Download Current Evidence In Therapeutic Hypothermia For Postcardiac

Current Evidence In Therapeutic
Hypothermia For Postcardiac
Arrest Care
The ring of the red notification phone breaks the relative calm of an otherwise typical Monday morning and heralds the arrival of a critically ill patient. The dispatcher announces that EMS is on the way with a 57-year-old
man in cardiac arrest, with an ETA of 3 minutes. Shortly after preparations
for their arrival are complete, EMS personnel enter with CPR in progress
and the patient already intubated. As monitor/defibrillator attachment, ETT
placement confirmation, additional IV access, and complete exposure of the
patient occur, you hear more about the clinical scenario from EMS. Mr.
I.C. is a 57-year-old male who was moving furniture when, as described
by witnesses, he complained of difficulty catching his breath and a slight
tightness in his chest. He began coughing violently, vomited once, gasped,
and collapsed. Emergency medical services personnel state that they arrived
approximately 20 minutes after the patient had collapsed, with CPR in
progress. The patient was intubated in the field, and EMS reports that the
initial rhythm was PEA. Upon the patient’s arrival in the ED, the rhythm
is noted to be ventricular fibrillation. Defibrillation is attempted twice over
the next 4 minutes, with concomitant administration of medications. During the next rhythm check, QRS complexes are noted on the monitor and a
pulse is palpated. The patient has had a return of spontaneous circulation,
apparently 50 minutes from onset of the arrest. As you initiate postresuscitation care, you consider the patient’s prognosis and wonder if he qualifies
for therapeutic hypothermia; ie, will therapeutic hypothermia make a difference in his outcome?
Editor-in-Chief
Professor, UT College of Medicine,
Chattanooga, TN
Andy Jagoda, MD, FACEP
Professor and Chair, Department of
Nicholas Genes, MD, PhD
Emergency Medicine, Mount Sinai
Assistant Professor, Department of
School of Medicine; Medical Director,
Emergency Medicine, Mount Sinai
Mount Sinai Hospital, New York, NY
School of Medicine, New York, NY
Editorial Board
William J. Brady, MD
Professor of Emergency Medicine
and Medicine Chair, Resuscitation
Committee & Medical Director,
Emergency Preparedness and
Response, University of Virginia
Health System Operational Medical
Director, Charlottesville-Albemarle
Rescue Squad & Albemarle County
Fire Rescue, Charlottesville, VA
Peter DeBlieux, MD Louisiana State University Health
Science Center Professor of Clinical
Medicine, LSUHSC Interim Public
Hospital Director of Emergency
Medicine Services, LSUHSC
Emergency Medicine Director of
Faculty and Resident Development
Wyatt W. Decker, MD
Professor of Emergency Medicine,
Mayo Clinic College of Medicine,
Rochester, MN
Francis M. Fesmire, MD, FACEP
Director, Heart-Stroke Center,
Erlanger Medical Center; Assistant
April 2011
Volume 13, Number 4
Author
Matthew Constantine, MD
Clinical Assistant Professor, Department of Emergency Medicine,
State University of New York, Downstate/Kings County Hospital,
Brooklyn, NY
Peer Reviewers
Marie-Carmelle Elie-Turenne, MD, FACEP
Assistant Professor, Department of Emergency Medicine, Critical
Care, Hospice and Palliative Care Medicine; University of Florida
School of Medicine, Gainesville, FL
Marc M. Grossman, MD, FACEP, CPHM
Associate Medical Director, City of Miami Fire-Rescue, Voluntary
Assistant Professor of Medicine and Neurology, University of Miami
Miller School of Medicine, Jackson Memorial Hospital Emergency
Services, Miami, FL
CME Objectives
Upon completion of this article, you should be able to:
1.
2.
3.
4.
List the major indications and contraindications for instituting
therapeutic hypothermia.
Describe the focus of the initial patient evaluation to help
determine possible benefits of therapeutic hypothermia.
Recognize the physiologic response to therapeutic
hypothermia as well as the clinical responses.
Be familiar with the practical aspects of applying therapeutic
hypothermia.
Date of original release: April 1, 2011
Date of most recent review: March 10, 2011
Termination date: April 1, 2014
Medium: Print and online
Method of participation: Print or online answer form and evaluation
Prior to beginning this activity, see “Physician CME Information” on
the back page.
Shkelzen Hoxhaj, MD, MPH, MBA
Scott Silvers, MD, FACEP
Chief of Emergency Medicine, Baylor Chair, Department of Emergency
College of Medicine, Houston, TX
Medicine, Mayo Clinic, Jacksonville, FL
Keith A. Marill, MD
Assistant Professor, Department of
Emergency Medicine, Massachusetts
General Hospital, Harvard Medical
School, Boston, MA
International Editors
Peter Cameron, MD
Academic Director, The Alfred
Emergency and Trauma Centre,
Monash University, Melbourne,
Australia
Corey M. Slovis, MD, FACP, FACEP
Professor and Chair, Department
of Emergency Medicine, Vanderbilt
University Medical Center; Medical
Giorgio Carbone, MD
Michael A. Gibbs, MD, FACEP
Director, Nashville Fire Department and
Chief, Department of Emergency
Professor and Chief, Department of
International Airport, Nashville, TN
Charles
V.
Pollack,
Jr.,
MA,
MD,
Medicine Ospedale Gradenigo,
Emergency Medicine, Maine Medical
FACEP
Jenny
Walker,
MD,
MPH,
MSW
Torino, Italy
Center, Portland, ME; Tufts University
Chairman, Department of Emergency
Assistant Professor; Division Chief,
School of Medicine, Boston, MA
Amin
Antoine Kazzi, MD, FAAEM
Medicine, Pennsylvania Hospital,
Family Medicine, Department of
Associate Professor and Vice Chair,
Steven A. Godwin, MD, FACEP
University of Pennsylvania Health
Community and Preventive Medicine,
Department
of Emergency Medicine,
Associate Professor, Associate Chair
System, Philadelphia, PA
Mount Sinai Medical Center, New
University of California, Irvine;
and Chief of Service, Department
York,
NY
Michael S. Radeos, MD, MPH
American University, Beirut, Lebanon
of Emergency Medicine, Assistant
Assistant Professor of Emergency
Ron M. Walls, MD
Dean, Simulation Education,
Hugo Peralta, MD
Medicine,
Weill
Medical
College
Professor
and
Chair,
Department
of
University of Florida COMChair of Emergency Services,
of Cornell University, New York;
Emergency Medicine, Brigham and
Jacksonville, Jacksonville, FL
Hospital Italiano, Buenos Aires,
Research Director, Department of
Women’s Hospital, Harvard Medical
Argentina
Gregory L. Henry, MD, FACEP
Emergency Medicine, New York
School, Boston, MA
CEO, Medical Practice Risk
Hospital Queens, Flushing, New York
Dhanadol Rojanasarntikul, MD
Scott Weingart, MD, FACEP
Assessment, Inc.; Clinical Professor
Attending Physician, Emergency
Assistant Professor of Emergency
of Emergency Medicine, University of Robert L. Rogers, MD, FACEP,
Medicine, King Chulalongkorn
FAAEM, FACP
Medicine, Mount Sinai School of
Michigan, Ann Arbor, MI
Memorial Hospital, Thai Red Cross,
Assistant Professor of Emergency
Medicine; Director of Emergency
Thailand; Faculty of Medicine,
John M. Howell, MD, FACEP
Medicine, The University of
Critical Care, Elmhurst Hospital
Chulalongkorn University, Thailand
Clinical Professor of Emergency
Maryland School of Medicine,
Center, New York, NY
Medicine, George Washington
Baltimore, MD
Maarten Simons, MD, PhD
Senior Research Editor
University, Washington, DC; Director
Emergency Medicine Residency
of Academic Affairs, Best Practices, Alfred Sacchetti, MD, FACEP
Joseph D. Toscano, MD
Director, OLVG Hospital, Amsterdam,
Assistant Clinical Professor,
Inc, Inova Fairfax Hospital, Falls
Emergency Physician, Department
The Netherlands
Department of Emergency Medicine,
Church, VA
of Emergency Medicine, San Ramon
Thomas Jefferson University,
Regional Medical Center, San
Philadelphia, PA
Ramon, CA
Accreditation: EB Medicine is accredited by the ACCME to provide continuing medical education for physicians. Faculty Disclosure: Dr. Constantine, Dr. Elie-Turenne, Dr. Grossman,
Dr. Jagoda, and their related parties report no significant financial interest or other relationship with the manufacturer(s) of any commercial product(s) discussed in this educational
presentation. Commercial Support: This issue of Emergency Medicine Practice did not receive any commercial support.
C
ardiac arrest is one of the most intense clinical
scenarios faced by the emergency clinician. The
challenges are twofold: restarting spontaneous circulation and simultaneously attempting to find―and
then reverse―the cause of the cardiac arrest. Chaos,
confusion, fear, misinformation, and missing information are all common obstacles to managing the
patient in cardiac arrest. To assist emergency clinicians in this situation, protocols such as Basic Life
Support and Advanced Cardiovascular Life Support
(ACLS) have been codified and refined in the past
decade.1-3 These protocols have helped clinicians to
think in a clear and goal-oriented manner and lead
to one of two clinical outcomes: If their efforts are
unsuccessful, the patient will be pronounced dead. If
their efforts are successful, however, they will oftentimes find themselves facing the question (though
perhaps not openly admitting it) of, “Now what?”
With the return of spontaneous circulation
(ROSC), one of the emergency clinician’s initial
challenges has been met. The heart is spontaneously
circulating blood. The second challenge of attempting to find and reverse the cause of the cardiac arrest
remains, however; efforts now shift to these investigative ends while the emergency clinician simultaneously attempts to keep the newly resuscitated
patient stable. Within the last several years, a more
specific continuing treatment plan―beyond that of
simple stability―has emerged. This plan is aimed at
addressing the patient’s postarrest pathology, which
includes the initial disease process that led to the
cardiac arrest and the aftermath of the event.4
No organ system is exempt from the insult
of cardiac arrest. Cardiac, neurologic, renal, and
hepatic functions all suffer, not only from the momentary decrease in perfusion, but also from the
massive inflammatory responses/cascades present
during reperfusion.5 Historically, hypothermia has
appeared to confer some degree of protection from
these insults.6 Case reports of victims of cold water drowning who make full neurologic recoveries
after having been in arrest for extended periods are
well-known.7-10 Brain death—or severe neurologic
compromise—is an unfortunate and devastating
result of cardiac arrest. This event undermines all
prior efforts to save the patient. Although other
organ systems can be compensated for, artificially
circumscribed, or even replaced (as is the case with
renal and liver failure after cardiac arrest), neurologic function must stand on its own. It can determine
the extent to which the patient is functional, even
despite a perfusing rhythm.
Simple speculation about the practice of inducing hypothermia after cardiac arrest, followed by
intense and promising research, has led to its use
for the specific purpose of improving neurologic
outcomes.11 A growing body of evidence12 suggests that control of body temperature (ie, preventing hyperthermia and, more specifically, inducing
hypothermia) should become the standard of care.
Many emergency medical services (EMS) providers
are also investigating the use of specific guidelines
and procedural protocols for inducing hypothermia
in postcardiac arrest patients.13 A wide variation still
exists in the technical application of hypothermia
therapy, however.
Table Of Contents
Critical Appraisal Of The Literature........................3
Etiology And Pathophysiology:
Postcardiac Arrest Syndrome.............................3
Differential Diagnosis: Disease
Management Considerations.............................5
Prehospital Care..........................................................6
Emergency Department Evaluation.........................7
Diagnostic Studies.......................................................8
Treatment......................................................................9
Clinical Pathway For The Application
Of Therapeutic Hypothermia...........................10
Critical Care Basics...................................................12
Cost-Effective Strategies...........................................13
Risk Management Pitfalls For
Therapeutic Hypothermia................................14
Controversies.............................................................16
Disposition.................................................................16
Summary....................................................................16
Case Conclusions......................................................17
References...................................................................17
CME Questions..........................................................22
Definition: Moderate Hypothermia
Early research suggested that at temperatures greater
than 30°C (86°F), the benefits of hypothermia outweigh
the risks of adverse effects, whereas temperatures less
than 30°C (86°F) are associated with a greater incidence
of more severe adverse effects.14 The goal temperature
for hypothermia used most often in studies showing
improvement of outcomes was 32°C (90°F) to 33.9°C
(93°F).11,15 The literature has recently proposed that this
range be referred to as moderate therapeutic hypothermia.16 The goal of this literature review is to assist the
emergency clinician in adapting the known body of
evidence and techniques into an easily applicable protocol to maximize outcomes after cardiac arrest. The
online version of this issue includes the Mount Sinai
Hospital Induced Hypothermia Protocol and PostROSC Care Package documents (available at www.
ebmedicine.net/MSSMProtocol), which readers may
find helpful in establishing institutional protocols.
Available Online At No Charge To Subscribers
EM Practice Guidelines Update: “Pediatric
Advanced Life Support: The 2010 AHA Guidelines,”
www.ebmedicine.net/PALS
Emergency Medicine Practice © 2011
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EBMedicine.net • April 2011
Critical Appraisal Of The Literature
reperfusion does not instantly stop or reverse these
cascades and in fact may exacerbate certain deleterious responses.25 This conglomeration of symptoms
resulting from the interactions of arrest-injured and
reperfusion-injured organ systems is referred to as
“postcardiac arrest syndrome.”26
In 2008, the International Liaison Committee on
Resuscitation published a consensus statement on
the epidemiology, pathophysiology, treatment, and
prognostication of postcardiac arrest syndrome.26
This document coherently defines and addresses
several of the major issues experienced by patients
with an arrest followed by ROSC and subdivides the
syndrome into 4 categories to help guide treatment
efforts:
• Postcardiac arrest brain injury
• Postcardiac arrest myocardial dysfunction
• Systemic ischemia/reperfusion response
• Persistent precipitating pathology
The MEDLINE® database was searched for articles
published from 1950 to October 2010 that used the
term hypothermia. This generalized search yielded
well over 3000 publications. The effort was narrowed to English publications using 1 or more of the
following terms: induced, therapeutic, cardiac arrest,
heart, brain, emergency, resuscitation, and central nervous system. This search produced approximately 500
publications, which formed the basis for this review.
Within this set, most of the publications involved
either animal studies or small, human studies.
The greatest difficulty in searching the literature
on hypothermia is the nature of the therapy. It is not
a single intervention, but rather a combination of
various interventions. Variations in inclusion/exclusion parameters, methodologies of cooling, goal
temperatures, timing, and outcome measures are a
major limitation to synthesizing the evidence.17-19
The results of 2 landmark prospective randomized clinical trials published in 2002 established the
foundation for inducing hypothermia in postcardiac
arrest patients.11,15 These 2 studies have been used
as the basis for many of the recommendations and
guidelines published in the last decade. (See Table 1.)
Bernard et al conducted a randomized controlled
trial of therapeutic hypothermia in patients from
Australia who had suffered cardiac arrest from ventricular fibrillation with ROSC. The study included
77 patients divided into normothermic and hypothermic groups. The absolute risk reduction of death or
severe disability from normothermic to hypothermic
groups was 23%, making the number needed to treat
4.5.15 The Hypothermia After Cardiac Arrest (HACA)
group conducted a multicenter randomized blinded
assessment of 273 patients presenting with ROSC
after ventricular fibrillation arrest. The absolute risk
reduction for an unfavorable neurologic outcome was
24% (a 69% probability of an unfavorable neurologic
outcome in the normothermic group minus a 45%
probability in the hypothermic group). Thus, the
number needed to treat to avoid 1 severe neurologic
outcome (including death) was 4.11
Postcardiac Arrest Brain Injury
The mechanisms of brain injury in response to both
decreased perfusion and subsequent reperfusion
involve a complex series of events that begins almost
immediately after the initial insult. Any period
of ischemia, regardless of length, initiates certain
responses and cascades of chemical events leading
to cell death. Whether through disruption of homeostasis, activation of proteases and oxygen radicals,
or cell-death signaling pathways, the end result is
the same for affected tissue.27,28 These processes can
last from hours to even days after the insult.5 Thus,
this period becomes the window of opportunity for
treatment.
