CHAPTER 92: CARDIOPULMONARY AND CARDIOCEREBRAL RESUSCITATION

Cardiac arrest is defined as the cessation of cardiac mechanical activity, as confirmed by the absence of signs of circulation. Cardiac arrest is traditionally categorized as being of cardiac or noncardiac origin. An arrest is presumed to be of cardiac origin unless it is known or likely to have been caused by trauma, submersion, drug overdose, asphyxia, exsanguination, or any other noncardiac cause as best determined by rescuers.¹

It is challenging to define what “unexpected” or “sudden” death is. Current practice defines sudden cardiac death as unexpected death without an obvious noncardiac cause that occurs within 1 hour of symptom onset (witnessed) or within 24 hours of last being observed in normal health (unwitnessed).²

The following is based on American Heart Association (AHA) statistical data from 2015¹:

• Each year 326,000 people experience emergency medical services (EMS)-assessed out-of-hospital cardiac arrests in the United States.

• Approximately 60% of out-of-hospital cardiac arrests are treated by EMS personnel.³

• Twenty-five percent of those with EMS-treated out-of-hospital cardiac arrest have no symptoms before the onset of arrest.⁴

• Among EMS-treated out-of-hospital cardiac arrests, 23% have an initial rhythm of ventricular fibrillation (VF) or ventricular tachycardia (VT) or are shockable by an automated external defibrillator.⁵

• The incidence of cardiac arrest with an initial rhythm of VF is decreasing over time; however, the incidence of cardiac arrest is not decreasing.⁶

• The median age for out-of-hospital cardiac arrest is 66 years.⁷

• Cardiac arrest is witnessed by a bystander in 38.7% of cases, by an EMS provider in 10.9% of cases, and is unwitnessed in 50.4% of cases.⁷

• In the Cardiac Arrest Registry to Enhance Survival (CARES) registry, 31,127 out-of-hospital cardiac arrests were treated in 2013. Survival to hospital discharge was 10.6% and survival with good neurological function (Cerebral Performance Category 1 or 2) was 8.3%. For bystander witnessed arrest with a shockable rhythm, survival to hospital discharge was 33.0%.⁷

• According to the CARES registry, in 2013 the majority of out-of-hospital cardiac arrests occurred at a home or residence (69.5%).⁷

• A family history of cardiac arrest in a first-degree relative is associated with a twofold increase in risk of cardiac arrest.^8,9

Based on the AHA Statistical Data from 2015¹:

• Each year, 209,000 people are treated for in-hospital cardiac arrest in the United States.¹⁰

• According to the Get With The Guidelines (GWTG)-Resuscitation database from 2014, 25.5% of adults who experienced in-hospital cardiac arrest with any first recorded rhythm in 2013 survived to discharge.¹

• In the United Kingdom National Cardiac Arrest Audit database between 2011 and 2013, the overall unadjusted survival rate was 18.4%. Survival was 49% when the initial rhythm was shockable and 10.5% when the initial rhythm was not shockable.¹¹

The initial attempts to treat cardiac arrest focused on chest compressions. Closed chest defibrillation and closed chest cardiac massage were first described in the 1960s.

In the initial publication, some patients were treated with chest compression without positive pressure. However with time, ventilation gradually became an essential pillar of cardiopulmonary resuscitation (CPR).

Given the prevalence and lethality of cardiac arrest, the AHA disseminated CPR and emergency cardiovascular care (ECC) information to healthcare professionals and the lay public in the 1970s.

The International Liaison Committee on Resuscitation (ILCOR) was formed in 1993. It currently includes representatives from the AHA, the European Resuscitation Council, the Heart and Stroke Foundation of Canada, the Australian and New Zealand Committee on Resuscitation, the Resuscitation Council of Southern Africa, the InterAmerican Heart Foundation, and the Resuscitation Council of Asia.¹²

In 1999, the AHA hosted the first ILCOR conference to evaluate resuscitation science and develop common resuscitation guidelines. The conference recommendations were published in the Guidelines 2000 for CPR and ECC. Since 2000, researchers from the ILCOR member councils have evaluated and reported their International Consensus on CPR and ECC Science with Treatment Recommendations (CoSTR) in 5-year cycles.¹²

Basic Life Support

Systems of Care

The 2015 AHA Updated Guidelines highlighted a new perspective on systems of care, differentiating in-hospital cardiac arrests (IHCAs) from out-of-hospital cardiac arrests (OHCAs).¹³

The care for all post–cardiac arrest patients, regardless of the location of the arrests, converges in the hospital, generally in an intensive care unit where post–cardiac arrest care is provided. The systems of care before that convergence are very different for the two settings. Patients who have an OHCA depend on their community for support. Lay rescuers must recognize the arrest, call for help, initiate CPR, and provide defibrillation (ie, public-access defibrillation [PAD]) until EMS assumes responsibility and transports the patient to an emergency department (ED) and/or cardiac catheterization lab. The patient is ultimately transferred to a critical care unit for continued care.

In contrast, patients who have an IHCA depend on a system of appropriate surveillance (rapid response or early warning system) to prevent cardiac arrest. If cardiac arrest occurs, patients depend on the smooth interaction of the institution’s various services and a multidisciplinary team of professional providers, including physicians, nurses, and respiratory therapists, among others.

