Reversal of mivacurium-induced neuromuscular blockade with a cholinesterase inhibitor: A systematic review.

BACKGROUND: Mivacurium is a short-acting non-depolarizing muscle relaxant, which is hydrolyzed by butyrylcholinesterase. The neuromuscular block (NMB) can be antagonized with cholinesterase inhibitors (CHEI), but the short duration of action of mivacurium questions the need. This systematic review evaluated if the use of CHEIs (neostigmine, pyridostigmine or edrophonium) facilitates reversal of mivacurium-induced NMB. METHOD: Randomized controlled trials and crossover-studies comparing spontaneous recovery with CHEI reversal in patients with mivacurium-induced NMB, assessed with quantitative neuromuscular monitoring, were included. Mean time from injection of the CHEI or allowing of spontaneous recovery to an endpoint representing full recovery was used as outcome. First response to train-of-four nerve stimulation (T1 ) described the level of NMB for administration of the CHEI. Moderate NMB refers to T1  ≥ 5% and deeper NMB refers to T1  < 5%. Systematic critical appraisal was performed using the Scottish Intercollegiate Guidelines Network guidelines. Overall quality assessment was done using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: Sixteen studies with data from 546 patients were included. Low quality of evidence was found that neostigmine and edrophonium administered at moderate NMB accelerated recovery with up to approximately 5.5-6.5 and 6.5-9.0 minutes, respectively. At deeper NMB only edrophonium accelerated recovery. The effect of neostigmine was not clarified at deeper mivacurium-induced NMB. No studies with reversal by pyridostigmine were identified. CONCLUSION: Low quality of evidence supports that neostigmine and edrophonium accelerate the recovery of mivacurium-induced NMB with 5-6.5 and 6-9.0 minutes respectively, when administered at moderate NMB. At deeper NMB only edrophonium accelerated the recovery.

Influence of intense neuromuscular blockade on surgical conditions during laparotomy: a pig model.

PURPOSE: Intense neuromuscular block may improve surgical conditions in ileus laparotomies; however, it is difficult to evaluate. The aim of this study was to investigate if neuromuscular block improved surgical conditions in pigs with artificial ileus laparotomy. METHODS: Six pigs were endotracheally intubated, mechanically ventilated, anesthetized with propofol and fentanyl, and randomized into two groups in a cross-over assessor-blinded design. Neuromuscular block was established with rocuronium. Artificial laparotomy for ileus was performed. We investigated the influence of intense neuromuscular block on surgical conditions with a subjective rating scale, force needed to close the fascia, incidences of abdominal contractions while suctioning the lungs, width of the wound diastase and operating time as outcome parameters. RESULTS: In all six pigs no abdominal contractions occurred while suctioning the lungs at intense neuromuscular block. Without neuromuscular block we detected abdominal contractions seen as hiccups and bucking. In all six pigs during intense neuromuscular block we found no visible electromyographic (EMG) activity in the abdominal muscles while suctioning the lungs. Without neuromuscular block suctioning the lungs elicited brief periods of abdominal EMG activity. No difference was found in the force needed to close the fascia when comparing no neuromuscular block with intense neuromuscular block. Furthermore, no significant differences were found in the width of the diastase, operating time and subjective ratings using a four-point rating scale when comparing no neuromuscular block with intense neuromuscular block. However, these outcomes were related to the order of the suturing round. CONCLUSION: Intense neuromuscular block prevented abdominal muscle contractions but did not influence the force needed to close the fascia.

Response to succinylcholine in patients carrying the K-variant of the butyrylcholinesterase gene.

