Patient's death as a result of mistakenly injection of pancuronium.

Pancuronium is a typical non-depolarizing, curare-mimetic, very potent muscle relaxant. Besides application in anesthesiology and intensive care, it is used in execution as a part of lethal injection. In medico-legal practice, there are cases of using this substance in order to commit suicide or to deprive other people of their lives. Accidental pancuronium intoxications are very rare. The authors present such case ended in sudden death of hospitalized woman after mistakenly injection of the drug. 57-year-old female alcoholic was admitted to the Acute Poisoning Centre after ethylene glycol ingestion. During the fifth day of treatment the nurse by mistake, instead of furosemide, intravenously administered her pancuronium. Sudden respiratory and circulatory arrest occurred, so she was intubated and resuscitation with artificial ventilation were undertaken, however within 1 hour and 45 minutes the patient died. Due to the vague background of a sudden deterioration in the patient's condition, the case was brought for prosecution. The autopsy and histopathological studies did not reveal the cause of death, but undertaken chemico-toxicological examinations identified the presence of pancuronium in blood, liver and kidney (190 ng/ml, 70 ng/g and 125 ng/g, respectively). Chemico-toxicological analysis proved that the cause of death of the 57-year-old hospitalized woman was pancuronium intoxication due to evident medical error during drug administration. In our case the concentration of pancuronium in blood was in therapeutic range (200-600 ng/ml). However, even a therapeutic pancuronium dose administered to patient the breath of whom is not supported and monitored can be a threat to his life.

Pancuronium enhances isoflurane anesthesia in rats via inhibition of cerebral nicotinic acetylcholine receptors.

PURPOSE: This study was conducted to elucidate the mechanism of enhancement of volatile anesthetics by neuromuscular blocking agents in rats and to consider the relevance of this enhancement to clinical anesthesia. METHODS: Male Sprague-Dawley rats were used. After confirming a movement in response to tail clamping under 1.1 % isoflurane anesthesia, response was determined when the tail clamp was applied at several points after microinjection of pancuronium into the lateral ventricle. Arousal responses to microinjection of nicotine into the lateral ventricle were assessed with or without pretreatment with intraventricular pancuronium. The intravenous 50 % effective dose (ED50) and 95 % effective dose (ED95) for neuromuscular blockade with pancuronium administered in a cumulative fashion at 1.1 % isoflurane were calculated. RESULTS: Intraventricular pancuronium dose-dependently reduced the response to tail clamping, and the dose required to show immobilization of 50 % of rats (intraventricular ED50) was 1.62 µg/kg. Pretreatment with pancuronium at 6 µg/kg significantly reduced the effect of awakening by nicotine under isoflurane anesthesia (P = 0.044). The intravenous ED50 and ED95 for neuromuscular blockade were 63 µg/kg (90 % confidence interval [CI] 52-75 µg/kg) and 133 µg/kg (90 % CI 109-158 µg/kg), respectively. The ratio of intraventricular ED50 to intravenous ED50 was 0.026. CONCLUSION: Pancuronium microinjection into the lateral ventricle dose-dependently enhances the depth of isoflurane anesthesia, which might be caused by inhibition of neuronal nicotinic acetylcholine receptor transmission in the cerebrum. Intravenous injection of pancuronium at high doses might increase the cerebrospinal concentration to a level at which an effect can be observed.

Comparative pharmacodynamics of pancuronium, cisatracurium, and CW002 in rabbits.

Pancuronium is a long-duration neuromuscular blocking drug (NMBD) that has been used in anesthetized rabbits at 0.1 mg/kg. However, there are limited data regarding the time course for recovery from this dose either spontaneously or with pharmacologic reversal. Here we defined the potency, onset, and recovery characteristics for the intermediate-duration NMBD cisatracurium and CW002 (a novel cysteine-inactivated molecule) in the rabbit, and test the hypothesis that these drugs may be alternatives to 0.1 mg/kg pancuronium for survival procedures. New Zealand white rabbits anesthetized with isoflurane were studied in a cross-over design. Potencies of cisatracurium and CW002 were defined as the effective dose for 95% depression of evoked muscle twitch (ED95). Responses to 3×ED95 were used to define onset (time to maximal effect), recovery index (RI; time from 25% to 75% recovery of twitch), and duration (time to complete recovery). Responses to all drugs were determined with and without reversal by neostigmine-glycopyrrolate or L-cysteine. CW002 was 4-fold more potent than was cisatracurium, but their onset, RI, and duration were similar. Pancuronium had similar onset and RI but longer duration, compared with cisatracurium and CW002. Reversal shortened the recovery index and duration for all 3 drugs. At 3×ED95, cisatracurium and CW002 had the same onset as did standard-dose pancuronium, but durations were shorter and more predictable. In addition, CW002 can be reversed without the potential side effects of cholinergic manipulation. We conclude that cisatracurium and CW002 are viable alternatives to pancuronium for survival studies in rabbits.

