Chemotherapy alters cisatracurium induced neuromuscular blockade characteristics: A prospective cohort study.

STUDY OBJECTIVE: To compare the characteristics of NMDR induced muscle paralysis in breast cancer patients with and without a history of recent chemotherapy with cyclophosphamide, doxorubicin and 5-fluorouracil (CAF) regimen. DESIGN: This is a non-randomized prospective cohort study. SETTING: Operating room of a university-affiliated teaching hospital. PATIENTS: Out of a total of 50 patients who had undergone mastectomy, 22 patients were allocated to the "Chemo group" and 28 patients to the "Non-Chemo group", based on a valid history of recent chemotherapy. INTERVENTION: After induction of anesthesia with thiopental and cisatracurium, neuromuscular monitoring was started for all patients. MEASUREMENTS: Initially the time to 100% single-twitch (ST) suppression was measured. Then, the time for the appearance of the first response to post-tetanic count (PTC) stimulation, Train-of-Four (TOF) stimulation, and TOF50% were measured consequently. MAIN RESULTS: Time to get STzero was significantly longer in the Chemo group than in the Non-chemo group. Time for the appearance of the first response of PTC and TOF and TOF50% was significantly shorter in the Chemo group than the other group. The mean duration of intense block was 27.66 minutes in the Chemo group versus 42.47 minutes in the Non-chemo group. CONCLUSION: This research demonstrated that in patients having undergone chemotherapy, the effect of NDMRs starts with a longer lag time and finishes earlier too. Thus, these patients are ready for intubation after a longer time. Moreover, we have to repeat cisatracurium injections after shorter intervals to maintain the desired level of blockade.

The effect of general anaesthesia and neuromuscular blockade on Eustachian tube compliance: a prospective study.

OBJECTIVE: The most common complications of hyperbaric oxygen treatment (HBOT) are related to pressure changes on gas-containing cavities. Therefore, inability to auto-inflate the middle ear may result in transient or permanent hearing loss. However, it seems that middle ear barotrauma (MEBt) does not develop more often in mechanically ventilated patients than in ambulatory patients. This might be explained by deep sedation of these patients. Therefore, the aim of this study was to determine whether anaesthesia and/or neuromuscular blockade can influence Eustachian tube (ET) function. METHODS: Forty patients who were undergoing surgery under general anaesthesia were enrolled in this prospective study. ET function was evaluated by tympanography performed three times: before induction of general anaesthesia (baseline), after induction with sufentanyl/propofol and after full blockade was achieved with a long-acting neuromuscular blocking agent. RESULTS: There were no differences in ear volume (P = 0.19) and ear pressure (P = 0.07). There was a significant variation in compliance on tympanography after the induction of general anaesthesia (P = 0.009). Compared to the baseline, this variation was characterized by an increase after induction of anaesthesia (24 ± 7.13%, P 〈 0.01) and neuromuscular blockade (23 ± 8.9%, P 〈 0.05). The difference between after induction and after neuromuscular blockade was not statistically significant (P = 0.13). DISCUSSION: The findings of this trial suggest that the administration of hypnotic drugs associated with opioids improves ET compliance. Therefore it may have favourable prophylactic effects on MEBt in ventilated intensive care unit patients scheduled for HBOT.

Comparative study of neuromuscular blocking and hemodynamic effects of rocuronium and cisatracurium under sevoflurane or total intravenous anesthesia.

UNLABELLED: Neuromuscular blockers (NMB) are important adjuvant to general anesthesia. Rocuronium bromide and cisatracurium besylate are considered relatively recently introduced non-depolarizing muscle relaxants. OBJECTIVES: This study evaluates the enhancement of cisatracurium and rocuronium-induced neuromuscular block during anesthesia with 1.5 MAC sevoflurane or total i.v. anesthesia (TIVA), hemodynamic effects and side effects. METHODOLOGY: 80 patients were randomly allocated into one of four equal Groups to receive either rocuronium (under sevoflurane or propofol TIVA) or cisatracurium (under sevoflurane or propofol TIVA). The NMB effects ofrocuronium and cisatracurium were studied by constructing dose-effect curves. Acceleromyography (TOF-Guard) and train-of-four (TOF) stimulation of the ulnar nerve were used (2 Hz every 15 sec). Cisatracurium and rocuronium were administered in increments until depression of T1/T0 > 95% was reached. Hemodynamic effects of both muscle relaxants together with sevoflurane or propofol were assessed using thoracic bioimpendance. RESULTS: Depression ofT1/T0 was enhanced under sevoflurane compared to TIVA. ED50 and ED95 values of both drugs were significantly lower under sevoflurane more than TIVA. Recovery index 25-75% and time to a TOF ration of 0.70 were prolonged significantly by sevoflurane compared to TIVA. Hemodynamically, rocuronium and cisatracurium did not exert significant changes, but the interaction of the relaxants and the anesthetic agents resulted in statistically significant decline in some hemodynamic parameters at certain periods which are not clinically significant and required no medications. CONCLUSION: We conclude that the effects of rocuronium and cisatracurium are significantly enhanced during sevoflurane compared with propofol anesthesia and the recovery is lower.

