Reducing the dose of neuromuscular blocking agents with adjuncts: a systematic review and meta-analysis.

BACKGROUND: Acute global shortages of neuromuscular blocking agents (NMBA) threaten to impact adversely on perioperative and critical care. The use of pharmacological adjuncts may reduce NMBA dose. However, the magnitude of any putative effects remains unclear. METHODS: We conducted a systematic review and meta-analysis of RCTs. We searched Medline, Embase, Web of Science, and Cochrane Database (1970-2020) for RCTs comparing use of pharmacological adjuncts for NMBAs. We excluded RCTs not reporting perioperative NMBA dose. The primary outcome was total NMBA dose used to achieve a clinically acceptable depth of neuromuscular block. We assessed the quality of evidence using the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) criteria. Data are presented as the standardised mean difference (SMD); I2 indicates percentage of variance attributable to heterogeneity. RESULTS: From 3082 records, the full texts of 159 trials were retrieved. Thirty-one perioperative RCTs met the inclusion criteria for meta-analysis (n=1962). No studies were conducted in critically ill patients. Reduction in NMBA dose was associated with use of magnesium (SMD: -1.10 [-1.44 to -0.76], P<0.001; I2=85%; GRADE=moderate), dexmedetomidine (SMD: -0.89 [-1.55 to -0.22]; P=0.009; I2=87%; GRADE=low), and clonidine (SMD: -0.67 [-1.13 to -0.22]; P=0.004; I2=0%; GRADE=low) but not lidocaine (SMD: -0.46 [-1.01 to -0.09]; P=0.10; I2=68%; GRADE=moderate). Meta-analyses for nicardipine, diltiazem, and dexamethasone were not possible owing to the low numbers of studies. We estimated that 30-50 mg kg-1 magnesium preoperatively (8-15 mg kg h-1 intraoperatively) reduces rocuronium dose by 25.5% (inter-quartile range, 14.7-31). CONCLUSIONS: Magnesium, dexmedetomidine, and clonidine may confer a clinically relevant sparing effect on the required dose of neuromuscular block ing drugs in the perioperative setting. SYSTEMATIC REVIEW REGISTRATION: PROSPERO: CRD42020183969.

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.

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.

[Assessing the depth-of-hypnosis]. / Måling av narkosedybde.

BACKGROUND: There has been a breakthrough in the understanding of anaesthetic drug effects during the last two decades, and new monitors aimed at quantifying such effects have been developed. MATERIAL AND METHODS: This review is based on publications from the last 15 years, oral presentations, and rewritten parts of the author's PhD thesis. RESULTS: General anaesthesia can be regarded as a combination of hypnosis (sleep), analgesia and muscle relaxation. Modern anaesthetic drugs aim at each of these effects separately. Pharmacological variation makes it impossible to find one dose suitable for all, so tools for measuring drug effects in the individual patient are warranted. Monitors for measuring depth-of-hypnosis and partly analgesic effect are commercially available. Among these, BIS (bispectral index), based on EEG, is by far the best documented. BIS is proven useful for preventing undesired awareness and overdosing, but there are major limitations. Use of such technology in clinical practice is under constant debate. INTERPRETATION: Even though the BIS technology is promising and used widely, no health authorities have so far recommended that such monitors should be compulsory during general anaesthesia, but rather that it should be considered on an individual basis. So far, it seems like this is a sensible approach in Norway as well.

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.

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)

Ultrasound-guided trigger point injections in the cervicothoracic musculature: a new and unreported technique.

BACKGROUND: Myofascial pain is defined as pain that originates from myofascial trigger points in skeletal muscle. It is prevalent in regional musculoskeletal pain syndromes, either alone or in combination with other pain generators. The myofascial pain syndrome is one of the largest groups of under diagnosed and under treated medical problems encountered in clinical practice. Trigger points are commonly seen in patients with myofascial pain which is responsible for localized pain in the affected muscles as well as referred pain patterns. Correct needle placement in a myofascial trigger point is vital to prevent complications and improve efficacy of the trigger point injection to help reduce or relieve myofascial pain. In obese patients, these injections may not reach the target tissue. In the cervicothoracic spine, a misguided or misplaced injection can result in a pneumothorax. Here, we describe an ultrasound-guided trigger point injection technique to avoid this potential pitfall. Office based ultrasound-guided injection techniques for musculoskeletal disorders have been described in the literature with regard to tendon, bursa, cystic, and joint pathologies. For the interventionalist, utilizing ultrasound yields multiple advantages technically and practically, including observation of needle placement in real-time, ability to perform dynamic studies, the possibility of diagnosing musculoskeletal pathologies, avoidance of radiation exposure, reduced overall cost, and portability of equipment within the office setting. To our knowledge, the use of ultrasound guidance in performing trigger point injection in the cervicothoracic area, particularly in obese patients, has not been previously reported. METHODS: A palpable trigger point in the cervicothoracic musculature was localized and marked by indenting the skin with the tip of a plastic needle cover. The skin was then sterile prepped. Then, using an ultrasound machine with sterile coupling gel and a sterile latex free transducer cover, the musculature in the cervicothoracic spine where the palpable trigger point was detected was visualized. Then utilizing direct live ultrasound guidance, a 25-gauge 1.5 inch needle connected to a 3 mL syringe was placed into the muscle at the exact location of the presumed trigger point. This guidance helps confirm needle placement in muscle tissue and not in an adipose tissue or any other non-musculature structure. RESULTS: The technique is simple to be performed by a pain management specialist who has ultrasound system training. CONCLUSION: Ultrasound-guided trigger point injections may help confirm proper needle placement within the cervicothoracic musculature. The use of ultrasound-guided trigger point injections in the cervicothoracic musculature may also reduce the potential for a pneumothorax by an improperly placed injection.