Pancuronium dose refinement in experimental pigs used in cardiovascular research.

OBJECTIVE: To quantify the dose of pancuronium required to obtain moderate neuromuscular blockade as monitored by acceleromyography (NMB(mod) : train-of-four count of ≤2) as a part of a balanced anaesthetic protocol in pigs used in cardiovascular research. STUDY DESIGN: Prospective cross-sectional study. ANIMALS: Five pigs (median body weight: 60 (range 60-63) kg). METHODS: Anaesthesia was induced with xylazine, ketamine, atropine and midazolam and maintained with isoflurane in O(2) :air and fentanyl. Pigs received 0.1 mg kg(-1) pancuronium initial bolus to reach NMB(mod) followed by 0.1 mg kg(-1) hour(-1) constant rate infusion (CRI). During anaesthesia a twitch count of 3 or measureable T4/T1 ratio indicated unsatisfactory NMB. In this case additional 0.4 mg boluses of pancuronium were administered IV to effect in addition to the CRI. Descriptive statistical analysis was performed to express the median and range of the bolus and CRI dose of pancuronium in pigs. Cardiovascular parameters were analyzed at selected time points with Friedman Repeated Measures Analysis on Ranks. Spearman Rank test was used to evaluate correlation between parameters. RESULTS: Acceleromyographic monitoring of NMB is feasible in anaesthetized pigs. The median initial dose and rate of pancuronium required to achieve NMB(mod) were 0.10 (range 0.10-0.13) mg kg(-1) and 0.11 (range 0.10-0.21) mg kg(-1) hour(-1) , respectively. The administration rate showed considerable individual variation. CONCLUSIONS AND CLINICAL RELEVANCE: These pancuronium doses can be used as a guideline to achieve NMB(mod) in pigs as part of a balanced anaesthetic protocol. Instrumental NMB monitoring is essential because of individual kinetic variations and compliance to monitoring guidelines.

Altered vascular endothelial growth factor expression during GnRH antagonist protocol in women of reproductive age with normal baseline hormone profiles.

OBJECTIVE: To explain the unexpected low response to GnRH antagonist protocol in reproductive women with normal baseline hormone profiles. DESIGN: Retrospective study. SETTING: University hospital. PATIENT(S): Twenty-five women undergoing their first IVF cycle. INTERVENTION(S): Follicular fluid (FF) from large follicles (>15 mm) was obtained during oocyte retrieval from unexpected low responders (n = 13, group A) and 12 age-matched normal responders (n = 12, group B). MAIN OUTCOME MEASURE(S): The FF markers known to reflect follicle environment (insulin-like growth factor [IGF] II, IGF-binding protein 4, müllerian-inhibiting substance, pregnancy-associated plasma protein A, soluble Fas, and vascular endothelial growth factor [VEGF]) were analyzed by ELISA. RESULT(S): The baseline characteristics (age, day 3 serum LH, FSH, E(2), duration and dose of r-FSH, GnRH antagonist) were not different between the two groups. The number of large follicles, oocytes retrieved, and serum E(2) levels on the day of hCG injection were significantly higher in group B. Whereas the other follicular markers did not differ between the two groups, VEGF was significantly higher in group A. In addition, the VEGF concentration showed an inverse correlation with the total number of oocytes retrieved. CONCLUSION(S): The unexpected low response in women with normal basal hormone profiles, during GnRH antagonist protocol, was associated with altered follicular VEGF expression.

Improved neuromuscular blockade using a novel neuromuscular blockade advisory system: a randomized, controlled, clinical trial.

