P. Maurette

BACKGROUND: Remifentanil-induced secondary hyperalgesia has been documented experimentally in both animals and healthy human volunteers, but never clinically. This study tested the hypotheses that increased pain sensitivity assessed by periincisional allodynia and hyperalgesia can occur after relatively large-dose intraoperative remifentanil and that small-dose ketamine prevents this hyperalgesia. METHODS: Seventy-five patients undergoing major abdominal surgery were randomly assigned to receive (1) intraoperative remifentanil at 0.05 microg x kg(-1) x min(-1) (small-dose remifentanil); (2) intraoperative remifentanil at 0.40 microg x kg(-1) x min(-1) (large-dose remifentanil); or (3) intraoperative remifentanil at 0.40 microg x kg(-1) x min(-1) and 0.5 mg/kg ketamine just after the induction, followed by an intraoperative infusion of 5 microg x kg(-1) x min(-1) until skin closure and then 2 microg x kg(-1) x min(-1) for 48 h (large-dose remifentanil-ketamine). Pain scores and morphine consumption were recorded for 48 postoperative hours. Quantitative sensory tests, peak expiratory flow measures, and cognitive tests were performed at 24 and 48 h. RESULTS: Hyperalgesia to von Frey hair stimulation adjacent to the surgical wound and morphine requirements were larger (P < 0.05) and allodynia to von Frey hair stimulation was greater (P < 0.01) in the large-dose remifentanil group compared with the other two groups, which were comparable. There were no significant differences in pain, pressure pain detection threshold with an algometer, peak flow, cognitive tests, or side effects. CONCLUSION: A relatively large dose of intraoperative remifentanil triggers postoperative secondary hyperalgesia. Remifentanil-induced hyperalgesia was prevented by small-dose ketamine, implicating an N-methyl-d-aspartate pain-facilitator process.

UNLABELLED: Perioperative opioids increase postoperative pain and morphine requirement, suggesting acute opioid tolerance. Furthermore, opioids elicit N-methyl-D-aspartate (NMDA)-dependent pain hypersensitivity. We investigated postfentanyl morphine analgesic effects and the consequences of NMDA-receptor antagonist (ketamine) pretreatment. The rat nociceptive threshold was measured by the paw-pressure vocalization test. Four fentanyl boluses (every 15 min) elicited a dose-dependent (a) increase followed by an immediate decrease of the nociceptive threshold and (b) reduction of the analgesic effect of a subsequent morphine administration (5 mg/kg): -15.8%, -46.6%, -85.1% (4 x 20, 4 x 60, 4 x 100 microg/kg of fentanyl, respectively). Ketamine pretreatment (10 mg/kg) increased the fentanyl analgesic effect (4 x 60 microg/kg), suppressed the immediate hyperalgesic phase, and restored the full effect of a subsequent morphine injection. Fentanyl also elicited a delayed dose-dependent long-lasting decrease of the nociceptive threshold (days) that was prevented by a single ketamine pretreatment before fentanyl. However, a morphine administration at the end of the fentanyl effects restored the long-lasting hyperalgesia. Repeated ketamine administrations were required to obtain a complete preventive effect. Although ketamine had no analgesic effect per se at the dose used herein, our results indicate that sustained NMDA-receptor blocking could be a fruitful therapy for improving postoperative morphine effectiveness. IMPLICATIONS: Fentanyl-induced analgesia is followed by early hyperalgesia (hours), acute tolerance to the analgesic effects of morphine, and long-lasting hyperalgesia (days). All these phenomena are totally prevented by repeated administrations of the NMDA-receptor antagonist, ketamine, simultaneously with fentanyl and morphine administration.

Tiret L (Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 258, Hōpital Broussais, 96 rue Didot, 75674 Paris Cédex 14, France), Hausherr E, Thicoipe M, Garros B, Maurette P, Castel J P and Hatton F. The epidemiology of head trauma in Aquitaine (France), 1986: A community-based study of hospital admissions and deaths. International Journal of Epidemiology 1990, 19: 133–140. This paper reports the findings of a study of head trauma conducted over a one-year period within a defined region with a population of 2.7 million (Aquitaine, France). It includes cases resulting in death prior to hospitalization or requiring hospitalization. During the one-year period, 391 deaths and 8549 hospital admissions due to head trauma occurred, yielding an annual estimate of 8940 head-injured people. The immediate case-fatality rate was 4.4%. Among non-fatal cases, 80% were mild, 11% moderate and 9% severe. The overall annual incidence was 281/100 000 in both sexes (384 and 185/100 000 in males and females respectively). The annual death rate was 22/100 000 (33 and 12, respectively). Patterns of incidence by age and sex were in general agreement with earlier studies. The main causes of head trauma were traffic accidents (60%) and falls (33%). One-third of hospitalized patients had no injury other than the head trauma. The most frequently associated injuries were those involving extremities, whereas the most severe were those involving the abdomen. The Injury Severity Score (ISS) ranged from 4 to 66, with a mean of 9 and a median of 5. At the eighth day following injury, 25% of hospital-treated patients were still hospitalized and 2% had died. The outcome correlated well with the ISS.

To determine what consequences cognitive, behavioural or somatic impairments had on disabilities and recovery after a head injury (HI), a population-based sample of 231 adult patients was studied 5 years after an HI. Eighty lower-limb-injured (LLI) patients were considered as controls. Sixty-four LLI and 176 HI patients were reviewed (114 minor, 35 moderate, and 27 severe HI). Prevalence values of headaches (44-54%), dizziness (26-37%), and anxiety (47-63%) were not significantly different in the three HI severity groups, but were significantly lower in patients with an isolated limb injury (12-15%). Memory problems and depressive mood increased with injury severity. Mental impairments were frequent in severe HI patients (18-40% of patients). In minor and moderate HI patients, most disabilities were related to associated injuries. According to the Glasgow Outcome Scale (GOS), recovery was not considered as good because of somatic, behavioural or cognitive complaints in 2.5%, 5.7% and 59.2% of surviving patients in each of the above HI groups. Somatic or behavioural complaints may have considerable consequences in some minor HI patients, and the long-term management of certain patients needs improvement because these impairments are misunderstood.