George G. Neuman

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

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 micro gram/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.

Antagonism of Mivacurium-induced Neuromuscular Blockade in Humans: Edrophonium Dose Requirements at Threshold Train-of-four Count of 4

Background:Mivacuriums 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 traln-of-four (TOF) ratios >0.70 compared to control has been reported to average ≤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 mivacurlum-induced neuromuscular block, TOF counts of 1, 2, 3, and 4 approximate 10%, 20%, 30%, and 40% return to control twitch height, respectively. Finally, ≥0.3 mg/kg edrophonium will accelerate recovery from mivacurium by approximately 7-8 min.

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 Atemperature against Δ T1 was performed for each individual. The slope of the regression line for the relationship between Δ°C and δ 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° C and this increased by 4.1 ± 1.2° C over the next 30 min. During this period T1 decreased by 24.8 ± 5.9% or-6.05%/° 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 Δ°C and ΔT1 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.RésuméLa réponse évoquée à l’EMG diminue ordinairement pendant les premières minutes de l’anesthésie. Le but de cette étude était de déterminer la relation possible entre les changements de température de la main qui surviennent à l’induction, et la dérive du signal de l’EMG. La réponse indirecte évoquée au 1er muscle interosseux dorsal a été mesurée avec un Relaxograph® Datex® chez 15 patients en chirurgie réglée. Le bras servant à l’expérience a été enveloppé dans des serviettes pour en atténuer la perte de chaleur. La température centrale, la température de la main et T1 ont été enregistrés aux deux minutes pendant 30 min. Les patients ont alors reçu un bolus de mivacurium 0,08 mg · kg−1 et des doses additionnelles administrées au besoin. La récupération complète a été définie comme un rapport de TOF > 90%. L’analyse de régression établissant la relation entre Δ température et ΔT1 a été effectuée pour chacun des sujets. La pente de régression pour la relation entre Δ°C et ΔT1 a été utilisée pour calculer un facteur de correction (FC) utilisable pour une mise au point finale du dernier T1 mesuré. La température initiale de la main était en moyenne de 30,8 ± 1,4° C. Elle augmentait de 4,1 ± 1,2° C pendant les 30 min suivantes. Pendant cette période, T1 diminuait de 28,4 ± 5,9% ou −6,05%/° C. La valeur finale moyenne de T1 à la fin de l’anesthésie (sans correction) était de 70,6 ± 7% du contrôle. La valeur moyenne corrigée de T1 était de 94,7 ± 8,5% (écart, 83–111%). En conclusion, il existe une corrélation entre Δ° C et AT1 au cours des 30 premières min d’anesthésie (r2 = 0,77, P < 0,0001). Toutefois, chez cinq des 15 sujets, il a été impossible d’appliquer la correction de température à la valeur finale de T1 à ±10% du contrôle. En conclusion, bien que les changements de température musculaire puissent jouer un rôle majeur dans la dérive de T1 observée avec le moniteur Datex, les autres facteurs en cause sont encore inconnus.

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 20s throughout the period of observation. After baseline stabilisation, an initial bolus of mivacurium 25 μg.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 μg.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 μg.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 μg.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.

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 included 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 subjects 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(TM) (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 [center dot] kg sup ‐1 [center dot] min sup ‐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 patent airway, and the hemoglobin oxygen saturation while breathing air was greater or equal to 96% at all times. TOF ratios less or equal to 0.90 were accompanied by diplopia and difficulty in tracking moving objects in all subjects. The ability to strongly appose 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.