Single Twitch Height Research Articles

Subparalyzing Doses of Rocuronium Reduce Muscular Endurance without Detectable Effect on Single Twitch Height in Awake Subjects.

Purpose To test the hypothesis that a low-dose rocuronium acts mainly by means of reducing muscular endurance rather than by reducing momentary force. Methods In a randomized placebo-controlled double-blinded study, eight healthy volunteers were studied in two sets of experiments. In the first set, the subjects made a sustained maximum effort with the dominant hand for 80 seconds while squeezing an electronic handgrip dynamometer at three minutes after intravenous administration of placebo, 0.04 or 0.08 mg/kg rocuronium. Handgrip force at initiation of testing (maximum handgrip force) and after 60 seconds was evaluated. In the second set, the ulnar nerve of the subjects was electrically stimulated every tenth second for at least 10 and a maximum of 30 minutes following the administration of placebo and 0.08 mg/kg rocuronium. Single twitch height of the adductor pollicis muscle was recorded. Results There was no significant difference in the effect on maximum handgrip force at time 0 between the three different doses of rocuronium. As compared with placebo, handgrip force after 0.08 mg/kg rocuronium was reduced to approximately a third at 60 seconds (214 N (120–278) vs. 69 (30–166); p=0.008), whereas only a slight reduction was seen after 0.04 mg/kg (187 (124–256); p=0.016). Based on these results, the sustained handgrip force after 0.2 mg/kg at 60 seconds was calculated to be 1.27% (95% CI [0.40, 4.03]) of the maximum force of placebo. No effect on single twitch height after 0.08 mg/kg rocuronium at four minutes after drug administration could be detected. Conclusions Subparalyzing doses of rocuronium show a distinct effect on muscular endurance as opposed to momentary force. The findings support the hypothesis that low doses of rocuronium act mainly by reducing muscular endurance, thereby facilitating, for example, tracheal intubation.

Therapeutic doses of neostigmine, depolarising neuromuscular blockade and muscle weakness in awake volunteers: a double-blind, placebo-controlled, randomised volunteer study.

Neostigmine reverses non-depolarising neuromuscular blockade, but may cause muscle weakness when administered after full recovery of neuromuscular function. We hypothesised that neostigmine in therapeutic doses impairs muscle strength and respiratory function in awake healthy volunteers. Twenty-one volunteers were randomised to receive two doses of either intravenous (i.v.) neostigmine 2.5mg with glycopyrrolate 450μg (neostigmine group, n=14) or normal saline 0.9% (placebo group, n=7). The first dose was administered immediately after obtaining baseline measurements, and the second dose was administered 15min later. All 14 volunteers in the neostigmine group received the first dose, mean (SD) 35 (5.8) μg.kg-1 , but only nine of these volunteers agreed to receive the second dose, 34 (3.5) ?g.kg-1 . The primary outcome was hand grip strength. Secondary outcomes were train-of-four ratio, single twitch height, forced expiratory volume in 1s, forced vital capacity, forced expiratory volume in 1s/forced vital capacity ratio, oxygen saturation, heart rate and mean arterial pressure. The first dose of intravenous neostigmine with glycopyrrolate resulted in reduced grip strength compared with placebo, -20 (20) % vs. +4.3 (9.9) %, p=0.0016; depolarising neuromuscular blockade with decreased single twitch height, -14 (11) % vs. -3.8 (5.6) %, p=0.0077; a restrictive spirometry pattern with decreased predicted forced expiratory volume in 1s, -15 (12) % vs. -0.47 (3.4) %, p=0.0011; and predicted forced vital capacity, -20 (12) % vs. -0.59 (3.2) %, p<0.0001 at 5min after administration. The second dose of neostigmine with glycopyrrolate further decreased grip strength mean (SD) -41 (23) % vs. +1.0 (15) %, p=0.0004; single twitch height -25 (15) % vs. -2.5 (6.6) %, p=0.0030; predicted forced expiratory volume in 1s -23 (24) % vs. -0.7 (4.4) %, p=0.0063; and predicted forced vital capacity, -27.1 (22.0) % vs. -0.66 (3.9) %, p=0.0010. Train-of-four ratio remained unchanged (p=0.22). In healthy volunteers, therapeutic doses of neostigmine induced significant and dose-dependent muscle weakness, demonstrated by a decrease in maximum voluntary hand grip strength and a restrictive spirometry pattern secondary to depolarising neuromuscular blockade.

