Combined opioid free and loco-regional anaesthesia enhances the quality of recovery in sleeve gastrectomy done under ERAS protocol: a randomized controlled trial.

BACKGROUND: It is debatable whether opioid-free anaesthesia (OFA) is better suited than multimodal analgesia (MMA) to achieve the goals of enhanced recovery after surgery (ERAS) in patients undergoing laparoscopic sleeve gastrectomy. METHODS: In all patients, anaesthesia was conducted with an i.v. induction with propofol (2 mg. kg-1), myorelaxation with cisatracurium (0.15 mg.kg-1), in addition to an ultrasound-guided bilateral oblique subcostal transverse abdominis plane block. In addition, patients in the OFA group (n = 51) received i.v. dexmedetomidine 0.1 µg.kg-1 and ketamine (0.5 mg. kg-1) at induction, then dexmedetomidine 0.5 µg. kg-1.h-1, ketamine 0.5 mg.kg-1.h-1, and lidocaine 1 mg. kg-1.h-1 for maintenance, while patients in the MMA group (n = 52) had only i.v. fentanyl (1 µg. kg-1) at induction. The primary outcome was the quality of recovery assessed by QoR-40, at the 6th and the 24th postoperative hour. Secondary outcomes were postoperative opioid consumption, time to ambulate, time to tolerate oral fluid, and time to readiness for discharge. RESULTS: At the 6th hour, the QoR-40 was higher in the OFA than in the MMA group (respective median [IQR] values: 180 [173-195] vs. 185 [173-191], p < 0.0001), but no longer difference was found at the 24th hour (median values = 191 in both groups). OFA also significantly reduced postoperative pain and morphine consumption (20 mg [1-21] vs. 10 mg [1-11], p = 0.005), as well as time to oral fluid tolerance (238 [151-346] vs. 175 min [98-275], p = 0.022), and readiness for discharge (505 [439-626] vs. 444 min [356-529], p = 0.001), but did not influence time to ambulate. CONCLUSION: While regional anaesthesia achieved most of the intraoperative analgesia, avoiding intraoperative opioids with the help of this OFA protocol was able to improve several sensible parameters of postoperative functional recovery, thus improving our knowledge on the OFA effects. CLINICAL TRIAL NUMBER: Registration number NCT04285255.

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 novel use of different bupivacaine preparations with combined regional techniques for postoperative pain management in non-opioid-based laparoscopic inguinal herniorrhaphy.

Opioids are important for surgical pain control but may not be appropriate for patients with narcotic abuse histories or opioid intolerance. We describe a laparoscopic bilateral inguinal herniorrhaphy performed without perioperative or postoperative narcotics. Postoperative analgesia involves a novel technique using 2 different bupivacaine formulations that act synergistically to avoid lag time and provide extended pain relief during the acute surgical recovery phase.

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.

Physical compatibility of cisatracurium with selected drugs during simulated Y-site administration.

PURPOSE: The physical compatibility of cisatracurium with selected drugs during simulated Y-site administration was studied. METHODS: Study drugs were selected based on the lack of physical compatibility data with cisatracurium and their use in intensive care units. Test admixtures were prepared by mixing 2.5-mL samples of varying concentrations of calcium gluconate, diltiazem, esomeprazole, regular insulin, nicardipine, pantoprazole, and vasopressin with either 2.5 mL of normal saline 0.9% (control) or 2.5 mL of cisatracurium (experimental) to simulate a 1:1 Y-site ratio. Drug infusions were prepared at the maximum concentrations used clinically. Physical compatibility of the admixtures was determined by visual and turbidimetric assessments performed in triplicate immediately after mixing and at 15, 30, and 60 minutes. Visual incompatibility was defined as a change in color, the formation of haze or precipitate, the presence of particles, or the formation of gas in the experimental groups compared with the controls. Disturbances invisible to the naked eye were determined by assessing changes in turbidity of experimental admixtures compared with the controls. RESULTS: None of the admixtures exhibited visual changes when mixed with cisatracurium. Six of the seven admixtures exhibited turbidimetric compatibility with cisatracurium. Pantoprazole admixtures demonstrated a significant difference in turbidimetric assessment between the control and experimental groups when mixed with cisatracurium (p < 0.001). CONCLUSION: Calcium gluconate, diltiazem hydrochloride, esomeprazole, regular insulin, nicardipine hydrochloride, and vasopressin demonstrated physical compatibility with cisatracurium over 60 minutes during simulated Y-site administration. Cisatracurium and pantoprazole should not be coadministered due to a significant difference in turbidity between control and experimental samples.

