Neostigmine For Reversal Research Articles

Residual Neuromuscular Blockade at Extubation: A Randomized Comparison of Sugammadex and Neostigmine Reversal of Rocuronium-Induced Blockade in Patients Undergoing Abdominal Surgery

Background: Residual neuromuscular blockade (NMB) is associated with increased risk of post-operative critical respiratory events. We compared incidence of residual NMB at tracheal extubation after reversal of rocuroniuminduced NMB with sugammadex versus neostigmine. Methods: Adult patients of American Society of Anesthesiologists Class 1-3, scheduled to undergo open abdominal surgery were included. Patients were randomized to receive sugammadex 4.0 mg/kg at ≥1-2 posttetanic counts after last rocuronium dose, or neostigmine 50mg/kg + glycopyrrolate 10mg/kg, according to usual care practices at each institution. Neuromuscular function was assessed using TOF-Watch® SX. Anesthesiologists were blinded to the TOF-Watch recording, except to ask the TOF-Watch operator whether ≥1 PTC had been reached before administering reversal. Use of a peripheral nerve stimulator was permitted. Clinical criteria defined by the institution were used to determine when to perform extubation. Primary efficacy variable was incidence of residual NMB (train-of-four [TOF] ratio <0.9) at extubation. Safety parameters were assessed by a blinded safety assessor. Results: The intent-to-treat group comprised 97 patients (sugammadex, n=51; neostigmine, n=46). Among patients with valid TOF data, a TOF ratio of ≥0.9 was reached at or before extubation in 48 of 50 (96.0%) sugammadex and 17 of 43 (39.5%) neostigmine patients (P<0.0001). One sugammadex (2.0%) and 15 neostigmine patients (34.9%) were extubated at TOF ratios ≤0.7. Median (95% CI) time from study drug administration to recovery to a TOF ratio ≥0.9 was 2.0 (1.8-2.5) minutes for sugammadex (n=49) versus 8.0 (3.8-16.5) minutes for neostigmine (n=18) (P<0.0001). Safety was comparable between groups, with no clinical evidence of recurrence of NMB. Conclusions: Significantly more sugammadex-treated patients recovered to a TOF ratio ≥0.9 at extubation and did so significantly faster than neostigmine-treated patients. This study confirms that sugammadex is more effective than neostigmine in reducing potential for residual blockade in the absence of objective NMB monitoring.

Reversal of neuromuscular blockade by sugammadex does not affect EEG derived indices of depth of anesthesia

According to previous studies neuromuscular blockade may affect the depth of anesthesia. One theory states that neuromuscular blockade prevents disturbing EMG signals, arousing from the muscles of the forehead, from falsely elevating bispectral index (BIS)-levels. According to the afferentation theory signals generated in muscle stretch receptors, accessing the brain through afferent nerve pathways, induce arousal. By blocking these signals neuromuscular blockade would increase depth of anesthesia. Arousal has previously been associated with neostigmine reversal. This study investigates the possible effect of sugammadex on the level of anesthesia as defined by BIS and spectral entropy levels. Thirty elective patients were enrolled. All patients received propofol and remifentanil by target controlled infusion and an intermediate level neuromuscular blockade induced and maintained by bolus doses of rocuronium. Depth of anesthesia was monitored by BIS and spectral entropy. The patients were given 2mg/kg sugammadex 5min after finishing of surgery. Propofol and remifentanil infusions were kept unchanged for another 10min while BIS and entropy values were recorded. Mean BIS and Entropy™ values remained unchanged after reversal of the rocuronium block. The mean averaged BIS, state entropy and response entropy values were 31.7 ± 9.9, 35.3 ± 12.9 and 36.8 ± 13.3 before and 32.0 ± 11.9, 36.3 ± 15.9 and 38.4 ± 18.0 after sugammadex administration, respectively. Sugammadex does not affect level of anesthesia as determined by BIS or entropy levels.

