[Neuromuscular monitoring: methods and machines]. / Uberwachung der neuromuskulären Blockade - Methoden und Geräte.

Muscle relaxing agents are clinically in use for general anaesthesia to optimize the conditions to the endotracheal intubation as well as the surgical conditions. Therefore different musclerelaxants with specific pharmacological characteristics are available. Many factors that depend on the condition of the patient and the used musclerelaxant agent influence the duration of the neuromuscular blockade. Rapid reversal of their effects, particularly in cases of profound blockades, proved to be difficult. In cases of postoperative residual paralysis hypoxic complications because of failure of the ventilation increase the morbidity and mortality of the perioperative period. To avoid these complications in cause of postoperative residual neuromuscular blockade it seems to be necessary to evaluate the status of the muscle function. For the tactile or visual assessment or the objective measurement of stimulation the train-of-four (TOF), double-burst (DBS) or tetanus-stimulation of peripheral nerves like the ulnar nerve may be used. Established methods for the objective monitoring of neuromuscular function is the mechanomyography (MMG), the acceleromyography (AMG), the electromyography (EMG), the kinemyography (KMG) and the phonomyography (PMG). A sufficient recovery of the neuromuscular transmission is reached to a TOF-ratio of 0,9 and should be aimed before the extubation at the end of surgery. No subjective evaluation of the neuromuscular recovery is able to identify residual paralysis above a TOF-ratio of 0,5. Recent studies suggest that objective methods should be used to monitor neuromuscular function to avoid postoperative residual blockades.

Fear induced by the blockade of GABAA-ergic transmission in the hypothalamus of the cat: behavioral and neurochemical study.

Intrahypothalamic injections of d-Tubocurarine (DT) and bicuculline (BM) in the cat produced a fear reaction characterized by terrific mewing, increased locomotor activity, jumps and attempt to escape from the chamber, pupillary dilatation, increased respiratory rate, and sometimes urination and defecation. HPLC analysis showed a significant increase in the noradrenergic system activity in the emotional brain areas (hypothalamus, midbrain, amygdala) and frontal cortex at the time of the fear drive. No changes in the cat's behavior and in the monoaminergic systems activity occurred after muscimol+d-Tubocurarine injections into the hypothalamus. Similar behavioral and neurochemical effects evoked by DT and BM suggest that the fear response evoked by DT does not result from the blockade of N-cholinergic transmission but rather from their action on GABAA receptor complex. The results obtained indicate that the central triggering mechanism for fear drive depends on the blockade of GABAA-ergic transmission.

The synergistic effect of two different nondepolarizing muscle relaxants on intraocular pressure.

STUDY OBJECTIVES: To evaluate the synergistic effect of neuromuscular blockade, produced by administering a priming dose of d-tubocurarine before or after pancuronium bromide, on endotracheal intubating conditions, intraocular pressure (IOP), and hemodynamic changes 1 minute following injection of intubating doses. To compare the results with equipotent doses of the individual muscle relaxants administered as a single bolus dose or in divided doses. DESIGN: Randomized study. SETTING: University medical center. PATIENTS: Ninety ASA physical status I and II inpatients (45 males, 45 females) assigned to one of six comparable groups (A-F). INTERVENTIONS: One hour after premedication, either normal saline (Groups A and B) or a priming dose of either d-tubocurarine (Groups C and F) or pancuronium (Groups D and E) was given intravenously (IV). Three minutes later, anesthesia was induced with 6 mg/kg of 2.5% thiopentone i.v. Then an intubating dose of pancuronium (Groups A, C, and E) or d-tubocurarine (Groups B, D, and F) was administered. The total dose given was equal to d-tubocurarine 0.4 mg/kg or pancuronium 0.07 mg/kg. Patients were intubated 1 minute after injection of an intubating dose of either relaxant. MEASUREMENTS AND MAIN RESULTS: IOP was measured with a Perkins applanation tonometer and blood pressure (BP) by a sphygmomanometer. Heart rate was derived from the electrocardiogram. Intubating conditions were scored according to given intubation criteria. Measurements were obtained at different times before and after intubation. In those patients given only one muscle relaxant for intubation either divided into priming and intubating doses or preceded by normal saline (Groups A, B, E, and F), there was a significant increase in IOP in response to intubation as compared with baseline (p < 0.05). In contrast, when d-tubocurarine was used as the priming drug for pancuronium blockade (Group C), IOP was significantly reduced in response to intubation, despite a concomitant increase in BP (p < 0.05). No significant change in IOP was observed when pancuronium was used as the priming drug for d-tubocurarine blockade (Group D). Although good to excellent intubating conditions were reported in Groups C and D, poor intubating conditions were reported when the priming muscle relaxant was the same as the relaxant used to intubate. CONCLUSIONS: A smooth, rapid-sequence intubation with a concomitant reduction in IOP as required for open-eye, full-stomach patients can be achieved with a judicious mixture of nondepolarizing muscle relaxants as described for d-tubocurarine and pancuronium in Groups C and D.