The effect of phenylephrine on the onset time of rocuronium

BackgroundSeveral studies have demonstrated that ephedrine shortens the onset time of muscle relaxants, and it does so probably by increasing the cardiac output. However, elevation of the systemic blood pressure through α adrenergic stimulation via ephedrine may affect the onset of muscle relaxants during the induction of anesthesia. We investigated the effect of phenylephrine, which is a selective α-1 agonist, on the onset time of rocuronium and the intubating conditions in adults after the administration of propofol.MethodsSixty-four patients were randomly assigned to two groups. Phenylephrine (0.9 µg/kg) (P group) or the same volume of saline (S group) was injected before rocuronium (0.6 mg/kg) administration. Anesthesia was induced with fentanyl 2 µg/kg and propofol 2 mg/kg. The onset time was defined as the time from the end of rocuronium injection to the time when a single twitch height gets to 0% or the minimum level. A well-trained anesthesiologist who was 'blinded' to the treatment groups evaluated the intubating conditions. The mean arterial pressure and heart rate were recorded before induction, before intubation, immediately after intubation and 1 minute and 2 minutes after intubation.ResultsThe onset time was 84 ± 18 sec in the P-group and 72 ± 14 sec in the S-group. There was no difference of the intubating conditions, the mean arterial pressure and the heart rate between the two groups.ConclusionsA small dose of phenylephrine, which has a limited effect on blood pressure, delayed the onset time of rocuronium after the administration of propofol, and the vasoconstriction effect of phenylephrine may affect the prolongation of the rocuronium onset time at the induction of anesthesia with using propofol.

Post Tetanic Count and Single Twitch Height at the Onset of Reflex Movement After Administration of Vecronium Under Total Intravenous Anesthesia.

Post Tetanic Count and Single Twitch Height at the Onset of Reflex Movement After Administration of Vecronium Under Total Intravenous Anesthesia.

Effects of Edrophonium and/or Pseudocholinesterase for the Reversal of Mivacurium-Induced Paralysis in vitro

Background: Mivacurium is a nondepolarizing neuromuscular blocking agent hydrolyzed by pseudocholinesterase. Anticholinesterase used in the reversal of mivacurium-induced muscle relaxation may also inhibit plasma pseudocholinesterase, and delay hydrolysis of mivacurium. In this study, the effects of edrophonium and/or bovine pseudocholinesterase (BpChE) in the reversal of mivacurium were investigated with the rat phrenic nerve-diaphragm preparation. Methods: Fifty Sprague-Dawley rats (150 - 200 g) were randomly allocated into 10 groups based on the dosage of edrophonium and BpChE. Each animal was anesthetized with thiopental sodium (40 mg/kg J.P.). The phrenic nerve-diaphragm was dissected and mounted in a bath containing an oxygenated Krebs' solution at 32. The phrenic nerve was stimulated at supramaximal intensity and the single twitch responses and train of four (TOF) ratio were measured. After stabilization of the twitch responses, mivacurium (1 /ml) was administered incrementally to obtain more than 95% twitch inhibition. Reversal of the mivacurium-induced block by edrophonium (0.01, 0.1, 1, or 10 ,/ml) and/or BpChE (0.1 u, or 1.0 u/ml) were tested. A single twitch height more than 75% of the baseline value was considered an adequate reversal. Results: Mivacurium-induced paralysis was recovered more effectively by BpChE 1.0 u/ml than the other groups. Edrophonium improved a single twitch in a dose dependent manner. Conclusions: Mivacurium-induced paralysis can be more effectively reversed by BpChE than edrophonium. Inhibition of pseudocholinesterase was not observed by increasing the dose of edrophonium.

