Running Head: INDUCED HYPOTHERMIA IMPROVE NEUROLOGIC OUTCOME

Does Medically Induced Hypothermia Improve Neurologic

Outcomes in Cardiac Arrest Patients?
Salena Barnes, RN
Georgia College and State University

INDUCED HYPOTHERMIA IMPROVE NEUROLOGIC OUTCOMES

Abstract
Cardiac arrest is an event, which can transpire at any place and anytime. An individual may
experience this life-changing event even without a history of heart disease. This traumatic event
can precipitate a cascade of events throughout an individuals body that can be detrimental.
Although many medical advances exist in technology, as well as procedures to improve patient
outcomes, many lives are still lost annually. However, those who survive often suffer from
neurological damage. The purpose of the paper is to evaluate the utilization of medically
induced hypothermia improving the neurologic outcomes in cardiac arrest patients.
Keywords: cardiac arrest, cardiopulmonary resuscitation, hypothermia, myocardial infarction,
neurological outcome, coma

INDUCED HYPOTHERMIA IMPROVE NEUROLOGIC OUTCOMES

Does Medically Induced Hypothermia Improve Neurologic Outcomes in Cardiac Arrest Patients?
Cardiac arrest is the sudden loss of cardiac function in an individual who may or may not
have been diagnosed with a heart disease. Furthermore, this is an abrupt halt of mechanical and/
or electrical activity of the heart, and the brain suffers from lack of oxygen (Wilson, 2013).
However, it is important to differentiate a heart attack from cardiac arrest. A heart attack can
lead to a cardiac arrest, as well as drug overdoses, drowning, poisoning and electrocution
(Wilson, 2013). Heart attacks occur when there is an interruption of the blood supply to the heart
by a blockage. A heart attack or myocardial infarction (MI), which causes sudden death of
cardiac muscle, may present with symptoms of chest pain, diaphoresis, and dyspnea or
sometimes with no symptoms (Cannon, 2013).
Ventricular fibrillation is the most prevalent rhythm in cardiac arrest. In ventricular
fibrillation, the heart ventricles quiver or start beating erratically, impeding the hearts ability to
pump blood throughout the body to vital organs (Natale et al., 2010). When the heart ceases to
circulate blood, death can occur within minutes. Once the heart ceases to pump, quality
cardiopulmonary resuscitation must begin to restore flow of oxygenated blood to the brain, as
well as the heart. Additionally, a defibrillator can be utilized to shock the individual to aid in
reestablishing a normal heart rhythm, thus improving the patients prognosis (Wilson, 2013).
Establishing return of spontaneous circulation is important, however, a cardiac arrest causes a
chain of reactions within an individuals body. This paper will explore the concept of medically
induced or therapeutic hypothermia, in addition, the neurologic outcomes of individuals who
treated with medically induced hypothermia versus those who were not after cardiac arrest.

INDUCED HYPOTHERMIA IMPROVE NEUROLOGIC OUTCOMES

Overview
The use of medically induced hypothermia has been considered for treatment of head
injuries since the 1900s (Varon & Acosta, 2008). In the mid-1900s, further research was done
utilizing therapeutic hypothermia in monkeys and canines. The research yielded benefits of
therapeutic hypothermia such as decreased metabolic rates and decreased cerebral oxygen
consumption. However, when hypothermia temperatures were less than 30o Celsius,
overwhelming complications were identified, such as ventricular fibrillation (Varon & Acosta,
2008). During the period these studies performed, there were complications such as infection
and unstable hemodynamics, which presented as a challenge. Consequently, the idea of induced
hypothermia was not acknowledged as a therapeutic choice. However, the animal research
continued (Keresztes & Brick, 2006; Soreide, 2014; Varon & Acosta, 2008).
By the 1980s, therapeutic hypothermia was being utilized on canines after cardiac arrest
(Varon & Acosta, 2008). The research yielded positive results that included an improved
neurological status, as well as survival rates (Weinrauch, Safar, Tisherman, Kuboyama, &
Radovsky, 1992). Once again, therapeutic hypothermia was explored by medicine as having
potential positive effects for humans. Moreover, it was not until two groundbreaking studies
published in 2002 introduced induced hypothermia as the ideal practice for cardiac arrest patients
(Calver, Braungardt, Kupchik, Cutler, & Jensen, 2005; Guly, 2011; Varon & Acosta, 2008).
Every year in the United States, over three hundred thousand individuals experience an
out-of-hospital cardiac arrest and the survival rate is less than ten percent (McNally et al., 2011).
Furthermore, less than seven percent of the individuals who survive recover with their pre-arrest
neurological function, and fifty percent of the survivors have significant long-term neurological
deficits (Geocadin & Eleff, 2009).

INDUCED HYPOTHERMIA IMPROVE NEUROLOGIC OUTCOMES

During a cardiac arrest, the vital organs are deprived of oxygen and glucose (Amantea,
Nappi, Bernardi, Bagetta, & Corasaniti, 2009). The brain has an exceptionally high metabolic
demand and consumes approximately twenty percent of cardiac output. Thus, leaving virtually
no reserves of oxygen and glucose, which effects cell homeostasis. Moreover, within ten to
twenty minutes glucose and glycogen stores are depleted throughout the body, resulting in
approximately ninety-five percent of brain damage after fifteen minutes. It is important to note
brain ischemia is a common cause of irreversible brain damage. Apoptosis of the brain cell
occurs due to a disruption in adenosine triphosphate production, dysfunction of sodium and
potassium pumps, lactic acid formation, intracellular acidosis, and cellular edema, which signals
cellular death. Glutamate is released from damaged cells and activates release of lipase,
proteases, and nucleases. Interference with intracellular mitochondrial respiration leads to
damage of the cellular cytoskeleton, resulting in necrotic cell death. Once reperfusion is
established, further injury can occur to the brain due to activation of microglial cells, increased
cytokines, increased free radicals, and nitric oxide release. Micro-hemorrhages and further
edema can occur due to the damaged capillaries. Due to the inflammation, the brains blood flow
remains impaired, even though systemic circulation has been reestablished (Amantea et al.,
2009).
Bernard et al. (2002) performed a study on a group of seventy-seven out-of-the hospital
cardiac arrest patients that were randomly assigned to a hypothermia group or a standard therapy
group. The patients assigned to the hypothermia group received therapeutic hypothermia at
33oCelcius within two hours after return of spontaneous circulation. The hypothermia group
were kept at this temperature for twelve hours. Out of the seventy-seven patients evaluated in
the study, forty-nine percent of the patients treated with hypothermia were either discharged