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.

[Pharmacological therapies for ARDS].

Acute respiratory distress syndrome (ARDS) is a noncardiogenic pulmonary edema resulting from increased capillary permeability. Numerous pharmacologic therapies have been studied for prevention and treatment of ARDS. Although several pharmacological therapies could improve patient's respiratory function, there have been no controlled studies which clearly demonstrated the clinical benefit for ARDS-related mortality. The role of corticosteroids in ARDS remains controversial. Available evidence is against early administration of high-dose corticosteroids (methylprednisolon 120 mg x kg-1 x day - 1). In contrast, low-dose corticosteroid therapy (methylprednisolon 0.5-2.5mgg kg-1 xday-1)remains controversial. With regard to sivelestat sodium, a specific inhibitor of neutrophil elastase, although the effectiveness in decreasing mortality was not clarified, increases in lung oxygenation and ventilator-free days have consistently been revealed. Other probable pharmacologic therapies for ARDS include continuous infusion of cisatracurium. In conclusion, there are not established drugs for ARDS, and further studies are necessary to reveal the clinical effectiveness of the above mentioned and novel pharmacologic therapies.

Effects on Intubating Conditions of Pretreatment with Remifentanil before Administration of Cisatracurium / 전남의대학술지

Cisatracurium provides superior hemodynamic stability with only minor release of histamine, and its metabolism via Hoffman elimination is independent of organ function. However, use of cisatracurium is limited because of reportedly slower onset and unsatisfactory intubating conditions. Many studies have shown that remifentanil might provide reliable intubating conditions; thus, we hypothesized that pretreatment with remifentanil before administration of cisatracurium might result in acceptable intubating conditions. Sixty healthy patients scheduled for elective surgery were enrolled and randomly divided into three groups: saline (Group I, n=20), remifentanil 0.5 microg/kg (Group II, n=20), and remifentanil 1.0 microg/kg (Group III, n=20). The anesthesia was induced with propofol 2.0 microg/kg given intravenously over 30 s followed by injection over 30 s of a different dose of remifentanil according to the study protocol. We examined the intubating condition by jaw relaxation, vocal cord state, and diaphragmatic response 90 s after administering cisatracurium. We also measured mean blood pressure, heart rate, and the onset time, which is the interval from the end of neuromuscular blocking agent administration until suppression of maximal T1 on a train-of four sequence. The mean values of the intubating condition after endotracheal intubation in Groups II and III were significantly lower than that in Group I (p<0.005), although the overall onset time of cisatracurium did not differ significantly between the three groups. Our results suggest that supplementation with remifentanil in an induction regimen with cisatracurium improves the quality of the intubating condition even though the onset time of cisatracurium is not shortened.

Effects on Intubating Conditions of Pretreatment with Remifentanil before Administration of Cisatracurium / 전남의대학술지

