Neuromuscular effects of isoflurane in patients with myasthenia gravis

Seventeen myasthenia gravis and seven control patients were studied mechano (MMG)- and electromyographically (EMG) during isoflurane/oxygen/air anaesthesia. In myasthenic patients the mean train-of-four ratio and neuromuscular block (by MMG) during 1.9 MAC isoflurane anaesthesia were 55 +/- 9% and 46 +/- 12%, respectively. The correlation between simultaneous MMG and EMG measurements was excellent (r2 = 0.933, P less than 0.001). The occurrence of HLA-B8 together with acetylcholine receptor antibodies seems to predispose myasthenic patients to a neuromuscular depression produced by isoflurane. Our current and prior results show that isoflurane possesses approximately twice as strong a neuromuscular blocking effect as halothane in myasthenic patients.     

Pretreatment with pancuronium before suxamethonium administration in patients heterozygous for the usual and the atypical plasma cholinesterase gene

The object of this study was to investigate whether pretreatment with pancuronium before i.v. injection of suxamethonium could cause prolonged neuromuscular blockade in patients heterozygous for the usual and the atypical plasma cholinesterase gene (E1uE1a). Forty-three patients, 23 with genotype E1uE1a and 20 with normal genotype (E1uE1u), were pretreated with pancuronium 0.01 mg.kg-1 followed by suxamethonium 1.5 mg.kg-1, and received either neurolept anaesthesia or halothane anaesthesia. Seven patients (E1uE1a) were given suxamethonium 1.5 mg.kg-1 without pretreatment. The duration and type of neuromuscular block were evaluated using train-of-four (TOF) nerve stimulation. Type of anaesthesia did not significantly influence the results. The duration of block following pretreatment was significantly longer in heterozygous patients than in normal patients. Time to 90% twitch height recovery was 10.7 +/- 1.2 min (mean +/- s.d.) in genotypically normal patients, and 18.0 +/- 4.2 min in patients with genotype E1uE1a. Pretreatment with pancuronium caused a significantly slower recovery of the TOF ratio (phase II block). Thus, a TOF ratio of 0.7 was always reached within 13 min in genotypically normal patients. In genotypically abnormal patients, the same TOF ratio was reached within 20 min in all but three patients. In these three patients time to 90% twitch height recovery was prolonged (18-31 min), and TOF ratio did not return to normal, but stabilized at about 0.35, 0.50, and 0.65, respectively. Injection of edrophonium restored normal neuromuscular function in 10 min. It is concluded that in patients heterozygous for the usual and the atypical gene, pretreatment with pancuronium in combination with an increased dose of suxamethonium may cause a phase II block and thus a prolonged neuromuscular block.     

The neuromuscular transmission monitor

The neuromuscular transmission monitor (NTM) is a new device for measuring neuromuscular transmission during anaesthesia. We have assessed its use in comparison with a force transducer and found for single twitch and train-of-four modes that there was a strong positive correlation between the two methods. This device appears reliable in use and provides a satisfactory alternative to conventional neuromuscular monitoring.     

A new dual function nerve stimulator

The Duostim model TV02 is a new peripheral nerve stimulator designed both for nerve identification in the performance of regional anaesthesia and for monitoring neuromuscular blockade. The output pulses are unipolar and of adjustable constant current. The provision of single twitch (1 Hz and 1/15 Hz) train-of-four and tetanic stimuli, together with indication of the current delivered and the small size of the unit, facilitate its clinical use. Performance was assessed and found to be according to specification.     

Halothane-induced variability in the neuromuscular transmission of patients with myasthenia gravis

The purpose of the present clinical study was to explore the skeletal muscle mechano (MMG)- and electromyographic (EMG) responses during halothane/oxygen/air anaesthesia in patients with myasthenia gravis (MG) compared with patients with normal neuromuscular transmission. The majority of MG-patients had a significant decremental response of the evoked muscle action potentials to a train-of-four (TOF) stimulation during halothane exposure (mean decrease of train-of-four ratio was 33% during the highest mean halothane concentration of 1.9 MAC). An excellent correlation was found between MMG- and EMG-measurements (r2 = 0.878, P less than 0.001). However, marked individual variations in the neuromuscular response to halothane were seen. Neither preoperative muscle fatigability nor acetylcholine receptor antibodies predicted the decremental muscle responses produced by halothane among MG-patients. The increased presence of HLA-B8 among myasthenics with halothane-suppressed muscle responses after TOF stimulation could be demonstrated (P less than 0.01).     

