Post-resuscitation care for survivors of cardiac arrest

Abstract

Cardiac arrest can occur following a myriad of clinical conditions. With advancement of medical science and improvements in Emergency Medical Services systems, the rate of return of spontaneous circulation for patients who suffer an out-of-hospital cardiac arrest (OHCA) continues to increase. Managing these patients is challenging and requires a structured approach including stabilization of cardiopulmonary status, early consideration of neuroprotective strategies, identifying and managing the etiology of arrest and initiating treatment to prevent recurrence. This requires a closely coordinated multidisciplinary team effort. In this article, we will review the initial management of survivors of OHCA, highlighting advances and ongoing controversies.

1. Introduction

Cardiac arrest (CA) is often the terminal event following progression of and decompensation from a wide range of pathophysiological events. With medical advances and improvements in the delivery of prehospital care, we are witnessing increasing rates of return of spontaneous circulation (ROSC) following CA. Once resuscitated, the next challenge is to manage these patients appropriately so as to not only prevent mortality but preserve neurological and cognitive function. Proper post-resuscitation care (PRC) has been shown to reduce mortality and morbidity.^1–3 To achieve this, a closely coordinated multidisciplinary team effort is required. The key steps involved in caring for these patients include:

• -Assessment and stabilization of cardiopulmonary status
• -Determining etiology of arrest
• -Neuroprotection
• -Preventing recurrence of arrest.

All these steps generally must start simultaneously once the patient regains a pulse. A schematic overview of managing patients post-ROSC is outlined in Fig. 1.

Fig. 1.

Algorithm highlighting the important pathways involved in caring for patient with ROSC post-cardiac arrest. ROSC – return of spontaneous circulation; CAB – circulation, airway, breathing; ECG – electrocardiogram; iv – intravenous, SBP – systolic blood pressure; MAP – mean arterial pressure; PCI – percutaneous coronary intervention; ET – endotracheal; K – potassium; Ed – Emergency Department, ICU – intensive care unit. * Can keep FIO₂ of 100% in case of carbon monoxide or cyanide poisoning.

2. Prehospital management

After ROSC, (defined as a palpable pulse and recordable blood pressure and if monitored, increase in ETCO₂ of >40 mm of Hg), emergency medical services (EMS) personnel should transport patients to facilities equipped with managing the complex needs of these patients. It may be safe to bypass closer medical facilities and transport patients to institutions capable of meeting the needs for PRC.^4–6 Prior to and during transport, intravenous access should be established and circulation, airway and breathing (CAB) supported in accordance with basic and advanced cardiac life support guidelines. If possible, a 12-lead electrocardiogram (ECG) should be obtained. If the field ECG is consistent with a ST-segment elevation myocardial infarction (STEMI), the cardiac catheterization team at the receiving facility should be alerted. Although some EMS systems currently initiate therapeutic hypothermia (TH) for neuroprotection in patients who remain comatose post-ROSC, there is lack of conclusive evidence of improvements in outcomes when compared to delayed initiation of hypothermia in the ED.⁷ Until, further evidence becomes available, the strategy of prehospital post-resuscitation hypothermia cannot be routinely recommended.

3. Emergency Department (ED) management

Initial management of patients post-ROSC involves a multi-system approach⁸ and should focus on several key areas simultaneously:

• -Adequate ventilation and oxygenation
• -Hemodynamic optimization
• -Cardiovascular stabilization
• -Management of metabolic derangements
• -Determining the etiology and initiating treatment of the etiology of arrest
• -Neurological assessment and consideration of therapeutic hypothermia.

Upon arrival in ED, patient's cardiopulmonary and neurological status should be promptly assessed. Continuous cardiac monitoring, pulse oximetry, capnography and NIBP (non-invasive blood pressure) monitoring should be initiated. This provides critical information on tissue oxygenation and perfusion and helps guide further resuscitative care.

A brief and focused history should be obtained if feasible. Since most patients may be unable to communicate, this may need to be obtained from EMS personnel, family, friends or bystanders who have witnessed the arrest. Up to 80% of patients have symptoms preceding the arrest.⁹ Historical evidence of chest pain, shortness of breath, palpitations, light headedness, abdominal pain, back pain, recent infection, loss of postural tone, focal neurological deficits, seizures, and evidence of trauma or bleeding may provide clues to specific etiologies. Information should also be obtained about past medical history, recent travel, medications, known allergies and whether patients were eating at the time of arrest.

