[Development of continuous monitoring of spontaneous respiration in the postoperative phase. 2. Cutaneous oxygen and carbon dioxide partial pressures following i.v. bolus application of fentanyl, buprenorphine, naloxone and amiphenazole in healthy adult subjects]

Abstract

Methods: In an attempt to develop a noninvasive monitoring technique for patients in the early postoperative period, cutaneous O2 and CO2 pressures (pctO2, pctCO2) were monitored in ten healthy adult volunteers of both sexes (5 male, 5 female, age 29 +/- 5 years, weight 68 +/- 11 kg) who received, in several sessions after a 60-min equilibration period, i.v. bolus doses of fentanyl (3 micrograms/kg and, 60 min later, another 1.5 micrograms/kg), buprenorphine (3 and 1.5 micrograms/kg), naloxone (1.8 and 0.9 micrograms/kg), and the respiratory analeptic amiphenazole (2 and 1 mg/kg) as well as combinations of fentanyl/amiphenazole or buprenorphine/naloxone in the aforementioned dosages. Data were collected and stored by a personal computer using the TCM3 system with a combination electrode for simultaneous measuring of pctO2 and pctCO2 (TINA, Radiometer) at 30-s intervals. The overall observation period was 240 min. Means, standard deviations, and ranges were calculated for individual data and data pooled for 15-min intervals. Groups were compared by means of Student's t-test and analysis of variance.

Results: Following i.v. fentanyl 3 micrograms/kg, pctO2 decreased and pctCO2 increased rapidly and statistically significantly. The changes were of similar intensity after the first and second doses (1.5 micrograms/kg) and normalized about 60 min after each injection. In contrast, following i.v. buprenorphine (3 and 1.5 micrograms/kg) the cutaneous partial pressures changed continuously and progressively during the observation period and did not reach the control values after 240 min. Naloxone and amiphenazole injections had no obvious influence on the time course of the blood gas tensions. If opiates and antagonists were combined, neither the fentanyl/amiphenazole group nor the buprenorphine/naloxone group differed significantly from the respective opiate groups.

Discussion and conclusion: As was discussed in detail in a previous communication, monitoring of opiate-induced respiratory depression must be nonstimulant and, preferably, noninvasive. Whereas the precision and/or limitations of monitoring partial oxygen saturations by pulse oximetry is well documented in the literature, knowledge of the value of cutaneous partial pressure monitoring is still limited and controversial for the adult patient population. The present study was performed to define the usefulness of cutaneous blood gas analysis in healthy volunteers receiving opiate dosages well known in recovery room patients. It is concluded that continuous monitoring of pctO2 and pctCO2 can indeed detect opiate-induced respiratory depression in adults. The well-known difference in respiratory pattern for fentanyl and buprenorphine could easily be determined. It was confirmed that naloxone and amiphenazole in the dosage range studied do not influence spontaneous respiration in healthy adults. Thus, the authors are convinced that continuous monitoring of cutaneous partial pressures of oxygen and carbon dioxide is sensitive enough to be used, in combination with pulse oximetry, in a monitoring concept for patients recovering from surgery and anaesthesia. Results in patients undergoing conventional pain management or patient-controlled analgesia with relatively high opiate dosages will be presented in following papers. Concerning the controversy about clinically relevant interactions between fentanyl and amiphenazole or buprenorphine and naloxone, the present study did not confirm any useful antagonism. Whether this is due to limitations of cutaneous monitoring, the difference between volunteers and patients, or pharmacological reasons must be evaluated in further investigations.