The incidence of out-of –hospital cardiac arrest is a common event, particularly in the Western world. There are 110,000 deaths from coronary disease in the United Kingdom each year, of which 75% are due to sudden cardiac death (Schilling et al., 1998; DoH 2005). Despite nearly 40 years of pre-hospital advance life support, the survival rate of hospital discharge following out-of-hospital cardiac arrest is very poor. Among the few survivors to hospital discharge, neurologic impairment often remains a lasting morbidity (Becker et al., 1993).
A large body of evidence from animal models indicate that hyperthermia (a temperature higher than the threshold value of 37C) due to brain injury or ischemia can exacerbate the degree of permanent neurological damage following cardiac arrest. Each degree Celsius higher than 37C can cause cerebral destruction through increased metabolic expenditure, excitatory neurotransmitters resulting in calcium cellular reflux and accumulation of oxygen free radicals (Busto et al., 1987).
To improve the outcome of patients who survive cardiac arrest requires not only reducing the ischemic process as quickly as possible, caused by cardiac arrest, but also preventing post resuscitation syndrome caused from reperfusion (Safar, 1993). Cerebral reperfusion after successful resuscitation can trigger harmful chemical cascades such as oxygen free radical production which can result in multifocal brain damage. Therapeutic hypothermia (TH) is considered as an effective method for reducing the deleterious neurological outcomes in patients who have out-of-hospital cardiac arrest. Clinical and animal studies have shown that TH following cardiac arrest reduces both the cerebral metabolic rate and oxygen demand and it is thought to attenuate reperfusion injury, global inflammation and endothelial dysfunction, all consequences of cerebral ischemia.
Over the last decade several research trials have demonstrated that the induction and maintenance of hypothermia following out-of-hospital ventricular fibrillation cardiac arrest improved neurological outcome. The use of induced hypothermia following cardiac arrest was introduced in the 1950’s. In the 1990’s, promising results in animal studies turned research to the feasibility of hypothermia in humans. Clinical feasibility studies in the late 1990’s have proved the use of hypothermia in humans to be safe and effective. Several randomized clinical studies were conducted since that time. In two randomized clinical trials, induced hypothermia resulted in significantly improved neurological outcomes (Holzer, 2002 and Bernard et al ., 2002). On the strength of these studies the International Liaison Committee on Resuscitation (ILCOR) published that unconscious adult patients with return of spontaneous circulation (ROSC) following out-of-hospital cardiac arrest should be cooled to 32-34C for 12-24 hours when the initial rhythm was ventricular fibrillation (VF) or ventricular tachycardia (VT).
Renewed interest on TH after cardiac arrest has re instigated the argument on the benefits of cooling patients to provide protection for the brain. However, TH can be a two-edged sword. Although significant benefits can be achieved, there are many potential side effects that if left untreated can negate the potential benefits. Many of these side effects can be prevented by high quality intensive care treatment. As a nurse working in a critical care unit once the decision is made to induce hypothermia, the focus of nursing care is the achievement and maintenance of hypothermia and the prevention of potential side effects. Careful monitoring of a patient’s vital signs, fluid balance, electrolyte levels and eventual re-warming are some of the essential critical care nursing skills required. Having the opportunity to improve quality measurements and best practice standards by increasing critical care nurses’ knowledge and understanding of the underlying physiological and pathophysiological mechanisms of hypothermia therapy is crucial when providing care for patients receiving TH. Therefore, critical care nurses should be familiar with the physiologic effects, current indications and complications of therapeutic hypothermia.
The object of this dissertation is to undertake a literature review on the current evidence available on the effectiveness of TH following cardiac arrest. To determine the effectiveness the following parameters will be addressed: i) the speed and best method of cooling, ii) the duration of cooling, iii) rate of re warming, iiii) and the associated complications.
Most patients who are resuscitated from cardiac arrest are unconscious and require care management at an intensive care unit. Therefore, it is vital evidence based practice is implemented.