INDUCED HYPOTHERMIA IMPROVE NEUROLOGIC OUTCOMES

home or to a rehabilitation facility with favorable neurologic outcomes. However, only twentysix percent (P=0.046) of the patients that received standard care could be discharged home or to
a rehabilitation facility. Adjustments made for baseline variances in age and time from collapse.
The odds ratio comparison for positive outcomes were made with patients receiving hypothermia
versus those who received normothermia or standard care was 5.25 (95 percent confidence
interval, 1.47 to 18.76; P=0.011) (Bernard et al., 2002). The use of hypothermia treatment was
associated with a decreased cardiac index, increased systemic vascular resistance, as well as
higher glucose levels. Thus, the study suggested therapeutic hypothermia improved outcomes in
out-of-hospital patients who were comatose after resuscitation. However, this was not a blind
study and the certain aspects of care may have varied between groups (Bernard et al., 2002).
The Hypothermia after Cardiac Arrest Study Group, was a randomized, control trial that
studied two hundred seventy-three patients who presented in the emergency room with a nonperfusing ventricular arrhythmia with return of spontaneous circulation (Hypothermia after
Cardiac Arrest Study Group, 2002). There were a total one hundred thirty-seven patients who
received therapeutic hypothermia (cooled between 32oCelsius to 34oCelsius) within four hours of
return of spontaneous circulation. This was maintained for twenty-four hours. The remaining
one hundred thirty-eight patients received normothermia or traditional treatment. The patients in
both groups were evaluated at six months for favorable neurological outcomes. Fifty-five
percent of the hypothermia group (75 out of 136) had favorable neurological outcomes, as
compared with thirty-nine percent (54 out of 137) of the normothermia patients (risk ratio 1.40;
95% confidence interval, 1.08 to 1.81). Survival rates at six months were forty-one percent (56
out 137 patients died), versus fifty-five percent in the normothermia group (76 out of 138
patients died; risk ratio 0.74; 95% confidence interval, 0.58 to 0.95). Furthermore, there was no

INDUCED HYPOTHERMIA IMPROVE NEUROLOGIC OUTCOMES

significant difference in the complication rate. This study yielded positive neurologic outcomes
and a reduction in mortality ("Mild herapeutic hypothermia to improve the neurologic outcome
after cardiac arrest," 2002).
Additionally, based on the evidence of these from previous studies, the International
Liaison Committee on Resuscitation recommended that all unconscious adult patients with return
of spontaneous circulation after out-of hospital arrest due to ventricular fibrillation receive
therapeutic hypothermia. The target temperature should be between 32oC to 34oCelsius for
twelve to twenty-four hours and in 2003 published indications for this procedure (Nolan et al.,
2010). By 2005, these recommendations were included in post-resuscitation support guidelines
(Sayre et al., 2009).
Search Strategy
The following articles were utilized for the literature review portion of the paper: primary
sources of research, case studies, randomized controlled trials (RCTs), and meta-analysis.
Literature reviews, opinion articles and secondary sources excluded from the literature review.
The following electronic databases were searched using a combination of keywords cardiac
arrest, cardiopulmonary resuscitation, hypothermia, myocardial infarction, neurological outcome,
and coma, PubMed, CINAHL, and EBSCO. This yielded one case study, one meta-analysis, and
several other primary sources.
Literature Review
The case report involved a 40 year old Caucasian male with a history of hypertension,
hyperlipidemia, tobacco use, and obesity (Nusbaum, Bassett, Gregoric, & Kar, 2014). The
patient went into a non-perfusing rhythm for three times, and survived approximately three and a
half hours of resuscitation efforts. Cardiopulmonary resuscitation was provided according to the

INDUCED HYPOTHERMIA IMPROVE NEUROLOGIC OUTCOMES

American Heart Association/American College of Cardiology Advanced Cardiac Life Support

(ACLS). Therapeutic hypothermia was initiated immediately with the goal temperature set to be
between 32oCelsius to 34oCelsius. The patient recovered with full pre-neurological function.
However, due to rhabdomyolysis he went into renal failure and hemodialysis was required. After
having orthotopic heart and cadaveric kidney transplants, the patient was discharged home from
the hospital on the one hundred and seventy-ninth day. There was no need for any type of
rehabilitation due to his full neurological recovery. The study revealed hypothermia has a
neuroprotective effect post-arrest. The lowering of body temperature decreases cerebral oxygen
demand and destructive enzymatic reactions, and reduces amounts of free radicals, intracellular
acidosis. (Nusbaum et al., 2014).
European medicine has recently incorporated therapeutic hypothermia into their
resuscitation guidelines for out-of-hospital cardiac arrest (Pleskot, Hazukova, Stritecka,
Cermakova, & Pudil, 2009). Many individuals experiencing out-of-hospital arrest share various
risk factors, outcomes, and are of an inhomogeneous population. This study focused on out-of
hospital cardiac arrest caused by ST-elevation myocardial infarction (STEMI). In addition, it
analyzed the long-term effects of therapeutic hypothermia on a homogeneous sample of patients
with witnessed out-of-the hospital cardiac arrest. There were forty-eight participants, in which
half received therapeutic hypothermia and the remaining half received traditional treatment after
invasive coronary angiography. The participants also had cardiopulmonary resuscitation with
return of spontaneous circulation prior to admission and received prompt invasive coronary
angiography.
At admission, the patient received a total of 2000 mL of rapidly infused normal saline
cooled to 4oCelsius. Invasive therapeutic hypothermia was initiated directly after the coronary

INDUCED HYPOTHERMIA IMPROVE NEUROLOGIC OUTCOMES

procedure with a target temperature of 34oCelsius (Pleskot et al., 2009). This temperature was
maintained for twenty-four hours, then followed by controlled rewarming at 0.2oCelsius per hour,
as well as controlled normothermia at 37oCelcius for another twelve hours. A probe in the
urinary catheter continuously monitored the temperature. An infrared tympanic thermometer
was used to assess the temperature of the patient every three to five minutes within the first
twenty-four hours. The group receiving hypothermia received prophylactic antibiotics and
analgesia-sedation with the goal Ramsey-Sedation Score of 2 to 3. The control group received
antibiotics if indicated based on laboratory results. All the clinical trial results were further
analyzed for clinical, procedural, as well as mortality data. The data analyzed again at the thirtyday and the one-year mark using Cerebral Performance Category Score (CPC) (Pleskot et al.,
2009).
There was a minor difference in the therapeutic group median time of arrival to the
hospital (6 minutes versus 6.5 minutes in the control group; P=0.16) (Pleskot et al., 2009).
Seventy-five percent of the initial rhythms were ventricular fibrillation versus other lethal
rhythms (P=0.75). The finding revealed no significant differences in baseline characteristics,
angiographic results, and no complications with cardiac catheterizations. After thirty days, the
mortality rate was 33.3% in both groups. At the one year mark, the mortality rate was 37.5% in
the therapeutic hypothermia and 50% in the control group (P=0.56). The therapeutic
hypothermia group also had more favorable neurologic outcomes at the one year mark versus the
control group (58.3% versus 20.8%; P=0.017). Through a multivariate analysis, therapeutic
hypothermia identified as an independent factor for a favorable neurologic outcome (P<0.02,
odds ratio: 12.73). The study revealed that therapeutic hypothermia was safe for practice and