Pharmacokinetics and pharmacodynamics of mivacurium stereoisomers in beagle dogs using twitch height and train-of-four response.

Mivacurium, a non-depolarizing neuromuscular blocking agent, consists of three isomers; trans-trans (57%), cis-trans (36%) and cis-cis (7%). The purpose of this study was to characterize the pharmacokinetics and pharmacodynamics of mivacurium after various inputs. Four beagle dogs weighing between 7.95 and 9.89 kg were anesthetized with isofluorane (5%) and received a bolus dose (0.010-0.020 mg kg(-1)) and two constant rate infusions (1.0-1.5 microg kg(-1) min(-1)) of mivacurium via the saphenous vein. Single twitch height (TH) and train-of-four (TOF) were evaluated every 15 and 30 s, respectively. Arterial blood samples were collected, processed and analysed for mivacurium using a stereospecific HPLC-fluorescence method. The disposition of mivacurium isomers was best described by a two compartment model. Mean Cl for the cis-trans, trans-trans and cis-cis isomers were 19.98, 13.53 and 3.47 mL min(-1) kg(-1) respectively and the corresponding mean Vdss were 0.29, 0.24 and 1.00 L kg(-1). The measurement of onset showed dose dependence as evidenced by a rapid onset at the higher doses. TOF measurements were more sensitive to the onset of action and required a longer period of time to recover to baseline values as compared with TH measurements.

Succinylcholine Duration and Critical Hemoglobin Desaturation in the Healthy Adult

Professor of Anesthesia; University of Calfornia, San Diego; San Diego, California(Accepted for publication February 5, 1998.)In Reply:- Although I fully agree with the slogan that prevention is better than intervention (and that message is well embraced by the FAO2parameter in the desaturation model in my article), the slogan for my conclusion “if VEis thought to be 0, or near 0,” then “a rescue option should be instituted aggressively and early,” is that it is better to be safe than sorry. One must remember that my analysis probably underestimated the danger of severe hypoxemia by assuming complete alveolar denitrogenation (rarely achieved) and by ignoring the fact that concomitantly administered anesthetics may delay functional recovery (frequently true), result in loss of airway patency (often true), and adversely change physiologic variables (e.g., decrease functional residual capacity and cardiac output). In addition, and very importantly, I presented mean data, which means that for half of the population the danger will be greater and for half of the population the danger will be less. In the final analysis every practitioner has to ask themselves, given the boundary conditions in my article +/- 1 min, if they would be willing to simply wait for succinylcholine to wear off if there is no ventilation and no obvious likelihood there will be ventilation. A negative answer seems obvious. I would not want to try and justify injury to the patient on the basis of the myriad of arguments for increasing the margin of safety of 1 mg/kg succinylcholine brought forward by Dr. Bourke; the arguments are either not substantial (e.g., minor discrepancies in succinylcholine dosing used in the literature), agreed on (decreasing the succinylcholine dosage shortens the duration of apnea), unrealistic (use 0.20 - 0.25 mg/kg of succinylcholine), or potentially dangerous (some patients might survive breathing spontaneously [diaphragmatic movement does not necessarily equate with respiration] with a single twitch height that is only 50% of control).Jonathan L. Benumof, M.D.Professor of Anesthesia; University of Calfornia, San Diego; San Diego, California

Critical hemoglobin desaturation will occur before return to an unparalyzed state following 1 mg/kg intravenous succinylcholine.

Critical Hemoglobin Desaturation Will Occur before Return to an Unparalyzed State following 1 mg/kg Intravenous Succinylcholine Jonathan Benumof;Rachel Dagg;Reuben Benumof; Anesthesiology

The Use of a Circumferential Cathode Improves Amplitude of Intraoperative Electrical Transcranial Myogenic Motor Evoked Responses

