Effect of an intubating dose of succinylcholine and atracurium on the diaphragm and the adductor pollicis muscle in humans

This study compares the neuromuscular blocking effect of succinylcholine (0.8 mg . kg-1) and atracurium (0.6 mg.kg-1) on the diaphragm (D) and the adductor pollicis (AP) in 20 patients anesthetized with nitrous oxide, oxygen, and fentanyl. The diaphragm was monitored by measuring transdiaphragmatic pressure following bilateral phrenic nerve stimulation. After succinylcholine, the time from injection of succinylcholine to maximum depression of the single twitch response (onset time) was of 50 +/- 11 s (+/- SD) for D compared to 80 +/- 24 s for AP (P less than 0.001). After succinylcholine, recovery from paralysis was earlier for D than AP. Single twitch height (TH) returned to 25% of its control value (T25) after 5 +/- 2 min for D compared to 7 +/- 3 min for AP (P less than 0.001). Complete recovery of TH (T100) was achieved after 9 +/- 4 min for D and 11 +/- 5 min for AP (P less than 0.01). Recovery index (T25-75) was of 2 +/- 1 min for both muscles. After atracurium, the onset time for D was of 137 +/- 31 s compared to 181 +/- 45 s for AP (P less than 0.001). The T25 was achieved after 38 +/- 7 min for D compared to 63 +/- 13 min for AP (P less than 0.001). The TH of D returned to T100 after 60 +/- 12 min compared to 87 +/- 17 min for AP (P less than 0.01). The train-of-four ratio returned to 1 after 64 +/- 15 min for D compared to 99 +/- 21 min for AP (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

The action of succinylcholine on the skeletal muscles of the frog: an electromyographic study

As a supplement to similar investigations in man, the preparalytic activity of succinylcholine was studied in cold-blooded animals with the aid of electromyography.
The recording was done from the gastrocnemius muscle in intact, decapitated and cordless animals.
A technique devised for intravenous injection into frogs is described.
In general, the normal action potentials proved to be biphasic with an average duration of 6.76 ± 0.48 msec. They showed only slight variation in duration and form.
Under the effect of succinylcholine a gradual shortening of the duration of the potentials was noted, leading to very small potentials of the fibrillation type. This is regarded as indicating a breaking down of the motor units.
Fasciculations following injection of succinylcholine were observed and recorded electromyographically in most cases.
Even in cordless frogs, fasciculations appeared spontaneously, which indicates that they can occur entirely without the aid of the spinal cord.     

Evaluation of the endotracheal intubating conditions of rocuronium (ORG 9426) and succinylcholine in outpatient surgery.

The time-course of action and tracheal intubating conditions of rocuronium and succinylcholine under intravenous anesthesia with propofol, alfentanil, and nitrous oxide were studied in 30 patients undergoing outpatient surgery. The neuromuscular effects of both drugs were quantified by recording the indirectly evoked twitch response of the adductor pollicis muscle after ulnar nerve stimulation (0.1 Hz, 0.2 ms supramaximal stimuli). Patients were given either 0.6 mg/kg rocuronium (n = 20) or 1 mg/kg succinylcholine (n = 10) intravenously. Sixty seconds after the administration of the muscle relaxant, the trachea was intubated and the intubating conditions were scored by a "blinded" assessor. Intubating conditions were not different (P = 0.34) between the rocuronium and succinylcholine groups. The onset and duration of neuromuscular blockade were shorter with succinylcholine than with rocuronium. The depression of the twitch response to 5% of control value occurred in 0.8 +/- 0.1 min with 1 mg/kg succinylcholine and 1.2 +/- 0.5 min with 0.6 mg/kg rocuronium (P less than 0.01). The recovery of the twitch response to 25%, 75%, and 90% of its control value was shorter after succinylcholine (P less than 0.001) and occurred at 8.1 +/- 2.6, 10.3 +/- 3.9, 11.3 +/- 4.6 and 25.3 +/- 5.0, 33.1 +/- 5.9, 36.1 +/- 6.3 min after succinylcholine and rocuronium, respectively. Also the time required for spontaneous recovery from 25% to 75% of the control twitch response was significantly shorter (P less than 0.001) after succinylcholine (2.2 +/- 1.4 min) than after rocuronium (7.8 +/- 2.1 min). It is concluded that in spite of the pharmacodynamic differences between succinylcholine and rocuronium, the intubating conditions after administration of both compounds are similar and develop at the same rate.     

