Neuroprognostication Practices in Postcardiac Arrest Patients : An International Survey of Critical Care Providers

Therapeutic hypothermia is commonly used in comatose survivors' post-cardiopulmonary resuscitation (CPR). It is unknown whether outcome predictors perform accurately after hypothermia treatment. Post-CPR comatose survivors were prospectively enrolled. Six outcome predictors [pupillary and corneal reflexes, motor response to pain, and somatosensory-evoked potentials (SSEP) >72 h; status myoclonus, and serum neuron-specific enolase (NSE) levels 72 h, and absent pupillary reflexes >72 h predicted poor outcome with a 100% specificity both in hypothermia and normothermia patients. In contrast, absent corneal reflexes >72 h, motor response extensor or absent >72 h, and peak NSE >33 ng/ml <72 h predicted poor outcome with 100% specificity only in non-sedated patients, irrespective of prior treatment with hypothermia. Sedative medications are commonly used in proximity of the 72-h neurological examination in comatose CPR survivors and are an important prognostication confounder. Patients treated with hypothermia are more likely to receive sedation than those who are not treated with hypothermia.

Therapeutic hypothermia has been shown to decrease neurologic damage in patients experiencing out-of-hospital cardiac arrest. In addition to being treated with hypothermia, critically ill patients are treated with an extensive pharmacotherapeutic regimen. The effects of hypothermia on drug disposition increase the probability for unanticipated toxicity, which could limit its putative benefit. This review examines the effects of therapeutic hypothermia on the disposition, metabolism, and response of drugs commonly used in the intensive care unit, with a focus on the cytochrome P450 enzyme system. A MEDLINE/PubMed search from 1965 to June 2006 was conducted using the search terms hypothermia, drug metabolism, P450, critical care, cardiac arrest, traumatic brain injury, and pharmacokinetics. Twenty-one studies were included in this review. The effects of therapeutic hypothermia on drug disposition include both the effects during cooling and the effects after rewarming on drug metabolism and response. The studies cited in this review demonstrate that the addition of mild to moderate hypothermia decreases the systemic clearance of cytochrome P450 metabolized drugs between approximately 7% and 22% per degree Celsius below 37degreesC during cooling. The addition of hypothermia decreases the potency and efficacy of certain drugs. This review provides evidence that the therapeutic index of drugs is narrowed during hypothermia. The magnitude of these alterations indicates that intensivists must be aware of these alterations in order to maximize the therapeutic efficacy of this modality. In addition to increased clinical attention, future research efforts are essential to delineate precise dosing guidelines and mechanisms of the effect of hypothermia on drug disposition and response.

To evaluate the predictive value of neurologic prognostic indicators for patients treated with hypothermia after surviving cardiopulmonary arrest. Patients who survived cardiopulmonary arrest were prospectively collected from June 2006 to October 2009. Detailed neurologic examinations were performed. Serum neuron specific enolase (NSE) measurements, brain imaging findings, somatosensory evoked potentials, and electroencephalogram (EEG) results were recorded. EEG patterns were blindly dichotomized with malignant patterns consisting of burst-suppression, generalized suppression, status epilepticus, and nonreactivity. Outcome measure of in-hospital mortality was assessed. A total of 192 patients (103 hypothermic, 89 nonhypothermic) were studied. The absence of pupillary light responses, corneal reflexes, and an extensor or absent motor response at Day 3 after cardiac arrest remained accurate predictors of poor outcome after therapeutic hypothermia (p 33 ng/ml levels measured 1-3 days after cardiac arrest remained associated with poor outcome (p = 0.017), but had a false-positive rate of 29.3% (95% confidence interval [CI] 0.164-0.361). Clinical examination (brainstem reflexes, motor response, and presence of myoclonus) at Day 3 after cardiac arrest remains an accurate predictor of outcome after therapeutic hypothermia. Sedative medications in both hypothermic and nonhypothermic patients may confound the clinical exam. NSE > 33 ng/ml has a high false-positive rate in patients treated with hypothermia and should be interpreted with caution.