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Biomedical subjects

G G Neuman

Publications and source records attributed to G G Neuman.

At least 19 recordsLinked to original sources
PubMed2001

Reexamined: the recommended endotracheal intubating dose for nondepolarizing neuromuscular blockers of rapid onset.

UNLABELLED: The results of any study of the relative importance of anesthetic depth versus intensity of neuromuscular block on conditions for endotracheal intubation can be manipulated by the investigator. Several independent factors, such as the depth of hypnosis induced, the interval between drug administration and laryngoscopy, the onset profile of the muscle relaxant, and the multiple of the 95% effective dose given, must be controlled. We attempted to design an induction sequence that provided good to excellent conditions for laryngoscopy and endotracheal intubation within 75-90 s of muscle relaxant administration with doses smaller than often suggested, while still administering only customary amounts of hypnotics and opioids. Alfentanil 12.5 microg/kg, propofol 2.0 mg/kg, and a test drug were administered rapidly. The test drugs were saline 0.05 mL/kg (n = 10), rapacuronium 1.0 or 1.2 mg/kg, or rocuronium 0.50 mg/kg (n = 30 each). Laryngoscopy was commenced 75 s after the test drug. Clinically acceptable conditions for intubation were achieved in all subjects after rocuronium or rapacuronium 1.2 mg/kg and in 28 of 30 patients after rapacuronium 1.0 mg/kg. In the Saline group, only 3 individuals achieved a good or excellent rating, and intubation was impossible in 2 of 10 individuals. For muscle relaxants of low potency, doses only 1.5 times the 95% effective dose can provide very satisfactory conditions for intubation if laryngoscopy is delayed to 75 s after drug administration. IMPLICATIONS: The dose of muscle relaxant usually recommended for facilitating tracheal intubation approximates at least two times the drug's effective dose (ED(95)). When the muscle relaxant in question has a rapid onset of action, this intubation dose may be decreased to 1.5 times the ED(95).

Adolescent↗
PubMed2001

Precurarization and priming: a theoretical analysis of safety and timing.

UNLABELLED: The priming principle suggests that the onset of neuromuscular block may be accelerated if an intubating dose is preceded by a priming dose administered a few minutes earlier. We thought it would be instructive to use a pharmacodynamic/pharmacokinetic model to estimate the risk associated with different priming doses and intervals. In any normal population, there is wide variability in the response to neuromuscular blocking drugs. For most relaxants, the coefficient of variation for the 50% effective dose (ED(50)) approximates 20%-25%. Thus, 1 patient in 50 (-2.05 SD) may have an ED(50) only half of the commonly cited value. By using published pharmacodynamic/pharmacokinetic data, we calculated the effect of administering 10%, 20%, or 30% of the ED(95) on the response of the adductor pollicis muscle in a population normally distributed with respect to drug sensitivity. A dose equivalent to 10% of the ED(95) will rarely produce a measurable neuromuscular effect. As this dose is increased, the potential for clinical weakness rapidly escalates. In 1 in 50 individuals, the usual recommendation of 10% of the intubation dose will produce measurable neuromuscular depression. For vecuronium, the optimal priming interval is 5 min. The safety and dependability of the priming principle is very much subject to the laws of probability. IMPLICATIONS: When using the priming principle to accelerate the onset of neuromuscular block, the initial dose should not exceed 10% the drug's ED(95). For drugs other than rocuronium, the optimal priming interval is not <5 min.

Androstanols↗
PubMed2001

The staircase phenomenon: implications for monitoring of neuromuscular transmission.