Site selectivity of competitive antagonists for the mouse adult muscle nicotinic acetylcholine receptor.

The muscle-type nicotinic acetylcholine receptor has two nonidentical binding sites for ligands. The selectivity of acetylcholine and the competitive antagonists (+)-tubocurarine and metocurine for adult mouse receptors is known. Here, we examine the site selectivity for four other competitive antagonists: cisatracurium, pancuronium, vecuronium, and rocuronium. We rapidly applied acetylcholine to outside-out patches from transfected BOSC23 cells and measured macroscopic currents. We have reported the IC(50) of the antagonists individually in prior publications. Here, we determined inhibition by pairs of competitive antagonists. At least one antagonist was present at a concentration producing > or =67% receptor inhibition. Metocurine shifted the apparent IC(50) of (+)-tubocurarine in quantitative agreement with complete competitive antagonism. The same was observed for pancuronium competing with vecuronium. However, pancuronium and vecuronium each shifted the apparent IC(50) of (+)-tubocurarine less than expected for complete competition but more than expected for independent binding. The situation was similar for cisatracurium and (+)-tubocurarine or metocurine. Cisatracurium did not shift the apparent IC(50) of pancuronium or vecuronium, indicating independent binding of these two pairs. The data were fit to a two-site, two-antagonist model to determine the antagonist binding constants for each site, L(alphaepsilon) and L(alphadelta). We found L(alphaepsilon)/L(alphadelta) = 0.22 (range, 0.14-0.34), 20 (9-29), 21 (4-36), and 1.5 (0.3-2.9) for cisatracurium, pancuronium, vecuronium, and rocuronium, respectively. The wide range of L(alphaepsilon)/L(alphadelta) for some antagonists may reflect experimental uncertainties in the low affinity site, relatively poor selectivity (rocuronium), or possibly that the binding of an antagonist at one site affects the affinity of the second site.

Clinical pharmacology of cisatracurium during nitrous oxide-propofol anesthesia in children.

STUDY OBJECTIVE: To describe, in pediatric patients, the effects of three doses of cisatracurium during nitrous oxide-propofol anesthesia and to determine if larger doses result in faster onset time. SETTING: College hospital. SUBJECTS: 75 ASA physical status I and II children, aged 15 to 60 months, undergoing surgery for hypospadias or undescendent testis. INTERVENTIONS: Patients were randomly assigned to one of three groups according to the dose of cisatracurium: Group A = 0.1 mg/kg (two x effective dose), Group B = 0.15 mg/kg (three x effective dose), and Group C = 0.2 mg/kg (4 x effective dose). MEASUREMENTS: Neuromuscular block was assessed with TOF-Guard (Biometer International, Odense, Denmark) accelerometry. Onset time (from cisatracurium injection to maximal depression of time to first twitch), duration of peak effect (time from cisatracurium injection to 5% recovery of time to first twitch), duration of clinical action (time from cisatracurium injection to 25% recovery of time to first twitch), and recovery index (recovery of time to first twitch from 25% to 75%) were recorded. MAIN RESULTS: Cisatracurium had no effect on heart rate or blood pressure at any dose. Compared with Group A, onset times in Groups B and C were shorter; and durations of peak effect and clinical action in Groups B and C were longer (P < 0.01) than those in Group A. There was no difference in recovery index among the three groups. There was no difference in onset times between Groups B and C. Compared with Group B, durations of peak effect and clinical action in Group C were longer (P < 0.05 or P < 0.01). CONCLUSION: Four times the effective dose of cisatracurium did not significantly shorten onset time beyond that produced with three times the effective dose in young children.