REVERSAL OF VECURONIUM WITH NEOSTIGMINE: A COMPARISON BETWEEN MALE AND FEMALE PATIENTS

We investigated the differences between males and females in the reversal effect of neostigmine on neuromuscular blockade. Thirty male and 30 female patients undergoing elective general anesthesia were studied. Vecuronium was given in all patients anesthetized with nitrous oxide, oxygen, and sevoflurane. After the surgical procedure, when T1 (1st response in train-of-four (TOF))/control returned to 0.25, neostigmine 40 microg/kg in combination with atropine 20 microg/kg was given to antagonize residual neuromuscular blockade. Three, six, nine, 12, and 15 minutes after neostigmine reversal, T1/control or TOF ratio (T4/T1) did not significantly differ between the sexes. Also, 15 minutes after neostigmine administration, the number of patients in whom recovery from neuromuscular blockade was sufficient to guarantee good respiratory function, i.e., TOF ratio > 0.74, did not significantly differ between the sexes. In contrast, 15 minutes after neostigmine, the number of patients in whom recovery from neuromuscular blockade was adequate to ensure satisfactory recovery from neuromuscular blockade including the return of the faculty of sight, i.e., TOF ratio > 0.9, was significantly less in the males than in females (6 vs. 14, P = 0.028). In conclusion, 15 min after neostigmine, TOF ratio less often returns to a value of more than 0.9 in males than in females.

The Effect of Neuromuscular Block and Noxious Stimulation on Hypnosis Monitoring During Sevoflurane Anesthesia

There are conflicting results on the influence of neuromuscular block (NMB) on the bispectral index (BIS). We investigated the influence of two degrees of NMB on BIS, Alaris auditory-evoked potential index (AAI), and the electromyogram (EMG) obtained with needle electrodes from the frontal and temporal muscles, immediately adjacent to the BIS-sensor. Twenty patients were anesthetized with sevoflurane, titrated for 30 min to an end-tidal concentration of 1.2% (baseline). Rocuronium was infused to 50% (partial) and 95% (profound) depression of the first twitch in a train-of-four response, the order being randomly chosen. Noxious tetanic electrical stimulation was applied at four occasions: 1) at baseline (control measurement), 2 and 3) at each degree of NMB, and 4) after neostigmine reversal. BIS, AAI, and EMG were obtained 2 min before and 2 min after each noxious stimulation. Median BIS and AAI at baseline were 44 (39-50) and 15 (14-16), respectively. The two degrees of NMB did not affect BIS, AAI, and EMG before noxious stimulation. In contrast, profound NMB altered the BIS and AAI responses to noxious stimulation when compared with partial NMB, (BIS P = 0.01, AAI P < 0.01), after neostigmine reversal (BIS P < 0.01, AAI P = 0.01) and compared with baseline (BIS P = 0.08, AAI P = 0.02). No significant increase in EMG was found. BIS and AAI responses to noxious tetanic electrical stimulation are affected by the degree of NMB during sevoflurane anesthesia whereas NMB does not affect BIS or AAI in the absence of noxious stimulation.

Room 224-226, 10/16/2000 9: 00 AM - 10: 30 AM (PD) Recovery Time of Cisatracurium-Induced NMB to a TOF Ratio ≥0.9 after Neostigmine Reversal

<b>Room 224-226, 10/16/2000 9: 00 AM - 10: 30 AM (PD) Recovery Time of Cisatracurium-Induced NMB to a TOF Ratio ≥0.9 after Neostigmine Reversal</b>

EFFECT OF NEOSTIGMINE ON REVERSAL OF RESIDUAL NEUROMUSCULAR BLOCKADE AFTER AN INFUSION OF ORG 9487

S445 Introduction: ORG 9487 is an investigational short-acting nondepolarizing muscle relaxant [1]. However, infusion of ORG 9487 appears to change its clinical effect from that of a short-acting to an intermediate-acting relaxant [2]. Therefore, patients may have prolonged neuromuscular blockade after discontinuation of an infusion of ORG 9487. This study was designed to evaluate the effect of neostigmine reversal on residual neuromuscular blockade after a 1 h infusion of ORG 9487 in adults. Methods: After IRB approval and written informed consent, 20 patients undergoing general surgery with an anticipated duration over 2 hours were studied. Anesthesia was induced with propofol 2.5 mg/kg, fentanyl 2 [micro sign]g/kg, and ORG 9487 1.5 mg/kg. Maintenance of anesthesia consisted of nitrous oxide 60% in oxygen with isoflurane, sevoflurane, desflurane, or propofol infusion. After T1 twitch height return to 5% of baseline, a continuous infusion of ORG 9487 will be started at initial infusion rate of 3 mg/kg/h. The infusion was adjusted to maintain T1 at 10% of baseline for 1 hour and was then discontinued. After surgery, patient with TOF ratio (T4/T1) less than 0.7 received neostigmine 0.05 mg/kg and 0.01 mg/kg glycopyrrolate to reverse the residual effect of ORG 9487. Neuromuscular blockade was assessed by peripheral nerve stimulation using a TOF-GUARD[registered sign] monitor (Organon Teknika NV, Turnhout, Beigium). Accelerometric assessment of TOF responses were recorded on a memory card and the data was analyzed using a software for TOF-GUARD[registered sign] card reader in computer. Results: Eleven patients required reversal of neuromuscular blockade with a T1 of 80 +/- 27 % and T4/T1 was 0.43 +/- 0.22. The time between end of infusion and reversal was 102 +/- 44 min. After reversal with neostigmine, the time for T1 to returned to 90 and 100% was 90 +/- 145 and 103 +/- 177 sec, respectively. Time of TOF ratio return to 0.7, 0.8, 0.9 and 1.0 after reversal was 138 +/- 130, 201 +/- 188, 304 +/- 267, and 449 +/- 397 sec, respectively. No recurarization effects and any airway problems were observed in all the patients after reversal. (Figure 1)Figure 1Discussion: After an infusion of ORG 9487, the residual neuromuscular blockade can be clinical reversed using neostigmine within 3 min.

