The optimal priming dose for atracurium

To determine the optimal priming dose for administration in divided doses, atracurium was given to 77 patients either in a single dose of 0.5 mg X kg-1 or in an initial dose of 0.04, 0.05, 0.06, 0.07, 0.08 or 0.09 mg X kg-1, followed three minutes later by the remainder of the 0.5 mg X kg-1 dose. Patients were anaesthetized throughout the study. When atracurium was given as a single bolus of 0.5 mg X kg-1, the mean time to complete neuromuscular block was 141.5 seconds. Administration in divided doses accelerated the onset time (p less than 0.01), that is the time from the intubating dose to the complete suppression of train-of-four (TOF) response. The TOF ratio decreased slightly but statistically significantly following the priming doses. When the priming dose was 0.05 mg X kg-1, the mean onset time was 70.9 seconds and priming with larger doses did not add any further advantage. It is concluded that 0.05 mg X kg-1 appears to be the optimal priming dose for the administration of atracurium in divided doses. When 0.05 mg X kg-1 is given three minutes before the intubating dose, tracheal intubation can be accomplished in less than 90 seconds.     

Double-blind comparison of lidocaine,tubocurarine and diazepam pretreatment in modifying intraocular pressure increases

One hundred and sixty patients, divided randomly into four groups received normal saline (5 ml), d-tubocurarine (0.05 mg X kg-1), diazepam (0.1 mg X kg-1) or lidocaine (1 mg X kg-1) as pretreatment, in a double blind manner, five minutes before anaesthetic induction with thiopentone and succinylcholine (1 mg X kg-1). Succinylcholine caused a significant increase in IOP in all groups. However, in the lidocaine group, this increase was significantly less than that observed in the control group. The post-succinylcholine increase in IOP was further aggravated by tracheal intubation in all except the lidocaine group. A further clinical trial with higher doses of lidocaine is suggested to assess its ability to obtund the succinylcholine-induced increase in IOP. Lidocaine in a dose of 1 mg X kg-1 IV prevents the rise in IOP which follows intubation.     

Rapid tracheal intubation with atracurium--a comparison of priming intervals

To determine the optimal interval between the administration of the priming dose and the intubating dose, atracurium was given to 44 patients either in a single dose of 0.5 mg X kg-1 or in an initial dose of 0.06 mg X kg-1 followed two, three or five minutes later with 0.44 mg X kg-1. When atracurium was given as a single bolus of 0.5 mg X kg-1 the time to 100 per cent twitch suppression (onset time) was 90.9 +/- 36 (mean +/- SD) seconds. When the priming interval was two minutes, the onset time of the intubating dose was 76.6 +/- 42.2 seconds (p = NS). But when the priming interval was three or five minutes, the onset times were 42.2 +/- 16.5 (p less than 0.01) and 52.6 +/- 28.8 (p less than 0.05) seconds respectively. Waiting for five minutes after the administration of the priming dose did not improve the intubating conditions. It is concluded that three minutes appears to be the optimal time interval for the administration of atracurium in divided doses. When a priming dose of atracurium is given three minutes before the intubating dose, it can provide an alternative to succinylcholine for rapid endotracheal intubation.     

Accelerated reversal of atracurium blockade with divided doses of neostigmine

The hypothesis that administration of neostigmine in divided doses might accelerate the antagonism of neuromuscular blockade was investigated. Neostigmine 0.05 mg X kg-1 was administered either in a single bolus dose (Group I, n = 16) or in an initial dose of 0.01 mg X kg-1 followed three minutes later by 0.04 mg X kg-1 (Group II, n = 16) for antagonism of atracurium-induced blockade. Reversal was attempted at 10 per cent spontaneous recovery of twitch height. The mean time (+/- SD) from the first injection of the drug until the train-of-four (TOF) ratio value had reached 0.75 was significantly shorter in Group II (p less than 0.05) than in Group I (391.8 +/- 83.3 and 468.6 +/- 150.3 seconds respectively). The rate of TOF ratio recovery was 2.5 times faster after neostigmine administration in divided doses. It is concluded that administration of neostigmine in divided doses, as described in this study, produced a significantly faster reversal of residual atracurium-induced neuromuscular blockade as compared to a single bolus administration.     