Infusions of rocuronium and cisatracurium exert different effects on rat diaphragm function.

OBJECTIVE: Aminosteroidal and benzylisoquinoline neuromuscular blocking agents are used in the intensive care unit to facilitate mechanical ventilation. The use of these agents has been associated with development of critical illness myopathy; however, the relative frequency of myopathy development among agents is not known. The aim of our study was to compare the effects of 24 h infusion of rocuronium or cisatracurium on the diaphragm in mechanically ventilated rats. DESIGN: Randomized, controlled experiment. SETTING: Basic animal science laboratory. SUBJECTS: Male Wistar rats, 14 weeks old. INTERVENTIONS: Rats were divided into four groups to receive either saline, rocuronium (low dose) or cisatracurium (low or high dose). MEASUREMENTS AND RESULTS: After 24 h, in vitro diaphragm tetanic force was decreased after rocuronium (-33% vs. saline), while the force was more preserved after cisatracurium, even in the high-dose group. Cross-sectional areas of the different diaphragm and gastrocnemius fibers were unaltered. Diaphragmatic MURF-1 mRNA was increased after rocuronium (+44% vs. saline), while unchanged in both cisatracurium groups. Calpain activity was increased after rocuronium (+75% vs. saline) and unchanged in the cisatracurium groups. MURF-1 mRNA expression and calpain activity were negatively correlated with diaphragm force. CONCLUSIONS: Cisatracurium infusion during controlled mechanical ventilation exerted less detrimental effects on diaphragm function and proteolytic activity than infusion of rocuronium, even with the higher effective dose. These data suggest that increased calpain activity and increased activation of the ubiquitin proteasome system play a role in the different effects of these agents.

Do muscle relaxants influence vascular tone in isolated coronary artery segments?

The aim of this study was to elucidate the influence of four neuromuscular blocking substances on coronary vascular tone using the model of isolated porcine coronary artery segments. We studied the effects of four muscle relaxants, atracurium, pancuronium, rocuronium, and vecuronium (0.1, 1, and 10 microg mL-1 each), on the contractile response to three vasoconstrictors: acetylcholine, histamine, and serotonin. None of the neuromuscular blocking agents under investigation exerted a significant influence on the vasoconstricting effects of these mediators except for pancuronium, which dose-dependently attenuated acetylcholine-mediated contractions (-10.8% attenuation for 10 microg mL-1 pancuronium, P < 0.05). There was no difference between vessels with intact endothelium and denuded preparations. It is concluded that high-dose pancuronium exerts an antimuscarinic effect in vascular smooth muscle. The other neuromuscular agents studied do not alter vascular reactivity of isolated porcine coronary arteries.

Cardiovascular responses to neuromuscular blockade in the anemic ovine fetus.

Currently little is known about the cardiovascular responses of the anemic fetus to neuromuscular blockade. We hypothesized that, despite marked anemia with potentially decreased cardiac reserve, the fetal responses to Pancuronium neuromuscular blockade would differ significantly when compared with neuromuscular blockade with Atracurium (a cardiovascular sparing agent). Ten fetal sheep (137 +/- 1 (SE) days gestation) were divided into three groups (21 experiments): Pancuronium (n = 7), Atracurium (n = 6), and Control (n = 8). Fetal anemia (Hct = 21.8 +/- 0.7%) was produced by serial hemorrhage over 3 days. Fetal arterial (FAP) and venous (FVP) pressures, heart rate (FHR), and arterial pH, pO2, and pCO2 were measured at -20, 0, 10, 20, 30, 60, and 90 minutes relative to neuromuscular blockade. Data were analyzed by three-way ANOVA for repeated measures. Pancuronium neuromuscular blockade increased FHR (15-20 bpm, P < .0001) and decreased FVP (-0.8 mm Hg, P < .0001). Atracurium had no effect on FHR, FAP, or FVP. Fetal pH (0.024, P < .0001) and pO2 (1-2 mm Hg, P = .0001) increased in both neuromuscular-blocked groups. Fetal pCO2 decreased in the Pancuronium-blocked animals (P = .02). We conclude that, in anemic fetuses, neuromuscular blockade with Atracurium produced minimal cardiovascular effects when compared to neuromuscular blockade with Pancuronium. Both agents produced small improvements in fetal pH and blood gases.

