Research

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]

Andreas Karabinis¹ , Kostas Mandragos² , Spiros Stergiopoulos³ , Apostolos Komnos⁴ , Jens Soukup⁵ , Ben Speelberg⁶ and Andrew JT Kirkham⁷

¹Director of Intensive Care Unit, Genimatas General Hospital, Athens, Greece

²Director of Intensive Care Unit, Red Cross General Hospital of Athens, Korgialenio, Benakio, Athens, Greece

³Assistant Professor of Surgery, Head of SICU and Trauma Unit, 4th Surgical Department, Athens Health Science University, Athens, Greece

⁴Director of Department of Intensive Care, General Hospital of Larissa, Larissa, Greece

⁵Anesthesiologist, Department of Anesthesiology and Intensive Care Medicine, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Strasse 40, 06097 Halle, Germany

⁶Internist-Intensivist, Intensive Care, St Elisabeth Ziekenhuis, Tilburg, The Netherlands

⁷Anaesthesia Clinical Development, GlaxoSmithKline, Greenford, Middlesex, UK

author email corresponding author email

Critical Care 2004, 8:R268-R280doi:10.1186/cc2896

Published:	28 June 2004

Abstract

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 μg 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.