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Pharmacogenomics, which offers a potential means by which to inform prescribing and avoid adverse drug reactions, has gained increasing consideration in other medical settings but has not been broadly evaluated during perioperative care.The Implementation of Pharmacogenomic Decision Support in Surgery (ImPreSS) Trial is a prospective, single-center study consisting of a prerandomization pilot and a subsequent randomized phase. We describe findings from the pilot period. Patients planning elective surgeries were genotyped with pharmacogenomic results, and decision support was made available to anesthesia providers in advance of surgery. Pharmacogenomic result access and prescribing records were analyzed. Surveys (Likert-scale) were administered to providers to understand utilization barriers.Of eligible anesthesiology providers, 166 of 211 (79%) enrolled. A total of 71 patients underwent genotyping and surgery (median, 62 years; 55% female; average American Society of Anesthesiologists (ASA) score, 2.6; 58 inpatients and 13 ambulatories). No patients required postoperative intensive care or pain consultations. At least 1 provider accessed pharmacogenomic results before or during 41 of 71 surgeries (58%). Faculty were more likely to access results (78%) compared to house staff (41%; P = .003) and midlevel practitioners (15%) ( P.0001). Notably, all administered intraoperative medications had favorable genomic results with the exception of succinylcholine administration to 1 patient with genomically increased risk for prolonged apnea (without adverse outcome). Considering composite prescribing in preoperative, recovery, throughout hospitalization, and at discharge, each patient was prescribed a median of 35 (range 15-83) total medications, 7 (range 1-22) of which had annotated pharmacogenomic results. Of 2371 prescribing events, 5 genomically high-risk medications were administered (all tramadol or omeprazole; with 2 of 5 pharmacogenomic results accessed), and 100 genomically cautionary mediations were administered (hydralazine, oxycodone, and pantoprazole; 61% rate of accessing results). Providers reported that although results were generally easy to access and understand, the most common reason for not considering results was because remembering to access pharmacogenomic information was not yet a part of their normal clinical workflow.Our pilot data for result access rates suggest interest in pharmacogenomics by anesthesia providers, even if opportunities to alter prescribing in response to high-risk genotypes were infrequent. This pilot phase has also uncovered unique considerations for implementing pharmacogenomic information in the perioperative care setting, and new strategies including adding the involvement of surgery teams, targeting patients likely to need intensive care and dedicated pain care, and embedding pharmacists within rounding models will be incorporated in the follow-on randomized phase to increase engagement and likelihood of affecting prescribing decisions and clinical outcomes.

Malignant hyperthermia (MH) is an inherited muscle disorder induced by volatile anesthetics and depolarizing muscle relaxants. While the incidence of MH is high in young, there are few reports on the clinical features of pediatric MH. In this study, we selected pediatric cases from an MH database and analyzed the clinical findings by age group. We hypothesized that there would be age-related differences in the clinical characteristics.A retrospective analysis of MH data collected in our database during 1960 to 2020 was performed to identify pediatric subjects (≤18 years) with a Clinical Grading Scale of ≥35, indicating "very likely" or "almost certain" MH. We compared clinical characteristics among the 0 to 24 month, 2 to 12 year, and 13 to 18 year (youngest, middle, and oldest, respectively) age groups.Data were available for 187 patients: 15 in the youngest age group, 123 in the middle-aged group, and 49 in the oldest age group. Of these, 55 patients (29.4%) had undergone muscle biopsy and muscle contracture test. The mortality rates during the study period were 13.3%, 13.8%, 20.4%, and 15.5% in the youngest, middle, and oldest cohorts and overall, respectively. In contrast, the overall mortality rate from 2000 to 2020 was 8.8%. The most frequent initial symptoms of MH were elevated temperature (46.7%) and generalized muscular rigidity (26.7%) in the youngest cohort, masseter spasm (35.0%) and generalized muscular rigidity (19.5%) in the middle cohort, and elevated end-tidal carbon dioxide (26.5%) and tachycardia (22.4%) in the oldest cohort. Physical examination revealed that elevated temperature, sinus tachycardia, and respiratory acidosis occurred frequently in all groups. The middle cohort had high frequencies of masseter spasm (58.4%; P = .02) and dark urine (75.5%; P = .01) compared to those in the oldest groups, and had a higher peak creatine kinase level compared to those in the 3 groups. Skeletal muscle symptoms tended to be more common in patients administered succinylcholine (generalized muscular rigidity, P = .053; masseter spasm, P.0001; dark urine, P.0001). In particular, masseter spasm and dark urine were more common in the middle cohort when succinylcholine was administered (masseter spasm: versus youngest cohort, P = .06, versus oldest cohort, P = .027; dark urine: versus youngest cohort, P = .0072, versus oldest cohort, P = .0015).The clinical characteristics of pediatric patients with MH vary according to age group. The difference in initial symptoms of MH depending on age group is noteworthy information for the early diagnosis of MH.

Background Administration of an optimal dose of anesthetic agent to ensure adequate depth of hypnosis with the lowest risk of adverse effects to the fetus is highly important in cesarean section. Sodium thiopental (STP) is still the first choice for induction of anesthesia in some countries for this obstetric surgery. We aimed to compare two doses of STP with regarding the depth of anesthesia and the condition of newborn infants. Methods In this clinical trial, parturient undergoing elective Caesarian section were randomized into two groups receiving either low-dose (5 mg/kg) or high-dose (7 mg/kg) STP. Muscle relaxation was provided with succinylcholine 2 mg/kg and anesthesia was maintained with O2/N2O and sevoflurane. The depth of anesthesia was evaluated using isolated forearm technique (IFT) and bispectral index (BIS) in various phases. Additionally, infants were assessed using Apgar score and neurobehavioral test. Results Forty parturient were evaluated in each group. BIS was significantly lower in high-dose group at skin incision to delivery and subcutaneous and skin closure. Also, significant differences were noticed in IFT over induction to incision and incision to delivery. Apgar score was significantly lower in high-dose group at 1 min after delivery. Newborn infants in low-dose group had significantly better outcomes in all three domains of the neurobehavioral test. Conclusion 7 mg/kg STP is superior to 5 mg/kg in creating deeper hypnosis for mothers. However, it negatively impacts Apgar score and neurobehavioral test of neonates. STP seems to has dropped behind as an acceptable anesthetic in Cesarean section. Trial registration IRCT No: 2016082819470 N45, 13/03/2019.

Malignant hyperthermia (MH) is a severe hypermetabolic disorder associated with dysregulation of calcium homeostasis and is triggered by inhalational anesthetics (isoflurane, sevoflurane, desflurane) and a depolarizing muscle relaxant (succinylcholine). We report the case of a 16-day-old infant undergoing laparoscopic surgery. The patient developed hyperthermia and hypercarbia with muscle rigidity. After the diagnosis of MH, dantrolene was administered with sufficient hydration. The patient was transferred to the pediatric intensive care unit for monitoring and treatment of acute renal injury due to myoglobinuria. Subsequently, two variants of the ryanodine receptor 1 (RYR1) gene were identified in the patient as the mutation point at c.1589G > A p.Arg530His and c.1841G > T p.Arg614Leu, which are known to be associated with MH. This was a rare case of MH in a 16-day-old infant that might be related to two RYR1 mutations inherited from the parents.