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.

Comparison between use of neuromuscular blocking agent and placebo with the intubating laryngeal mask airway.

INTRODUCTION: The intubating laryngeal mask airway (ILMA) is a specially-designed airway device that can be used for endotracheal intubation without direct laryngoscopy. The advantage of this device is that it allows blind endotracheal intubation with a predictably high success rate. The use of neuromuscular blocking agents in facilitating the use of the ILMA has been investigated in the Western population with a quoted successful intubation rate of 88-96 percent. This randomised, double-blind study aimed to see if the use of neuromuscular blocking agent is necessary for successful intubations. METHODS: A total of 150 patients, rated categories 1 and 2 on the American Society of Anesthesiology Physical Status Classification System, were induced with propofol 2.5 mg/kg and fentanyl 2 microg/kg. After insertion of the ILMA, the patients received either saline or 0.6 mg/kg of rocuronium. After 90 seconds, tracheal intubation was attempted using the specially-designed silicon endotracheal tube. In addition to the success rate of intubation, the incidence of complications was also recorded. RESULTS: The success rate for tracheal intubation within three attempts was 93.3 percent for the saline group and 92.0 percent for the rocuronium group; this was statistically insignificant. The time to securing the airway was 11.5 seconds for the saline group, compared to 10.0 seconds in the rocuronium group, but this was statistically insignificant. The incidence of coughing during insertion of the endotracheal tube was 42.7 percent in the saline group as compared to 1.3 percent in the rocuronium group (p-value is less than 0.001). 12 percent of the patients in the saline group moved during intubation, while none was reported to move in the rocuronium group (p-value is 0.003). These results compared favourably with rates quoted in studies conducted on Western populations. CONCLUSION: The intubating laryngeal mask airway-assisted intubation yields a high success rate, which was similar between the paralysed and non-paralysed patients, with no statistical significance. However, the non-paralysed patients were prone to coughing and movements during intubation, requiring supplemental propofol.

[Analgesia, sedation and relaxation in the child with mechanical ventilation]. / Analgesia, sedación y relajación en el niño con ventilación mecánica.

The basic concepts of sedation and analgesia and the tools to asses the level of sedation and analgesia are review. The different methods of sedation and the non pharmacological interventions are described. Sedatives, analgesics and muscle relaxants, their pharmacodynamics and pharmacokinetics in children, their indications in specific situations (intubation, pain control, sedation and neuromuscular blocking) are reviewed. The etiology of patient-ventilator asynchrony in ventilated children and how to treat it are analyzed, giving guides of how to adapt sedation to the level of mechanical ventilation therapy. Finally, general recommendations are given for the analgesia and sedation in mechanically ventilated children.

Electromyographically guided trigger point injections in the cervicothoracic musculature of obese patients: a new and unreported technique.

BACKGROUND: Myofascial pain is defined as pain that originates from myofascial trigger points in skeletal muscle. It is prevalent in regional musculoskeletal pain syndromes, either alone or in combination with other pain generators. The myofascial pain syndrome is one of the largest groups of under-diagnosed and under-treated medical problems encountered in clinical practice. Trigger points are commonly seen in patients with myofascial pain that can be responsible for localized pain in the affected muscles as well as referred pain patterns. Correct needle placement in a myofascial trigger point is vital to prevent complications and improve efficacy of the trigger point injection to help reduce or relieve myofascial pain. In the obese patients, these injections may not reach the target tissue. In the cervicothoracic spine, a misguided or misplaced injection can result in a pneumothorax. Here, we review an electromyographically guided trigger point injection technique to avoid this potential pitfall. METHODS: Using a disposable Teflon coated hypodermic injection needle attached to an electromyography (EMG) machine, a trigger point injection can be performed utilizing electromyographic guidance. This guidance by observing motor unit action potentials (MUAPs) on the EMG screen helps confirm the needle placement to be within the muscle tissue and not in an adipose tissue or any other non-musculature structure. RESULTS: The technique is simple when performed by a pain management specialist who has electromyographic training. CONCLUSION: This technique helps confirm proper needle placement within the cervicothoracic musculature in an obese patient in whom the musculature is not readily palpated. This, thus, reduces the potential for a pneumothorax by an improperly placed injection.

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.

Neurosedative and muscle-relaxant activities of ethyl acetate extract of Baphia nitida AFZEL.