A focused physical examination should be performed in the ED. Pupils should be checked for size, symmetry and response to light. Lungs should be assessed for ventilation adequacy. Stridor and wheezing may point to underlying upper or lower airway obstruction and asymmetric breath sounds should raise concern for an associated pneumothorax (PTX). Cardiac examination should focus on identifying dysrhythmias, adequacy of circulation assessed by blood pressure and pulse strength in all 4 limbs. Presence of cardiac murmurs should be noted. Low intensity or distant heart sounds should prompt consideration for underlying pericardial tamponade. Abdomen should be assessed for evidence of distension, guarding or presence of pulsatile masses. Rectal exam should be considered to evaluate for gastrointestinal bleeding. The patient should also be assessed for complications related to cardiopulmonary resuscitation (CPR).

All patients presenting with ROSC should undergo a thorough and detailed neurological exam to evaluate mental status (using a validated scale such as the Glasgow Coma Score (GCS)) and identify focal neurological findings. Patients who remain comatose (unable to follow verbal commands or a GCS of ≤8) and whose first recorded rhythm was ventricular fibrillation (VF) benefit from Therapeutic Hypothermia (TH) and this should be initiated as soon as feasible.^10,11

3.1. Initial workup

The workup should focus on assessing organ function and identifying underlying causes (Table 1).

• -A basic metabolic panel including a magnesium level can identify electrolyte abnormalities,¹² a complete blood count with differential may aid in identifying infection or anemia. An arterial blood gas (ABG) permits assessment for acidosis, hypoxia and hypercapnea while providing feedback on ventilatory status. Serum lactate levels are helpful to assess tissue perfusion. Resuscitated patients with elevated lactate levels require serial measurements; greater lactate clearance at 24 h is associated with improved survival.¹³ Baseline coagulation tests and cardiac biomarkers (troponin, CPK-MB) may be obtained and serially followed as needed though the utility of initial troponin levels in directing initial management of patients post-ROSC remains unclear.¹⁴ Toxicology testing can be considered in selected cases, although results rarely change initial management. When available, point-of-care testing should be utilized to expedite clinical decision making.
• -A 12-lead ECG should be analyzed in all patients with CA for presence of ST-segment deviation, T-wave abnormalities, dysrhythmias, conduction defects, QT-interval and presence of low voltage (which may indicate tamponade).⁸ An initial as well as repeat 12-lead ECG's are critical for early recognition of ongoing myocardial ischemia and presence of arrhythmias that require treatment. A 64-lead continuous ST mapping obtained using a chest vest may enhance sensitivity and specificity compared to a standard 12-lead ECG for detecting underlying coronary artery occlusion,¹⁵ however, additional studies are warranted prior to recommending routine implementation of this strategy.
• -
  Imaging studies:

  • •
    Chest X-Ray (CXR): A portable CXR can identify pulmonary etiologies or complications such as pulmonary edema, PTX, pneumonia and verify correct positioning of endotracheal tube patients who are intubated.
  • •
    CT: In comatose patients, non-contrast CT of brain may help in early detection of underlying stroke as well as cerebral edema. The presence of cerebral edema on CT post-CA is associated with decreased survival.¹⁶ A CT of abdomen and pelvis should be considered in patients with suspected abdominal etiology. A contrast chest CT is helpful in the workup for suspected pulmonary embolism (PE) or aortic dissection.
  • •
    Echocardiography and Ultrasonography (US): Bedside echocardiography can be performed if there is suspicion of underlying cardiac ischemia and the initial ECG is non-diagnostic. Global hypokinesis is expected but regional wall motion abnormalities suggest ischemia. In patients with suspected PE who cannot undergo CT, echocardiographic evidence of right ventricular dysfunction or in some instances direct visualization of clot can confirm the diagnosis. Pericardial tamponade and structural heart diseases such as hypertrophic cardiomyopathy can also be identified rapidly through bedside echocardiography. In addition, US can be used to assess for presence of PTX, pulmonary edema, intra-abdominal bleeding, and volume status based on the size of inferior vena cava.¹⁷
  • •
    Electroencephalogram (EEG): Status epilepticus can lead to CA and non-convulsive status epilepticus (NCSE) is often seen post-arrest.¹⁸ Continuous EEG has a high sensitivity for detecting this and should be performed as soon as feasible in comatose patients.⁸ Patients undergoing TH should have continuous EEG monitoring to detect seizures and to help differentiate seizures from hypothermia induced shivering.

Table 1.

Common causes of cardiac arrest.