Parasympathetic nervous activity after administration of atropine and neostigmine using heart rate spectral analysis.

Recently, heart rate spectral analysis has become recognized as a powerful tool for quantitatively evaluating autonomic nervous system activity. The purpose of this study was to analyze parasympathetic nervous activity by heart rate spectral analysis after administration of atropine and neostigmine for reversal of residual neuromuscular blockade. For our study, 36 female patients (26-37 years of age), ASA physical status (PS) I, who were scheduled for laparoscopic examination, were randomly allocated to one of the following four groups: In group A (1∶1), 9 patients received 1.0mg atropine followed 4 min later by 1.0 mg neostigmine. In group B (1∶2), 9 patients received 0.5 mg atropine followed 4 min later by 1.0 mg neostigmine. In group C (1∶2.5), 9 patients received 1.0 mg atropine followed 4 min later by 2.5 mg neostigmine. In group D (1∶2 mix), 9 patients received a mixed solution of atropine 0.5 mg and neostigmine 1.0mg. After finishing the laparoscopic examination, additional anesthesia was maintained with 70% nitrous oxide, 30% oxygen, and 0.5% isoflurane. The control data were obtained 10 min after finishing the laparoscopic examination. After that, the data on atropine were obtained between 2 and 4min after administration of atropine, and the data on neostigmine were obtained between 5 and 7 min after administration of neostigmine. We selected power spectral density of the high-frequency component (HF-p) in heart rate spectral analysis as an index to assess parasympathetic activity. In groups A, B, and C, the HF-p decreased after administration of atropine. In groups B and C, the HF-p increased after administration of neostigmine as compared to the control. In group A, the HF-p increased after neostigmine but did not differ from the control. The difference between groups D and B was not statistically significant. From the results of this study, we concluded that the muscarinic effect of neostigmine could not be sufficiently blocked by atropine at 1/2 dosages of neostigmine, but could be sufficiently blocked by atropine at equivalent dosages of neostigmine, under light isoflurane anesthesia.

Pseudocholinesterase-mediated Hydrolysis Is Superior to Neostigmine for Reversal of Mivacurium-induced Paralysis In Vitro