Cisatracurium provides superior hemodynamic stability with only minor release of histamine, and its metabolism via Hoffman elimination is independent of organ function. However, use of cisatracurium is limited because of reportedly slower onset and unsatisfactory intubating conditions. Many studies have shown that remifentanil might provide reliable intubating conditions; thus, we hypothesized that pretreatment with remifentanil before administration of cisatracurium might result in acceptable intubating conditions. Sixty healthy patients scheduled for elective surgery were enrolled and randomly divided into three groups: saline (Group I, n=20), remifentanil 0.5 microg/kg (Group II, n=20), and remifentanil 1.0 microg/kg (Group III, n=20). The anesthesia was induced with propofol 2.0 microg/kg given intravenously over 30 s followed by injection over 30 s of a different dose of remifentanil according to the study protocol. We examined the intubating condition by jaw relaxation, vocal cord state, and diaphragmatic response 90 s after administering cisatracurium. We also measured mean blood pressure, heart rate, and the onset time, which is the interval from the end of neuromuscular blocking agent administration until suppression of maximal T1 on a train-of four sequence. The mean values of the intubating condition after endotracheal intubation in Groups II and III were significantly lower than that in Group I (p<0.005), although the overall onset time of cisatracurium did not differ significantly between the three groups. Our results suggest that supplementation with remifentanil in an induction regimen with cisatracurium improves the quality of the intubating condition even though the onset time of cisatracurium is not shortened.

Magnesium sulphate has beneficial effects as an adjuvant during general anaesthesia for Caesarean section.

BACKGROUND: The use of low concentrations of volatile anaesthetics with avoidance of opioids may induce intraoperative awareness and adverse haemodynamic responses during Caesarean section. Magnesium is well known to reduce anaesthetic requirements and to block noxious stimuli. We investigated whether i.v. magnesium sulphate modulates anaesthetic depth and analgesic efficacy during Caesarean section. METHODS: Seventy-two patients undergoing Caesarean section were randomly assigned to receive i.v. saline (control group) or magnesium sulphate 30 mg kg(-1) bolus+10 mg kg(-1) h(-1) continuous infusion (Mg 30 group) or 45 mg kg(-1) bolus+15 mg kg(-1) h(-1) continuous infusion (Mg 45 group) after induction. Bispectral index (BIS) value, mean arterial pressure (MAP), and midazolam, fentanyl, and atracurium consumptions were recorded. RESULTS: BIS values [mean (sd)] at 7.5 and 10 min after surgery and before delivery in the control [64 (9), 66 (8), 67 (8), P<0.001] and the Mg 30 groups [62 (8), P<0.01; 64 (7), 63 (9), P<0.001] were higher than in the Mg 45 group [56 (8), 55 (8), 55 (7)]. MAP was greater in the control group (P<0.05) than in the Mg 30 and Mg 45 groups during the pre-delivery period. The magnesium groups required less midazolam (P<0.05), fentanyl (Mg 30, P<0.05; Mg 45, P<0.01), and atracurium (P<0.001) vs the control group. CONCLUSIONS: Preoperative i.v. magnesium sulphate attenuated BIS and arterial pressure increases during the pre-delivery period. Magnesium sulphate can be recommended as an adjuvant during general anaesthesia for Caesarean section to avoid perioperative awareness and pressor response resulting from inadequate anaesthesia, analgesia, or both.

Atracurium during induced hyperthermia.

During hyperthermic intraperitoneal chemotherapy (HIPEC), we observed a partial recovery from neuromuscular block in a hyperthermic patient after hours of monitored adequate surgical relaxation and continuous infusion of atracurium during normothermia. This recovery is indicative of the higher clearance of atracurium during hyperthermia. This case report emphasizes the clinical relevance of the well-known temperature dependence of the Hofmann elimination of atracurium. Moreover, this report illustrates the importance of monitoring muscle relaxation during HIPEC. Clinicians should be aware that the usual continuous infusion rate of atracurium at 0.3 mg.kg(-1).h(-1) may be inadequate in hyperthermic patients.

Corrección de la curva dosis-respuesta acumulativa de atracurio y rocuronio / Correction of the cumulative dose-response to atracurium and rocurionium