The "intubating dose" of succinylcholine: the effect of decreasing doses on recovery time

BACKGROUND: The usually cited "intubation dose" of succinylcholine is 1.0 mg/kg. In the majority of patients, this dose will produce apnea of sufficient duration that significant hemoglobin desaturation may occur before neuromuscular recovery takes place in those whose ventilation is not assisted. This study was undertaken to examine the extent to which reducing this dose would decrease the duration of action of succinylcholine. METHODS: During stable desflurane/oxygen/opioid anesthesia and after adequate twitch stabilization, neuromuscular function was recorded with an acceleromyographic monitor. Supramaximal stimuli were delivered at 0.10 Hz. Patients received 0.40, 0.60, or 1.0 mg/kg succinylcholine, and twitch height was monitored for at least 20 min thereafter. RESULTS: The onset times to maximal effect were 105 +/- 23 s, 81 +/- 19 s, and 71 +/- 22 s, respectively. The lowest dose (0.40 mg/kg) did not reliably produce 100% twitch depression. The times to 90% twitch recovery at the adductor pollicis in the three groups were 6.6 +/- 1.5 min, 7.6 +/- 1.6 min, and 9.3 +/- 1.2 min, respectively. CONCLUSIONS: Reducing the dose of succinylcholine from 1.0 mg/kg to 0.60 mg/kg shortens the duration of effect at the adductor pollicis by more than 90 s. The authors believe that even this modest decrease in the duration of drug-induced paralysis is often worth pursuing.     

Effects of ephedrine on intubating conditions following priming with rocuronium

BACKGROUND: Onset of action of muscle relaxants is influenced by cardiac output and muscle blood flow. Ephedrine reduces the onset time of rocuronium. Onset is also shortened by priming. Accordingly, we hypothesized that priming combined with ephedrine is superior to either technique used separately. METHODS: Four groups of randomly allocated patients (n = 31), ASA I - II, were induced with propofol 2.5 mg kg(-1). In groups I and II, 0.04 mg kg(-1) of rocuronium was followed by a 3-min priming interval. Induction was followed by an intubation dose of 0.04 mg kg(-1). Then a 30-s intubation was attempted. In groups III and IV the same sequence was repeated except for sham priming and an intubation dose of 0.44 mg kg(-1). In groups I and II, ephedrine (210 microg kg(-1)) was injected before propofol. In groups II and V, an equivalent volume of normal saline was injected. Jaw relaxation, vocal cord position, and diaphragmatic response were used to assess intubating conditions. RESULTS: All patients of group I were intubated 30 s after the intubating dose and within a 20-s interval compared with 74% of patients in groups II and III, and 84% of patients in group IV. Intubating conditions were graded good to excellent in all patients in group I compared with 42% of those in group II, 35% in group III and 52% in group IV (P < 0.01 vs. group I). During the priming interval, no adverse effects were observed or reported. CONCLUSIONS: Ephedrine in combination with propofol significantly improved clinical intubating conditions at 30 s following priming with rocuronium compared with priming with ephedrine without priming.     

Duration of action of vecuronium after an intubating dose of rapacuronium, vecuronium, or succinylcholine

Rapacuronium (RAP) is a new, rapid-onset, short-duration, nondepolarizing neuromuscular blocker. If RAP is used to facilitate endotracheal intubation, what will the duration of a subsequent maintenance dose of vecuronium (VEC) be? We investigated the duration of action of a maintenance dose of VEC after intubation with RAP, VEC, or succinylcholine (SUC). Adult surgical patients under general anesthesia were randomly allocated to receive a tracheal intubating dose of RAP 1.5 mg/kg, VEC 0.1 mg/kg, or SUC 1 mg/kg. The anesthetic was induced with propofol and maintained with propofol, nitrous oxide, and oxygen. Neuromuscular function was monitored with electromyography. Recovery of the intubating dose of neuromuscular blocker was allowed to occur spontaneously until the first twitch of the train-of-four (T1) reached 50% of baseline, and then VEC 0.025 mg/kg (0.5 x 95% effective dose [ED(95)]) was administered. The onset, duration, and recovery to T1 = 25% and 50% were recorded. The durations of action (recovery of T1 25%) after intubating doses of RAP, VEC, and SUC were 13.7 +/- 5.3, 43.2 +/- 13.2, and 9.2 +/- 3.7 min (mean +/- SD), respectively (P < 0.0001). The times to maximum depression of T1 after a maintenance dose of VEC (0.5 x ED(95)) were 5.4 +/- 2.9, 5.1 +/- 2.5, and 5.3 +/- 2.8 min (mean +/- SD) for the RAP, VEC, and SUC groups, respectively. Recoveries to T1 25% after VEC for the RAP, VEC, and SUC groups were 18.9 +/- 11.5, 21.5 +/- 8.03, and 12.8 +/- 8.4 min, and at T1 50% they were 21.5 +/- 9.1, 30.8 +/- 9.5, and 15.5 +/- 9.7 min (mean +/- SD), respectively (P < 0.001, RAP and VEC versus SUC). The duration of action of a maintenance dose of VEC was similar after an intubating dose of RAP or VEC but was shortened when preceded by an intubating dose of SUC. IMPLICATIONS: The duration of action of a maintenance dose of vecuronium was longer after an endotracheal intubating dose of rapacuronium compared with succinylcholine.     