Edrophonium and Neostigmine for Reversal of the Neuromuscular Blocking Effect of Vecuronium

The effect of edrophonium for reversal of the non-depolarizing neuromuscular blockade produced by a continuous infusion of vecuronium was compared to that of neostigmine in 20 adult patients during neurolept anaesthesia. When antagonism was attempted at 10% twitch height recovery, reversal time to a train-of-four ratio of 0.7 was significantly shorter following neostigmine 0.04 mg/kg than after edrophonium 0.75 mg/kg (9.8 min and 18.7 min, respectively) but the same after edrophonium 1.5 mg/kg (10.3 min). There was no statistically significant difference in reversal time between neostigmine 0.04 mg/kg given at 10% twitch height and edrophonium 0.75 mg/kg given at 25% twitch height recovery (6.0 min). Additional doses of atropine were necessary following edrophonium 1.5 mg/kg.     

Comparison of thumb acceleration and thenar EMG in a pharmacodynamic study of alcuronium

We compared thumb acceleration (Acc) and thenar electromyography (EMG) techniques by evaluating the neuromuscular blocking properties of alcuronium in 14 ASA physical status I patients. The dose-response curves determined by the two techniques were parallel but the EMG-curve was shifted 25% to the right (P less than 0.001). Acc reflected 8-11% greater neuromuscular block than simultaneous EMG in every patients (P less than 0.05). Concurrently, the duration of greater than 90% neuromuscular block maintained by alcuronium 280 micrograms/kg was significantly longer when measured by the Acc transducer (30 vs. 19 min, P less than 0.001). Although the TOF ratios were in good correlation (r2 = 0.82), clinically significant differences existed between the two simultaneous techniques. The results underline the importance of the method of assessment of neuromuscular transmission when evaluating the action of neuromuscular blocking drugs.     

Postoperative residual block after intermediate-acting neuromuscular blocking drugs

The frequency and duration of postoperative residual neuromuscular block on arrival of 150 patients in the recovery ward following the use of vecuronium (n = 50), atracurium (n = 50) and rocuronium (n = 50) were recorded. Residual block was defined as a train-of-four ratio of <0.8. An additional group of 10 patients received no neuromuscular blocking drugs during anaesthesia. The incidence of postoperative residual neuromuscular block was 64%, 52% and 39% after the use of vecuronium, atracurium and rocuronium, respectively. Similar numbers of patients were not able to maintain a sustained head or leg lift for 5 s on arrival in the recovery ward. The mean [range] times to attaining a train-of-four ratio of > or =0.8 after arrival in the recovery ward were 9.2 [1-61], 6.9 [1-24] and 14.7 [1.5-83] min for vecuronium, atracurium and rocuronium, respectively. None of the 10 patients who did not receive neuromuscular blocking drugs had train-of-four ratios <0.8 on arrival in the recovery ward. It is concluded that a large proportion of patients arrive in the recovery ward with a train-of-four ratio <0.8, even with the use of intermediate-acting neuromuscular blocking drugs. Although the residual block is relatively short lasting, it may occasionally be prolonged, requiring close observation and monitoring of such patients in the recovery ward.     

