2.4. Bases filosóficas
2.4.1. Bases epistemológicas:
T E D DY S . YOU N
Our preliminary observations suggest that treatment with moderate hypothermia appears to improve outcomes in patients with coma after resuscitation from out- of- hospital arrest.
— Bernard et al.1
Research Question: Does moderate hypothermia (33°C) in patients who
remain unconscious after resuscitation from out- of- hospital cardiac arrest within 2 hours after the return of spontaneous circulation improve neurologic outcome?1
Funding: None noted. Year Study Began: 1996 Year Study Published: 2002
Study Location: Four participating hospitals (both in the emergency depart-
N E U R O C R I T I C A l C A R E 130
Who Was Studied: Patients with an initial cardiac rhythm of ventricular fibril-
lation (VF) at the time of arrival of the ambulance, successful return of spon- taneous circulation (ROSC), persistent coma after ROSC, and transfer to 1 of 4 participating emergency departments.
Who Was Excluded: Patients aged <18 years (men) or <50 years (women,
to exclude the possibility of pregnancy), patients who had cardiogenic shock (a systolic blood pressure <90 mm Hg despite epinephrine infusion), or possi- ble causes of coma other than cardiac arrest (i.e., drug overdose, head trauma, or stroke). Patients were also excluded if an ICU bed was not available at the participating hospital.
How Many Patients: 77
Study Overview: See Figure 19.1 for a summary of the study design.
Study Intervention: Patients in the hypothermia group underwent vigor-
ous cooling once in the emergency department with extensive application of ice packs around the head, neck, torso, and limbs until they reached a core temperature of 33°C. The patients were sedated and paralyzed with small doses of midazolam and vecuronium. At hour 18, they were actively rewarmed by external warming using a heated air blanket with continu- ous sedation and paralytic to suppress shivering. Patients assigned to nor- mothermia were initially sedated and paralyzed; however, they did not receive any further dosing once they reached the target core temperature of 37°C. Passive rewarming was only used if there was mild spontaneous hypothermia.
Upon arrival in emergency department patients, cardiac arrest patients were enrolled in the
hypothermia protocol on odd-numbered days, and the normothermia protocol on
even-numbered days. Treated for 24 hours
Hypothermia Protocol (33°C); followed by active rewarming over 6 hours at 18
hours from time of cardiac arrest
Normothermia Protocol (~37°C)
Therapeutic Hypothermia for Cardiac Arrest, Part II 131
Follow- Up: Assessment by a rehabilitation medicine specialist at the time of
discharge from the hospital.
Endpoints: Primary outcomes: neurologic outcome at discharge from the hos-
pital. Secondary outcomes: hemodynamic/ physiological, biochemical, hema- tologic values of hypothermia.
RESULTS
• At the time of discharge, 21 of 43 patients in the hypothermia group (49%) were considered to have a good outcome (discharge to home or to a rehabilitation facility), versus 9 of 34 patients in the normothermia group (26%), P = 0.046, 95% confidence interval (CI),
13%– 43% (see Table 19.1).
• The unadjusted odds ratio for a good outcome in the hypothermia group as compared with the normothermia group was 2.65 (95% CI range, 1.02– 6.88; P = 0.046). After adjustment for baseline differences
in age and time from collapse to return of spontaneous circulation, the odds ratio improved to 5.25 (95% CI range, 1.47– 18.76; P = 0.011).
• There was no difference in the frequency of adverse events.
• There was no significant difference in hemodynamic, biochemical, or hematological values between the two arms, except for a lower cardiac index and hyperglycemia.
Table 19.1. Outcome of Patients at Discharge from the Hospital
Outcome Hypothermia %
(n = 43)
Normothermia % (n = 34)
Normal or minimal disability (able to
care for self, discharged to home) 34.9 20.6 Moderate disability (discharged to a
rehabilitation facility) 14.0 6.0 Severe disability, awake but completely
dependent (discharged to a long- term nursing facility)
0 2.9
Severe disability, unconscious (discharged to a long- term nursing facility)
0 2.9
N E U R O C R I T I C A l C A R E 132
Criticisms and Limitations: For this study, several limitations existed. First,
it was a much smaller sample size than the HACA trial.2 The definition of
coma for the study was never defined. Interestingly, the study was not a true randomization. Instead, study coordinators enrolled patients to the hypother- mia protocol on odd- numbered days and the normothermia protocol on even- numbered days, leading to the uneven number of patients in each arm. Finally, the patients were actively rewarmed, which can lead to hypotension and cere- bral edema. However, this would have led to worse outcomes in the hypother- mia group, if anything.