[Effects of precurarization on oxygen arterial saturation measure with pulse oximetry and neuromuscular function]. / Efectos de la precurarización sobre la saturación arterial de oxígeno medida por pulsioximetría y la función neuromuscular.

OBJECTIVE: To study changes in arterial oxygen saturation (SpO2) measured by pulse oximetry, and the effect of neuromuscular function after precurarization with different nondepolarizing muscle relaxants. PATIENTS AND METHOD: One hundred twenty-four patients scheduled for elective surgery were randomly assigned to four groups according to the NDPMR received: d-tubocurarine 0.05 mg/kg, atracurium 0.05 mg/kg, vecuronium 0.01 mg/kg or pancuronium 0.015 mg/kg. We recorded SpO2 before precurarization and 4 minutes after administering the dose. We also recorded signs and symptoms of muscle weakness after the 4-minute period of precurarization. RESULTS: We observed a statistically significant decrease in SpO2 4 minutes after starting precurarization in the groups receiving pancuronium, vecuronium and atracurium. These three groups were also significantly different from the d-tubocurarine group with regard to signs and symptoms of muscle weakness; the incidences of such symptoms were similar among the three groups, the only exception being the greater difficulty patients in the pancuronium group had in maintaining the Valsalva maneuver for 10 seconds. The lowest incidence of clinical signs of muscle weakness were in the d-tubocurarine group. We found a significant relation between decreased SpO2 caused by precurarization and the variables of inability to maintain the Valsalva maneuver for 10 seconds and to raise the head for more than 4 seconds. CONCLUSIONS: SpO2 measured by pulse oximetry is an effective method for monitoring breathing function in the precurarized patient, as it detects early changes in arterial oxygen saturation related to respiratory muscle weakness. The agent d-tubocurarine is recommended for precurarization, because of its scarce effect on neuromuscular function at the dose used in this study.

Effect of isoflurane and sevoflurane on the magnitude and time course of neuromuscular block produced by vecuronium, pancuronium and atracurium.

We have compared the ability of equipotent concentrations of isoflurane and sevoflurane to enhance the effect of non-depolarizing neuromuscular blocking drugs. Ninety ASA I and II patients of both sexes, aged 18-50 yr, were stratified into three blocker groups (Vec, Pan and Atr), to undergo neuromuscular block with vecuronium (n = 30), pancuronium (n = 30) or atracurium (n = 30), respectively. Within each group, patients were allocated randomly to one of three anaesthetic subgroups to undergo maintenance of anaesthesia with: (1) alfentanil-nitrous oxide-oxygen (n = 10); (2) alfentanil-nitrous oxide-oxygen-isoflurane (n = 10); or (3) alfentanil-nitrous oxide-oxygen-sevoflurane (n = 10) anaesthesia. During maintenance of anaesthesia, end-tidal concentrations of isoflurane, sevoflurane and nitrous oxide were 0.95, 1.70 and 70%, respectively. Both the evoked integrated electromyogram and mechanomyogram of the adductor pollicis brevis muscle were measured simultaneously. In the Vec and Pan groups, a total dose of 40 micrograms kg-1 of vecuronium or pancuronium, respectively, was given, and in the Atr group a total dose of atracurium 100 micrograms kg-1. Each blocker was given in four equal doses and administered cumulatively. We showed that 0.95% isoflurane and 1.70% sevoflurane (corresponding to 0.8 MAC of each inhalation anaesthetic, omitting the MAC contribution of nitrous oxide) augmented and prolonged the neuromuscular block produced by vecuronium, pancuronium and atracurium to a similar degree.

Interactions of calcium channel blockers with non-depolarising muscle relaxants in vitro.

The effects of two calcium channel blockers (verapamil and nicardipine) on indirectly elicited muscle twitch and possible interactions between these drugs and non-depolarising muscle relaxants (vecuronium, atracurium, pancuronium) were investigated using isolated rat phrenic nerve-hemidiaphragm preparations. Both verapamil 10(-5) M and nicardipine 10(-6) M caused significant depression of twitch amplitude. Verapamil significantly increased vecuronium- and atracurium-induced neuromuscular block, but not that produced by pancuronium. Nicardipine potentiated atracurium-induced neuromuscular block but had no effect on pancuronium- and vecuronium-induced twitch depression. Neostigmine 10(-6) M did not produce any significant changes in the maximal recovery of twitch depression induced with calcium channel blockers and muscle relaxants combinations; also, neostigmine had no effect on maximal recovery time of twitch depression.

