The Role of Remifentanil Versus other Opioids in ICU Sedation

Ashraf Dahaba MD, MSc, Phd

Department of Anaesthesiology and Intensive Care Medicine

Graz Medical University, Austria.

Intensive Care Unit (ICU) patients are often exposed to numerous stressful or noxious stimuli. ICU patients usually receive a “sedative-based regimen” of a hypnotic agent such as midazolam or propofol and an opioid such as fentanyl, sufentanil or alfentanil, where there is always the potential for prolonged duration of action especially in patients with hepatic impairment [1]. Recent guidelines concerning the use of analgesics and sedatives in ICU patients state that “pain should be treated prior to the sedation of an agitated, critically ill patient” [2]. An alternative to “hypnotic-based regimens”, are “analgesia-based sedative regimens”, with opioid pain relief first then a sedative agent is administered if and when required. Remifentanil’s unique properties of organ-independent metabolism that is not affected by renal or hepatic impairment, and its highly predictable rapid onset and offset of action, make it a useful tool for sedation and analgesia in ICU patients.

In a randomized, double blind study we compared the efficacy and safety of a remifentanil based regime to a standard morphine based regime in mechanically ventilated ICU subjects [3]. A number of randomized studies have also compared the efficacy of remifentanil in providing analgesia-based sedation with that of morphine [3, 4, 5], fentanyl [4, 5, 6], or sufentanil [7] in post-surgical, trauma and/or medical ICU patients (n³40). Midazolam [3, 4, 5] or propofol [4, 6, 7] were administered if additional sedation was required.

In our study remifentanil provided optimal sedation (Sedation-Agitation Scale of 4) for significantly longer duration (78%) compared to morphine (67%), with fewer infusion rate adjustments (0.3 changes/h vs. 0.4 changes/h) [3]. Whereas, remifentanil was as at least as effective as morphine [5], fentanyl [5, 6] and sufentanil [7] in providing effective analgesia-based sedation (optimal sedation for ³78% of the time). This indicates that remifentanil’s rapid onset and offset of action (3-4 min), that is independent of the duration of infusion or the total dose given [8, 9] enables a stable level of sedation to be rapidly achieved and maintained.

In our study the percentage of hours during which patients had no or mild pain (Pain Intensity scale of 1 or 2) with remifentanil (96%) was similar to morphine (93%) [3]. Conversely, compared with fentanyl recipients, remifentanil recipients experienced at least moderate pain for significantly greater proportions of the extubation (1.4% vs. 6.5%), post-extubation (3.6% vs. 10.2%), and post-treatment (5.1% vs. 13.5%) periods [6], probably reflecting a possible drawback of remifentanil’s rapid offset of action following its discontinuation. This highlights the need for a smooth transition to alternative analgesia prior to discontinuing remifentanil infusion.

Remifentanil possess sedative-sparing effects, as fewer patients in our study required additional midazolam sedation with remifentanil (30%) compared to morphine (45%). Furthermore, in those patients who required additional sedation, midazolam requirements were approximately 2.5 times higher in the morphine group (0.5 µg/kg/min) than in the remifentanil group (0.2 µg/kg/min) [3]. Similarly, fewer patients required a propofol infusion with remifentanil (35%) than with fentanyl (40%) in another study [6].

The extubation time was significantly shorter in the remifentanil group of our study (17 min) compared to the morphine group (73 min) [3], indicative of remifentanil’s short terminal half-life of less than 10 min [9]. Similarly, the extubation time was significantly shorter with remifentanil than with morphine [4, 5], fentanyl [5] or sufentanyl [7]. In our study remifentanil was also associated with a shorter ICU discharge time [3]. This suggests that, despite a higher remifentanil acquisition costs, its hypnotic-sparing effect means that the expense of hypnotic agents may be reduced, as well as the potential savings by reducing the length of ICU stay.

During our study drug infusion, the mean arterial pressure was significantly lower in the remifentanil group than in the morphine group. Thus remifentanil could be considered as providing clinically acceptable effectiveness in attenuating the cardiovascular responses induced by endotracheal intubation [3]. Remifentanil was associated with an acceptable degree of haemodynamic stability generally similar to that of fentanyl [6] in ICU patients requiring mechanical ventilation for up to  3 days. There was no significant difference in drug-related adverse events between remifentanil (22%) and morphine recipients (16%) in our study [3]. Similarly, there was no difference between remifentanil and fentanyl recipients in the incidence of hypotension (10% vs. 9%), nausea (9% vs. 6%), fever (5% vs. 9%) or vomiting (5% vs. 6%) [6].

In conclusion, analgesia-based sedation with remifentanil is generally well tolerated in this patient population and is as least as efficacious as morphine, fentanyl and sufentanil for the provision of optimal analgesia-sedation for mechanically ventilated ICU patients. Remifentanil allows a more rapid emergence from sedation, facilitates earlier extubation and quicker ICU discharge that might contribute in ICU cost reduction.

References

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8. Kapila A, Glass PSA et al. Anesthesiology 1995; 83: 968-75