BACKGROUND: Conventional incremental bolus administration of neuromuscular blocking (NMB) drugs is associated with limitations in intraoperative control, potential delays in recovery, and residual blockade in the postanesthetic period. To overcome such limitations, we developed a novel adaptive control computer program, the Neuromuscular Blockade Advisory System (NMBAS). The NMBAS advises the anesthesiologist on the timing and dose of NMB drugs based on a sixth-order Laguerre model and the history of the patient's electromyographic responses. Here, we tested the hypothesis that the use of the NMBAS improves NMB compared to standard care. METHODS: We conducted a prospective, randomized, controlled, blinded, parallel-group, clinical trial with n = 73 patients (ASA physical status I-III) undergoing abdominal surgery under general anesthesia > or =1.5 h with NMB using rocuronium. Patients were allocated to standard care or NMBAS-guided rocuronium administration. The primary outcome variable was the incidence of intraoperative events reflecting inadequate NMB. Secondary outcome variables included train-of-four (TOF) ratios at the end of surgery before reversal, the total doses of rocuronium, reversal agents, anesthetics and other drugs, the incidence of postoperative adverse events, and the incidence of anesthesiologist noncompliance with NMBAS recommendations. RESULTS: Of 73 enrolled patients, n = 30 per group were eligible for analysis. Patient demographics were comparable between the groups. The incidence in total intraoperative events associated with inadequate NMB was significantly lower in the NMBAS group compared to standard care (8/30 vs 19/30; P = 0.004). Mean TOF ratios at the end of surgery before reversal were higher in the NMBAS group (0.59 [95% CI, 0.48-0.69] vs 0.14 [95% CI, 0.04-0.24]; P < 0.0001). Total administered doses of rocuronium, reversal drugs, and other drugs, and the incidence of postoperative adverse events were not different. CONCLUSIONS: Compared to standard practice, NMBAS-guided care was associated with improved NMB quality and higher TOF ratios at the end of surgery, potentially reducing the risk of residual NMB and improving perioperative patient safety.

Skin reactions to intradermal neuromuscular blocking agent injections: a randomized multicenter trial in healthy volunteers.

BACKGROUND: Numerous reports confirm the performance of intradermal tests for the diagnosis of anaphylaxis during anesthesia; however, there is controversy over their diagnostic value regarding the newer neuromuscular blocking agents (NMBAs). METHODS: One hundred eleven healthy volunteers were randomly assigned to receive intradermal injections of two NMBAs, at five increasing concentrations. A concentration was considered as a reactive concentration when it led to a positive reaction in more than 5% of the subjects. These concentrations were compared with the maximal concentration recommended for the diagnosis of sensitization to NMBAs. RESULTS: The maximal nonreactive concentrations were 10 m for suxamethonium; 10 m for pancuronium, vecuronium, rocuronium, and cisatracurium; and 10 m for atracurium and mivacurium. Except for mivacurium, these nonreactive concentrations were close to the maximal concentrations used for the diagnosis of sensitization against NMBAs. For mivacurium, the nonreactive concentrations were higher than the maximal concentration currently recommended in clinical practice. CONCLUSION: The aminosteroidal NMBAs pancuronium, vecuronium, and rocuronium and the benzylisoquinoline cisatracurium have a similar potency to induce a nonspecific skin reactivity. If the criteria for positivity and the maximal concentrations of the commercially available compounds recommended by French practice guidelines are used, the risk of false-positive results is limited, and only minor modifications of these recommendations could be suggested. A slight reduction in the maximal concentration used for rocuronium from 1:100 to 1:200 and an increase from 1:1,000 to 1:200 for mivacurium can be proposed.

Interaction between mivacurium and pancuronium: impact of the order of administration.

INTRODUCTION: Potentiation of mivacurium by low-dose pancuronium is mostly due to an inhibition of plasma butyryl cholinesterase (BchE) resulting in a decreased rate of hydrolysis of mivacurium. Nevertheless, an interaction at the receptor site could not be ruled out. By changing the order of the muscle relaxant injections, we may lessen the pharmacokinetic interaction and assess the impact at the acetylcholine receptor level. METHODS: Twenty patients scheduled for general anesthesia with propofol and fentanyl, and isoflurane were randomized into two groups receiving, mivacurium 100 microg kg-1 followed by pancuronium 15 microg kg-1 (group 1) or pancuronium 15 microg kg-1 followed by mivacurium 100 microg kg-1 (group 2). BchE before and after injection of each relaxant was measured. Neuromuscular block was assessed with a force transducer at the adductor pollicis measuring the elicited twitch to ulnar nerve stimulation. RESULTS: The neuromuscular block was greater when pancuronium was administered before mivacurium (100% versus 96+/-3%; P<0.05). Times to recovery of the elicited twitch response to 25% and 75% of control value were increased by 100% (P<0.05). After pancuronium, decreases in BchE of 11% and 14% in groups 1 and 2 were observed, respectively. CONCLUSION: Interaction between mivacurium and low dose pancuronium is significant only when mivacurium is injected after pancuronium.