Introducción: La curva dosis-respuesta acumulativa es un método práctico para evaluar las dosis efectivas de atracurio y rocuronio. Debido a sus características farmacocinéticas, los resultados de dicha curva subestiman la potencia de ambos fármacos en comparación con los que resultan de la administración de dosis únicas. El objetivo de la presente investigación es corregir aquella técnica y hacer las dos estadísticamente equivalentes. Material y métodos: En dos grupos de pacientes electivos se utilizó atracurio o rocuronio para calcular sus potencias por el método de las dosis únicas (n = 45 c/u) o acumulativas (n = 11 c/u). El efecto de cada dosis se determinó por electromiografía, y después de sus transformaciones logaritmo-probits, considerando gamma como la relación probit/log, se obtuvieron las DE 50 y 90 resolviendo la ecuación de Hill para cada sujeto. La técnica acumulativa se corrigió al utilizar las cifras actuales para las dosis y sus efectos, en lugar de los valores acumulativos a partir de la segunda administración. Resultados: Las DE 50 de las técnicas de dosis única, acumulativa y corregida fueron: 172 ± 73, 264 ± 52 y 162 ± 81 mcg/kg respectivamente, cuando se utilizó rocuronio, y 141 ± 61, 193 ± 53 y 141 ± 70 respectivamente, cuando se utilizó atracurio. En el caso de las DE 90 los valores fueron 233 ± 98, 327 ± 65, 254 ± 126 y 222 ± 96, 279 ± 77 y 254 ± 126, en el mismo orden. No se detectaron diferencias significativas entre los métodos de dosis única y corregida, mientras que los valores de las dosis acumulativas fueron significativamente mayores. Discusión y conclusiones: En las condiciones de la presente investigación, una sencilla corrección del método acumulativo reproduce razonable y estadísticamente la potencia del atracurio y del rocuronio evaluada por las dosis únicas.(AU)

Introduction: The cumulative dose-response curve is a practical method to evaluate the effective doses of atracurium and rocuronium. When compared with those obtained by single administrations, the resulting figures underestimate their potency due to pharmacokinetic features. The purpose of this trial is to correct the cumulative technique and to make both statistically equivalent. Material & Methods: Single (n = 45 e/a) or cumulative (n = 11 e/a) doses of atracurium or rocuronium were administered to elective patients and maximal effect assessed by electromyography. A regression line was obtained after log dose-probit effect transformation, and considering gamma as the probit/log ratio, ED 50 and 90 were calculated resolving the Hill equation for each patient. The cumulative technique was corrected by using actual figures instead of cumulative ones, starting at second administration. Results: ED 50 were 172 ± 73, 264 ± 52 y 162 ± 81 mcg/kg as single, cumulative dose or corrected respectively for rocuronium and 141 ± 61, 193 ± 53 y 141 ± 70 for atracurium. ED 90 was 233 ± 98,327 ± 65, 254 ± 126, 222 ± 96, 279 ± 77 y 254 ± 126 in the same order. Non-significant differences between single dose and corrected method were noticed. Cumulative values were significantly larger. Conclusion: In keeping with the conditions of the present trial, a simple correction made to the cumulative method reasonably and statistically reproduces atracurium and rocuronium potencies evaluated by single dose-responses technique.(AU)

IntroduþÒo: A curva dose-resposta acumulativa é um método prático de avaliaþÒo das doses efetivas de atracúrio e rocuronio. Dada suas características farmacocinéticas, os resultados dessa curva subestimam a potÛncia de ambos fármacos em comparaþÒo com os resultados decorrentes da administraþÒo de dose únicas. O objetivo da presente pesquisa é corrigir aquela técnica e tornar as duas estatisticamente equivalentes. Material e métodos: Dois grupos de pacientes eletivos receberam atracúrio ou rocur¶nio com o objetivo de calcular as potÛncias destes fármacos pelo método das doses únicas (n = 45 c/u) ou acumulativas (n = 11 c/u). Foi determinado o efeito de cada dose por eletromiografia, e por transformaþÒo log-probits (considerando gama a relaþÒo probit/log), obtiveram-se as DE 50 e 90 resolvendo a equaþÒo de Hill para cada sujeito. A técnica acumulativa foi corrigida utilizando as cifras atuais para doses e seus efeitos, em lugar dos valores acumulativos, a partir da segunda administraþÒo. Resultados: As DE 50 das técnicas de dose única, acumulativa e corrigida foram: 172 ± 73, 264 ± 52 e 162 ± 81 mcg/kg, respectivamente, quando se utilizou rocur¶nio, e 141 ± 61, 193 ± 53 e 141 ± 70, respectivamente, quando se utilizou atracúrio. No caso das DE 90 os valores foram 233 ± 98, 327 ± 65, 254 ± 126 e 222 ± 96, 279 ± 77 e 254 ± 126, na mesmo ordem. NÒo foram observadas diferenþas significativas entre os métodos (de dose única e corrigida), ao passo que os valores das doses acumulativas foram significativamente maiores. DiscussÒo e conclus§es: Nas condiþ§es da presente pesquisa, uma simples correþÒo do método acumulativo reproduz de forma razoável e estatisticamente as potÛncias do atracúrio e rocuronio avaliadas por doses únicas.(AU)

