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Does choice of sedative agent affect duration of ICU stay, mortality or neurological outcome in patients undergoing therapeutic hypothermia?


The effect of therapeutic hypothermia on sedative drug clearance and neurological prognostication is unknown. Hypothermia has been shown to affect clearance of drugs metabolised by the cytochrome p450 system (fentanyl, midazolam and muscle relaxants) [1]. We undertook a retrospective study to ascertain whether the use of remifentanil sedation was associated with reduced duration of ICU stay, ventilation, mortality or neurological outcome compared with fentanyl in patients undergoing therapeutic hypothermia.


Data were collected on all patients undergoing therapeutic hypothermia in a 2.5-year period using the Carevue ICU Database (Phillips) and case-note review. All patients received propofol and either remifentanil or fentanyl as sedation. Patient demographic data included age, weight, sex, APACHE II, time to return of spontaneous circulation and arrest type. Measured outcomes were ICU-free days, ventilator-free days, ICU mortality, hospital mortality and neurological outcome at hospital discharge. Good neurological outcome was classified as Pittsburgh Cerebral Performance Criteria grade 1 to 2 at hospital discharge [2]. Predictive models used multivariable logistic regression.


Eighty-three patients received therapeutic hypothermia (crude ICU mortality 43%, median APACHE II score 18); of which 54 received fentanyl sedation and 29 remifentanil. In the multivariable models, remifentanyl was not associated with ICU (P = 0.35) or hospital (P = 0.22) mortality or good neurological outcome (P = 0.75). However, remifentanyl was associated with a positive trend towards an increase in both ventilator-free and ICU-free days (both P = 0.08).


Use of remifentanil was not associated with a reduction in ICU or hospital mortality, nor with good neurological outcome. However, there was a trend to increased ventilator-free and ICU-free days. This effect needs to be confirmed prospectively with a larger dataset. Caution must be exercised regarding the effect of delayed sedative drug metabolism on neurological assessment in patients who have undergone therapeutic hypothermia, especially drugs metabolised by the cytochrome p450 system.


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  2. The HACA Study Group: Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Eng J Med 2002, 346: 549-556. 10.1056/NEJMoa012689

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Gillies, M., Pratt, R., Borg, J. et al. Does choice of sedative agent affect duration of ICU stay, mortality or neurological outcome in patients undergoing therapeutic hypothermia?. Crit Care 13 (Suppl 1), P400 (2009).

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  • Fentanyl
  • Remifentanil
  • Neurological Outcome
  • Therapeutic Hypothermia
  • Sedative Drug