Community Lay Rescuer AED Programs

It is recommended that PAD programs for patients with OHCA be implemented in public locations where there is a relatively high likelihood of witnessed cardiac arrest (ie, airports, casinos, sports facilities). There is clear and consistent evidence of improved survival from cardiac arrest when a bystander performs CPR and rapidly uses an automatic external defibrillator (AED). Thus, immediate access to a defibrillator is a primary component of the system of care. The implementation of a PAD program requires four essential components: (1) a planned and practiced response, which ideally includes identification of locations and neighborhoods where there is high risk of cardiac arrest, placement of AEDs in those areas, ensuring that bystanders are aware of the location of the AEDs, and, typically, oversight by a healthcare professional (HCP); (2) training of anticipated rescuers in CPR and use of the AED; (3) an integrated link with the local EMS system; and (4) a program of ongoing quality improvement. Figure 92–1 outlines the 2015 guideline recommendations for the initial approach to a patient who is unresponsive.

Chest Compressions

Untrained lay rescuers should provide compression-only (hands-only) CPR, with or without dispatcher guidance, for adult victims of cardiac arrest. The rescuer should continue compression-only CPR until the arrival of an AED or rescuers with additional training. All lay rescuers should, at a minimum, provide chest compressions for victims of cardiac arrest. In addition, if the trained lay rescuer is able to perform rescue breaths, he or she should add rescue breaths in a ratio of 30 compressions to 2 breaths. The rescuer should continue CPR until an AED arrives and is ready for use, EMS providers take over care of the victim, or the victim starts to move.

Chest Compression Rate

In most studies, more compressions are associated with higher survival rates, and fewer compressions are associated with lower survival rates. New to the 2015 Guidelines Update are upper limits of recommended compression rate and compression depth, based on preliminary data suggesting that excessive compression rate and depth adversely affect outcomes.

For the critical outcome of survival to hospital discharge, evidence exists from two observational studies^14,15 representing 13,469 adult patients. They compared chest compression rates of greater than 140/min, 120 to 139/min, less than 80/min, and 80 to 99/min with the control rate of 100 to 119/min. When compared with the control chest compression rate of 100 to 119/min, there was a 4% decrease in survival to hospital discharge with compression rates of greater than 140/min, a 2% decrease in survival to hospital discharge with compression rates of 120 to 139/min, a 1% decrease in survival to hospital discharge with compression rates of less than 80/min, and a 2% decrease in survival to hospital discharge with compression rates of 80 to 99/min.

The study showed chest compression depth declined with increasing chest compression rate. The relationship of reduced compression depth at different compression rates was as follows: for a compression rate of 100 to 119/min, 35% of compressions had a depth less than 3.8 cm; for a compression rate of 120 to 139/min, 50% of compressions had a depth less than 3.8 cm; and for a compression rate of 140/min or greater, 70% of the compressions had a depth less than 3.8 cm.

Treatment Recommendations

The 2015 guidelines recommend a manual chest compression rate of 100 to 120/min.

Chest Compression Depth

During manual CPR, rescuers should perform chest compressions to a depth of at least 2 inches (5 cm) for an average adult, while avoiding excessive chest compression depths (greater than 2.4 inches [6 cm]).

The reason for emphasis on accurate chest compression depth is the following: compressions create blood flow primarily by increasing intrathoracic pressure and directly compressing the heart, which in turn results in critical blood flow and oxygen delivery to the heart and brain. Rescuers often do not compress the chest deeply enough despite the recommendation to “push hard.” Although a compression depth of at least 2 inches (5 cm) is recommended, as noted above the 2015 Guidelines Update incorporates new evidence about the potential for an upper threshold of compression depth (greater than 2.4 inches [6 cm]) beyond which complications may occur. Compression depth may be difficult to judge without use of feedback devices, and identification of upper limits of compression depth may be challenging.

For the critical outcome of survival to hospital discharge, three observational studies^16,17,18 suggest that survival may improve with increasing compression depth. In the largest study (9136 patients), a covariate-adjusted spline analysis showed a maximum survival at a mean depth of 4.0 to 5.5 cm (1.6 to 2.2 inches), with a peak at 4.6 cm (1.8 inches).¹⁸

Another important study showed injuries were reported in 63% with compression depth more than 6 cm (more than 2.4 inches) and 31% with compression depth less than 6 cm. Injuries were reported in 28%, 27%, and 49% with compression depths less than 5 cm (less than 2 inches), 5 to 6 cm (2 to 2.4 inches), and more than 6 cm (more than 2.4 inches), respectively.¹⁹

Treatment Recommendations

The 2015 guidelines recommend a chest compression depth of approximately 5 cm (2 inches) while avoiding excessive chest compression depths (greater than 6 cm [greater than 2.4 inches] in an average adult) during manual CPR.

Compression-Ventilation Ratio

The critical outcome of survival with favorable neurologic outcome at discharge was studied in two observational studies.^20,21 Of the 1711 patients included, those who were treated under the 2005 guidelines with a compression-ventilation ratio of 30:2 had slightly higher survival than those patients treated under the 2000 guidelines with a compression-ventilation ratio of 15:2 (8.9% vs 6.5%; relative risk [RR] 1.37; 95% confidence interval [CI], 0.98–1.91).