The ischemic event disrupts many of the autoregulatory mechanisms of cerebral blood evidenced
by both microcirculatory and macrocirculatory dysfunctions. On a microcirculatory level, ongoing ischemia may result even after ROSC, possibly secondary to a no-reflow phenomenon.29 This outcome is
currently attributed to thrombus formation, though
controversies surround the exact mechanisms involved.30 On the macrocirculatory level, variations
in mean arterial pressure (MAP) fail to prompt the
correct compensatory changes in cerebral blood
flow.31,32 Initially after ROSC, the brain may, in fact,
become hyperemic, leading to worsening edema and
other reperfusion injuries.33 The clinical significance
of each of these contributing injuries is not well
categorized; however, these responses may cause as
much damage to the patient as the pathology that
led to the arrest.
Etiology And Pathophysiology:
Postcardiac Arrest Syndrome
Any patient who experiences a period of cardiac
arrest undergoes at least 2 pathologic processes. The
first is the disease process that led to the arrest; the
second is the body’s reaction to the period of arrest,
or global hypoperfusion. During arrest, each of the
body’s systems (whether initially in a state of poor
health or not) suffers a great insult. A severely decreased provision of substrate in each organ system
leads to a cascade of events designed to compensate for or ameliorate the sudden loss.24 Sudden
April 2011 • EBMedicine.net
Postcardiac Arrest Myocardial Injury
The myocardium is as sensitive to global ischemic
events as the brain. The emergency clinician may
thus be dealing with both the cardiac pathology that
led to the arrest and the myocardium’s response
3
Emergency Medicine Practice © 2011
to the ROSC. The heart may initially become hyperkinetic secondary to endogenous or exogenous
catecholamines circulating in the body.34,35 Global
hypokinesis with noted decreases in cardiac output
and increases in end-diastolic filling pressures may
also be observed.36,37 Fortunately, these effects are
often transient, with the myocardium returning to
its baseline status within 72 hours.38,39 During this
period, the myocardium appears to remain responsive to exogenous catecholamines37; however, the
peri-code period may be adversely affected by large
doses of exogenous catecholamines, which may have
subsequent effects on overall mortality outcomes.
Rivers et al demonstrated that patients who had
received more than 15 mg of epinephrine during the
code had significantly lower cardiac index, systemic
oxygen consumption, and systemic oxygen delivery,
as well as increased systemic vascular resistance and
6-hour lactate levels.34
very similar to those seen in severe sepsis and septic
shock.40,41 There is a release of inflammatory cytokines such as interleukin-6, tumor necrosis factor
alpha, and endotoxins.42 Endothelial damage leads
to activation of fibrin pathways and the potential
for thrombi formation.43 This is especially deleterious in the microcirculation because the end organs
and tissue beds are dependent upon this system for
adequate perfusion; even after ROSC, tissue beds
may continue to suffer from ischemic damage.44 Adrenal tissue is also known to suffer after periods of
ischemia as measured by cortisol levels, which commonly decrease. Studies have shown that patients
who died early from refractory shock had lower
cortisol levels than did patients who died later from
other causes such as neurologic issues.45
Separate from this septic-type response, the
brain also appears to release several neurohormonal mediators secondary specifically to ischemia. Apoptosis appears to occur via several stages
involving free radicals and subsequent peroxynitrite,
CA2+-dependent protease calpain, accumulation
of glutamate, and various phospholipases, as well
as poly (ADP-ribose) polymerase.28 Following this
model, several animal studies have demonstrated
Systemic Ischemic Reperfusion Response
As both the brain and heart suffer from a period
of hypoperfusion, so does essentially every organ
system. Whole-body oxygen deprivation causes an
activation of immune and coagulation responses
Table 1. Published Guidelines Specific To Therapeutic Hypothermia
Organization
Recommendations
Task Force on Scandinavian Therapeutic Hypothermia Guidelines,
Clinical Practice Committee, Scandinavian Society of Anaesthesiology
and Intensive Care Medicine20
•
http://onlinelibrary.wiley.com/doi/10.1111/j.1399-6576.2008.01881.x/pdf
Use of Hypothermia After Cardiac Arrest, Canadian Association of
Emergency Physicians, Critical Care Committee21
http://www.caep.ca/template.asp?id=37C951DE051A45979A9BDD0C
5715C9FE
•
•
•
•
•
Adult Advanced Life Support: Australian Resuscitation Council Guidelines 200622
•
http://onlinelibrary.wiley.com/doi/10.1111/j.1742-6723.2006.00890.x/
abstract
•
2010 American Heart Association Guidelines for CPR and Emergency
Cardiovascular Care Science23
•
Level I* evidence supports use of hypothermia after VF; therapy is
also recommended for patients with ROSC after asystole and PEA
Protocol should be standardized and initiated as soon as possible
Evidence is insufficient to support recommendations on optimal
target temperature, duration of cooling, and rewarming time.
Patients with nonperfusing VT or VF and ROSC who remain unresponsive should undergo therapeutic hypothermia (Grade A**)
Patients with asystole or PEA thought to be of cardiac origin and
ROSC but who remain unconscious should be considered for therapeutic hypothermia (Grade D***)
Patients under 18 years of age and pregnant women may benefit
from this therapy, but its role is unproven; consideration in these
populations should be on a case-by-case basis (Grade D***)
Unconscious adult patients with ROSC after out-of-hospital cardiac
arrest, when the initial rhythm was VF, should be cooled to 32°C
(90°F) to 34°C (93°) for 12 to 24 hours
Such cooling may also be beneficial in unconscious adult patients
with ROSC after out-of-hospital cardiac arrest when the initial
rhythm was not VF or after cardiac arrest in the hospital
Therapeutic hypothermia should be considered for any patient who
is unable to follow verbal commands after ROSC
http://circ.ahajournals.org/content/vol122/18_suppl_3/
Abbreviations: PEA, pulseless electrical activity; RCT, randomized controlled trial; ROSC, return of spontaneous circulation; VF, ventricular fibrillation;
VT, ventricular tachycardia.
*Level I evidence: Large, randomized trials with clear-cut results; low risk of false-positive error or false-negative error.
**Grade A: Consistent Level 1 evidence - systematic review [with homogeneity] of RCTs; individual RCT [with narrow confidence interval] studies.
***Grade D: Inconsistent or inconclusive studies of any level.
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that even mild hypothermia decreases the amount of
apoptotic neuronal tissue by decreasing or inhibiting
the cascade production of several of these neurospecific mediators.46-48 Equally important, these same
models have demonstrated that inhibition of the
cascade is most effective when it occurs early after
the ischemic insult.46
sion. Although patients were able to reach the goal
temperature by the time of intervention, the study
was not sufficiently powered to show a statistically
significant difference in infarct size though the current evidence suggests there is a difference.54
Another possible deterrent to therapeutic
hypothermia in the patient with AMI is the risk of
increased bleeding, as coagulopathy is a known side
effect of subnormal body temperature. A prospective study in 2002 by Bernard et al demonstrated
improvements in neurologic outcomes secondary
to hypothermia in postcardiac arrest patients.15 The
study did not demonstrate any significant difference in adverse events, such as major hemorrhage,
in patients undergoing PCI or thrombolytic therapy
who were randomly assigned to hypothermia or
normothermia groups. Patients in both groups also
received standard treatments such as antiplatelet
and anticoagulation therapies.15 In a more recent
study, Schefold et al prospectively observed that
the combination of reperfusion strategies―including
anticoagulation and thrombolysis―and hypothermia
was not associated with an excessive risk of bleeding complications.55 Therefore, the evidence indicates that induced hypothermia can be safely used
in conjunction with other major interventions for
management of AMI. This finding will likely grow
in importance considering the most recent ACLS
guidelines, which recommend considering PCI for
cardiac arrest survivors with concerns for non-STsegment elevation myocardial infarction (NSTEMI)
as well as for patients with STEMI.56 This guidance
may increase the number of patients who receive
PCI after cardiac arrest and, therefore, the number of
patients who receive hypothermia and PCI.
Postcardiac arrest care in patients with a suspected PE may be complicated by the need to leave
the emergency department (ED) for imaging studies. Fortunately, most of the cooling devices, both
external and internal, are portable and can easily go
to the radiology suite with the patient. If this is not
possible, disconnecting the patient from the device
for the relatively short period required to perform
a computed tomography (CT) scan usually will not
allow the patient’s temperature to rise more than
0.5°C to 1.0°C (1°F to 2°F). This increase may be of
no consequence, and if the patient returns slightly
above the goal range of 32°C (90°F) to 34°C (93°F),
his or her temperature can be returned to the target
by reinitiating the cooling system.
A more concerning question related to postarrest care in patients with a suspected PE is the use of
anticoagulation and thrombolytic therapies. Study
data on the use of thrombolytic therapy for the treatment of PE during induced hypothermia are limited.
There have, however, been case reports mentioning
the use of thrombolytics for PE during hypothermia treatment. Hovland et al reported such a case
in 2008, with no major bleeding complications.57
Differential Diagnosis: Disease Management
Considerations
The differential diagnosis of patients being considered for induced hypothermia is essentially the same
as that for patients with cardiac arrest. This differential, though initially broad, narrows on the basis of
the patient’s history and the physical examination
findings. Much of this initial work-up, however, will
likely take place during the initiation of the hypothermia care, and thus the workup of cardiac arrest
parallels the cooling activities. It is important to note
that the available data do not show that implementing hypothermia care causes significant delays in
addressing the etiologies of cardiac arrest in terms of
diagnosis or interventions. This issue was specifically addressed in a recent study by Batista et al, who
found that cardiac reperfusion via catheterization
was not delayed by administration of hypothermia
care.49 The effect of hypothermia care on the timing
of other diagnostic and interventional modalities has
not been specifically addressed.
Conversely, questions have also been raised
about how the diagnosis and management of cardiac
arrest as well as its underlying pathology might
affect hypothermia care. For example, do certain diagnoses such as acute myocardial infarction (AMI),
pulmonary embolism (PE), intracranial hemorrhage,
and sepsis affect the initiation or continuation of
induced hypothermia?
With regard to percutaneous coronary intervention (PCI), recent evidence has shown that patients
who receive concurrent hypothermia therapy do not
experience worse outcomes than those patients who
receive PCI alone.50-52 A randomized controlled trial
by Dixon et al clearly showed that hypothermia was
both safe and feasible when combined with PCI;
however, they were unable to show that the size of
the infarct was reduced, an outcome suggested by
previous animal models.53 Additionally, the investigators were unable to meet goal temperature at the
time of reperfusion. Batista et al demonstrated that
induction of hypothermia and a concomitant PCI
was not associated with an increase in the number of
adverse events or with a significant delay in time to
reperfusion.49 Götberg et al looked at mild hypothermia with a goal temperature of less than 35°C
(95°F) performed during reperfusion therapy.54 They
reported a 38% reduction in infarct size on magnetic resonance imaging (MRI) scans after reperfuApril 2011 • EBMedicine.net
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Without direct evidence, we are left to extrapolate
opinions from the studies of the use of thrombolytics
for AMI. Intracranial hemorrhage presents challenges similar to those raised in the discussion of
PE. As stated earlier, patient transport for CT with
or without the cooling device in tow is both feasible
and unlikely to cause any significant variations in
the patient’s temperature.
Although known significant bleeding or intracranial hemorrhage was previously discussed
as a relative contraindication to the initiation of
hypothermia, intracranial bleeding is not necessarily a reason to discontinue hypothermia care once
started. Several studies investigating the use of
hypothermia for neurologic protection after devastating neurologic events have shown great promise.58-62 A randomized controlled trial by Todd et
al specifically addressed the care of aneurysmal
subarachnoid hemorrhage (SAH) after surgical
intervention. Although no significant benefit was
observed in the hypothermic group, there were no
significant increases in morbidity or mortality.60
On the basis of the available data, the decision to
continue hypothermia care if the patient is subsequently found to have SAH may be reasonable.
These issues should be discussed with the appropriate specialists.
Sepsis is another etiology of cardiac arrest; however, it is not the easiest diagnosis to make. Many of
the markers used to identify severe sepsis and septic
shock are the markers of inflammation that are
also elevated in postresuscitative syndrome.40-42,63
The patient history is essential in localizing the
infection. Unfortunately, the initial presentation of
cardiac arrest often comes with a limited history. If
the available information does point to either severe
sepsis or septic shock, induced hypothermia may be
contraindicated. This determination is predicated
on the known side effect of hypothermia decreasing
the immune response. Early studies into hypothermia showed that patients in deep hypothermia (less
than 30°C [86°F]) or cooled for more than 24 hours
were more prone to developing infections.16,64-66
In counterpoint, if current theories about many of
the deleterious effects of sepsis being secondary to
overactivation of the patient’s immune system are
correct, it is tempting to extrapolate from animal
data on immunosuppression during sepsis and assume that suppression by induced hypothermia may
actually be of benefit.67-70 Unfortunately, to date, no
clinical trials of specific anti-inflammatory agents in
patients with severe sepsis have shown significant
benefits,71,72 nor have the data on hypothermia suggested its utility solely as an immunosuppressive
agent in sepsis. Thus, the effects of hypothermia on
neurologic outcome after a cardiac arrest with septic
etiology are unknown. For now, enough evidence
does not exist to recommend sepsis as an absolute
Emergency Medicine Practice © 2011
contraindication to hypothermia care; if hypothermia care has been implemented before the identification of sepsis as the cause of a cardiac arrest, it is
reasonable to continue the therapy.
Prehospital Care
Extrapolating from animal studies, the more quickly
therapeutic hypothermia is induced after ROSC,
the better the outcome.6,73 It therefore is not surprising that some EMS systems have moved towards
implementing field initiation of hypothermia. Wake
Forest EMS in North Carolina and the entire New
York City EMS system have started field initiation
of hypothermia intra-arrest. Although data on the
effectiveness of this strategy are still emerging, these
locales have shown that such therapy is possible in
the field. Both services use small, vehicle-powered
coolers to keep bags of saline at refrigerator temperature (ie, 4°C [39°F]). Additionally, EMS providers must review current treatment protocols that
may interfere with hypothermia, such as the use
of paralytics during rapid sequence intubation, as
these medications may subsequently alter the initial
neurologic examination findings.
Another prehospital issue that has emerged
is the transport of patients to designated cardiac
arrest centers. The management of postcardiac
arrest patients requires skilled staff, coordination between multiple services, and the availability of advanced services such as catheterization
laboratories. Centers with more experience using
hypothermia protocols may also care for these
patients more effectively. Similar to their policies
regarding patients with stroke and STEMI, some
EMS systems are transporting their postcardiac arrest patients to these advanced centers, bypassing
closer hospitals (eg, Arizona and New York City
have adopted this strategy).