The sedative, anxiolytic and muscle-relaxant effects of the ethyl acetate leaf extract of Baphia nitida (BN) was investigated in intact mice, using the hole-board head-dip test for exploratory behavioural effect, elevated plus maze (EPM) and Y-maze (YM) models of anxiety; chimney, inclined screen, traction and climbing tests for muscle-relaxant effects. In each of these tests, BN (100-400mg/kg, p.o.), diazepam (1mg/kg, i.p.) or distilled water (10ml/kg, p.o.) was administered, 30 or 60min before performing the tests in mice. For exploratory behavioural test, number of head-dip within 15min was counted. For EPM and YM tests, the cumulative time spent in open and closed arms was recorded within 5min. In the muscle-relaxant tests, mice were subjected to modified models such as chimney, inclined screen, traction and climbing tests. BN produced a significant (P<0.05) dose-related decrease in exploratory behaviour in the head-dip test and prolongation of cumulative time spent in open arms of both EPM and YM. BN did not show any significant effect in the chimney and traction tests, but produced significant, dose-dependent muscle relaxation in the inclined screen and climbing tests. Furthermore, BN (200-1200microg/ml) non-competitively shifted the curves of acetylcholine contractions of the toad Rectus abdominis muscle to the right. Oral doses of BN (0.1-20g/kg) did not produce mortality, but the LD(50) when given intraperitoneally, was 645.65mg/kg. Results suggest that the leaf extract of Baphia nitida has sedative, anxiolytic and skeletal muscle-relaxant effects and support its neurosedative use in traditional African medicine.

Neurosedative and muscle relaxant activities of aqueous extract of Bryophyllum pinnatum.

The saline leaf extract of Bryophyllum pinnatum was investigated on neuropharmacological activities to ascertain claims of local use. When tested in mice, it produced a dose-dependent prolongation of onset and duration of pentobarbitone-induced hypnosis, reduction of exploratory activities in the head-dip and evasion tests. Moreover, a dose-dependent muscle in-coordination was observed in the inclined screen, traction and climbing tests. It delayed onset to convulsion in both strychnine- and picrotoxin-induced seizures in addition to minimal protection against picrotoxin seizures.

Choice of the hypnotic and the opioid for rapid-sequence induction.

The choice of hypnotics and opioids for rapid-sequence induction, and the use of premedication, is influenced by the choice of the muscle relaxant. Anaesthetic agents have a major influence on the quality of intubation when rapid-sequence induction is achieved without a muscle relaxant. Premedication is important, along with a high dose of propofol (2.5 mg kg-1 or more) and a short-acting opioid such as alfentanil (30-40 micrograms kg-1) or remifentanil (up to 4 micrograms kg-1). It has also been demonstrated that i.v. lidocaine can improve intubating conditions. When a muscle relaxant is used, the choice of the anaesthetic agents depends on the onset of action of the relaxant. With a rapid-acting compound such as rocuronium at a dose of 0.6 mg kg-1, the hypnotic agents need to be supplemented with only a small dose of opioids, e.g. alfentanil 10-20 micrograms kg-1. When succinylcholine, rocuronium 1.0 mg kg-1 or rapacuronium 1.5 mg kg-1 are used, excellent intubating conditions may be obtained by relatively smaller doses of hypnotic agents even without opioids; however, haemodynamic and intraocular pressure changes are better controlled when small doses of opioids are administered.

[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.

Clinical pharmacology of neuromuscular blocking agents.

The clinical pharmacology of neuromuscular blocking agents is described. During neuromuscular blockade, succinylcholine attaches to receptors in the motor end plate and depolarizes the neuromuscular junction, making the end plate refractory to acetylcholine. The nondepolarizing relaxants have a structure similar to that of succinylcholine and bind to the same receptors. Instead of depolarizing the junction, they block acetylcholine from binding to the receptor and cause channel blockade. As the concentration of nondepolarizing relaxant increases relative to acetylcholine, neuromuscular transmission is compromised. This relationship is used clinically to facilitate recovery from nondepolarizing agents. Succinylcholine is popular because its onset is faster than that of the nondepolarizing relaxants and metabolism by pseudocholinesterase clears it quickly. It is commonly given as an i.v. bolus to facilitate tracheal intubation. The onset of these agents varies widely and is dose dependent. Large doses are usually given to hasten the onset of paralysis; subsequent doses are adjusted according to response. The nondepolarizing agents interact with inhaled anesthetics, magnesium, and many antimicrobials. Drugs like neostigmine, edrophonium, and pyridostigmine antagonize neuromuscular blockade; an anticholinergic drug is typically administered to counteract the cardiovascular effects. The most serious adverse effects of succinylcholine are malignant hyperthermia syndrome, masseter muscle rigidity, and bradycardia. Some nondepolarizing relaxants (atracurium, mivacurium, and pancuronium) are associated with histamine release, occasionally causing serious hypotension and tachycardia. Neuromuscular blocking agents are essential to anesthesia. Older compounds produce greater toxicity than newer compounds, and several of these older compounds therefore are no longer in clinical use.