The critical outcome of survival to hospital discharge was tested in four observational studies.^20,21,22,23 Of the 4183 patients included, those who were treated under the 2005 guidelines with a compression-ventilation ratio of 30:2 had slightly higher survival than those patients treated under the 2000 guidelines with a compression-ventilation ratio of 15:2 (11.0% vs 7.0%; RR 1.75; 95% CI, 1.32–2.04).

For the critical outcome of survival to 30 days, one observational study²⁴ found that patients treated under the 2005 guidelines had slightly higher survival than those patients treated under the 2000 guidelines (16.0% vs 8.3%; RR 1.92; 95% CI, 1.28–2.87).

For the critical outcome of any return of spontaneous circulation (ROSC), two observational studies^20,21 found that patients treated under the 2005 guidelines had a ROSC more often than those patients treated under the 2000 guidelines (38.7% vs 30.0%; RR 1.30; 95% CI, 1.14–1.49).

Treatment Recommendation

The 2015 guidelines suggest a compression-ventilation ratio of 30:2 compared with any other compression-ventilation ratio in patients in cardiac arrest.

Ventilation During CPR with Advanced Airway

The 2015 guideline suggest that it may be reasonable for the provider to deliver 1 breath every 6 seconds (10 breaths per minute) while continuous chest compressions are being performed (ie, during CPR with an advanced airway).

Bystander Naloxone in Opioid-Associated Life-Threatening Emergencies

New for the 2015 guideline is that for patients with known or suspected opioid addiction who are unresponsive with no normal breathing but a pulse, it is reasonable for appropriately trained lay rescuers and BLS providers to administer intramuscular (IM) or intranasal (IN) naloxone in addition to providing standard basic life support (BLS) care. In 2014, the naloxone autoinjector was approved by the US Food and Drug Administration for use by lay rescuers and HCPs.³

Shock First Versus CPR First

Numerous studies have addressed the question of whether a benefit is conferred by providing a specified period (typically 1.5 to 3 minutes) of chest compressions before shock delivery, as compared to delivering a shock as soon as the AED can be readied. No difference in outcome has been shown. For witnessed adult cardiac arrest when an AED is immediately available, it is reasonable that the defibrillator be used as soon as possible. For adults with unmonitored cardiac arrest or for whom an AED is not immediately available, it is reasonable that CPR be initiated while the defibrillator equipment is being retrieved and applied and that defibrillation, if indicated, be attempted as soon as the device is ready for use. CPR should be provided while the AED pads are applied and until the AED is ready to analyze the rhythm.

Chest Recoil

Based on the 2015 guidelines it is reasonable for rescuers to avoid leaning on the chest between compressions, to allow full chest wall recoil for adults in cardiac arrest. Figure 92–2 summarizes the new 2015 guidelines recommendations for a high-quality CPR.

Advanced Life Support

Mechanical CPR Devices

The 2015 updated guidelines suggest against the routine use of automated mechanical chest compression devices to replace manual chest compressions.²⁴ For the critical outcome of survival to 1 year, one randomized controlled trial (RCT)²⁵ using the Lund University Cardiac Arrest System (LUCAS) device showed no benefit or harm when compared with manual chest compressions (5.4% vs 6.2%; RR, 0.87; 95% CI, 0.68-1.11). For the critical outcome of survival to 180 days, one RCT²⁶ using a LUCAS device enrolling 2589 OHCA patients showed no benefit or harm when compared with manual chest compressions when quality of chest compressions in the manual arm was not measured (8.5% vs 8.1%; RR, 1.06; 95% CI, 0.81-1.41).

Drugs During Cardiopulmonary Resuscitation

Epinephrine Versus Vasopressin

A single RCT²⁷ (n = 336) compared multiple doses of single-dose epinephrine (SDE) with multiple doses of standard-dose vasopressin in the ED after OHCA. For the critical outcome of survival to discharge with favorable neurologic outcome (cerebral performance category [CPC] 1 or 2), there was no advantage with vasopressin (RR, 0.68; 95% CI, 0.25-1.82; P = .44). For the important outcome of ROSC, there was no observed advantage with vasopressin (RR, 0.93; 95% CI, 0.66-1.31; P = .67). The 2015 guidelines suggest vasopressin should not be used instead of epinephrine in cardiac arrest.²⁴

Epinephrine Versus Vasopressin in Combination with Epinephrine

For the critical outcome of survival to hospital discharge with CPC of 1 or 2, three RCTs^28,29,30 (n = 2402) comparing SDE with vasopressin and epinephrine combination therapy showed no superiority with vasopressin and epinephrine combination (RR, 1.32; 95% CI, 0.88-1.98). For the important outcome of ROSC, six RCTs^{28,29,30,31,32,33} showed no ROSC advantage with vasopressin and epinephrine combination therapy (RR, 0.96; 95% CI, 0.89-1.04; P = .31). The 2015 guidelines suggest against adding vasopressin to SDE during cardiac arrest

Single-Dose Epinephrine Versus High-Dose Epinephrine

In adult patients in cardiac arrest in any setting, high-dose epinephrine (HDE) (at least 0.2 mg/kg or 5-mg bolus dose) was compared with SDE (1-mg bolus dose). For the critical outcome of survival to hospital discharge with CPC 1 or 2, two RCTs comparing SDE with HDE^34,35 (n = 1920) did not show advantage with HDE (RR, 1.2; 95% CI, 0.74-1.96). For the critical outcome of survival to hospital discharge, five RCTs comparing SDE with HDE (n = 2859) did not show any survival to discharge advantage with HDE (RR, 0.97; 95% CI, 0.71-1.32). The 2015 guidelines suggest against the routine use of HDE in cardiac arrest (weak recommendation, low-quality evidence).

