Prévention par la naloxone des effets secondaires de l'analgésie péridurale par morphine pour douleur cancéreuse

Abstract

Forty cancer patients were randomly assigned to two groups (n = 20). All had incapacitating pain unresponsive to the usual non opioid analgesic drugs. An epidural catheter was set up at the level of the most painful metamere, and made to pass subcutancously so as to exit either in the supraclacicular fossa, or on the patient's flank. At T 0, the patients were given 4 mg morphine hydrochloride diluted in 10 ml normal saline. Thirty min later, patients in the naloxone group (group N) were given a 0.4 mg bolus, followed by a constant rate infusion of 5 μg · kg −1 · h −1, of naloxone hydrochloride during 18 h. Patients in group P (placebo) were given normal saline instead. The degree of pain was studied with a visual analogue scale and analgesia was assessed by a clinician on a five point scale. These two parameters were obtained half an hour after the injection of morphine and 2, 4, 6 and 24 hours later. At the same times, the patients were questionned about adverse side-effects : nausea, vomiting, pruritus, dysuria, urinary retention. Respiratory depression was assessed clinically and biologically (blood gas measurements at the afore mentioned times). Heart rate, systolic and diastolic blood pressure were also measured. There was no statistically significant difference between the groups in quality and duration of analgesia. Pain reached its lowest level 4 h after the injection of morphine, returning to half its original value at the 24th h. This was also true for the incidence of nausea (11 in group N, 5 in group P), vomiting (3 in both groups), and urinary retention (6 in group P, 5 in group N). However, 1 case of pruritus occured in the naloxone group, and 4 in the placebo group. There were also two cases of respiratory depression in group P ; in fact, breathing rate was lower in this group than in group N throughout the study, but with no increase in Pa co 2. Lastly, systolic blood pressure was significantly lower than at T 0 in group P (− 5.4 mmHg), and higher in group N (+ 7.6 mmHg). These results might tend to show some beneficial effect of naloxone in the prevention of respiratory depression and pruritus in cancer patients given epidural morphine. However, a larger group of patients, such as that of a multi-center trial, is needed to substantiate them.