For the prehospital provider and medical control
personnel, choosing a facility to receive patients
with an out-of-hospital cardiac arrest now involves
several interventional considerations. The 2010 iteration of the American Heart Association’s Guidelines
for Cardiopulmonary Resuscitation and Emergency
Cardiovascular Care recommend transportation to
facilities capable of PCI for patients with cardiac
arrest from possible acute coronary syndrome if the
facility can be reached within an appropriate time.56
For more information on the 2010 ACLS Guidelines,
see the March 2011 issue of EM Practice Guidelines
Update at www.ebmedicine.net/ACLS. The guidelines also recommend inducing hypothermia care
in appropriate postcardiac arrest patients.23 Because
a potential conflict exists between centers that have
varying services available, these issues are best addressed prior to implementing a treatment protocol.
6
EBMedicine.net • April 2011
Emergency Department Evaluation
tions required for hypothermia care. Additionally, if
the patient has not clearly expressed wishes concerning end-of-life care, it falls to the emergency clinician
to evaluate whether he or she would benefit from
the therapy. Although end-of-life care may suggest
advanced age, there are no specific recommendations based solely on age. Neurologic condition is a
primary outcome metric; therefore, if the patient has
a poor baseline status regardless of age, initiation of
hypothermia care may be futile.
Protection of neurologic function is a primary
goal of induced hypothermia; therefore, a baseline
mental status must be established before initiation
of treatment. If the postcardiac arrest patient returns
to near full mental status, sits up, opens his or her
eyes, and begins interacting with the surroundings,
hypothermia care would not be expected to confer much benefit, and any improvement would be
impossible to measure from such a high-functioning
baseline. On the other end of the spectrum, the comatose patient with no response to painful stimuli,
no brainstem reflexes, or no independent respirations has a defined baseline from which efforts may
be gauged and would qualify for entry into the
induced hypothermia protocol. A Glasgow Coma
Scale (GCS) score of 3 is not necessarily a marker
of dismal prognosis.80 Most patients are between
the extremes of fully awake and profoundly comatose, so a short and focused neurologic examination
must be performed. This evaluation should consist
of determining the GCS score and conducting tests
of basic brainstem function. Certainly, the physical
examination for a patient in cardiac arrest must be
extensive and thorough. If patients are able to follow
commands, hypothermia is contraindicated; if they
are responsive to voice but not able to follow commands (GCS motor score < 6), most centers will still
induce. Corneal, pupillary, and oculocephalogyric
(doll’s eye sign) reflexes should be tested. Assessment of overbreathing is made easier by temporarily lowering the ventilator rate to 6 to 8 breaths per
Inclusion criteria for use of induced hypothermia at
the author’s facility are listed in Table 2. The criteria
focus on the timing of patient presentation and the
patient’s clinical status and overall baseline health.
Of note, the patient must be postcardiac arrest.
This criterion is included to acknowledge that any
nonperfusing rhythm is eligible. Initially, studies on
induced hypothermia focused on patients who were
in ventricular fibrillation or pulseless ventricular
tachycardia.11,15 This constraint has given way to
acceptance as candidates those patients with any
nonperfusing rhythm.73-79
Timing issues are central to induced hypothermia care. The benefit of hypothermia has been
shown to be significant in animal and humans if
started within 6 hours of ROSC.11,12 After this period, there appears to be no significant benefit. The
amount of time that the patient is in arrest is also
significant. The best evidence shows that a time 30
minutes from arrest to ROSC is optimal for seeing
benefit from therapeutic hypothermia; however,
the possibility of benefit when ROSC occurs at 35
or even 45 minutes is unclear.11 Since unwitnessed
arrests are impossible to time, and even witnessed
arrests may be difficult to accurately recount, the
author’s facility notes the “start” time of the arrest as
the beginning of medical intervention, ie, the arrival
of the code team or EMS provider.
Other clinical inclusion criteria are measures of
the patient’s circulatory status and mental status.
Although mild to moderate hypothermia does not
significantly worsen the patient’s hemodynamics, the
inability to maintain a MAP of at least 65 mm Hg is a
relative contraindication to hypothermia. This is a detail best worked out with the facility’s intensivist staff,
as it is not specifically addressed in the literature.
Table 3 shows exclusion criteria for inducing
hypothermia at the author’s facility. There are absolute criteria and several relative contraindications. A
primary tenet of the list is known advanced directives that are in contrast to the aggressive interven-
Table 3. Exclusion Criteria For Induced
Hypothermia
Table 2. Inclusion Criteria For Induced
Hypothermia (Must Have All)
•
•
•
•
•
•
•
•
•
•
Postcardiac arrest status (any rhythm as a cause of arrest is
eligible)
ROSC < 30 minutes from EMS/code team arrival
Time at induction < 6 hours from ROSC
Comatose status (patient does not follow commands)
MAP ≥ 65 mm Hg (may include use of vasopressor drugs)
•
•
DNR advanced directive, MOLST, poor baseline status, or
terminal disease
Traumatic etiology for the arrest
Active bleeding or known intracranial bleeding (relative)
Cryoglobulinemia (relative)
Pregnancy (relative; consider obstetrician/gynecologist consultation)
Recent major surgical procedure (relative)
Severe sepsis/septic shock as cause of arrest (relative)
Abbreviations: EMS, emergency medical services; MAP, mean arterial
pressure; ROSC, return of spontaneous circulation.
Abbreviations: DNR, do not resuscitate; MOLST, medical orders for
life-sustaining treatment.
Used with permission, Elmhurst Hospital Center, New York, NY.
Used with permission, Elmhurst Hospital Center, New York, NY.
April 2011 • EBMedicine.net
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Emergency Medicine Practice © 2011
minute. Evidence has shown that in the time immediately after cardiac arrest, routine assessments
of neurologic functions such as spontaneous breathing and fixed dilated pupils do not hold reliable
prognostic value.80 Thus, these examinations should
not be used to determine whether the patient will
benefit from the therapy, but rather to establish a
baseline from which improvement can be measured.
Any medications administered may affect neurologic findings and thus should be documented;
however, the use of these medications should not
render the patient ineligible for therapy.
Blood gas results are affected by hypothermia
secondary to alterations in laboratory analysis of the
sample. Most blood gas analyzers will change the
temperature of the sample to normothermia. The
partial pressures of gasses are directly proportional
to their temperature based on Boyle’s Law. Thus, the
laboratory results will show the CO2 and O2 values
as increased from their in vivo values. Consequent
lowering of the pH will occur. In general, the partial
pressure values will be falsely elevated by 5 mm Hg,
and the pH falsely lowered by 0.012 for every 1°C
below 37°C (approximately every 2°F below 98.6°F).
Drug metabolism is generally dependent on enzyme processes that are frequently temperature-dependent and become slower during hypothermia.84
The half-life of most drugs will increase, therefore
prolonging the duration of action of the medications.
As a general rule, lower dosing will be mandated
for most metabolized medications. Likewise, infusion rates may require adjustment. In certain circumstances, bolus dosing may be safer and easier to
manage for drugs that are infused and titrated under
normal conditions.
Cardiac arrhythmias are frequently seen during
the hypothermia process, but intervention is rarely
required.16,85,86 During mild hypothermia, bradycardia is common, and the patient’s peripheral resistance may also rise by approximately 10 mm Hg.
These combined effects may lower overall cardiac
output. Typical hemodynamic strategies are aimed
at maximizing cardiac output and, therefore, tissue
perfusion. Hypothermia therapy may thus seem
counterproductive in postresuscitative care. Fortunately, lowering of cardiac output is often matched
by an overall decrease in whole-body metabolism,
such that the lower demand for substrate is met by a
lower supply from cardiac output.16
In most situations, the small changes in heart rate,
MAP, and cardiac output caused by the hypothermia
Diagnostic Studies
Induced hypothermia affects all aspects of physiology. Many of the physiologic changes that occur either
require no specific response or are easily dealt with
using simple intervention and monitoring techniques.
Induced hypothermia is frequently associated
with changes in metabolic, liver function, and hematologic profiles. Volume changes occur as a result of
cold diuresis, and there may be changes in drug metabolism. (See Table 4.) Platelet function and coagulation are both adversely affected by hypothermia.
Mild platelet dysfunction begins at temperatures
below 35°C (95°F), whereas coagulation changes
will be seen only at temperatures of 33°C (91°F) and
below.81,82 In very mild hypothermia (ie, temperatures above 35°C [95°F]), no increased bleeding will
be seen. None of the studies analyzing outcomes of
hypothermia in patients with known or discovered
intracranial hemorrhage showed any significant increase in bleeding61,62,74; however, because even mild
coagulopathy or platelet dysfunction may be deleterious to the multiple-trauma patient, hypothermia
is contraindicated in this situation. Desmopressin
has been shown to reverse the platelet dysfunction
induced by hypothermia.83
Table 4. Common Laboratory Changes Associated With Induced Hypothermia16
Value
Chemistry
Blood gas
Change
Correction/Intervention
Potassium, magnesium
Check frequently and replace as needed to maintain values in normal range
Bicarbonate
Monitor along with blood gas values; replacement is generally unnecessary
Amylase, AST, ALT
Monitoring only
CO2
Mathematically correct for changes in temperature, as the reported values are likely
obtained by altering the temperature of the laboratory sample
O2
pH
Hematology
WBC
Monitoring only
PT/PTT
Usually none; however, may give correction factors if severe bleeding or discovery
of occult bleeding such as intracranial hemorrhage
Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; PT, prothrombin time; PTT, partial thromboplastin time; WBC, white
blood cell.
Emergency Medicine Practice © 2011
8
EBMedicine.net • April 2011
care are negligible. Severe, life-threatening arrhythmias generally occur at temperatures below 30°C
(86°F) and are thus avoided during mild to moderate
hypothermia.14 The common ECG changes seen are
PR, QT, and QRS prolongations. (See Table 5.) Severe
arrhythmias may be atrial fibrillation and ventricular
fibrillation. Even though these dysrhythmias are typically not seen during mild to moderate hypothermia,
their development is a contraindication to the continuation of the therapy. If life-threatening arrhythmias develop, any hypothermia treatment should be
discontinued and the patient slowly warmed.
near the body’s core (ie, in the axilla and groin and
around the head).88 Although readily available and
easy to set up, these systems do not allow for strict
control; maintaining a setting for 24 hours is technically challenging and often results in wide variations
in temperature.89 A more practical approach may be
to initially cool the body with ice packs while another system is set up to maintain the temperature.
Commercially available external systems generally offer the added benefit of a thermostat system
(for monitoring the patient’s core temperature) that
maintains the temperature within a narrow range.
The Blanketrol® II and III hyper/hypothermia systems (Cincinnati Sub-Zero Products, Inc., Cincinnati,
Ohio) are essentially a set of blankets that circulate
water. The water temperature is controlled via a bedside unit. This system features a temperature input
that allows feedback from a probe placed within the
patient. The water temperature is then adjusted as
needed to maintain the chosen body temperature.
The same principles of external cooling are used
with pad systems that circulate temperature-controlled water and wrap around certain parts of the
body. Examples include the CoolBlueTM Surface Pad
System (Innercool Therapies, San Diego, California) and the Arctic Sun 5000 Targeted Temperature
ManagementTM system (Medivance Inc., Louisville,
Colorado). These systems also provide feedback
through a temperature probe placed on or within
the body. In general, the water-circulating external
contact devices have a cooling rate of 1°C to 2°C per
hour (Fahrenheit not listed for device).16 If a patient
starts out at approximately normal body temperature, cooling may take up to several hours. Other
modalities, however, may be used in addition to the
external devices to shorten induction time.
Treatment
The use of hypothermia as a therapy is divided into
3 phases: induction, maintenance, and rewarming. During the induction phase, the patient’s body
temperature is taken from the presenting state to the
goal temperature. During the maintenance phase,
the patient’s temperature is held steady at goal, generally for a period of 24 hours from the time of initiation of induction. The rewarming phase begins at the
end of this period, as the body is slowly returned to
a normothermic state.
The process of induced hypothermia results in a
cold diuresis that must be taken into consideration
during patient management. In a patient who may
already require fluid resuscitation as a consequence
of the pre-arrest pathology, this additional diuresis
will be counterproductive. Treatment is simply the
replacement of ongoing losses. The author recommends strict intake and output monitoring, with
subsequent 1:1 replacement of all urinary losses
in addition to any ongoing fluid resuscitation as
directed by hemodynamic monitoring protocols. See
“Critical Care Basics,” page 12.
Internal Cooling Systems
Internal systems are, most commonly, intravascular
devices. A simple example of this type of cooling is the
infusion of cold saline, which offers the distinct advantage of a rapid decrease in temperature of approximately 2°C to 4°C (3.5°F to 7°F) per hour.16,88,90 Saline
infusion may also be used in conjunction with other
Cooling Systems
Cooling systems are typically either external or internal devices. External systems involve cool objects
that are placed next to the skin,16 while internal
systems are largely intravascular in nature, and the
heat exchange takes place within the circulatory
system of the patient rather than on the external
body surface. In addition, a relatively new third
approach exists, involving delivery of coolant to the
nasopharyngeal passages. This device, the RhinoChillTM (BeneChill, Inc., San Diego, California), has
been shown to be feasible, safe, and effective in the
prehospital environment.87
Table 5. Common Cardiac Changes
Parameter
Cardiac activity
MAP
Cardiac output
External Cooling Systems
External systems are the most common systems for
cooling the body. On the most basic level, exposure,
cold air, cold water immersion, and ice can be used
to both cool and maintain temperature. Ice packs are
economical and work to induce cooling when placed
April 2011 • EBMedicine.net
Heart rate
ECG
PR interval
QRS duration
QT interval
Atrial or ventricular fibrillation
Abbreviations: ECG, electrocardiogram; MAP, mean arterial pressure.
9
Emergency Medicine Practice © 2011
Clinical Pathway For The Application Of Therapeutic Hypothermia
YES
Patient with cardiac arrest
followed by ROSC?
ROSC within 30-60 minutes of start of code
(arrival of EMS if in the field)?
Initiation of hypothermia within 6 hours of ROSC (Class I)?
NO
NO
Continue with standard postresuscitative care
NO
Continue with standard postresuscitative care
YES
Patient deemed a candidate after a quick review of baseline
mental and functional status and goals of care
(per patient and/or family wishes)?
YES
Conduct focused examination to establish comatose state and
baseline neurologic function
•
GCS (does not portend prognosis) (Class II)
•
Brainstem reflexes
Initiate induction phase of cooling
Hypothermia Protocol
Induction phase
•
Reach goal of 32°C-34°C within 1 hour (Class I)
•
Set up chosen devices
Temperature maintenance device
Temperature monitoring device
•
Monitor for shivering
Critical Care Basics
•
Establish central venous access
•
Conduct arterial pressure monitoring
•
Manage mechanical ventilation
Maintenance Phase
•
Assess for shivering
Evaluate need for analgesia and sedation (recommend paralysis only as needed)
•
Assess for changes in laboratory values with correction of
electrolyte levels
•
Monitor in/outs; maintain euvolemia
Address Inciting Pathology
•
Radiologic assessments
CT scan
Angiography
•
Cardiac interventions
PCI
Thrombolysis
•
Stroke interventions
tPA (intra-arterial as needed)
Aneurysm surgical procedure
•
Medications
None contraindicated during hypothermia
l
l
l
l
l
l
l
l
l
l
Rewarming phase
•
Rewarm approximately 0.5°C (1°F) per hour (Class I)
•
Assess for electrolyte shifts, particularly potassium
•
Assess mental status and neurologic function
Abbreviations: CT, computed tomography; EMS, emergency medical services; GCS, Glasgow Coma Scale; PCI, percutaneous coronary intervention;
ROSC, return of spontaneous circulation; tPA, tissue plasminogen activator.
See Class of Evidence descriptions on page 11.
Emergency Medicine Practice © 2011
10
EBMedicine.net • April 2011
systems. Additionally, crystalloids are ubiquitous in
the clinical arena. Storage of several liters in a cooling
unit will provide an easily accessible and inexpensive
method to immediately begin cooling a patient.