Relationships between block-of-twitch and train-of-four fade in the mouse phrenic nerve-diaphragm preparation.

The relationships between the block-of-twitch and train-of-four fade in the presence of nondepolarizing neuromuscular blocking drugs (d-tubocurarine, vecuronium and pancuronium) were examined in vitro by measuring the contractile tension from mouse phrenic nerve-diaphragm preparations. The slope of the block/fade relationship differed between onset of and recovery from neuromuscular block following single doses of d-tubocurarine, vecuronium or pancuronium. Decreasing the dose of d-tubocurarine or using a divided dose technique to accelerate onset (i.e., priming) increased the amount of fade for a given amount of block. In addition, the block/fade relationships for cumulative dosing and sequential dilution were the same when measurements were made at steady-state for several doses. It is concluded that the block/fade relationship in the mouse phrenic nerve-diaphragm preparation is variable, and is related to the time course of the neuromuscular block. In addition, the block/fade relationships for d-tubocurarine, vecuronium and pancuronium did not differ when determined at steady-state.

Pancuronium, vecuronium, and d-tubocurarine inhibit and succinylcholine stimulates choline acetyltransferase activity.

The effects of the nondepolarizing muscle relaxants (NDMR), pancuronium, vecuronium, and d-tubocurarine and a depolarizing muscle relaxant, succinylcholine, were studied on choline acetyltransferase (ChAT) activity. A radiochemical assay was used in the determination of ChAT activity using purified placental enzyme. Pancuronium at concentrations of 10(-7) M, 10(-6) M, 10(-5) M, 10(-4) M, and 10(-3) M inhibited ChAT activity by 3, 10, 15, 40 and 85 per cent, respectively; vecuronium at concentrations of 10(-6) M, 10(-5) M, 10(-4) M, and 10(-3) M inhibited ChAT activity by 5, 10, 26 and 57 per cent, respectively; d-tubocurarine at concentrations of 10(-6) M, 10(-5) M, 10(-4) M, and 10(-3) M inhibited ChAT activity by 0, 4, 12.5 and 29 per cent, respectively; whereas succinylcholine at concentrations of 10(-7) M, 10(-6) M, 10(-5) M, and 10(-4) M activated ChAT activity by 8, 10, 1, and 2 per cent, respectively. Even though our present data demonstrated a significant dose-dependent inhibitory effect on ChAT activity by pancuronium, vecuronium and d-tubocurarine, it is unlikely that this inhibitory effect will contribute to the mechanism of action of NDMR. Our data, however, may suggest an additional mechanism for the phenomena of tetanic and train-of-four fades that are seen following the administration of nondepolarizing muscle relaxants.

The use of fetal neuromuscular blockade during intrauterine procedures.

Advances in fetal therapy have led to the utilization of such techniques as intravascular transfusion of the Rh-affected fetus, bladder shunt placement in the fetus with obstructive uropathy, and percutaneous umbilical blood sampling. Fetal movement makes these procedures technically more difficult while increasing the risk of fetal injury. However, maternal sedation rarely results in adequate suppression of fetal activity. Thus we tested the sedative effects of intramuscular d-tubocurarine (3 or 1.5 mg/kg) or pancuronium bromide (0.3 mg/kg) injected into the fetal gluteal region under ultrasound guidance in conjunction with 70 invasive in utero procedures. Short-term paralysis of the fetus was induced in all cases. No deleterious effects of this technique were noted on initial examination of the neonates. Neuromuscular blockade was found to be a very useful adjunct to both diagnostic and therapeutic procedures involving the fetus.

Suppression of shivering decreases oxygen consumption and improves hemodynamic stability during postoperative rewarming.

