pancuronium and Kidney-Failure--Chronic

The duration and possible accumulation of atracurium and pancuronium were studied in 59 patients (29 anephric and 30 normal) anaesthetized with 0.5% halothane in O2/N2O and supplemented by fentanyl. Equipotent doses of atracurium (0.5 mg.kg-1) and pancuronium (0.1 mg.kg-1) were given for intubation. Atracurium had a lower potency in anephric patients. The duration (first twitch response (TI) return to 20% of control) for atracurium was 28 min in anephric and 36 in normal patients. The corresponding mean times for pancuronium were 171 and 123 min, but with a very wide variation range 20-380 min and 45-360 min, respectively). The duration of up to 8 incremental doses of atracurium (0.1 mg kg-1) was 27-29 min in normal patients and of up to 13 increments was 25-34 min in anephric patients. Pancuronium (0.015 mg kg-1) was given in a maximum of 4 increments. In normal patients the mean durations were 40-56 min, and in anephric patients 65-100 min. The duration of pancuronium, but not of atracurium, was prolonged with repeated injections (up to 2.7 times) in anephric patients. After pancuronium the spontaneous recovery was significantly slower in anephric patients, while the induced recovery was rapid and reliable in all groups. We conclude that atracurium is a safe and reliable muscle relaxant in normal and anephric patients, while pancuronium in both groups has a disturbing variation in duration and, in addition, signs of significant accumulation in anephric patients. The use of a nerve stimulator is mandatory.

Topics: Adult; Atracurium; Clinical Trials as Topic; Female; Humans; Kidney Failure, Chronic; Male; Neuromuscular Junction; Pancuronium; Random Allocation; Time Factors

Dose-response relations for atracurium, vecuronium and pancuronium were determined in patients in end-stage renal failure for the initial neuromuscular blockade (using three cumulative doses) and for the maintenance of stable 90% response (during continuous infusion). All measurements were during renal transplant surgery, and the interaction of azathioprine on neuromuscular blockade was estimated. Mean ED95 doses were (microgram kg-1): atracurium 375.6, vecuronium 67.2, pancuronium 86.6; the initial blockade required significantly larger doses than in normal patients (37%, 20% and 45%, respectively, using ED50 values). Mean infusion rates for 90% sustained blockade in renal failure were (microgram kg-1 h-1): atracurium 409.4, vecuronium 78.3, pancuronium 14.2. The atracurium dose was not influenced by renal function, whereas vecuronium and pancuronium requirements were significantly reduced by 23.2% and 61.5%, respectively, compared with normal patients (previous study). Azathioprine was injected at the rate of 1 mg kg-1 min-1 for 3 min at stable 90% neuromuscular blockade with constant-rate infusion of the neuromuscular blocking drug. This produced a relatively small and transient antagonism of blockade--probably of negligible clinical significance.

Topics: Adolescent; Adult; Atracurium; Azathioprine; Dose-Response Relationship, Drug; Drug Interactions; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Neuromuscular Junction; Pancuronium; Vecuronium Bromide

Plasma concentrations of pancuronium following single dose administration in six patients, and following multiple dose administration in four patients, all undergoing renal transplantation surgery, were measured using a fluorimetric method. A two-compartment open model was used in the pharmacokinetic analysis of the data. Comparison of the pharmacokinetic findings with data previously obtained for patients undergoing elective surgery but having normal renal function indicated that the clearance of the drug was reduced significantly in the patients with renal failure, and that in these individuals the half-life was increased significantly. Measurement of the evoked mechanical twitch response concurrently with plasma concentration monitoring of pancuronium confirmed that the prolongation of half-life in the patients with renal failure was often but not always associated with an extended duration of neuromuscular blockade and furthermore that the rate of recovery from block might also be prolonged. The clinical implications of these findings are discussed.