Timing of Administration of Epinephrine

In-Hospital Cardiac Arrest

For IHCA, for the critical outcome of survival to hospital discharge, one observational study³⁶ in 25,095 IHCA patients with a nonshockable rhythm showed an improved outcome with early administration of adrenaline. Compared to the reference interval of 1 to 3 minutes, adjusted odds ratio (OR) for survival to discharge was 0.91 (95% CI, 0.82-1.00) when epinephrine was given after 4 to 6 minutes, 0.74 (95% CI, 0.63–0.88) when given after 7 to 9 minutes, and 0.63 (95% CI, 0.52-0.76) when given at more than 9 minutes after onset of arrest.

For IHCA, for the critical outcome of neurologically favorable survival at hospital discharge, an improved outcome was observed from early administration of adrenaline: compared with a reference interval of 1 to 3 minutes, the adjusted OR was 0.93 (95% CI, 0.82-1.06) with epinephrine given after 4 to 7 minutes, 0.77 (95% CI, 0.62-0.95) when given after 7 to 9 minutes, and 0.68 (95% CI, 0.53-0.86) when given at more than 9 minutes after onset of arrest.

For IHCA, for the important outcome of ROSC, an improved outcome from early administration of adrenaline adjusted OR compared with a reference interval of 1 to 3 minutes of 0.90 (95% CI, 0.85-0.94) when given after 4 to 7 minutes, 0.81 (95% CI, 0.74-0.89) when given after 7 to 9 minutes, and 0.70 (95% CI, 0.61-0.75) when given after 9 minutes.

For the critical outcome of neurologically favorable survival at hospital discharge (assessed with CPC 1 or 2), four observational studies^37,38,39,40 involving more than 262,556 OHCAs showed variable benefit from early administration of epinephrine.

For the important outcome of ROSC, there was very-low-quality evidence (downgraded for risk of bias, indirectness, and imprecision) from four observational studies^38,41,42,43 of more than 210,000 OHCAs showing an association with improved outcome and early administration of adrenaline. One study⁴² showed increased ROSC for patients receiving the first vasopressor dose early (less than 10 vs more than 10 minutes after EMS call; OR, 1.91; 95% CI, 1.01-3.63).

The 2015 guidelines recommendations for cardiac arrest with an initial nonshockable rhythm are that if epinephrine is to be administered, it is given as soon as possible after the onset of the arrest.

Antiarrhythmic Drugs for Cardiac Arrest

Antiarrhythmic drugs can be used during cardiac arrest for refractory ventricular dysrhythmias. Refractory VF/pVT is defined differently in many trials, but generally refers to failure to terminate VF/pVT with three stacked shocks or with the first shock.

For the important outcome of ROSC, one RCT involving 504 OHCA patients showed higher ROSC with administration of amiodarone (300 mg after 1 mg of adrenaline) compared with no drug (64% vs 41%; P = .03; RR, 1.55; 95% CI, 1.31-1.85).⁴⁴

The 2015 guideline recommendations for antiarrhythmia drugs for cardiac arrest suggest the use of amiodarone in adult patients with refractory VF/pVT to improve rates of ROSC. The guidelines also suggest the use of lidocaine or nifekalant as an alternative to amiodarone in adult patients with refractory VF/pVT. The 2015 guidelines recommend against the routine use of magnesium in adult patients.

Brief history of Therapeutic Hypothermia

The use of therapeutic hypothermia (TH) to mitigate various types of injury, in particular posthypoxic injury to the brain, has been studied since the late 1930s.⁴⁵ Interest was initially kindled by reports of survival after prolonged exposure to cold, or submersion in ice-cold water, indicating a possible protective effect of low temperature on hypoxic injuries.⁴⁶

Use of hypothermia after cardiac arrest was first described in the late 1950s,^47,48 but proof that hypothermia could improve outcome in these patients remained elusive.^49,50 At the time, it was thought that protective effects of TH were purely a result of hypothermia-induced lowering of metabolism; therefore, it was presumed that very low temperatures (25-28°C) were needed to provide significant neuroprotection.

This perception changed in the late 1980s, when animal studies demonstrated that significant protective effects also occurred with mild hypothermia (30-34°C), with far fewer side effects, and that a variety of destructive mechanisms were moderated by hypothermia rather than just reductions in brain metabolism.⁴⁹ In the late 1990s a number of small nonrandomized, clinical trials provided better evidence for the efficacy of TH.^51,52,53,54 This led to the initiation of two landmark multicenter RCTs to test TH treatment, the results of which were published side-by-side in 2002.^55,56 Both reported clear and significant improvements in outcome in cardiac arrest patients treated with therapeutic cooling.