BACKGROUND: Repeated indirect stimulation enhances the evoked mechanical response of muscle (the staircase phenomenon). There are few data that document the magnitude of this effect in man. Inexpensive acceleromyographic monitors of neuromuscular function are now available. If these units are to be used as scientific tools or clinical monitors, additional information regarding how to achieve proper baseline stabilization and calibration is needed. METHODS: Anesthesia was induced and maintained with nitrous oxide, propofol, and an opioid. Tracheal intubation or laryngeal mask insertion was accomplished without muscle relaxants. Thirty adult patients classified as American Society of Anesthesiologists physical status I or II were divided into groups of 10. The mechanical response of the thumb to supramaximal ulnar nerve stimulation was recorded continuously with an acceleromyograph. Group 1 had train-of-four stimuli at 15-s intervals for 25 min. Group 2 had single stimuli at 1.0 Hz for 10 min. Group 3 had the same stimuli as group 1 except that a 50-Hz tetanus of 5 seconds' duration immediately preceded instrument calibration. RESULTS: In group 1, average twitch height (T1) increased rapidly to 148+/-19% (mean +/- SD) of control at 15 min and then more slowly to reach 158+/-26% of control at 25 min. The train-of-four fade ratio did not vary with the duration of stimulation. In group 2, T1 increased to 172+/-19% of control after 400 stimuli (6.7 min) and 180+/-22% of control at 10 min In group 3, average T1 did not decrease below 97+/-5% or increase above 105+/-15% of control at any time. CONCLUSIONS: A 5-s, 50-Hz tetanus administered before initial twitch calibration considerably shortens the time required to achieve baseline stability.

Adolescent↗
PubMed2000

An alternate method for estimating the dose-response relationships of neuromuscular blocking drugs.

Slopes of the dose-response relationships for all available neuromuscular blocking drugs appear to be essentially parallel and to approximate a log-dose/logit value of 4.75. We tested the possibility of estimating both 50% effective dose (ED(50)) and 95% effective dose (ED(95)) values from a single dose-response data point when that slope is postulated. We compared the ED(50) and ED(95) values of rocuronium and succinylcholine calculated by using traditional log-dose/logit regression analysis with the same values obtained by averaging individual estimates of potency as determined by using the Hill equation. After the induction of anesthesia (propofol/alfentanil), tracheal intubation was accomplished without the administration of neuromuscular blocking drugs. Anesthesia was maintained with nitrous oxide and propofol. The evoked electromyographic response to 0.10-Hz single stimuli was continuously recorded. After baseline stabilization, a single IV bolus of succinylcholine (0.08-0.26 mg/kg, n = 50) or rocuronium (0. 13-0.30 mg/kg, n = 40) was administered and the peak effect noted. By using log-dose/logit regression analysis, we calculated ED(50) and ED(95) values for rocuronium of 0.17 and 0.33 mg/kg and 0.14 and 0.27 mg/kg for succinylcholine. When potency was calculated from the Hill equation, the resultant ED(50) and ED(95) values did not differ by more than +/-4% from those obtained by using regression analysis. Averaging of single-dose estimates of neuromuscular potency provides a useful adjunct and reasonable alternative to conventional regression analysis.

Action Potentials↗
PubMed2000

Dose-response and onset/offset characteristics of rapacuronium.

BACKGROUND: A rigorous study of the dose-response relation of rapacuronium has, to our knowledge, yet to be performed. In addition, there is little information available regarding the onset or offset profile of rapacuronium when administered in subparalyzing doses. These issues necessitate further study. METHODS: Forty-seven adult patients, American Society Anesthesiologists physical status I or II, were studied. Tracheal intubation was accomplished without muscle relaxants. Anesthesia was maintained with use of nitrous oxide, propofol, and alfentanil. The electromyogram of the first dorsal interosseous muscle was measured using a monitor. Single stimuli at 0.10 Hz were administered. A single dose of rapacuronium was administered. After log-dose or logit transformation of the data, the best-fit line of regression was determined using the method of least squares. For each subject, the authors estimated the 50% effective dose (ED50) and 95% effective dose (ED95) from the Hill equation using the slope obtained from regression analysis. The onset times to 50 and 90% of peak effect were estimated in a subset of 10 individuals in which peak twitch depression decreased to the range of 90-99%. RESULTS: The calculated ED50 and ED95 values for rapacuronium were 0.39 +/- 0.08 (SD) and 0.75 +/- 0.16 mg/kg, respectively. After a single ED95 dose, 90% of the drug's peak effect was evident in 77 +/- 17 s. After this dose, rapacuronium has a clinical duration of 6.1 +/- 1.1 min. CONCLUSIONS: The authors found the ED95 of rapacuronium to be substantially less than suggested by previous estimates. Rapacuronium has an onset profile that is not different from that previously reported for succinylcholine. The rate of spontaneous recovery was faster after rapacuronium than the authors previously observed after mivacurium administration but was slower than after succinylcholine, using an identical protocol.