Pseudocholinesterase deficiency, sometimes called butyrylcholinesterase deficiency, is a rare disorder in which the neuromuscular blocking drugs succinylcholine and mivacurium cannot be metabolized properly in the blood plasma. This disorder can either be acquired as a result of certain comorbidities or it can be inherited genetically. Anesthesia providers must understand the pathophysiology of pseudocholinesterase deficiency and be prepared to safely and effectively manage patients who show signs and symptoms consistent with the disorder after the use of the indicated neuromuscular blocking drugs. This article summarizes the pharmacologic and physiologic data relevant to understanding the basic pathophysiology associated with pseudocholinesterase deficiency and illustrates a case study of a young woman suspected of having the disorder after a prolonged delay in emergence from general anesthesia.

Succinylcholine is still used in clinical practice. Its duration is highly variable and neuromuscular monitoring is recommended to assess its recovery. Unfortunately, depolarizing neuromuscular block cannot be evaluated by train-of-four (TOF) as no fade occurs. Only single twitch (ST) allows to monitor depolarizing block. The TOFScan monitor proposes a modified TOF ratio (T4/Tref) not referring to fade within a TOF series. We hypothesized that the T4/Tref allows to assess recovery from succinylcholine. This observational study aims to compare recovery from depolarizing block simultaneously assessed with T4/Tref and ST. After Ethics Committee approval and written informed consent 45 patients receiving a single dose of succinylcholine were included. ST recovery, measured with TOF-Watch SX, and T4/Tref recovery, measured by TOFScan, were assessed simultaneously. Difference between measurements was compared using Mann–Whitney U test and overall concordance with the intraclass correlation coefficient (ICC). The ICC was 0.85 [95% CI 0.82–0.87]. The first T4/Tref ratio ≥ 90% was 97% [95% CI 93–101%] the corresponding ST value was 91% [95% CI 87–97%]. The first T4/Tref ratio ≥ 100% was 103% [95% CI 102–107%], the corresponding ST value was 104% [95% CI 100–106%]; median [95% confidence interval of the median]. Time to recovery to 90% and 100% of baseline did not differ between ST or T4/Tref. It was10.0 [8.0–13.0] min vs 10.0 [8.0–12.0] min, P = 0.307 and 10.0 [9.0–15.0] min vs 10.0 [8.0–15.0] min, P = 0.546; respectively; median [IQR]. Agreement between both parameters was excellent. The T4/Tref can be used accurately to measure recovery from depolarizing neuromuscular block.

Background Neuromuscular monitoring should be applied routinely to avoid residual neuromuscular block. However, anaesthetists often refrain from applying it, even when the equipment is available. We aimed to increase neuromuscular monitoring in six Danish anaesthesia departments via e-learning. Methods Interrupted time series study, with baseline data from a previous study and prospective data collection after implementation of the module, which was available for 2 weeks from 21 November 2016. We included all patients receiving general anaesthesia with muscle relaxants until 30 April 2017. Main outcome was application of acceleromyography, grouped as succinylcholine only and non-depolarising relaxants. Secondary outcomes were last recorded train-of-four ratio (non-depolarising) relaxants and score on a ten-question pre- and post-course multiple-choice test. Results The post-intervention data consisted of 6525 cases (3099 (48%) succinylcholine only, 3426 (52%) non-depolarising relaxants). Analysing all departments, we found a positive pre-intervention trend in application of acceleromyography for both groups, of estimated 7.5% and 4.8% per year, respectively (p < .001). The monitoring rate increased significantly for succinylcholine in two departments post-intervention (p = .045 and .010), and for non-depolarising relaxants in one department (p = .041), but followed by a negative trend of -37.0% per year (p = .041). The rate was already close to 90% at the time of the intervention and the mean last recorded train-of-four ratio was 0.97 (SD 0.21), also without a significant change. The median score on the post-course test increased from 7 (IQR 5-8) to 9 (IQR 8-10) (p < .001, Wilcoxon Signed-Ranks Test). Conclusion We found no overall effect of the e-learning module on application of neuromuscular monitoring, although the post-course test indicated an effect on anaesthetists' knowledge in this field. Trial registration Trial registration: Clinicaltrials.gov identifier: NCT02925143.

Background Patients at risk of malignant hyperthermia need trigger-free anesthesia. Therefore, anesthesia machines prepared for safe use in predisposed patients should be free of volatile anesthetics. The washout time depends on the composition of rubber and plastic in the anesthesia machine. Therefore, new anesthesia machines should be evaluated regarding the safe preparation for trigger-free anesthesia. This study investigates wash out procedures of volatile anesthetics for two new anesthetic workstations: Dräger Atlan A350 and General Electric Healthcare (GE) Carestation 650 and compare it with preparation using activated charcoal filters (ACF). Methods A Dräger Atlan and a Carestation 650 were contaminated with 4% sevoflurane for 90 min. The machines were decontaminated with method (M1): using ACF, method 2 (M2): a wash out method that included exchange of internal parts, breathing circuits and soda lime canister followed by ventilating a test lung using a preliminary protocol provided by Dräger or method 3 (M3): a universal wash out instruction of GE, method 4 (M4): M3 plus exchange of breathing system and bellows. Decontamination was followed by a simulated trigger-free ventilation. All experiments were repeated with 8% desflurane contaminated machines. Volatile anesthetics were detected with a closed gas loop high-resolution ion mobility spectrometer with gas chromatographic pre-separation attached to the bacterial filter of the breathing circuits. Primary outcome was time until Results Time to Conclusion Both wash out protocols resulted in a significant reduction of trace gas concentrations. However, due to the complexity of the protocols and prolonged total preparation time, feasibility in clinical practice remains questionable. Especially when time is limited preparation of the anesthetic machines using ACF remain superior.

Neuromuscular blockade (NMB) is a critical part of many surgical procedures. Data on practice patterns of NMB agents (NMBAs) and NMB reversal in recent years in the US ambulatory surgical care setting are limited.This retrospective analysis of US adult outpatients was conducted using the Premier Healthcare Database. We describe anesthesia practice trends in NMB management and assess the association of patient, procedural, and site characteristics with NMB reversal approach using multivariable logistic regression.Approximately 5.2 million outpatient surgical encounters involving NMB and 4.6 million involving rocuronium or vecuronium between January 2014 and June 2019 were included. Following the introduction of sugammadex to US clinical practice (~2016), there was an increased use of rocuronium or vecuronium and a decrease in succinylcholine alone. Before 2016, NMB was pharmacologically reversed with neostigmine in approximately two-thirds of outpatient encounters. Over time, active reversal increased; by 2019, 42.3% and 36.0% of encounters were reversed by neostigmine and sugammadex, respectively, with 21.7% undergoing spontaneous recovery. Choice of NMBA (rocuronium or vecuronium alone), time since 2016, obesity, peripheral vascular disease, and procedures on the digestive, ocular, and female genital systems (vs musculoskeletal procedures) were independently and positively associated with pharmacologic reversal (versus spontaneous reversal). Conversely, advanced age; Western geography; and cardiovascular, endocrine, hemic/lymphatic, respiratory, and ear, nose, and throat procedures were independently and negatively associated with pharmacologic reversal of NMB.Among pharmacologic reversals, time since 2016 was positively and independently associated with sugammadex compared with neostigmine (odds ratios [ORs], ranged from 1.8 in 2017 to 3.2, P.0001 in 2019). Those administered rocuronium or vecuronium without succinylcholine, with increased age and history of certain comorbidities, and those undergoing ocular or respiratory procedures (compared with musculoskeletal) were positively associated with reversal with sugammadex and endocrine procedure negatively and independently associated with reversal with sugammadex. There was variability in the association of several factors with NMB reversal choices by geographic region, particularly in patients' race, ethnicity, and size of affiliated hospital.Overall, active pharmacological reversal of NMB increased in US adult outpatients following the introduction of sugammadex, although there remains significant practice variability. The multifactorial relationship between patient-, procedural-, and environmental-level characteristics and NMB management is rapidly evolving. Additional research on how these anesthesia practice patterns may be impacted by the shift to the ambulatory care setting and how they may impact patient outcomes and health disparities is warranted.