The effect of peripheral hypothermia on a vecuronium-induced neuromuscular block

Seven healthy patients were investigated during midazolam-fentanyl nitrous oxide-oxygen anaesthesia. The mechanical twitch response of the adductor pollicis muscle was recorded simultaneously during bilateral supramaximal train-of-four (TOF) stimulation of the ulnar nerves at the wrist. Intense neuromuscular block was evaluated using the post-tetanic count (PTC) method. Core temperature and the peripheral skin temperature of one arm were kept normal and stable. Following cooling of the other arm to a peripheral hand skin temperature of 27 degrees C, vecuronium was administered in a bolus dose of 0.05 mg.kg-1 followed by maintenance doses of 0.02 mg.kg-1. In the hypothermic and the normothermic arm the onset time following the bolus dose was 180 +/- 40 (mean +/- s.d.) seconds and 140 +/- 30 s, respectively, the duration of action was 26.4 +/- 4.5 and 16.5 +/- 4.0 min and the recovery time was 265 +/- 90 and 130 +/- 60 s (P less than 0.01). The time course of action following maintenance doses showed a similar marked difference between the hypothermic and the normothermic arm. In the normothermic arm a close correlation was found between the number of post-tetanic twitches and the time to first response to TOF stimulation. In contrast, in the hypothermic arm the number of post-tetanic twitches showed great variation with a poor correlation to the duration of intense neuromuscular block. It is concluded that the time course of action of a vecuronium-induced neuromuscular block is markedly prolonged during peripheral hypothermia and intense neuromuscular block cannot reliably be assessed using the PTC method at low peripheral temperature.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relationship between posttetanic count and response to carinal stimulation during vecuronium-induced neuromuscular blockade

The correlation between degree of peripheral neuromuscular blockade and response to carinal stimulation was evaluated in two groups of 25 patients: one group was anaesthetized with thiopental, N2O and halothane, and the other group received thiopental, N2O and fentanyl. The degree of peripheral blockade was evaluated using train-of-four (TOF) and posttetanic twitch (PTC) stimulation of the ulnar nerve. The degree of diaphragmatic paralysis was evaluated indirectly by stimulating the carina and observing the corresponding muscular response, which was graded as severe, mild or absent. During halothane anaesthesia a PTC of 0 always indicated that no response to carinal stimulation could be elicited. On the appearance of the first response to posttetanic twitch stimulation (PTC = 1), 2% of the patients showed a mild response to carinal stimulation. At the first response to TOF stimulation, 48% of the patients reacted with a mild response. During thiopental, N2O, fentanyl anaesthesia one of 25 patients showed a mild response to carinal stimulation at a PTC of 0. When PTC was 1, 20% of the patients reacted mildly to the stimulation. At the first response to TOF stimulation, 92% showed a response to carinal stimulation; 24% of these responses were severe, necessitating intervention. It is concluded that the TOF response elicited peripherally is a late sign of neuromuscular recovery of the diaphragm, and that the method of counting posttetanic twitches is superior to the TOF response in evaluating early recovery of this muscle. Further, to ensure total diaphragmatic paralysis, the neuromuscular blockade of the peripheral muscles should be so intense that no response to posttetanic twitch stimulation (PTC = 0) can be elicited.     

The cuff method: a pilot study of a new method of monitoring neuromuscular function

BACKGROUND: A new method of monitoring neuromuscular blockade based on a modified blood pressure cuff that incorporates stimulating electrodes was compared with mechanomyography (MMG) ('gold standard'). METHODS: Forty adults and 20 children (ASA I-II) underwent neuromuscular blockade monitoring on the contralateral arms and on the same arm using the new cuff method and MMG. Only train-of-four (TOF) ratios > 0.1 and T(1) heights > 0 were studied. Supramaximal stimulation was also assessed. A device based on a PC with an analogue-to-digital conversion card was used to control and synchronize MMG and the cuff method. The agreement between both methods was assessed using the statistical method of Bland and Altman. RESULTS: When TOF ratios were >0.7, the bias between the two methods was -0.04 with the limits of agreement ranging from -0.21 to -0.12 (95% CI -0.06 to -0.02). The T(1) > 0 heights bias was -0.01 with the limits of agreement ranging from -0.26 to 0.24 (95% CI -0.02 to -0.003). The sensitivity of the cuff method was 88%, with a specificity of 85% and an accuracy of 86%. CONCLUSION: This pilot study indicates that the cuff method could be useful to monitor neuromuscular blockade according to the bias and limits of agreement compared with MMG, particularly when the degree of blockade was evaluated by TOF ratios > 0.7. The new cuff method is easy and simple to use. However, further studies in a larger number of patients are necessary to confirm these favourable preliminary results.     