Efeito da administração do atracúrio sobre a recuperação do bloqueio neuromuscular induzido pelo pancurônio / Effect of atracurium on pancuronium-induced neuromuscular block recovery

JUSTIFICATIVA E OBJETIVOS: Freqüentemente em cirurgias abdominais, na fase de fechamento da parede, há necessidade de doses adicionais de bloqueador neuromuscular. O objetivo deste estudo foi analisar, na vigência de recuperação parcial do bloqueio neuromuscular induzido pelo pancurônio, o efeito da administração de dose complementar de atracúrio sobre a recuperação espontânea do bloqueio neuromuscular. MÉTODO: Foram estudados 30 pacientes, divididos em dois grupos, 14 pacientes formaram o grupo pancurônio e 16 pacientes, o grupo atracúrio. A função neuromuscular foi monitorizada de forma contínua por acelerometria do músculo adutor do polegar, utilizando a seqüência de quatro estímulos (SQE), através da estimulação supramáxima do nervo ulnar. A indução da anestesia foi feita com propofol, fentanil, pancurônio 0,08 mg.kg-1 e a manutenção com N2O 60 por cento em oxigênio e isoflurano na concentração expirada de 0,5 por cento. Quando a primeira contração da seqüência de quatro estímulos (T1) recuperou 25 por cento, o grupo pancurônio recebeu pancurônio 0,025 mg.kg-1 e o grupo atracúrio, 0,20 mg.kg-1 de atracúrio. Após a dose complementar foram anotados os tempos para recuperação espontânea de T1 igual a 10 por cento, 25 por cento, 75 por cento, do índice de recuperação (IR25-75 por cento) e da relação T4/T1 igual a 0,8. RESULTADOS: Os tempos de recuperação espontânea após dose complementar de pancurônio ou atracúrio não diferiram quando avaliados pela recuperação de T1 em 10 por cento (45,00 ± 15,50 vs 49,69 ± 9,41), 25 por cento (61,64 ± 18,58 vs 64,25 ± 12,51) e 75 por cento (94,00 ± 28,52 vs 84,69 ± 16,50). O IR25-75 por cento (32,36 ± 13,76 vs 20,44 ± 9,24) e o tempo de recuperação da relação T4/T1 = 0,8 (176,86 ± 29,57 vs 141,50 ± 29,57) foram menores no grupo do atracúrio. CONCLUSÕES: Nas condições deste estudo, a complementação com atracúrio não promoveu alteração na recuperação espontânea inicial do bloqueio neuromuscular induzido pelo pancurônio e promoveu diminuição de 20 por cento no tempo de recuperação total.

Óxido Nítrico produzido durante a sepse intensifica a redução nos valores da razão de "train-of-four" (TOF) induzida por d-Tubocurarina e pancurônio / Produced Nitric oxide during sepse intensifies the reduction in the values of the reason of “train-of-four” (TOF) induced for d-Tubocurarine and pancuronium