Inadvertent injection of nonepidural drugs into the epidural space is a rare situation, which is under-reported, and can lead to serious complications, such as cardiovascular and respiratory complications, paraplegia, or quadriplegia, and can worsen the patients' outcome from surgery. Succinylcholine administered epidurally leads to the appearance of fasciculation and shortness of breath and can prolong neuromuscular blockade. We report a case of accidental administration of 100 mg of succinylcholine via an epidural catheter as a test dose instead of 2 ml 0.5% bupivacaine in a patient planned for major abdominal surgery. After 2 min, the patient complained of shortness of breath; dysarthria; and fasciculation in the trunk, upper limbs, and face. This was managed with induction to general anesthesia (GA). In the postoperative period, no neurological or cardiovascular complications were observed. There is no adequate drug as an antidote of accidentally given nonepidural drugs via an epidural catheter. Succinylcholine given via epidural catheter has been shown to prolong neuromuscular blockade. Proper labeling and storage of syringes are of utmost importance for avoiding these unpleasant situations.

Background New therapies are created to address specific problems and enjoy popularity as they enter widespread clinical use. Broader use can reveal unknown adverse effects and impact the life cycle significantly. Succinylcholine, a depolarizing neuromuscular blocker, was the product of decades of research surrounding the ancient compound, curare. It was introduced into practice in the 1950s by Burroughs Wellcome and Company (BW Co) and was welcomed due to its rapidly acting muscle relaxation effects. Global clinical use revealed adverse effects, both minor and major, in particular, hyperkalemia and malignant hyperthermia. We investigated when practitioners and the manufacturer became aware of these adverse effects, how information about these side effects was disseminated, and whether the manufacturer met the regulatory requirements of the time, specifically regarding the timely reporting of adverse effects. Sources Primary literature search using online and archived documents was conducted at the Wood Library-Museum of Anesthesiology, Schaumburg, IL. We consulted documents submitted by BW Co to federal authorities, through the Freedom of Information Act (FOIA), Food and Drug Administration (FDA) reports, promotional advertisements, package inserts, published articles, and textbooks. Results Initial clinical testing in humans in 1952 found no adverse effects on cardiovascular or respiratory systems. Fasciculations and myalgia were early side effects described in case reports in 1952. Large-scale clinical trials in 1953 found abnormally long recovery times among some patients; the discovery of abnormal pseudocholinesterase enzyme activity was not fully demonstrated until the early 1960s. Bradycardia was first reported in 1957 in children, and in 1959 in adults. In 1960, animal studies reported a transient increase in plasma potassium; further experiments in 1969 clearly demonstrated succinylcholine-induced hyperkalemia in burn patients. Malignant hyperthermia was first described in 1966. Similar cases of elevated temperatures and muscle rigidity were described globally but the underlying mechanism was not elucidated until the 1990s. Standard anesthesia textbooks did not report major side effects of succinylcholine until 1960 and included newly documented side effects with each edition. BW Co's packaging contained warnings as early as the 1950s but were later updated in 1962 and beyond to reflect the newly discovered hyperkalemia and malignant hyperthermia. Conclusion Particularly given the regulatory environment of the time, BW Co appropriately reported the adverse effects of succinylcholine after market entry; it updated promotional and packaging material in a timely manner to reflect newly discovered adverse effects. The toxicity, though alarming and put clinicians on alert, did not seem to heavily impact succinylcholine's use, given its various desirable properties. It is still a choice muscle relaxant used today, although there are efforts to develop superior agents to replace succinylcholine.

Objective Nondepolarizing neuromuscular blocking agents (NMBAs) are associated with perioperative complications in noncardiac surgery; however, little is known about their effect on cardiac surgery. This study assessed the effect of neuromuscular blockade (NMB) on the incidence of postoperative pulmonary complications (PPCs) after cardiac surgery and operating conditions. Design Prospective, randomized clinical trial with blinded outcomes assessment. Setting University hospital, single institution. Participants Adult patients having cardiac surgery requiring cardiopulmonary bypass. Interventions One hundred patients were randomized to receive succinylcholine (group SUX) for intubation with no further NMB administered or cisatracurium (group CIS) for intubation and maintenance NMB. The primary outcome was a composite incidence of PPCs in the 72 hours after elective cardiac surgery. PPCs included failure to extubate within 24 hours, need for reintubation, pneumonia, aspiration, unanticipated need for noninvasive respiratory support, acute respiratory distress, and mortality from respiratory arrest. The secondary outcome was the adequacy of operating conditions as assessed by blinded surgeon survey (including a rating of surgical conditions on a Likert scale from 1 = poor to 5 = excellent), anesthesiologist report, and patient questionnaire. Measurements and Main Results The composite incidence of PPCs did not differ between groups (8 of 50 patients in both groups; 16%). Mean surgeon rating of surgical conditions was lower in the SUX group (4.65 ± 0.85 v 4.96 ± 0.20, p = 0.02). Conclusion Although avoiding nondepolarizing NMBA is feasible, doing so worsened operating conditions and did not reduce the incidence of postoperative pulmonary complications.

BACKGROUND Succinylcholine is a preferred muscle relaxant for rapid sequence intubation. Postoperative myalgia (POM) is one of its commonest adverse effects with unknown pathogenesis. Various modalities were examined to reduce POM. We hypothesized that duloxetine may reduce the incidence and severity of fasciculation or succinylcholine-induced POM in outpatient surgeries. METHODS This randomized double-blinded trial involved controlled 70 adult participants scheduled for elective direct microlaryngoscopic surgeries. Before induction of general anesthesia by 2 h, 35 patients received duloxetine 30 mg orally (group D) and 35 patients received similar oral starch placebo capsules (group C). Fasciculations, POM, sedation score, time to first rescue analgesia, total analgesic consumption 24 h after surgery, patients' satisfaction, and adverse effects were recorded. RESULTS Incidence of fasciculation was 77.1% and 94.3% in groups D and C (p value = 0.04), whereas its severity was not significant between groups (p value = 0.09). Incidence and severity of POM were significantly lower in group D (p values = 0.004 and 0.021). Positive correlation was recorded between fasciculations and POM scores (r = 0.732 and p

Rhabdomyolysis in adults after anesthetic administration is uncommon in those without underlying risk factors. We present a 34-year-old female with history of severe gastroesophageal reflux disease (GERD), hypothyroidism, and migraines who developed severe rhabdomyolysis following an uncomplicated general anesthetic for esophagogastroduodenoscopy (EGD) and placement of Bravo esophageal pH monitor. The patient did not have any known risk factors for malignant hyperthermia, and halogenated agents were not used during the procedure. We speculate that the rhabdomyolysis was caused by the use of succinylcholine. Providers should be aware that even patients without known risk factors may be at risk for developing rhabdomyolysis, and it is important to remain vigilant about this potentially life-threatening complication.