Commercially available intravascular systems
use a catheter-based heat exchange process. For
example, CoolLine®, CoolGard 3000 and Fortius
CatheterTM systems (Zoll Medical Corporation,
Chelmsford, Massachusetts) circulate cooled fluid
within balloons, whereas the Celsius Control SystemTM (Innercool Therapies, San Diego, California)
uses metal-based catheters that are in direct contact
with the bloodstream. These systems have the ability
to rapidly cool the patient and then accurately maintain the temperature at a set point with minimal
variations; however, they require an invasive and
potentially time-consuming procedure. Intravascular
devices may also increase the risk of venous thrombosis, although the limited data that exist show an
increased risk after several days and not necessarily
within the first 24 hours of use.91-93
transition from normothermia to goal temperature;
therefore, there may be an advantage to reaching
the goal temperature as quickly as possible. Several
modalities are available for rapid induction, ranging
from low-cost methods such as the administration
of cooled crystalloid and devices that allow controlled immersion to more invasive methods such as
intravascular thermal exchange devices. Each device
has certain advantages and disadvantages, and their
use will most often be dependent upon the resources
available at the time. At the author’s institution, iced
saline is used for induction, and a surface blanket
machine is used for continued maintenance while
the patient remains in the ED. Alternatively, induction can be achieved with iced saline and maintenance provided by ice bags placed in the patient’s
groin and axilla. Although this method is almost
cost-free, it has been associated with poorer temperature control and possibly increased complication
rates.89
Temperature blankets can be placed as soon as
the patient has achieved ROSC and is stable enough
to be manipulated. Once the device is fully connected and the probe is in place, the goal temperature is
set and the machine is allowed to begin cooling the
patient. These blankets may be placed before other
necessary procedures such as CT, and even invasive
interventions such as PCI may be performed with
most devices in place.
Use of external systems alone may result in
a prolonged induction phase. Rapid temperature
reduction is achieved with the administration of
cooled (4°C [39°F]) normal saline (or other crystalloid/colloid based on the clinical scenario). In many
situations, the patient benefits from maximization
of volume status through fluid resuscitation. With
use of this method alone, temperature reduction of
approximately 2.5°C to 3.5°C (4.5°F to 6°F) per hour
has been observed.94 Thus, a normothermic patient
can be cooled from 37°C (98.6°F) to 33.5°C (92°F),
Cooling System Summary
To summarize, cooling systems can be placed into 2
basic categories, external and internal. Within each
of these categories, there are low-cost and essentially
“do-it-yourself” options to expose the patient to precooled items that are readily available in the clinical
environment. These methods offer the advantage of
a low cost but have the disadvantage of lack of control. Alternatively, each category includes a variety
of technologically advanced systems. The greatest
advantage of advanced cooling technologies is their
capability to react to the patient’s temperature and
alter the exposing medium to maintain body temperature at a set point.
Induction
Induction should be the shortest of the 3 phases.
The majority of adverse effects occur during the
Class Of Evidence Definitions
Each action in the clinical pathways section of Emergency Medicine Practice receives a score based on the following definitions.
Class I
• Always acceptable, safe
• Definitely useful
• Proven in both efficacy and
effectiveness
Level of Evidence:
• One or more large prospective
studies are present (with rare
exceptions)
• High-quality meta-analyses
• Study results consistently positive and compelling
Class II
• Safe, acceptable
• Probably useful
Level of Evidence:
• Generally higher levels of
evidence
• Non-randomized or retrospective studies: historic, cohort, or
case control studies
• Less robust RCTs
• Results consistently positive
Class III
• May be acceptable
• Possibly useful
• Considered optional or alternative treatments
Level of Evidence:
• Generally lower or intermediate
levels of evidence
• Case series, animal studies, consensus panels
• Occasionally positive results
Indeterminate
• Continuing area of research
• No recommendations until
further research
Level of Evidence:
• Evidence not available
• Higher studies in progress
• Results inconsistent, contradictory
• Results not compelling
Significantly modified from: The
Emergency Cardiovascular Care
Committees of the American
Heart Association and represen-
tatives from the resuscitation
councils of ILCOR: How to Develop Evidence-Based Guidelines
for Emergency Cardiac Care:
Quality of Evidence and Classes
of Recommendations; also:
Anonymous. Guidelines for cardiopulmonary resuscitation and
emergency cardiac care. Emergency Cardiac Care Committee
and Subcommittees, American
Heart Association. Part IX. Ensuring effectiveness of communitywide emergency cardiac care.
JAMA. 1992;268(16):2289-2295.
This clinical pathway is intended to supplement, rather than substitute for, professional judgment and may be changed depending upon a patient’s individual
needs. Failure to comply with this pathway does not represent a breach of the standard of care.
Copyright © 2011 EB Practice, LLC d.b.a. EB Medicine. 1-800-249-5770. No part of this publication may be reproduced in any format without written consent of
EB Practice, LLC d.b.a. EB Medicine.
April 2011 • EBMedicine.net
11
Emergency Medicine Practice © 2011
which is within the goal range of 32°C (90°F) to 34°C
(93°F) in 1 hour. Combined with additional devices,
this method can achieve induction more expediently.
Studies demonstrating the effectiveness of
cooled fluids in therapeutic hypothermia have used
an initial goal of 30 mL/kg and an infusion rate of
approximately 100 mL/min.95-97 For the average
adult, this regimen requires approximately 2 L as a
maximum initial infusion. Depending on the size
and type of catheter used, this rate may be best accomplished by using a pressure bag. The 2 L therefore should be delivered in approximately 20 minutes. It may take several additional minutes to reach
maximal temperature effect. If the patient is still not
below 34°C (93°F) after the initial maximum dose,
we recommend waiting 15 minutes for the temperatures to equilibrate. If the goal is still not reached
after this period, additional boluses of 250 mL of
cooled fluid may be given every 10 minutes until the
patient’s core temperature is less than 34°C (93°F).
Conversely, if the patient reaches a temperature less
than 34°C (93°F) at any time before the completion
of the maximal fluid dose, the cooled fluids can be
discontinued. If further fluid is needed, room temperature saline may be given from this point.
Many temperature control systems have a monitoring probe. Regardless of the actual configuration
of the device, evidence suggests that the most efficient placement during the induction phase is within
the esophagus.16 This placement offers the earliest
feedback on the patient’s true core temperature.
Both bladder and rectal placements of the probe are
certainly easier and effective to a point; however,
there may be a lag between the patient’s true core
temperature and the rectal temperature, which can
lead to a delay in the machine sensing whether the
patient is at a desired temperature. Although the
monitoring capabilities of the cooling systems vary,
the evidence suggests that, given a choice, esophageal placement is ideal.
Within the esophagus, the best placement of the
probe is behind the right atrium. This site is landmarked externally as approximately 4 cm cephalad
to the xiphoid process. The probe can be measured
before insertion and a notation made of the probe
before placement. If the probe cannot be placed in
the esophagus, it should be inserted in the rectum to
approximately 5 cm. Assuming the patient is intubated and has vascular access, once the temperature
blankets are applied, all of the necessary systems are
in place for hypothermia therapy. Further procedures will be necessary as part of the standard approach to a critically ill patient and are discussed in
the following section.
control methods alone. If the methodology up to
this point has overshot the goal and the patient’s
temperature subsequently drops below 32°C (90°F)
(although not below 30°C [86°F]), no drastic warming measures are necessary. Most surface devices,
if set to automatic mode, will begin to warm the
patient in order to attain the set temperature. If the
temperature rises above 34°C (93°F), there will be a
shift back into “induction” mode. In these cases, it is
recommended to give additional 250-mL boluses of
cooled fluid every 10 minutes until a temperature of
less than 34°C (93°F) is reached.
Critical Care Basics
Regardless of whether postcardiac arrest patients are
treated with induced hypothermia care, they are still
critically ill and will benefit from invasive monitoring and aggressive management. Table 6 lists
recommended monitoring devices and procedures
for each patient. In general, access to the head, neck,
and arms is not inhibited by any of the systems used
in induced hypothermia.
Although hypothermia has adverse effects on
basic hemodynamic parameters such as heart rate
and blood pressure, the goals of resuscitation for
postcardiac arrest patients are similar to the goals
used in the care of the severely septic patient. Taking
into account that the etiology of the cardiac arrest
may have continuing deleterious effects on the
patient’s homeostasis, the pathophysiology of the
disorder parallels that of severe sepsis and septic
shock. The effects of inflammatory mediators and
cascades that occur secondary to the initial insults
lead to many of the same homeostatic disruptions seen in sepsis. The current recommendations
therefore support a similar strategy of hemodynamic
optimization, by ensuring adequate tissue perfusion through maintenance of perfusion pressure and
cardiac output.2
The hemodynamic goal in treating these parallel
pathologies is adequate tissue perfusion and thus
substrate delivery. Ensuring tissue perfusion involves maintaining adequate perfusion pressure and
adequate cardiac output. Cardiac output is further
dependent upon preload, afterload, inotropy, and
heart rate. Assessment of these efforts via specific
monitoring devices provides ongoing feedback for
further adjustments and prognosis.
Table 6. Procedures Recommended For
Hemodynamic Monitoring
Maintenance Phase
•
•
•
•
Once a core temperature of less than 34°C (93°F) is
reached, the patient is in the maintenance phase.
This phase can be managed with blanket or surface
Emergency Medicine Practice © 2011
12
Full sterile neck line with central venous pressure monitoring
Full sterile arterial line
Foley catheter with hourly urine monitoring
Orogastric tube on suction
EBMedicine.net • April 2011
Perfusion pressure at the tissue bed is dependent
on the MAP. Studies of shock and sepsis show that
a MAP of at least 65 mm Hg is generally adequate
to maintain perfusion of vital organs, including
the heart itself.98 Injury to the brain may cause an
increase in intracranial pressure. A higher MAP may
be theoretically beneficial by maintaining adequate
cerebral perfusion pressure. Studies of postcardiac
arrest have shown no worse outcome for patients
with a MAP as high as 90 to 100 mm Hg.15,78 If the
patient is hypertensive during the postresuscitation
period, it is suggested that the allowable upper limit
of MAP is 100 mm Hg, based on these same data.
No specific agents are recommended for control of MAP in the patient undergoing hypothermia
therapy. Norepinephrine is often used as a firstchoice pressor and vasopressin as a second-line
agent. For hypertensive patients, nitroglycerin may
be used. These choices are based in part on evidence
of adequate outcomes with these agents for shock in
general99 and in part on the author’s experience and
comfort with their use in a variety of clinical experiences. Of note, any pressor or vasodilator agent has
specific use requirements and side effect profiles that
dictate its applicability in certain clinical scenarios
and treatment environments.
Adequacy of preload cannot be assessed
through a single measurement; several tools should
be used simultaneously to obtain the best estimation
of the patient’s preload status. Measurement of central venous pressure (CVP) has been used in early
goal-directed sepsis therapy100; however, evidence
has shown that it is most useful when low and that
interpretation of CVP becomes less helpful when
the initial values are within the normal range.101,102
Therefore, if a normal CVP value is 8 to 10 mm Hg,
the further the patient’s reading is below this mark,
the more likely the need for preload support. Additional evaluations include sonographic assessment
of respiration changes in inferior vena cava (IVC)
diameter,103 pulse pressure variation,104 passive leg
raise, and simple bedside echocardiography. The
combination of these assessments should guide decisions regarding volume replacement. If the patient is
already at goal temperature, room temperature isotonic fluids should be used in aliquots of 200 to 500
mL, followed by reassessment of these same clinical
parameters.
The final division in the tissue perfusion scheme
is ensuring adequate cardiac output by the adequacy of inotropy. Cardiac output is a combination
of stroke volume and heart rate. Stroke volume is
affected by the aforementioned preload and afterload and is dependent upon the intrinsic ability of
the heart to pump (inotropy). Cardiac output can
be further affected by manipulating inotropy, thus
allowing the heart rate to be solely a compensatory
mechanism that is best managed intrinsically. In the
past, measurements of cardiac output and inotropy
involved the use of pulmonary artery catheters, with
subsequent measurements and calculations. Mixed
venous oxygen saturation measured from a central
venous catheter placed in the superior vena cava
can be used as a surrogate marker. As blood moves
through the capillary bed, oxygen is removed by
processes of cellular transport and simple diffusion.
If cardiac output is below the baseline level, oxygen
uptake is increased by the tissues as compensation.
When returned to the venous side, this blood will be
less saturated. A saturation of 70% has been shown
to correlate with adequate tissue perfusion and thus
adequate cardiac output.105,106
Cost-Effective Strategies For Therapeutic Hypothermia
• Therapeutic hypothermia is unlikely to add
significantly to the overall cost of caring for
patients in acute situations and offers significant
benefits in decreasing disability (with its inherent costs).
• Cooling machines and supplies are the only significant added costs of therapeutic hypothermia.
The machines range in price, and few data on
head-to-head comparisons support the benefit
of one machine or type over another. Thus,
financial constraints are not an evidence-based
hindrance to applying this therapy.
• Many EDs and hospitals already stock temperature control equipment as a way of treating pathologic hyperthermia and hypothermia.
Many of these machines and modalities are
easily adapted to the purpose of inducing, or asApril 2011 • EBMedicine.net
sisting with maintenance of, hypothermia.
• Ice and cooled saline are already available in
hospitals and therefore represent no real costs
for this therapy. These less expensive measures
may be more difficult to regulate, however, and
require more vigilance by emergency clinicians
in terms of monitoring patients.
• Total costs need not be absorbed by one department or specialty within the hospital system.
Cardiac arrest can occur in-hospital or out-ofhospital, and subsequent care is likely to involve
many different hospital services, making application of this therapy a multidisciplinary effort.
The allocation of resources, particularly personnel, may thus be shared among multiple services
and departments.
13
Emergency Medicine Practice © 2011
In the postcardiac arrest state, as in the septic
state, inflammatory cytokines and other mediators also act as cardiodepressants. Evidence shows
that a global dysfunction may occur after ROSC
from cardiac arrest, regardless of the etiology. This
global dysfunction is generally transitory and is
not associated with decreased coronary flow (ie,
ischemia).26 To overcome this in vivo depression of cardiac
activity, inotropes such as dobutamine may be considered. An echocardiogram should be performed
to further define the extent of dysfunction and the
response to pharmacologic interventions, as well
as to evaluate for more invasive assistance such as
intra-aortic balloon pumps.
Recent literature regarding the treatment of
septic shock supports the use of lactate clearance as
a marker of adequate tissue perfusion.107 Unfortu-
nately, this option has not been studied specifically
during hypothermia therapy. If this value is taken
into account when the patient’s hemodynamic status
is evaluated, it should be kept in mind that hypothermia may cause lactate levels to rise during the
induction period.14 Thus, after the goal temperature is reached, a new baseline serum lactate assay
should be obtained to serve as the starting point
from which to evaluate tissue perfusion.
Shivering Response
During the initial stages of induced hypothermia,
efforts are focused on implementation of cooling and
ongoing care of the critically ill patient. Once the
therapy is initiated, the emergency clinician must
remain vigilant in ensuring that all facets of care are
addressed. Shivering is by far the most insidious
and counterproductive adverse effect of the hypo-
Risk Management Pitfalls For Therapeutic Hypothermia
(Continued on page 15)
1. “A patient has arrived from a nursing home
with ROSC after being found unresponsive
during the morning shift change. The patient
is nonverbal and noninteractive, with little
apparent cognitive ability secondary to a prior
stroke. Am I obligated to induce hypothermia?”