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provided positive long-term neurological outcomes for patients who experience out-of-hospital
arrest due to a STEMI (Pleskot et al., 2009).
Swine has been researched in using induced hypothermia following an induced cardiac arrest
(Gong et al., 2013). The study used thirty-seven inbred Chinese Wuzhishan minipigs of both
sexes approximately four months old. The pigs only had access to water overnight prior to the
experiment and were sedated and intubated the following day. In addition, the pigs received
respiratory monitoring a Swan-Ganz catheter for continuous cardiac monitoring. A 5-French
pacing catheter was advanced into the right ventricle to cause ventricular fibrillation. Once the
lethal rhythm was obtained, mechanical ventilation was discontinued and cardiopulmonary
resuscitation was initiated. The pigs were bagged on room air via the endotracheal tube and
received cardiopulmonary resuscitation that included compressions (ratio 30:2), use of
epinephrine as needed, and defibrillation. Excluded from the study was any pig that did not have
return of spontaneous circulation after twenty minutes of cardiopulmonary resuscitation.
Following the return of spontaneous circulation, which was within eight minutes, the pigs
were randomly placed in groups to receive mild hypothermia (n=16) or normothermia (n=16).
The remaining five pigs were surgical controls. The surgical control group underwent surgery
without ventricular fibrillation or hypothermia (Gong et al., 2013). The pigs were immediately
cooled to the target temperature of 33oCelsius using a central venous catheter. For twelve hours
this, temperature was maintained. The controlled rewarming was at 0.5oCelcius per hour via the
Coolguard 3000 system. Cerebral samples obtained from the frontal cortex of the swine at the
twenty-four, and seventy-two hour mark, at which time the mitochondria were obtained for
analysis. The results at seventy-two hours, showed mitochondrial edema was similar in both
groups (P>0.05). Thus suggesting the mitochondrial edema was blocked in all groups by the

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cyclosporine, which suggest participation of permeability transition. However, at twenty-four

hours the mitochondrial samples obtained in the therapeutic hypothermic group showed a
reduction in edema compared to normothermia (P<0.05). The normothermia pigs showed
increased mitochondrial swelling compared to the surgical control pigs (P<0.05). The outcomes
propose that mild therapeutic hypothermia hinder mitochondrial membrane permeability caused
by ischemic changes (Gong et al., 2013).
Further, a retrospective study was done on therapeutic hypothermia in adult cardiac arrest
patients due to drowning in the Han River in Seoul, Korea (Choi et al., 2012). The study
included twenty individuals (13 females and 7 males) with ages ranging from seventeen to
seventy-two years old. Fifty-five percent of the drowning were suicide attempts, three cases
involved alcohol intoxication, and the remainder precipitating factors were unknown. Seventyfive percent of the events were witnessed with submersion times ranging from two to twenty-five
minutes.
The patients received therapeutic hypothermia by external cooling devices with a target
core temperature of 33oCelsius. The patient was rewarmed or cooled to achieve the target
temperature for twenty-four hours. Furthermore, the patient was rewarmed over an eight-hour
period. Of the twenty patients treated with hypothermia, twenty percent (n=4) had encouraging
neurological outcomes with a CPC 1-2, ten percent (n=2) were in a vegetative state at discharge
(CPC 4), and in seventy percent (n=14) death occurred (CPC 5). The most prevalent
complication was pancreatitis and rhabdomyolysis. The major causes of mortality in these
patients were acute respiratory distress syndrome (30 %), hypoxia induced brain injury (30%)
and there multiple organ dysfunction (10%). A type II Beta error resulted due to the small
sample size and the need for a larger sample size to predict outcomes. The study concluded that

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therapeutic hypothermia in adult cardiac arrest patient after drowning did not show any
advantages versus standard treatment (Choi et al., 2012).
The purpose of the next study was to assess the outcome of therapeutic hypothermia of
the survival of patients in a coma, after cardiac arrest with return of spontaneous circulation
(Petrovi et al., 2011). The study sample included a total of eighty-two comatose patients (mean
age 62, 67% male) who experienced an out-of-hospital cardiac arrest followed by return of
spontaneous circulation (within 240 minutes). There were two groups of patients, forty-five
patients treated with hypothermia, and the remaining patients were the control group. Thirtyeight of the patients in the therapeutic hypothermia group received intravascular cooling in
conjunction with external cooling; whereas seven patients received external cooling (pads
applied to the chest, back and extremities).
The patients treated with therapeutic hypothermia did not have any complications,
however, there was significant variance noted in the groups neurologic outcomes. Twenty-one
of the therapeutic hypothermia group had full neurological function (CPC 1), three patients had a
good neurological outcome (CPC 2), one patient remained in a coma, and twenty patients finally
died (CPC 5). The normothermic group had seven patients regain full neurological function
(CPC 1), and thirty patients remained in a coma and finally died (CPC 5). Twenty-three patients
survived in the hypothermia group while a total of seven in the normothermia group (P=0.003).
The researchers concluded that therapeutic hypothermia improves neurological outcomes and
decreases the mortality rate associated with cardiac arrest (Petrovi et al., 2011).
Won Young et al. (2014) performed a study to determine the rate of good neurologic
results based on the length of time resuscitative efforts were performed in out-of-hospital cardiac
arrest patients treated with therapeutic hypothermia. In addition, survival rates with prolonged

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downtimes were noted and the correlation between downtime and neurologically intact survival
in comatose adults was examined. The observational study was done January 2008 until
September 2012, which included individuals greater than eighteen with non-traumatic out-of
hospital cardiac arrest. These patients were in a coma after return of spontaneous circulation and
received therapeutic hypothermia. The length of time in which the patient was pulseless until the
time of return of spontaneous circulation is downtime.
In the study one hundred and five patients treated with hypothermia, however 18 patients
were excluded due to unknown downtimes. Subsequently, 86 patients remained for analysis and
the average down time was 18.5 (range 10.0-32.3) minutes. Thirty-eight percent (n=33) had a
good neurologic outcome (CPC 1-2). The downtime was separated into four groups (< 10 min,
11-20 min, 21-30 min, >30 min), good neurologic outcomes were 62.5%, 37%, 25%, and 21.7%
(P=0.02). In addition, downtimes greater than twenty minutes had a 22.9% good neurological
outcome, which increased to 37.5% in those patients with an initial shockable rhythm. The
analysis revealed that comatose patients who have been resuscitated and treated with therapeutic
hypothermia have a neurologically intact survival rate of 23%, even with prolonged downtimes
greater than twenty minutes (Won Young et al., 2014).
Moreover, Castrejn et al. (2009) conducted research with mild hypothermia in treatment
of patients who had a prolonged cardiac arrest caused by ventricular fibrillation or tachycardia.
Twenty-eight patients were the control group with standard care, and forty-one patients received
hypothermia. The patients in both groups had no significant difference in baseline characteristics
or in the time of treatment of the cardiac arrest (Castrejn et al., 2009). The therapeutic
hypothermia group received analgesia, sedation, and a paralytic agent after infusion of 4oCelsius
of Ringers or saline solution. The target core temperature was 33-34oCelsius for twelve to