The metabolic hydrolysis of mivacurium (and succinylcholine) is markedly impaired in the presence of hereditary or acquired defects of pseudocholinesterase. Clinical reports are conflicting as to the utility of anticholinesterases, in the reversal of mivacurium paralysis. In the current study, the role of exogenous cholinesterases and/or of anticholinesterase, neostigmine, in the reversal of deep mivacurium-induced paralysis, was studied. The rat phrenic-diaphragm preparation, in a fixed volume of Krebs solution, was chosen to eliminate the confounding effects on the dissipation of neuromuscular effects caused by hydrolysis, elimination, and redistribution of the drug. In the phrenic-diaphragm preparation, mivacurium was administered to obtain >90% single twitch inhibition. Single twitch responses (0.1 Hz) were monitored for 60 min, after which the response to train-of-four stimulation was tested. The reversal of mivacurium by 0.5, 1.0, or 2.0 units/ml of (true) acetylcholinesterase, bovine pseudocholinesterase, or human plasma cholinesterase and by neostigmine, 0.1, 1.0, or 10.0 micrograms/ml tested. The efficacy of human plasma cholinesterase, 1 unit/ml in combination with each of the above neostigmine concentrations, also was examined. The reversal of succinylcholine-induced paralysis by the acetylcholinesterase, bovine pseudocholinesterase, or human plasma cholinesterase (1 unit/ml) alone and in the presence of neostigmine (10.0 micrograms/ml) was additionally tested as a positive control. A train-of-four ratio > 0.75 was considered adequate reversal. Acetylcholinesterase was a poor hydrolyzer of mivacurium, as bioassayed by reversal of paralysis. Bovine pseudocholinesterase in concentrations of 0.5 and 1.0 units/ml did not effectively reverse single twitch and train-of-four responses by 60 min, but bovine pseudocholinesterase (2 units/ml) and all concentrations of human plasma cholinesterase did. Neostigmine alone, tested at all concentrations, was an incomplete reversal drug. Clinical or therapeutic concentrations (0.1 and 1.0 micrograms/ml) of neostigmine did not, but pharmacologic concentrations (10 micrograms/ml) interfere with the efficacy of human plasma cholinesterase (1 unit/ml). Bovine pseudocholinesterase and human plasma cholinesterase equally reversed the effects of succinylcholine but acetylcholinesterase did not, whereas the addition of 10 micrograms/ml neostigmine to the enzymes inhibited the reversal of succinylcholine. Human plasma cholinesterase will reverse mivacurium more effectively than bovine pseudocholinesterase, but both will effectively reverse succinylcholine. Acetylcholinesterase has no effects on either relaxant. The anticholinesterase neostigmine was an incomplete reversal drug. Pharmacologic concentrations of anticholinesterases do, while clinical or therapeutic concentrations do not, completely inhibit the metabolic activity of pseudocholinesterases.

Influence and Relative Sensitivities of 50-Hz and 100-Hz Tetanic Stimuli on Subsequent Tetanic Fade Ratios in Patients Receiving Vecuronium

We studied the possible effects of repetitive (1-min interval) 50- and 100-Hz tetanic stimuli on 50-Hz and 100-Hz tetanic fade ratios (RF50HZ and RF100HZ). We also evaluated the sensitivity of the recorded responses to these two tests to assess residual neuromuscular block (isometric adductor pollicis mechanical activity), either during spontaneous recovery, or 15 min after neostigmine administration, in 22 adult anesthetized (thiopental, fentanyl, N2O/O2) patients receiving vecuronium. Two 50-Hz and two 100-Hz, 5-s duration, tetanic stimulations were randomly assessed at 1-min intervals: in a spontaneous (SPO) group (n = 11), when train-of-four (TOF) ratio spontaneously regained 0.7, and in a neostigmine (NEO) group (n = 11), 15 min after 40 micrograms/kg neostigmine was given intravenously at 25% return of control twitch tension. In the SPO group, when TOF ratio was 0.7, RF50HZ was 0.92 +/- 0.01 before and after subsequent tetanic stimulation, while RF100HZ was 0.48 +/- 0.05 and 0.47 +/- 0.05, respectively (not significant [NS]). In the NEO group, when TOF ratio was approximately 0.9, RF50HZ was 0.93 +/- 0.01 before and after subsequent tetanic stimulation, while RF100HZ was 0.80 +/- 0.02 and 0.78 +/- 0.02, respectively (NS). From patient to patient, both RF50HZ and RF100HZ were also identical. In conclusion, in patients receiving vecuronium, 1) 5-s, 50- and 100-Hz tetanic stimuli may be repeated without changes at 1-min intervals and, 2) in contrast to RF50HZ, recorded RF100HZ enables one to determine residual neuromuscular block during spontaneous recovery (P < 0.001) such as after neostigmine reversal (P < 0.05).

The Bullard Laryngoscope for Emergency Airway Management in a Morbidly Obese Parturient

The Bullard Laryngoscope for Emergency Airway Management in a Morbidly Obese Parturient

Anesthetic Implication of Snake-Bite Envenomation

Anesthetic Implication of Snake-Bite Envenomation

Neostigmine and Edrophonium Reversal of Mivacurium-induced Neuromuscular Block

Neostigmine and Edrophonium Reversal of Mivacurium-induced Neuromuscular Block

The Influence of Atropine Dose on Recovery from Vecuronium-induced Neuromuscular Blockade