The largest study, performed in 11 centers in Europe, enrolled 275 patients with witnessed cardiac arrest and an initial rhythm of VF or pulseless VT. The authors observed a 15.8% absolute (35.1% relative) improvement in outcome in the hypothermia group (P < .01).⁵⁵ The other RCT enrolled 77 patients across four centers in Australia, reporting an absolute improvement of 22.3% (relative improvement 43.7%) in patients with witnessed VT/VF treated with hypothermia compared with controls (P < .05).⁵⁶ A meta-analysis calculated that one additional case of good neurological outcome would be gained for every six patients treated with TH.⁵⁷ Guidelines from various medical societies such as the AHA, European Resuscitation Council (ERC), and Neurocritical Care Society (NCS) began recommending cooling after cardiac arrest.^58,59

A larger RCT, the Therapeutic Temperature Management study, compared temperature management at 33.0°C to maintaining a core temperature of 36.0°C.⁶⁰ The study enrolled 939 patients with witnessed cardiac arrest regardless of initial rhythm, including those with persistent hypoxia and hypotension who had been excluded from previous studies, with predefined subgroup analyses to correct for various risk factors. The results of this study were negative.⁶⁰ Rates of survival with good neurological outcome were 46.5% in the 33°C group versus 47.8% in the 36°C group (P = .78). The rate of survival with excellent outcome (no neurological residual) was 41.6% versus 39.4%, whereas survival with mild neurological impairment was 4.9% versus 8.4%.⁶⁰ The authors concluded that maintaining core temperature at 36°C has equally good outcomes as cooling to 33°C.

Pathways for the Management of Survivors of OUT-OF-HOSPITAL AND IN-Hospital Cardiac Arrest

At our institution, similar to many tertiary medical centers, algorithms for the management of patients post cardiac arrest have been developed. Our first algorithm was published in 2010.⁶¹ We continue to update it, as new scientific information and updated guidelines are published.⁶² The term “therapeutic hypothermia” has now been replaced with targeted temperature management (TTM). Our 2015 updated TTM pathway is divided into three steps.

• Step I. From the field through the ED into the cardiac catheterization laboratory and to the critical care unit (Fig. 92–3A).

• Step II. Induced hypothermia protocol in the critical care unit (Fig. 92–3B).

• Step III. The management following the rewarming phase including the recommendation for out-of-hospital therapy and the ethical decision to define goals of care (Fig. 92–3C).

Step I: Presentation to the Emergency Department, Proceeding to the Cardiac Catheterization Laboratory and to the Critical Care Unit

Upon arrival of a survivor of OHCA to the ED, the initial assessment (see Fig. 92–3A) includes vital signs, physical examination, and neurologic examination with Glasgow Coma Score. Immediate 12-lead electrocardiogram (ECG) is obtained and laboratory testing performed.

Initial laboratory testing includes complete blood count (CBC) with differential, basic metabolic panel, cardiac marker (troponin, creatine phosphokinase [CPK], CPK-MB), B-type natriuretic peptide (BNP), prothrombin time (PT), partial thromboplastin time (PTT), international normalized ratio (INR), lipid profile, phosphorus, calcium, magnesium, lactate, β-human chorionic gonadotropin (β-HCG) (for women), thyroid-stimulating hormone (TSH), and toxicology screening. We recommend head computed tomography (CT) without contrast only if it is clinically indicated and will not delay transfer to the cardiac catheterization laboratory.

The patient is stabilized in the ED where antiarrhythmic and vasopressor therapy may be administered, in addition to ventilator support.

The ED physician receives the EMS report of the primary rhythm and duration of CPR. This reported arrhythmia is the key decision point in our pathway.

The prognostically important distinction is between patients with documented VF or sustained VT who had a restoration of spontaneous circulation (ROSC) in < 30 minutes and patients with reported asystole or pulseless electrical activity (PEA).

1. If the initial rhythm was VF or VT with an ROSC of ≤ 30 minutes, the cardiac arrest team is activated, and the patient will proceed to the cardiac catheterization laboratory.

2. If the initial reported arrhythmia was PEA or asystole, the next step will depend on the ECG performed in the ED. If the ECG performed in ED is suggestive of priority acute coronary syndrome (ACS; including ST-segment elevation myocardial infarction [MI], left bundle branch block, or acute posterior wall MI), the MI team should be activated, and the care is similar to those patients with reported VF or VT arrest.

3. If priority ECG findings are not seen, but the etiology of the arrest is most likely owing to primary cardiac disease, the cardiology fellow will admit the patient to the cardiac care unit. We recommend an emergency echocardiogram.

4. If the etiology is likely noncardiac, the patient will be admitted to the medical intensive care unit.

The cardiac arrest team includes the following 10 people. The traditional ACS-MI team comprises the following members:

1. Interventional cardiologist on-call team leader

2. Critical care unit director

3. Cardiology fellow on call

4. Interventional cardiology fellow on call

5. Cath lab nurse on call

6. Cath lab technician on call

7. Critical care unit nurse manager on call

In addition, the following personnel form the team:

• 8. The neurologist on call

• 9. The critical care attending on call

• 10. The medical resident screener

The MI team is activated by a single page to the central call center by the ED physician.

Steps in the emergency department:

1. Decision to initiate induced hypothermia is made jointly by the ED physician and the cardiology or critical care physician. It is very important to review the hospital center’s inclusion and exclusion criteria and decide whether the patient is a candidate for the TH protocol.

