Page 274 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

178 PART 2: General Management of the Patient

studies demonstrating worrisome electrolyte abnormalities and pneu- unclear whether the immune system is globally suppressed by hypother-
monia in cooled head injury patients, 77,78 no definitive recommendations mia or whether some pulmonary-specific mechanism is the culprit for
exist currently for treatment of traumatic brain injury with induced this increased pneumonia risk. Induced hypothermia does not seem to
hypothermia, although it is likely that future work will establish a role lead to a significantly increased risk of bacteremia, urinary tract infec-
for cooling in this disease entity. tion, or other infectious complications. Whether patients undergoing
Induced hypothermia has also been studied in the setting of acute induced hypothermia should be treated prophylactically with antibiotics
liver failure, such as from acetaminophen toxicity. As many as 50% remains to be determined.
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of patients with acute liver failure succumb from complications of While cardiac arrhythmias are a theoretical risk of induced hypo-
increased intracranial pressure, and induced hypothermia to 32°C to thermia, human studies in which target temperatures were above 32°C
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33°C has been shown to reduce intracranial pressure as much as 20 did not exhibit significant arrhythmia. It has been shown that the QTc
to 30 mm Hg in patients awaiting orthotopic liver transplantation. interval can be severely prolonged during the induction of hypother-
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Cooling also lowers arterial ammonia concentration and ammonia mia, though no association with life-threatening arrhythmias have been
delivery to the brain, which may be one of the mechanisms by which reported. 91,92 It is possible that deeper cooling may provoke electrical
hypothermia acts, because ammonia delivery to the brain contributes dysfunction, therefore, additional clinical precautions need be taken
to increased brain edema and intracranial pressure. It remains an when hypothermia (32°C-34°C) is performed.
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open question whether hypothermia could be used to treat the hepatic
encephalopathy of cirrhosis, also felt to be mediated by ammonia or at
least compounds for which ammonia acts as a surrogate marker. UNRESOLVED QUESTIONS
Neonatologists have studied induced hypothermia in the setting of There are a number of unresolved questions regarding the use of
hypoxic-ischemic encephalopathy after perinatal asphyxia, an important induced hypothermia. First, the optimal degree of cooling has yet to be
cause of acute neurologic injury at the time of birth. In a piglet model established. As described earlier, hypothermia can have adverse effects
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of brain ischemia, early cooling to 33°C to 35°C improved neurologic such as shivering, reduced immune system function, and other possible
outcomes by both functional and histologic criteria, whereas a delay in complications. 93,94 Therefore, the therapeutic window of hypothermia
cooling by even 30 minutes negated this benefit. 84,85 Initial clinical trials must be defined to provide maximum benefit. Most clinical research has
have demonstrated the feasibility of selective head cooling in infants, concentrated on the use of mild (34°C-36°C) or moderate (30°C-34°C)
with minimal differences in complications between cooled patients and hypothermia. Evaluation of deep hypothermia has been confined largely
normothermic controls. Larger randomized clinical trials are in prog- to specific applications such as brain cooling during surgery and reduced
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ress at the time of this writing. cerebral perfusion. Some animal investigations have compared different
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A number of surgical applications of induced hypothermia have been depths of cooling directly. It is possible that different disease states may
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evaluated, including aortic arch repair and cardiac bypass surgery. In require different depths of cooling to provide optimal protection.
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these settings, hypothermia induction and rewarming can be controlled The timing of hypothermia is another crucial question. There are
precisely and used for presumed important portions of the procedure in three general time periods in which hypothermia may be considered,
question. Unlike the clinical scenarios described earlier, surgical hypother- although only two are realistic for clinicians. Preinsult hypothermia, or
mia does not attempt to treat a pathophysiologic problem but rather to cooling some time before the onset of an ischemic process, is only possi-
prevent one from occurring. On a cautionary note, however, an extensive ble in the setting of surgical intervention, in which ischemia is iatrogenic
meta-analysis showed only a modest trend toward morbidity benefit in the and controlled. 97,98 Induced hypothermia initiated immediately during
setting of cardiac bypass surgery, with a trend toward decreased stroke rate an ischemic process, such as during stroke or myocardial infarction but
offset by increased perioperative complications and myocardial injury. 88 before reperfusion has been initiated, is feasible but poorly studied in the
clinical setting. A more dramatic example of this, the induction of hypo-
RISKS OF HYPOTHERMIA thermia during CPR, is theoretically attractive and a promising area of
current research but has not been attempted clinically. Postreperfusion
Hypothermia is not without risk of adverse effects. As the body cools, hypothermia, or cooling after definitive treatment such as thrombolytic
a series of physiologic changes take place, including shivering, altera- therapy or resuscitation, has been the most commonly attempted timing
tions in the clotting cascade, immunologic suppression, and cardiac strategy and is certainly the most clinically convenient. Recent large-
membrane changes that increase the risk of arrhythmia (see Chap. 36). scale clinical trials have demonstrated significant benefit from induced
These effects are poorly characterized and depend on the extent and hypothermia after resuscitation from cardiac arrest. These studies raise
2,3
duration of cooling. Therefore, the optimal therapeutic window of hypo- a secondary timing question related to postreperfusion hypothermia:
thermia needs to be established. Is the delay in hypothermia initiation clinically important? Cooling to
Shivering, a common occurrence during the induction of hypother- target core body temperatures may take several hours in clinical settings. 99,100
mia, can serve to counteract the mechanisms thought to be beneficial A variety of laboratory data suggests that earlier induction of hypother-
from the cooling itself, raising metabolic rates and myocardial oxygen mia confers a greater benefit. 27,101
demands. Pharmacologic options to control shivering include opioid The duration of the hypothermic state required for protection also
and neuroleptic medications. Simply covering the arms and legs during remains to be clearly established. Clinical studies to date have all main-
central cooling has demonstrated some reduction in shivering as well, tained mild hypothermic conditions for at least 12 hours, with most
supporting the notion that an increase in peripheral to central temp- current postarrest protocols using 24 hours as a standard recommenda-
erature gradient may be responsible for triggering a shivering response. tion. 2,3,91 However, animal studies have shown benefit from hypothermia
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A recent study demonstrated that meperidine and buspirone acted syn- lasting only 2 to 6 hours. 26,27 Certainly, a shorter duration of cooling
ergistically to reduce shivering, and this technique has been used would have a number of clinical advantages, including minimizing the
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successfully with endovascular cooling in myocardial infarction. 55 logistical difficulties of maintaining a constant cooled state and also
Hypothermia induces a poorly characterized diuresis in which patients minimizing the potential adverse effects from hypothermia. Conversely,
may develop significant hypokalemia, hypomagnesemia, and/or hypo- a longer duration of cooling (48 or 72 hours) might reduce neurologic
phosphatemia. Careful attention to electrolytes during the period of injury mechanisms that occur following cardiac arrest and reperfusion.
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cooling and rewarming is required, and aggressive supplementation The question of hypothermia duration has not been addressed directly
should be given when indicated. in clinical studies at this time.
A study of stroke patients demonstrated a risk of pneumonia with Finally, a number of other aspects of induced hypothermia remain to
hypothermia, consistent with the cardiac arrest study results. It is be examined. How quickly should patients be rewarmed at the end of a
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