Topics: Adult; Aged; Biopharmaceutics; Clinical Trials as Topic; Dose-Response Relationship, Drug; Female; Half-Life; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Pancuronium; Transplantation, Homologous

Topics: Humans; Kidney Failure, Chronic; Neuromuscular Junction; Pancuronium; Peritoneal Dialysis; Postoperative Complications

Fifteen patients with and ten patients without renal failure (RF) were given vecuronium as the sole muscle relaxant during anaesthesia. RF patients were divided into two subgroups according to the daily diuresis (RF I, below 0.5 l/d; RF II, over 0.5 l/d). Vecuronium was given in small doses until the electromyographic twitch response showed 90% relaxation. The results showed great individual variations, and there were no statistically significant differences between the study groups in the parameters studied (ED90 dose, total consumption of the drug in mg kg-1 min-1, vecuronium plasma concentrations, twitch response) during induction and anaesthesia. After reversal of relaxation, the twitch response recovered more slowly in the RF I group than in the others (P less than 0.05). No complications occurred and it is confirmed that it is safe to use vecuronium as a muscle relaxant in patients with RF.

Topics: Adult; Blood Gas Analysis; Blood Pressure; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Muscle Contraction; Neuromuscular Blocking Agents; Pancuronium; Risk; Vecuronium Bromide

Dose-response relationships for a 1:4 weight ratio-mixture of pancuronium and metocurine were studied during inhalational anesthesia with halothane and isoflurane in patients with and without renal failure. The time for recovery from 10 to 20% of control thumb twitch tension also was determined. In subjects with normal renal function, relaxant doses required for 95% twitch height suppression (ED95) were 50% of those predicted by simple addition of effects when used with a balanced anesthetic technique, 37% of predicted when used with 1.3 MAC halothane, and 25% of predicted when used with 1.3 MAC isoflurane (P less than 0.05). In subjects with renal failure, ED95 values for the combination were 40% of predicted when used with 1.2 MAC halothane and 45% of predicted when used with 1.2 MAC isoflurane (NS). For relaxants used singly in renal failure, pancuronium alone was slightly enhanced by 1.2 MAC halothane (85% of predicted), while 1.1 MAC isoflurane reduced the ED95 to 57% of predicted (P less than 0.05). Similar results were obtained for metocurine alone when used in renal failure (77 and 58% of predicted when used with halothane and isoflurane, respectively) (NS). Predicted values are published results for balanced anesthesia in normals. Recovery times were prolonged twofold in renal failure (P less than 0.05). Thus, the combination of pancuronium and metocurine is synergistic to the same degree in normals and in renal failure patients, but the total blockade produced by the combination is enhanced by halothane and isoflurane only in normals.

Topics: Adult; Dose-Response Relationship, Drug; Drug Synergism; Female; Halothane; Humans; Isoflurane; Kidney Failure, Chronic; Male; Methyl Ethers; Middle Aged; Pancuronium; Tubocurarine

Vecuronium (initial dose 0.1 mg kg-1; incremental doses 0.04 mg kg-1) was given to 21 normal and 21 anephric patients. There were no gross differences between the two groups in the effect or in the duration of action of either initial or incremental doses, except in two anephric patients who were resistant to the agent. Reversal with neostigmine was satisfactory. In normal patients the initial dose of vecuronium was slower in onset of action than was atracurium 0.5 mg kg-1 (26 patients): the first two incremental doses of vecuronium were administered significantly earlier than the corresponding increments of atracurium (0.2 mg kg-1), but the duration of action of increments over-all was not greatly different. However, in anephric patients, except in the resistant patients, the behaviour of vecuronium was similar to that of atracurium (26 patients). A comparison with an initial dose of tubocurarine 0.5 mg kg-1 given to 20 anephric patients and tubocurarine 0.6 mg kg-1 given to 21 normal and 20 anephric patients showed tubocurarine to be longer acting and considerably less predictable. This was particularly so in the anephric group, in which its action sometimes persisted after neostigmine had been given.