Effects of varying concentrations of halothane on the activity of the genioglossus, intercostals, and diaphragm in cats: an electromyographic study

To determine the possible differential effects of depth of inhalation anesthetics on inspiratory muscle activity, the following were studied in seven adult cats: the phasic activity of the diaphragm, the external intercostals, and the genioglossus, by means of electromyography (EMG) and its moving time average (MTA). The animals spontaneously breathed 1.0-3.0% halothane in O2, while arterial PCO2 was maintained constant at approximately 60 mmHg by adjusting CO2 in the inspired gas mixture. Muscle activity was evaluated in terms of peak height of MTA, with measurements at 1% halothane used as control values. Halothane anesthesia attenuated inspiratory muscle activity significantly (P less than 0.05) in a dose-dependent fashion; muscle activity decreased most in the genioglossus, least in the diaphragm, and intermediately in the intercostals. Respiratory frequency, inspiratory time, and inspiratory duty cycle did not change significantly with increasing concentration of halothane.     

Differential sensitivity of abdominal muscles and the diaphragm to mivacurium: an electromyographic study.

BACKGROUND: Respiratory muscles are considered to be more resistant to muscle relaxants as compared with peripheral muscles. However, the relative sensitivity of respiratory muscles participating to the pump function has not been compared. We used electromyography to compare pharmacodynamic parameters of the diaphragm and abdominal muscles after mivacurium. METHODS: Forty adults undergoing elective surgery were randomly allocated in five dosing groups of mivacurium (50, 100, 150, 200, and 250 microg/kg). Patients anesthetized with propofol and fentanyl underwent intubation without relaxants. Anesthesia was maintained with nitrous oxide and propofol. The right phrenic nerve, the left 10th intercostal nerve, and the ulnar nerve were stimulated. Electromyography of the diaphragm and abdominal muscles was recorded from surface electrodes. Mechanomyography was used to measure adductor pollicis evoked contraction. After a 5-min stable recording period, patients received a single intravenous bolus (20 s) dose of mivacurium. By using log dose-probit effect regression analysis, dose-response curves were constructed. Effective doses and 95% confidence intervals were derived for the diaphragm and abdominal muscles and were compared. RESULTS: The dose-response regression line of abdominal muscles differed from that of the diaphragm. Calculated ED50 and ED90 were higher for the diaphragm than for the abdominal muscles (104 [82-127] and 196 [177-213] microg/kg, and 67 [51-82] and 161 [143-181] microg/kg, respectively). The onset of block was faster and recovery of control responses were shorter at the diaphragm than at the abdominal muscles. CONCLUSION: Diaphragm and abdominal muscles have differential sensitivity to mivacurium. The diaphragm is more resistant to mivacurium than abdominal muscles are.     

Cardiovascular effects of an intubating dose of rocuronium 0.6 mg kg-1 in anaesthetized patients, paralysed with vecuronium

We have studied, in adult patients, ASA I-II, the cardiovascular effects of an intubating dose of rocuronium 0.6 mg kg-1. After induction, patients were paralysed with vecuronium and the trachea intubated. Heart rate (HR) and non-invasive mean arterial pressure (MAP) were measured every 1 min. After stabilization of HR and MAP, defined as < 3% change over three measurements, rocuronium (n = 20) or saline (n = 10) was injected at random. Mean HR increased initially from 66.6 to 72.1 beat min-1, 4 min after rocuronium, and then decreased gradually to 69.6 beat min-1, that is a net increase of 3.3 beat min-1 over 10 min (P < 0.001), whereas after saline there was a gradual decrease from 65.8 to 60.9 beat min-1 (P < 0.001) over 10 min. From the third minute, HR was significantly higher in the rocuronium group. Mean MAP decreased in both groups within 10 min to a similar extent after rocuronium and saline, that is from 74.9 to 72.1 mm Hg and from 74.7 to 72.2 mm Hg, respectively (both P < 0.001). There were no differences in MAP at any time between the rocuronium and saline groups. We conclude that an intubating dose of rocuronium, in the absence of haemodynamic effects related to paralysis itself, resulted in a limited increase in HR without change in MAP, probably because of its weak vagolytic activity.      