2. The physician places an order to initiate hypothermia protocol.

Our goal is to transfer the patient to the percutaneous coronary intervention (PCI) center as soon as possible with a target door-to-balloon time of < 90 minutes.

The management of the patient at this point is according to our Priority risk, Advanced risk, Intermediate risk, and Negative/low risk (PAIN) pathway following the priority ACS algorithm.⁶³

Following cardiac catheterization, several steps occur while the patient is still in the catheterization laboratory:

1. The femoral arterial sheath can be maintained as an arterial catheter, which may be necessary to obtain blood pressure readings and arterial blood gas analyses.

2. The intravascular hypothermia catheter is inserted under strict aseptic technique (if it was not done earlier).

All patients are then transferred from the catheterization laboratory to the critical care unit where invasive hypothermia is initiated.

Step II: Induced Therapeutic Hypothermia Protocol in the Critical Care Unit

The clinicians review the case and confirm the appropriateness of induced hypothermia (see Fig. 92–3B). In summary, we recommend induced hypothermia for patients > 18 years of age, who sustained a cardiac arrest and remain in coma. Patient must be comatose, not following commands or demonstrating purposeful movements. Patients excluded from the hypothermia protocol include patients who are awake, suffered prolonged ischemic times, experience refractory shock, demonstrate multiorgan failure, or have severe underlying illnesses, including terminal illnesses and do-not-resuscitate (DNR) status.

The hypothermia protocol is divided into three phases as seen in Fig. 92–3B:

• Phase 1: Cooling phase for the first 24 hours

• Phase 2: Rewarming phase

• Phase 3: Maintenance phase

Phase 1: Cooling Phase for the First 24 Hours

We recommend 24 hours of the cooling therapy at a temperature goal of 33°C. As will be discussed later in this chapter, the dose of the temperature management is controversial and some centers cool patients to 36°C. Endovascular catheters are an effective method of inducing therapeutic hypothermia (if a core cooling method is chosen). The catheters are usually inserted into the inferior vena cava through the femoral vein. Continuous core temperature monitoring is required and generally accomplished using a temperature probe in the bladder (urinary catheter) or the rectum.

Monitoring of clinical condition and potential complications during the cooling phase

As there are many physiologic effects of hypothermia, we recommend continuous monitoring and hourly documentation of vital signs; core temperature; cardiac rhythm; hemodynamic, respiratory, neurology status; and urine output. Common hemodynamic changes observed with cooling include hypertension, decreased cardiac output, and increased systemic vascular resistance. The hypertension and the increased systemic vascular resistance are believed to result from the cold-induced vasoconstriction.

Serum electrolyte imbalance is common during the cooling phase and results from the cooling-induced intracellular shifts of potassium, magnesium, calcium, and phosphate, resulting in low levels of all these electrolytes. During the rewarming phase these electrolytes shift back to the extracellular space. Our protocol therefore recommends measurements of the basic metabolic panel every 4 hours for a total of 48 hours, measuring electrolytes (calcium, magnesium, and phosphate), PT, PTT, and INR, and a CBC every 12 hours up to 48 hours.

Additional possible side effects of cooling to be monitored include the following:

1. Coagulopathy. Coagulopathy is generally not significant with careful temperature monitoring and avoiding temperature of < 33°C. If active bleeding occurs during the cooling phase, evaluation of coagulation factors and platelets should be performed and deficiencies corrected.

2. Hyperglycemia. Hypothermia suppresses insulin release and causes insulin resistance. Our insulin infusion protocol for the management of hyperglycemia in critical care unit is used.⁶⁴

3. Infection. Infection is usually multifactorial including emergency intubation and intravenous catheter insertion and aspiration pneumonia at the time of arrest. Furthermore, the hypothermia itself can suppress white blood cell production and impairs neutrophil and macrophage function. All measures to reduce ventilator associated pneumonia are employed including elevating the head of the bed.

4. Shivering. Our protocol aims to prevent shivering by administration of sedation and neuromuscular blocking agents on induction of hypothermia.

Phase 2: Rewarming Phase

After 24 hours of the target temperature, the rewarming phase starts. Controlled rewarming is a very important phase of this protocol. Rewarming should be slow; we recommend a rate of 0.25°C per hour; therefore, it typically requires 16 hours to rewarm to 37°C. Potential complications during the rewarming phase include the following:

1. Hypotension—owing to peripheral vasodilatation during the rewarming phase.

2. Electrolyte imbalance—increased levels of potassium, magnesium, calcium, and phosphate owing to intracellular shifting of these ions back to the serum during the rewarming phase.

Phase 3: Maintenance of Normothermia Phase

The maintenance phase is the last phase of the therapeutic hypothermia protocol. Normothermia maintenance takes effect when the patient’s temperature reaches 37°C. We recommend continuation of the cooling device to maintain a temperature of 37°C and avoid fever, which can potentially worsen a cerebral injury. The duration of the additional maintenance phase is usually between 24 and 48 hours.

Step III

The management following hypothermia and rewarming depends on the neurologic prognosis (see Fig. 92–3C). At least 72 hours after cardiac arrest, the neurologic examination is performed by the neurology team. The neurologic examination may be affected by the hypothermia protocol, including requirements for sedation and therapeutic paralysis, so that the formulation of a neurologic prognosis may be delayed. In general, we defer neurologic prognostication until 6 days after arrest in patients undergoing hypothermia protocol.

