractions have ceased (akinesia) or is severely reduced (hypokinesia). Myocardial stunning always occurs after prolonged ischemia, which is a mechanism to protect the cell from continued ischemic damage by downregulating metabolism (and thus contractility). Stunning may persist for hours, days and weeks. It reduces cardiac output and lower blood pressure. Cardiogenic shock may develop as a result of stunning.

The systemic response to reperfusion and ischemia causes a state similar to SIRS (systemic inflammatory response syndrome) with risk of disseminated intravascular coagulation, hypotension, impaired vasoregulation, etc.

With regard to the underlying cause of cardiac arrest, the key challenge is to identify and treat reversible causes, e.g. myocardial ischemia.

Yan et al showed that globally the incidence of ROSC in OHCA is roughly 30%, the rate of survival to hospital admission is 22%, but the rate of survival to hospital discharge is only 8.8%, which demonstrates that the majority of patients will not survive post-resuscitation care. Among those who survive to hospitalization, 50-65% die within 24 hours (Soar et al). The causes of death among these patients are complications related to PACS:

• 60% die from neurological injuries.
• 30% die from hemodynamic failure and multiorgan dysfunction.
• 10% die from recurrent arrhythmias.

To monitor and evaluate the victim after ROSC, the following modalities and investigations are routinely used:

• Computed tomography (CT): brain, thorax, abdomen
• Magnetic resonance imaging (MRI): brain
• Neurological examination
• Coronary angiography, PCI
• Invasive measurement of blood pressure, cardiac output (CO), pulse oximetry (POX), capnography
• ECG
• EEG
• Renal function, hepatic function, electrolyte concentrations, blood count, leukocytes, CRP, pro-calcitonin, glucose.

Targeted temperature management (TTM)

Core body temperature can be controlled using several methods, with varying complexity, cost and precision. Available methods include ice packs, intravenous infusion of cold fluids, intranasal cooling with evaporated air, surface cooling systems using circulating water/air, and ECMO. The latter is the most efficient and precise method for controlling body temperature, although it requires vast resources. The most common temperature targets in TTM are as follows:

• Targeted normothermia (<37.6°C), which implies avoiding fever and hypothermia.
• Targeted hypothermia (32-34 °C).
• Targeted mild hypothermia (36°C).

The pathophysiological rationale behind targeted hypothermia is the theoretical and experimental evidence indicating neuroprotective benefits. Cerebral hypothermia reduces neuronal metabolism, decreases production of reactive oxygen-species (ROS), supports the blood-brain barrier and reduces intracerebral inflammation, thus limiting neuronal cell death (Tahsili-Fahadan et al).

The 2020 AHA Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care issued five class 1 recommendations for the use of targeted temperature management. With the publication of the TTM2 trial (Dankiewicz et al), subsequent guidelines (ERC) issued weaker recommendations for the use of temperature management.

In the past two decades, several large randomized clinical trials have examined the effect of TTM on mortality and neurological function, including meticulous evaluations of cognitive function among survivors (Lilja et al, Cronberg et al, Lüsebrink et al). The TTM2 trial, the largest and arguably most generalizable trial to date, showed no benefit of using TTM as compared with targeted normothermia. The use of targeted temperature management has become controversial since the publication of the TTM2 trial. Four randomized clinical trials have tested TTM with results summarized in Table 1.

Trial	Inclusion	Study size	Strategy	Endpoint	Results (TTM vs control group)	Consluions
Bernard et al	OHCA with VF	77	33°C for 12 hours vs. normothermia	Discharge with good neurological outcome	49% vs. 26% (p=0.046)	TTM is beneficial
HACA trial (Hypothermia After Cardiac Arrest)	OHCA with VF/VT	275	32-34°C for 24 hours vs. normothermia	Favorable neurologic outcome at 6 months	55% vs. 39% (p=0.009)	TTM is beneficial
TTM1	OHCA, any rhythm	939	33°C vs 36°C	Mortality to end of follow-up	50% vs. 48% (p=0.51)	TTM is not benficial
TTM2	OHCA with VF	1861	33°C vs normothermia	Mortality at 6 months	50% vs. 48% (p=0.37)	TTM is not benficial
HYPERION	Non-shockable rhythms	581	33°C vs normothermia	Favorable neurologic outcome after 90 days:	10.2% vs. 5.7% (p=0.04)	TTM is beneficial

In addition to the studies listed in Table 1, follow-up studies of the TTM1 population showed that there were no differences in cognitive function, memory, anxiety, or depression at 33°C vs 36°C (Lilja et al). Moreover, TTM1 and TTM2 trials are generally given more weight when judging the evidence, given their size, power to study mortality, international representation and standardized protocols.