Introduction Variants of butyrylcholinesterase are frequently associated with prolonged response to suxamethonium or mivacurium. Butyrylcholinesterase (BChE) can be characterized by phenotyping and determination of genotype. Inappropriate timing of blood sampling might interfere with phenotyping methods. However, guidelines regarding delay between exposure to anaesthesia and testing are not clearly defined. In this study, the BChE activity and phenotype in an early (T1) and late (T2) phase were compared and the phenotype/genotype correlation was assessed. Methods Patients with a prolonged paralysis after mivacurium or suxamethonium were selected after ethical committee approval and written consent. BChE activity was based on butyrylthiocholine hydrolysis rate and phenotyping on differential inhibition of BChE activity with dibucaine and fluoride. DNA sequencing allowed genotypic characterization. Results We included the results of 20 patients with prolonged neuromuscular block (NMB) induced by mivacurium or suxamethonium. In these patients, BChE activity was different at T1 and T2 (2120 [1506-2733] U L(-1)and 4055 [2810-5301] U L-1, respectively;P = 0.0014; values are mean [95% CI]). When phenotyping was possible, phenotyping at T1 and T2 yielded identical results. Phenotyping failed to identify one new variant (p.Tyr146Cys) and the K variant in 14 of 16 patients. Conclusion Anaesthesia interfered with BChE activity, but not with phenotyping. Phenotyping can be performed on blood drawn during or immediately after recovery of mivacurium or suxamethonium to screen for clinically relevant variants of BChE. However, accurate diagnosis of BChE deficiency needs further confirmation by determination of genotype.

Introduction This study sought to describe the phenotype and genotype characteristics of patients referred to our laboratory to undergo further assessment due to a suspicion of a prolonged effect of suxamethonium attributed to BChE deficiency. Methods All patients referred to our laboratory from January 2016 to December 2019 due to the suspicion of a prolonged effect of suxamethonium were included in this study. The determination of BChE activity and genotyping using complete nucleotide sequencing of the entire complementary DNA-coding region with flanking intron–exon boundaries were completed. Results During this four-year period, 58 patients were referred to our laboratory for the investigation of prolonged neuromuscular block due to BChE deficiency. Among them, 52 showed a BChE deficiency related to BCHE gene mutations. The most commonly detected genotype was compound homozygous atypical variant (p.Asp98Gly)/homozygous Kalow variant (p.Ala569Thr) (p.[Asp98Gly;Ala567Thr];[p.Asp98Gly;Ala567Thr]). Further, we recorded four new BCHE variants, which seem to be associated with prolonged post suxamethonium apnoea: p.(Trp205Cys), p.(Leu222His), p.(Glu469Gln), and p.(Lys276Ter). Conclusion During a four-year period, among the 58 patients referred to our laboratory, we have found four new BCHE variants, which seem to be associated with prolonged post suxamethonium apnoea (p.(Trp205Cys), p.(Leu22His), p.(Glu469Gln), and p.(Lys276Ter)).

Background Drug errors during neuraxial anaesthesia or analgesia are not well known. Objectives To review the clinical consequences associated with incorrect administration of neuromuscular blocking drugs (NMBDs) during spinal or epidural anaesthesia, and to investigate human factors and strategies available to help prevent such errors. Design A review of reports of neuraxial administration of NMBDs in humans. Data sources Published reports of errors involving NMBDs. We searched the period between 1965 and 2019. Eligibility criteria Error reports in any language. Nonneuraxial drug errors were excluded. Results We identified 20 reports involving seven different NMBDs inadvertently administered via the epidural or intrathecal routes. All patients developed systemic neuromuscular junction blockade. Fourteen errors occurred while patients were awake. The onset of action was delayed following epidural rocuronium and suxamethonium. The duration of action was prolonged following epidural administration of vecuronium, pancuronium, cisatracrium and suxamethonium. Five patients required emergency airway interventions. Intrethecal gallamine caused convulsions and muscle spasms migrating up the body. Syringe swap was the primary cause for the majority of errors and perceptual errors were the most common. Implementation of recommendations could have prevented the errors. Conclusion Following the epidural injection of NMBDs the effects are delayed and prolonged. There was no serious morbidity reported following neuraxial administration of the NMBDs used in current practice. Perceptual errors resulting in incorrect syringe choice were the commonest cause. Four measures can be introduced to reduce such errors.

Background The evidence base for the widely accepted standard regimen of succinylcholine for rapid sequence induction (1.0 mg kg− 1) remains unclear. Methods We performed a systematic review and meta-analysis of randomized trials comparing any succinylcholine regimen with the standard regimen (1.0 mg kg− 1) and reporting on intubating conditions and/or apnoea times. Results were expressed as absolute risk differences (ARD) for dichotomous data and mean differences (MD) for continuous data. Results We retrieved six trials with relevant data of 864 patients (ASA 1 or 2, aged 18–65 years, body mass index − 2). Four regimens (0.3, 0.4, 0.5, 0.6 mg kg− 1) were compared with 1.0 mg kg− 1 in at least three trials each, and three (0.8, 1.5, 2 mg kg− 1) in one each. With 0.3 to 0.5 mg kg− 1, the likelihood of excellent intubating conditions was significantly decreased (ARD − 22% to − 67%). With 0.3 and 0.4 mg kg− 1, but not with 0.5, 0.6, 0.8, 1.5 and 2.0 mg kg− 1, the likelihood of unacceptable intubating conditions was significantly increased (ARD + 22% and + 32%, respectively). With 2.0 mg kg− 1, but not with 0.8 or 1.5 mg kg− 1, the likelihood of excellent intubating conditions was significantly increased (ARD + 23%). Apnoea times were significantly shorter with regimens ≤0.8 mg kg− 1 (MD − 1.0 to − 3.4 min) but were not reported with 1.5 or 2.0 mg kg− 1. Conclusions With succinylcholine regimens ≤0.5 mg kg− 1, excellent intubating conditions are less likely and apnoea times are shorter, compared with 1 mg kg− 1. With 0.3 and 0.4 mg kg− 1, unacceptable intubating conditions are more common. Succinylcholine 1.5 mg kg− 1 does not produce more often excellent conditions compared with 1 mg kg− 1, while 2.0 mg kg− 1 does, but the database with these regimens is weak and apnoea times remain unknown. Limited information size and strong statistical heterogeneity decrease the certainty of the evidence.