Durante a sepse, grandes quantidades de óxido nítrico (NO) são sintetizadas pela enzima NO sintase tipo II. Em preparações neuromusculares, o NO produz ou acentua a fadiga de transmissão. 'Train-of-four'(TOF) são pulsos elétricos de 2 Hz aplicados ao nervo motor durante 2 segundos (4 contrações musculares) e o quociente entre as tensões musculares produzidas pela quarta (T4) e primeira (T1) contrações musculares (RTOF = T4/T1) é utilizado para avaliação do bloqueio da transmissão neuromuscular. A redução de RTOF é determinada por bloqueio dos receptores nicotínicos (Nn) facilitatórios e por estimulação dos receptores muscarínicos (M2) inibitórios do terminal nervoso motor. Estudos utilizando preparações neuromusculares de animais sépticos tratadas com bloqueadores neuromusculares em doses que reduzem os valores de RTOF sem promover alterações nas amplitudes das contrações musculares a 0,2 Hz não foram executados. Assim, utilizando preparações nervo ciático-músculo tibial anterior de ratos, verificamos que as menores doses de d-tubocurarina (d-TC), pancurônio (PANC) e galamina (GAL) capazes de produzir 30 por cento de redução em RTOF nos animais sham foram, respectivamente: 54,29 ± 2,86 mg/kg (n=7), 69,02 ± 6,13 mg/kg (n=5), 2,94 ± 0,33 mg/kg (n=4). A dose de d-TC foi menor em animais sépticos (34,53 ± 2,76 mg/kg, n=4), que em animais sham, porém os efeitos foram mais intensos e prolongados na sepse. d-TC (26,50 ± 0,68 mg/kg (n=5), promoveu 30 por cento de redução em RTOF nos animais sham submetidos à infusão de nitroprussiato de sódio (10 mg/kg/min). O tratamento com S-metilisotiouréia (SMT, 13 mg/kg) antagonizou a redução de RTOF em animais sépticos. As menores doses de PANC e GAL que reduziram RTOF em 30 por cento foram semelhantes em todos os grupos experimentais estudados e GAL promoveu efeitos similares em todas as condições experimentais. A redução de RTOF produzida por PANC foi menor que a induzida por d-TC e foi antagonizada pela administração de SMT....

Óxido Nítrico produzido durante a sepse intensifica a redução nos valores da razão de "train-of-four" (TOF) induzida por d-Tubocurarina e pancurônio / Produced Nitric oxide during sepse intensifies the reduction in the values of the reason of “train-of-four” (TOF) induced for d-Tubocurarine and pancuronium

Durante a sepse, grandes quantidades de óxido nítrico (NO) são sintetizadas pela enzima NO sintase tipo II. Em preparações neuromusculares, o NO produz ou acentua a fadiga de transmissão. 'Train-of-four'(TOF) são pulsos elétricos de 2 Hz aplicados ao nervo motor durante 2 segundos (4 contrações musculares) e o quociente entre as tensões musculares produzidas pela quarta (T4) e primeira (T1) contrações musculares (RTOF = T4/T1) é utilizado para avaliação do bloqueio da transmissão neuromuscular. A redução de RTOF é determinada por bloqueio dos receptores nicotínicos (Nn) facilitatórios e por estimulação dos receptores muscarínicos (M2) inibitórios do terminal nervoso motor. Estudos utilizando preparações neuromusculares de animais sépticos tratadas com bloqueadores neuromusculares em doses que reduzem os valores de RTOF sem promover alterações nas amplitudes das contrações musculares a 0,2 Hz não foram executados. Assim, utilizando preparações nervo ciático-músculo tibial anterior de ratos, verificamos que as menores doses de d-tubocurarina (d-TC), pancurônio (PANC) e galamina (GAL) capazes de produzir 30 por cento de redução em RTOF nos animais sham foram, respectivamente: 54,29 ± 2,86 mg/kg (n=7), 69,02 ± 6,13 mg/kg (n=5), 2,94 ± 0,33 mg/kg (n=4). A dose de d-TC foi menor em animais sépticos (34,53 ± 2,76 mg/kg, n=4), que em animais sham, porém os efeitos foram mais intensos e prolongados na sepse. d-TC (26,50 ± 0,68 mg/kg (n=5), promoveu 30 por cento de redução em RTOF nos animais sham submetidos à infusão de nitroprussiato de sódio (10 mg/kg/min). O tratamento com S-metilisotiouréia (SMT, 13 mg/kg) antagonizou a redução de RTOF em animais sépticos. As menores doses de PANC e GAL que reduziram RTOF em 30 por cento foram semelhantes em todos os grupos experimentais estudados e GAL promoveu efeitos similares em todas as condições experimentais. A redução de RTOF produzida por PANC foi menor que a induzida por d-TC e foi antagonizada pela administração de SMT....

Preemptive analgesia in rhegmatogenous retinal detachment surgery: is it effective?