Potentiation of atracurium by pancuronium and d-tubocurarine

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.     

Premedication using intrarectal midazolam. Study of effective dosage in pediatric anesthesia

The object of this study was to determine the optimal dose of midazolam given per rectum which would produce sedation adequate for inducing inhalational anaesthesia in paediatric practice. Five doses were studied: 0.15, 0.25, 0.30, 0.35 and 0.40 mg X kg-1. The criteria used to appreciate the effectiveness of the sedation at 30 min were the change in the child's behaviour, with a scale of 6 levels, and the acceptance of the mask and anaesthetic vapours. There was a significant correlation between the dose administered and the degree of sedation, as well as between the dose administered and the lack of reaction to the mask. Significantly better results were found with the higher doses of 0.35 and 0.40 mg X kg-1, when compared with the children who had received 0.15 and 0.25 mg X kg-1. Only in the groups who received 0.35 and 0.40 mg X kg-1 were the degrees of sedation and acceptance of induction considered as adequate. The dose of 0.35 mg X kg-1 seemed to be the best dose for adequately premedicating a child.     

Pentobarbital antagonizes the effect of morphine on cardiac acceleration response to noxious stimulation

The effects of morphine alone and in combination with pentobarbital on the cardiac acceleration response to somatic noxious stimulation were studied in 145 rats. It was found that pentobarbital in subanesthetic doses (1-10 mg X kg-1) weakened the inhibitory effect of morphine on the cardiac acceleration response; it antagonized the effect of morphine in a dose-dependent manner. The maximal antagonism was observed with a pentobarbital dose of 10 mg X kg-1. With this dose of pentobarbital, even 200 mg X kg-1 or morphine was unable to block the cardiac acceleration response (without pentobarbital, morphine blocked the response in a dose of 10 mg X kg-1). Caffeine (10 mg X kg-1), on the contrary, strengthened the effect of morphine on the cardiac acceleration response: there was a significant (P less than 0.05) shift to the left along the dose axis in the position of morphine dose-effect curve for the cardiac acceleration response. It has been suggested that the effect of morphine on the cardiac acceleration response to noxious stimulation results primarily from activation of inhibitory control mechanisms concerned with this response; pentobarbital depresses the inhibitory control mechanisms and, therefore, weakens the effect of morphine.     

Use of atracurium in a patient with plasma cholinesterase deficiency

The use of atracurium during anaesthesia for abdominal hysterectomy in a 37-year-old patient with homozygous plasma cholinesterase [EsEs] deficiency is described. Intubation was achieved utilizing 0.47 mg X kg-1 of atracurium. Subsequent doses of 0.08 mg X kg-1, 0.12 mg X kg-1 and 0.12 mg X kg-1 were given 34, 57 and 78 minutes respectively after the initial dose. At the time of reversal of the residual effects of neuromuscular blockade, 26 minutes after the last dose, spontaneous respiration had resumed. The duration of action of the drug was not different from that described in normal patients. Atracurium would appear to be a safe drug to provide neuromuscular relaxation in patients with plasma cholinesterase deficiency, where surgical procedures of intermediate duration are being undertaken.     

Hemodynamic effects of vecuronium in man

The cardiovascular effects of vecuronium (Organon NC 45 or Norcuron) in man were determined through different protocols using continuous recording of heart rate, arterial blood pressure and parameters obtained by a Swan-Ganz catheter. In healthy anaesthetized patients (n = 23), the effects of a dose of 0.1 mg X kg-1 pancuronium (group A) were compared to those of two doses of vecuronium: 0.1 mg X kg-1 (group B) and 0.3 mg X kg-1 (group C). Pancuronium induced an increase in heart rate (+12%), arterial pressure (+16%) and cardiac index (+8%). No change occurred with vecuronium. In patients under mechanical ventilation in an intensive care unit, we compared the effects of pancuronium 0.1 mg X kg-1 (group D; n = 10), d-tubocurarine (group E; n = 11), vecuronium 0.1 mg X kg-1 (group F; n = 9) and 0.3 mg X kg-1 (group G; n = 10). Pancuronium induced an increase in heart rate (+12%), arterial pressure (+8%) and cardiac index (+9%). d-Tubocurarine induced an increase in heart rate (+6%), a decrease in arterial pressure (-24%) and cardiac index (-17%). No change was observed after vecuronium 0.1 mg X kg-1. After vecuronium 0.3 mg X kg-1, the changes were minimal: a slight decrease in arterial pressure (-5%), a very slight (+3%) and transient (3 min) increase in heart rate were observed. The doses were approximately equipotent in groups A, B and C, whereas the dose of 0.3 mg X kg-1 in group G is about 10 times the 90% effective dose of vecuronium. In geriatric patients with per- or postoperative circulatory deficiency (group H; n = 10, mean age 83 yr), no hemodynamic side effects were observed. Vecuronium seems to be a non-depolarizing neuromuscular blocking agent devoid of cardiovascular side-effects at the generally usual doses.     