The early trials (Bernard et al, HACA trial) were not powered to explore mortality, but reported mortality benefits with TTM in patients with shockable rhythm. TTM1 and TTM2 were powered for mortality but could not detect a mortality benefit with TTM compared with normothermia. Furthermore, TTM2 stand in contrast with results from the HYPERION trial which showed a benefit on neurological function. The routine use of TTM in post-resuscitation care is therefore controversial. Current guideline recommendations (AHA, ERC, European Society of Intensive Care Medicine) grade the evidence for TTM as having very low quality to moderate quality.

Contraindications to targeted temperature management (TTM)

• Hypothermia should generally not be used for conscious patients (GCS > 8).
• Hypothermia should be avoided in patients with active bleeding, since cooling of blood results in impaired coagulation and increased bleeding.
• Cardiac arrest due to trauma, hemorrhage, or sepsis (these have not been studied in the randomized trials).
• Treatment with anticoagulants is a relative contraindication due to bleeding risk.
• Hypotension or hemodynamically unstable patients, since hypothermia lowers blood pressure.

Note that lowering body temperature to 33°C may induce bradycardia, which requires intervention if cardiac output becomes insufficient, or lactate increases or SVO₂ decreases. In these scenarios, the body temperature is elevated. Lowering of body temperature may also cause hypocapnia (PaCO₂ must be monitored).

Cerebral and cardiovascular imaging post-resuscitation

Early in the hyperacute phase (at hospitalization), computed tomography (CT) and coronary angiography are often performed, depending on the likelihood of discovering the cause of the cardiac arrest. Cardiac arrest preceded by neurological symptoms (headache, seizures, etc) is more likely to be of cerebrovascular origin. Chest pain and palpitations suggest a cardiac cause, regardless of whether ischemic ECG changes are present after ROSC. Dyspnea, hypoxia, and signs of deep vein thrombosis suggest a pulmonary cause of cardiac arrest.

The sensitivity and specificity for ischemic ECG changes (ST-segment depression, ST-segment elevation) are lower after cardiac arrest, as compared to such changes in other scenarios. Non-specific ST-T changes are very common after ROSC, as are disturbances on the ECG recordings. Repeated ECG recordings may be required to obtain a representative ECG.

Coronary angiography and percutaneous coronary intervention (PCI)

A standard 12-lead ECG must be obtained in all patients after ROSC, with the purpose of identifying individuals with ST-segment elevation, or other ECG changes suggesting the presence of an acute epicardial occlusion. Guidelines currently recommend (class I recommendation) urgent coronary angiography with the intent to perform PCI in patients with ST-segment elvation after ROSC.

The effect of immediate coronary angiography and percutaneous coronary intervention (PCI) following successful resuscitation in out-of-hospital cardiac arrest has been investigated in several randomized trials and observational studies. Patients who exhibit ST-segment elevations after ROSC have a very high probability of cardiac arrest caused by acute coronary artery occlusion. Patients who exhibited ST elevations prior to collapse or after ROSC should undergo urgent coronary angiography. Reperfusion by means of PCI results in improved electrical stability and can salvage hibernating myocardium.

Regarding patients without ST-segment elevations after ROSC, three randomized trials have been completed (COACT, PEARL and TOMAHAWK), which collectively included 1167 cases of out-of-hospital cardiac arrest. A meta-analysis of these studies demonstrated that urgent coronary angiography does not increase survival in this group. Patients who underwent urgent coronary angiography were instead at increased risk of severe bleeding, neurological injuries and need for dialysis. Three more randomized studies (ARREST, COUPE and DISCO studies) are underway examining the efficacy of immediate coronary angiography when ECG does not show ST elevations (Bhuta et al).

•Patients with ST-segment elevations prior to collapse or after ROSC should undergo urgent coronary angiography.
• Urgent angiography should be considered in the absence of ST-segment elevations if there is high probability of acute coronary artery occlusion.
• Patients without ST-segment elevations may undergo delayed angiography. Patients placed on ECMO in the coronary laboratory often undergo angiography after initiation of ECMO.
• Electrical or hemodynamic instability suggests coronary artery occlusion.

Computerized tomography (CT) of brain, thorax and abdominal organs

CT scans may be done immediately after ROSC to detect cerebrovascular causes of cardiac arrest. CT of thoracic organs, and abdominal organs is considered early to identify actionable causes.

Neurologic status and magnetic resonance imaging

Neurologic status and brain MRI imaging should be done to estimate the extent of brain damage and improve prognostication.

