Page 273 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

CHAPTER 26: Therapeutic Hypothermia 177

TABLE 26-1 Post-Cardiac Arrest Therapeutic Hypothermia Exclusion Criteria INDUCED HYPOTHERMIA IN STROKE
• 12 hours since return of spontaneous circulation (ROSC) The rationale for the consideration of induced hypothermia in acute
• Glasgow Motor score >5 ischemic stroke is similar to that for cardiac arrest and myocardial
• Minimal premorbid cognitive status (eg, bed bound and nonverbal before arrest) infarction. Stroke is a difficult clinical problem with severe outcomes;
• Other reason for coma not only is stroke the second most common cause of death in the world,
• Sepsis as etiology for arrest but it is also the leading cause of disability in patients over 65 years of
• DNR age. Moreover, few improvements in acute stroke care have enhanced
59
• Uncontrollable bleeding the general outcome of the disease. Treatment with thrombolytic
60
• Significant trauma, especially intra-abdominal such as splenic or liver laceration agents such as tissue plasminogen activator, while a powerful option
Note: These do not represent absolute exclusion criteria; careful consideration should be given on a case- when a patient presents within 3 hours of ischemic stroke onset, carries
by-case basis. significant risks and has only demonstrated improvement in a subset
of stroke patients. 61,62 In part, this is so because irreversible damage
to brain tissue may have occurred already before restoration of blood
in survival or neurological recovery in out-of-hospital cardiac arrest flow. However, reperfusion of ischemic neuronal tissues may also pro-
patients cooled to 33°C, compared to those kept at 36°C. 53 duce additional damage via free radical production and induction of
Current literature suggests that patients should be cooled for approxi- programmed cell death and the other so-called IR injury mechanisms
mately 24 hours at a temperature between 32°C and 34°C (with the described earlier (reviewed in ref. 42).
63
24-hour interval starting at the achievement of goal temperature, not the The benefit of induced hypothermia in the setting of stroke remains
initiation of the cooling process). Avoidance of temperatures below 32°C unclear, as the limited data have shown conflicting results (reviewed
is important to minimize potential adverse effects from reduced body in refs. 63, 64). In a variety of model systems, hypothermia reduces
temperature. Cooling may induce shivering and could result in patient injury, as measured by biochemical and histologic markers. Cooling
discomfort if sedation is not adequately established. In the published also appears to extend the time in which brain tissue can suffer
studies of hypothermia after cardiac arrest, patients uniformly received ischemia without irreversible damage. 66,67 In several animal models,
neuromuscular blockade and sedation, and it is likely most patients cooling to 32°C to 34°C for greater than 24 hours provided signifi-
will require such pharmacologic treatment. The disadvantages of this cant benefit, whereas shorter periods of hypothermia provided more
management strategy is that neurologic examination is not interpretable, inconsistent results. 68,69 Several pilot studies have evaluated the feasi-
and paralytic agents carry the risk of long-term neuromyopathy, though bility and safety of cooling after ischemic stroke in humans. In one
post-cardiac arrest patients undergoing hypothermia will generally study, cooling to 33°C to 34°C appeared to reduce intracranial pres-
only be paralyzed for approximately 36 to 48 hours. Special attention sure in patients with severe middle cerebral artery strokes. In a trial
70
should be placed on monitoring these patients for electrical evidence of of induced hypothermia after thrombolysis, cooling stroke patients to
seizures, as seizures are common in the post-cardiac arrest population 32°C for at least 12 hours demonstrated a nonsignificant trend toward
(occurring in as many as 20%-25% of postarrest patients). improved functional outcomes compared with normothermic con-
Patients should be rewarmed slowly at a rate of 0.25°C to 0.5°C per hour. trols. These pilot studies were limited by small sample size. Larger
60
Rewarming often requires active intervention, which can include randomized trials of induced hypothermia in stroke are currently
warmed intravenous fluids and warming blankets. Rebound pyrexia is underway in Europe.
54
common in this population for up to 48 to 72 hours after rewarming While the induction of hypothermia after ischemic stroke requires
and therefore a period of controlled normothermia is recommended additional refinement before becoming the established standard of care,
along with aggressive treatment of fevers if they should occur. aggressive prevention of hyperthermia is clearly indicated. A number of
epidemiologic and clinical studies have shown that even modest eleva-
INDUCED HYPOTHERMIA IN MYOCARDIAL INFARCTION tions in temperature increase stroke severity and patient mortality. 71,72
Antipyretic medications in combination with either forced-air cooling
Induced hypothermia to 32°C to 34°C has been shown in a variety of or cooling blankets are sufficient to maintain core temperatures below
model systems to limit the size of a myocardial infarction in ischemia 37°C. A clinical investigation using such modest measures demonstrated
without reperfusion and to limit myocardial injury when reperfusion is significant mortality risk reduction. 73
established. Given that current clinical practice is directed toward early
reperfusion of myocardial tissue via thrombolytic therapy or percutane-
ous coronary intervention (PCI), it is the IR model that has received ADDITIONAL CLINICAL APPLICATIONS
the most current attention. A recent trial in pigs used an endovascular
cooling catheter to induce hypothermia during ischemia and after reper- The induction of hypothermia has been used experimentally in a num-
fusion of 60-minute coronary occlusions. Hypothermia to 34°C had ber of other clinical scenarios from surgical to critical care applications.
a substantial protective effect, with smaller infarct size, better cardiac One such indication is traumatic brain injury, in which an extensive
output, and improved microvascular flow. 55 body of laboratory work suggests that hypothermia may improve out-
Endovascular cooling has also been studied in induced hypothermia comes for severe trauma. In one clinical study of 87 patients, hypo-
74
during PCI in humans. In a pilot study, patients were randomized to cooled thermia to 33°C to 35°C for at least 72 hours provided a significant
75
(34°C-35°C) or normothermic PCI. Cooling was maintained for 3 hours functional benefit at 1 year after injury. However, a larger randomized
after intervention. No patients suffered adverse effects from cooling, and trial of 392 patients failed to find a significant benefit at 6 months after
there was a trend toward smaller infarct size in the cooled patients. More cooling to 33°C for 48 hours. While this has been widely interpreted
10
56
recently, a study examined two randomized trials of induced hypothermia as a “negative study,” the authors have pointed out that the likely reason
in PCI patients and found that the hypothermia-treated population had a for finding no benefit was that owing to technical challenges (including
significant relative reduction in infarct size compared to their controls in taking 4 hours to get informed consent), the average time to cooling was
both anterior and inferior infarcts. Larger studies will be required to con- nearly 8 hours after injury. There are no animal studies that suggest any
57
firm these findings. Additionally, studies have looked at induced hypother- improvement in neurologic results at this late time—the longest delay in
58
mia in conjunction with PCI and have found that it is safe and feasible. cooling that shows any positive effect is about 1 hour following injury.
Given that no major randomized studies have shown benefit from induced Another clue to these conflicting results was provided by a clinical trial
hypothermia in myocardial infarction, there is currently no clinical recom- in which hypothermia was found to have no benefit in patients who
mendation for its use. However, it is possible that hypothermia will become did not exhibit elevated intracranial pressure. Thus hypothermia may
76
a standard technique to reduce infarct damage in the next decade. be useful in only a subset of brain injury patients. Taken together with

section02.indd 177 1/13/2015 2:05:16 PM