Propofol and remifentanil versus midazolam and fentanyl for sedation during therapeutic hypothermia after cardiac arrest: a randomised trial.

PURPOSE: To compare two protocols for sedation and analgesia during therapeutic hypothermia: midazolam and fentanyl versus propofol and remifentanil. The primary outcome was the time from discontinuation of infusions to extubation or decision not to extubate (offset time). Secondary outcomes were blood pressure, heart rate, use of vasopressors and inotropic drugs, pneumonia and neurological outcome. METHODS: This was an open, randomised, controlled trial on 59 patients treated with therapeutic hypothermia (33-34 °C for 24 h) after cardiac arrest in two Norwegian university hospitals between April 2008 and May 2009. The intervention was random allocation to sedation and analgesia with propofol/remifentanil or midazolam/fentanyl. RESULTS: Twenty-nine patients received propofol and remifentanil, and 30 midazolam and fentanyl. Baseline characteristics were similar. Sedation and analgesia were stopped in 35 patients, and extubation was performed in 17 of these. Sedation had to be continued for 24 patients. Time to offset was significantly lower in patients given propofol and remifentanil [mean (95 % confidence intervals) 13.2 (2.3-24) vs. 36.8 (28.5-45.1) h, respectively, p < 0.001]. Patients given propofol and remifentanil needed norepinephrine infusions twice as often (23 vs. 12 patients, p = 0.003). Incidence of pneumonia and 3-month neurological outcome were similar in the two groups. CONCLUSIONS: Time to offset was significantly shorter in patients treated with propofol and remifentanil. However, the clinical course in 40 % of patients prevented discontinuation of sedation and potential benefits from a faster recovery. The propofol and remifentanil group required norepinephrine twice as often, but both protocols were tolerated in most patients.

Antiplatelet effect of clopidogrel is reduced in patients treated with therapeutic hypothermia after cardiac arrest.

BACKGROUND: The platelet inhibitor clopidogrel is administered to patients treated with therapeutic hypothermia following cardiac arrest due to acute coronary syndromes. Interactions with proton pump inhibitors and genetics are factors with a known potential to attenuate the platelet inhibition of clopidogrel. In patients treated with therapeutic hypothermia, reduced gastrointestinal function and hypothermia may also reduce the effect of clopidogrel. To investigate the net platelet inhibition of clopidogrel, we have measured the platelet reactivity index in patients treated with therapeutic hypothermia. METHODS AND RESULTS: Twenty-five Caucasian patients treated with clopidogrel and therapeutic hypothermia were prospectively included. Therapeutic hypothermia was defined as 33-34°C and delivered for 24h. Clopidogrel loading doses (300-600 mg) were administered enterally the day of admission and followed by 75 mg daily. Blood samples were collected on day 1 (n=25) and day 3 (n=16). The samples were analysed for inhibition by clopidogrel with a vasodilator stimulated phosphoprotein phosphorylation kit. On day 1 and day 3, platelet reactivity index was 0.77±0.09 and 0.57±0.16, respectively. The number of patients with a satisfactory antiplatelet effect (defined as platelet reactivity index <0.5) were 0 (0%) and 5 (31%), respectively. CONCLUSION: In patients treated with therapeutic hypothermia after cardiac arrest, the effect of clopidogrel on platelets was virtually nonexistent on day 1 after administration, with some improvement on day 3.