Pathways for the patients will divide based on whether the patient has a favorable neurologic prognosis or an unfavorable neurologic prognosis. An unfavorable neurologic prognosis would be defined as expectation for a persistent coma or vegetative state, or severe disability. If the prognosis appears unfavorable, we recommend activating the ethics committee to meet with the family and clinicians to define the goals of care. From our experience, in most instances, life support is limited or withdrawn in such patients.

If the neurological prognosis appears favorable, then the key question regarding further therapy is based on whether the cardiac arrest was because of MI. If there is no evidence of acute MI (negative cardiac markers), then we recommend electrophysiology service consultation for consideration of implantable cardioverter-defibrillator (ICD) placement and treatment of heart failure based on our heart failure pathway.⁶⁵ If acute MI is confirmed by positive cardiac markers we advise care based on the left ventricular ejection fraction (LVEF), as it is defined by echocardiography or other imaging modalities. If LVEF ≤ 35%, we recommend activation of the ESCAPE pathway for sudden cardiac death prevention⁶⁶ and to consider ICD placement if LVEF ≤ 35% at 40 days post-MI. Also, we recommend managing heart failure according to our heart failure pathway.⁶⁵ If LVEF > 35%, we recommend following our PAIN pathway for the management of ACS⁶³ including the following:

• Lifestyle modification

• Cardiac rehabilitation

• Secondary prevention medication (dual oral antiplatelet, β-blocker, high-dose statin, angiotensin-converting enzyme inhibitor/angiotensin receptor block)

Unresolved Practical Questions Regarding TTM

How Low Should We Go?

As mentioned earlier, the Therapeutic Temperature Management study compared temperature management at 33°C to maintaining a core temperature of 36°C.⁶⁰ and concluded that maintaining core temperature at 36°C has equally good outcomes as cooling to 33°C. This observation seems to contradict the findings of all previous studies and may have been a result of selection bias. Our group hypothesizes that a potential difference in outcome based on degree of cooling will depend on the severity of brain injury. Our group opinion regarding this difference in outcome depending on the selection of patients for TTM appears in Figure 92–4. As seen in this figure, we can divide patients who survive cardiac arrest into five groups based on the degree of their post-arrest brain injury.

1. Very severe brain injury

2. Severe brain injury

3. Moderate brain injury

4. Mild brain injury

5. Very minimal brain injury

Patients who fall into the first or the last category are unlikely to be considered for TTM in any healthcare system (as seen in the lower half of our figure). Patients who fall into groups 2, 3, and 4 are expected to have variable outcome. Patients in group 2, with severe brain injury, are expected to have poor outcome with any TTM. Patients in group 4 with mild brain injury are expected to have a good outcome with any TTM. However, for patients in group 3, with moderate brain injury, the dose of TTM may affect outcome.

Our hypothesis is derived by applying Bayes’ Theorem to the relationship between post-TTM degree of brain injury and pre-TTM degree of brain injury. Our hypothesis is seen in Fig. 92–5. In this figure we have plotted the pre-TTM degree of brain injury on the x-axis with score of 0 to 100 and the post-TTM degree of brain injury on the y-axis with score of 0 to 100, where a score of 0 means no brain injury and a score of 100 means irreversible brain injury.

• As outlined earlier, we have five groups of patients based on their severity of brain injury: very minimal, mild, moderate, severe, and very severe.

• The equivocal line (Z) represents where the pretreatment group brain injury is exactly the same as the posttreatment group brain injury.

• The other two lines represent the different temperature doses of 33°C and 36°C.

• It is the delta (Δ) between these lines that defines if the therapy has a potential benefits.

On the left end of this figure, the delta is very small for patients with very minimal or mild brain injury. This is the same case for patients with severe or very severe brain injury, where the delta between the two doses of therapy is very small. However, for patients with moderate brain injury, the delta is quite large. In our hypothesized algorithm there is a potential to reduce the post-TTM degree of brain injury from a high to a low score. Based on this hypothesis, our group suggests that the dose of temperature management should be 33°C because it is difficult prognostically to determine moderate brain injury level. We have to remember that this is only a hypothesis and larger studies enrolling solely patients with moderate brain injury should be conducted. Our group believes that the Achilles heel of the field of TTM is our current limitations in the prognostication of postarrest brain injury.

Endovascular Versus Surface Cooling

Technologies can be broadly divided into invasive (core cooling) and noninvasive (surface cooling) methods.⁶⁷ There is no evidence for a difference in outcome based on cooling method.

The advantages of invasive cooling over surface cooling are:

1. Greater speed of hypothermia/normothermia induction when core cooling is used; however, it is unclear whether more rapid induction improves outcome.

2. Fewer and smaller temperature fluctuations in the maintenance phase.

3. Continuous central temperature measurement in some types of endovascular catheter is possible.

4. No risk of surface cooling-induced skin lesions.

5. Ease of accessibility to patient, that is, no need to cover large areas of the skin to achieve cooling.

6. Less medication may be needed to control shivering because there is more effective shivering suppression with skin counter warming (ie, the entire surface area can be warmed using warm air, leading to a significantly diminished shivering response).^49,68,69

The advantages of surface cooling over invasive cooling are:

1. Ease of use; can be applied by nurses without a physician being present.

2. No invasive procedure required; therefore, no risk of mechanical complications.

3. Can be started immediately, without waiting for catheter insertion procedure, so potentially less delay in initiation of cooling.

