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].
BACKGROUND
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 microg 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.
Karabinis
Andreas
A
Genimatas General Hospital, Athens, Greece. akarab@ath.forthnet.gr
Mandragos
Kostas
K
Stergiopoulos
Spiros
S
Komnos
Apostolos
A
Soukup
Jens
J
Speelberg
Ben
B
Kirkham
Andrew J T
AJ
D000759:Adjuvants, Anesthesia / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000494:pharmacology / Q000627:therapeutic use*; D001930:Brain Injuries / Q000503:physiopathology / Q000628:therapy; D016903:Drug Monitoring; D005260:Female; D005283:Fentanyl / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D007362:Intensive Care Units; D008297:Male; D008874:Midazolam / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D008875:Middle Aged; D019635:Neurosurgical Procedures; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use*; D011182:Postoperative Care; D015742:Propofol / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000077208:Remifentanil; D012121:Respiration, Artificial; D013997:Time Factors; D016896:Treatment Outcome
D000759:Adjuvants, Anesthesia; D000701:Analgesics, Opioid; D006993:Hypnotics and Sedatives; D010880:Piperidines; D000077208:Remifentanil; D008874:Midazolam; D005283:Fentanyl; D015742:Propofol