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twenty-four hours and was reached using an isothermal blanket. Rewarming performed
passively with sedation and relaxation was discontinued upon the patients core temperature
reaching 36oCelsius. Upon discharge, eighteen of the patients in the hypothermia group
possessed a good neurological status versus five in the control group (risk ratio=2.46; 95%
confidence interval, l.11-3.98; P=0.029). When the patients neurological status was reevaluated
at six months, neurological status was good in nineteen patients (43.3%) in the hypothermia
group, and six (21.4%) in the control group (risk ratio=2.16; 95% confidence interval, 1.05-3.36;
P=0.038). The results demonstrated that hypothermic treatment post-arrest prolonged by
ventricular fibrillation or ventricular tachycardia improves neurological outcomes for patients
with anoxic encephalopathy. However, the effects of hypothermia are influenced by
confounding factors (Castrejn et al., 2009).
Therapeutic hypothermia performed by invasive or noninvasive means following cardiac
arrest. Undine Pittl et al. (2013) performed a study, which compared two different cooling
devices for management of temperatures in cardiac arrest survivors (2013). Out-of-hospital
cardiac arrest, as well as in-hospital patients who survived cardiac arrest between April 2008 and
August 2009 were included in the randomized single facility study. The therapeutic hypothermia
was administered by the invasive Coolgard system (n=39) or the noninvasive ArticSun surface
cooling (n=39) with a target core body temperature of 33oCelsius for twenty-four hours. The
effectiveness of both cooling systems was measured by neuron-specific enolase (NSE) levels as
an alternate parameter for brain damage. At the seventy-two hour mark there was no significant
differences in NSE level in both groups (16.5 ng/ml, interquartile range 11.8-46.5 surface cooled
patients versus 19.0 ng/ml, interquartile range 11.0-42.0 in invasive cooled patients, (P=0.99).
Undine Pittl et al. (2013) reported similar neurological and clinical outcomes, however, as a

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limitation, the study was not powered to discover differences in clinical outcomes. Moreover,
the study revealed that the target temperature was more effectively managed with the invasive
Coolguard system (33.0 versus 32.7oCelsious noninvasive cooling; p<0.001). The study revealed
more bleeding complications with the invasive cooling (n=17 (43.6%) versus n=7 (17.9%);
P=0.03). The bleeding complication noted in the study were mild mucosal bleeding at the
catheter site. The hypothermia therapy was not discontinued due to bleeding complications (U.
Pittl et al., 2013).
Oddo and Rossetti (2014b) performed a prospective cohort study, which analyzed various
variables (baseline demographics, cardiac arrest, clinical examination, hypothermic
electroencephalography EEG, normothermia SSEP and NSE) of 134 adult patients treated with
therapeutic hypothermia after cardiac arrest (2014). Oddo and Rossetti (2014b) proceeded with a
multimodal approach to minimize false-positive prediction of poor patient outcomes. The
patients received noninvasive hypothermia based on American Heart Association guidelines,
which was maintained for twenty-four hours. Sedation, analgesia and neuromuscular blockades
were administered during therapeutic hypothermia and discontinued once the passive rewarming
goal temperature (above 35oCelcius) had been achieved. The research revealed that seventy-two
patients had a poor neurological outcome and sixty-two had a good neurological outcome (Oddo
& Rossetti, 2014a). Furthermore, the multivariable ordinal logit model revealed the absence of
electroencephalography reactivity (p<0.0001), incomplete recovery of brainstem reflexes in
normothermia (P=0.013), in addition to NSE higher than 33 g/L (p=0.029, but somatosensoryevoked potential was not a sole predictors of poor outcomes. The study further showed that
electroencephalography correlated with NSE, yet the EEG reactivity and NSE are independently
related to outcomes. This also suggests these tests provide complimentary information. In

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summary, EEG and NSE are the best outcome predictors for prognosis of premature post-anoxic
coma. Thus, somatosensory responses do not provide any complimentary data.
A meta-analysis was done to evaluate the sensitivity and false positive rate of
neurological examinations, as well as the somatosensory evoked potentials to predict poor results
in adult patient that received therapeutic hypothermia after cardiopulmonary resuscitation (M. J.
Kamps et al., 2013). A total of ten studies were selected and 1,153 patient were included in the
analysis. Those included in the study were adult patients that experienced a cardiac arrest and
were treated with therapeutic hypothermia. Patients with a preexisting neurologic disease or
deficit, as well as, those not reporting sufficient data for analysis of the SSEP, Glascow coma
score (GCS), corneal, and pupillary reflexes were excluded from the study. Furthermore, 492
patients for nine studies were used to calculate the false positive rate for bilaterally absent
cortical N20 response of SSEP. The false positive rate for SSEP was 0.007 (confidence interval
of 0.001-0.047) to predict poor outcomes. The GCS was evaluated in 811 patients from nine
studies. The results demonstrated a GCS of one to two at seventy-two hours had an elevated
false positive of 0.21 (confidence interval of 0.08-0.43). Moreover, the corneal reflex and pupil
reactivity assessed at the seventy-two hour mark after the arrest were assessed in 429 and 566
patients. A false positive result of 0.02 (confidence interval of 0.002-0.13) was obtained with
bilaterally absent corneal reflexes and bilaterally absent pupillary reflexes had a false positive
result of 0.004 (confidence interval of 0.001-0.03). The researchers concluded that at seventytwo hours after cardiac arrest motor response initiated by painful stimuli, as well as corneal
reflexes are unreliable tools for prediction of poor outcomes in patients treated with therapeutic
hypothermia. Furthermore, the reliability of the pupillary response to light and SSEP is very
similar to that of patients not treated with hypothermia (M. J. Kamps et al., 2013).

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Discussion
One of the first studies in which therapeutic hypothermia was used following cardiac
arrest was done by Williams and Spencer (1958). The study reported four patients had favorable
neurological outcomes post-arrest and resuscitation (Williams & Spencer, 1958). The patients
received therapeutic hypothermia by surface cooling (30oC-34oC) for twenty-four to seventy-two
hours. In 2000, the American Heart Association and the International Liaison Committee on
Resuscitation standardized cardiopulmonary resuscitation, which improved the quality of
cardiopulmonary resuscitation, aiding in improved neurological outcomes (Nolan et al., 2010;
Sayre et al., 2009)
Bernard et al. (2002) and Hypothermia after Cardiac Arrest Study Group, both conducted
randomized controlled trials that demonstrated improved neurological outcomes for comatose
patients with out-of-hospital ventricular fibrillation or non-perfusing ventricular tachycardia.
Additionally, the Castrejn et al. (2009) study with control groups showed improve neurological
outcomes after therapeutic hypothermia. A case study by Nusbaum et al. (2014) revealed good
neurological outcomes after a patient was in cardiac arrest for three and half hours. Won Young
et al. (2014) revealed that even with prolonged downtimes, patients who have suffered a cardiac
arrest can have good neurological outcomes. Petrovi et al. (2011) is another example of coma
patients treated with therapeutic hypothermia after cardiac arrest having better neurological
outcomes and decreases in mortality rates. Pleskot et al. (2009) showed that therapeutic
hypothermia was safe and provided good long-term neurological outcomes for patients who
experienced out-of-hospital arrest due to a STEMI. However, a retrospective study done by Choi
et al. (2012) showed no neurological improvement in-patient who went into cardiac arrest due to
drowning and received external hypothermia. Conversely, this retrospective study included a