Timely application of objective neuromuscular monitoring can avoid residual neuromuscular blockade. We assessed the frequency of objective neuromuscular monitoring with acceleromyography and the last recorded train-of-four ratio in a cohort of Danish patients. We extracted data from all patients receiving general anaesthesia from November 2014 to November 2016 at six hospitals in the Zealand Region of Denmark. Acceleromyography was available in all operating rooms and data were recorded automatically. The primary outcome measure was acceleromyography use in patients receiving neuromuscular blocking agents, divided into non-depolarising agents and succinylcholine only. The dataset included 76,743 cases, of which 30,430 received a neuromuscular blocking drug. Non-depolarising drugs were used in 16,525 (54%) and succinylcholine as the sole drug in 13,905 (46%) cases. Acceleromyography was used in 14,463 (88%) patients who received a non-depolarising neuromuscular blocking drug and in 4224 (30%) receiving succinylcholine alone. Acceleromyography use varied between the departments from 58% to 99% for non-depolarising drugs and from 3% to 79% for succinylcholine alone. The median (IQR [range]) of the last recorded train-of-four ratio before tracheal extubation was 0.97 (0.90–1.06 [0.01–2.20]) when non-depolarising drugs were used, and was less than 0.9 in 22% of cases. The OR for oxygen desaturation was higher with the use of succinylcholine [2.51 (95%CI 2.33–2.70) p

BACKGROUND Rapid sequence induction (RSI) is a standard procedure, which should be implemented in all patients with a risk of aspiration/regurgitation during anaesthesia induction. OBJECTIVE The primary aim was to evaluate clinical practice in RSI, both in adult and paediatric populations. DESIGN Online survey. SETTINGS A total of 56 countries. PARTICIPANTS Members of the European Society of Anaesthesiology. MAIN OUTCOME MEASURES The aim was to identify and describe the actual clinical practice of RSI related to general anaesthesia. RESULTS From the 1921 respondents, 76.5% (n=1469) were qualified anaesthesiologists. When anaesthetising adults, the majority (61.7%, n=1081) of the respondents preoxygenated patients with 100% O2 for 3 min and 65.9% (n=1155) administered opioids during RSI. The Sellick manoeuvre was used by 38.5% (n=675) and was not used by 37.4% (n=656) of respondents. First-line medications for a haemodynamically stable adult patient were propofol (90.6%, n=1571) and suxamethonium (56.0%, n=932). Manual ventilation (inspiratory pressure

Neuromuscular blocking agents (NMBAs) with a non-depolarising mechanism of action carry the risk of postoperative residual paralysis and are associated with postoperative pulmonary complications (POPC). Owing to the shorter duration of action, the depolarising NMBA succinylcholine may be associated with less postoperative residual paralysis, and hence fewer POPC. We tested the association of succinylcholine administration during anaesthesia and POPC.In a retrospective cohort study of registry data from two large US academic medical centres, 244 850 adult noncardiac surgical patients undergoing general anaesthesia were included. The primary outcome was POPC, defined as post-extubation haemoglobin oxygen de-saturation to90%, or re-intubation requiring intensive care unit admission within 7 days after surgery. The association between succinylcholine and POPC and its dose-dependency were tested in a hierarchical fashion using a multivariable logistic regression model.A total of 13 206 patients (5.4%) experienced POPC. Use of succinylcholine was associated with increased risk of POPC (adjusted odds ratio [ORIn contrast to our prediction, succinylcholine administration was associated with an increased risk of POPC. This association was dose-dependent and magnified in surgeries of shorter duration.

Intracranial and Hemodynamic Changes after Succinylcholine Administration in Cats. By Cottrell JE, Hartung J, Giffin JP, and Shwiry B. Anesthesia & Analgesia 1983; 62:1006–9. Reprinted with permission. Bolus injections of succinylcholine (1.5 mg/kg) significantly increased intracranial pressure (ICP) in cats under normal conditions from control levels of 8 +/- 1 mmHg to 16 +/- 3 mmHg (+/- SEM, P less than 0.01), and in the presence of artificially increased ICP from control levels of 27 +/- 1 mmHg to 47 +/- 4 mmHg (P less than 0.01). These approximately 100% increases in ICP were accompanied by a transitory decrease in mean arterial pressure (approximately 10 s), followed by a 15 to 20% increase (P less than 0.05). Pulmonary arterial pressure increased 20 to 30% (P less than 0.05). These results, when considered in conjunction with results previously obtained in humans, suggest that succinylcholine may be contraindicated in neurosurgical patients.

BACKGROUND The concept of the effect-site concentration of anesthetic agents is important. The effect compartment model can be explained using the concepts of effect-site concentration and effect-site equilibration rate constant (ke0). This study confirms that the time-to-peak effect (tpe ) can be measured easily in clinical practice by applying a priming dose and train-of-four (TOF) during general anesthesia induction, and ke0 can be calculated from the tpe of the four muscle relaxants that are commonly used in general anesthesia. METHODS Eighty patients who received general anesthesia were divided into the succinylcholine, rocuronium, atracurium, or vecuronium groups. Priming doses of muscle relaxants were administered. The effects of muscle relaxants were quantified by recording the twitch response of the adductor pollicis muscle after stimulating the ulnar nerve. The tpe was measured at the lowest TOF value. ke0 was calculated from the measured tpe . RESULTS The ke0 values of the succinylcholine, rocuronium, atracurium, and vecuronium groups were 0.076 (0.030)/min, 0.228 (0.122)/min, 0.062 (0.011)/min, and 0.077 (0.019)/min, respectively. CONCLUSIONS It is possible to estimate ke0 from the tpe of muscle relaxants using a priming dose and TOF during general anesthesia induction.

ResumoJustificativa e objetivosA ação epidural de agentes bloqueadores neuromusculares pode ser explicada à luz de suas características físico‐químicas e propriedades do espaço epidural. Na literatura existem poucos casos sobre a administração acidental em espaço epidural de agente neuromuscular que se manifesta principalmente com a instituição de bloqueio neuromuscular ou fasciculações.Relato de casoRelatamos um caso de administração acidental de succinilcolina como uma dose teste epidural em uma paciente submetida à laparotomia programada, sob anestesia combinada geral e peridural. Aproximadamente dois minutos após a injeção de succinilcolina, a paciente queixou‐se de falta de ar, enquanto fasciculações leves apareceram em seu tronco e rosto, tratadas com a instituição imediata de anestesia geral. Exceto pela duração relativamente longa do bloqueio neuromuscular em comparação com a administração intravenosa, sequelas neurológicas ou cardiovasculares ou outros sintomas de toxicidade local ou sistêmica não foram observados.ConclusõesA administração oral de diazepam parece diminuir os efeitos adversos da administração epidural acidental de succinilcolina. A meticulosidade e discriminação dos rótulos das seringas, bem como os cuidados persistentes mantidos durante todos os procedimentos de anestesia, continuam a ser de importância crucial.AbstractBackground and objectivesEpidural action of neuromuscular blocking agents could be explained under the light of their physicochemical characteristics and epidural space properties. In the literature there are few cases of accidental neuromuscular agent's epidural administration, manifesting mainly with neuromuscular blockade institution or fasciculations.Case reportWe report a case of accidental succinylcholine administration as an epidural test dose, in a female patient undergoing scheduled laparotomy, under combined general and epidural anesthesia. Approximately 2min after the succinylcholine injection the patient complained for shortness of breath, while mild fasciculations appeared in her trunk and face, managed by immediate general anesthesia institution. With the exception of a relatively longer duration of neuromuscular blockade compared with intravenous administration, no neurological or cardiovascular sequelae or other symptoms of local or systemic toxicity were observed.ConclusionsOral administration of diazepam seems to lessen the adverse effects from accidental epidural administration of succinylcholine. The meticulous and discriminative labeling of syringes, as well as keeping persistent cautions during all anesthesia procedures remains of crucial importance.