[Delay of clinical recovery from paralysis induced by atracurium: comparison between orbicularis oculi and adductor pollicis]. / Délai de récupération clinique d'une paralysie induite par l'atracurium: comparaison entre orbiculaire des paupières et adducteur du pouce.

OBJECTIVE: To compare with train-of-four stimulation the delays of the beginning of the spontaneous recovery of the orbicularis oculi and of the adductor pollicis after profound neuromuscular blockade with atracurium. STUDY DESIGN: Prospective, comparative open study. PATIENTS AND METHODS: Twenty-eight physical class ASA 1 and 2 patients under general anaesthesia (propofol, N2O, fentanyl) and profound neuromuscular blockade with atracurium. Train-of-four stimulation, every 10 s, of the ulnar nerve at the wrist (for assessing by tactile means the response of the adductor pollicis) and of the temporal branch of the facial nerve (for assessing visually the response of the orbicularis oculi). On each site, measurement of the delay between the end of the maintenance of deep neuromuscular blockade (last dose of atracurium) and the beginning of the recovery (first response to train-of-four stimulation). RESULTS: In each case, the recovery of the orbicularis oculi began earlier than the recovery of the adductor pollicis (26 +/- 9 min vs 34 +/- 9 min, P < 0.001). The delays of recovery at each site were strongly correlated (r = 0.87; P < 0.001) but the time lag between the responses varied greatly: 1 to 21 min, mean: 8 +/- 5 min, coefficient of variation: 56.6%. CONCLUSION: The orbicularis oculi should not be monitored alone for assessment of recovery from profound neuromuscular blockade by atracurium, as it predicts poorly the time of the recovery of the adductor pollicis.

Potentiation of atracurium by pancuronium during propofol-fentanyl-N2O anesthesia.

At the end of abdominal surgery deep neuromuscular blockade is required for peritoneal closure. Ideally injecting an intermediate acting drug like atracurium after a long acting drug such as pancuronium should deepen the neuromuscular block without the fear of an inadequate reversal at the completion of surgery. Thirty patients ASA I or II status, without known allergy to myorelaxant and without neuromuscular, hepatic or renal failure were included in this study. Anesthesia was induced and maintained with propofol, fentanyl, and N20. Normal core temperature was maintained by active warming of the upper part of the body. Blood electrolytes and the acid-base status were within the normal range. The accelerographic responses to Train-Of-Four supramaximal stimulation (TOF) of the ulnar nerve was monitored at the thumb. After obtaining a stable response with the accelerograph, the patients randomly received pancuronium (0.10 mg.kg-1, group I, n = 10 and group II, n = 10) or atracurium (0.50 mg.kg-1, group III, n = 10). An additional dose of atracurium (0.16 mg.kg-1, group I and III) or pancuronium (0.03 mg.kg-1, group II) was injected when the first response of TOF stimulation (T1) reached 25% of its initial value. Then the time to obtain a 25% twitch height of T1 (T25), the recovery index (RI 25-75), the delay to obtain 4 responses to TOF and an adequate recovery [TOF ratio of 0.70 (TOF70)] were monitored. Injection of 60% ED95 of atracurium after pancuronium resulted in a similar recovery of neuromuscular function as after 45% ED95 of pancuronium as shown by the same recovery of T25 (66.5 +/- 4.2 min versus 71.4 +/- 7.8 min, group I versus group II, p > 0.05) and TOF70 (131.6 +/- 15.7 min versus 144.0 +/- 17.5, group I versus II, p > 0.05). Nevertheless the RI 25-75 of group I was of intermediate duration between those of group II and III. Electrolytes and acid-base status were similar between groups at the beginning of surgery. Thus this study shows a synergistic effect of the combination of atracurium after pancuronium occurring in non hypothermic patients anesthetized without halogenated agents. Because the duration of action of the drug administered first governs the duration of action of the subsequent neuromuscular myorelaxant, the neuromuscular function should be closely monitored at the end of surgery if neuromuscular drugs are used in combination.

Genetic susceptibility to atracurium-induced bronchoconstriction.