BACKGROUND: Succinylcholine is usually metabolized quickly by the butyrylcholinesterase enzyme (BChE) but genetic variants of BChE may prolong the duration of action. The Kalow (K) variant is the most common mutation in the butyrylcholinesterase gene (BCHE), being present in 25% of Caucasians. The significance of the K-variant for the duration of action of succinylcholine has not been well studied. Our hypothesis was that the duration of action of succinylcholine would be prolonged in patients heterozygous for the K-variant genotype compared with the normal genotype (wild-type). METHODS: We included 70 adult surgical patients who received succinylcholine 1 mg/kg for rapid sequence induction. Neuromuscular monitoring was performed using ulnar nerve stimulation and acceleromyography. Duration of action of succinylcholine was defined as the time to 90% recovery of first twitch in train-of-four (T(1) 90%), BChE activity was determined, and the presence of BCHE K and A (atypical) variants were determined using DNA analysis. RESULTS: The wild-type BCHE was present in 38 patients, and 21 were heterozygous for the K-variant. Mean (SD) T(1) 90% in patients heterozygous for the K-variant, 11.6 (3.5) minutes, was longer than in patients with the wild-type genotype, 9.5 (2.7) minutes (P = 0.023), with a mean (95% confidence interval) difference of 2.1 (0.3-4.0) minutes. Patients heterozygous for the K-variant had a BChE activity of 5978 U/L compared with 7703 U/L in the wild-type group (P = 0.0045). CONCLUSION: We conclude that the mean duration of action of succinylcholine is prolonged for the patient heterozygous for the K-variant allele by at most 4 minutes relative to the wild-type, but this difference is small relative to the wide variability and overlap in recovery times among all patients.

Deep neuromuscular blockade and low insufflation pressure during laparoscopic hysterectomy.

INTRODUCTION: Establishment of sufficient muscle relaxation is essential in laparoscopic surgery. During laparoscopy, surgeons can experience abdominal contractions in their patients. Deep neuromuscular block (NMB) has the potential to prevent such episodes. In this study, we explored if deep NMB reduces the incidence of sudden abdominal contractions as compared with standard NMB. METHODS: This was a pre-planned secondary analysis of a randomized, controlled study. A total of 110 patients scheduled for laparoscopic hysterectomy were randomized to either deep NMB and 8 mmHg pneumoperitoneum (deep NMB group) or single-bolus NMB and 12 mmHg pneumoperitoneum (standard NMB group). NMB was established with rocuronium and reversed with sugammadex. Two gynaecologists registered episodes of sudden abdominal contractions, alarms from the insufflator due to increased intraabdominal pressure and incidences with tightness of the abdominal wall. RESULTS: No sudden abdominal contractions were detected in the deep NMB group as compared with 12 episodes in the standard NMB group (p < 0.001). The insufflator alarmed in no versus ten procedures (p = 0.001) in the deep and standard NMB group, respectively. The gynaecologists registered increasing abdominal tensions in no versus eight procedures (p = 0.006) in the deep and standard NMB group, respectively. CONCLUSION: Deep NMB in combination with 8 mmHg pneumoperitoneum prevented sudden abdominal contractions during laparoscopic hysterectomy. FUNDING: This work was funded in part by a research grant from the Investigator Initiated Studies Program of Merck Sharp & Dohme Corp, USA. The opinions expressed in this paper are those of the authors and do not necessarily represent those of Merck Sharp & Dohme Corp. TRIAL REGISTRATION: The study was assigned with EudraCT number 2012-003787-51 and registered with clinicaltrials.gov (NCT01722097).

Improving Neuromuscular Monitoring and Reducing Residual Neuromuscular Blockade With E-Learning: Protocol for the Multicenter Interrupted Time Series INVERT Study.