Comparison between a new acceleration transducer and a conventional force transducer in the evaluation of twitch responses

An acceleration transducer elicits an output voltage proportional to the deformation of the piezo crystal, in accordance with the twitch responses of the applied fingers. The reliability of such a transducer was evaluated by comparing induced twitch responses with those from a force transducer applied on the contralateral arm of an individual during neuromuscular block with vecuronium. The results obtained from twitch responses with the acceleration transducer during neuromuscular block were almost identical to those obtained with the force transducer. Also, the twitch heights due to acceleration of the examined thumb correlated extremely well with the twitch height due to twitch tension with the force transducer. It is concluded that the acceleration transducer may be a useful and reliable device for monitoring neuromuscular block, although responses during tetanic stimulation such as tetanic fade cannot be determined by the transducer.     

Neuromuscular monitoring in myasthenic syndrome

We describe the anaesthetic management of a 72-year-old man with myasthenic syndrome. Pre-operatively, he was treated with 3,4-diaminopyridine and showed a strong hand grip. During general anaesthesia with nitrous oxide and sevoflurane in oxygen, a mechanomyograph and two accelerographs were set up for the hands and left foot to monitor neuromuscular function. Insufficient force and acceleration of contraction with 1 Hz stimulation was observed in the hands. In the foot, the twitches produced by 1 Hz and train-of-four stimulation could barely be detected using the accelerograph, and the train-of-four ratio fluctuated between 70 and 100%. No neuromuscular blocking drugs were used during surgery. After discontinuation of sevoflurane, responses to train-of-four stimulation remained small, but a strong response to tetanic stimulation was observed, with post-tetanic facilitation. Extubation was successful, and recovery from anaesthesia was uneventful. Tetanic stimulation and post-tetanic facilitation are important in monitoring neuromuscular function in patients with myasthenic syndrome whose train-of-four responses are insufficient.     

Onset and duration of action of rocuronium--from tracheal intubation, through intense block to complete recovery

BACKGROUND: The primary objective of this study was to establish the relation between the post tetanic count (PTC) and the time to reappearance of the first response (T1) in train-of-four (TOF) nerve stimulation following rocuronium 0.6 mg/kg, 0.9 mg/kg, and 1.2 mg/kg. The secondary objective was to evaluate the intubation conditions after 1 min. METHODS: One hundred and eight patients were randomised to one of three doses of rocuronium: 0.6, 0.9 or 1.2 mg/kg. Tracheal intubation was performed at 60 s by a blinded investigator. During propofol, fentanyl, midazolam anaesthesia the neuromuscular block was monitored by mechanography using TOF stimulation every 12 s. At 6 min intervals, a tetanic stimulation (50 Hz) was applied for 5 s preceded and followed by a 30 s period of 1 Hz stimulation until the reappearance of T1. RESULTS: There was a significant difference in recovery following the high dose and the two lower doses. The relation between time (min) to reappearance of T1 (t) and PTC can be expressed as follows: t(0.6 and 0.9 mg/kg)(min)=18.8-6.46 PTC and t(1.2 mg/kg)(min)=26.1-9.12 PCT. T1 was seen at a mean PTC level of 8 or 9 in all three groups. The intubation conditions were graded as excellent or good in all patients except in two patients following the 0.6 mg/kg dose of rocuronium. CONCLUSION: The PTC method can be used to predict the time to first response to TOF nerve stimulation during intense rocuronium induced neuromuscular blockade. The relation between PTC and the time to T1 was prolonged after 1.2 mg/kg compared with 0.6 mg/kg and 0.9 mg/kg. No further improvement in intubation conditions at 60 s was evident by increasing the rocuronium dose from 0.9 mg/kg to 1.2 mg/kg.     

Effect of epidurally administered bupivacaine on atracurium-induced neuromuscular blockade

The effect of epidurally administered bupivacaine on duration, intensity and reversal characteristics of atracurium-induced neuromuscular blockade was studied in 30 healthy patients anaesthetized with thiopentone, fentanyl, midazolam and nitrous oxide. Fifteen patients received, in addition, epidural anaesthesia with bupivacaine. The remaining patients served as controls. The ulnar nerve was stimulated at the wrist and the evoked twitch response from the adductor pollicis was measured with a force displacement transducer. Neuromuscular blockade was induced with atracurium 0.5 mg i.v. and maintained with repeated doses of atracurium 0.15 mg/kg whenever the twitch height had recovered to 15% of the initial twitch height. After operation, the neuromuscular blockade was reversed with neostigmine when the twitch height had recovered to 15%. In the epidural group the clinical duration of neuromuscular blockade, time until first response to train-of-four (TOF) and reversal time were all significantly prolonged (P less than 0.05). Post-tetanic count (PTC) after 20 min was also significantly lower in the epidural group (P less than 0.05). It is therefore concluded that epidurally administered bupivacaine prolongs atracurium-induced neuromuscular blockade. The clinical implication of the modest prolongation is, however, limited.     