Thirty-three patients undergoing elective myocardial revascularization were prospectively randomized into two study groups (Group S and Group P) to permit evaluation of the effects of shivering on oxygen consumption per minute (VO2), carbon dioxide production per minute (VCO2), and hemodynamic performance. Group S was allowed to shiver during the postoperative rewarming period, and Group P received hourly injections of pancuronium bromide and Metubine (metocurine) sulfate with sedation to block the shivering response. Group S demonstrated significantly higher increases in VO2 and VCO2, lower systolic blood pressure and mixed venous oxygen saturation, and a greater use of inotropic support than the patients in Group P. Suppression of the shivering response minimized increases in VO2 and VCO2, improved hemodynamic stability, and resulted in a decreased need for inotropic support.

Dose-response curves for pancuronium and tubocurarine: comparison of single and cumulative dose techniques.

Dose-response curves for pancuronium and tubocurarine were constructed using single-dose and cumulative-dose methods of administration. The dose-response curves for pancuronium were similar using the two methods, and resulted in an ED95 (dose required to produce 95% block of the twitch height) of 60 and 59 micrograms kg-1 using single-dose and cumulative-dose methods respectively. Although the dose-response curves for tubocurarine differed in their slopes and intercepts (significantly (P less than 0.01) for intercepts), the magnitudes of the ED95, 449 and 529 micrograms kg-1 respectively, were not significantly different. A cumulative-dose method for determination of the potency (ED95) of relatively long-acting drugs, such as pancuronium and tubocurarine, gives results which are similar to those obtained using a single bolus method, but has the advantage of requiring fewer subjects.

Cardiovascular and neuromuscular responses to high-dose pancuronium-metocurine in pediatric burned and reconstructive patients.

The efficacy of the combined use of pancuronium and metocurine (Pm-MTC) in high doses to produce rapid-onset muscle paralysis was evaluated in 15 patients with acute burns and 18 recovered burned patients scheduled for reconstructive surgery. Two and three times the previously determined ED95 of the combination for each group was used. (ED95 for Pm-MTC combination is 0.032/0.129 mg/kg for acute burns and 0.013/0.051 mg/kg for reconstructive patients.) Doubling ED95 produced 95% paralysis in 3.1 +/- 0.9 min in acutely burned children and in 4.3 +/- 0.7 min in reconstructive children (mean +/- SEM). These onset times were not significantly different from each other. Tripling the ED95 of the combination in burned children reduced the onset time to 1.3 +/- 0.14 min, but this was not significantly different from 2 X ED95 onset time in burned patients. The administration of 3 X ED95 to the reconstructive group, however, resulted in a significantly more rapid onset time of 1.8 +/- 0.4 min compared with 2 X ED95 in the same population. With 3 X ED95 the onset times between burn and reconstructive patients were not significantly different. Time for recovery of twitch to 25% of control twitch height (75% twitch depression) was significantly prolonged in burned patients compared with reconstructive patients for equipotent doses administered. Although the occasional patient showed prominent changes in heart rate and blood pressure, overall cardiovascular stability was impressive.(ABSTRACT TRUNCATED AT 250 WORDS)

Onset of pancuronium and d-tubocurarine blockade with priming.

The synergistic effect of pancuronium bromide (PCB) and d-tubocurarine (DTC) on the onset time of neuromuscular blockade was tested in 108 ASA physical status I and II adults anaesthetized with thiopentone, nitrous oxide and halothane. Either saline or a small (priming) dose (DTC, 0.04 mg X kg-1, or PCB, 0.007 mg X kg-1) was administered 3 min before a paralyzing dose of either DTC or PCB. The total dose of relaxant was equivalent to DTC, 0.4 mg X kg-1, or PCB, 0.07 mg X kg-1. Neuromuscular activity was measured using train-of-four stimulation applied every 12 s. Time to 50 per cent first twitch blockade was 63 +/- 4.6 s (mean +/- SEM) with DTC and 88 +/- 5.2 s with PCB (p less than 0.002). Times to 90 per cent blockade were not different between the two drugs (161 +/- 20 s and 141 +/- 21 s respectively). Priming a DTC blockade with either DTC or PCB or priming a PCB blockade with PCB produced an acceleration of less than 10 s at all levels of blockade. Compared with PCB alone, priming PCB blockade with DTC reduced the time to 50 per cent blockade to 71 +/- 4.5 s (p less than 0.02) and to 90 per cent blockade to 111 +/- 8 s (p less than 0.05). Priming did not affect the duration of action significantly, except in the case of PCB priming of DTC, where duration was increased from 39 +/- 4.4 to 57 +/- 4 min (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of muscle movement on the electroencephalogram during anesthesia with alfentanil.