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small number of patients resulting in a type II () error. Gong et al. (2013) studies with minipigs
revealed therapeutic hypothermia inhibits mitochondrial membrane permeability, thus providing
neuroprotection to the cardiac arrest induced swine. Research studies to evaluate the best
outcome indicators for prognostication of patients treated with therapeutic hypothermia assist
with planning care for patients (M. Kamps et al., 2013; Oddo & Rossetti, 2014b).
The use of therapeutic hypothermia alters the reliability of currently used
electrophysiological and current medical practices (M. J. Kamps et al., 2013). Cooling the body
alters the bodys metabolic function, cerebral perfusion, inflammatory cascades, and neuroexcitatory pathways. These medically induced changes have the potential to alter or influence
the recovery time of the brain. Many patients treated with hypothermia receive sedatives,
analgesics, and in some cases muscle relaxers which can change neurological results during
assessments. Therefore, neurological assessments should be timed after neurological altering
medications are discontinued and diagnostic tests have been done to check serum levels. In
addition, parameters should be standardized. Moreover, a multimodal approach would assist in
minimizing false positive predictions of poor neurologic outcomes and uniform assessments of
the various variables would strengthen research finding (Oddo & Rossetti, 2014a).
Today healthcare facilities are using invasive and noninvasive types of therapeutic
hypothermia. In the current research studies, timing of diagnostic tests varied, as well as when
the neurological outcomes were measured (M. J. Kamps et al., 2013). Undine Pittl et al. (2013)
revealed that both means of cooling were efficient in cooling comatose patients and there was no
difference in the NSE in the survivors. However, invasive hypothermia treatment had better
temperature management and was associated with bleeding risks (Undine Pittl et al., 2013). In
order to fill in the missing gaps concerning hypothermia, researchers need to establish a standard

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protocol concerning therapeutic hypothermia and establish ideal timing for withdrawal of
therapy. Therapeutic hypothermia has potential benefits that need exploring.
Future Research
While mild hypothermia improves neurological outcomes in cardiac arrest patients,
further development of a standardized protocol should be considered for use in this population.
Moreover, further research is required to determine the appropriate candidates, the best period
for initiating therapeutic hypothermia, the optimal cooling time for the best outcome, and the
ideal temperature for the best neurological recovery. Furthermore, more studies are needed to
confirm whether invasive or noninvasive cooling mechanisms have the least associated risk and
improved patient outcomes. Finally, exploration of best procedure and timing for rewarming of
the patient, as well as, prevention of rebound hyperthermia warrants examination. Cardiac arrest
can have profound effects on an individual and their life. Therefore, further research could prove
to be a huge leap in overall improvement of neurologic outcomes, as well as survival rates.
Conclusion
Cardiac arrest survival rates remain low. Many different factors contribute to individual
overall outcomes. Therefore, it is vital to preserve as much neurological function as possible
throughout this ordeal. Research has discovered providing high quality cardiopulmonary
resuscitation, advanced cardiopulmonary support, and medically induced hypothermia are
effective in improving neurological outcomes for individuals who have experienced a cardiac
arrest. In conclusion, there remains many unanswered questions regarding the use of medically
induced hypothermia in post-arrest patients. Research has shown that cooling patients after
cardiac arrest between 32o to 34oCelcius slows the metabolism, which in turn diminishes the
oxygen, nutrient demand, and inhibits brain reperfusion injuries. Moreover, it aids in decreasing

INDUCED HYPOTHERMIA IMPROVE NEUROLOGIC OUTCOMES

20

the inflammatory process, edema, and apoptosis (Amantea et al., 2009). There is a call for
further research to determine optimal timing and modalities throughout the initiation of
medically induced hypothermia.
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Pleskot, M., Hazukova, R., Stritecka, H., Cermakova, E., & Pudil, R. (2009). Long-term
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From pathophysiology to prevention, prognosis and potential preservation. Injury, 45(4),
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of mild hypothermia and detrimental effect of deep hypothermia after cardiac arrest in
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Williams, G. R., Jr., & Spencer, F. C. (1958). The clinical use of hypothermia following cardiac
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Won Young, K., Giberson, T. A., Uber, A., Berg, K., Cocchi, M. N., & Donnino, M. W. (2014).
Neurologic outcome in comatose patients resuscitated from out-of-hospital cardiac arrest
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1042-1046. doi: 10.1016/j.resuscitation.2014.04.005

INDUCED HYPOTHERMIA IMPROVE NEUROLOGIC OUTCOMES

Appendix A

25

INDUCED HYPOTHERMIA IMPROVE NEUROLOGIC OUTCOMES

Citation

Purpose

Nusbaum, D. M.,
Bassett, S. T.,
Gregoric, I. D., &
Kar, B. (2014). A
Case of Survival
after Cardiac
Arrest and 3 1/2
Hours of
Resuscitation. Tex
as Heart Institute
Journal, 41(2),
222-226.
doi:10.14503/THI
J-13-3192

40 year old
male pt.
survived
cardiac arrest
that lasted 3
hours. Use of
hypothermia
protocol
resulted in full
recovery of
neurological
functions

Source
Type
Case
Report

Design

Results

Narrative

40 year old
man survived
a CA after
approx. 3.5
hours
neurologically
intact with the
use of
hypothermia

Major
Conclusions
Hypothermia
has a
neuroprotective
effect.

26
Future Implications
A good source of
information for the
project to provider
arguments for
receiving syndromic
surveillance data

INDUCED HYPOTHERMIA IMPROVE NEUROLOGIC OUTCOMES

Citation

Purpose

Gong, P., Hua,

R., Zhang, Y.,
Zhao, H., Tang,
Z., Mei, X.,
& ... Li, C.
(2013).
Hypothermiainduced neuroprotection is
associated with
reduced
mitochondrial
membrane
permeability in
a swine model
of cardiac
arrest. Journal
Of Cerebral
Blood Flow
And
Metabolism:
Official Journal
Of The
International
Society Of
Cerebral Blood
Flow And
Metabolism, 33(
6), 928-934.
doi:10.1038/jcb
fm.2013.33

Determine if
mild
hypothermia
(wholebodied)
inhibits
mitochondrial
membrane
permeability
leading to
neuroprotection
using inbred
Chinese
Wuzhishan
mini pigs.

Source
Type
Primar
y

Design

Results

This study used

37 (21 males; 16
females) inbred
Chinese
Wuzhish
minipigs using
three-way
ANOVA
(factors:
temperature,
time, and
gender),
followed by
Bonferroni test
for multiple
comparisons.
Levenes test
was used to
assess
homogeneity of
variance, and
GreenhouseGeisser
corrections were
used when
indicated
Statistical
significance was
defined as
Po0.05.
Statistics were
performed using
the software
package SPSS
16.0.