Adult↗
PubMed1999

Molar potency is not predictive of the speed of onset of atracurium.

UNLABELLED: In an effort to determine the extent to which atracurium may represent an exception to the rule that molar potency predicts onset time, we studied the onset profile of atracurium after a dose selected to produce approximately 95% twitch depression. We compared these results with data obtained in a previous study after the administration of vecuronium, rocuronium, and cisatracurium. Eighteen ASA physical status I and II patients were studied. After the induction of anesthesia, tracheal intubation was accomplished without relaxants. The evoked electromyographic response to 0.10-Hz single stimuli was continuously recorded. After baseline stabilization, a single bolus of atracurium, averaging 0.21 mg/kg, was administered. If peak twitch depression did not fall within the range of 90%-98%, the patient was excluded. The time to 50% and 90% of peak effect was recorded. The time to 90% of maximal effect (192 +/- 23 s) was not different from that previously observed for vecuronium (201 +/- 20 s). The time to 50% of peak effect (110 +/- 15 s) was shorter (P < 0.05) after atracurium administration than after vecuronium (125 +/- 9 s). The onset times recorded for atracurium were slower than previously observed after rocuronium and more rapid than that which was seen after cisatracurium (P < 0.001). The observed onset profile of atracurium was considerably slower than anticipated, based on the drug's molar potency. The 95% effective dose (microM/kg) may not be a reliable predictor of a muscle relaxant's onset time, when the drug administered is a mixture isomers of varying potency. IMPLICATIONS: The speed of onset of atracurium is slower than predicted, based on its molar potency. Potency of a relaxant may not be a reliable predictor of its time to peak effect, when the drug administered is a mixture of isomers with widely different neuromuscular activities.

Adult↗
PubMed1999

Molar potency is predictive of the speed of onset of neuromuscular block for agents of intermediate, short, and ultrashort duration.

BACKGROUND: The times to peak effect of rocuronium, vecuronium, cisatracurium, mivacurium, and succinylcholine were evaluated to confirm that the correlation between potency and onset time observed for long-acting relaxants also held for drugs of intermediate and short duration. METHODS: The authors recruited 99 patients classified as American Society of Anesthesiologists physical status score 1 or 2 for the study. After anesthesia was induced, tracheal intubation was accomplished without relaxants. Anesthesia was maintained with nitrous oxide and 3% or 4% end-tidal desflurane plus intravenous narcotic supplementation. The evoked electromyographic response to single stimuli administered at 0.10 Hz was recorded continuously. Drug doses were selected to produce approximately 95% twitch depression. If peak twitch depression did not fall in the range of 90% to 98%, the patient was excluded from the study. The time to 50% to 90% of peak effect was plotted as a function of the administered dose. RESULTS: There was no difference in the onset profiles of mivacurium and vecuronium, or in the time to 50% of peak effect between succinylcholine and rocuronium. For all other parameters, onset times ranked as follows: succinylcholine < rocuronium < vecuronium-mivacurium < cisatracurium (P < 0.05). When the log of the ED95 in micromoles per kilogram for all five drugs was plotted against the log of onset time to 50% peak effect, the R2 value for the best fit line was more than 0.98. CONCLUSIONS: The inverse correlation between the molar potency and speed of onset previously described for agents of long duration also applies to nondepolarizing agents of intermediate and short duration. The onset time of succinylcholine also appears to be compatible with this relation.

Adult↗
PubMed1997

Relationship of the train-of-four fade ratio to clinical signs and symptoms of residual paralysis in awake volunteers.