4. No risk of catheter-induced thrombus formation.

5. Can be more easily applied outside the intensive care unit setting.

A study by Deye and coworkers compared endovascular to surface cooling in a prospective, multicenter RCT.⁷⁰ The authors enrolled 400 patients; 203 were treated with endovascular cooling (using Zoll femoral Icy catheters) and 197 with external cooling (ice packs, fans, and a home-made tent). The main findings were as follows: significantly shorter time to target temperature (33°C), greater stability of temperature (defined as time within target ± 1°C) in the maintenance phase, and reduced nursing workload (10 vs 38 minutes, P < .001) in the endovascular group; more minor side effects in the endovascular group (P = .009); a nonsignificant trend toward more favorable outcome at 28 days (36.0% vs 28.4%, OR 1.41 [95% CI, 0.93-2.16], P = .107; for shockable rhythm 53.7% vs 37.1%, OR 1.97 [95% CI, 0.99-3.9], P = .269) and at 90 days (34.6% vs 26.0%, OR 1.51 [95% CI, 0.96-2.35], P = .07) in the endovascular group; and fewer cases of severe overshoot (below 30°C) in the endovascular group (n = 0 vs n = 3).⁷⁰ Strict fever control was maintained for a minimum of 3 days following rewarming in both groups. This study had some limitations, especially the fact that newer and more powerful surface cooling devices, such as the Arctic Sun system, were not used and surface cooling was accomplished using fairly basic tools and devices. We believe that the cooling method should be determined by institutional protocol.

Highlights from the 2015 Guideline Recommendation for Post–Cardiac Arrest Care

Out-of-Hospital Cooling

Based on the 2015 guidelines, the routine prehospital cooling of patients with rapid infusion of cold intravenous fluids after ROSC is not recommended.²⁴

Hemodynamic Goals After Resuscitation

It may be reasonable to avoid and immediately correct hypotension (systolic blood pressure less than 90 mm Hg, mean arterial pressure less than 65 mm Hg) during post–cardiac arrest care.²⁴

Why? Studies of patients after cardiac arrest have found that a systolic blood pressure less than 90 mm Hg or a mean arterial pressure of less than 65 mm Hg is associated with higher mortality and diminished functional recovery, while systolic arterial pressures of greater than 100 mm Hg are associated with better recovery. Although higher pressures appear superior, specific systolic or mean arterial pressure targets could not be identified, because trials typically studied a bundle of many interventions, including hemodynamic control. Also, because baseline blood pressure varies from patient to patient, different patients may have different requirements to maintain optimal organ perfusion.

Early Coronary Angiography

Based on the 2015 guidelines, coronary angiography should be performed emergently (rather than later in the hospital stay or not at all) for OHCA patients with suspected cardiac etiology of arrest and ST-segment elevation on ECG. Emergency coronary angiography is reasonable for select (eg, electrically or hemodynamically unstable) adult patients who are comatose after OHCA of suspected cardiac origin but without ST-segment elevation on ECG. Coronary angiography is reasonable in post–cardiac arrest patients for whom coronary angiography is indicated, regardless of whether the patient is comatose or awake.²⁴

Targeted Temperature Management

All comatose (ie, lacking meaningful response to verbal commands) adult patients with ROSC after cardiac arrest should have TTM, with a target temperature between 32°C and 36°C selected and achieved, then maintained constantly for at least 24 hours.²⁴

Continuing Temperature Management Beyond 24 Hours

Actively preventing fever in comatose patients after TTM is reasonable. In observational studies, fever after rewarming from TTM is associated with worsened neurologic injury, although studies are conflicting. Because preventing fever after TTM is relatively benign and fever may be associated with harm, preventing fever is suggested.²⁴

Prognostication After Cardiac Arrest

The earliest time to prognosticate a poor neurologic outcome using clinical examination in patients not treated with TTM is 72 hours after cardiac arrest, but this time can be even longer after cardiac arrest if the residual effect of sedation or paralysis is suspected to confound the clinical examination.²⁴

Why? Clinical findings, electrophysiologic modalities, imaging modalities, and blood markers are all useful for predicting neurologic outcome in comatose patients, but each finding, test, and marker is affected differently by sedation and neuromuscular blockade. In addition, the comatose brain may be more sensitive to medications, and medications may take longer to metabolize after cardiac arrest. No single physical finding or test can predict neurologic recovery after cardiac arrest with 100% certainty. Multiple modalities of testing and examination used together to predict outcome after the effects of hypothermia and medications have been allowed to resolve are most likely to provide accurate prediction of outcome.

Organ Donation

All patients who are resuscitated from cardiac arrest, but who subsequently progress to death or brain death, should be evaluated as potential organ donors. Patients who do not achieve ROSC and who would otherwise have resuscitation terminated may be considered as potential kidney or liver donors in settings where rapid organ recovery programs exist.²⁴

Why? There has been no difference reported in immediate or long-term function of organs from donors who reach brain death after cardiac arrest when compared with donors who reach brain death from other causes. Organs transplanted from these donors have success rates comparable to organs recovered from similar donors with other conditions.