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Biomedical subjects

A F Kopman

Publications and source records attributed to A F Kopman.

At least 19 recordsLinked to original sources
PubMed2005

Dose-response relationship of rocuronium: a comparison of electromyographic vs. acceleromyographic-derived values.

BACKGROUND: Acceleromyography (AMG) is being employed with increasing frequency as a research tool. However, there is almost no information available regarding the accuracy of values for drug potency obtained using AMG. This study was an attempt to determine if AMG-derived ED(50/95) values are interchangeable with those measured with a more traditional neuromuscular monitor. METHODS: Thirty adult patients were studied. Anesthesia was induced and maintained with N20, propofol, and supplementation opioid. Tracheal intubation was accomplished without muscle relaxants. Simultaneous ipsilateral AMG and EMG responses to 0.10 Hz stimulation was recorded. Following instrument calibrations, a single dose of rocuronium was administered. The first patient received a bolus of 0.17 mg kg(-1) of rocuronium. Using the Hill equation with a postulated slope of 4.50, the ED(50) was calculated. The second subject received a dose which approximated the calculated ED(50) for patient no. 1. Successive subjects were given a dose based on the running average of the estimated ED(50). RESULTS: The AMG-derived ED50/95 values for rocuronium (0.163 +/- 0.055 and 0.314 +/- 0.105 mg mg(-1)) were virtually identical to those established using EMG (0.159 +/- 0.043 and 0.306 +/- 0.084 mg kg(-1)). While mean peak twitch depression (Delta T1) was the same in both groups for individual subjects Delta T1 differed by +/- 20% (95% confidence interval). DISCUSSION: Acceleromyography-derived twitch heights for individual patients are not necessarily interchangeable with information obtained using electromyography. Nevertheless, acceleromyography appears to be a valid methodology for determining the drug potency when a population rather than an individual subject is being studied.

Acceleration↗
PubMed2005

Acceleromyography vs. electromyography: an ipsilateral comparison of the indirectly evoked neuromuscular response to train-of-four stimulation.

BACKGROUND: There is a considerable body of evidence which suggests that data obtained using acceleromyography (AMG) cannot be used interchangeably with observations obtained by mechanomyographic (MMG) or electromyograhic (EMG) methods. All previous such studies evaluated the responses from contralateral limbs. This investigation was undertaken to determine if these previously described differences were in part a function of observing the responses from opposing limbs. METHODS: We compared the ipsilateral EMG and AMG response to an ED(95) bolus of atracurium in 50 subjects. In half of the individuals the thumb was free to move freely; in half, a small elastic preload was applied to the thumb. Train-of-four (TOF) recovery was followed until a TOF ratio >0.90 was recorded by both monitors. Acceleromyography vs. EMG differences and the resultant 95% confidence limits for twitch height (T1) and the TOF ratio were determined. RESULTS: When the AMG TOF value had recovered to a value of 0.72 +/- 0.03; the simultaneously evoked EMG value averaged only 0.59 +/- 0.08. This difference was statistically significant (P < 0.001). Although the mean difference AMG vs. EMG was little more than 0.10, differences in an individual might be twice that amount. When the AMG TOF value had recovered to 0.90, the simultaneously evoked EMG value averaged 0.85. Again the 95% confidence limits for individual observations was very wide. With EMG, once the TOF ratio returns to a value of 0.70, T1 has returned to 95% of control. In contrast with AMG, return of T1 -95% of control requires a TOF ratio of almost 0.90. Addition of an elastic preload to the thumb decreased control TOF variability without effecting the relationship between twitch height and the TOF ratio. CONCLUSION: Acceleromyographic TOF values tend to overestimate the extent of EMG recovery. Acceleromyographic TOF values <0.90 are indicative of incomplete neuromuscular recovery.

Acceleration↗
PubMed2004

Model to describe the degree of twitch potentiation during neuromuscular monitoring.

BACKGROUND: Neuromuscular block is estimated by comparing the evoked peak twitch with a control value measured in the absence of neuromuscular block. In practice, this control value is often difficult to determine because repeated motor nerve stimulation enhances the evoked mechanical response of the corresponding muscle, resulting in an increased twitch response. This is known as twitch potentiation or the staircase phenomenon. It is probably the result of myosin light chain phosphorylation creating an increased twitch force for a given amount of Ca(2+) released at each action potential. Modelling of potentiation may improve studies of neuromuscular blocking agents using mechanomyography or accelerometry. METHODS: We used one- and two-exponential models to describe the degree of myosin light chain phosphorylation and associated twitch potentiation. These models were fitted to accelerographic twitch force measurements for various stimulation patterns and frequencies used in neuromuscular monitoring. RESULTS: Fitting a two-exponential model to twitch data for various stimulation rates and patterns provides better prediction than a one-exponential model. A one-exponential model performs poorly when the stimulation rate varies during measurement. CONCLUSIONS: We conclude that a two-exponential model can predict the degree of twitch potentiation for the stimulation patterns and frequencies tested more accurately than a one-exponential model. However, if only one stimulation frequency is used, a one-exponential model can provide good accuracy. We illustrate that such a potentiation model can improve the ability of pharmacodynamic-pharmacokinetic neuromuscular block models to predict twitch response in the presence of a neuromuscular blocking agent.

Electric Stimulation↗
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↗