Dose-response effects of intravenous ranitidine on gastric pH and volume in outpatients

The dose-response effects of intravenous ranitidine given 45 min to 5 h earlier on gastric pH and volume were evaluated in six groups of 25 outpatients, each undergoing elective surgery under general anesthesia. Patients in Group 1 received no ranitidine and served as controls. Patients in Groups 2-6 received ranitidine intravenously in incremental doses of 0.5 mg X kg-1 body weight from 0.5 mg to 2.5 mg (Group 2, 0.5 mg; Group 3, 1.0 mg; Group 4, 1.5 mg; Group 5, 2.0 mg; and Group 6, 2.5 mg). Ninety-six per cent of patients in the control group (Group 1) had gastric pH less than or equal to 2.5 while 36% of the patients had gastric content volumes greater than or equal to 25 ml with pH less than or equal to 2.5. Ranitidine, in incremental doses of 05.-2.5 mg X kg-1 body weight, caused a significant reduction of gastric acidity and volume. The ED50 of ranitidine producing a gastric pH greater than 2.5 was 0.36 mg X kg-1, and the ED95 was 0.98 mg X kg-1 body weight. The ED95 of ranitidine producing a gastric volume less than 25 ml was 1.96 mg X kg-1. At the dose of 1.5 mg X kg-1 of ranitidine, 100% of the patients had gastric contents with pH greater than 2.5. The proportion of patients with volume less than 25 ml was 68% with ranitidine, 0.5 mg X kg-1, and gradually increased to 100% with 2.5 mg X kg-1 body weight.(ABSTRACT TRUNCATED AT 250 WORDS)     

The neuromuscular blocking and cardiovascular effects of doxacurium chloride in patients receiving nitrous oxide narcotic anesthesia

The purpose of this study was to evaluate neuromuscular and cardiovascular effects of doxacurium chloride, a new long-acting neuromuscular blocking agent, during a stable state of nitrous oxide and narcotic anesthesia. Ninety-three ASA physical status I or II patients were studied after informed written consent had been obtained. Eighty-one patients (group A) received doxacurium. The 81 patients were divided into nine subgroups according to the dose of doxacurium administered (0.01-0.06 mg.kg-1). Patients in a control group (group B) (n = 12) received pancuronium. To assess neuromuscular responses, a force displacement transducer recorded the twitch response of the adductor pollicis muscle following ulnar nerve stimulation. The ED50 and ED95 for doxacurium were estimated to be 0.013 mg.kg-1 and 0.023 mg.kg-1, respectively. The time to maximum twitch suppression following a dose of 1.0 (ED95) and 1.7 (ED95) was 10.3 +/- 1.3 min and 7.6 +/- 0.8 min, respectively. After an ED95 dose of doxacurium the time to spontaneous recovery to 95% of control twitch height was 73.7 +/- 8.7 min. With larger doses of doxacurium, 0.04 mg.kg-1 (1.7 X ED95) and 0.05 mg.kg-1 (2.2 X ED95), the time to spontaneous recovery to 95% of control twitch height was 125.8 +/- 24.8 and 204.0 +/- 21.2 minutes, respectively. When 25% twitch height recovery or more was present the reversal of doxacurium induced neuromuscular blockade was prompt.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reproductive and teratogenic effects of lidocaine in Sprague-Dawley rats