BACKGROUND: Muscle relaxants facilitate endotracheal intubation under general anesthesia and improve surgical conditions. Residual neuromuscular blockade occurs when the patient is still partially paralyzed when awakened after surgery. The condition is associated with subjective discomfort and an increased risk of respiratory complications. Use of an objective neuromuscular monitoring device may prevent residual block. Despite this, many anesthetists refrain from using the device. Efforts to increase the use of objective monitoring are time consuming and require the presence of expert personnel. A neuromuscular monitoring e-learning module might support consistent use of neuromuscular monitoring devices. OBJECTIVE: The aim of the study is to assess the effect of a neuromuscular monitoring e-learning module on anesthesia staff's use of objective neuromuscular monitoring and the incidence of residual neuromuscular blockade in surgical patients at 6 Danish teaching hospitals. METHODS: In this interrupted time series study, we are collecting data repeatedly, in consecutive 3-week periods, before and after the intervention, and we will analyze the effect using segmented regression analysis. Anesthesia departments in the Zealand Region of Denmark are included, and data from all patients receiving a muscle relaxant are collected from the anesthesia information management system MetaVision. We will assess the effect of the module on all levels of potential effect: staff's knowledge and skills, patient care practice, and patient outcomes. The primary outcome is use of neuromuscular monitoring in patients according to the type of muscle relaxant received. Secondary outcomes include last recorded train-of-four value, administration of reversal agents, and time to discharge from the postanesthesia care unit as well as a multiple-choice test to assess knowledge. The e-learning module was developed based on a needs assessment process, including focus group interviews, surveys, and expert opinions. RESULTS: The e-learning module was implemented in 6 anesthesia departments on 21 November 2016. Currently, we are collecting postintervention data. The final dataset will include data from more than 10,000 anesthesia procedures. We expect to publish the results in late 2017 or early 2018. CONCLUSIONS: With a dataset consisting of thousands of general anesthesia procedures, the INVERT study will assess whether an e-learning module can increase anesthetists' use of neuromuscular monitoring. TRIAL REGISTRATION: Clinicaltrials.gov NCT02925143; https://clinicaltrials.gov/ct2/show/NCT02925143 (Archived by WebCite® at http://www.webcitation.org/6s50iTV2x).

[Danish Cholinesterase Research Unit diagnoses patients with prolonged paralysis after succinylcholine and mivacurium]. / Dansk Kolinesterase Kartotek udreder patienter med forlænget paralyse efter suxamethon og mivacurium.

The Danish Cholinesterase Research Unit (DCRU) is a nationwide unit for patients carrying mutations in the butyrylcholinesterase enzyme (BChE). BChE hydrolyzes the neuromuscular blocking drugs succinylcholine and mivacurium. Patients with mutations in the butyrylcholinesterase gene are at risk of experiencing a prolonged effect of the drugs, such as weakness or paralysis for hours. In order to diagnose the referred patients correctly, DCRU combines results such as BChE activity, genotyping, pedigree and clinical reactions to succinylcholine or mivacurium.

[When muscle relaxants have unexpected prolonged duration during anaesthesia]. / Uventet lang virkningsvarighed afmuskelrelaksantia kan forebygges

Muscle relaxation facilitates tracheal intubation and improves surgical conditions during anaesthesia. However, unexpected prolonged muscle relaxation may occur. This article describes important causes of prolonged muscle relaxation and gives suggestions for its prevention. Drug interactions, incomplete reversal, co-morbidity, inaccurate neuromuscular monitoring and critical illness may prolong the effect of muscle relaxants. The anaesthetist must titrate the muscle relaxants using objective neuromuscular monitoring and proper reversal of the blockade when needed.

Neuromuscular blockade for improvement of surgical conditions during laparotomy: protocol for a randomised study.