Topics: Adolescent; Adult; Aged; Anesthesia, General; Atracurium; Blood Pressure; Female; Heart Rate; Humans; Intubation, Intratracheal; Isoquinolines; Kidney Failure, Chronic; Male; Middle Aged; Muscle Contraction; Neostigmine; Neuromuscular Blocking Agents; Pancuronium; Time Factors; Tubocurarine; Vecuronium Bromide

Neuromuscular blockade during surgery was provided with vecuronium in 24 adult patients in end-stage renal failure and in 21 normal patients who served as controls. Dose response curves were constructed which showed that the effective doses required to produce 50, 90 and 95 per cent neuromuscular blockade in patients with renal failure were 27.5, 43 and 49 micrograms X kg-1 respectively. These were not significantly different from the doses of 31, 49 and 57 micrograms X kg-1 in the normal patients. Repeated small doses of 0.01 mg X kg-1 had a significantly longer duration of action and were associated with some cumulation in the renal failure group. Recovery from the block occurred rapidly after neostigmine, was no different in renal failure and was not associated with recurarization. It is concluded that, when given to subjects in renal failure, vecuronium offers advantages over established agents such as shorter duration of action and easy reversibility.

Topics: Adult; Anesthesia, General; Dose-Response Relationship, Drug; Humans; Kidney Failure, Chronic; Metabolic Clearance Rate; Neuromuscular Blocking Agents; Neuromuscular Junction; Pancuronium; Synaptic Transmission; Vecuronium Bromide

Neuromuscular transmission was measured using train-of-four stimulation, during and after anaesthesia, in 20 patients with end-stage renal failure. Neuromuscular blockade was provided with pancuronium in single doses of either 3 or 6 mg per 70 kg, and antagonized at 10% recovery with atropine and neostigmine 2.5 mg per 70 kg. Reversal was followed by progressive recovery of muscle twitch in every patient during the 3 h of the study. Recovery was more rapid after the smaller dose of pancuronium and was inversely correlated with the duration of blockade. It is concluded that, when pancuronium is antagonized with neostigmine in patients with renal failure, neuromuscular transmission recovers without evidence of recurarization. However, when large doses of pancuronium are antagonized with neostigmine 2.5 mg, recovery may be insufficient to ensure normal ventilatory function.

Topics: Adult; Aged; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Neostigmine; Neuromuscular Junction; Pancuronium; Synaptic Transmission; Time Factors

To determine the influence of renal failure on the pharmacokinetics and neuromuscular blockade of Org NC 45 (Norcuron), a new monoquaternary homologue of pancuronium, 13 patients under halothane and nitrous oxide anesthesia were studied. Org NC 45 was administered by 2-min infusion in doses of 0.28 mg kg-1 (normal renal function group, n = 4) and 0.14 mg kg-1 (renal failure group, n = 5). Four additional patients with normal renal function were given Org NC 45 0.14 mg kg-1 to determine the onset, duration and recovery rate of neuromuscular blockade. The serum concentration of Org NC 45 was determined by normal-phase high performance liquid chromatography (sensitivity 50 ng ml-1), and a two-compartment open pharmacokinetic model was fitted to resulting data. Estimates of distribution half-life (T 1/2 alpha), elimination half-life (T 1/2 beta), volume of distribution at steady state (Vss) and clearance of Org NC 45 did not differ significantly between patients with normal renal function and those with renal failure. The onset, duration and recovery rate times of the neuromuscular blockade by Org NC 45 0.14 mg kg-1 in patients with normal renal function and those with renal failure did not differ significantly.