Mild
Hypothermia
Improved
Mitochondrial
Membrane
Potential;
Mild
Hypothermia
Improved
Mitochondrial
Respiration;
Mild
Hypothermia
Improved
Mitochondrial
Respiration;
Mild
Hypothermia
Reduced
Apoptosis

27

Major Conclusions

Future
Implications
Mild hypothermia
Assessed during
reduced MMP in
rewarming 12 hrs
brain cortex, 24 hours after mild
after ROSC, it
hypothermia
improved
applied). Maybe
neurological
should have done
outcomes and
during first 12
alleviated
hours. Study
microscopic changes focused on frontal
in the cerebral cortex cortex, no info
caused by global
collected on
ischemic-reperfusion. hippocampus. Study
At 72 hours after
performed on both
ROSC, NT and HT
sexes, but hormonal
groups had similar
differences due to
histopathology3 and
sexual dimorphism
cellular findings in
may affect the
the present
outcome of cerebral
experiment. Thus, we ischemia. Overall
speculate that the
small sample size.
neuro-protective
effects of mild
hypothermia on
cerebral injury caused
by cardiac arrest
might be associated
with reduced MMP,
and the processes
underlying neuronal
death and the
neuroprotective
effects of mild
hypothermia might
occur predominantly
within the first 24
hours (or perhaps 48
hours).

INDUCED HYPOTHERMIA IMPROVE NEUROLOGIC OUTCOMES

Citation
Citation

Purpose
Purpose

28

Source
Results
Major
Future
Source Design
Design
Results
Major
Future
Type
Conclusions
Implications
Type
Conclusions
Implications
Bernard SA,
Because cerebral Primar Descriptive The demographic The demographic
We conclude that
Kamps,
M.
A.,
To
assess
the
Primary
MetaEarly
prognostication
Early
Studies are
Gray TW,
ischemia may
y
survey
characteristics of characteristics of
induced
Horn,
J.,
Oddo,
sensitivity
analysis
after
cardiac
arrest
prognostication
needed to
Buist MD,
persist for some
(RCT).
the patients were the patients were
hypothermia
M.,
Fugate,
J.
E.,
and
FPR
of
focuses
on
the
after
cardiac
elucidate
whether
Jones BM,
hours after
Place in
similar in the
similar in the
improves
outcomes
Storm, C.,
neurological
prediction ofand
an hypothermia
arrest inand
the
prognostic
Silvester
W,
resuscitation,
5
historical
hypothermia
in the
patients
who are
Cronberg,
T.,
&
examination
outcome
no
better
hypothermia
era
value
clinical
Gutteridge G,
the use of induced
overview.
normothermia
normothermia
comatoseofafter
C.
and SSEP
than a Twentyvegetative groups.
is difcult
neurological
etHoedemaekers,
al.
hypothermia
to
groups.
Twenty-and resuscitation
from
E.
(2013).
ranges
for
state
or
severe
inuenced
by
parameters
Treatment of
decrease cerebral
one of the 43
one of the 43
out-of-hospital
Prognostication oxygen
of prognosis
disability.
To avoidpatients
the treated
hypothermiacardiac
improves
if
comatose
demandof
patients
treated
arrest.
neurologic
outcomes
in
withdrawal
of
itself
and
use
of
performed
later
survivors after has been
with hypothermia with hypothermia
However, treatment
outcome
in cardiac
adultaspatients
treatment
sedatives. At 72 assignment
than 72 h was
afternot
out
of hospital
proposed
a
(49
percent)in patients
(49 percent)
arrest
patients
after
treated
with
with
a
potentially
h
after
the
the
arrest
and
to is
cardiac arrest
treatment option.
survived and had survived and had a blinded, and there
mild therapeutic6 Al-mild
outcome,good arrest,
thethat
motortheidentify
the that
with
though this
a favorable
good outcome
outcome
possibility
hypothermia:
a
hypothermia
prognostic
tests
must
response
to
optimal
time
induced
suggestion has
that is, they were is, they were
some aspects of care
meta-analysis
of
after
CPR.
have
a
high
painful
stimuli
point for
clinical
Citation
Purpose
Source
Design
Results
Major
Future
hypothermia.
been supported by
discharged home discharged home
differed
between
current
for
corneal theneurological
type
Implications
Nthe
Engl
J Med
studies in animal
orspecicity
to a
or to aand theConclusions
groups.
literature.
predicting a poor
reexes
are
prognostication.
Petrovi, M., models,
The
aimthe
of
Primary The study was
82 patients:
45 Mild
Therefurther
are still
2002;
7-12
rehabilitation
rehabilitation
Therefore,
Intensive
Care
prognosis
with
a
unreliable
for
Pani, G., studiesthis
study
conducted onfacility as
patients
were as therapeutic
based
346:557-63.
in humans
facility
studiesno
aredata
required
Medicine,
narrow condence
Joveli, 39(10),
A., that have
wasbeen
to
consecutive comatose
withthe early
hypothermia
on large
compared
withtreated
9 compared
with
9
to confirm
these
1671-1682.
The hypothermia,
resultsof theprediction
of after
Canji, T.,
evaluate
patients admitted
our
applied
studies
reported
to datethe
ofinterval.
theto34
treated
34 treated
findings
and
doi:10.1007/s0013
of
this
meta-analysis
poor
outcome
indetermine
Srdanovi, I.,have been
impact of
clinic after cardiac
patients
cardiac arrest
revealing
with arrest and 37with
normothermia
the the
4-013-3004-y
strongly indicate
that
patients
treated
Popov, T., & uncontrolled
mild or
and return ofnormothermia
were
treated
improved
optimal
(26 (26 per- cent,
optimal duration of
notcent,
all currently
used
with neurological
Golubovi, M.retrospective.
hypothermia
spontaneous percirculation,
conservatively.
period of
P=0.046).
hypothermia.
clinical
parameters
hypothermia.
(2011).
on
between February
2005
In
the
group
outcome
and
maintaining
P=0.046).
can
be
applied
to
Therapeutic
neurological
and May 2009. The
treated with
reduced
mild
patients aftertherapeutic
hypothermia and outcome
patients were divided
mortality in
hypothermia,
hypothermia.
neurological
and survival
into two groups: the
hypothermia
the studied
whether it is
outcome after
of the
patients treated with
protocol, 21
group of
12, 24 or 48
cardiac arrest.
patients in
mild hypothermia and
(46.7%)
comatose
h, but it is
Vojnosanitetski
coma, after
the patients treated
patients had
survivors.
clear that the
Pregled.
cardiac
conservatively. The
full
effect of mild
Military-Medical arrest and
intravascular in
neurological
hypothermia
And
return of
combination with
restitution
is more
Pharmaceutical
spontaneous
external method of
(CPC 1), 3
beneficial if
Review, 68(6),
circulation.
cooling or only external (6.7%) patients
the
495-499.
M.
cooling was used during had good
temperature
the first 24 hours, after
neurologic
between 32
which spontaneous
outcome (CPC
and 34C is
rewarming started. The
2), 1 (2.2%)
reached
endpoints were survival patient
sooner
rate and neurological
remained in
outcome. The
coma and 20
neurological outcome
(44.4%)
was observed with
patients finally
Cerebral Performance
died (CPC 5).
Category Scale (CPC).
Follow-up was 30 days.