The aim of this dissertation is to systematically review existing evidence on the use of TH for comatose survivors of out-of-hospital cardiac arrest, and to construct a research evidence based protocol for an adult intensive care unit to serve as an important instrument whereby, critical care nurses can standardize and improve the neurological outcomes of patients who have experienced cardiac arrest and have been successfully resuscitated.
Pathophysiological Mechanisms Following Cardiac Arrest
The onset of cardiac arrest is sudden and dramatic, typically related to VT, VF or both. During cardiac arrest, cerebral perfusion stops. Within 10 seconds, loss of consciousness will occur. Within four to six minutes brain death can occur (Eleff et al., 1991). Patients successfully resuscitated after cardiac arrest mainly receive supportive care, with only 5 -30% of patients surviving to hospital discharge. Cardiac arrest survivors suffer from ischemic brain injury leading to poor neurologic outcome. According to Safar (1993) and Lee et al. (2002), the level of neurological damage has been estimated to be between 10% and 70%.
Neurological damage occurs during the temporary phase of interrupted cerebral blood flow and resulting anoxia. This limited cerebral blood flow also primes the brain for further damage from reperfusion related injury. Immediately postresuscitation the brain becomes depleted of oxygen within 20 seconds. This is followed by the consumption of adenosine triphosphate (ATP) and glucose stores within 5 minutes. Anaerobic glycolysis follows leading to a decrease in energy stores (Ning et al., 2002).
In addition to energy depletion lipolysis occurs, inorganic acids and fatty acids accumulate resulting in intra and extracellular acidosis build up. The deficiency of intracellular ATP affects transmembrane transport electrolytes and structures such as sodium (Na+), potassium (K+), calcium (Ca++) and ATP – dependent ion pump. There is an increase in interstitial K+ and intracellular Ca++, as well as a large influx of Na+ and Chloride (Cl-) into the cells (Vaagenes et al., 1996).
This sequence of events leads to a state of cellular hyperexcitability resulting in cell death. Even if resuscitation is successful and blood flow and energy storage is normalised, there is continued tissue injury secondary to delayed necrosis of the tissue as well as apoptosis of the neuronal tissue. This type of damage during reperfusion is thought to be due to rapid metabolism of accumulating arachidonic acids leading to free oxygen radical formation. Cellular damage after the initial ischemia and reperfusion injury triggers an inflammatory response caused by the release of pro-inflammatory mediators such as tumour necrosis factor alpha and interleukin from astrocytes following reperfusion. These casade of events are exacerbated when the patient’s temperature increases by 0.5C over 37C (Alzaga, 2006).
Previous strategies for reducing neurological damage following cardiac arrest have been unsuccessful. Prospective, randomized, controlled human trials have investigated the use of thiopentone , corticosteroids and a calcium antagonist, but none of these agents showed benefit (The brain resuscitation clinical trial study group, 1986). Induced hypothermia is the only therapy that demonstrates improved neurological outcomes following cardiac arrest (Bernard et al. 2002).
SEARCH STRATEGY
In order to evaluate the research on therapeutic hypothermia a comprehensive review of the published literature was necessary. The following databases were searched: the Cochrane Central Register of Controlled Trials; Medline via PubMed; Sciencedirect; and CINAHL from 1950 to 2010 to identify relevant published trials. The search headings included the following keywords: neuroprotection, therapeutic hypothermia, induced hypothermia and cooling following cardiac arrest. Articles were limited to the English language. A hand search of the references of relevant studies and reviews was also performed. All relevant literature was critically appraised, with the emphasis on evidence from randomized and quasi-randomized trials rather than smaller studies and case reports. All the available evidence was graded using Sackett’s original evidence based approach (see appendix 1). A total of six controlled studies were identified which were relevant to use of therapeutic hypothermia. Two studies used historical controls and four trials were randomized and quasi-randomized. One trial conducted by Callaway et al. (2002) was excluded because it investigated whether application of hypothermia during advanced cardiac life support was feasible.