Effects of succinylcholine on respiratory and nonrespiratory muscle strength in humans

Succinylcholine was administered to 10 healthy unanesthetized volunteers to assess its effect on respiratory and nonrespiratory muscle strength and the ventilatory response to CO2. Iso hypercapnia with PETCO2 8-10 mmHg above control was maintained throughout the study, succinylcholine infusion rates were increased from 20 micrograms X kg-1 X min-1 until grip strength (GS) was 20% of control. CO2-stimulated ventilation was 16.1 +/- 1.8 l/min (mean +/- SD), approximately three times control, and remained at that level throughout the study because of nonsignificant decreases in tidal volume and increases in respiratory frequency. Respiratory strength, as measured by maximum inspiratory pressure (IP), maximum expiratory pressure (EP), and forced vital capacity (FVC), was spared relative to GS. When GS = 50% of control, IP = 86 +/- 8% of control, EP = 78 +/- 15%, and FVC = 86 +/- 9%. Wide variation occurred from subject to subject in the succinylcholine versus GS dose-response curve position. However, in all subjects the slope of the dose-response curve was very steep.     

Effects of diltiazem on contractility and electromyographic activity of non-fatigued diaphragm in dogs

BACKGROUND: No data are available for diltiazem on muscle function (contractility and electomyographic activity) of non-fatigued diaphragm. METHODS: Eighteen pentobarbital-anesthetized dogs were divided into 3 groups of 6 each: Group I received no drug; Group II received small-dose of diltiazem (0.1 mg.kg-1.h-1); Group III received large-dose of diltiazem (0.5 mg.kg-1.h-1). Diaphragmatic contractility was assessed by transdiaphragmatic pressure (Pdi), the difference between esophageal and gastric pressures. Diaphragmatic electromyographic activity (Edi) was measured by means of electrodes placed at the anterior portion of the crural and costal parts of the diaphragm. After measuring baseline values of Pdi and Edi at 20 Hz and 100 Hz stimulation, the study drug was administered for 30 min. RESULTS: With infusion of diltiazem, Pdi and Edi to each stimulus did not change in Groups II and III. In Group I, these variables also showed no change. CONCLUSIONS: Diltiazem, at doses below 0.5 mg.kg-1.h-1, does not affect contractility and electromyographic activity of non-fatigued canine diaphragm.     

Effect of ephedrine on the intubation conditions using rocuronium versus succinylcholine

Objective

The goal of this study was to determine if ephedrine could improve intubating conditions when it is administered before the muscle relaxant (rocuronium and succinylcholine).

Patients and methods

In this prospective randomized double-blind study, 80 patients ASA I- II, scheduled for elective surgery, were allocated randomly to receive: succinylcholine 1 mg/kg + ephedrine 70 μg/kg (Group I, n = 20); rocuronium 0.6 mg/kg + ephedrine 70 μg/kg (Group II, n = 20); succinylcholine 1 mg/kg + 0.9% saline (Group III, n = 20); rocuronium 0.6 mg/kg + 0.9% saline (Group IV, n = 20). Induction of anaesthesia started with administration of the first syringe containing either ephedrine or saline, then 30 s later propofol 2.5 mg/kg and fentanyl 3 μg/kg, were administered followed by the contents of the second syringe containing either rocuronium or succinylcholine. Thirty seconds after injection of the muscle relaxant, another blinded staff anaesthetist performed intubation of the patient. Intubating conditions were evaluated according to criteria's of the conference of Copenhagen. Heart rate, systolic blood pressure and diastolic were also noted. Kruskall-Wallis test for non-parametric variable and Student t test for quantitative variables were used for statistical analysis.

Results

There was no significant difference between the groups concerning age, sex, BMI and ASA status. Pretreatment by ephedrine improved significantly (p < 0.0001) intubating conditions after succinylcholine and rocuronium.

Conclusion

Use of ephedrine 30 seconds before induction with propofol, fentanyl followed by rocuronium or succinylcholine provides faster good conditions of intubation.     