BACKGROUND: Recovery of the train-of-four (TOF) ratio to a value > 0.70 is synonymous with adequate return of neuromuscular function, but there is little information available concerning the subjective experience that accompanies residual neuromuscular block wherein the TOF ratio is in the range of 0.70 to 0.90. METHODS: Ten American Society of Anesthesiologists' (ASA) physical status 1 volunteers were studied. Control measurements including grip strength in kilograms and ability to perform a 5-s head- and leg-lift. In addition, a standard wooden tongue depressor was placed between each subject's incisor teeth, and he or she was told not to let the investigator remove it. All subjects were easily able to retain the device despite vigorous attempts to dislodge it. Neuromuscular function was monitored with a Datex (Datex Medical Instrumentation, Inc., Tewksbury, MA) 221 electromyographic (EMG) monitor. TOF stimulation was given every 20 s, and the measured TOF fade ratio was continuously recorded. A 5 mg/kg bolus of mivacurium was then administered, and an infusion at 2 mg.kg-1.min-1 was begun. The infusion was continued until the TOF ratio decreased to < 0.70 and was adjusted to keep it in the range of 0.65 to 0.75. Signs and symptoms of weakness were recorded when the TOF ratio had been stable +/-0.03 for at least 10 min during an interval when there were no adjustments in the infusion. All tests noted previously were repeated at this time. The TOF ratio was then allowed to recover to 0.85-0.90. When stable at this level, all tests were repeated, and the infusion was discontinued. TOF measurements were continued until a ratio of 1.0 was attained and until a final set of observations was recorded. RESULTS: The TOF ratio in all subjects was reduced to < 0.70. No volunteers required intervention to maintain a patient airway, and the hemoglobin oxygen saturation while breathing air was > or = 96% at all times. TOF ratios < or = 0.90 were accompanied by diplopia and difficulty in tracking moving objects in all subjects. The ability to strongly oppose the incisor teeth did not return until the TOF ratio (on average) exceeded 0.85. A sustained 5-s head-lift was not achieved until the TOF ratio averaged 0.60 (range, 0.45-0.75). At a TOF ratio of 0.70, grip strength averaged 59% of control (range, 50-75%). With certain exceptions (vision, ability to clench the teeth tightly), there was wide variation in symptomatology between patients for any given TOF ratio. It is impossible to give reliable TOF break-points at which symptoms and signs will be present or absent. CONCLUSIONS: All subjects had significant signs and symptoms of residual block at a TOF ratio of 0.70; none considered themselves remotely "street ready" at this time. The authors believe that satisfactory recovery of neuromuscular function after mivacurium-induced neuromuscular block requires return of the TOF ratio to a value > 0.90 and ideally to unity.

Adult↗
PubMed1996

Residual postoperative paralysis. Pancuronium versus mivacurium, does it matter?

BACKGROUND: Based on a train-of-four (TOF) ratio greater than 0.70 as the standard of acceptable clinical recovery, undetected postoperative residual paralysis occurs frequently in postanesthesia care units. In most published studies, detailed information regarding anesthetic management is not provided. The authors reexamined the incidence of postoperative weakness after the administration of long- and short-acting neuromuscular blockers because few, if any, such comparative studies are available. METHODS: Ninety-one adult patients were studied. In group 1 (mivacurium, n = 35), anesthesia was induced with propofol/ fentanyl and maintained with nitrous oxide, desflurane, and opioid supplementation. The response of the adductor pollicis to ulnar nerve stimulation was estimated by palpating the thumb. Mivacurium (0.20 mg/kg) was administered for tracheal intubation, and an infusion was adjusted to maintain the TOF count at 1. When surgery was completed, the infusion was discontinued. When a second twitch could be detected, 7.0 micrograms/kg atropine and then 0.5 mg/kg edrophonium were administered. At 5 and 10 min, the mechanical TOF response was measured. Additional measurements were recorded if possible. Patients were tracheally extubated and discharged from the operating room when they could respond to verbal commands and no TOF fade was palpable. In group 2 (pancuronium-desflurane anesthesia, n = 29), the protocol was identical to that of group 1, except that 0.07 mg/kg pancuronium was administered for tracheal intubation. Additional increments (0.5 to 1 mg) were given as needed. Antagonism was accomplished with 0.05 mg/kg neostigmine and 0.01 mg/kg glycopyrrolate. In group 3 (pancuronium propofol-opioid, n = 27), the protocol was identical to that of group 2, except that anesthesia was maintained with nitrous oxide and a propofol-alfentanil infusion. In all groups, patients were assessed until a TOF ratio of 0.90 or more was achieved. RESULTS: All of the patients in group 1 had TOF ratios greater than 0.80 on arrival in the postanesthesia care unit. Twenty of 35 patients had TOF ratios 0.90 or more while they were still in the operating room. Thirty-three of 35 patients had TOF ratios 0.90 or more within 30 min of reversal, and this value was reached in all patients by 45 min. Recovery parameters in groups 2 and 3 did not differ from each other. Hence data from these groups were pooled. Fifty-four of 56 patients who received pancuronium had TOF values of 0.70 or more, the remaining two patients had values of 0.6 to 0.7. In contrast to the mivacurium group, however, only four patients achieved a TOF ratio of 0.90 or greater while still in the operating room. Finally, eight of these patients did not achieve this degree of recovery within 90 min of reversal. CONCLUSIONS: These results suggest that if nondepolarizing neuromuscular blockers are administered using tactile evaluation of the TOF count as a guide, critical episodes of postoperative weakness in the postanesthesia care unit should occur infrequently even with long-acting relaxants. Nevertheless, if full recovery is defined as return to a TOF ratio of 0.90 or more, then short-acting agents would appear to offer a wider margin of safety.