Measurement of motor evoked responses to transcranial electrical stimulation (tc-MER) is a technique for intraoperative monitoring of motor pathways. Since most anesthetics significantly reduce motoneuronal excitability, optimal stimulation paradigms should be sought. We compared the efficiency of stimulus delivery using two different configurations of the cathode component of the stimulating electrode pair (circumferential: Fz, F3, F4, A1, and A2 versus a single cathode at Fz). The anode was positioned at Cz with both cathode configurations. Fourteen neurologically normal patients undergoing spinal surgery were anesthetized with sufentanil-N (2) O-ketamine. Partial neuromuscular blockade (single twitch height 25%) was maintained with vecuronium. Compound action potentials to transcranial stimulation with both cathode configurations were recorded from the tibialis anterior muscle. All recordings were completed before spinal manipulation. The median amplitude response using the Fz cathode configuration was 256 mu V (10th-90th percentiles: 50-641 mu V). With the circumferential cathode configuration, tc-MER amplitude increased to 281 (87-1479) mu V (P < 0.01). There was no significant difference in onset latency between electrode configurations. The observed tc-MER amplitude augmentation with the use of a circumferential cathode might allow tc-MER monitoring in those patients who do not have sufficiently reproducible responses when a single cathode is used. A possible explanation is that the circumferential cathode alters the direction of electrical currents in the cortex, resulting in more efficient depolarization of cortical motor neurons. (Anesth Analg 1996;82:1011-4)

The Use of a Circumferential Cathode Improves Amplitude of Intraoperative Electrical Transcranial Myogenic Motor Evoked Responses

Measurement of motor evoked responses to transcranial electrical stimulation (tc-MER) is a technique for intraoperative monitoring of motor pathways. Since most anesthetics significantly reduce motoneuronal excitability, optimal stimulation paradigms should be sought. We compared the efficiency of stimulus delivery using two different configurations of the cathode component of the stimulating electrode pair (circumferential: Fz, F3, F4, A1, and A2 versus a single cathode at Fz). The anode was positioned at Cz with both cathode configurations. Fourteen neurologically normal patients undergoing spinal surgery were anesthetized with sufentanil-N2O-ketamine. Partial neuromuscular blockade (single twitch height 25%) was maintained with vecuronium. Compound action potentials to transcranial stimulation with both cathode configurations were recorded from the tibialis anterior muscle. All recordings were completed before spinal manipulation. The median amplitude response using the Fz cathode configuration was 256 microV (10th-90th percentiles: 50-641 microV). With the circumferential cathode configuration, tc-MER amplitude increased to 281 (87-1479) microV (P < 0.01). There was no significant difference in onset latency between electrode configurations. The observed tc-MER amplitude augmentation with the use of a circumferential cathode might allow tc-MER monitoring in those patients who do not have sufficiently reproducible responses when a single cathode is used. A possible explanation is that the circumferential cathode alters the direction of the electrical currents in the cortex, resulting in more efficient depolarization of cortical motor neurons.

RETRACTED: Post-tetanic count and single twitch height at the onset of reflex movement after administration of vecuronium under different types of anaesthesia

We have studied post-tetanic count (PTC) and single twitch height at the onset of reflex movement to carinal stimulation after administration of vecuronium with five different types of anaesthesia. Seventy-five adult patients were allocated randomly to five groups of 15 patients each, to receive one of the following anaesthetics: neuroleptanaesthesia (fentanyl and droperidol) or 1 MAC of either halothane, isoflurane, enflurane or sevoflurane with 66% nitrous oxide in oxygen. During spontaneous recovery from vecuronium-induced neuromuscular block, the carina was stimulated with a suction catheter every 150 s. Single twitch heights at the onset of reflex movement were similar (2.0-2.7% of control values) between the five groups. In contrast, PTC at the onset of reflex movement to carinal stimulation differed (7.4-17.0) between groups.