罗库溴铵用于老年人的有效剂量探讨

目的　用单次剂量法评估罗库溴铵在老年人和中年人剂量反应的差异 ,并探讨其可能的机制。方法　择期全麻手术患者 80例 ,分成中青年组 (30～ 4 5岁 )和老年组 (>6 5岁 ) ,每组 4 0例。按罗库溴铵用量将老年组再分成 10 0、15 0、2 0 0、2 5 0和 2 75 μg/kg五个亚组 ,中青年组分为 10 0、15 0、2 0 0、2 5 0和 30 0 μg/kg五个亚组 ,每亚组 8例。丙泊酚和芬太尼诱导及手控气囊面罩通气下 ,用加速度仪以连续 4次刺激方式刺激尺神经 ,获取静脉注射罗库溴铵后T1最大抑制 (Tmax)程度和时间。结果　老年组罗库溴铵的ED50 、ED90 和ED95分别为 (115 0 8± 35 10 ) μg/kg、(2 4 7 4 4± 32 95 )μg/kg和 (2 6 3 10± 34 15 ) μg/kg ,中青年组分别为 (15 0 5 0± 2 9 2 8) μg/kg、(2 74 0 4± 30 6 3) μg/kg和 (2 89 4 9± 31 70 ) μg/kg。老年组的ED50 、ED90 及ED95分别是中青年组的 76 %、90 3%和 91 2 %(P <0 0 1)。老年组的血清钾、血浆总蛋白和白蛋白浓度低于中青年组 (P <0 0 5 )。结论　罗库溴铵在正常体重老年人的作用强度大于中青年。年龄组间罗库溴铵作用强度的差异可能与电解质和血浆蛋白水平的差异有关     

Comparison of different priming techniques on the onset time and intubating conditions of rocuronium

BACKGROUND AND OBJECTIVE: The aim was to compare the effects of two different priming doses and priming intervals with the standard intubating dose of rocuronium on the onset time and intubation conditions. METHODS: After induction of anaesthesia, 75 patients were randomly assigned to one of five groups. Patients in Group 1 received a priming dose of rocuronium 0.06 mg kg(-1) followed 2 min later by rocuronium 0.54 mg kg(-1), Group 2 received a priming dose of 0.10 mg kg(-1) followed 2 min later by a rocuronium injection of 0.50 mg kg(-1). Group 3 was given a priming dose of 0.06 mg kg(-1) followed 3 min later by administration 0.54 mg kg(-1), where Group 4 received a priming dose of 0.10 mg kg(-1) followed 3 min later by injection of 0.50 mg kg(-1). Group 5 received a placebo injection followed 3 min later by rocuronium 0.60 mg kg(-1). RESULTS: Priming with a 3 min priming interval shortened the onset time of rocuronium irrespective of the dosage of (P < 0.001). Clinical duration of action was significantly longer after priming in Group 4 than in Group 5. Clinically acceptable intubation conditions were obtained in all patients. CONCLUSIONS: Priming with a 3 min priming interval was effective when rapid tracheal intubation with rocuronium was necessary. However, priming with rocuronium should be used carefully with special attention given to the possibility of hypoxia and aspiration of gastric contents in awake patients.     

肥胖对女性患者罗库溴铵剂量-效应曲线的影响

目的观察肥胖对女性患者罗库溴铵剂量-效应曲线的影响,并计算肥胖女性患者罗库溴铵的95%有效剂量(ED95)。方法选择择期行全身麻醉女性患者80例,年龄18~45岁,ASAⅠ或Ⅱ级,手术时间1.5h。根据BMI 20~25kg/m2和30~35kg/m2分为N组与B组,每组40例。两组患者根据随机数字表法各分为0.075、0.1、0.15、0.3 mg/kg四个剂量组,分别为N1~N4组和B1~B4组。麻醉诱导同时开启注射泵,待患者意识消失后,校对肌松监护仪,启动TOF模式,N1~N4组和B1~B4组分别给予罗库溴铵单次剂量0.075、0.1、0.15、0.3mg/kg。记录各组患者给予罗库溴铵的首次剂量、第一个肌颤搐反应(T1)的最大抑制程度和肌松药起效时间。采用直线回归法建立罗库溴铵量效关系回归方程,计算N组和B组患者的ED50和ED95及其95%CI。结果 N组和B组的量效关系回归方程分别为Y1=3.464X1-2.230和Y2=3.843X2-2.750。B组ED50、ED75、ED90、和ED95分别为0.103、0.145、0.201和0.251 mg/kg明显小于N组0.122、0.176、0.254和0.324mg/kg(P0.05)。N组与B组T1最大抑制程度均随药量的增加而增大(P0.05)。结论肥胖影响年轻女性患者罗库溴铵的量效曲线,使其对罗库溴铵的敏感性增强,肥胖女性罗库溴铵ED95为0.251mg/kg。