Corrección de la curva dosis-respuesta acumulativa de atracurio y rocuronio / Correction of the cumulative dose-response to atracurium and rocurionium

Introducción: La curva dosis-respuesta acumulativa es un método práctico para evaluar las dosis efectivas de atracurio y rocuronio. Debido a sus características farmacocinéticas, los resultados de dicha curva subestiman la potencia de ambos fármacos en comparación con los que resultan de la administración de dosis únicas. El objetivo de la presente investigación es corregir aquella técnica y hacer las dos estadísticamente equivalentes. Material y métodos: En dos grupos de pacientes electivos se utilizó atracurio o rocuronio para calcular sus potencias por el método de las dosis únicas (n = 45 c/u) o acumulativas (n = 11 c/u). El efecto de cada dosis se determinó por electromiografía, y después de sus transformaciones logaritmo-probits, considerando gamma como la relación probit/log, se obtuvieron las DE 50 y 90 resolviendo la ecuación de Hill para cada sujeto. La técnica acumulativa se corrigió al utilizar las cifras actuales para las dosis y sus efectos, en lugar de los valores acumulativos a partir de la segunda administración. Resultados: Las DE 50 de las técnicas de dosis única, acumulativa y corregida fueron: 172 ± 73, 264 ± 52 y 162 ± 81 mcg/kg respectivamente, cuando se utilizó rocuronio, y 141 ± 61, 193 ± 53 y 141 ± 70 respectivamente, cuando se utilizó atracurio. En el caso de las DE 90' los valores fueron 233 ± 98, 327 ± 65, 254 ± 126 y 222 ± 96, 279 ± 77 y 254 ± 126, en el mismo orden. No se detectaron diferencias significativas entre los métodos de dosis única y corregida, mientras que los valores de las dosis acumulativas fueron significativamente mayores. Discusión y conclusiones: En las condiciones de la presente investigación, una sencilla corrección del método acumulativo reproduce razonable y estadísticamente la potencia del atracurio y del rocuronio evaluada por las dosis únicas.

Introduction: The cumulative dose-response curve is a practical method to evaluate the effective doses of atracurium and rocuronium. When compared with those obtained by single administrations, the resulting figures underestimate their potency due to pharmacokinetic features. The purpose of this trial is to correct the cumulative technique and to make both statistically equivalent. Material & Methods: Single (n = 45 e/a) or cumulative (n = 11 e/a) doses of atracurium or rocuronium were administered to elective patients and maximal effect assessed by electromyography. A regression line was obtained after log dose-probit effect transformation, and considering gamma as the probit/log ratio, ED 50 and 90 were calculated resolving the Hill equation for each patient. The cumulative technique was corrected by using actual figures instead of cumulative ones, starting at second administration. Results: ED 50 were 172 ± 73, 264 ± 52 y 162 ± 81 mcg/kg as single, cumulative dose or corrected respectively for rocuronium and 141 ± 61, 193 ± 53 y 141 ± 70 for atracurium. ED 90 was 233 ± 98,327 ± 65, 254 ± 126, 222 ± 96, 279 ± 77 y 254 ± 126 in the same order. Non-significant differences between single dose and corrected method were noticed. Cumulative values were significantly larger. Conclusion: In keeping with the conditions of the present trial, a simple correction made to the cumulative method reasonably and statistically reproduces atracurium and rocuronium potencies evaluated by single dose-responses technique.