This practice is not the standard of care at this
time; thus, the emergency clinician reserves the
right to decide on a case-by-case basis which patients may or may not benefit from this therapy.
The emergency clinician reserves the right to
decide when clinical and/or extraclinical factors
(such as resource allocation) make the application impractical.
4. “I’m called to the bedside by the nurse because
the most recent ECG of a patient receiving
therapeutic hypothermia appears to have a lot
of artifact that she can’t seem to get rid of. On
close inspection, the patient appears to have a
fine tremor. The nurse asks if I would like to
administer another dose of paralytic.”
Paralysis should be used only as a last resort for
shivering control, as masking seizure activity may
result in worsening of neurologic status despite
any benefits gained by therapeutic hypothermia.
Sedation and analgesia should be used first.
2. “I was treating a patient with chest pain and a
very concerning history when she suddenly arrested. After several minutes, we were able to
bring her back. An ECG taken after the arrest
showed lateral wall myocardial infarction. I activated the cath team, but should I have waited
until the patient was cooled before letting her
go for the procedure?”
Treating a patient with induced hypothermia
should not delay or inhibit the application of any
other emergent procedures or investigations (eg,
cardiac catheterization, surgical intervention,
interventional radiology) related to the underlying pathology of cardiac arrest. Most times, the
interventions can be performed simultaneously.
5. “While working medical control for my local
EMS system, I received a call about a patient
postcardiac arrest with ROSC. The EMS providers stated that they had been training to
perform hypothermia and asked if they should
begin therapy before my assessment of the
patient.”
Emergency medical services are a vital part of
the hypothermia care paradigm, as the therapy
has been shown to be more effective when
3. “As an emergency clinician, I’m excited about
the prospect of having an additional therapy
Emergency Medicine Practice © 2011
for my postcardiac arrest patients. I have all
of the tools in my ED and would like to get
started right away. What else do I need to do?”
Therapeutic hypothermia is a multidisciplinary
treatment modality; before initiation of any
hypothermia protocol, all potential services
that may be caring for the patients should be
involved in the discussion. These services may
include neurology, intensive care medicine,
emergency medicine, and EMS.
14
EBMedicine.net • April 2011
thermic process. The shivering response is seen at a
core temperature of approximately 35.5°C (96°F).108
Initially, the body responds to cooling by increasing
sympathetic tone, causing peripheral vasoconstriction. As the body continues to cool, however, the
same sympathetic stimulation leads to increased
production of heat through shiver mechanisms. This
shivering leads to an increase in metabolism, oxygen consumption, excess work of breathing, heart
rate, and general stresslike response.109,110 Each of
these reactions may be detrimental to the goals of
hypothermia; however, the greatest detriment is the
generation of heat, which directly counteracts the
entire focus of the therapy. Although shivering is
most commonly seen during the induction phase,
it can occur during any phase of the hypothermia
process; thus, patients should be assessed every 15
minutes during treatment.
The treatment of shivering focuses on proper
sedation of the patient. An obvious “quick fix” to
shivering is to paralyze the patient. No muscle
movement essentially means that no heat is generated; however, the shivering response is centrally
mediated.110 Simply turning off muscle movement
does not hinder the central nervous system’s attempts to warm the body. Other stress responses that
are detrimental to the overall goals of hypothermia
will also be masked, rather than mitigated, by paralytics. Masking the level of possible seizure activity
can be dangerous; therefore, sedation should be the
primary intervention used against shivering.16
Many sedating and anesthetic medications are
available in most EDs, though several choices have
specific advantages in helping to mitigate shivering. Fentanyl citrate has a very rapid onset of action
and short half-life, making it ideal for titration. It is
Risk Management Pitfalls For Therapeutic Hypothermia
(Continued from page 14)
delivered early. The initial cooling process can
be started easily in the field with ice or cooled
saline. If the receiving emergency clinician does
not feel that hypothermia care is warranted, then
there is no obligation to continue it.
6. “The patient receiving therapeutic hypothermia suddenly went into atrial fibrillation. I
decided to attempt cardioversion, and the first
shock converted the patient to normal sinus
rhythm. After several minutes, however, the
atrial fibrillation returned. Then the patient’s
blood pressure started falling.”
The development of a life-threatening arrhythmia
is a contraindication to hypothermia care. The
patient should be rewarmed to normothermia.
9. “While beginning to rewarm the patient, I
noticed a change in the T wave morphology
on the monitor. A subsequent ECG showed
peaked T waves. Did I miss renal failure in the
patient?”
A too-rapid rate of rewarming will cause severe
electrolyte shifts, particularly hyperkalemia. The
rate of rewarming should not exceed 1°C (2°F)
per hour and ideally should be more toward
0.5°C (1°F) per hour.
7. “When using therapeutic hypothermia I continue to have difficulty maintaining a constant
temperature. Every time I adjust the device or
add saline to recool the patient, I end up overshooting my goal.”
First and foremost, check the patient for shivering. Wide temperature swings are not the norm
and may be a sign of occult or fine shivering.
Second, consider a different placement for the
particular feedback device. If possible, esophageal placement should be attempted.
10. “A patient who has undergone hypothermia
care is neurologically devastated several days
after rewarming. I am asked why it did not
work.”
Hypothermia care offers no guarantees. Efforts
should be made to explain to providers and
family that this therapy will increase the patient’s chances for attaining a good neurologic
outcome; however, it is difficult to predict which
patients will fully recover on the basis of the
available data.
8. “After several hours of stability during
therapeutic hypothermia, my patient became
gradually more tachycardic. Although she was
initially weaned from pressors, her blood pres-
April 2011 • EBMedicine.net
sure started falling again. I used ultrasound
only to find her IVC had collapsed, and her
heart was pumping vigorously.”
Cold will cause a diuresis. Although all patients
may require some form of maintenance fluid,
hypothermic patients should have urine output
monitored closely and subsequently matched
in return.
15
Emergency Medicine Practice © 2011
Disposition
known to be effective in reducing pain and respiratory discomfort. The sensation of temperature
is mitigated through similar pathways as pain;
thus, blunting the opioid receptors decreases the
sensation of hypothermia and therefore shivering.
In a recent systematic review, Chamorro et al analyzed sedation regimens used during hypothermia
protocols in the intensive care unit and found that
fentanyl was the most common opioid used.111
We recommend maximizing the dose before the
addition of other agents to achieve both sedation
control and shivering control. Agents that may
be added are magnesium,112,113 meperidine,114
propofol,115 dexmedetomidine,116 ketamine, and/
or benzodiazepine regimens. Regardless of the
preferred regimen, sedation should be maximized
before paralytics are used.
If paralytics are necessary to control shivering,
they should be given in bolus doses, as the maximal effects of sedation may be enough to keep the
shivering from returning once the paralytic has been
metabolized. Continuous electroencephalographic
monitoring has been used in some centers to check
for nonconvulsive status epilepticus. If paralytics are
used, the author strongly recommends this modality
to ensure that seizure activity does not go unrecognized and therefore untreated.
All patients undergoing induced hypothermia are
admitted to a critical care setting. Depending upon
specific hospital resources, any or all parts of a
hypothermia protocol can be administered in the
ED or the intensive care unit. Both induction and
maintenance may be completed in the ED; however,
completion of these tasks should not delay transfer
of the patient to a critical care setting, where advanced care can be given as needed.
Rewarming
In its simplest form, rewarming will occur naturally
if the cooling devices are removed and the body is
simply allowed to return to its own set temperature; however, several studies have shown that this
technique may be associated with additional and unforeseen complications secondary to a too-rapid rise
in temperature.118-121
We recommend that the same device be used for
maintenance and rewarming. By gradually raising
the set point and continuing to actively control shivering, emergency clinicians can achieve slow and
controlled warming with minimal adverse effects.
Once the patient’s temperature is at 36°C (97°F), passive warming should be permitted, since shivering is
less likely to occur.108 Similar to the cooling process,
the rewarming process can cause rapid shifts of electrolyte levels between intracellular and extracellular
spaces. Specifically, levels of certain electrolytes such
as potassium may rise quickly instead of decreasing
quickly, as occurs with cooling.122 Hyperkalemia is
a dangerous side effect of warming. Frequent blood
draws during the rewarming period as well as a
slow and controlled rate of rewarming will minimize
rapid changes in electrolyte levels.
If a warming program is not available, the set
point of the device should be changed hourly in
appropriate increments until a core temperature
of 36°C (97°F) is reached. From this point on, the
patient may be allowed to return to his or her own
homeostatic temperature set point. Hyperthermia
should be treated similarly as in any critical care
patient and may be particularly detrimental to a
patient with central neurologic injury. It may even
become necessary to continue using the same cooling methods in order to maintain normothermia.
Controversies
There are essentially 2 arguments against therapeutic hypothermia. The first concerns the relative lack
of supporting evidence. The evidence provided in
this review, as well as that analyzed in more formal
meta-analyses, has shown improved neurologic outcomes with this therapy.117 This said, these results
are based on a relatively small number of patients.12
Thus, the criticism remains that the evidence upon
which this intervention is based is small and stems
mostly from a single study protocol that addressed
only one pathology, cardiac arrest from ventricular
fibrillation.
The second issue with therapeutic hypothermia
is its lack of generalizability. As mentioned above,
most of the evidence comes from a trial involving
patients with cardiac arrest with ventricular fibrillation. Only 8% of patients screened for inclusion in
the HACA trial were accepted.12 Because the data
come from such a limited sample, they may not be
applicable to individual practices, especially given
that cardiac arrest is a relatively rare event within
emergency medicine. Considering that this therapy
may be applied to only a few patients, the issue then
becomes cost and resource allocation. There certainly are low-cost ways to induce hypothermia, including use of ice and cold saline; however, some of the
available technologies are relatively expensive.
Emergency Medicine Practice © 2011
Summary
As with any new intervention, hypothermia therapy
may appear at first impression to be a time-intensive, labor-intensive, and resource-intensive undertaking that is beyond the scope and expectations of
most EDs. Most of the techniques described previously, however, are already part of emergency practice. Emergency medicine has seen a growth in both
16
EBMedicine.net • April 2011
run at approximately 100 mL per minute. After 15 minutes and 1700 mL of cold saline, the temperature probe
reading was 33.9°C (92°F), and the cooled saline infusion
was discontinued. During the induction phase, a triplelumen central venous catheter was placed under full sterile conditions with ultrasound guidance into the patient’s
right internal jugular vein. A sterile right radial arterial
line and orogastric and Foley catheters were placed. At
this point, the patient’s vital signs were pulse rate, 107
beats per minute; BP, 110/52 mm Hg (MAP, 71 mm Hg)
(norepinephrine infusion); respiratory rate, 21 breaths per
minute (greater than ventilator setting of 16); O2 saturation, 96% on 50% FiO2, and a temperature of 33.4°C
(92°F). An initial CVP reading from the central line gave
a value of 8 cm H2O, which is below the threshold for
volume resuscitation; however, a decision was made to
conduct several other investigations of the preload status.
On ultrasound examination, the IVC was measured at
1.3 cm and nearly reached full collapse upon administration of a pressurized ventilated breath. After a passive leg
raise technique was used, the patient’s MAP increased
slightly, as did the CVP. An ultrasound probe on the IVC
concomitantly showed an increase in diameter, with less
collapse upon pressurized ventilation. A 500-mL bolus
of normal saline was initiated, after which the patient’s
hemodynamic status improved, and his temperature was
well maintained at 32.9°C (91°F). Shivering was noted; a
fentanyl drip was started for sedation, and the shivering
stopped. After several hours in the ED, the patient was
moved to the ICU. After 24 hours of induced hypothermia, the patient was rewarmed. The machine was reset
at increasing temperatures of 0.5°C (1°F) over an hour.
When Mr. I.C. reached a temperature of 36°C (97°F), the
temperature blankets were removed, and sedation was
discontinued. The patient progressed well over the rest of
his hospital course. During the next several days, Mr. I.C.
regained consciousness, followed commands, and breathed
spontaneously. He was liberated from the ventilator on
day 3 of his hospital stay. On day 7, the patient was
discharged to home, having regained his baseline mental status and was without residual deficit. A 1-month
follow-up appointment found the patient continuing to
do well, having resumed most of his daily functions and
having returned to work.
the number of critically ill patients treated in the
ED and the duration of treatment pending critical
care bed availability, a development that has made
use of ventilator management, sterile central access,
sedation medications, and fluid resuscitation more
common. The only addition to established practice
required by induced hypothermia is performance
of these tasks while the patient is being cooled. The
only additional equipment required is the cooling
device itself. All of the other interventions are easily
set up using equipment that is already available; for
example, cold saline can be prepared ahead by simply refrigerating part of the department’s stock.
Unfamiliarity may be the greatest hurdle to use of
this therapy. Establishing a protocol similar to the
examples presented in this review to facilitate the
administration of the therapy is recommended. Any
plans and protocols for use should be discussed with
and agreed upon by other hospital staff who may
be involved in further care of the patient. A unified
and hospital-wide policy will help to smooth the
implementation of this new therapy and will likely
improve the outcomes.
Case Conclusion
Once the patient’s pulse was palpated, further investigation was undertaken. His first set of vitals included a
pulse rate of 121 beats per minute; BP, 87/41 mm Hg
(MAP, 53 mm Hg); respiratory rate, 12 breaths per minute (on ventilation); temperature, 36°C (97°F) (oral); and
O2 saturation, 98% on 100% FiO2 via the ventilator. An
initial ECG showed sinus tachycardia with significant Q
waves noted inferiorly. The chest radiograph showed mild
nonfocal congestion and no pneumothorax. A primary
survey showed no obvious trauma or prior surgical scars,
and the patient was unresponsive to deep sternal rub. Fluid therapy and an infusion of norepinephrine resulted in a
BP reading of 97/52 mm Hg (MAP, 67 mm Hg). On neurologic examination, the patient had no eye-opening and
decorticate motor response. The patient appeared to have
no pupil or corneal reflexes; however, doll’s eye sign was
present. The patient was being mechanically ventilated
at a rate of 12 breaths per minute, but he was noted to be
breathing at a rate of 16 to 18 breaths per minute (a noted
change from the initial set of vital signs). His deep tendon
reflexes were symmetric. A repeated physical examination
revealed slightly improved vital signs (less tachycardia,
but pressors still required to remain normotensive). No
other remarkable physical examination features were
noted. Mr. I.C. was rolled and placed between 2 cooling
blankets. The blankets are designed to go directly against
the skin, so there were no sheets or gowns covering him.
The blankets were assembled to the machine, and a probe
was placed in the patient’s esophagus; his core temperature was 36.4°C (97.5°F). Rapid cooling was facilitated
with an infusion of cold saline at 5.5°C (42°F). Two liters
of saline were placed in a pressure bag, and the fluid was
April 2011 • EBMedicine.net
References
Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references are
equally robust. The findings of a large, prospective,
randomized, and blinded trial should carry more
weight than a case report.
To help the reader judge the strength of each
reference, pertinent information about the study,
such as the type of study and the number of patients
in the study, will be included in bold type following
the reference, where available.
17
Emergency Medicine Practice © 2011
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
Guidelines for cardiopulmonary resuscitation and emergency cardiac care. Emergency Cardiac Care Committee and
Subcommittees, American Heart Association. Part I. Introduction. JAMA. 1992;268(16):2171-2183. (Practice guidelines)
ECC Committee, Subcommittees and Task Forces of the
American Heart Association. 2005 American Heart Association guidelines for cardiopulmonary resuscitation and
emergency cardiovascular care. Circulation. 2005;112(24
suppl):IV1-IV203. (Practice guidelines)
Chehardy P, Doherty A, Dracup K, et al. Cardiopulmonary
resuscitation and emergency cardiovascular care: education. Ann Emerg Med. 2001;37(4 suppl):S49-S59. (Practice
guidelines)
Negovsky VA. The second step in resuscitation--the treatment of the ‘post-resuscitation disease’. Resuscitation.