PURPOSE: To evaluate the efficacy of preemptive analgesia in surgical repair of retinal detachment (RD) using scleral buckle and cryopexy under general anesthesia. METHODS: Thirty patients who were scheduled for rhegmatogenous RD surgical repair using scleral buckle and cryopexy and who were American Society of Anesthesiologists physical status I, II, or III were included in this study. The patients were randomly divided into two equal groups. The surgery was done under general anesthesia in both groups, but in Group 2, sub-Tenon anesthesia was given as preemptive analgesia after induction anesthesia and before start of surgery. Both groups were statistically comparable as regards patient age and weight and duration of anesthesia and surgery. RESULTS: The incidences of intraoperative oculocardiac reflex and postoperative vomiting were significantly lower in Group 2 compared with Group 1 (P < 0.001 and 0.0113, respectively). The time of first postoperative analgesic dose was significantly shorter in Group 1 (46.67 +/- 18.84 minutes) compared with Group 2 (162.67 +/- 29.391 minutes) (P < 0.001). The total analgesic consumption per 24 hours was significantly higher in Group 1 compared with Group 2 (P < 0.001). The time of discharge from the hospital was significantly shorter in Group 2 (8.8 +/- 2.704 hours) compared with Group 1 (12.4 +/- 3.481 hours) (P = 0.0018). CONCLUSION: The use of sub-Tenon block as preemptive analgesia after induction of general anesthesia and before the start of rhegmatogenous RD surgical repair was effective in reducing postoperative pain and analgesic requirements compared with an unblocked group. The use of sub-Tenon block was also effective in reducing intraoperative incidence of oculocardiac reflex and postoperative incidence of vomiting.

[Hemostatic profile of women using low-dose oral contraceptive Mercilon. (Preliminary report)]. / Khemostazen profil pri zheni upotrebiavashti niskodoziraniia oralen kontratseptiv--Mercilon (predvaritelno suobshtenie).

The authors have investigated the hemostatic profile at 20 women using low-dosed oral contraceptive Mercilon (Organon) in continuation of six months. Statistically significant changes are found for factor X of hemocoagulation, plasminogen, protein C, protein S and antithrombin III. It is concluded that Mercilon causes activation of the coagulation system, which is balanced by the activation of the fibrinolytic system.

Ventajas del uso de dosis de cebado / Advantages of the use of priming doses

Introducción: En la práctica clínica se han ensayado diversas formas de administrar los relajantes muculares con vistas a lograr menores tiempos y mejores condiciones de intubación. Objetivos: Determinar las condiciones y el tiempo de intubación que se lograron al utilizar el principio de dosis de cebado en los pacientes quirúrgicos, y evaluar los valores de la altura del twicht en ese período. Material y método: Se realizó una investigación tipo ensayo clínico en 120 pacientes sometidos a cirugía laparoscópica, subdivididos en 2 grupos. La técnica de dosis de cebado se realizó en 60 pacientes. Los relajantes musculares utilizados fueron: pancuronio (Grupo I) dosis de 0,1 mg/kg, vecuronio (Grupo II) 0,1 mg/kg y atracurio (Grupo III) 0,5 mg/kg. A los pacientes de este grupo se les administró el 10 por ciento de la dosis total calculada en los 4 minutos previos a la administración de la dosis restante. Resultados: Al monitorizar la FNM durante la intubación se observó que el tiempo óptimo de intubación, cuando se utilizaron dosis de cebado con atracurio y vecuronio, fue de 112,12 ñ 3,2 y 118ñ1,4 seg. respectivamente, menores al del grupo pancuronio. Las condiciones de intubación obtenidas según los criterios de Lund y Stouner presentaron un 95 por ciento de condiciones excelentes en los grupos II y III y un 60 por ciento en el grupo I. La altura del twitch en igual período fue semejante para los grupos II y III. Al usar dosis de cebado fue de 28,5 ñ 3,1 y 33,1 ñ 0,8 por ciento respectivamente y de 48,1 ñ 1,5 y 49,1 ñ 2,6 por ciento cuando ésta no se utilizó. Estas diferencias resultaron ser estadísticamente significativas (p<0,05). Como consecuencia de esta técnica, en el Grupo II se encontraron, en un 10 por ciento del total, dificultades para respirar y otro 10 por ciento refirió experiencia subjetiva de parálisis respiratoria y en el 20 por ciento del Grupo III se observaron dificultades respiratorias. Tres pacientes del Grupo I y dos de cada Grupo II y III presentaron diplopia. Conclusiones: Las condiciones de intubación fueron más rápidas cuando se empleó dosis de cebado para los tres fármacos, que cuando no se la utilizó. La laringoscopía y la intubación tuvieron mejores condiciones con los fármacos de acción intermedia (vecuronio y atracurio). La altura del twitch disminuyó más cuando se emplearon dosis de cebado en los tres fármacos que cuando no se utilizaron...(AU)

Impact of the initial doses of rocuronium and pancuronium on subsequent maintenance for neuromuscular block.