Adult↗
PubMed1996

Re-establishment of paralysis using mivacurium following apparent full recovery from mivacurium-induced neuromuscular block.

Recent published data suggest that despite apparently satisfactory recovery from nondepolarising block (train-of-four ratios in excess of 0.90), even very small doses of additional relaxant may re-establish significant paralysis. We sought to verify this observation and quantify its magnitude. Twelve adult patients were studied under nitrous oxide-propofol-opioid anaesthesia and neuromuscular block was monitored electromyographically. Train-of-four stimuli were delivered to the ulnar nerve every 20 s throughout the period of observation. After baseline stabilisation, an initial bolus of mivacurium 25 micrograms.kg-1 was administered and the twitch depression noted. When the twitch was stable for two consecutive stimuli, a second bolus, calculated to produce approximately 90% twitch depression, was administered. Recovery was then allowed to proceed spontaneously until the train-of-four ratio reached 0.95. At that time a second 25 micrograms.kg-1 dose was administered and the effect on twitch height recorded. Using the slope for the log-dose/logit dose-response relationship of mivacurium (5.5), it was possible to estimate any change in the ED50 of mivacurium. The control ED50 of mivacurium (calculated from the initial dose of mivacurium) averaged 43 micrograms.kg-1. When the same dose of drug was given at 95% recovery of the train-of-four ratio, the ED50 was reduced to 19 micrograms.kg-1 (p < 0.0001). Hence, there remains a considerable reduction in the neuromuscular margin of safety even at a train-of-four ratio of 0.95.

Adolescent↗
PubMed1995

The influence of changes in hand temperature on the indirectly evoked electromyogram of the first dorsal interosseous muscle.

The evoked EMG response commonly decreases in amplitude during the first few minutes of anaesthesia. The purpose of this study was to determine if a relationship exists between changes in hand temperature, which are known to occur with induction of anaesthesia, and drift in the EMG signal. The indirectly evoked response of the 1st dorsal interosseous muscle was measured using a Datex Relaxograph in 15 patients undergoing elective surgery. The test arm was wrapped in towels in order to minimize heat loss. Core body temperature, hand temperature, and T1 were recorded at two minute intervals for the next 30 min. Patients then received a bolus of mivacurium 0.08 mg.kg-1 and additional doses were given as needed. Complete recovery was defined as a TOF ratio > 0.90. Regression analysis plotting delta temperature against delta T1 was performed for each individual. The slope of the regression line for the relationship between delta degree C and delta T1 was then used to calculate a correction factor (CF) which might be used to "fine tune" the last measured T1. The initial hand temperature averaged 30.8 +/- 1.4 degrees C and this increased by 4.1 +/- 1.2 degrees C over the next 30 min. During this period T1 decreased by 24.8 +/- 5.9% or -6.05%/degrees C. The final mean T1 value at the end of anaesthesia (uncorrected) was 70.6 +/- 7% of control. The average corrected T1 value was 94.7 +/- 8.5% (range, 83-111%). It is concluded that there was a correlation between delta degree C and delta T1 during the first 30 min of anaesthesia (r2 = 0.77, P < 0.0001). However, in 5 of 15 individuals it was not possible to "temperature correct" the final T1 value to within +/- 10% of control. Hence, while changes in muscle temperature probably play a major role in the T1 drift seen with the Datex monitor, other factors remain to be identified.