Tactile Evaluation of Train-of-four Count as an Indicator of Reliability of Antagonism of Vecuronium- or Atracurium-induced Neuromuscular Blockade

Recent evidence suggests that edrophonium is not the agent of choice to reverse profound neuromuscular blockade but remains an efficacious drug when the level of neuromuscular blockade to be antagonized is modest. We studied 90 healthy adults in an attempt to address the questions: 1) How much variability in such neuromuscular parameters as single twitch height and the train-of-four (TOF) fade ratio (T4/T1) exist when the TOF count first returns to four palpable responses? 2) Is edrophonium a reliable antagonist at this measured point of recovery? 3) What is the optimal dose of edrophonium needed to produce prompt (less than 10 min) and satisfactory (T4/T1 greater than 0.7) reversal when the fourth response of the thumb to indirect TOF stimulation just becomes palpable? Patients were given a bolus atracurium or vecuronium (n = 45 in each group) followed by an iv infusion sufficient to maintain single twitch as measured by electromyography at 10-15% of control values. At the end of surgery, the infusion was terminated and spontaneous recovery was allowed to begin. Once the tactile TOF count was four, edrophonium 0.3, 0.5, or 0.75 mg/kg was administered. At a count-of-four the first twitch averaged 37% of control (+/- 8.5% standard deviation; pooled data from all groups) and the mean T4/T1 ratio was 0.14 +/- 0.049. After atracurium neuromuscular blockade, edrophonium 0.3 mg/kg produced adequate antagonism in 10 min. At this time the mean T4/T1 ratio was 0.79 +/- 0.07 and the lowest observed value was 0.67. Increasing the edrophonium dose to 0.75 mg/kg accelerated recovery by 4-5 min.(ABSTRACT TRUNCATED AT 250 WORDS)

The Effect of Metoclopramide on the Time from Disapprearance of 1 Hz Single Twitch Height to Reappearance of that following injection of Succinylcholine

The Effect of Metoclopramide on the Time from Disapprearance of 1 Hz Single Twitch Height to Reappearance of that following injection of Succinylcholine

Duration of Action of Neostigmine and Pyridostigmine in the Elderly

This study was undertaken to assess differences between young and elderly patients with respect to the duration of antagonism of metocurine neuromuscular blockade by neostigmine (NEO) or pyridostigmine (PYR). Patients were given either NEO (seven elderly and ten young) or PYR (seven elderly and eight young) and received nitrous oxide in oxygen (60:40) and 1 MAC halothane. Neuromuscular transmission was assessed by using evoked compound electromyography. Metocurine 0.1 mg/kg was given, followed by a continuous infusion to achieve 90% reduction in baseline single twitch height. After at least 30 minutes, either NEO (0.07 mg/kg) or PYR (0.14 mg/kg) and atropine (0.02 mg/kg) were given IV. After injection of NEO or PYR, the duration of maximal response (DOMR) was recorded. Mean (+/- SE) ages were 38 +/- 5 and 68 +/- 2 years in the two groups of patients receiving PYR. In the elderly, PYR significantly prolonged DOMR compared to younger patients (35.3 +/- 8.2 vs 14.4 +/- 4.2 minutes, respectively). The mean ages in the two groups of patients receiving NEO were 41.5 +/- 4 and 72 +/- 2 years. The elderly group demonstrated a significant increase in the DOMR compared to younger patients (32 +/- 10 vs 11 +/- 2 minutes, respectively). It is concluded that, compared to younger patients, the duration of action of NEO and PYR in the aged patient is prolonged.

POST-TETANIC COUNT AND PROFOUND NEUROMUSCULAR BLOCKADE WITH ATRACURIUM INFUSION IN PAEDIATRIC PATIENTS

In 38 paediatric surgical patients given atracurium by infusion, the degree of neuromuscular blockade was monitored using the post-tetanic twitch response. This was assessed by counting the number of visible responses when single twitch stimulation was applied at 1 Hz for 30 s after a 5-s tetanic stimulation at 50 Hz. A post-tetanic count of less than 10 correlated with a single twitch height of less than 5% of control, and ensured adequate paralysis. Once the count was greater than 15, the blockade could be antagonized readily.