INTRODUCTION: During laparotomy, surgeons frequently experience difficult surgical conditions if the patient's abdominal wall or diaphragm is tense. This issue is particularly pertinent while closing the fascia and placing the intestines into the abdominal cavity. Establishment of a deep neuromuscular blockade (NMB), defined as a post-tetanic-count (PTC) of 0-1, paralyses the abdominal wall muscles and the diaphragm. We hypothesised that deep NMB (PTC 0-1) would improve surgical conditions during upper laparotomy as compared to standard NMB with bolus administration. METHODS: This is an investigator-initiated, assessor- and patient-blinded, randomised study. A total of 128 patients scheduled for elective upper laparotomy will be included and randomised to either continuous deep NMB or standard NMB defined as bolus administrations. Surgical conditions are evaluated using a five-point rating scale every 30 min. Primary outcome is the average score for a patient's surgical condition. Secondary outcomes are, among others, surgical rating score during fascial closure, wound dehiscence, wound infection requiring surgical drainage and incisional hernia at the six-month follow-up. CONCLUSIONS: This randomised, double-blinded study investigates potential effects of deep NMB on surgical conditions and patient outcomes during elective laparotomy. FUNDING: The study is funded in part by a research grant from the Investigator Initiated Studies Program of Merck Sharp & Dohme Corp. TRIAL REGISTRATION: NCT02140593.

[Challenges when improving surgical conditions by use of neuromuscular blockade]. / Udfordringer ved brug af muskelrelaksantia til forbedring af kirurgiske forhold.

Neuromuscular blockade (NMB) may pose a clinical dilemma between surgeons' requirements of muscle relaxation and the risk of residual blockade. This review has aimed at describing the challenges when using NMB for optimizing surgical conditions and reasons for inadequate relaxation despite use of NMB. Interdisciplinary collaboration, proper neuromuscular monitoring, knowledge on differences in pharmacodynamics and pharmacokinetics of NMB are essential factors when optimizing surgical conditions by use of NMB.

[Danish Cholinesterase Research Unit diagnoses patients with prolonged paralysis after succinylcholine and mivacurium].

The Danish Cholinesterase Research Unit (DCRU) is a nationwide unit for patients carrying mutations in the butyrylcholinesterase enzyme (BChE). BChE hydrolyzes the neuromuscular blocking drugs succinylcholine and mivacurium. Patients with mutations in the butyrylcholinesterase gene are at risk of experiencing a prolonged effect of the drugs, such as weakness or paralysis for hours. In order to diagnose the referred patients correctly, DCRU combines results such as BChE activity, genotyping, pedigree and clinical reactions to succinylcholine or mivacurium.

[The perioperative management of myasthenia gravis patients].

Myasthenia gravis (MG) is a disease affecting the acetylcholine receptor in the neuromuscular junction. Symptoms of MG are muscle weakness and fatigue. Anaesthesia and operation to MG patients need collaboration among the MG patients' health-care professionals. It is recommended that pyridostigmine is continued on the day of surgery. Most anaesthetic drugs are well tolerated by MG patients, but benzodiazepines and opiates may only be used with caution. For neuromuscular blockade rocuronium seems to be the best choice as it can be antagonized with sugammadex at the end of the surgical procedure.

[The perioperative management of myasthenia gravis patients]. / Håndtering af det perioperative forløb for patienter med myasthenia gravis.

Myasthenia gravis (MG) is a disease affecting the acetylcholine receptor in the neuromuscular junction. Symptoms of MG are muscle weakness and fatigue. Anaesthesia and operation to MG patients need collaboration among the MG patients' health-care professionals. It is recommended that pyridostigmine is continued on the day of surgery. Most anaesthetic drugs are well tolerated by MG patients, but benzodiazepines and opiates may only be used with caution. For neuromuscular blockade rocuronium seems to be the best choice as it can be antagonized with sugammadex at end of the surgical procedure.

[Parental presence during treatment of injured and acutely ill children]. / Forældretilstedeværelse ved modtagelse og behandling af tilskadekomne og akut syge børn er formentlig hensigtsmæssig.

This review studies the literature on the effects of parental presence during treatment of injured and acutely ill children. Parents wish to stay with their child, and clinicians increasingly find it beneficial, probably correlated with increased experience. Studies indicate that the treatment of the child is not compromised by parental presence but only a few quasi-randomised, quantitative studies have been published, and many circumstances concerning parental presence have not been investigated sufficiently.