To determine whether the dose of atropine affects the rate of neostigmine-induced recovery from vecuronium-induced neuromuscular blockade, the authors monitored isometric adductor pollicis mechanical activity in 36 anesthetized (thiopental, fentanyl, nitrous oxide) adult patients (ASA physical status 1 or 2). Once surgery was completed and twitch height had spontaneously regained 25% of its initial value, the patients were randomly allocated into three groups (A10, A15, A20; n = 12 in each group) according to the dose of atropine (10, 15, or 20 micrograms/kg) that was mixed with 40 micrograms/kg neostigmine. Twitch height, train-of-four, and 50- and 100-Hz tetanic fade were recorded for 15 min after the administration of the reversal agents. No significant differences were found among the three groups in the final twitch height (95% +/- 2%), train-of-four (87% +/- 1%, 88% +/- 2%, 89% +/- 1%), and 50-Hz tetanic fade (90% +/- 1%, 94% +/- 1%, 93% +/- 1%) (mean +/- SEM). Fifteen minutes after reversal, fade in response to 100-Hz tetanus was statistically greater in the A10 group than in the two other groups (70% +/- 3% of control versus 84% +/- 4% and 81% +/- 2%) (mean +/- SEM, P less than 0.05). The present results demonstrate that larger doses of atropine facilitate neostigmine's reversal of vecuronium neuromuscular blockade. The clinical implications of the differences observed in this study remain to be determined.

Reversal of atracurium neuromuscular block with neostigmine in the dog

A dose response relationship and the time of onset to 50 per cent and 100 per cent peak action were investigated for neostigmine reversal of atracurium in the dog. Two levels of neuromuscular block were used, 10 per cent and 50 per cent of the first twitch of the train of four. The ED50 from the first group was 0.1 mg kg-1 and for the second group was 0.019 mg kg-1. There was little difference between the onset times at the two levels of block. It is concluded that the main factor in determining the dose of neostigmine is the depth of the initial blockade.

Adverse reactions and interactions of the neuromuscular blocking drugs.

The adverse reactions seen following administration of neuromuscular blocking agents are mainly cardiovascular. Due to the lack of specificity for the nicotinic receptor at the neuromuscular junction, these agents may interact with receptors in autonomic ganglia and muscarinic receptors in the heart. Furthermore, muscle relaxants may have histamine-releasing properties. The cardiovascular effects vary with potency and specificity of the drug, depending mainly on the chemical structure. Pancuronium, fazadinium and especially gallamonium block cardiac muscarinic receptors, and tachycardia may be seen. Atracurium, metocurine and in particular d-tubocurarine have histamine-releasing properties and may cause flushing, hypotension and tachycardia. Vecuronium has no effect on the cardiovascular system. The effect of succinylcholine on heart rate differs between children, where bradycardia is seen, and adults in whom tachycardia may follow. However, bradycardia may occur in adults following a single dose. Succinylcholine increases plasma potassium, especially in patients with nerve damage, and arrhythmias may be observed. The neuromuscular adverse effects of succinylcholine, such as fasciculations and increased gastric and intraocular pressure, may be prevented by precurarisation. Many drugs interact with neuromuscular blocking agents and there is often a potentiation of the neuromuscular effect. This is of clinical importance in the case of antibiotics, inhalational anaesthetics, lithium and cyclosporin. Difficulty in reversing the block may occur with calcium channel blockers and polymyxin. However, some drugs, such as phenytoin, carbamazepine and lithium, may cause resistance to neuromuscular blocking agents. Furthermore, clinically important interactions exist between individual neuromuscular blocking drugs. Precurarisation with a non-depolarising drug prolongs the onset of succinylcholine, and conversely a prolonged effect of non-depolarising drugs is seen following succinylcholine. The effect of succinylcholine is markedly prolonged if the drug is administered during recovery from pancuronium blockade or following neostigmine for reversal. Succinylcholine is hydrolysed by plasma cholinesterase, and drugs which decrease the activity of this enzyme may produce a prolonged block, i.e. contraceptive pills, cyclophosphamide, echothiopate and organophosphate.

Use of low-dose neostigmine intravenously in the treatment of supraventricular tachycardia: An immediate bradycardic effect

Neostigmine was first used 50 years ago to treat sinus tachycardia and paroxysmal auricular tachycardia. Then there were reports of successful treatment by neostigmine of other forms of supraventricular tachycardias. However, reports of sudden death using neostigmine for reversal of neuromuscular blockade at the end of an operation, which were not properly treated with atropine abandoned the use of neostigmine as an antiarrhythmic drug. Low-dose neostigmine intravenously was used in the treatment of supraventricular tachycardia in three patients described herein. It gave an immediate bradycardic effect in all three patients. The use of a low-dose neostigmine intravenously for an immediate treatment of supraventricular tachycardia is a novel suggestion. It has to be further evaluated and compared to the conventional drugs used like digoxin, verapamil, propranolol or esmolol.