Using aperiodic analysis, we examined the impact on the electroencephalogram (EEG) of muscle activity from opiate-induced rigidity with alfentanil. We compared two groups of patients, one receiving alfentanil with neuromuscular blocking agents and the other group receiving no relaxants. The alfentanil-induced muscle rigidity exerted a noticeable effect on the EEG, with a moderate effect on total power at 1 Hz; a marked effect on the total number of waves, cumulative percent power at 3 Hz, and average power at 17 to 19 Hz; and a striking effect on F90, the frequency below which 90% of the power resides. The presence of electromyographic (EMG) noise in the EEG consistently altered the variables derived from the EEG, so that anesthetic depth appeared less than it actually was. This was true in spite of the fact that we gave slightly more alfentanil in the group not receiving a relaxant. Although the observed muscle activity was greater than that usually seen clinically, and may have differed qualitatively, the results do serve as a warning that muscle noise can interfere with the EEG. Currently, there is no computerized technique that will reject or account for this noise, and we must depend on observation to recognize the EMG patterns within the EEG, either with the raw recording or with a detailed analysis (such as aperiodic analysis), and to compensate for this noise if possible. Techniques that average the EEG or that present a single number have difficulty providing this information. These results do not detract from the usefulness of the EMG contained in EEG recordings as a supplementary or complementary indicator of anesthetic lightness.

Pharmacodynamics of vecuronium, atracurium, tubocurarine and their combinations in the rat in vivo.

In the in vivo rat sciatic nerve tibialis muscle preparation the potency and pharmacodynamics of vecuronium, atracurium, pancuronium, tubocurarine and their combinations were studied. Considering the potency only, there was no beneficial difference between the pure compounds and their combinations. As both vecuronium and atracurium are almost free from side-effects individually, a combination of the two relaxants brings no advantage.

Vecuronium and d-tubocurarine combination: potentiation of effect.

To evaluate possible potentiation of neuromuscular blocking effect of a combination of vecuronium and d-tubocurarine, cumulative dose-response curves were constructed to compare the potency of this combination with vecuronium and d-tubocurarine given alone. Ten patients each were given incremental injections of 80 micrograms/kg d-tubocurarine or 5 micrograms/kg vecuronium plus 40 micrograms/kg d-tubocurarine, the data for incremental administration of 10 micrograms/kg vecuronium being used from our previously published study (7). The results showed the combination of vecuronium plus d-tubocurarine to be significantly more potent (P less than 0.05) than would be expected from a simple additive effect of the individual drugs given alone. The ED95 doses of d-tubocurarine and vecuronium were 530 micrograms/kg and 57 micrograms/kg, respectively, when administered alone, but when administered together, the ED95 doses were 160 and 20 micrograms/kg, respectively.

Potentiation of the combination of pancuronium and metocurine by halothane and isoflurane in humans with and without renal failure.

Dose-response relationships for a 1:4 weight ratio-mixture of pancuronium and metocurine were studied during inhalational anesthesia with halothane and isoflurane in patients with and without renal failure. The time for recovery from 10 to 20% of control thumb twitch tension also was determined. In subjects with normal renal function, relaxant doses required for 95% twitch height suppression (ED95) were 50% of those predicted by simple addition of effects when used with a balanced anesthetic technique, 37% of predicted when used with 1.3 MAC halothane, and 25% of predicted when used with 1.3 MAC isoflurane (P less than 0.05). In subjects with renal failure, ED95 values for the combination were 40% of predicted when used with 1.2 MAC halothane and 45% of predicted when used with 1.2 MAC isoflurane (NS). For relaxants used singly in renal failure, pancuronium alone was slightly enhanced by 1.2 MAC halothane (85% of predicted), while 1.1 MAC isoflurane reduced the ED95 to 57% of predicted (P less than 0.05). Similar results were obtained for metocurine alone when used in renal failure (77 and 58% of predicted when used with halothane and isoflurane, respectively) (NS). Predicted values are published results for balanced anesthesia in normals. Recovery times were prolonged twofold in renal failure (P less than 0.05). Thus, the combination of pancuronium and metocurine is synergistic to the same degree in normals and in renal failure patients, but the total blockade produced by the combination is enhanced by halothane and isoflurane only in normals.