The reproductive and teratogenic effects of lidocaine were studied in 155 Sprague-Dawley rats chronically implanted with osmotic minipumps. Three different lidocaine doses were used as follows: a low dose (100 mg X kg-1 X day-1); an intermediate dose (250 mg X kg-1 X day-1); and a high dose (500 mg X kg-1 X day-1). In the low and intermediate dose groups, lidocaine was administered for two weeks before mating and throughout pregnancy to evaluate reproductive and teratogenic effects. In the high-dose group, lidocaine was administered from days 3 to 17 of pregnancy to evaluate teratogenic effects. On day 21, cesarean section was performed and all of the 1,040 offspring, including those from control and positive control (retinoic acid) groups, were preserved and subsequently examined microscopically to detect external, visceral, and skeletal abnormalities. None was found in lidocaine-treated groups; reproductive indices also were normal. The only treatment effect was a reduction in mean fetal weight in the high-dose group. In a subsequent experiment this was found to be secondary to slightly delayed fetal development. It is concluded that lidocaine is devoid of significant adverse reproductive and teratogenic effects in Sprague-Dawley rats.     

Clinical use of vecuronium during celioscopy

In order to determine if vecuronium can be used for short operations, 40 women were studied during laparoscopy, randomly assigned to four groups: suxamethonium 1 mg X kg-1 in a single bolus followed by an infusion (group A), vecuronium 0.05 mg X kg-1 (group B), vecuronium 0.06 mg X kg-1 (group C) and vecuronium 0.07 mg X kg-1 (group D). Mean duration of operation was 22-25 min. Tracheal intubation can be performed in good conditions in all patients in group A and D, in 5/10 in group B and in 7/10 in group C. During laparoscopy, muscular relaxation was considered excellent in all patients in group A and D, 5/10 sufficient and 5/10 excellent in group C, 5/10 insufficient and 5/10 sufficient in group B. There were 7 reinjections in group B, 2 in group C and 1 in group A. The delay between the end of the procedure and extubation was the same in group A and C (7 min). This delay was significantly higher in group D (9 min). The delay between extubation and positive head lift test was significantly higher in group D. We conclude that the time course of action of vecuronium 0.06 mg X kg-1 is that required for a pelvic laparoscopy of 22-25 min; however, the conditions of intubation are not always perfect. Intubation is easier with a 0.07 mg X kg-1 dose; this dose induces a slight delay for extubation and positive head lift test. In all cases, the patient must be closely watched in a recovery ward.     

Effect of enflurane and fentanyl on the clinical characteristics of long-term succinylcholine infusion

The characteristics of the neuromuscular block produced by prolonged succinylcholine infusion were compared in 40 patients anaesthetized with either nitrous oxide with enflurane (1-2 per cent inspired) or nitrous oxide and fentanyl. Neuromuscular transmission was monitored using train-of-four stimulation and the infusion rate was adjusted to keep the first twitch at 10-15 per cent of its control value. Initially, all patients, exhibited a depolarizing-type block all twitches of the train-of-four being roughly the same size, and the infusion rates were similar in the enflurane (54 microgram X kg-1/min) and the fentanyl (58 microgram X kg-1/min) groups. Tachyphylaxis developed later in both groups and correlated well with the onset of phase II block (dual block). This occurred sooner and at a lower cumulative dose in the enflurane group. Fourth to first twitch ratios decreased to 50, 25 and 0 per cent in 31, 46 and 59 minutes in the enflurane group, at cumulative succinylcholine doses of 2.2, 3.2 and 4.2 mg X kg-1 respectively. Corresponding figures for the fentanyl group were 52, 73 and 86 minutes, with dose of 3.4, 5.0 and 5.9 mg X kg-1. Infusion rates increased markedly after establishment of dual block, but were similar with enflurane (0.99 mg X kg-1/min) and fentanyl (1.12 mg X kg-1/min). Ten minutes after stopping the infusion fourth to first twitch ratios failed to reach 50 per cent in most patients given enflurane who had received more than 6 mg X kg-1 succinylcholine over more than 90 minutes. Corresponding figures for fentanyl patients were 13 mg x kg-1 and 150 minutes. The block in all 15 patients (9 enflurane, 6 fentanyl) who did not recover spontaneously was successfully antagonized with atropine and neostigmine.     