Comparison of Edrophonium and Neostigmine for reversal of the effects of Vecuronium

Comparison of Edrophonium and Neostigmine for reversal of the effects of Vecuronium

Recovery times following edrophonium and neostigmine reversal of pancuronium, atracurium, and vecuronium steady-state infusions.

The ability of edrophonium and neostigmine to antagonize nondepolarizing neuromuscular blockade produced by steady-state infusions of atracurium, pancuronium, and vecuronium was studied in 71 adult patients anesthetized with nitrous oxide and halothane. Infusion rates of blocking drugs were adjusted so that single twitch depression as measured by the evoked integrated EMG of the hypothenar muscles was kept at 10% of control. Two minutes after the termination of the infusion either edrophonium (0.75 mg/kg) or neostigmine (0.05 mg/kg) was administered. Single twitch depression and train-of-four (T4/T1) fade was recorded during the recovery period. T4/T1 fade ratios observed at 20 min postreversal were 0.80 (atracurium-edrophonium); 0.76 (vecuronium-edrophonium); 0.44 (pancuronium-edrophonium); 0.95 (atracurium-neostigmine); 0.89 (vecuronium-neostigmine); and 0.68 (pancuronium-neostigmine). Under conditions of this study neostigmine produced more rapid and complete recovery than did edrophonium. Although edrophonium produced adequate antagonism of atracurium if 20-30 min were allowed to elapse, edrophonium reversal of pancuronium was rarely acceptable even at 30 min. Increasing the dose of edrophonium to 1.0 mg/kg produced single twitch values of 0.90 at 5 min postreversal but did not increase the rate of recovery of the train-of-four fade ratio. Neostigmine reversal of pancuronium, on the other hand, generally produced T4/T1 ratios of greater than 0.70 in 20-30 min. Although the pattern of recovery seen after reversal of vecuronium was in general quite similar to that seen after atracurium, two patients in the vecuronium-edrophonium group showed delayed recovery and also failed to respond significantly to subsequent doses of neostigmine.(ABSTRACT TRUNCATED AT 250 WORDS)

Microcomputer use in measuring onset, duration, and recovery from nondepolarizing skeletal muscle relaxants in rabbits

AbstractThis report describes a method which has been developed to use an Apple II Plus microcomputer in studies of the time course and dose response of potential skeletal muscle relaxant drugs. Rabbits are anesthetized with pentobarbital, tracheotomized, and the right common carotid artery is cannulated for direct measurement of blood pressure and heart rate. The ulnar nerve is stimulated at the elbow. Twitch, “train‐of‐four” (T4), tetanus, and posttetanic potentiation (PTP) are monitored by a force displacement transducer. These analog physiological signals are led from a polygraph through an lsaac Cyborg analog‐to‐digital converter attached to the microcomputer where they are stored in digital form. Each animal receives the test drug twice. Spontaneous recovery is allowed following the first administration while the second dose is reversed with neostigmine. The rate of onset, time and magnitude of maximal effect, time and rate of recovery, and time and magnitude of cardiovascular changes are all automatically calculated for both the control and the neostigmine reversal experimental phases. The effect of the test dose on each parameter is rated to provide a composite score for each dose of the test compound as the dose‐response series is completed. All parameters are plotted using a dot‐matrix printer and data are stored to disk. When doses, in 0.1‐log intervals, from the dose which produces no measurable effect to those doses producing unacceptably long durations, have been administrated, the computer uses the composite scores to report an optimal dose. Using regression analysis, the dose required to provide a 90% depression of twitch is calculated. This calculated dose is compared to equiefficacious doses of other test compounds. A tabular, graphic, and narrative report of the drug's effects is generated by the computer with comparison to other compounds of pctential interest. These programs and methods provide efficient data collection and data analysis. They provide for standard report generation. Finally, they allow for comparisons to be made among many pharmacologic parameters of many test compounds, thus providing understanding of the mechanisms of action of the test compounds.

Neostigmine Reversal of d-Tubocurarine and Pancuronium Bromide Combinations in Man

This study measured the neostigmine reversal of a non-depolarizing block in 17 patients, each given d-tubocurarine and pancuronium bromide in an alternating sequence. Reversal times were similar to those previously reported for pancuronium bromide alone. It is concluded that the anaesthetist may alternate between d-tubocurarine and pancuronium bromide without fear of difficulty with neostigmine reversal.