Facilitation of rapid endotracheal intubations with divided doses of nondepolarizing neuromuscular blocking drugs.

The authors sought to determine whether prior administration of a small, subparalyzing dose of nondepolarizing muscle relaxant would shorten the onset time of an intubating dose of muscle relaxant. Initially, in 60 anesthetized patients, twitch response of adductor pollicis to ulnar nerve stimulation was studied after a small dose of pancuronium 0.015 mg . kg-1, metocurine 0.03 mg . kg-1, or d-tubocurarine 0.04 mg . kg-1, followed 3 min later by pancuronium 0.08 mg . kg-1 or atracurium 0.4 mg . kg-1 administered iv. After 60 s, the minimum neuromuscular block, in all patients was 79.0 +/- 5.0%. A 95% depression or twitch tension occurred between 59.1 +/- 5.3 and 86.1 +/- 5.9 s. In another 60 patients, intubating conditions under similar regimen were studied, except the small dose of muscle relaxant was given immediately prior to induction of anesthesia. At the end of 60 s, good to excellent intubating conditions were present in 100% of the patients following the second dose of pancuronium and in 83% of the patients following atracurium. In 17% of the patients, after atracurium intubating conditions were fair. When nondepolarizing neuromuscular blocking drugs are administered in divided doses, neuromuscular blockade adequate for endotracheal intubation is achieved in less than 90 s. This facilitates rapid endotracheal intubation in a time comparable to using succinylcholine, without undesirable effects of the depolarizing neuromuscular blocking drugs.

The pharmacokinetics of d-tubocurarine with surgery involving salvaged autologous blood.

The disposition of d-tubocurarine (dTc) was assessed when a bolus and infusion dosage regimen was used to obtain relaxation during major orthopedic surgery on the spine. Renal clearance of dTc was 0.63 +/- 0.23 ml X min-1 X kg-1 and was correlated with creatinine clearance. Total plasma clearance of 1.21 +/- 0.40 ml X min X -1 X kg-1 was lower than that found in many previous studies, and the predetermined continuous dTc infusion produced an apparent plateau in plasma concentrations of 1.8 +/- 0.3 micrograms X ml-1. Despite the operative blood loss, these concentrations were greater than anticipated and were associated with a more intense neuromuscular blockade than the infusion was designed to produce. Autologous blood transfusion was used to reduce the reliance on homologous donor blood, and the erythrocytes from the 2.2 +/- 1.2 1 of blood loss during the procedure were reinfused after intraoperative salvage, washing, and centrifugation. With 80 +/- 23 mg dTc administered, 1.4 +/- 0.8% was recovered from the fluid discarded after centrifugation. These results indicate that even massive intraoperative blood loss will not entail a significant reduction in the amount of dTc present in the body.

Combination of pancuronium and metocurine: neuromuscular and hemodynamic advantages over pancuronium alone.

Combination of pancuronium and metocurine or pancuronium and d-tubocurarine produces potentiation of neuromuscular blocking effects such that administration of relatively small doses of these drugs can yield clinically effective neuromuscular blockade. The clinical characteristics of the block produced in A.S.A. class I-II patients during N2O-narcotic-thiopental anesthesia by the pancuronium-metocurine combination at the calculated ED95 (N = 8) and at twice the ED95 (N = 9) were compared with the block produced by pancuronium alone at its ED95 (N = 20) and at twice the ED95 (N = 6). Onset time (from drug injection to 95% twitch suppression) and the maximum twitch depression achieved were comparable between corresponding groups, but the 25% recovery time (from drug injection to 25% recovery of twitch height) was significantly shorter in the groups that received the pancuronium-metocurine combination. Furthermore, at twice the ED95, heart rate increased significantly more in the pancuronium group than in the pancuronium-metocurine combination group. Mean systemic blood pressure did not change significantly in either group. We conclude that patients given a combination of pancuronium and metocurine in large doses experience less hemodynamic change and more rapid recovery of neuromuscular function than do patients given equivalent doses of pancuronium alone.