Comparative clinical study of the effects of vecuronium and suxamethonium during oto-rhino-laryngeal and tracheobronchial laser surgery

52 patients selected at random were assigned to four groups according to the surgery and muscle relaxant used: vecuronium (group A) and suxamethonium (group B) in ENT, vecuronium (group C) and suxamethonium (group D) for laser surgery. The first dose of vecuronium was 0.05 mg X kg-1, followed by repeat doses of 0.0125 mg X kg-1; suxamethonium was first given in a dose of 1 mg X kg-1, this being followed by a drip of 3 mg X kg-1. The anaesthetic protocol was the same for all groups. The results showed a shorter onset of action with suxamethonium (group A: 210 +/- 30 s, group B: 75 +/- 15 s, group C: 200 +/- 50 s, group D: 80 +/- 20 s) and a similar duration of action for the initial doses of the two drugs (group A: 9 +/- 3 min, group B: 6 +/- 3 min, group C: 11 +/- 4 min, group D: 7 +/- 2 min). Continuing the muscle relaxation proved easier with the suxamethonium; signs of decurarization occurred rather unexpectedly with vecuronium. No adverse effect was seen with vecuronium, whilst the diastolic blood pressure rose 20% during the first 25 min following the administration of suxamethonium. It can be concluded that, in the absence of monitoring of the curarization, the repeated administration of vecuronium with a first dose of 0.05 mg X kg-1 brought few advantages compared with the continuous infusion of suxamethonium.     

Comparison of the effects of succinylcholine and atracurium on intracranial pressure in monkeys with intracranial hypertension

The effects of succinylcholine (1.5 mg X kg-1 IV) administered five minutes after a defasciculating dose of curare (0.05 mg X kg-1 IV), were compared with the effects of atracurium (0.5 mg X kg-1 IV) on intracranial pressure (ICP) in 13 cynomolgus monkeys with intracranial hypertension (ICP approximately 25 mmHg). Neither succinylcholine nor atracurium increased ICP during general anaesthesia with 60 per cent N2O/O2, 0.5-1 per cent halothane. During a rapid sequence induction and intubation with thiopentone 5 mg X kg-1 IV, ICP increased equally with intubation following both atracurium (25 +/- 1 to 32 +/- 2 mmHg) and succinylcholine (25 +/- 1 to 31 +/- 2 mmHg) (p less than 0.05). Intubation was also associated with significant increases in PaCO2, CVP and MAP. We conclude that in this primate model of intracranial hypertension, neither atracurium nor succinylcholine (when given following a defasciculating dose of curare) elevates ICP. In terms of the elevation of ICP associated with intubation, atracurium was found to offer no advantage over succinylcholine.     

Intubating conditions after vecuronium and atracurium given in divided doses (the priming technique)

Intubating conditions have been assessed at 60 s following administration of vecuronium 0.1 mg kg-1 or atracurium 0.5 mg kg-1 given either as a single dose after induction of anaesthesia with thiopentone or in divided doses; vecuronium 0.015 mg kg-1 followed 4 or 6 min later by 0.085 mg kg-1, or atracurium 0.075 mg kg-1 followed 4 or 6 min later by 0.425 mg kg-1. In the divided dose groups the smaller initial (priming) dose was given prior to induction of anaesthesia. Onset and duration of clinical relaxation were assessed using a peripheral nerve stimulator. The intubating conditions at 60 s improved significantly, with the use of relaxants in divided doses being acceptable in 80 and 70% of patients, respectively, with vecuronium and atracurium, but the conditions are not as good as those commonly found using suxamethonium. Priming at 6 min has no advantage over priming at 4 min. The onset of complete block was accelerated with priming, but the difference was not significant. The duration of clinical relaxation of vecuronium was significantly prolonged by giving it in divided doses. Unpleasant awareness of muscle weakness was observed in 15 patients, requiring early induction of anaesthesia in five of them.     