Cardiovascular causes	Acute coronary syndromes
	Arrhythmias
	Structural heart disease: Hypertrophic cardiomyopathy, ARVD
	Cardiac tamponade
	Aortic dissection or aortic aneurysm rupture
	Blunt cardiac trauma: commotio cordis
Pulmonary causes	Pulmonary embolism
	Status asthmaticus
	Airway obstruction : foreign body, mucus plugging
	Pneumothorax
	Hypoxia
Electrolyte abnormalities	Hypokalemia/hyperkalemia
	Hypomagnesemia
	Hypocalcemia/hypercalcemia
	Acidosis
	Renal failure
Infection	Sepsis
Hypovolemia	Bleeding
	Gastrointestinal losses
	Diuretic therapy
Toxins	Cocaine abuse
	Amphetamines
	Opiate overdose
	Cardio active agents
	Benzodiazepine overdose
	Tricyclic antidepressants

ARVD – arrhythmogenic right ventricular dysplasia.

3.2. Ventilation

Following resuscitation, the airway should be assessed to ensure adequate oxygenation and ventilation in all patients. A safe airway should be established and comatose patients intubated (if not done prior to arrival). Mechanical ventilator settings should be adjusted as needed based on ABG results. Patients who develop ARDS should be managed with low tidal volume ventilation with PEEP adjusted to keep plateau pressures ≤30 cm of H₂O.²¹

Awake patients with appropriate respiratory effort and able to maintain their airway can be monitored without intubation. Controlled use of supplemental oxygen to achieve SpO₂ ≥94% is recommended in the non-intubated patients post-resuscitation. Similarly, in patients who are intubated FIO₂ should be quickly titrated to maintain SpO₂ ≥94%. Higher PaO₂ levels may lead to adverse neurological outcomes secondary to generation of free radicals and brain lipid peroxidation in the context of global ischemia followed by reperfusion.^8,19

PaCO₂ should also be kept in normal range. Hyperventilation can lead to decrease in PaCO₂, and decrease cerebral perfusion leading to worsening of post-ischemic cerebral injury.²⁰ Additionally, hyperventilation decreases expiratory time leading to air trapping and increase in intrathoracic pressure. This impedes preload and decreases cardiac output which can be deleterious in hypotensive patients. Generally, PaCO₂ should be maintained around 40–45 mm of Hg and, if monitored, end-tidal CO₂ (capnometry) level should be kept between 35–40 mm of Hg.⁸

3.3. Hemodynamic optimization

Post-CA, it is essential to maintain perfusion to vital organs to prevent further clinical deterioration. Irrespective of the etiology of arrest, there may be temporary myocardial dysfunction and inability to maintain adequate cardiac output.^22,23 For optimal organ perfusion a MAP (mean arterial pressure) ≥65 mm of Hg should be targeted. The first step in ensuring this is adequate volume resuscitation with isotonic fluids (0.9% normal saline or ringer's lactate) to achieve a central venous pressure of 8–12 cm of H₂O. Cold saline may be used for volume loading if TH is being considered. If, after adequate volume supplementation (usually 2–3 L of isotonic fluids), the MAP remains <60–65 mm of Hg; vasopressors and inotropic agents should be added. The available agents include norepinephrine, dopamine, epinephrine, phenylephrine, dobutamine and milrinone. There is paucity of data to definitively recommend one agent and choice of agents should be dictated by goals of therapy, side effects and familiarity of providers. While optimization is underway, hemodynamic parameters should be monitored frequently through periodic NIBP monitoring or, in some instances invasive direct arterial pressure monitoring.

3.4. Cardiovascular stabilization and role of coronary angiography

Coronary artery occlusion remains a leading cause of out-of-hospital cardiac arrest (OHCA).^24,25 An initial 12-lead ECG should be obtained in all patients post-arrest.⁸ If STEMI is noted, reperfusion therapy should be strongly considered: either via primary percutaneous coronary intervention (PCI) or intravenous fibrinolytic therapy as both have been shown to be efficacious.²⁶ Traumatic or prolonged CPR (>10 min) is a relative contraindication to fibrinolytic use²⁷ and the risk and benefits of fibrinolysis should be considered in this sub-group. PCI can be safely performed in patients undergoing TH²⁸ but the safety of fibrinolytic therapy for STEMI in conjunction with TH is less well established. Preliminary studies suggest that the risk of stent thrombosis is no different in patients treated with or without TH.²⁹ Consideration may be given to performing angiography (and possible PCI) in all patients following ROSC who do not have an alternate explanation of arrest irrespective of the ECG findings^30,31 but the benefit of routinely implementing this approach remains controversial and it has been challenging to identify patients who would benefit most from invasive assessment and treatment. Future research should be directed towards developing modalities identifying these patients appropriately. Body surface potential mapping as mentioned previously is one such modality.¹⁵

Continuous cardiac monitoring should be performed in all patients to monitor for arrhythmias in the post-arrest period. When detected, arrhythmias should be managed as appropriate per current resuscitation guidelines.⁸ Patients with MI who continue to be hypotensive despite revascularization may need mechanical augmentation with devices such as intra-aortic balloon pump or percutaneous mechanical circulatory support in addition to vasoactive agents and fluids provided no contraindications exist.

