In 60 adult patients undergoing general surgical procedures, the effect of pancuronium or d-tubocurarine "pretreatment" on the injection of a 0.1 mg X kg-1 bolus of atracurium was measured in two separate studies. In study 1, the patients received either 0.5 mg (approximately 0.007 mg X kg-1) or 1.0 mg (approximately 0.015 mg X kg-1) pancuronium, or placebo (saline) three minutes before the injection of atracurium 0.1 mg X kg-1. In study 2, the patients received 0.05 mg X kg-1 or 0.1 mg X kg-1 d-tubocurarine, or a placebo. The degree of neuromuscular blockade was assessed by evoked mechanogram (adductor pollicis muscle) using supramaximal train-of-four stimulation. Patients receiving pancuronium or d-tubocurarine pretreatment (equal to an ED5-ED15 dose) showed significantly greater inhibition of twitch (ED70-ED80) and train-of-four ratio compared with the placebo groups (ED35-ED40). Pretreatment with the larger dose of d-tubocurarine (0.1 mg X kg-1) was associated with significant neuromuscular blockade. It is concluded that pancuronium and d-tubocurarine pretreatments potentiate the clinical action of 0.1 mg X kg-1 atracurium in man by 35-100 per cent.
Using a randomized blind cross-over design, the comparative efficacy of clonidine in prolonging tetracaine spinal anaesthesia was studied in six mongrel dogs. Lumbar subarachnoid injections (1 ml) of: tetracaine 4 mg with clonidine 150 micrograms, tetracaine 4 mg with epinephrine 200 micrograms, tetracaine 4 mg, clonidine 150 micrograms, epinephrine 200 micrograms, and five per cent dextrose in H2O (vehicle) were administered randomly to each animal at 5-7 day intervals. Subarachnoid tetracaine produced a motor blockade of 186 +/- 58 (mean +/- SEM) min. Both clonidine and epinephrine produced a similar prolongation of tetracaine motor blockade, 135 per cent (p less than 0.01) and 116 per cent (p less than 0.05) respectively, compared with tetracaine alone. No motor blockade was observed in dogs receiving clonidine, epinephrine or five per cent dextrose in H2O. The addition of clonidine to tetracaine spinal anaesthesia produced a significant increase in duration of sensory blockade, 56 per cent (p less than 0.01) and 107 per cent (p less than 0.01) respectively, when compared to tetracaine with and without epinephrine. Subarachnoid clonidine alone produced a sensory blockade of 76 +/- 17 minutes, while only one animal receiving subarachnoid epinephrine had a sensory blockade (40 minutes). No neurologic deficits were observed in any of the animals. The study concludes that during spinal anaesthesia with tetracaine in dogs, clonidine is as effective as epinephrine in prolonging motor blockade, but is more effective in prolonging sensory blockade.
We studied the relationship between arterial carbon dioxide tension (PaCO2) and fresh gas flow (FGF) during use of the Bain breathing circuit for Caesarean section anaesthesia. Thirty-one patients undergoing Caesarean section were anaesthetised using the Bain circuit with intermittent positive pressure ventilation. The PaCO2 were measured at FGF of 70 ml X kg-1 X min-1, 80 ml X kg-1 X min-1, and 100 ml X kg-1 X min-1. The FGF requirement to maintain a given PaCO2 during Caesarean section anaesthesia is the same as the requirements for nonpregnant subjects, despite the increase in carbon dioxide production associated with pregnancy. This is probably because the total FGF determined by body weight and given during Caesarean section anaesthesia is 15-20 per cent higher than nonpregnant levels, due to the weight gain associated with pregnancy. A FGF of 100 ml X kg-1 of pregnant weight/min maintains PaCO2 of 4.44 kPa predelivery, which is in the desirable range of PaCO2 during Caesarean section.
Esmolol, an ultra-short-acting cardioselective beta-adrenergic blocker, was investigated in a double-blind prospective protocol for its ability to control haemodynamic responses associated with tracheal intubation after thiopentone and succinylcholine. Thirty ASA physical status I patients received a 12-minute infusion of esmolol (500 micrograms X kg-1 X min-1 for four minutes, then 300 micrograms X kg-1 X min-1 for 8 minutes) or saline. Five minutes after the start of the drug/placebo infusion, anaesthesia was induced with 4 mg X kg-1 thiopentone followed by succinylcholine for tracheal intubation. Prior to induction esmolol produced significant decreases in heart rate (HR) (9.3 +/- 1.8 per cent) and rate-pressure product (RPP) (13.1 +/- 1.8 per cent), systolic blood pressure (SAP) (4.3 +/- 1.5 per cent) and mean arterial blood pressure (MAP) (1.7 +/- 2.0 per cent). Increases in HR, SAP and RPP after intubation were approximately 50 per cent less in patients given esmolol compared to patients given placebo. There were highly significant differences in HR (p less than 0.0001), and RPP (p less than 0.0005) and significant differences in SAP (p less than 0.05) when the maximal esmolol post-intubation response was compared to the maximal placebo response. Infusion of esmolol in the dose utilized in this study significantly attenuated but did not completely eliminate cardiovascular responses to intubation.
The synergistic effect of pancuronium bromide (PCB) and d-tubocurarine (DTC) on the onset time of neuromuscular blockade was tested in 108 ASA physical status I and II adults anaesthetized with thiopentone, nitrous oxide and halothane. Either saline or a small (priming) dose (DTC, 0.04 mg X kg-1, or PCB, 0.007 mg X kg-1) was administered 3 min before a paralyzing dose of either DTC or PCB. The total dose of relaxant was equivalent to DTC, 0.4 mg X kg-1, or PCB, 0.07 mg X kg-1. Neuromuscular activity was measured using train-of-four stimulation applied every 12 s. Time to 50 per cent first twitch blockade was 63 +/- 4.6 s (mean +/- SEM) with DTC and 88 +/- 5.2 s with PCB (p less than 0.002). Times to 90 per cent blockade were not different between the two drugs (161 +/- 20 s and 141 +/- 21 s respectively). Priming a DTC blockade with either DTC or PCB or priming a PCB blockade with PCB produced an acceleration of less than 10 s at all levels of blockade. Compared with PCB alone, priming PCB blockade with DTC reduced the time to 50 per cent blockade to 71 +/- 4.5 s (p less than 0.02) and to 90 per cent blockade to 111 +/- 8 s (p less than 0.05). Priming did not affect the duration of action significantly, except in the case of PCB priming of DTC, where duration was increased from 39 +/- 4.4 to 57 +/- 4 min (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)