Remifentanil versus sufentanyl narco-sedation in a surgical and medical critical care unit with prevention of narcotic-induced hyperalgesia: a randomized double blind study

Background

The authors hypothesized that the efficacy of a remifentanil-based regimen (R) with prevention of narcotic-induced hyperalgesia (NIH) [1] by magnesium sulphate (MS), ketamine (K) or clonidine (C) was greater than that of a conventional sufentanyl-based regimen (S).

Methods

One hundred patients were randomly allocated to receive a blinded infusion of either R at a rate of 0.15 μg/kg/min (± 0.10 μg/kg/min) (G1: n = 50) or S at 0.35 μg/kg/min (± 0.15 μg/kg/min) (G2: n = 50). The opioid infusion was titrated, in the first intent, to achieve optimal sedation as defined by a Sedation Agitation Scale (SAS) of 4. NIH in G1 was realised by infusion of MS (0.008 mg/kg/hour), K (0–8 μg/kg/min) or C (0–0.01 μg/kg/ min) depending on hemodynamic stability. A tramadol open-label (0.25 mg/kg/hour) infusion was started if additional analgesia was required. Sedation was performed in all patients with a propofol infusion (0–6 mg/kg/min). The SAS was maintained between 3 and 4. For statistical analysis a Shapiro-Wilk test, Wilcox test and a Student t test were used.

Results

The mean percentage hours of optimal sedation was significantly longer in the R group (108.3 ± 26.3 = 5.5 days) than in the S group (86.5 ± 6.5). This was achieved with less frequent infusion rate adjustments (0.34 ± 0.25 changes/hour) than in the S group (0.42 ± 0.22 changes/hour). The mean durations of mechanical ventilation were comparable in both groups (76 ± 14 hours SD). The extubation times were significantly longer in the S group (22.1 ± 4.4 hours, 75 ± 5 min) than in the R group (4.1 ± 2.0 hours, 10 ± 6 min), respectively (P < 0.001). The total mean hospitalisation time in the ICU was reduced by 48 ± 8 hours in G1 compared with G2 (P < 0.005). The R mean infusion rate was 0.12 ± 0.9 μg/kg/min, whereas the S mean infusion rate was 0.38 ± 0.14 μg/kg/min. More subjects in the S group (32 of 50) than in the R group (6 of 50) required tramadol (P < 0.001). The mean EVA at the end of the ICU stay was for G1: 1 ± 1 and for G2: 2 ± 3 (P < 0.005). The incidence of adverse events was low and comparable across the two treatment groups. The global hospitalisation cost shows a 26% reduction for patients in G1 despite a raise of 8% when R is used compared with S.

Conclusion

A remifentanil-based regimen was more effective in the provision of optimal analgesia sedation than a standard sufentanyl-based regimen. The remifentanil-based regimen allowed a more rapid emergence from sedation and facilitated earlier extubation, and so diminished total ICU hospitalisation time and cost. The prevention of NIH allows an optimal narco-sedative level without increased doses of remifentanyl and lower needs for analgesics at the end of ICU hospitalisation.