3.5. Therapeutic hypothermia

Neurological injury is a major cause of death following successful resuscitation.³² Post-resuscitation TH has been demonstrated to improve neurological outcomes in comatose patients whose initial recorded rhythm was VF.^10,11 Harmful pathways that accompany reperfusion injury seem to be inhibited by hypothermia and exacerbated by hyperthermia. According to the 2010 AHA guidelines,⁸ all comatose patients with ROSC after out of hospital VF arrest should be cooled to 32 °C–34 °C for 12–24 h. TH should be considered for comatose patients with ROSC after in-hospital CA from any rhythm or OHCA from PEA or Asystole. Active rewarming is contraindicated in patients who develop spontaneous hypothermia (temperature >32 °C) after ROSC post-CA within the first 48 h.

TH should be induced as soon as possible, preferably within 6 h of CA based on animal studies. TH can be induced using cold saline infusion,⁷ endovascular³³ or surface cooling devices.³⁴ Unintentional overcooling should be avoided. All hospitals should establish standardized protocols for initiation and management of TH based on local logistics and staff training.

During initiation and maintenance of TH, core body temperature should be monitored continuously using esophageal probe, bladder temperature catheter in non-anuric patients or central venous probe.^10,11 Axillary, oral, tympanic and rectal temperatures can differ from core body temperature and should be avoided.⁸ Shivering has an adverse impact on maintenance of hypothermia and patients should be sedated and if needed administered paralytics to avoid this complication of TH.

Important complications of TH include increased susceptibility to infections,^11,35 bleeding,³⁴ electrolyte depletion, bradyarrhythmias and hyperglycemia.³⁶ Appropriate precautions should be taken to prevent infections and when appropriate, antibiotics initiated. Frequent electrolyte monitoring should be performed during TH³⁷ and appropriate hemodynamic support maintained. Insulin therapy may be required to prevent hyperglycemia.

Rewarming post-TH should be gradual and not exceed 0.5 °C/h as rapid rewarming can lead to cerebral edema, hyperkalemia and seizures.

3.6. Glycemic control

Unless hypoglycemia is the cause of arrest, post-arrest patients usually demonstrate hyperglycemia. Hyperglycemia is detrimental³⁸ and impairs neurological recovery.³⁹ Optimal blood glucose range in patients post-CA remains unknown but strict normoglycemia is not required.⁴⁰ Strict blood sugar control with intensive insulin therapy targeting values lower than 110 mg/dl can lead to hypoglycemia⁴¹ which has been associated with increased mortality.⁴² Additionally, strict glucose control compared with moderate glucose control has not been shown to confer any mortality benefit in these patients.⁴³ Thus, moderate glycemic control (144–180 mg/dl) is preferred and insulin therapy should be targeted to this goal.⁸

3.7. Management of specific etiology of arrest

Table 2 briefly summarizes management of common etiologies of CA.

Table 2.

Management of common causes of cardiac arrest.

Acute coronary syndrome	Coronary revascularization: PCI/fibrinolytic therapy
Hypoxia	Management of underlying etiology, supportive mechanical ventilation (if needed)
Pulmonary embolism	Anticoagulation, consideration should be given to fibrinolysis and thrombectomy.
Electrolyte abnormalities	Hypokalemia: Supplementation
	Hyperkalemia: Calcium chloride/calcium gluconate, sodium bicarbonate, albuterol nebulizers, sodium polystyrene sulfonate or diuresis as may be appropriate clinically
	Hypomagnesemia: intravenous magnesium supplementation (always use in hypokalemic patients)
	Acidosis: Reverse underlying cause, consider bicarbonate for patients with severe metabolic acidosis
	Hypoglycemia: intravenous dextrose
Cardiac tamponade	Pericardiocentesis
Pneumothorax	Needle thoracostomy followed by chest tube insertion
Anaphylaxis	Epinephrine
Toxins	Use of antidotes as appropriate.
Anemia/hypovolemia	Isotonic crystalloid fluids, packed RBCs.
Severe hypothermia	Gentle rewarming
Stroke	Revascularization for ischemic stroke depending on timing, consideration to neurosurgical decompression for hemorrhagic stroke.