The goal of this study was to develop a murine model of atracurium-induced bronchoconstriction in which to evaluate the mechanism of action of this airway response. We evaluated nine inbred strains of mice for the development of atracurium-induced bronchoconstriction. The maximal difference in the magnitude of the airway response to atracurium noted between the highly responsive DBA/2 mice and the minimally responsive SJL mice was greater than 20-fold. This phenotype appears to reflect an intrinsic difference in the lungs of these animals because the extent of neuromuscular blockade was not significantly different in DBA/2 and SJL mice. Atracurium-induced airway hyperresponsiveness in DBA/2 mice was eliminated in a dose-dependent manner by pretreatment with atropine or pancuronium. These data are consistent with a postganglionic vagal efferent mechanism which produces a differential pulmonary response to this neuromuscular blocker. A genetic predisposition to atracurium-induced bronchoconstriction appears to exist in certain inbred strains of mice. Thus, a mouse model may be useful for mapping the gene(s) that control this trait and for suggesting responsible candidate genes. Our results suggest that the inbred laboratory mouse will be useful to study the mechanism by which atracurium produces bronchoconstriction.

Prolonged neuromuscular blockade in two critically ill patients treated with atracurium.

Recent literature suggests that the risk of prolonged neuromuscular blockade associated with atracurium compared with other nondepolarizing neuromuscular blocking agents may be minimal. Two patients experienced prolonged weakness associated with the administration of atracurium. Both received atracurium 0.5-0.7 mg/kg/hour in combination with methylprednisolone 500-600 mg/day. Electromyographic results and creatine kinase levels were suggestive of muscular weakness in both patients. Despite high-dose corticosteroid therapy, the electromyographic evidence supporting prolonged weakness did not suggest typical corticosteroid myopathy. Although some clinicians advocate routine administration of atracurium in critically ill patients due to the relative lack of reports of prolonged weakness, this may be premature. Although there are fewer reports of atracurium-associated prolonged weakness compared with pancuronium and vecuronium, the patients we describe suggest that it may occur.

Response to pancuronium after loss of atracurium-induced neuromuscular blockade.

OBJECTIVE: To describe a previously unreported event in which a patient became refractory to atracurium-induced neuromuscular blockade, but subsequently was adequately paralyzed with a standard dosage of pancuronium. CASE SUMMARY: A previously healthy 17-year-old woman who sustained multiple trauma developed tolerance to an atracurium infusion she was receiving while undergoing mechanical ventilation. On day 3 of neuromuscular blockade, she became unresponsive to atracurium as evidenced by excessive physical movement, increased peak airway pressures, and overbreathing assist control ventilation. Repeat boluses and increases in the atracurium infusion rate to a maximum of 1.27 mg/kg/h failed to provide a desired clinical response. A bolus dose of pancuronium 0.15 mg/kg was administered and the constant infusion was then changed to pancuronium 0.078 mg/kg/h. Within minutes, decreased respirations, peak airway pressures, and agitation were noted. The pancuronium infusion rate was then tapered to 0.045 mg/kg/h over 72 hours and continued to maintain adequate neuromuscular blockade. DISCUSSION: Potential pharmacokinetic and pharmacodynamic causes of loss of neuromuscular blockade in this patient are postulated. Possible explanations for loss of neuromuscular blockade include increased degradation of atracurium and/or a change in acetylcholine receptor physiology. CONCLUSIONS: The development of resistance to a specific neuromuscular blocking agent in the intensive care setting does not necessarily imply cross-tolerance or resistance to alternative agents. Also, loss of respiratory control by one neuromuscular blocking agent may be overcome by changing agents.

Pharmacodynamics of atracurium in clinical practice: effect of plasma potassium, patient demographics, and concurrent medication.

To determine which factors influenced the pharmacodynamics of atracurium in clinical practice, the steady-state plasma concentration of atracurium for 90% paralysis (Cpss90) was measured in 100 adult patients. Neuromuscular block was maintained at 88%-92% of the control response by adjusting the target concentration being delivered by preprogrammed intravenous atracurium infusion. The Cpss90 was measured empirically from plasma samples taken when the block had been stable for 15 min with no adjustment in the infusion rate for 20 min. To describe how factors influenced the Cpss90 of atracurium, a model was developed by multiple stepwise linear regression analysis. Influencing variables retained in the final model were plasma potassium concentration, intraoperative administration of gentamicin, and premedication with papaveretum and hyoscine. The model predicted that the Cpss90 of atracurium would decrease with decreasing serum potassium according to the relationship log10(Cpss90) = 2.380 + 0.171 x [K mmol/L] (n = 100; ANOVA, P < 0.001). Intraoperative administration of gentamicin modified this relationship resulting in a 25.1% decrease in the predicted Cpss90 (n = 15; ANOVA, P < 0.001). Premedication with papaveretum and hyoscine also modified this relationship resulting in a 21.2% decrease in predicted Cpss90 (n = 30; ANOVA, P < 0.001). The model predicted that administration of both would decrease the Cpss90 by 41.0%. Patients aged > or = 70 yr had a slight, but statistically insignificant, increase in the Cpss90 compared to younger adult patients. No other factor was found to influence the Cpss90, including patient sex, body fluid, and other drugs administered in the perioperative period, including calcium channel antagonists and ranitidine.(ABSTRACT TRUNCATED AT 250 WORDS)