INDUCED HYPOTHERMIA IMPROVE NEUROLOGIC OUTCOMES

Citation

Purpose

Choi, S P, C S
Youn, K N
Park, J H Wee, J
H Park, S H Oh,
S H Kim, and J
Y Kim. 2012.
"Therapeutic
hypothermia in
adult cardiac
arrest because
of
drowning."Acta
Anaesthesiologi
ca
Scandinavica
56, no. 1: 116123. MEDLINE
with Full Text,
EBSCOhost
(accessed
November 17,
2014).

The purpose
of the present
study was to
report the
results of the
treatment of
patients that
suffered
cardiac arrest
secondary to
drowning.
Study
investigated
the
utilization of
therapeutic
hypothermia
on
consecutive
patients with
cardiac arrest
because
of drowning
between
2005 and
2008

Source
type
Primary

29

Design

Results

Retrospective

Twenty patients were

treated with therapeutic
hypothermia. Four patients
(20%) exhibited a favorable
neurological outcome
(CPC12). Two patients
(10%) remained in a
vegetative state at discharge
(CPC 4), and 14 patients
(70%) died (CPC 5).
The most common
complications during
therapeutic hypothermia
were pancreatitis and
rhabdomyolysis. A longer
duration of advanced
cardiac life support (P
=0.035), an absence of
motor response to pain after
3 days (P =0.003), an
abnormal brain imaging (P
=0.005) and a lack of
cortical response to
somatosensory evoked
potential (P =0.008) were
related to an unfavorable
outcome (CPC 35).

Major
Conclusions
The present
study did not
demonstrate
an advantage
of therapeutic
hypothermia
in adult
cardiac arrest
after
drowning
compared
with previous
studies treated
with
conventional
therapy.
Further
prospective
studies are
needed to
evaluate the
effects of
therapeutic
hypothermia

T
r
s
d
d
n
A
s
n
a
r
s
h
d
tw
c
f
f
s
la
p
a
o
a
a
th
h
a
d

INDUCED HYPOTHERMIA IMPROVE NEUROLOGIC OUTCOMES

30

INDUCED HYPOTHERMIA IMPROVE NEUROLOGIC OUTCOMES

Citation

Purpose

Zimmermann, S.,
Flachskampf, F.
A., Schneider,
R., Dechant, K.,
Alff, A.,
Klinghammer,
L., & ...
Achenbach, S.
(2013). Mild
therapeutic
hypothermia
after out-ofhospital cardiac
arrest
complicating STelevation
myocardial
infarction: longterm results in
clinical
practice. Clinical
Cardiology, 36(7
), 414-421.
doi:10.1002/clc.2
2131

Invasive
MTH
influences
long-term
prognosis
after
OHCA
due to
STEMI.

Source
type
Primar
y

Design

Results

31

Major
Conclusions
We analyzed 48
: Median time delay
MTH via
patients who
until arrival of
intravascular
underwent
emergency medical
cooling
emergency coronary service was 6 minutes improves
angiography for
(MTH group) vs 6.5
neurological
STEMI after
minutes (controls) (P long-term
witnessed OHCA. In = 0.16). Initial
prognosis after
24 consecutive
rhythm was
OHCA due to
patients, MTH was
ventricular
STEMI and is
performed via
fibrillation in 75% vs safe in clinical
intravascular cooling 66.7% (P = 0.75).
practice.
(CoolGard System,
There were no
34C maintained for differences regarding
24 hours) after
baseline
initialization by
characteristics,
rapid infusion of
angiographic
cold saline. Clinical, findings, and success
procedural, and
of cardiac
mortality data were
catheterization
compared to 24
procedures. MTH
historical controls.
was not associated
Neurological
with a higher
recovery was
frequency of bleeding
assessed using the
complications or of
Cerebral
pneumonia. ThirtyPerformance
day mortality was
Category score
33.3% in both
(CPC) at 30-day and groups. One-year
1-year follow-up
mortality was 37.5%
(MTH group) vs 50%
(controls) (P = 0.56).
At 1 year, favorable
neurological outcome
(CPC 2) was
significantly more
frequent in the MTH
group (58.3% vs
20.8%, P = 0.017).
Multivariate analysis
identified MTH as
independent predictor
of favorable
neurological outcome
(P < 0.02, odds ratio:
12.73).

Future
Implications
Study
population is
small, regarding
clinical aspects,
we analyzed a
very
homogeneous
group of
patients, but
significant
confounders
may still exist.

INDUCED HYPOTHERMIA IMPROVE NEUROLOGIC OUTCOMES

32

Citation

Purpose

Source
Design
Results
Major
type
Conclusions
Pittl, U.,
Compared the Primary
Between
NSE at 72 h Invasive
INDUCED HYPOTHERMIA IMPROVE NEUROLOGIC OUTCOMES
Schratter, A.,
efficacy of two
April 2008
did not
cooling has
Desch, S.,
different
and August
differ
advantages with
Diosteanu, R.,
cooling
2009, 80
signicantly respect to
Lehmann, D.,
devices for
patients
between the temperature
Demmin, K., &
temperature
after
2 groups
management
Thiele, H.
management in
survived in- with 16.5
over surface
(2013). Invasive SCA survivors
hospital
ng/ml,
cooling;
versus non(IHCA) and interquartile however, did
invasive cooling
out-ofrange 11.8 not result in
after in- and outhospital
46.5 in
different
of-hospital
cardiac
surfaceoutcome as
cardiac arrest: a
arrest
cooled
measured by
randomized trial.
(OHCA)
patients
NSE release in
Clinical
were
versus 19.0 SCA survivors.
Research In
included in
ng/ml,
Bleeding
Cardiology:
this
interquartile complications
Official Journal
prospective, range 11.0 were more
Of The German
randomized, 42.0 in
frequently
Cardiac Society,
single center invasiveencountered by
102(8), 607-614.
study.
cooled
invasive cooling
doi:10.1007/s003
Hypothermi patients, p =
92-013-0572-3
a was
0.99.
induced
Neurologica
after
l and
randomizati clinical
on by either outcome
invasive
was similar
Cool- gard
in both
cooling or
groups.
non-invasive Target
ArcticSun
temperature
surface
of 33.0 C
cooling at
was
33.0 C core maintained
body
more stable
temperature in the
for 24 h
invasive
followed by group (33.0
active
versus 32.7
rewarming. C, p\0.001).
The primary Bleeding
endpoint
complicatio
was dened ns were
as the
more
efcacy of
frequent
both cooling with
systems,
invasive
measured by cooling (n =
neuron17 [43.6 %]
specic
versus n = 7
enolase
[17.9 %]; p
(NSE) levels = 0.03).
as a
surrogate

Future Implications
The study is not
33
powered to detect
differences in clinical
outcome. Second, in
some patients, the
accuracy of intervals,
such as time to ROSC,
cooling onset or target
temperature might be
unreliable since
information on the
time when the patient
collapsed relies solely
on witnesses. Although
care was taken to
identify exact time
points of relevant
events by interviewing
paramedics and
emergency physicians,
these may be subject
to reporting or
measurement errors.
Third, our institution is
a tertiary care center
for patients with
cardiac diseases. It is
therefore possible that
some SCA survivors
presumed not to be of
cardiac origin were
referred to other
hospitals. The
randomized cohort
might therefore not be
entirely representative
for the whole
population of patients
with ROSC following
SCA.