Study objective Malignant hyperthermia (MH) is a rare yet potentially fatal pharmacogenetic disorder triggered by exposure to inhalational anesthetics and the depolarizing neuromuscular blocking agent succinylcholine. Epidemiologic data on the geographic variation in MH prevalence is scant. The objective of this study is to examine the prevalence of recorded MH diagnosis in patients discharged from hospitals in four states in the United States. Design Observational study. Setting Healthcare Cost and Utilization Project (HCUP) State Inpatient Database (SID) for California (2011), Florida (2011), New York (2012) and Wisconsin (2012). Patients A total of 164 hospital discharges that had a recorded diagnosis of MH using the International Classification of Disease, 9th Revision, Clinical Modification code 995.86. Methods MH prevalence was assessed by patient demographic and clinical characteristics. Main results The prevalence of MH per 100,000 hospital discharges ranged from 1.23 (95% Confidence Interval [CI], 0.80–1.66) in New York to 1.91 (95% CI, 1.48–2.34) in California, and the prevalence of MH per 100,000 surgical discharges ranged from 1.47 (95% CI, 0.93–2.02) in New York to 2.86 (95% CI, 2.00–3.71) in Florida. The prevalence of MH in male patients was more than twice the prevalence in female patients. Of the 164 patients with MH diagnosis, 11% were dead on discharge. Conclusions There exists a modest variation in the prevalence of recorded MH diagnosis in hospital discharges in California, Florida, New York and Wisconsin. Epidemiologic patterns of MH diagnosis in hospital discharges appear to be similar across the four states. Further research is needed to better understand the geographic variation and contributing factors of MH in different populations.

The aim of this review is to examine data relating to perioperative management of the patient with neuromuscular disorders RECENT FINDINGS: Patients with pre-existing neuromuscular disorders are at risk for a number of postoperative complications that are related to anesthetic drugs that are administered intraoperatively. Careful preoperative assessment is necessary to reduce morbidity and mortality. In particular, the risk of postoperative respiratory failure and need for long-term ventilation should be reviewed with patients. The use of succinylcholine should be avoided in muscular dystrophies, motor neuron diseases, and intrinsic muscle disease due to a risk of malignant hyperthermia, hyperkalemia, rhabdomyolysis, and cardiac arrest. The use of quantitative neuromuscular monitoring should be strongly considered whenever nondepolarizing neuromuscular blocking agents are administered. A number of case series and reports have been recently published demonstrating that sugammadex can be safely used in patients with neuromuscular disease; the risk of residual neuromuscular is nearly eliminated when this agent is administered intraoperatively.Careful assessment and management of patients with underlying neuromuscular diseases is required to reduce postoperative complications. This article reviews the anesthetic implications of patients undergoing surgery with neuromuscular disorder.

BackgroundSugammadex allows rapid recovery from rocuronium-induced neuromuscular blockade. Succinylcholine is often used for brief surgeries but is associated with myalgia, headache, histamine release, and increased lactate levels. Thus, we hypothesized that succinylcholine may affect emergence agitation (EA) and compared the effects of succinylcholine and rocuronium-sugammadex on EA in patients undergoing closed reduction of a nasal bone fracture under general anesthesia.MethodsForty-two patients were prospectively enrolled and allocated randomly to the succinylcholine group (group SC) or the rocuronium-sugammadex group (group RS; eachn = 21). Neuromuscular block and its reversal were achieved with succinylcholine and normal saline in group SC, whereas rocuronium and sugammadex were administered in group RS. After surgery, the incidence of EA as a primary outcome, the incidence of dangerous EA, and duration of EA as secondary outcomes were compared.ResultsThe incidence of EA was higher in group SC than in group RS (90.5% vs. 47.6%, respectively; relative risk [RR] 4.3; 95% confidence interval [CI] 1.2 to 15.7;P = .006). The incidence of dangerous EA increased in group SC compared to group RS (33.3% vs. 4.8%, respectively; RR 2.1; 95% CI 1.3 to 3.4;P = .045). The duration of agitation was longer in group SC than in group RS [106.5 (65.1) vs. 40.4 (26.0) sec; mean difference 66.1 s; 95% CI 31.0 to 101.1; effect size 1.3;P = .001).ConclusionSuccinylcholine increases the incidence, severity, and duration of EA compared to rocuronium-sugammadex in patients undergoing closed reduction of a nasal bone fracture.Trial registrationCRiS Registration numberKCT0002673. Initial registration date was 31 January 2018 (Retrospectively registered).

At a recent consensus conference, the Malignant Hyperthermia Association of the United States addressed 6 important and unresolved clinical questions concerning the optimal management of patients with malignant hyperthermia (MH) susceptibility or acute MH. They include: (1) How much dantrolene should be available in facilities where volatile agents are not available or administered, and succinylcholine is only stocked on site for emergency purposes? (2) What defines masseter muscle rigidity? What is its relationship to MH, and how should it be managed when it occurs? (3) What is the relationship between MH susceptibility and heat- or exercise-related rhabdomyolysis? (4) What evidence-based interventions should be recommended to alleviate hyperthermia associated with MH? (5) After treatment of acute MH, how much dantrolene should be administered and for how long? What criteria should be used to determine stopping treatment with dantrolene? (6) Can patients with a suspected personal or family history of MH be safely anesthetized before diagnostic testing? This report describes the consensus process and the outcomes for each of the foregoing unanswered clinical questions.

Onset times and conditions for intubation after rocuronium versus suxamethonium at cesarean section have been evaluated, but no study thus far has examined the influence of these neuromuscular blocking drugs on the surgical conditions or their effect on the duration of surgery and the ease of fetal delivery. We aimed to compare the surgical conditions for delivery in parturients who received deep neuromuscular block with rocuronium with those who had induction with suxamethonium.Ninety patients undergoing cesarean section under general anesthesia were randomized to receive either rocuronium 0.6 mg/kg or suxamethonium 1 mg/kg for tracheal intubation and delivery. Times to delivery and the quality of surgical conditions, using a five-point Surgical Rating Scale for Delivery (SRSD) ranging from 1 (poor) to 5 (excellent), were evaluated.The median SRSD (range) was found to be significantly better in the rocuronium group [4 (3-5) points vs 3 (2-4) points with suxamethonium (P 0.001)]. Whereas the mean (SD) induction-to-intubation interval was longer with rocuronium [106 (34) s vs 68 (32) s with suxamethonium (95% CI of the difference 24 to 52 s, P 0.001)], the incision-to-delivery interval was shorter in the rocuronium group [147 (68) s vs 196 (51) s with suxamethonium (95% CI of the difference -75 to -24 s, P 0.001)]. The mean induction-to-delivery intervals were similar [268 (73) s vs 276 (63) s, respectively].Whereas the induction-to-delivery intervals were comparable, we found rocuronium superior to suxamethonium in allowing better surgical conditions for fetal delivery, which enabled an easier delivery and a shorter incision-to-delivery interval.