Decreased Sensitivity to Metocurine in Patients with Upper Motoneuron Disease

Responses to the nondepolarizing muscle relaxant, metocurine, were studied in eight hemiplegic and eight unmatched patients with normal motor strength during the general anesthetic given for various neurosurgical operations. Metocurine, 0.3 mg/kg, was administered intravenously, and indirectly evoked thumb twitch tensions were measured on both sides in the hemiplegic patients, and on one side in the normal patients. Arterial blood samples were obtained as twitch tension was recovering, and serum metocurine concentrations were determined using a specific radioimmunoassay. Percentage of paralysis was plotted as a function of log [metocurine] and the data were compared by analysis of covariance. For the normal motor strength patients, r = 0.84; for the unaffected arm of the hemiplegic patients, r = 0.69; and for the affected arm of the hemiplegic patients, r = 0.86, all significant at P less than 0.001. The mean plasma metocurine concentrations at 20, 25, 50, 75, and 80% paralysis were significantly different for all groups (P less than 0.001). The regression lines, in turn, did not overlap and were significantly different, each from the other (P less than 0.005). We were, however, unable to detect any significant deviation from parallelism among the three regression lines. We also measured time to 50% return of single twitch height for each data group as follows (mean +/- SEM: for NMS patients, 242 +/- 73 min; for the unaffected arm of hemiplegic patients, 116 +/- 60 min; and for the affected arm of hemiplegic patients, 59 +/- 36 min. By ANOVA and the Bonferroni test, each value was different from the other at P less than or equal to 0.01.(ABSTRACT TRUNCATED AT 250 WORDS)

Stable muscle relaxation during abdominal surgery using combined intravenous bolus and demand infusion: clinical appraisal with ORG NC45.

In order to obtain stable muscle relaxation for intra-abdominal operation, a continuous demand perfusion of ORG NC45 was administered following a loading dose of 0.07 mg . kg-1. The patients had previously been anaesthetized with methohexitone, fentanyl and nitrous oxide. The perfusion rate of ORG NC45 was regulated so that the mechanical muscular response of the adductor pollicis following a supra-maximal stimulation of the ulnar nerve was maintained at 10 per cent of its initial value. The level of relaxation thus obtained was always adequate for the surgeons. During the course of the operation the requirement for more relaxant decreased progressively, becoming stable after one half hour. Nevertheless, during stable administration, individual variations were quite marked, being 44 to 483 micrograms/M2 BSA/10 min (average 225 micrograms/M2 BSA/10 min). The duration of the infusion varied from 60 to 107 minutes (average 103 minutes). After its termination the time taken from recovery varied between 3 and 82 minutes (average 27 minutes). Having regained a single twitch height of 75 per cent patients awoke rapidly after the administration of nitrous oxide was terminated. No signs of recurarization were noticed in any of the patients. In conclusion, this method of administration of ORG NC45 assures a stable level of curarization without side-effects. However, because of the different individual levels of sensitivity which were noted, this mode of administration requires careful monitoring to avoid inappropriate dosage.

Neuromuscular Transmission In Peripatus

The electrical and mechanical responses of body, leg and jaw muscle of Peripatus to electrical excitation of their motor-nerves were examined. A small twitch was obtained from each muscle, whose strength increased stepwise with increasing stimulus strength. In jaw and body muscles as many as ten increments in height were obtained with increasing stimulus strength. Only a single twitch height was obtained from the claw retractor muscle. Tetanus:twitch ratio under supraminal stimulation was less than 2:1 for jaw muscles, about 50:1 for the claw retractor and about 6:1 for muscles moving the legs. The jaw-muscle twitch duration was 0.6 s, that for the leg muscles 1.2 s and for body muscles about 3.0 s. Large miniature junctional potentials were frequently recorded regardless of electrode location. Responses to neural stimulation consing stimulus strength, generally with three steps. With repetitive stimulation, facilitation of the second and third junctional potentials occurred, plus summation. A few fibres gave spikes to a single shock: most gave a few spikes sporadically, during repetitive stimulation only. No abrupt tension increments occurred in whole muscles when individual fibres spiked. We saw no evidence for peripheral inhibitory axons. The excitation of Peripatus muscle is by local graded junctional potentials at distributed nerve-on-muscle fibre synapses, together with action potentials. The latter are initiated only by larger junctional potentials compounded of multiple smaller ones summated and/or facilitated. The details of neuromuscular physiology are not compatible with the phylogenetic status commonly proposed for Peripatus.