Adolescent↗
PubMed1994

Antagonism of mivacurium-induced neuromuscular blockade in humans. Edrophonium dose requirements at threshold train-of-four count of 4.

BACKGROUND: Mivacurium's rapid rate of recovery has led to the suggestion that routine reversal of its residual effects may be unnecessary once signs of spontaneous recovery are evident. When antagonism is attempted at 90% twitch depression, the time saved to return to train-of-four (TOF) ratios > 0.70 compared to control has been reported to average < or = 8 min. This study was an attempt to determine whether similar savings in time could be achieved once spontaneous recovery was well underway. Also investigated was the ability of a TOF count of 4 to serve as a marker that might predict the dose of edrophonium necessary for satisfactory antagonism of mivacurium. METHODS: Fifty-eight adult patients were studied under nitrous oxide/propofol/opioid anesthesia. Neuromuscular block was monitored electromyographically and maintained by infusion of mivacurium at a level sufficient to abolish any palpable response of the thumb. TOF stimuli were delivered to the ulnar nerve at the wrist every 20 s throughout the period of observation. When the infusion was terminated, an observer was asked to note the time when the 1st through the 4th twitches first became detectable. In group 1, recovery to a TOF ratio > 0.90 was allowed to proceed spontaneously. In groups 2, 3, and 4, 0.3, 0.5, and 0.75 mg/kg edrophonium, respectively, was administered when the 4th response to TOF stimulation first became palpable. Times to TOF ratios of 0.70 and 0.90 were recorded in all groups. RESULTS: TOF counts of 1, 2, 3, and 4 first became palpable at 8 +/- 4% (SD), 20 +/- 6%, 33 +/- 9%, and 44 +/- 10% of control twitch height. Fade on TOF stimulation could no longer be detected once the TOF ratio exceeded a value of 0.41 +/- 0.07 (range 0.25-0.51). Once the 1st evoked response was palpable, the 2nd, 3rd, and 4th responses could be detected 2.5 +/- 1.1 (SD), 4.6 +/- 1.6, and 6.1 +/- 1.6 min later. Spontaneous recovery to TOF fade ratios of 0.7 and 0.9 occurred on average 10.7 +/- 2.3 and 16.9 +/- 4.7 min, respectively, after a threshold count of 4. Administration of 0.3 mg/kg edrophonium shortened the recovery process by about 7.5 min. Increasing the dose of edrophonium beyond 0.3 mg/kg did not further accelerate recovery. CONCLUSIONS: After recovery from profound mivacurium-induced neuromuscular block, TOF counts of 1, 2, 3, and 4 approximate 10%, 20%, 30%, and 40% return to control twitch height, respectively. Finally, > or = 0.3 mg/kg edrophonium will accelerate recovery from mivacurium by approximately 7-8 min.

Adult↗
PubMed1993

Laparoscopy explosion hazards with nitrous oxide.

BACKGROUND: During laparoscopic surgery utilizing carbon dioxide as the insufflating agent, nitrous oxide will diffuse into the peritoneal cavity if it is used as part of the anesthetic. Bowel perforation and the subsequent release of volatile bowel gas could create a explosion hazard. METHODS: Two related studies were undertaken. The first quantified the transfer of nitrous oxide, over time, in 19 female patients undergoing laparoscopy. The second established the lower limits of flammability of a range of concentrations of methane and hydrogen diluted with nitrogen (simulated bowel gas) in a range of concentrations of nitrous oxide diluted with carbon dioxide (simulated peritoneal gas). RESULTS: The mean concentrations of N2O at 10, 20, and 30 min from the time of insufflation were 19.9 +/- 4.8%, 30.3 +/- 6.8%, and 36.1 +/- 6.9%, respectively. The maximum reported concentrations of methane and hydrogen in bowel gas are 56% and 69%, respectively. The concentration of nitrous oxide necessary to support combustion of 56% methane is approximately 47%. By contrast, the concentration of nitrous oxide needed to support combustion of 69% hydrogen is approximately 29%. CONCLUSIONS: The authors have shown that it is possible for nitrous oxide to reach concentrations in the peritoneal cavity that can support combustion of bowel gas.

Adult↗