A retrospective observational study of neuromuscular monitoring practice in 30,430 cases from six Danish hospitals

Timely application of objective neuromuscular monitoring can avoid residual neuromuscular blockade. We assessed the frequency of objective neuromuscular monitoring with acceleromyography and the last recorded train-of-four ratio in a cohort of Danish patients. We extracted data from all patients receiving general anaesthesia from November 2014 to November 2016 at six hospitals in the Zealand Region of Denmark. Acceleromyography was available in all operating rooms and data were recorded automatically. The primary outcome measure was acceleromyography use in patients receiving neuromuscular blocking agents, divided into non-depolarising agents and succinylcholine only. The dataset included 76,743 cases, of which 30,430 received a neuromuscular blocking drug. Non-depolarising drugs were used in 16,525 (54%) and succinylcholine as the sole drug in 13,905 (46%) cases. Acceleromyography was used in 14,463 (88%) patients who received a non-depolarising neuromuscular blocking drug and in 4224 (30%) receiving succinylcholine alone. Acceleromyography use varied between the departments from 58% to 99% for non-depolarising drugs and from 3% to 79% for succinylcholine alone. The median (IQR [range]) of the last recorded train-of-four ratio before tracheal extubation was 0.97 (0.90–1.06 [0.01–2.20]) when non-depolarising drugs were used, and was less than 0.9 in 22% of cases. The OR for oxygen desaturation was higher with the use of succinylcholine [2.51 (95%CI 2.33–2.70) p < 0.001] and non-depolarising drugs [2.57 (95%CI 2.32–2.84) p < 0.001] as compared with cases where no neuromuscular blockade drug was used. In conclusion, acceleromyography was almost always used in cases where non-depolarising neuromuscular blocking drugs were used, but a train-of-four ratio of 0.9 was not always achieved. Monitoring was used in less than 30% of cases where succinylcholine was the sole drug used.     

Postoperative neuromuscular block following atracurium or alcuronium in children

Postoperative neuromuscular block (NMB) was evaluated in 60 children who received randomly either atracurium or alcuronium to induce and maintain an 85-95 per cent NMB during balanced anaesthesia. The EMG-monitor was turned away from the anaesthetist 10-15 min before the end of surgery. The average NMB was comparable between the groups at the time of reversal with neostigmine 50 micrograms.kg-1 (84 +/- 9 per cent, mean +/- SD) as were the NMB and the train-of-four ratio when the tracheas were extubated on a clinical basis (32 +/- 20 per cent and 50 +/- 18 per cent, respectively). Patients who had been paralyzed with atracurium arrived at the recovery room earlier and on arrival had greater train-of-four ratios than the patients paralyzed with alcuronium (P less than 0.01). Time to a train-of-four ratio of greater than 90 per cent was significantly shorter in the atracurium group (10 +/- 5 min vs 26 +/- 15 min, P less than 0.001). Thus, an intermediate-acting muscle relaxant offers a safer recovery profile of the NMB than a long-acting muscle relaxant in paediatric patients.     

Neuromuscular blockade can be assessed accelerographically over the vastus medialis muscle in patients positioned prone