[Anesthesia for renal transplantation: continuous neuromuscular blockade with atracurium and the management of intraoperative hypertension with nifedipine]. / Anästhesie zur Nierentransplantation: Kontinuierliche neuromuskuläre Blockade mit Atracurium und Behandlung der intraoperativen Hypertonie mit Nifedipin.

Patients undergoing kidney transplantation often suffer from essential hypertension and coronary artery disease, for which perioperative treatment with nifedipine proved to be effective. If calcium-channel blockers and nondepolarizing muscle relaxants are used simultaneously, their synergistic effect at the neuromuscular cleft must be considered. On the other hand because of its extrarenal elimination no significantly altered effects are expected for patients with terminal renal failure. This prospective study comprised 30 patients undergoing kidney transplantation who were 2 kg over normal weight after a preoperative dialysis and infusion of lactated Ringer solution. Fifteen minutes after introduction of balanced anaesthesia with isoflurane, nitrous oxide and fentanyl, patients were assigned to the treatment group (N) with hypertension (mean arterial pressure (MAP > 110 mmHg) and subsequent management with nifedipine or to the control group (0). Treatment was aimed at keeping MAP between 90 and 110 mmHg. The neuromuscular status was electromyographically assessed by the train-of-four-principle. There were evaluated the duration of action of the initial dose of atracurium (0.5 mg/kg) from injection time to T1 = 2% (WZ 2), the dose of atracurium for a continuous neuromuscular blockade (DD 98 in mg/kg/h), the recovery time and the recovery index. Fourteen patients with hypertension received a bolus of 10 micrograms/kg nifedipine. A significant reduction in blood pressure (p < 0.05) to the desired range was achieved by a subsequent infusion of nifedipine of 5 to 40 micrograms/kg/h. In 16 patients MAP was kept between 90 and 100 mmHg without any additional therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Continuous infusions of atracurium and vecuronium, compared with intermittent boluses of pancuronium: dose requirements and reversal.

This study was designed to determine the effect of prolonged infusion on the ease of reversal of atracurium and vecuronium, and whether factors which potentiate the block delayed reversal. In phase one, 40 patients were randomized (double blind) to determine the steady state conditions for atracurium and vecuronium. Fourteen atracurium patients and 17 vecuronium patients were evaluable. The unblinded second phase involved the steady state conditions using halothane or isoflurane and atracurium infusions. The infusion required for 95% twitch depression (TD95) for atracurium was 7.6 +/- 1.1 micrograms.kg-1 x min-1. The requirement for vecuronium changes with time: TD95 at 30 min was 1.01 +/- 0.16, at 60 min 0.89 +/- 0.12 and after 90 min 0.85 +/- 0.17 micrograms.kg-1 x min-1 (P < 0.05). The mean TD95 was 0.94 +/- 0.23 micrograms.kg-1 x min-1. Multivariate regression analysis of the infusion data revealed a vecuronium model predicting TD95 by the duration of infusion (P < 0.05) and weight (P = 0.05). Atracurium TD95 was predicted by age (P = 0.05). The addition of an inhalation agent to atracurium reduced the infusion rate by 2.01 +/- 0.28 micrograms.kg-1 x min-1 (P = 0.0001) for each increase in MAC. The mean reversal times for atracurium with three different anaesthetics and for vecuronium were not different. Reversal of pancuronium blockade, from less profound twitch depression (86.4 vs 95%) took twice as long as for atracurium and vecuronium for which the following predictors were identified: age, weight, duration of infusion, level of blockade, and type of anaesthetic, using a stepwise regression model.(ABSTRACT TRUNCATED AT 250 WORDS)