PURPOSE: To determine the impact of the neuromuscular blocking agent given for intubation on the duration of effect of multiple maintenance doses of pancuronium and rocuronium. METHODS: Seventy-eight subjects were randomly assigned to receive one of four dosing combinations for intubation and neuromuscular maintenance: rocuronium for intubation and maintenance, rocuronium for intubation and pancuronium for maintenance, pancuronium for intubation and rocuronium for maintenance, or pancuronium for both. Each time that the first twitch response returned to 25% of the baseline value, the duration of the dose was determined and another maintenance dose was administered. The duration of action of the maintenance doses was compared between the groups. RESULTS: Twitch suppression from the first maintenance dose was shorter for subjects who received rocuronium for both doses (Group RR) compared with that for subjects that received pancuronium (Groups PR & PP) as their intubation dose (17.6 vs 34 & 59.8 min, respectively, P < 0.05). Subjects who received rocuronium followed by pancuronium (Group RP) showed a shorter duration of twitch suppression after the first maintenance dose than the group that received pancuronium for both doses (Group PP) (21.3 vs 59.8 min, P < 0.05). By the third maintenance dose, the influence of the intubating dose on the maintenance dose duration had essentially diminished. CONCLUSIONS: For combinations of rocuronium and pancuronium, the duration of twitch suppression after a maintenance dose is only dependent on the first agent given for the first two maintenance doses administered.

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.

Effect of neuromuscular blockade on oxygen consumption and energy expenditure in sedated, mechanically ventilated children.

OBJECTIVE: To quantify the effects of neuromuscular blockade (NMB) on energy expenditure for intubated, mechanically ventilated, critically ill children. DESIGN: A prospective, unblinded clinical study. Each subject was studied twice, before and after establishment of NMB. SETTING: A tertiary care pediatric intensive care unit. PATIENTS: Critically ill children undergoing mechanical ventilation and receiving ongoing sedation were eligible, if they had a cuffed endotracheal tube and were physiologically stable. INTERVENTIONS: A total of 20 children (age, 1 to 15 yrs) were studied in an unblinded, crossover fashion. All were mechanically ventilated via a cuffed endotracheal tube, with ventilator rate and tidal volume adequate to provide complete ventilation, and F(IO2) <0.6. Absence of gas leak around the endotracheal tube was assured, and all patients were sedated using continuous infusions of midazolam and/or fentanyl; no changes in ventilator settings, nutritional input, or inotropic drug dose were permitted during the study period. Each patient underwent indirect calorimetry immediately before establishment of NMB. NMB was then induced, and indirect calorimetry was repeated. Complete blockade was verified using a peripheral nerve stimulator. In each case, the two sets of measurements were completed within a 1-hr period. MEASUREMENTS AND MAIN RESULTS: Data analyzed included identifying and diagnostic information, oxygen consumption, and carbon dioxide production. Energy expenditure was calculated using standard formulas. Oxygen consumption and energy expenditure values obtained before and after the establishment of NMB were compared by using paired Student's t-test. NMB reduced oxygen consumption from 6.54+/-0.49 mL/kg/min to 5.90+/-0.40 ml/kg/min, and energy expenditure was reduced from 46.5+/-3.7 kcal/kg/24 hrs to 41.0+/-2.8 kcal/kg/24 hrs (p < .001 in each case). The reduction in oxygen consumption was 8.7+/-1.7%, and that in energy expenditure 10.3+/-1.8%, of pre-NMB values, respectively. CONCLUSION: NMB significantly reduces oxygen consumption and energy expenditure in critically ill children who are sedated and mechanically ventilated; the degree of reduction is small.

[Effects of priming technique on onset profile of cisatracurium]. / Auswirkung der Priming-Technik auf die Anschlagszeit von Cisatracurium.