4. Neuroprognostication

Neuroprognostication in patients post-CA is clinically challenging. While it's important to guide medical decision making regarding withdrawal of care, no single test reliably predicts poor outcomes, especially in the first 24 h post-arrest.⁸ Generally, multiple independent prognosticators should be used to assess the severity of neurological damage.⁴⁴ Prior to attempting neuroprognostication, any potential confounding factors such as hypotension, seizures, toxins or neuromuscular blockers should be excluded. The exact timing of neuroprognostication in patients who have undergone TH remains unknown.⁴⁵ According to 2010 AHA recommendation, all neuroprognostication efforts should be avoided in the first 72-h post-arrest in patients treated with TH.⁸ In patients not treated with TH, neuroprognostication can be considered 24-h post-arrest.

Findings on neurological exam associated with poor prognosis in patients not undergoing TH include: absent corneal reflex at 24 h, absent pupillary reflex at 24 h, absent or withdrawal response to pain at 24 h and no motor response at 24 and 72 h.⁴⁶ In patients undergoing TH, a score of ≥5 on GCS motor scale (GCS-M) and normal brain stem reflexes have been associated with favorable prognosis while a bilateral lack of pupillary reflex, corneal reflex and a score of 1–2 on GCS-M have been associated with unfavorable outcome.⁴⁴

When available, somatosensory evoked potentials (SSEP) can be helpful in neuroprognostication. Bilateral absence of N20 cortical response to median nerve stimulation on SSEP is associated with poor prognosis.^8,44 Results of SSEPs are not affected by sedation and preliminary results suggest that SSEPs may be useful in patients undergoing TH.^44,47

No EEG finding can reliably predict poor outcome in first 24 h post-arrest.⁸ In patients not treated with TH, an EEG showing generalized suppression to <20 μV, burst suppression pattern associated with generalized epileptic activity or diffuse periodic complexes on flat background is associated with poor outcome.^8,48 In patients treated with TH, a reactive or a continuous EEG background after rewarming is associated with favorable prognosis while burst suppression pattern, electro-cerebral inactivity or status epilepticus are associated with unfavorable prognosis.⁴⁴

Findings on neuroimaging are less well defined but loss of gray white matter interface and diffuse ischemia on CT or MRI are associated with poor prognosis.^8,44

Biomarkers such as Neuron Specific Enolase and S100-B have been evaluated for prognostication in patients post-CA. Elevated levels of these biomarkers have been associated with poor prognosis but there is variability and lack of standardization in these studies.⁴⁴ Sole reliance on biomarkers for neuroprognostication is not recommended at this time.⁸

5. Preventing re-arrest

The most important measure to prevent re-arrest is identifying and treating the etiology of initial arrest. If any further episodes of CA occur while the patient is being monitored, then they should be treated with CPR, defibrillation, vasopressors and antiarrhythmic therapy as appropriate. At this time evidence is insufficient to routinely recommend or refute using antiarrhythmic agents prophylactically.⁸

6. Role of specialized centers

Managing patients post-CA involves a team based approach and requires complex coordination of care including acute hemodynamic stabilization, management of mechanical ventilation, consideration of TH and interventions such as emergent PCI. These objectives are best achieved at centers having expertise in dealing with this complex subset of patients. Centers dealing with larger volume of post-CA patients have been shown to have superior outcomes⁵ and lower in-hospital mortality rates.⁴⁹ Regional centers for care of patients who survive CA have been proposed by international organizations⁴ and there is a need for local regulatory authorities to formulate and implement an action plan to achieve this goal. CA can unfortunately happen to anyone, and everyone should at-least get the best possible shot at survival by implementation and utilization of available evidence based therapies.

7. Summary

Management of patients following resuscitation from CA is complex and requires specialized institutions capable of providing advanced care therapies. Optimal management requires consideration of multiple processes simultaneously. In addition to CABs of advanced cardiac life support, neuroprotection with TH should be initiated in comatose patients. The presence of coronary artery occlusion as a cause of arrest should be determined through analysis of the 12-lead ECG and when present, treated expeditiously. Patients should be monitored closely in a critical care setting and neuroprognostication should be performed no earlier than 24 h in patients not undergoing TH and after 72 h in patients undergoing TH.

Conflicts of interest

All authors have none to declare.