General aspect

• Avoid hypokalemia, since it increases the risk of arrhythmias.
• Steroids are not routinely given.
• Sedation is done with short-acting pharmacological agents.
• Proton pump inhibitors (PPI) should be administered should be administered routinely.
• Thrombosis prophylaxis (deep vein thrombosis) should be administered routinely.
• Blood sugar should be between 5 and 10 mmol/L.
• Broad-spectrum antibiotics are administered if there are clinical and/or biomarker signs of infections.
• Parenteral nutrition is initiated in low doses if TTM is used.

Airways, ventilation and oxygen

• Tracheal ventilation may be terminated if the cardiac arrest time was brief, with immediate awakening and normal breathing after ROSC. In other cases, endotracheal intubation should be retained.
• If intubation is discontinued, 100% oxygen face mask should be used to maintain an oxygen saturation at 94-98%.
• Target values:
  • Oxygen saturation by pulse oximetry: 94-98%
  • PO₂: 10-13 kPa (75-100 mmHg)
  • PaCO₂: 4.5-6.0 kPa (35-45 mmHg)
  • Tidal volume: 6-8 ml/kg of ideal body weight

Circulation

• Bedside echocardiography should be performed as early as possible by an experienced echocardiographer.
• Vasopressors and inotropic agents are used if blood pressure or cardiac output requires pharmacological support.
• An aortic balloon pump, left ventricular assist device (LVAD) or AV-ECMO should be considered if inotropic drugs and vasopressors are insufficient.
• Target diuresis: >0.5 ml/kg/h
• Systolic blood pressure should be >90 mmHg, and mean arterial blood pressure should be >65 mmHg.

Seizures

• Seizures are treated with conventional drugs and doses.
• EEG (electroencephalography) should be obtained rapidly if there is suspicion of seizures.

Electrolyte disorders

Hypokalemia, hypomagnesemia, and hypocalcemia may occur in cardiac arrest. Acidosis increases the risk of ventricular arrhythmias and should be treated.

Acute myocardial infarction (acute coronary syndrome)

If ventricular arrhythmias (VF, VT) persist after ROSC, infusion of amiodarone (1200 mg/24 hours) should be considered. Lidocaine is highly effective against ischemic ventricular arrhythmias (2-4 mg/min). Antiarrhythmics may be discontinued after 24–48 hours without ventricular arrhythmias.

The occurrence of monomorphic VT or polymorphic VT during the acute phase is a weak predictor of future risk of ventricular arrhythmias.

Bradycardia due to inferior myocardial infarction is generally responsive to atropine and isoprenaline (isoproterenol). The bradycardia is usually transient and a permanent pacemaker is mostly not required. Bradycardia due to anterior myocardial infarction is mostly permanent and requires a pacemaker.

In acute myocardial infarction, monomorphic VT is a worse prognostic factor than polymorphic VT (Hai et al), the reason for which is unknown.

Polymorphic VT with QT prolongation (torsade de pointes)

Torsade de pointes is a polymorphic VT caused by acquired or congenital long QT syndrome (LQTS). Torsade de pointes occurs exclusively in individuals with long QT time (congenital or acquired). Torsade de pointed is characterized by the twisting of the QRS axis around the baseline, with a coil-shaped appearance on ECG. Torsade de pointes is treated as follows:

• Magnesium sulfate 2 g iv, regardless of serum magnesium level. Magnesium injections can be repeated and an infusion should be started.
• Injection or infusion potassium iv to 4.5 to 5.0 mmol/L.
• Torsade de pointes that occur during bradycardia or after long pauses can be treated by increasing heart rate (>70 beats per minute): If the patient has a pacemaker, increase the pacing rate. In the absence of a pacemaker, start infusion of isoproterenol. Temporary transcutaneous pacing may be required until isoproterenol can be started.
• Lidocaine 1 mg/kg i.v should be considered in all patients with torsade de pointed.

The cause of QT prolongation must be found and eliminated if possible.

Polymorphic VT without QT prolongation

Polymorphic VT suggests acute myocardial ischemia, but may occur in other conditions. Polymorphic VT without QT prolongation can be treated with beta-blockers, amiodarone, lidocaine, mexiletine or quinidine. Sedation is a potent measure against polymorphic VT. Revascularization may be required to terminate polymorphic VT due to myocardial ischemia.

References

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Hai J.J, Un K.C, Wong C.K, et al. Prognostic implications of early monomorphic and non-monomorphic tachyarrhythmias in patients discharged with acute coronary syndrome.  Heart Rhythm . 2018;15:822–829. 29454138

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