Pharmacokinetic and Other Considerations for Drug Therapy During Targeted Temperature Management.

OBJECTIVE: To synthesize an emerging body of literature describing pharmacokinetic alterations and related pharmacodynamic implications affecting drugs commonly used in patients receiving targeted temperature management following cardiac arrest. DATA SOURCES: Peer-reviewed articles indexed in PubMed. STUDY SELECTION: A systematic search of the PubMed database for relevant preclinical studies and clinical and observational trials of physiologic changes and drug pharmacokinetic and pharmacodynamic alterations, especially during targeted temperature management/therapeutic hypothermia, but also from cardiac surgery and acute stroke hypothermia models. DATA EXTRACTION: Detailed review of information contained in published scientific work. DATA SYNTHESIS: Physiologic changes during targeted temperature management significantly alter both the pharmacokinetic and the pharmacodynamic parameters of medications. Current literature describes these alterations and provides practical considerations for management of medications. Medication selection should center on the pharmacokinetics and pharmacodynamics of agents in an attempt to ameliorate potential adverse effects. CONCLUSIONS: This review provides an overview of physiologic changes associated with targeted temperature management and practical considerations for the management of medications. Clinicians should understand and anticipate potential drug-therapy interactions of targeted temperature management and mitigate adverse outcomes by appropriate medication selection, dosing, and monitoring. We discuss complications of hypothermia including shivering, electrolyte abnormalities, hemodynamic changes, arrhythmias, and seizures. We review management of these complications as well as considerations for sedation, analgesia, anticoagulation, and prognostication. Approach to interpretation of the clinical significance of drug interactions during targeted temperature management therapy is also addressed.

Reversible brain death after cardiopulmonary arrest and induced hypothermia.

OBJECTIVE: To describe a patient with transient reversal of findings of brain death after cardiopulmonary arrest and attempted therapeutic hypothermia. DESIGN: Case report. SETTING: Intensive care unit of an academic tertiary care hospital. PATIENT: A 55-yr-old man presented with cardiac arrest preceded by respiratory arrest. Cardiopulmonary resuscitation was performed, spontaneous perfusion restored, and therapeutic hypothermia was attempted for neural protection. After rewarming to 36.5°C, neurologic examination showed no eye opening or response to pain, spontaneous myoclonic movements, sluggishly reactive pupils, absent corneal reflexes, and intact gag and spontaneous respirations. Over 24 hrs, remaining cranial nerve function was lost. The neurologic examination was consistent with brain death. Apnea test and repeat clinical examination after a duration of 6 hrs confirmed brain death. Death was pronounced and the family consented to organ donation. Twenty-four hrs after brain death pronouncement, on arrival to the operating room for organ procurement, the patient was found to have regained corneal reflexes, cough reflex, and spontaneous respirations. The care team faced the challenge of offering an adequate explanation to the patient's family and other healthcare professionals involved. INTERVENTIONS: Induced hypothermia and brain death determination. MEASUREMENTS AND MAIN RESULTS: This represents the first published report in an adult patient of reversal of a diagnosis of brain death made in full adherence to American Academy of Neurology guidelines. Although the reversal was transient and did not impact the patient's prognosis, it impacted his eligibility for organ donation and cast doubt about the ability to determine irreversibility of brain death findings in patients treated with hypothermia after cardiac arrest. CONCLUSIONS: We strongly recommend caution in the determination of brain death after cardiac arrest when induced hypothermia is used. Confirmatory testing should be considered and a minimum observation period after rewarming before brain death testing ensues should be established.