Safety and efficacy of analgesia-based sedation with remifentanil versus standard hypnotic-based regimens in intensive care unit patients with brain injuries: a randomised, controlled trial [ISRCTN50308308]

Introduction This randomised, open-label, observational, multicentre, parallel group study assessed the safety and efficacy of analgesia-based sedation using remifentanil in the neuro-intensive care unit. Methods Patients aged 18-80 years admitted to the intensive care unit within the previous 24 hours, with acute brain injury or after neurosurgery, intubated, expected to require mechanical ventilation for 1-5 days and requiring daily downward titration of sedation for assessment of neurological function were studied. Patients received one of two treatment regimens. Regimen one consisted of analgesia-based sedation, in which remifentanil (initial rate 9 mug kg(-1) h(-1)) was titrated before the addition of a hypnotic agent (propofol [0.5 mg kg(-1) h(-1)] during days 1-3, midazolam [0.03 mg kg(-1) h(-1)] during days 4 and 5) (n = 84). Regimen two consisted of hypnotic-based sedation: hypnotic agent (propofol days 1 - 3; midazolam days 4 and 5) and fentanyl (n = 37) or morphine (n = 40) according to routine clinical practice. For each regimen, agents were titrated to achieve optimal sedation (Sedation - Agitation Scale score 1 - 3) and analgesia (Pain Intensity score 1 - 2). Results Overall, between-patient variability around the time of neurological assessment was statistically significantly smaller when using remifentanil (remifentanil 0.44 versus fentanyl 0.86 [P = 0.024] versus morphine 0.98 [P = 0.006]. Overall, mean neurological assessment times were significantly shorter when using remifentanil (remifentanil 0.41 hour versus fentanyl 0.71 hour [P = 0.001] versus morphine 0.82 hour [P < 0.001])). Patients receiving the remifentanil-based regimen were extubated significantly faster than those treated with morphine (1.0 hour versus 1.93 hour, P = 0.001) but there was no difference between remifentanil and fentanyl. Remifentanil was effective, well tolerated and provided comparable haemodynamic stability to that of the hypnotic-based regimen. Over three times as many users rated analgesia-based sedation with remifentanil as very good or excellent in facilitating assessment of neurological function compared with the hypnotic-based regimen. Conclusions Analgesia-based sedation with remifentanil permitted significantly faster and more predictable awakening for neurological assessment. Analgesia-based sedation with remifentanil was very effective, well tolerated and had a similar adverse event and haemodynamic profile to those of hypnotic-based regimens when used in critically ill neuro-intensive care unit patients for up to 5 days.