Study Objective Inclusion body myositis is a painless inflammatory myopathy affecting older adults. It manifests as progressive muscle atrophy and weakness, typically affecting proximal lower extremity muscles initially but insidiously progressing to affect other muscles, including bulbar (oropharyngeal) muscles and the diaphragm, and leading to dysphagia and respiratory insufficiency. This study reviews the perioperative outcomes of patients with inclusion body myositis who received general anesthesia. Design Observational retrospective study. Setting Academic tertiary referral center. Patients Patients with inclusion body myositis from October 1, 2009, to September 30, 2015, undergoing procedures requiring general anesthesia. Interventions Perioperative health records were reviewed. Measurements Perioperative outcomes and complications were assessed, with emphasis on respiratory complications and unexpected reactions to succinylcholine and nondepolarizing neuromuscular blocking drugs. Main Results Sixteen patients with inclusion body myositis underwent 18 procedures requiring general anesthesia. Succinylcholine was used during induction in 6 cases (33.3%) and nondepolarizing neuromuscular blocking drugs in 11 cases (61.1%). For 13 patients (72.2%), the trachea was extubated at the end of surgery, and none had postoperative respiratory complications. The 5 patients who continued to have tracheal intubation were expected to require continuous mechanical ventilation postoperatively. Three patients died within 30 days of surgery. One patient underwent a tracheostomy for planned long-term mechanical ventilation but life support was withdrawn after 22 days, and 2 severely deconditioned patients died at 11 and 15 days following general anesthesia for endoscopic procedures. Conclusions Our patients with inclusion body myositis had uneventful perioperative outcomes following general anesthesia with depolarizing and nondepolarizing muscle relaxants. The small patient cohort in our series precludes a definitive conclusion regarding the safety of anesthetic agents in this patient population.

Background: The effects of rocuronium at two different doses, that is, 0.6 mg/kg (2 × ED95) and 0.9 mg/kg (3 × ED95), were compared with succinylcholine (2 mg/kg) when used for endotracheal intubation in adult patients for elective surgeries under general anesthesia. Materials and Methods: Ninety patients were divided into three groups of 30 each. Groups A, B received injection rocuronium at 0.6 mg/kg, 0.9 mg/kg respectively and Group C received succinylcholine at 2 mg/kg. Onset of action of relaxant, intubation conditions, time taken to intubate and duration of action were compared. Statistical Analysis Used: To compare the statistical difference in the age, weight, height of the study subjects, onset of action of relaxant, intubation conditions, time taken to intubate, and duration of action analysis of variance and unpaired t-test were used. Results: The onset time was considerably shorter with rocuronium 0.9 mg/kg than 0.6 mg/kg. The onset time of rocuronium 0.9 mg/kg was found to be significantly longer than succinylcholine 2 mg/kg. Time taken to intubate was shortest with succinylcholine 2 mg/kg. The time taken to intubate with the rocuronium 0.9 mg/kg was found to be comparable to that of rocuronium 0.6 mg/kg. Intubation score of rocuronium 0.9 mg/kg was the best (17.75), which was comparable with succinylcholine. However, the intubation score obtained with rocuronium 0.6 mg/kg was inferior. Duration of action was shortest with succinylcholine. The duration of action is prolonged when the dose of rocuronium is increased from 0.6 to 0.9 mg/kg. Conclusion: Rapid sequence induction of anesthesia with propofol and fentanyl, succinylcholine allowed a more rapid endotracheal intubation sequence and created superior intubation conditions than rocuronium. However, the technique of using a large dose of rocuronium to achieve perfect conditions for tracheal intubation may have application whenever succinylcholine is relatively contraindicated.

Tracheoesophageal fistula develops in 5 % to 15 % of patients with esophageal cancer. Metal stent placement can be used for treatment. Stent placement can result in aspiration, hemorrhage, perforation, migration, and pneumonia. Patients may present for medical attention with unanticipated worsening of the fistula and stent displacement requiring special anesthetic care. We discuss the perianesthetic management of a patient with malignant tracheoesophageal fistula and stent migration who presented for endoscopic esophageal stent replacement.

Butyrylcholinesterase deficiency prolongs the effects of the drugs it degrades; succinylcholine and mivacurium. Existing literature on butyrylcholinesterase deficiency is dominated by genetic and biochemical studies. We searched MEDLINE, Embase, Web of Science and Biosis to systematically review the causes and clinical consequences of butyrylcholinesterase deficiency. We considered outcomes clinically relevant if neuromuscular blockade, induced by succinylcholine or mivacurium, was assessed using clinical criteria or neuromuscular monitoring. We included 66 studies: 25 randomised controlled trials; 13 clinically controlled trials; 26 prospective observational studies; 1 retrospective study; and 1 qualitative study. Data heterogeneity precluded quantitative synthesis. Studies described genetic, physiological, acquired or pharmacologically induced causes of butyrylcholinesterase deficiency. The prolongation of neuromuscular blockade by butyrylcholinesterase deficiency was most pronounced with homozygosity of a genetic variant, but other more common factors included increasing age, pregnancy, severe liver disease, burn injuries and drug interactions.

BACKGROUND Myopathies are generally considered to increase the risk for succinylcholine-induced hyperkalaemia and may affect the duration of action of neuromuscular blockers. Centronuclear (myotubular) myopathy (CNM) is congenital and produces various degrees of muscular weakness and associated complications such as respiratory failure. The effects of succinylcholine and the potentially lethal consequences of hyperkalaemia on patients with CNM are unknown due to its rarity. One source of information is the dog, as CNM occurs naturally in dogs. Because of its remarkable similarity with the disease in man, canine CNM can serve as a model to further our knowledge of the effects of succinylcholine. OBJECTIVES We examined the kalaemic and neuromuscular effects of succinylcholine in dogs with and without autosomal-recessive CNM. DESIGN A prospective, experimental study. SETTING Anaesthesiology laboratory, College of Veterinary Medicine, Cornell University, New York, USA. PATIENTS Six dogs with autosomal-recessive CNM and six control dogs. INTERVENTIONS Dogs received succinylcholine 0.3 mg kg during isoflurane anaesthesia. MAIN OUTCOME MEASURES Whole blood potassium concentration was measured 5 min before and after succinylcholine administration. Neuromuscular function was measured with acceleromyography and single twitch stimulation. RESULTS All dogs recovered uneventfully from anaesthesia. The increase in potassium concentration [mean (SD)] following succinylcholine was similar between groups: CNM 0.5 (0.4) mmol l and control 0.7 (0.4) mmol l (P = 0.47). Recovery of the single twitch to 25, 75 and 90% was longer in the CNM group (all P

The duration of neuromuscular block (NMB) following succinylcholine administration is characterised by a high interindividual variability. However, this has not yet been quantified in a large sample of surgical patients. The significance of underlying clinical factors is unknown.The objective of this study was to profile the variability in NMB duration following a standard dose of succinylcholine and to investigate contributing clinical and genetic factors.A prospective, observational study.Tertiary referral centre.In a total of 1630 surgical patients undergoing a rapid sequence induction and intubation, clinical risk factors for a prolongation in NMB duration following succinylcholine were assessed. In a subset of 202 patients, additional biochemical and molecular genetic investigations of butyrylcholinesterase were performed.A standard 1 mg kg dose of succinylcholine after administration of an induction drug and an opioid.NMB duration measured as the time between administration of succinylcholine until reappearance of palpable muscular response to supramaximal transcutaneous ulnar nerve stimulation.NMB varied from 80 s to 44 min with a median duration of 7.3 min. Sixteen percent of patients had NMB duration in excess of 10 min. A multivariable survival model identified physical status, sex, age, hepatic disease, pregnancy, history of cancer and use of etomidate or metoclopramide as independent risk factors for a prolonged NMB. Three novel butyrylcholinesterase variants were identified: p.Ile5Thr; p.Val178Ile; and p.Try231Ser.Neuromuscular blockade duration in excess of 10 min occurred in 16% of a general surgical population following a single dose of succinylcholine. The multivariable model of clinical risk factors for prolonged NMB revealed a negative predictive value of 87%, thereby indicating that absence of such risk factors may reliably predict a shorter duration of NMB. In patients with clinical risk factors for a prolonged NMB or with butyrylcholinesterase mutations, an alternative to succinylcholine should be considered.