DEFINITION OF THERAPEUTIC HYPOTHERMIA
Therapeutic hypothermia is defined as the controlled lowering of core temperature for therapeutic reasons. The core body temperature is usually defined as the temperature of blood in the heart, major arteries, internal organs and the temperature of the brain (Hartemink et al. 2004). It is assumed that these temperatures are identical in most conditions, in practice, however there can be variations. The definition of core body temperature and as such hypothermia is interpreted differently in different settings.
To address this the Resuscitation Council UK produced guidelines related to the classification of different phases of hypothermia in order to unify the definitions used when referring to hypothermia. The Resuscitation Council define hypothermia as a condition in which the core temperature of the body is less than 35C. This is then further subdivided into mild (35-32C), moderate (32-30C) and severe (below 30C) hypothermia.
Therapeutic hypothermia affects many intracellular processes as well as physiological and patho-physiological changes. Hypothermia has been shown to decrease multiple mechanisms of secondary injury after ischemia and reperfusion. These include energy failure, oxidant injury, cerebral oedema, blood-brain barrier permeability and inflammation amongst others. Hypothermia also leads to a reduction of metabolic rate. Specifically, the cerebral metabolism such as oxygen consumption, glucose utilization and lactate concentration. It is estimated that for each 1C decrease in brain temperature, the cerebral metabolic rate decreases by 6 to 7% (Polderman et al. 2004).
Because the cerebral metabolic rate for oxygen is the main determinant of cerebral blood flow, hypothermia may provide for a relative improvement in oxygen supply to areas of ischemic brain. Following an ischemic attack and reperfusion injury, hypothermia is thought to decrease the concentrations of excitatory amino acids and lactate thereby, decreasing further mitochondrial damage and cell death (Polderman et al. 2004).
HISTORICAL DEVELOPMENT OF THERAPEUTIC HYPOTHERMIA
The historical development of therapeutic hypothermia (TH) has been intermittently used for clinical purposes since ancient times. The Greek physician, Hippocrates, advocated packing soldiers in snow and ice to reduce haemorrhage. Historical figures such as Julius Caesar and Richard the Lion-Heart were relieved of ailments by ice cold treatments.
Later during the war of 1812, Baron de Larrey, a French army surgeon during Napoleon’s Russian campaign packed injured limbs in ice prior to amputation to render the procedure painless. In 1937, a neurosurgeon, Temple Fay pioneered “human refrigeration” (cooling patients to 32C for 24hours) as treatment for malignancies and head injuries. Smith and Fay, in 1940, reported the physiologic effects that induced TH caused in a series of cancer patients.
In the 1950’s, Bigelow and McBirnie using animal models, documentated and promoted the beneficial effect of TH for the brain and heart during intracardiac surgery. Interestingly, the application of cold temperature has become a crucial component of modern cardiac surgery. In 1955, Rosomoff and Gilbert demonstrated, in dogs, the protective benefit of hypothermia during but also after focal brain ischemia. During the 1960’s, Peter Safar recommenced the use of resuscitative hypothermia after successful resuscitation from cardiac arrest in his ABC of post cardiac care. Although, there were clinical trials, this potential treatment lay dormant for 20 years because of its questionable benefits, difficulties encountered in inducing and maintaining hypothermia and its potential for injurious systemic complications. Despite the lack of sufficient weight on TH some clinicians continued to investigate its potential benefits.
In the mid 1980’s animal studies provided a fresh impetus for clinical use of hypothermia and provided important insights into the mechanisms underlying hypothermia’s protective effects. A core temperature below 30C was shown not to be required to achieve benefits, protective effects could be achieved with mild to moderate (32-34C) hypothermia resulting in fewer side effects. In the late 1980’s the application of mild hypothermia was shown to be beneficial in an animal model of cardiac arrest, renewing interest in the use of mild hypothermia in cardiac arrest patients (Leonov et al., 1990; Sterz et al., 1991). Additionally, the advent of intensive care unit’s and high care facilities have made it possible to manage associated side effects more effectively, leading to a renewed interest in the clinical use of TH.
In general, the protective, preservative and resuscitative effects of hypothermia have been studied in animal models and in clinical settings. Human studies comprised initially of case reports and feasibility trials, until two landmark prospective randomized multi-centre studies were published in 2002.