1972;1(1):1-7. (Review)
Neumar RW. Molecular mechanisms of ischemic neuronal
injury. Ann Emerg Med. 2000;36(5):483-506. (Review)
Dietrich WD, Busto R, Alonso O, et al. Intraischemic but
not postischemic brain hypothermia protects chronically
following global forebrain ischemia in rats. J Cereb Blood Flow
Metab. 1993;13(4):541-549. (Animal model)
Bolte RG, Black PG, Bowers RS, et al. The use of extracorporeal rewarming in a child submerged for 66 minutes. JAMA.
1988;260(3):377-379. (Case report)
Biggart MJ, Bohn DJ. Effect of hypothermia and cardiac
arrest on outcome of near-drowning accidents in children. J
Pediatr. 1990;117(2, pt 1):179-183. (Retrospective; 55 patients)
Tyndal CM Jr, Rose MW, McFalls RE, et al. Profound accidental hypothermia in the deep South: clinical experience.
Perfusion. 1996;11(1):57-60. (Case report)
Lund FK, Torgersen JG, Flaatten HK. Heart rate monitored
hypothermia and drowning in a 48-year-old man: survival
without sequelae: a case report. Cases J. 2009;2:6204. (Case
report)
Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after
cardiac arrest. N Engl J Med. 2002;346(8):549-556. (Prospective, randomized, controlled; 273 patients)
Nolan JP, Morley PT, Vanden Hoek TL, et al. Therapeutic hypothermia after cardiac arrest: an advisory statement by the
advanced life support task force of the International Liaison
Committee on Resuscitation. Circulation. 2003;108(1):118-121.
(Practice guideline)
Mechem CC, Goodloe JM, Richmond NJ, et al; U.S. Metropolitan Municipalities EMS Medical Directors Consortium.
Resuscitation center designation: recommendations for
emergency medical services practices. Prehosp Emerg Care.
2010;14(1):51-61. doi:10.3109/10903120903349804. (Review)
Polderman KH. Mechanisms of action, physiological effects,
and complications of hypothermia. Crit Care Med. 2009;37(7
suppl):S186-S202. (Review)
Bernard SA, Gray TW, Buist MD, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced
hypothermia. N Engl J Med. 2002;346(8):557-563. (Prospective, randomized, controlled; 77 patients)
Polderman KH, Herold I. Therapeutic hypothermia and
controlled normothermia in the intensive care unit: practical
considerations, side effects, and cooling methods. Crit Care
Med. 2009;37(3):1101-1120. (Review)
Liss HP. A history of resuscitation. Ann Emerg Med.
1986;15(1):65-72. (Review)
Varon J, Sternbach GL. Cardiopulmonary resuscitation: lessons from the past. J Emerg Med. 1991;9(6):503-507. (Review)
Varon J, Acosta P. Therapeutic hypothermia: past, present, and future. Chest. 2008;133(5):1267-1274. doi:10.1378/
chest.07-2190. (Review)
Castrén M, Silfvast T, Rubertsson S, et al. Scandinavian clinical practice guidelines for therapeutic hypothermia and postresuscitation care after cardiac arrest. Acta Anaesthesiol Scand.
Emergency Medicine Practice © 2011
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
18
2009;53(3):280-288. doi:10.1111/j.1399-6576.2008.01881.x.
(Practice guidelines)
Canadian Association of Emergency Physicians, CAEP
Critical Care Committee. Guidelines for the use of hypothermia after cardiac arrest. CJEM. 2006;8(2):106-108. (Practice
guidelines)
Australian Resuscitation Council. Adult advanced life
support: Australian Resuscitation Council guidelines 2006.
Emerg Med Australas. 2006;18(4):337-356. doi:10.1111/j.17426723.2006.00890.x. (Practice guidelines)
Peberdy MA, Callaway CW, Neumar RW, et al. Part 9:
post-cardiac arrest care: 2010 American Heart Association
Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010;122(18 Suppl
3):S768-86. doi: 10.1161/CIRCULATIONAHA.110.971002
(Practice guidelines)
Negovsky VA, Gurvitch AM. Post-resuscitation disease--a
new nosological entity: its reality and significance. Resuscitation. 1995;30(1):23-27. (Practice guidelines)
Opie LH. Reperfusion injury and its pharmacologic modification. Circulation. 1989;80(4):1049-1062. (Review)
Neumar RW, Nolan JP, Adrie C, et al. Postcardiac arrest
syndrome: epidemiology, pathophysiology, treatment, and
prognostication: a consensus statement from the International Liaison Committee on Resuscitation (American
Heart Association, Australian and New Zealand Council on
Resuscitation, European Resuscitation Council, Heart and
Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation Council of Asia, and the Resuscitation
Council of Southern Africa); the American Heart Association
Emergency Cardiovascular Care Committee; the Council on
Cardiovascular Surgery and Anesthesia; the Council on Cardiopulmonary, Perioperative, and Critical Care; the Council
on Clinical Cardiology; and the Stroke Council. Circulation.
2008;118(23):2452-2483. (Review, consensus statement)
Bano D, Nicotera P. Ca2+ signals and neuronal death in brain
ischemia. Stroke. 2007;38(2 suppl):674-676. doi:10.1161/01.
STR.0000256294.46009.29. (Review)
Lipton P. Ischemic cell death in brain neurons. Physiol Rev.
1999;79(4):1431-1568. (Review)
Ames A III, Wright RL, Kowada M, et al. Cerebral ischemia,
II: the no-reflow phenomenon. Am J Pathol. 1968;52(2):437453. (Animal model)
Böttiger BW, Krumnikl JJ, Gass P, et al. The cerebral ’noreflow’ phenomenon after cardiac arrest in rats--influence
of low-flow reperfusion. Resuscitation. 1997;34(1):79-87.
(Animal model)
Sundgreen C, Larsen FS, Herzog TM, et al. Autoregulation
of cerebral blood flow in patients resuscitated from cardiac
arrest. Stroke. 2001;32(1):128-132. (Prospective observational;
18 patients, 6 healthy controls)
Nishizawa H, Kudoh I. Cerebral autoregulation is impaired
in patients resuscitated after cardiac arrest. Acta Anaesthesiol
Scand. 1996;40(9):1149-1153. (Prospective observational; 8
patients)
Snyder JV, Nemoto EM, Carroll RG, et al. Global ischemia in
dogs: intracranial pressures, brain blood flow and metabolism. Stroke. 1975;6(1):21-27. (Animal model)
Rivers EP, Wortsman J, Rady MY, et al. The effect of the
total cumulative epinephrine dose administered during
human CPR on hemodynamic, oxygen transport, and
utilization variables in the postresuscitation period. Chest.
1994;106(5):1499-1507. (Prospective, nonrandomized, controlled trial of inception cohorts; 49 patients)
Prengel AW, Lindner KH, Ensinger H, et al. Plasma catecholamine concentrations after successful resuscitation
in patients. Crit Care Med. 1992;20(5):609-614. (Prospective
descriptive; 10 patients)
Kern KB. Postresuscitation myocardial dysfunction. Cardiol
Clin. 2002;20(1):89-101. (Review)
EBMedicine.net • April 2011
37. Kern KB, Hilwig RW, Berg RA, et al. Postresuscitation left
ventricular systolic and diastolic dysfunction: treatment with
dobutamine. Circulation. 1997;95(12):2610-2613. (Animal
model)
38. Laurent I, Monchi M, Chiche JD, et al. Reversible myocardial
dysfunction in survivors of out-of-hospital cardiac arrest. J
Am Coll Cardiol. 2002;40(12):2110-2116. (Prospective observational; 165 patients)
39. Kern KB, Hilwig RW, Rhee KH, et al. Myocardial dysfunction after resuscitation from cardiac arrest: an example of
global myocardial stunning. J Am Coll Cardiol. 1996;28(1):232240. (Animal model)
40. Gando S, Nanzaki S, Morimoto Y, et al. Out-of-hospital cardiac arrest increases soluble vascular endothelial adhesion
molecules and neutrophil elastase associated with endothelial injury. Intensive Care Med. 2000;26(1):38-44. (Prospective
observational; 44 patients, 8 healthy controls)
41. Geppert A, Zorn G, Karth GD, et al. Soluble selectins
and the systemic inflammatory response syndrome after
successful cardiopulmonary resuscitation. Crit Care Med.
2000;28(7):2360-2365. (Prospective observational; 25 patients, 7 controls)
42. Adrie C, Adib-Conquy M, Laurent I, et al. Successful cardiopulmonary resuscitation after cardiac arrest as a “sepsis-likeˮ
syndrome. Circulation. 2002;106(5):562-568. (Prospective
observational; 11 patients)
43. Böttiger BW, Motsch J, Böhrer H, et al. Activation of blood
coagulation after cardiac arrest is not balanced adequately
by activation of endogenous fibrinolysis. Circulation.
1995;92(9):2572-2578. (Prospective observational; 23 patients)
44. Wolfson SK Jr, Safar P, Reich H, et al. Dynamic heterogeneity
of cerebral hypoperfusion after prolonged cardiac arrest in
dogs measured by the stable xenon/CT technique: a preliminary study. Resuscitation. 1992;23(1):1-20. (Animal model)
45. Hékimian G, Baugnon T, Thuong M, et al. Cortisol levels and
adrenal reserve after successful cardiac arrest resuscitation.
Shock. 2004;22(2):116-119. (Prospective observational; 33
patients)
46. Xu L, Yenari MA, Steinberg GK, et al. Mild hypothermia reduces apoptosis of mouse neurons in vitro early
in the cascade. J Cereb Blood Flow Metab. 2002;22(1):21-28.
doi:10.1097/00004647-200201000-00003. (Animal model)
47. Adachi M, Sohma O, Tsuneishi S, et al. Combination effect
of systemic hypothermia and caspase inhibitor administration against hypoxic-ischemic brain damage in neonatal rats.
Pediatr Res. 2001;50(5):590-595. (Animal model)
48. Povlishock JT, Buki A, Koiziumi H, et al. Initiating mechanisms involved in the pathobiology of traumatically induced
axonal injury and interventions targeted at blunting their
progression. Acta Neurochir Suppl. 1999;73:15-20. (Animal
model)
49. Batista LM, Lima FO, Januzzi JL Jr, et al. Feasibility and
safety of combined percutaneous coronary intervention
and therapeutic hypothermia following cardiac arrest.
Resuscitation. 2010;81(4):398-403. doi:10.1016/j.resuscitation.2009.12.016. (Prospective observational; 90 patients)
50. Parham W, Edelstein K, Unger B, et al. Therapeutic hypothermia for acute myocardial infarction: past, present,
and future. Crit Care Med. 2009;37(7 suppl):S234-S237.
doi:10.1097/CCM.0b013e3181ab311d. (Review)
51. Ly HQ, Denault A, Dupuis J, et al. A pilot study: the Noninvasive Surface Cooling Thermoregulatory System for Mild
Hypothermia Induction in Acute Myocardial Infarction (the
NICAMI Study). Am Heart J. 2005;150(5):933. doi:10.1016/j.
ahj.2005.02.049. (Prospective observational; 90 patients)
52. Kandzari DE, Chu A, Brodie BR, et al. Feasibility of
endovascular cooling as an adjunct to primary percutaneous coronary intervention (results of the LOWTEMP pilot
study). Am J Cardiol. 2004;93(5):636-639. doi:10.1016/j.amj-
April 2011 • EBMedicine.net
card.2003.11.038. (Prospective observational; 18 patients)
53. Dixon SR, Whitbourn RJ, Dae MW, et al. Induction of mild
systemic hypothermia with endovascular cooling during
primary percutaneous coronary intervention for acute myocardial infarction. J Am Coll Cardiol. 2002;40(11):1928-1934.
(Randomized controlled; 42 patients)
54. Götberg M, Olivecrona GK, Koul S, et al. A pilot study of
rapid cooling by cold saline and endovascular cooling before
reperfusion in patients with ST-elevation myocardial infarction. Circ Cardiovasc Interv. 2010;3(5):400-407. doi:10.1161/
CIRCINTERVENTIONS.110.957902. (Randomized controlled; 20 patients)
55. Schefold JC, Storm C, Joerres A, et al. Mild therapeutic
hypothermia after cardiac arrest and the risk of bleeding
in patients with acute myocardial infarction. Int J Cardiol.
2009;132(3):387-391. doi:10.1016/j.ijcard.2007.12.008. (Prospective observational; 31 patients)
56. O’Connor RE, Brady W, Brooks SC, et al. Part 10: acute
coronary syndromes: 2010 American Heart Association
guidelines for cardiopulmonary resuscitation and emergency
cardiovascular care. Circulation. 2010;122(18 suppl 3):S787S817. doi:10.1161/CIRCULATIONAHA.110.971028. (Practice
guidelines)
57. Hovland A, Bjørnstad H, Hallstensen RF, et al. Massive
pulmonary embolism with cardiac arrest treated with continuous thrombolysis and concomitant hypothermia. Emerg
Med J. 2008;25(5):310-311. doi:10.1136/emj.2007.056390. (Case
report)
58. Komotar RJ, Zacharia BE, Mocco J, et al. Controversies in
the surgical treatment of ruptured intracranial aneurysms:
the First Annual J. Lawrence Pool Memorial Research
Symposium--controversies in the management of cerebral
aneurysms. Neurosurgery. 2008;62(2):396-407; discussion 405407. doi:10.1227/01.neu.0000316006.26635.b0. (Consensus
statement)
59. Fingas M, Clark DL, Colbourne F. The effects of selective
brain hypothermia on intracerebral hemorrhage in rats.
Exp Neurol. 2007;208(2):277-284. doi:10.1016/j.expneurol.2007.08.018. (Animal model)
60. Todd MM, Hindman BJ, Clarke WR, et al; Intraoperative
Hypothermia for Aneurysm Surgery Trial (IHAST) Investigators. Mild intraoperative hypothermia during surgery for
intracranial aneurysm. N Engl J Med. 2005;352(2):135-145.
doi:10.1056/NEJMoa040975. (Prospective, randomized,
controlled; 1001 patients)
61. Gasser S, Khan N, Yonekawa Y, et al. Long-term hypothermia in patients with severe brain edema after poor-grade
subarachnoid hemorrhage: feasibility and intensive care
complications. J Neurosurg Anesthesiol. 2003;15(3):240-248.
(Prospective controlled; 156 patients)
62. Seule MA, Muroi C, Mink S, et al. Therapeutic hypothermia
in patients with aneurysmal subarachnoid hemorrhage,
refractory intracranial hypertension, or cerebral vasospasm. Neurosurgery. 2009;64(1):86-92; discussion 92-93.
doi:10.1227/01.NEU.0000336312.32773.A0. (Retrospective
observational; 441 patients)
63. Adrie C, Laurent I, Monchi M, et al. Postresuscitation disease
after cardiac arrest: a sepsis-like syndrome? Curr Opin Crit
Care. 2004;10(3):208-212. (Review)
64. Polderman KH. Induced hypothermia and fever control for
prevention and treatment of neurological injuries. Lancet.
2008;371(9628):1955-1969. (Review)
65. Schwab S, Georgiadis D, Berrouschot J, et al. Feasibility and
safety of moderate hypothermia after massive hemispheric
infarction. Stroke. 2001;32(9):2033-2035. (Prospective observational; 50 patients)
66. Kurz A, Sessler DI, Lenhardt R. Perioperative normothermia to reduce the incidence of surgical-wound infection
and shorten hospitalization. Study of Wound Infection and
Temperature Group. N Engl J Med. 1996;334(19):1209-1215.
