Clinical paperPredictors of poor neurologic outcome in patients after cardiac arrest treated with hypothermia: A retrospective study☆
Introduction
Outcome studies in patients with anoxic-ischemic encephalopathy focus on the early prediction of an outcome no better than a vegetative state or severe disability. Clinical signs, electrophysiological and/or biochemical tests with a false positive rate of 0% and a narrow confidence interval are currently used early after cardiac arrest to identify a subset of patients with a poor prognosis.1
Hypothermia has a marked effect on the cerebral changes that occur during the post-cardiac arrest period by influencing metabolism, cerebral blood flow, inflammatory response and neuro-excitatory pathways.2 These hypothermia induced changes by itself may prolong the time to recovery of the brain. Sedatives additionally influence the time to regaining consciousness, and therefore prognostication after hypothermia. Midazolam is frequently used in patients after cardiac arrest.3 Hypothermia influences the metabolism of midazolam with an increase in plasma concentrations, possibly because of depressed cytochrome P 450(CYP)3A4 and CYP3A5 activity.4 Together with impaired hepatic and renal function that may occur as a result of whole-body ischemia–reperfusion, midazolam and its active metabolites can accumulate resulting in an unpredictably prolonged sedative effect.
Currently used predictors of outcome in patients with anoxic-ischemic encephalopathy are based on studies performed before the use of mild therapeutic hypothermia.1, 5 There is increasing evidence in the literature that these parameters may not be applicable to patients after hypothermia.6 We determined the effect of mild therapeutic hypothermia on the validity of the currently used clinical practice parameters as described by the Quality Standards Subcommittee of the American Academy of Neurology (AAN).1 In addition, we studied the natural course of the clinical neurological parameters of patients with post-anoxic encephalopathy during and after treatment with hypothermia.
Section snippets
Patients
We conducted a retrospective cohort study of consecutive adult patients with return of spontaneous circulation (ROSC) after cardiac arrest who were admitted to the ICU of the Radboud University Nijmegen Medical Centre between January 2007 and November 2009 and treated with mild hypothermia. The patients were identified from the National Intensive Care Evaluation (NICE) database using “cardiac arrest, with or without respiratory arrest” as the diagnosis on admission. Since no intervention was
Results
We identified 162 patients from the NICE database who were admitted to the ICU after cardiac arrest between January 2007 and November 2009. We excluded 43 patients that were not cooled to hypothermia and 16 patients because of missing data (most frequently because of transfer to another hospital) or failure to obtain the GOS. The data of the remaining 103 patients were analyzed.
Discussion
The prognosis of post-anoxic encephalopathy in patients treated with hypothermia is difficult to predict in an early phase. After treatment with mild hypothermia, the motor score of the GCS gradually improved during the first 7 days after ROSC. At day 3, the current clinical practice parameters such as the motor score, pupillary reflex or corneal reflex were unreliable in predicting a poor outcome. The predictive value of EEG patterns in predicting a poor outcome was low, except for reactivity
Conclusions
Our analysis clearly shows that no single clinical or electrophysiological parameter has sufficient accuracy to determine prognosis and decision making in patients after cardiac arrest, treated with hypothermia. We demonstrated that the current clinical AAN guidelines cannot be safely applied to these patients. Early prognostication in patients with post-anoxic encephalopathy will probably require a multimodal approach, combining a number of clinical and electrophysiological tests. Prospective
Conflict of interest statement
The authors declare that they have no competing interests.
Acknowledgement
None.
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A Spanish translated version of the abstract of this article appears as Appendix in the final online version at doi:10.1016/j.resuscitation.2011.02.020.