J. F. Crul

Post-operative analgesia by high thoracic epidural versus intramuscular nicomorphine after thoracotomy. Part III

One hundred and twenty‐nine patients were subjected to three different types of thoracic operations. The patients were randomly allocated to balanced intravenous anaesthesia including i.v. nicomorphine during surgery and epidural nicomorphine post‐operatively (epidural group, n = 58) or to balanced intravenous anaesthesia without i.v. opiates but with high thoracic epidural regional block during the operation and with post‐operative intramuscular nicomorphine (intramuscular group, n = 71). Post‐operative nicomorphine was only given at the request of the patients, and as frequently as needed to obtain satisfactory pain relief. Patients in the epidural group were given nicomorphine exclusively by epidural injection. Post‐operatively, both groups (i.m. and epidural) obtained effective and rapid onset of analgesia, but the pain assessments by the patient and the medical team favoured the epidural group. The requirements of nicomorphine over a period of 3 days were significantly lower in the epidural group 42 mg (s.d.= 18) versus 92 mg (s.d. = 33) in the intramuscular group. Significantly fewer pulmonary complications were observed in the epidural group: 7 atelectases compared to 27 in the intramuscular group. The epidural group showed no signs of ventilatory depression in spite of a catheter inserted at the T3‐T4 level.

Post‐operative Analgesia by Epidural Versus Intramuscular Nicomorphine after Thoracotomy. Part II

One hundred and sixty‐three patients subjected to three different types of thoracic operation were allocated randomly either to balanced intravenous anaesthesia including i. v. opiates with post‐operative intramuscular opiates (intramuscular group) or to balanced intravenous anaesthesia without i. v. opiates but with high thoracic epidural regional block during the operation as well as epidural nicomorphine post‐operatively (epidural group). Post‐operative nicomorphine in either group was given only at the request of the patient and as frequently as needed to obtain satisfactory pain relief. Patients in the epidural group were given nicomorphine exclusively by epidural injection. Patients in the epidural group required significantly less nicomorphine for effective pain relief (29 mg (sd = 10) over a period of 3 days compared to 52 mg (sd = 27) in the intramuscular group. Significantly fewer pulmonary complications in the epidural group were observed (9 atelectases in 83 patients in the epidural group compared to 24 atelectases in 80 patients in the intramuscular group). Only one patient developed pneumonia (intramuscular group). Although the epidural catheter was inserted at the T3‐T4 level, no signs of ventilatory depression were found; on the contrary, respiration in the epidural group was significantly better than the intramuscular group. None of the patients, in either analgesia group, needed to be ventilated post‐operatively.

Intradermal Histamine Release by 3 Muscle Relaxants

The induration and redness caused by intradermal injections of equipotent doses of atracurium, vecuronium and d‐tubocurarine were measured in six healthy, male volunteers. Atracurium and d‐tubocurarine were almost indistinguishable in their reactions. Vecuronium caused a significantly smaller response than both atracurium and d‐tubocurarine. We therefore suggest that of these three drugs, vecuronium may cause the least histamine release and is, perhaps, the drug of choice in patients with a history of asthma or allergy.

Relative Potency of Org NC45, Pancuronium, Alcuronium and Tubocurarine in Anaesthetized Man

The relative potency, time-course of action and cardiovascular effects of Org NC 45, a new non-depolarizing neuromuscular blocking agent, have been compared with those of pancuronium, alcuronium and tubocurarine in 64 anaesthetized patients. The relative potency (ED50) to Org NC 45 was 1.74, 3.69 and 8.57 respectively. In doses which caused useful surgical relaxation, duration of action of Org NC 45 was 34%, 39% and 26% that of pancuronium, alcuroniuym and tubocurarine. After administration of repeated doses no cumulation was seen for Org NC 45. The new drug was free from any effect on arterial pressure and heart rate.

Hypothermia and the Pharmacokinetics and Pharmacodynamics of Pancuronium in the Cat

We tested the effect of hypothermia on the pharmacokinetics and pharmacodynamics of pancuronium in the cat. In 14 cats given pancuronium, 120 microgram/kg i.v., we found that neuromuscular block lasted between 2.5 and 3.0 times longer at 29 degrees C (N = 5) than at 34 degrees C (N = 5) or 39 degrees C (N = 4). The apparent plasma elimination half-life was 46 +/- 7 min (S.E.) at 29 degrees C as compared to 21 +/- 2 and 25 +/- 6 min at 34 and 39 degrees C, respectively. The volume of distribution of the central compartment and total volume of distribution at steady state were less at 29 and 34 dgrees C than at 39 degrees C. Total plasma clearance was 4.3 +/- 0.4 ml/kg/min at 29 degrees C and 10.7 +/- 0.9 and 10.9 +/- 1.5 ml/kg/min at 34 and 39 degrees C, respectively. The reduced plasma clearance resulted at least in part from a markedly reduced biliary and urinary excretion of pancuronium at 29 degrees C as compared to 34 and 39 degrees C. In four other cats, the plasma concentration of pancuronium was correlated with depression of twitch tension under steady-state conditions. The ED50 of pancuronium (plasma concentration required for a 50% depression of twitch tension) was 0.035 and 0.073 microgram/ml at 29 and 38 degrees C, respectively. We conclude that a pancuronium neuromuscular block is prolonged at 29 degrees C because of an increased sensitivity of the neuromuscular junction to pancuronium and delayed biliary and urinary excretion.

The Comparative Potency and Pharmacokinetics of Pancuronium and Its Metabolites in Anesthetized Man

To determine the potency of pancuronium and its metabolites, 3-OH-, 17-OH- and 3,17-OH-pancuronium, cumulative dose-response curves were determined in five anesthetized patients with each drug. Pancuronium (ED50 = 0.041 mg/kg) was 2 times more potent than 3-OH-pancuronium (ED50 = 0.082 mg/kg), 50 times more potent than 17-OH-pancuronium (ED50 = 2.0 mg/kg) and 54 times more potent than 3,17-OH--pancuronium (ED50 = 2.15 mg/kg). In 21 other patients, one equipotent dose of either pancuronium or one of its metabolites was given as an i.v. bolus. Onset time and duration of neuromuscular blockade from 3-OH- and 3,17-OH-pancuronium did not differ significantly from that of pancuronium; 17-OH-pancuronium had a shorter duration of action than did pancuronium. Although pancuronium tended to have a slightly longer elimination half-life, the pharmacokinetics of the four drugs did not differ significantly. The elimination half-lifes were 110, 68, 73 and 71 min for pancuronium and its 3-OH, 17-OH and 3,17-OH derivatives, respectively. We conclude that although pancuronium is more potent than its 3-OH, 17-OH and 3,17-OH metabolites, the pharmacokinetics of these three metabolites do not differ from each other and from that of pancuronium.