19
Emergency Medicine Practice © 2011
67.
68.
69.
70.
71.
72.
73.
74.
75.
76.
77.
78.
79.
80.
81.
82.
doi:10.1056/NEJM199605093341901. (Prospective, randomized, controlled; 200 patients)
Fischer E, Marano MA, Van Zee KJ, et al. Interleukin-1
receptor blockade improves survival and hemodynamic
performance in Escherichia coli septic shock, but fails to
alter host responses to sublethal endotoxemia. J Clin Invest.
1992;89(5):1551-1557. doi:10.1172/JCI115748. (Animal
model)
Ohlsson K, Björk P, Bergenfeldt M, et al. Interleukin-1 receptor antagonist reduces mortality from endotoxin shock. Nature. 1990;348(6301):550-552. doi:10.1038/348550a0. (Animal
model)
Tracey KJ, Fong Y, Hesse DG, et al. Anti-cachectin/
TNF monoclonal antibodies prevent septic shock during lethal bacteraemia. Nature. 1987;330(6149):662-664.
doi:10.1038/330662a0. (Animal model)
Beutler B, Milsark IW, Cerami AC. Passive immunization
against cachectin/tumor necrosis factor protects mice from
lethal effect of endotoxin. Science. 1985;229(4716):869-871.
(Animal model)
van der Poll T, Opal SM. Host-pathogen interactions in
sepsis. Lancet Infect Dis. 2008;8(1):32-43. doi:10.1016/S14733099(07)70265-7. (Review)
Eichacker PQ, Parent C, Kalil A, et al. Risk and the efficacy
of antiinflammatory agents: retrospective and confirmatory
studies of sepsis. Am J Respir Crit Care Med. 2002;166(9):11971205. (Meta-analysis)
Kuboyama K, Safar P, Radovsky A, et al. Delay in cooling
negates the beneficial effect of mild resuscitative cerebral
hypothermia after cardiac arrest in dogs: a prospective, randomized study. Crit Care Med. 1993;21(9):1348-1358. (Animal
model)
Arrich J; European Resuscitation Council Hypothermia
After Cardiac Arrest Registry Study Group. Clinical application of mild therapeutic hypothermia after cardiac
arrest. Crit Care Med. 2007;35(4):1041-1047. doi:10.1097/01.
CCM.0000259383.48324.35. (Practice guidelines)
Sunde K, Pytte M, Jacobsen D, et al. Implementation of
a standardised treatment protocol for post resuscitation
care after out-of-hospital cardiac arrest. Resuscitation.
2007;73(1):29-39. (Prospective interventional; 119 patients)
Busch M, Soreide E, Lossius HM, et al. Rapid implementation of therapeutic hypothermia in comatose out-ofhospital cardiac arrest survivors. Acta Anaesthesiol Scand.
2006;50(10):1277-1283. doi:10.1111/j.1399-6576.2006.01147.x.
(Prospective interventional; 27 patients)
Holzer M, Müllner M, Sterz F, et al. Efficacy and safety
of endovascular cooling after cardiac arrest: cohort study
and Bayesian approach. Stroke. 2006;37(7):1792-1797.
doi:10.1161/01.STR.0000227265.52763.16. (Retrospective
cohort; 1038)
Oddo M, Schaller MD, Feihl F, et al. From evidence to
clinical practice: effective implementation of therapeutic
hypothermia to improve patient outcome after cardiac arrest.
Crit Care Med. 2006;34(7):1865-1873. (Retrospective cohort;
109 patients)
Bernard SA, Jones BM, Horne MK. Clinical trial of induced
hypothermia in comatose survivors of out-of-hospital cardiac arrest. Ann Emerg Med. 1997;30(2):146-153. (Prospective
interventional; 22 patients)
Rittenberger JC, Sangl J, Wheeler M, et al. Association between clinical examination and outcome after cardiac arrest.
Resuscitation. 2010;81(9):1128-1132. doi:10.1016/j.resuscitation.2010.05.011. (Retrospective; 272 patients)
Valeri CR, MacGregor H, Cassidy G, et al. Effects of temperature on bleeding time and clotting time in normal male
and female volunteers. Crit Care Med. 1995;23(4):698-704.
(Prospective observation; 54 patients)
Valeri CR, Feingold H, Cassidy G, et al. Hypothermiainduced reversible platelet dysfunction. Ann Surg.
Emergency Medicine Practice © 2011
1987;205(2):175-181. (Animal model)
83. Ying CL, Tsang SF, Ng KF. The potential use of desmopressin to correct hypothermia-induced impairment of primary
haemostasis--an in vitro study using PFA-100. Resuscitation.
2008;76(1):129-133. doi:10.1016/j.resuscitation.2007.07.009.
(Bench research)
84. Tortorici MA, Kochanek PM, Poloyac SM. Effects of hypothermia on drug disposition, metabolism, and response: a focus of hypothermia-mediated alterations on the cytochrome
P450 enzyme system. Crit Care Med. 2007;35(9):2196-2204.
(Review)
85. Lewis ME, Al-Khalidi AH, Townend JN, et al. The effects of
hypothermia on human left ventricular contractile function
during cardiac surgery. J Am Coll Cardiol. 2002;39(1):102-108.
(Prospective observational; 10 patients)
86. Mattheussen M, Mubagwa K, Van Aken H, et al. Interaction
of heart rate and hypothermia on global myocardial contraction of the isolated rabbit heart. Anesth Analg. 1996;82(5):975981. (Animal model)
87. Castrén M, Nordberg P, Svensson L, et al. Intra-arrest
transnasal evaporative cooling: a randomized, prehospital,
multicenter study (PRINCE: Pre-ROSC IntraNasal Cooling
Effectiveness). Circulation. 2010;122(7):729-736. doi:10.1161/
CIRCULATIONAHA.109.931691. (Prospective, randomized,
controlled; 194 patients)
88. Larsson IM, Wallin E, Rubertsson S. Cold saline infusion and
ice packs alone are effective in inducing and maintaining
therapeutic hypothermia after cardiac arrest. Resuscitation.
2010;81(1):15-19. doi:10.1016/j.resuscitation.2009.09.012.
(Prospective interventional; 38 patients)
89. Merchant RM, Abella BS, Peberdy MA, et al. Therapeutic hypothermia after cardiac arrest: unintentional overcooling is
common using ice packs and conventional cooling blankets.
Crit Care Med. 2006;34(12 suppl):S490-S494. doi:10.1097/01.
CCM.0000246016.28679.36. (Prospective observational; 32
patients)
90. Kämäräinen A, Virkkunen I, Tenhunen J, et al. Induction
of therapeutic hypothermia during prehospital CPR using
ice-cold intravenous fluid. Resuscitation. 2008;79(2):205-211.
doi:10.1016/j.resuscitation.2008.07.003. (Prospective interventional; 17 patients)
91. Prunet B, Lacroix G, Bordes J, et al. Catheter related venous
thrombosis with cooling and warming catheters: two case
reports. Cases J. 2009;2:8857. doi:10.1186/1757-1626-00020000008857. (Case report)
92. Simosa HF, Petersen DJ, Agarwal SK, et al. Increased risk
of deep venous thrombosis with endovascular cooling in
patients with traumatic head injury. Am Surg. 2007;73(5):461464. (Retrospective cohort; 11 patients)
93. Inderbitzen B, Yon S, Lasheras J, et al. Safety and performance of a novel intravascular catheter for induction and
reversal of hypothermia in a porcine model. Neurosurgery.
2002;50(2):364-370. (Animal model)
94. Polderman KH, Rijnsburger ER, Peerdeman SM, et al.
Induction of hypothermia in patients with various types of
neurologic injury with use of large volumes of ice-cold intravenous fluid. Crit Care Med. 2005;33(12):2744-2751. (Prospective interventional; 134 patients)
95. Virkkunen I, Yli-Hankala A, Silfvast T. Induction of
therapeutic hypothermia after cardiac arrest in prehospital patients using ice-cold Ringerʼs solution: a pilot study.
Resuscitation. 2004;62(3):299-302. doi:10.1016/j.resuscitation.2004.04.003. (Prospective observational; 13 patients)
96. Bernard S, Buist M, Monteiro O, et al. Induced hypothermia
using large volume, ice-cold intravenous fluid in comatose
survivors of out-of-hospital cardiac arrest: a preliminary
report. Resuscitation. 2003;56(1):9-13. (Prospective interventional; 22 patients)
97. Rajek A, Greif R, Sessler DI, et al. Core cooling by central
venous infusion of ice-cold (4 degrees C and 20 degrees
20
EBMedicine.net • April 2011
C) fluid: isolation of core and peripheral thermal compartments. Anesthesiology. 2000;93(3):629-637. (Prospective
observational; 18 patients)
98. Dellinger RP, Levy MM, Carlet JM, et al. Surviving Sepsis Campaign: international guidelines for
management of severe sepsis and septic shock: 2008.
Crit Care Med. 2008;36(1):296-327. doi:10.1097/01.
CCM.0000298158.12101.41. (Practice guidelines)
99. De Backer D, Biston P, Devriendt J, et al. Comparison of
dopamine and norepinephrine in the treatment of shock.
N Engl J Med. 2010;362(9):779-789. doi:10.1056/NEJMoa0907118. (Prospective, randomized, controlled; 1679
patients)
100. Rivers E, Nguyen B, Havstad S, et al. Early goal-directed
therapy in the treatment of severe sepsis and septic shock.
N Engl J Med. 2001;345(19):1368-1377. doi:10.1056/NEJMoa010307. (Prospective, randomized, controlled; 263
patients)
101. Jain RK, Antonio BL, Bowton DL, et al. Variability in central
venous pressure measurements and the potential impact on
fluid management. Shock. 2010;33(3):253-257. doi:10.1097/
SHK.0b013e3181b2bb22. (Prospective observational; 100
patients)
102. Otero RM, Nguyen HB, Huang DT, et al. Early goal-directed
therapy in severe sepsis and septic shock revisited: concepts, controversies, and contemporary findings. Chest.
2006;130(5):1579-1595. doi:10.1378/chest.130.5.1579. (Review)
103. Keller AS, Melamed R, Malinchoc M, et al. Diagnostic accuracy of a simple ultrasound measurement to estimate central
venous pressure in spontaneously breathing, critically ill
patients. J Hosp Med. 2009;4(6):350-355. doi: 10.1002/jhm.503.
(Prospective observational; 63 patients)
104. Muller L, Louart G, Bousquet PJ, et al. The influence of
the airway driving pressure on pulsed pressure variation
as a predictor of fluid responsiveness. Intensive Care Med.
2010;36(3):496-503. doi:10.1007/s00134-009-1686-y. (Prospective interventional; 57 patients)
105. Perner A, Haase N, Wiis J, et al. Central venous oxygen
saturation for the diagnosis of low cardiac output in septic
shock patients. Acta Anaesthesiol Scand. 2010;54(1):98-102.
doi:10.1111/j.1399-6576.2009.02086.x. (Prospective observational; 56 patients)
106. Weinbroum AA, Biderman P, Soffer D, et al. Reliability of
cardiac output calculation by the fick principle and central
venous oxygen saturation in emergency conditions. J Clin
Monit Comput. 2008;22(5):361-366. doi:10.1007/s10877-0089143-y. (Prospective observational; 15 patients)
107. Jones AE, Shapiro NI, Trzeciak S, et al. Lactate clearance vs
central venous oxygen saturation as goals of early sepsis
therapy: a randomized clinical trial. JAMA. 2010;303(8):739746. doi:10.1001/jama.2010.158. (Prospective, randomized,
controlled; 300 patients)
108. Lopez M, Sessler DI, Walter K, et al. Rate and gender dependence of the sweating, vasoconstriction, and shivering
thresholds in humans. Anesthesiology. 1994;80(4):780-788.
(Prospective interventional; 16 patients)
109. Leslie K, Sessler DI. Perioperative hypothermia in the
high-risk surgical patient. Best Pract Res Clin Anaesthesiol.
2003;17(4):485-498. (Review)
110. De Witte J, Sessler DI. Perioperative shivering: physiology and pharmacology. Anesthesiology. 2002;96(2):467-484.
(Review)
111. Chamorro C, Borrallo JM, Romera MA, et al. Anesthesia
and analgesia protocol during therapeutic hypothermia
after cardiac arrest: a systematic review. Anesth Analg.
2010;110(5):1328-1335. doi:10.1213/ANE.0b013e3181d8cacf.
(Systematic review)
112. Wadhwa A, Sengupta P, Durrani J, et al. Magnesium
sulphate only slightly reduces the shivering threshold in
April 2011 • EBMedicine.net
humans. Br J Anaesth. 2005;94(6):756-762. doi:10.1093/bja/
aei105. (Prospective, randomized, controlled; 9 patients)
113. Zweifler RM, Voorhees ME, Mahmood MA, et al. Magnesium sulfate increases the rate of hypothermia via surface
cooling and improves comfort. Stroke. 2004;35(10):2331-2334.
doi:10.1161/01.STR.0000141161.63181.f1. (Prospective interventional; 22 patients)
114. Kimberger O, Ali SZ, Markstaller M, et al. Meperidine and
skin surface warming additively reduce the shivering threshold: a volunteer study. Crit Care. 2007;11(1):R29. doi:10.1186/
cc5709. (Prospective interventional; 80 patients)
115. Matsukawa T, Kurz A, Sessler DI, et al. Propofol linearly
reduces the vasoconstriction and shivering thresholds. Anesthesiology. 1995;82(5):1169-1180. (Prospective interventional;
5 patients)
116. Talke P, Tayefeh F, Sessler DI, et al. Dexmedetomidine does
not alter the sweating threshold, but comparably and linearly decreases the vasoconstriction and shivering thresholds.
Anesthesiology. 1997;87(4):835-841. (Prospective, randomized,
interventional; 9 patients)
117. Cheung KW, Green RS, Magee KD. Systematic review of
randomized controlled trials of therapeutic hypothermia
as a neuroprotectant in post cardiac arrest patients. CJEM.
2006;8(5):329-337. (Systematic review)
118. Lavinio A, Timofeev I, Nortje J, et al. Cerebrovascular
reactivity during hypothermia and rewarming. Br J Anaesth.
2007;99(2):237-244. doi:10.1093/bja/aem118. (Prospective
observational; 118 patients)
119. Alam HB, Rhee P, Honma K, et al. Does the rate of rewarming from profound hypothermic arrest influence the
outcome in a swine model of lethal hemorrhage? J Trauma.
2006;60(1):134-146. doi:10.1097/01.ta.0000198469.95292.ec.
(Animal model)
120. Maxwell WL, Watson A, Queen R, et al. Slow, medium, or
fast re-warming following post-traumatic hypothermia
therapy? An ultrastructural perspective. J Neurotrauma.