Topics: Adult; Chromatography, High Pressure Liquid; Half-Life; Humans; Kidney Failure, Chronic; Kinetics; Metabolic Clearance Rate; Middle Aged; Neuromuscular Blocking Agents; Pancuronium; Vecuronium Bromide

Topics: Adult; Anesthesia, General; Dose-Response Relationship, Drug; Female; Humans; Kidney Failure, Chronic; Kinetics; Male; Pancuronium

We present 3 patients with chronic renal failure who had postoperative paralysis due to the administration muscle relaxants. One of them received gallamine, a non-depolarizing blocking agent that is mainly excreted by the kidney (70--90%). Two of them received pancuronium bromide, also a non-depolarizing blocking agent which is partially excreted by the kidneys (37--44%). All of them received succinylcholine. Succinylcholine is hydrolyzed by the serum cholinesterase into succinylmonocholine and choline. These active metabolites are excreted by the kidney. These patients serve as examples of the importance of considering the route of excretion of drugs and their metabolites in clinical situations involving the renal failure patient. The pharmacology of drugs administered relative to surgical procedures is reviewed.

Topics: Adult; Anesthesia; Arteriovenous Shunt, Surgical; Female; Humans; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Middle Aged; Neuromuscular Blocking Agents; Pancuronium; Paralysis; Succinylcholine; Transplantation, Homologous

Objective studies about the duration of action pancuronium (PCM) in renal failure patients are scarce. This study was undertaken to obtain more complete information on spontaneous reversal from PCM-induced neuromuscular block by monitoring the twitch height to full recovery in the absence of any potentiating agent. Thumb abduction was monitored by a deplacement transducer in end-stage renal failure (ESRF) and in control patients without renal failure (RF) during neuroleptanalgesia after 0.04 mg/kg and 0.08 mg/kg PCM administration. In the small dosage series, the prologation of action in ESRF becomes significant for the 75% recovery level (mean values +/- s.e.mean:control: 42 +/- 7 min, ESRF: 71 +/- 10 min, P less than or equal to 0.05). In the second series (0.08 mg/kg), the 50% recovery level is already significantly delayed in ESRF patients (control: 91 +/- 7 min, ESRF: 163 +/- 27 min, P less than or equal to 0.05). The 100% twitch height recovery is obtained with 0.04 mg/kg PCM within 65+/- 7 min for patients without RF and within 103 +/- 9 min in ESRF patients (P less than or equal to 0.01). For the 0.08 mg/kg PCM dose, these figures are, respectively, 139 +/- 9 min and 214 +/- 20 min (P less than or equal to 0.01). The prolongation of PCM action in ESRF is in agreement with the pharmaco-kinetics of the drug. Large dosages of PCM must be avoided in ESRF patients because it delays spontaneous full recovery for too long.

Topics: Adult; Drug Evaluation; Female; Humans; Kidney Failure, Chronic; Male; Nerve Block; Neuromuscular Junction; Pancuronium

Plasma concentrations of pancuronium were measured using a fluorimetric method in six patients with normal renal function and seven patients in chronic renal failure. A tow-compartment open model was used in the pharmacokinetic analysis of the data. With this model, the clearance of pancuronium was found to be reduced significantly in the patients with renal failure, and in these individuals the volume of the central (distribution) compartment was increased significantly. The clinical implications of these findings are discussed.

Topics: Adult; Female; Humans; Kidney; Kidney Failure, Chronic; Male; Middle Aged; Models, Biological; Pancuronium

Topics: Female; Humans; Kidney Failure, Chronic; Liver Diseases; Middle Aged; Pancreatic Cyst; Pancuronium; Postoperative Complications; Renal Dialysis

Topics: Humans; Kidney Failure, Chronic; Pancuronium

Topics: Adjuvants, Anesthesia; Adolescent; Adult; Aged; Child; Evaluation Studies as Topic; Humans; Kidney Failure, Chronic; Kidney Transplantation; Middle Aged; Pancuronium; Transplantation, Homologous

Topics: Adult; Aged; Androstanes; Anesthesia, General; Female; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Nephrectomy; Neuromuscular Junction; Neuromuscular Nondepolarizing Agents; Pancuronium