Compared to atracurium, cisatracurium releases less laudanosine and histamine, but it has a longer onset time. The primary objective of this study was a blinded, randomized comparison of intubation scores and onset times of a threefold ED 95 of cisatracurium using the priming technique with two priming substances cisatracurium itself and pancuronium. To test the effect of priming with cisatracurium or pancuronium on the onset of cisatracurium, 45 patients were anaesthetised with 0.15-0.25 mg/kg alfentanil, 0.25-0.3 mg/kg edomidate i.v. and O2/N2O, and were randomisely divided into one of three groups. After induction, 15 patients were primed with sodium chloride and thereafter received 0.15 mg/kg cisatracurium, 15 patients were primed with 0.01 mg/kg cisatracurium, another 15 patients were primed with 0.015 mg/kg pancuronium and the last two groups received 0.14 mg/kg cisatracurium three minutes later. Neuromuscular response was monitored by adductor pollicis electromyogram (EMG) by stimulating in a TOF pattern. Times for T1 reduction to 75%, 50%, 25% and 0% and T1 recovery to 25% were taken. Intubation was performed 120 seconds after the main relaxant dose and scored in four grades. The two priming groups showed a significantly faster onset of neuromuscular blockade than the control group (cisatracurium priming group: T1 = 0: 178.4 +/- 16.3 sec., pancuronium priming group 171.2 +/- 15.3 sec. vs. control group: T1 = 0: 205.5 +/- 18.9 sec.). Both primed groups showed no significantly better intubation scores, compared with the control group. Using the priming principle, cisatracurium will give good intubation scores 120 seconds after injection with a clinical duration profile comparable to an equipotent dose of atracurium.

Tactile evaluation of the response to double burst stimulation decreases, but does not eliminate, the problem of postoperative residual paralysis.

BACKGROUND: Routine perioperative monitoring with accelero-myography might prevent residual block, whereas routine tactile evaluation of the response to train-of-four (TOF) nerve stimulation does not. The purpose of this prospective, randomised and blinded study was to evaluate the effect of manual evaluation of the response to double burst stimulation (DBS3.3) upon the incidence of residual block. METHODS: Sixty adult patients scheduled for elective abdominal surgery were included in the study. Pancuronium 0.08 to 0.1 mg kg-1 was given for relaxation and tracheal intubation. For maintenance of neuromuscular block, pancuronium 1-2 mg was administered. The patients were randomly allocated into two groups. In group DBS (double burst stimulation) the degree of block during anaesthesia was assessed by manual evaluation of the response to TOF nerve stimulation. During reversal, when no fade was detectable in the TOF response, the stimulation pattern was changed to DBS3.3. The trachea was extubated when the anaesthetist judged the neuromuscular function to have recovered adequately and no fade in the DBS3.3 response could be felt. In group CC (clinical criteria) patients were managed without the use of a nerve stimulator, and the level of neuromuscular block and reversal were evaluated solely on the basis of clinical criteria. In both groups, the TOF ratio was measured by mechanomyography immediately after tracheal extubation. Also, the ability to sustain head lift for 5 s, to protrude the tongue, to open the eyes, and to lift one arm to the opposite shoulder were tested. RESULTS: The TOF ratio, as measured immediately after tracheal extubation, was significantly lower in group CC than in group DBS (means: 0.68 and 0.78, respectively), and the incidence of residual neuromuscular block defined as a TOF ratio < 0.7 was significantly higher in group CC than in group DBS (57 and 24%, respectively). The time from the first TOF measurement until the TOF ratio reached 0.8 was significantly longer in group CC than in group DBs (means: 11.5 and 6.2 min, respectively). No significant differences between the two groups of patients were found in duration of anaesthesia, in times from end of surgery to injection of neostigmine, tracheal extubation or TOF ratio 0.8, in dose of pancuronium, or in any other postoperative variable. CONCLUSION: Routine perioperative manual evaluation of the responses to TOF and DBS3.3 decreased the incidence and the degree of residual block following the use of pancuronium. It did not, however, exclude clinically significant residual paralysis, nor did it influence the amount of pancuronium used during the operation, the duration of anaesthesia or the time from end of surgery to tracheal extubation or to sufficient recovery of neuromuscular function (TOF = 0.8).