2005;22(8):873-884. doi:10.1089/neu.2005.22.873. (Animal
model)
121. Kawahara F, Kadoi Y, Saito S, et al. Slow rewarming improves jugular venous oxygen saturation during rewarming.
Acta Anaesthesiol Scand. 2003;47(4):419-424. (Prospective,
randomized, controlled; 100 patients)
122. Polderman KH, Peerdeman SM, Girbes AR. Hypophosphatemia and hypomagnesemia induced by cooling in patients
with severe head injury. J Neurosurg. 2001;94(5):697-705.
doi:10.3171/jns.2001.94.5.0697. (Prospective observational;
41 patients)
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Emergency Medicine Practice © 2011
1. Emergency medical services are critical in the
care of a patient with an out-of-hospital cardiac
arrest. They also contribute to hypothermia
therapy in all of the following ways EXCEPT:
a. Administering cooled saline by placing ice packs to start the cooling process
b. Documenting the time frame of arrest as well as the presenting rhythms
c. Controlling the patient’s airway with intubation
d. Administering paralytic agents to treat shivering
4. Cardiac arrhythmias always require intervention.
a. True
b. False
5. The ideal placement for the temperature probe
of common commercial cooling systems is
where changes in core temperature can be
sensed most quickly. What is the best anatomic
location for probe placement?
a. Rectum
b. Axilla
c. Oropharynx
d. Esophagus
e. Forehead
2. A patient is transported to the ED in cardiac
arrest. Compressions have been in progress for
approximately 15 minutes, starting immediately after EMS arrival. Return of spontaneous
circulation is soon attained, and the patient
is comatose, with a GCS score of 3. The first
blood pressure reading is 64/22 mm Hg by arterial line. Pressors are initiated; however, after
several liters of fluid, high-dose norepinephrine, and a vasopressin drip, the patient’s MAP
is 55 mm Hg. Therapeutic hypothermia should
not be initiated for which of the following
reasons?
a. The patient’s initial GCS score is a negative prognostic sign so soon after ROSC.
b. Multiple vasopressors have failed to maintain a MAP greater than 65 mm Hg.
c. The time from arrest to initiation of compressions cannot be established.
d. The patient has an arterial line that may be a significant source of bleeding during cooling.
e. The etiology of the arrest cannot be determined.
6. Which of the following procedures are contraindicated during therapeutic hypothermia?
a. Arterial line placement
b. Central venous catheter placement
c. Thoracostomy
d. Lumbar puncture
e. None of the above
7. Although most common during the induction
phase, shivering is possible during any period
of therapeutic hypothermia.
a. True
b. False
8. Which of the following medications is effective at mitigating or terminating the shivering
response?
a. Magnesium
b. Meperidine
c. Fentanyl
d. Propofol
e. All of the above
3. Which of the following statements best describes alterations in blood gas readings caused
by measurements at lower temperatures?
a. The partial pressure of O2 will be falsely elevated, while the partial pressure of CO2 will be given accurately secondary to the decrease in overall metabolism.
b. The partial pressure values will be falsely elevated by 5 mm Hg for every 1°C below 37°C.
c. The partial pressure of CO2 will be falsely elevated, while the partial pressure of O2 will be given accurately secondary to the decrease in overall metabolism.
d. The partial pressure values will be falsely elevated by 20 mm Hg for every 1°C below 37°C.
e. All blood gas readings are accurate when reported at normal temperatures and do not require any correction.
Emergency Medicine Practice © 2011
9. All of the following statements regarding the
rewarming process are true EXCEPT:
a. Passive rewarming is allowed once the patient’s temperature has reached 36°C (97°F).
b. Rewarming may cause massive shifts of potassium out of cells, creating a dangerous level of hyperkalemia.
c. Rewarming must take place at the relatively slow pace of no more than 1°C (2°F) per hour.
d. After rewarming, hyperthermia poses no risk to the patient as he or she has already been exposed to the protective effects of the therapy.
22
EBMedicine.net • April 2011
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Emergency Medicine Practice © 2011
Physician CME Information
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Emergency Medicine Practice © 2011
24
EBMedicine.net • April 2011
Pt Name:
MSSM ED Critical Care
Induced Hypothermia Protocol
Date:
Time of Screening:
:
MRN:
Place Sticker
Your Name:
Inclusion Criteria (Must have All)
Exclusion Criteria
� Post Cardiac Arrest (Any rhythm as cause of arrest is eligible)
� ROSC < 30 min from EMS/Code Team Arrival
� Time now <6 hrs from ROSC
� Comatose (Does not follow commands)
� MAP > 65 on no more than one vasopressor
� Pt has DNR, MOLST, poor baseline status, or terminal disease
� Active or Intracranial Bleeding
� Traumatic etiology for arrest
� Cryoglobulinemia
� Pregnancy (Relative-Consider OB/Gyn consult)
� Recent Major Surgery (Relative)
� Severe Sepsis/Septic Shock as cause of Arrest (Relative)
Neurologic Exam
Eye Opening
Spontaneous --------*� 4
Voice ----------------- � 3
Pain ------------------ � 2
None ----------------- � 1
Verbal
Motor
Oriented -------------*� 5 Obeys ----------------*� 6
Confused ------------*� 4 Localizes ------------ � 5
Inappropriate ------- � 3 Withdraws ---------- � 4
Sounds --------------- � 2 Decorticate ---------- � 3
None ----------------- � 1 Decerebrate --------- � 2
Intubated ------------ � 1 None ----------------- � 1
DTRs:
Bicep L
R
Knee L
R
List any Sedatives or Paralytics On-Board at time of Exam:
Brainstem
Pupils React
Corneal
Spont. Resps
Doll’s Eyes
Toes
L
� yes � no
� yes � no
� yes � no
� yes � no
R
If any Starred (*) Item is checked off on the neuro exam, the patient is ineligible for the protocol.
Protocol
•If there is a question regarding eligibility, discuss Case with the ICU Fellow or Attending
:
•Time of Discussion:
If pt is deemed ineligible by ICU, list reason:
•List Initial Arrest Rhythm:
List Number of Minutes from Start of CPR to ROSC:
•Send blood for: CMP, LFTs, Superstat I, Lactate, CBC, PT/PTT, CK/MB/Troponin, Lipase/Amylase
•Completely expose patient and place cooling blanket above and below with nothing between blanket & skin.
•Place temp probe in mid-esophagus (~4 cm above xiphoid via oral/nasal); if unable to place in esophagus, probe can be placed rectally (5 cm)
•Hook both cooling blankets and the probe to the same blanketrol machine.
•Set temperature to 33º C and Set the machine to “Auto Control”.
:
List Initial Patient Temperature:
°C
•List time Now (Starting Protocol):
•If initial temperature is < 33º C, allow patient to warm to 33º C.
•Begin opioids & sedation protocol (See page 3). Titrate to RASS Score -3/-4 (Ramsay Score 4/5 in the ICU).
•Infuse refrigerated crystalloid, preferably through large bore, peripheral IV.
Administer at ~100 ml per minute using pressure bag (evacuate air first). Maximum initial infusion is 30 cc/kg;
if patient not < 34º C after this amount, wait 15 minutes before giving further 250 cc boluses Q 10 minutes.
•Administer Tylenol 650 mg GT Q 6 hours unless pt has allergy.
•If during induction, pt has shivering unrelieved by the above meds, Vecuronium 0.1 mg/kg x1 can be used
:
•Total Cold Crystalloid Infused:
Time that Pt reaches 34º C:
•If patient’s temperature rises above 34º C, infuse 250 cc boluses of cold crystalloid Q 10 min until <34º C.
•Assess for shivering Q 15 minutes. If any signs of shivering, see the protocol on page 5.
•Maintain temperature 32-34º C for 24 hours (ideal temperature is 33º C).
•If significant bleeding or severe hemodynamic instability, consider rewarming. See ehced.org for protocol.
:
•Time of Rewarming:
Reason Necessary:
•Maintain MAP>80: Multiple Pressors and/or Dobutamine may be used during protocol, if fluid loading ineffective.
Protocol provided by Scott D. Weingart, MD FACEP; Director, Division of ED Critical Care, Mount Sinai School of Medicine, New York, NY. Protected by Creative
Commons BY-NC-SA 3.0 license. This protocol is for informational purposes only; check all recommendations and adapt to your individual institution.
4/3/09
Scan this worksheet when pt’s bed is ready and Give Original to ICU Resident
MSSM ED Critical Care
Post-ROSC Care Package
Induction of Hypothermia
See First Page
Procedures
•
•
•
•
Full sterile neck line with CVP monitoring
Full sterile femoral arterial line (Axillary if femoral contraindicated/unsuccessful)
Foley Catheter with hourly urine monitoring
Orogastric Tube on suction
Ventilation
•
•
•
•
•
•
•
•
Place patient on AC Mode
Set Vt to 8 ml/kg Ideal Body Weight (see last page)
Set IFR to 60 lpm
Set Initial rate to 18 bpm
Set Initial O2 to 50%
Titrate FiO2/PEEP to achieve corrected ABG Saturation 94-96%.
Often pulse ox will not read well due to peripheral vasoconstriction
Send an ABG, DO NOT INDICATE THE PATIENT’S TEMPERATURE ON THE ABG ORDER
Hemodynamic Goals
• Ensure Adequate Preload
Assess by passive leg raise, pulse pressure variation, and echo. CVP may provide some indication if very low. Use
normal saline, lactated ringers, or isolyte boluses. Use room temperature fluid if patient at goal temperature.
Replace patient’s urine losses 1:1
• MAP > 65 at all times, MAP > 80 is preferred to augment cerebral perfusion
Preferred initial pressor is norepinephrine, may add vasopressin if necessary
If MAP is < 80 and CVP > 10 perform passive straight leg raise to assess fluid responsiveness.
If MAP > 100, start nitroglycerin infusion
• Corrected ScvO2 > 70
Can be measured by PreSEP catheter or central venous O2 saturation (send blood gas as mixed venous)
If ScvO2 < 70 and HB < 7 (some would advocate <10 as trigger), transfuse patient
If HB > 7, evaluate echocardiogram and consider inotropes vs. balloon pump/revascularization
• Lactate
Hypothermia will raise lactate levels and post-arrest patients will have high lactate. Send a baseline level after
the patient achieves goal temperature. From this point on, the lactate should stay the same or drop. If lactate is
increasing, the patient is under-resuscitated or seizing
Cardiac Testing
• Get EKG immediately upon arrival; at the start of hypothermia induction; and Q 1 hour for the first 4 hours
• If possible, get a bedside transthoracic echo at the start of induction. In the ED, this should be performed by the
emergency physician or cardiology. Look specifically for qualitative LV function, RV function, pericardial effusion/
tamponade, & gross valve function
Protocol provided by Scott D. Weingart, MD FACEP; Director, Division of ED Critical Care, Mount Sinai School of Medicine, New York, NY. Protected by Creative Commons
BY-NC-SA 3.0 license. This protocol is for informational purposes only; check all recommendations and adapt to your individual institution.
2
MSSM ED Critical Care
Post-ROSC Care Package
Sedation & Pain Control
•
•
•
•
To gain the full benefits of hypothermia, it is imperative that the patient is adequately sedated
Optimize fentanyl infusion rate first
Add on propofol or dexmedetomidine if necessary
Titrate to RASS Score -3/-4 (Ramsay Score of 4/5 if in the ICU)
Richmond Agitation Sedation Scale (RASS) *
Richmond Agitation Sedation Scale (RASS)
Score Term
Description
+4
Combative
Overtly combative, violent, immediate danger to staff
+3
Very agitated
Pulls or removes tube(s) or catheter(s); aggressive
+2
Agitated
Frequent non-purposeful movement, fights ventilator
+1
Restless
Anxious but movements not aggressive vigorous
0
Alert and calm
-1
Drowsy
Not fully alert, but has sustained awakening
(eye-opening/eye contact) to voice (>10 seconds)
-2
Light sedation
Briefly awakens with eye contact to voice (<10 seconds)
-3
Moderate sedation
Movement or eye opening to voice (but no eye contact)
-4
Deep sedation
No response to voice, but movement or eye opening
to physical stimulation
-5
Unarousable
No response to voice or physical stimulation
Verbal
Stimulation
Physical
Stimulation
Procedure for RASS Assessment
Labs1. &Observe
Electrolytes
patient
•
•
•
•
•
•
•
•
•
Send Superstat
(ABGrestless,
with Electrolytes)
4 hours,
a. Patient isI alert,
or agitated. and Lactate Q 1 hour for first
(score
0 to +4)then Q 4 hours
On2.arrival,
send state
CMP,patient’s
CBC, Lytes,
Lipase,
Cardiac
Enzymes,
Type and Hold, & Pan-Cultures
If not alert,
namePT/PTT,
and say to
open eyes
and look
at speaker.
Send CMP (complete metabolic panel) and CBC Q 4 hours
b. Patient awakens with sustained eye opening and eye contact.
(score –1)
Send Cardiac Enzymes Q 6 hours
Patient awakens
with eye opening
eyewith
contact,
but not sustained.
(score –2)
Keep c.
Magnesium
at high-normal
at alland
times
aggressive
IV repletion
Replete
Potassium
if <movement
3.4 with IV
KCl
d. Patient
has any
in response
to voice but no eye contact.
(score –3)
Keep
iCal
at
high
normal
at
all
times
3. When no response to verbal stimulation, physically stimulate patient by
Keep shaking
Sodiumshoulder
at least and/or
140 atrubbing
all times,
150 is preferable
sternum.
Keep e.
Glucose
<
150
with
Insulin
Drip
(preferred)
or Subcutaneous Regular
Insulin
Patient has any movement to physical stimulation.
(score –4)
(score –5)
f. Patient has no response to any stimulation.
DVT Prophylaxis
• If no contraindication, Heparin 5000 units subcutaneous Q 8 hours
* Sessler CN, Gosnell M, Grap MJ, Brophy GT, O'Neal PV, Keane KA et al. The Richmond AgitationStress
Ulcer
Sedation
Scale: Prophylaxis
validity and reliability in adult intensive care patients. Am J Respir Crit Care Med 2002;
166:1338-1344.
• Nexium
40 mg IVSS x 1
* Ely EW, Truman B, Shintani A, Thomason JWW, Wheeler AP, Gordon S et al. Monitoring sedation status
over time in ICU patients: the reliability and validity of the Richmond Agitation Sedation Scale (RASS).
VAP Prophylaxis
JAMA 2003; 289:2983-2991.
• Head of bed to 30°
• Place in-line closed suction and perform aggressive pulmonary toilet
Protocol provided by Scott D. Weingart, MD FACEP; Director, Division of ED Critical Care, Mount Sinai School of Medicine, New York, NY. Protected by Creative Commons
BY-NC-SA 3.0 license. This protocol is for informational purposes only; check all recommendations and adapt to your individual institution.
3
MSSM ED Critical Care
Post-ROSC Care Package
Additional Testing
• Consider Head CT if possible neurologic cause to arrest. Note: even an intracranial bleed is not a contra-indication to
continuation of induced hypothermia. Consider letting the patient drift to 34°C and administration of dDAVP.
• If there is a question of brain death, consider a CTA of the brain to assess for flow.
• Consider CTA Chest if there is a strong suspicion of PE as the cause of arrest. Bedside dopplers by EP or sono
technician may be a good first step
• EEG if seizures (convulsive or non-convulsive) are suspected
Revascularization for STEMI
• PCI is preferred, consult with CPORT fellow/attending and CCU fellow. Hypothermia does not need to be
discontinued for PCI.
• If PCI is not available or will be delayed, thrombolysis should be administered. Thrombolysis can be given during
hypothermia. CPR performed prior to ROSC should not stop reperfusion therapy. Use standard doses of Retevase.
Consult with CPORT fellow/attending.
Transport to radiology or ICU
• Disconnect the hypothermia machine and leave the blankets and temperature probe in place.
• If the patient returns to the ED, hook the machine back up.
• If the patient’s temperture is >34.5, infuse 250 cc boluses of cold crystalloid Q 10 min until <34° C
Protocol provided by Scott D. Weingart, MD FACEP; Director, Division of ED Critical Care, Mount Sinai School of Medicine, New York, NY. Protected by Creative Commons
BY-NC-SA 3.0 license. This protocol is for informational purposes only; check all recommendations and adapt to your individual institution.
4