Clinical use in adults of 2 new muscle relaxants: atracurium and vecuronium

115 general and urologic surgery adult patients, ASA class I-II, were divided in four groups according to initial bolus and relaxant used: group A atracurium 0.6 mg X kg-1, group B 0.5 mg X kg-1, group C vecuronium 0.1 mg X kg-1 and group D pancuronium 0.1 mg X kg-1. When the single twitch recovered to 25% of control height (T25), subgroups were individualized depending on whether repeat doses of 1/3 of initial bolus were given or not, and whether reversal was spontaneous or obtained by a standard dose of neostigmine 2.5 mg and atropine 1.25 mg. By ulnar nerve stimulation at the wrist, the force of thumb adduction was recorded on a polygraph; single twitch (tw), train of four (tof) and ratio tof 4/1 (Rtof) were measured. Anaesthesia was induced with thiopentone and fentanyl without premedication and maintained with fentanyl and N2O in oxygen; the trachea was intubated once the block was at its maximum. The onset time of maximal block was 5 min for groups A, B and C, and 7.9 min for group D. T25 was 39.9 +/- 8.5 min for group A, 34.4 +/- 9.7 min for group B, 28.9 +/- 9.9 min for group C and 70.7 +/- 25.9 min for group D. A Rtof equal to 75% was achieved in less than 65 min with atracurium and vecuronium, but much later with pancuronium. Reversal at T25 was efficient, but not really required, for atracurium and vecuronium, but necessary and useful for pancuronium.(ABSTRACT TRUNCATED AT 250 WORDS)     

Premedication with intramuscular midazolam: effect on induction time with intravenous midazolam compared to intravenous thiopentone or ketamine

Our study sought to determine whether premedication with intramuscular midazolam would decrease the time to induction of anaesthesia with intravenous midazolam, and if so whether induction of anaesthesia would be as rapid as with thiopentone or ketamine, intravenously. Eight-nine patients, ASA physical status I or II, received midazolam 0.2 mg X kg-1, thiopentone 3.0 mg X kg-1, or ketamine 2.0 mg X kg-1 intravenously 60-90 min after intramuscular injection of either midazolam 0.07 mg X kg-1 or matching placebo. Time to induction of anaesthesia or the dose required to induce anaesthesia with intravenous midazolam was not decreased by midazolam premedication. Both with or without premedication, midazolam induction time was longer than with thiopentone or ketamine. Midazolam induction was associated with a lower incidence of blood pressure increase than with ketamine induction, and a lower incidence of apnea than that with either thiopentone or ketamine.     

Efficacy of pulsatile versus continuous insulin administration on hepatic glucose production and glucose utilization in type I diabetic humans

To evaluate the role of pulsatile insulin administration, hepatic glucose production (HGP) and utilization were studied in type I diabetic patients in the fasting state and during a euglycemic insulin (1 mU X kg-1 X min-1 i.v.) clamp with continuous and pulsatile insulin administration. In the latter study, insulin was infused at twice the continuous rate with 3-min-on/7-min-off intervals, thereby reducing total insulin delivery by 40%. The restraining effect of pulsatile insulin on basal HGP (1.91 +/- 0.35 mg X kg-1 X min-1) was equipotent to continuous insulin exposure (1.80 +/- 0.17 mg X kg-1 X min-1). During the insulin-clamp studies, HGP was equally suppressed by pulsed (0.62 +/- 0.12 mg X kg-1 X min-1) as by continuous insulin infusion (0.63 +/- 0.12 mg X kg-1 X min-1). Insulin-stimulated glucose utilization was not significantly altered in either study (2.55 +/- 0.27 vs. 2.92 +/- 0.23 mg X kg-1 X min-1). When in further studies the total insulin dose given during the pulsatile study was infused continuously (0.6 mU X kg-1 X min-1), HGP in the basal state and residual HGP during the insulin-clamp study were 25-30% higher than in the pulsatile experiments, whereas glucose utilization was not significantly different. In conclusion, by reducing total hormone delivery by up to 40%, but given in a pulsatile fashion, insulin is equally potent in controlling HGP as continuous insulin administration. This greater efficacy of pulsatile exposure in suppressing HGP is accompanied by an equipotent effect on glucose utilization.(ABSTRACT TRUNCATED AT 250 WORDS)