Pharmacokinetics of meperidine in spinal anaesthesia

Abstract

Five male patients undergoing haemorrhoidectomy received intrathecal meperidine 1 mg.kg I as the sole anaesthetic agent. Plasma concentration-time profiles were investigated. The peak plasma concentration of meperidine was lntrathecal opioid administration has received less clinical investigation than the epidural route. The intrathecal route has been used to provide analgesia after surgery and for the control of pain in labour and myocardial infarction, i-6 We recently reported the use of intrathecal meperidine as the sole agent for spinal anaesthesia. 7 Since there is no quantitative information available for intrathecal meperidine in doses used for spinal anaesthesia, we performed a study of the kinetics of intrathecal meperidine when used in a dose of I mg.kg -l for spinal anaesthesia. Key words MethodsFive male patients of ASA physical status I or II presenting for haemorrhoidectomy were studied. The mean age was 38 ---15 years, and the mean weight was 61.6 ---6.5kg (---SD). The protocol was approved by the hospital review committee and informed consent was obtained from the patients. No premedication was given.The protocol described in the original report by Famewo and Naguib 7 was employed in this study. In summary, subarachnoid puncture was performed with the patient in the sitting position, using a 22-gauge spinal needle at the lumbar vertebral level of L3/4 or L4/5. Preservative-free meperidine in a dose of 1 mg'kg -J was injected intrathecally using the undiluted concentration of 50 mg.ln1-1, lntraoperative monitoring included ECG, blond pressure, tidal volume, end-tidal CO2 and arterial blood gases.The onset and duration of sensory block as determined by the pinprick method were noted. The onset and duration of motor weakness of the lower extremities were also noted.Postoperatively, patients were monitored closely. Blood pressure, heart rate, and respiratory rate were recorded at hourly intervals, while arterial blood gases were determined at four hourly intervals for the first 24 hours after the end of surgery. One of the authors was always available for immediate assessment of patients should there by any complaint or problem, and any side effects were noted.

The Rational Use of Intrathecal and Extradural Opioids

“…Diamorphine [16,144] and buprenorphine [37] have also been used intrathecally with good effect. Pethidine is the only drug that has been used successfully intrathecally as the sole anaesthetic agent, for genito-urinary [130] and lower abdominal and lower limb surgery [172]. The doses were 0.1 mg kg" 1 and 100 mg, respectively; the effects may have been related to the local anaesthetic properties of pethidine.…”

Intrathecal Pethidine: Pharmacology and Clinical Applications

“…Several studies have measured concentrations of pethidine in plasma and CSF after intrathecal injection. Following a dose of 1 mg/kg, plasma concentrations of pethidine reached maximum mean levels (C max ) of 107-341 ng/ml [16][17][18][19] which is less than the reported minimum effective analgesic concentration (MEAC) of 460 ng/ml 20 . Mean time to maximum concentration (t max ) varied from 45 to 168 min.…”

“…In the first report of spinal anaesthesia using pethidine, Mircea et al described a large series of 713 patients who received intrathecal pethidine in doses ranging from 0.8 to 1 mg/kg or fixed doses of 50 mg or 75 mg for abdominal, perineal and lower limb surgery 5 . Numerous other reports followed and have described the use of intrathecal pethidine for anaesthesia for a variety of surgical procedures, including surgery on the lower limb and hip 5,25-30 , perineal and urological surgery 5,16,18,[30][31][32][33][34][35][36] , lower abdominal surgery 5,25,30,37 and caesarean section 24,[38][39][40][41][42] .…”

“…Andrivet et al reported that two of 10 patients who received intrathecal pethidine 1 mg/kg for orthopaedic surgery developed respiratory depression and required treatment with naloxone 63 . Sangarlangkarn et al gave a fixed dose of pethidine 100 mg intrathecally that was equivalent to a mean dose of 1.8 mg/kg and found that one patient required assisted ventilation 25 31 1 mg/kg 15% 20% 30% 25% Cozian 32 1 mg/kg ns ns 12.5% 62.5% Naguib 16 1 mg/kg 20% 20% nil 60% Talafre 38 1 mg/kg 50% ns 40% 38% Spiers 28 1 mg/kg ns ns ns ns Tauzin-Fin 18 1 mg/kg 1 (3.3%) nil nil nil Lewis 34 1 mg/kg 10% 3.3% 6.7% 13.3% Kafle 39 1 mg/kg 32% 0 8% 32% Nguyen Thi 24 1 mg/kg 36% 0 32% 10.7% Grace 35 0.75 mg/kg 5% ns 10% 35% Grace 35 0.5 mg/kg 4.8% ns 15% 15% Conway 29 0.8 mg/kg 9 (64%) 6 (42.8%) 6 (42.8%) nil Sangarlangkarn 25 100 mg 2 (10%) ns 55% 10% Norris 37 60 mg ns ns ns ns Acalovschi 43 0.5 mg/kg nil nil 4.5% 6.3% Kavuri 26 0.5 mg/kg 17% ns 0 33% Patel 33 0.5 mg/kg 14% ns 0 4.5% Trivedi 27 0.5 mg/kg 0 0 6.3% 6.3% ns=not specified reported respiratory depression in two patients who received a fixed dose of 50 mg 64 . The first patient was an 81-year-old woman who weighed 73 kg and who had received premedication of diazepam 10 mg. She had an upper sensory level of T8 and required naloxone.…”