PURPOSE: To study accelerographic monitoring of neuromuscular blockade over the vastus medialis muscle in anesthetized patients in the prone position. METHODS: Sixty adult patients were divided into four groups of 15: prone (P)-post-tetanic count (PTC), P-train-of-four (TOF), supine (S)-PTC or S-TOF group. In the P-PTC and P-TOF groups, the muscular branch of the femoral nerve was stimulated and the movement of the vastus medialis muscle was measured accelerographically. In the S-PTC and S-TOF groups, the depth of neuromuscular blockade was assessed mechanically at the thumb. After administration of vecuronium 0.1 mg.kg(-1), TOF stimuli were delivered every 20 sec in all groups. Onset of neuromuscular blockade (time from vecuronium to the minimum level of T1 (first response of TOF) was compared between the P-PTC or P-TOF group and S-PTC or S-TOF group. Recoveries of PTC and those of TOF were compared between the P-PTC and S-PTC groups and P-TOF and S-TOF groups, respectively. RESULTS: Onset of neuromuscular blockade in the P-PTC or P-TOF group was shorter than in the S-PTC or S-TOF group (132 +/- 43 vs 233 +/- 40 sec, mean +/- SD, P < 0.001). Recoveries of PTC in the P-PTC and S-PTC groups followed a similar time course. Recoveries of T1/control in the P-TOF and S-TOF groups were also comparable. In contrast, train-of-four ratio (T4/T1, TOFR) in the P-TOF group was higher than in the S-TOF group 60-120 min after vecuronium (P < 0.05). CONCLUSIONS: The degree of neuromuscular blockade can be assessed accelerographically over the vastus medialis muscle even when patients are in the prone position. When evaluated accelerographically over the vastus medialis muscle, onset of neuromuscular blockade is quicker and TOFR is higher than that assessed at the thumb.     

A comparison of a prototype electromyograph vs. a mechanomyograph and an acceleromyograph for assessment of neuromuscular blockade

The extent of neuromuscular blockade during anaesthesia is frequently measured using a train-of-four stimulus. Various monitors have been used to quantify the train-of-four, including mechanomyography, acceleromyography and electromyography. Mechanomyography is often considered to be the laboratory gold standard of measurement, but is not commercially available and has rarely been used in clinical practice. Acceleromyography is currently the most commonly used monitor in the clinical setting, whereas electromyography is not widely available. We compared a prototype electromyograph with a newly constructed mechanomyograph and a commercially available acceleromyograph monitor in 43 anesthetised patients. The mean difference (bias; 95% limits of agreement) in train-of-four ratios was 4.7 (−25.2 to 34.6) for mechanomyography vs. electromyography; 14.9 (−13.0 to 42.8) for acceleromyography vs. electromyography; and 9.8 (−31.8 to 51.3) for acceleromyography vs. mechanomyography. The mean difference (95% limits of agreement) in train-of-four ratios between opposite arms when using electromyography was −0.7 (−20.7 to 19.3). There were significantly more acceleromyography train-of-four values > 1.0 (23%) compared with electromyography or mechanomography (2–4%; p < 0.0001). Electromyography most closely resembled mechanomyographic assessment of neuromuscular blockade, whereas acceleromyography frequently produced train-of-four ratio values > 1.0, complicating the interpretation of acceleromyography results in the clinical setting.     

Epidurally administered mepivacaine delays recovery of train-of-four ratio from vecuronium-induced neuromuscular block

BACKGROUND: The aim of this study was to examine the efficacy of epidurally administered mepivacaine on recovery from vecuronium-induced neuromuscular block. METHODS: Eighty patients were randomly assigned to one of two study groups. They were either given epidurally a bolus of 0.15 ml kg(-1) of mepivacaine 2%, followed by repetitive injections of 0.1 ml kg(-1) h(-1) throughout the study, or were not given epidurally. General anaesthesia was induced and maintained with fentanyl, propofol and nitrous oxide. Neuromuscular block was induced with vecuronium 0.1 mg kg(-1) and monitored using acceleromyographic train-of-four (TOF) at the adductor pollicis. Patients in each treatment group were randomized to receive neostigmine 0.04 mg kg(-1) at 25% recovery of the first twitch of TOF or to recover spontaneously to a TOF ratio of 0.9. The effect of epidural mepivacaine on speed of spontaneous and facilitated recovery of neuromuscular function was evaluated. RESULTS: The time from administration of vecuronium to spontaneous recovery to a TOF ratio of 0.9 was significantly longer in the epidural mepivacaine group [105.4 (14.2) min] as compared with the control group [78.5 (9.1) min, P < 0.01]. Neostigmine administered at 25% of control in T1 shortened recovery from neuromuscular block, however the time required for facilitated recovery to a TOF ratio of 0.9 in the epidural group was significantly longer than that in the control group [7.6 (1.6) min vs 5.8 (2.1) min, P < 0.01]. CONCLUSIONS: In clinical anaesthesia, it should be recognized that epidurally administered mepivacaine delays considerably the TOF recovery from neuromuscular block.