Other Relevant Studies and Information:
• Since the publication of this trial and the HACA trial outlined in Chapter 18,1,2 several smaller studies on therapeutic hypothermia have
been performed.3,4
• Recent randomized controlled trials have sought to refine two key variables with therapeutic hypothermia: target temperature ranges for therapeutic hypothermia and time to target temperature (with the use of pre- hospital versus in- hospital cooling protocols.
• Nielsen et al.5 found that when comparing a targeted temperature
range of 33°– 36°C (i.e., prevention of fever), cooling to 33°C provided no additional benefit versus cooling to 36°C. This may suggest a permissive hypothermia range of 33°– 36°C may be acceptable if clinicians feel uncomfortable cooling specific patients down to the lower range.
• Kim et al.6 performed the largest blinded randomized controlled
trial in therapeutic hypothermia to answer a focused question as to whether out- of- hospital initiation of therapeutic hypothermia by rapid infusion of cold saline confers any benefit to neurological outcome. They found that there was an increased risk for systemic complications associated with a rapid 2- liter infusion of cold saline (i.e., pulmonary edema and risk for cardiac rearrest) that outweighed any benefit in neurologic outcome or survival.
Summary and Implications: The Australian trial was one of two studies that
demonstrated that active cooling for mild- to- moderate hypothermia improved the rate of favorable neurologic outcome and reduced mortality. In 2003, the International liaison Committee on Resuscitation’s Advanced life Support Task Force7 began recommending that (1) unconscious adult patients with
Therapeutic Hypothermia for Cardiac Arrest, Part II 133
spontaneous circulation after out- of- hospital cardiac arrest should be cooled to 32°– 34°C for 12– 24 hours when the initial rhythm was VF, and (2) such cooling may also be beneficial for other rhythms for patients experiencing an in- hospital cardiac arrest.
Especially in the context of the aforementioned more recent Nielsen et al. study,5 further studies are necessary to determine the ideal method, duration,
and range for therapeutic hypothermia in this patient population.
CLINICAL CASE: THERAPEUTIC HYPOTHERMIA FOR POST– CARDIAC ARREST
Case History:
A 45- year- old male carpenter is rushed to the emergency department by ambulance after his wife sees him outside on the ground clutching his chest 5 minutes after he was last seen normal moving wood outside the house. She immediately performs cardiopulmonary resuscitation when she finds him on the ground unconscious. She asks her daughter to call 911. Paramedics arrive within 20 minutes from the time of arrest and find that he is in VF. A return of spontaneous circulation occurs after 1 dose of epinephrine and administra- tion of 300 J of direct current shock.
The paramedics arrive within 30 minutes of the time of arrest to the emer- gency department. On examination, the patient’s vital signs are stable and a pulse is palpable. The patient has a temperature of 37°C on admission. Neurologically, the patient is comatose, and has decorticate posturing to nox- ious stimuli, but all brainstem reflexes are intact.
Based on the results of the HACA and Australian trials, should this patient undergo therapeutic hypothermia?
Suggested Answer:
Both the HACA and Australian trials established that cooling this patient to a range of 32°– 34oC for 12– 24 hours will improve survival or neurological out-
come by 14%– 23%. The ideal method of cooling is still unknown, but could include surface cooling versus more invasive vascular methods. Especially in the context of the aforementioned more recent Nielsen et al. study,5 further
studies are necessary to determine the ideal method, duration, and range for therapeutic hypothermia in this patient population.
N E U R O C R I T I C A l C A R E 134
References
1. 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;346:557– 563.
2. Hypothermia after Cardiac Arrest Study G. Mild therapeutic hypother- mia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002;346:549– 556.
3. Hachimi- Idrissi S, Corne l, Ebinger G, Michotte Y, Huyghens l. Mild hypo- thermia induced by a helmet device: a clinical feasibility study. Resuscitation. 2001;51:275– 281.
4. laurent I, Adrie C, Vinsonneau C, et al. High- volume hemofiltration after out- of- hospital cardiac arrest: a randomized study. J Am Coll Cardiol. 2005;46(3):432– 437. 5. Nielsen N, Wetterslev J, Cronberg T, et al. Targeted temperature management at
33°C versus 36°C after cardiac arrest. N Engl J Med. 2013;369(23):2197– 2206. 6. Kim F, Nichol G, Maynard C, et al. Effect of prehospital induction of mild hypo-
thermia on survival and neurological status among adults with cardiac arrest. JAMA. 2014;311(1):45– 52.
7. Nolan JP, Morley PT, Hoek Tl, Hickey RW. Therapeutic hypothermia after cardiac arrest: an advisory statement by the Advanced life Support Task Force of the International liaison Committee on Resuscitation. Resuscitation. 2003;57:231– 235.