Introdução: A curva dose-resposta acumulativa é um método prático de avaliação das doses efetivas de atracúrio e rocuronio. Dada suas características farmacocinéticas, os resultados dessa curva subestimam a potência de ambos fármacos em comparação com os resultados decorrentes da administração de dose únicas. O objetivo da presente pesquisa é corrigir aquela técnica e tornar as duas estatisticamente equivalentes. Material e métodos: Dois grupos de pacientes eletivos receberam atracúrio ou rocurônio com o objetivo de calcular as potências destes fármacos pelo método das doses únicas (n = 45 c/u) ou acumulativas (n = 11 c/u). Foi determinado o efeito de cada dose por eletromiografia, e por transformação log-probits (considerando gama a relação probit/log), obtiveram-se as DE 50 e 90 resolvendo a equação de Hill para cada sujeito. A técnica acumulativa foi corrigida utilizando as cifras atuais para doses e seus efeitos, em lugar dos valores acumulativos, a partir da segunda administração. Resultados: As DE 50 das técnicas de dose única, acumulativa e corrigida foram: 172 ± 73, 264 ± 52 e 162 ± 81 mcg/kg, respectivamente, quando se utilizou rocurônio, e 141 ± 61, 193 ± 53 e 141 ± 70, respectivamente, quando se utilizou atracúrio. No caso das DE 90' os valores foram 233 ± 98, 327 ± 65, 254 ± 126 e 222 ± 96, 279 ± 77 e 254 ± 126, na mesmo ordem. Não foram observadas diferenças significativas entre os métodos (de dose única e corrigida), ao passo que os valores das doses acumulativas foram significativamente maiores. Discussão e conclusões: Nas condições da presente pesquisa, uma simples correção do método acumulativo reproduz de forma razoável e estatisticamente as potências do atracúrio e rocuronio avaliadas por doses únicas.

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.

Laryngeal injuries and intubating conditions with or without muscular relaxation: an equivalence study.

PURPOSE: The need for muscular relaxation to improve intubating conditions and to reduce the incidence of laryngeal morbidity is still controversial. The aim of this study was to determine the incidence of symptomatic laryngeal injuries (SLI) and of acceptable intubating conditions (including both good and excellent conditions), both with and without cisatracurium during induction of anesthesia, along with moderate doses of remifentanil and propofol. METHODS: In this prospective, randomized double-blind equivalence trial, the intubating conditions were compared in 130 ASA I or II female patients. All subjects received remifentanil 2 microg x kg(-1) i.v. and propofol 2.5 mg x kg(-1) i.v., with either cisatracurium 0.15 mg x kg(-1) i.v. (group Cisatracturium), or saline (group Placebo). Tracheal intubating conditions were assessed with the Copenhagen Score. A systematic screening for postoperative hoarseness and sore throat was performed 24 and 48 hr after anesthesia, followed by a nasofibroscopic examination when laryngeal symptoms persisted at 48 hr. RESULTS: Twenty-four hr after anesthesia, the incidence of postoperative hoarseness and sore throat in the Cisatracurium and Placebo groups was 26.5% and 21.5%, respectively, and 48 hr after anesthesia, the incidence was 7.8% and 6.1%, respectively (P = 0.32 and P = 0.50 between groups, respectively). In the clinically evaluable population, the incidence of SLI, assessed at 48 hr by nasofibroscopy, was equivalent in both groups, 1.6% vs 1.5% in group Placebo and group Cisatracurium, respectively (P < 0.001 for equivalence test), as was the occurrence of acceptable intubating conditions (95.4% vs 100%, P < 0.05 for equivalence test). However, the occurrence of excellent intubating conditions was more frequent in group Cisatracurium than in group Placebo (P = 0.0003). CONCLUSION: Following induction of anesthesia with propofol and moderate-dose remifentanil, cisatracurium did not confer a higher rate of good-to-excellent conditions for tracheal intubation, nor did muscle relaxation with cisatracurium decrease the rate of SLI after tracheal intubation.

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.

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.