Citation

Purpose

Source
Design
Results
Major
type
Conclusions
Won Young, K.,
The aim of
Primary This
105 patients were Those patients
INDUCED HYPOTHERMIA IMPROVE NEUROLOGIC OUTCOMES
Giberson, T. A.,
this study
prospective,
treated with TH
who have
Uber, A., Berg,
was to
observational and 19 were
been
K., Cocchi, M.
determine
, study was
excluded due to
successfully
N., & Donnino,
the rate of
conducted
unknown
resuscitated
M. W. (2014).
good
between
downtime, leaving and treated
Neurologic
neurologic
January 2008 86patients for
with TH have
outcome in
outcome
and
analysis. The
neurologically
comatose
based on the
September
median downtime intact survival
patients
duration of
2012.
was 18.5 (10.0
rates of 23%
resuscitated from resuscitation
Inclusion
2.3) min and 33
even with
out-of-hospital
efforts in
criteria
patients (38.0%)
downtime >20
cardiac arrest
OHCA
consisted of
had a good
min
with prolonged
patients
adult nonneurologic
downtime and
treated with
traumatic
outcome. When
treated with
TH
OHCA
downtime was
therapeutic
patients who divided into four
hypothermia.
were
groups (10 min,
Resuscitation,
comatose
110 min, 2130
85(8), 1042after return of min,>30 min),
1046.
spontaneous
good neurologic
doi:10.1016/j.res
circulation
outcomes were
uscitation.2014.0
(ROSC) and
62.5%, 37%, 25%,
4.005
received TH. and 21.7%,
The primary respectively (p =
endpoint was 0.02). However,
good
even with
neurologic
downtime >20
outcome
min, 22.9% had a
dened as a
good neurologic
cerebral
outcome, and this
performance percentage
category
increased to37.5%
score of 1 or in patients with an
2. Downtime initial shockable
was calculate rhythm.
as the length
of time
between the
patient being
recognized as
pulseless and
ROSC
Citation
Purpose
Source
Design
Results
Major
type
Conclusions
Oddo, M., &
Study
Primary Prospective
Variable related to Combination
Rossetti, A. O.
examined the
cohort study. the cardiac arrest
of clinical
(2014). Early
comparative
One hundred (cardiac rhythm
examination,
multimodal
performance
thirty-four
time to return of
electroencephoutcome
of these
consecutive
spontaneous
alography
prediction after
predictors or
adults treated circulation),
reactivity, and
cardiac arrest in
addressed
with
clinical
serum neuronpatients treated
their optimal
therapeutic
examination
specific
with
combination.
hypothermia (brainstem
enolase offers
hypothermia.
after cardiac
reflexes and
the best

Future Implications
Our study was limited
34
by relatively small
sample size and the
observational design.
This was also a singleenter study, and results
may not be
generalizable to other
settings. Some
selection bias may
have occurred if
individual clinicians
opted not to use TH
for a patient with a
longer down time,
although this is not
part of the criteria for
TH as used at our
hospital. Further data
are needed to validate
these ndings. Another
potential concern is
that our data included
non-sustained ROSC.

Future Implications
Being single center, its
generalizability is not
implicit, but the
internal validity
resulting from a
uniform assessment of
variables is
strengthened. These
findings should be
confirmed by

INDUCED HYPOTHERMIA IMPROVE NEUROLOGIC OUTCOMES

35

Appendix B

Improving Neurological Outcomes in Patients

after Cardiac Arrest
Georgia College Research Visionary Group

November 26, 2014

Author: Salena Barnes, BSN, RN

November 26, 2014

Overview
Every year your thousands of individuals experience cardiac arrest, many are resuscitated, and
admitted to the hospital (McNally et al., 2011). After patients have been successfully
resuscitated, and return of spontaneous circulation has been established it is vital that we take
every opportunity to improve their neurological outcomes (McNally et al., 2011).
Cardiac Arrest
A cardiac arrest is when the heart stops beating, the individual therefore stops breathing, and an
anoxic injury occurs due to the lack of perfusion to the brain (Wilson, 2013). Annually over a
three hundred thousand individuals experience this traumatic event (McNally et al., 2011).
However, cardiac arrest is a potentially reversible condition through use of cardiopulmonary
resuscitation and with return of spontaneous circulation with the necessary medical intervention
provided. Nevertheless, patients who are resuscitated may die to various complications or suffer
from detrimental neurological outcomes (Geocadin & Eleff, 2009).
Post-Resuscitation
The most important concern is the amount damage sustained to the vital organs, especially the
brain, which has a high metabolic demand. Most individuals die from damage to the brain, heart
and the cascade of inflammatory process initiated by the cardiac arrest (Amantea et al., 2009).
Pathophysiology
For the duration of the cardiac arrest, with little to no perfusion of blood the patient suffers from
lack of oxygen or ischemia (Wilson, 2013). The brain has a high metabolic demand, therefore
oxygen, energy stores, and nutrients are depleted in a matter of minutes. Moreover, this causes
increases in lactate and acid levels, as well as inflammatory process. Thus, leading to vast cell
damage and leading to cell death. Its important to note that even if return of spontaneous
circulation is obtained by the individual the patient will experience a reperfusion injury of the
brain due to the elevated level of oxygen free radicals (Amantea et al., 2009; Wilson, 2013).
Conclusion
Currently the use of therapeutic hypothermia is strongly recommended (Class 1) for the
management of patients with ST segment elevation myocardial infarction (STEMI) and comatose
patients who experience out-of-hospital cardiac arrest caused by ventricular fibrillation or
pulseless ventricular tachycardia. It is also recommended for those receiving a percutaneous
coronary intervention (Bernard et al., 2002; "Mild Therapeutic Hypothermia to Improve the
Neurologic Outcome after Cardiac Arrest," 2002; O'Gara et al., 2013). Current research has
focuses on improving neurological outcomes in cardiac arrest patients through cooling the brain,
and body to slow the bodys metabolism. Therefore, complications such as fevers, seizures, and
hypoglycemia may result after cardiac arrest, thus causing further damage to cells (Amantea et
al., 2009). Most hospitals have a protocol concerning initiation of therapeutic hypothermia in
comatose STEMI patient who experience an out-of-hospital cardiac arrest. The studies have
shown up to a 40% intact neurological survival rates in those who received hypothermia after
return of spontaneous circulation compared to a 10% or less survival by those who did not
receive this treatment (Amantea et al., 2009; McNally et al., 2011). To create protocols for other
possible candidates for hypothermia further research needs to be done to cover all possible

conditions which may benefit from therapeutic hypothermia. Funding is vital for the life
changing research and for advancement of future medical practices.

References

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brain damage: pathophysiology and role of inflammatory mediators. The FEBS Journal,
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(2002). Treatment of comatose survivors of out-of-hospital cardiac arrest with induced
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Wilson, B. P. (2013). Cardiac arrest: Magill's Medical Guide (Online Edition).