The bispectral index (BIS) monitor is a quantitative electroencephalographic (EEG) device that is widely used to assess the hypnotic component of anaesthesia, especially when neuromuscular blocking drugs are used. It has been shown that the BIS is sensitive to changes in electromyogram (EMG) activity in anaesthetized patients. A single study using an earlier version of the BIS showed that decreased EMG activity caused the BIS to decrease even in awake subjects, to levels that suggested deep sedation and anaesthesia.We administered suxamethonium and rocuronium to 10 volunteers who were fully awake, to determine whether the BIS decreased in response to neuromuscular block alone. An isolated forearm technique was used for communication during the experiment. Two versions of the BIS monitor were used, both of which are in current use. Sugammadex was used to antagonise the neuromuscular block attributable to rocuronium.The BIS decreased after the onset of neuromuscular block in both monitors, to values as low as 44 and 47, and did not return to pre-test levels until after the return of movement. The BIS showed a two-stage decrease, with an immediate reduction to values around 80, and then several minutes later, a sharp decrease to lower values. In some subjects, there were periods where the BIS was60 for several minutes. The response was similar for both suxamethonium and rocuronium. Neither monitor was consistently superior in reporting the true state of awareness.These results suggest that the BIS monitor requires muscle activity, in addition to an awake EEG, in order to generate values indicating that the subject is awake. Consequently, BIS may be an unreliable indicator of awareness in patients who have received neuromuscular blocking drugs.ACTRN12613000587707.

Objective: The purpose of our study was to determine the effect of induced apnea on quality of cardiopulmonary structures during computerized tomographic (CT) angiography images in children with congenital heart diseases. Methods: Pediatric patients with congenital heart defects undergoing cardiac CT angiography at our facility in the past 3 years participated in this study. The earlier patients underwent cardiac CT angiography without induced apnea and while, later, apnea was induced in patients, which was followed by electrocardiogram gated cardiac CT angiography. General anesthesia was induced using sleep dose of intravenous propofol. After the initial check CT, on request by the radiologist, apnea was induced by the anesthesiologist by administering 1 mg/kg of intravenous suxamethonium. Soon after apnea ensued, the contrast was injected, and CT angiogram carried out. CT images in the “apnea group” were compared with those in “nonapnea group.” After the completion of the procedure, the patients were mask ventilated with 100% oxygen till the spontaneous ventilation was restored. Results: We studied 46 patients, of whom 36 with apnea and yet another 10 without. The quality of the image, visualization of structures such as cardiac wall, outflow tracts, lung field, aortopulmonary shunts, and coronary arteries were analyzed and subjected to statistical analysis (Mann–Whitney U, Fischer's exact test and Pearson's Chi-square test). In the induced apnea group, overall image quality was considered excellent in 89% (n = 33) of the studies, while in the “no apnea group,” only 30% of studies were excellent. Absent or minimal motion artifacts were seen in a majority of the studies in apnea group (94%). In the nonapnea group, the respiratory and body motion artifacts were severe in 50%, moderate in 30%, and minimal in 20%, but they were significantly lesser in the apnea group. All the studied parameters were statistically significant in the apnea group in contrast to nonapnea group (P < 0.000). Conclusion: The image quality of cardiac CT angiography greatly improves, and motion artifact significantly decreases with the use of induced apnea in pediatrics patients being evaluated for congenital heart disease. This technique poses no additional morbidity of significance.

Increasing numbers of adult patients with complex congenital heart conditions are presenting for noncardiac surgery later in life. These disorders can present challenges for surgical and anesthesia providers. Specifically, single ventricle lesions offer anatomic and physiologic concerns during the perioperative period. Single ventricle physiology represents a delicate balance between systemic and pulmonary blood flow. Any alterations in blood flow through these systems can produce undesirable hemodynamic changes, especially during the perioperative period. We present a case of an adult patient with a single left ventricle who presented for laparoscopic total colectomy due to inflammatory bowel disease. His abnormal anatomy coupled with the hemodynamic disruptions caused by laparoscopy presented significant anesthetic challenges. We highlight the anesthetic concerns of single ventricle physiology, specifically pertaining to laparoscopic surgery. We provide recommendations for safely managing these patients perioperatively. With detailed preoperative evaluation and close hemodynamic monitoring during the perioperative period, these patients can experience successful surgical and anesthetic outcomes.

Malignant hyperthermia (MH) is a rare hypermetabolic disorder of skeletal muscles that manifests as a life-threatening crisis in susceptible individuals, after exposure to triggering agents, most commonly halothane and succinylcholine. MH presents with multiple nonspecific signs and laboratory findings such as tachycardia, hyperthermia, hypercarbia, acidosis, and muscle rigidity. Caffeine halothane contracture test is not available at most centers in India. Larach et al. have described a clinical grading scale for determining the MH raw score based on clinical findings and biochemical tests. The high degree of suspicion, early recognition and aggressive treatment should commence immediately. It is imperative to avoid triggering agents, such as volatile anesthetics and succinylcholine, and promote the use of total intravenous anesthesia in MH susceptible patients. We report a case of 6-month-old child undergoing laparotomy under general anesthesia, who presented with signs and symptoms of MH, had MH rank 5 and raw score 36.

Background: The development of liver failure is a major problem in critically ill patients. The hepatotoxicity of many drugs, as one important reason for liver failure, is poorly screened for in human models. Rocuronium and succinylcholine are neuromuscular blocking agents used for tracheal intubation and for rapid-sequence induction. Objective: We used an in-vitro test with a permanent cell line and compared rocuronium and succinylcholine for hepatotoxicity. Design: In-vitro study. Setting: A basic science laboratory, University Hospital Rostock, Germany. Material/(Patients): The basic test compound is the permanent human liver cell line HepG2/C3A. In a standardised microtitre plate assay the toxicity of different concentrations of rocuronium, succinylcholine and plasma control was tested. Interventions: After two incubation periods of 3 days, the viability of cells (XTT test, lactate dehydrogenase release and trypan blue staining), micro-albumin synthesis and the cyto chrome 1A2 activity (metabolism of ethoxyresorufin) were measured. Main Outcome Measures: Differences between rocuronium and succinylcholine were assessed using the Kruskal-Wallis one-way test and two-tailed Mann-Whitney U test. Results: Rocuronium, but not succinylcholine, led to a significant dose-dependent decrease of viability, albumin synthesis and cytochrome 1A2 activity of test cells. Conclusion: An in-vitro test with a cell line showed hepatotoxicity of rocuronium that was dose-dependent. Further studies are needed to investigate the underlying mechanisms of the effects of rocuronium on hepatic cellular integrity.

A 9-year-old boy undergoing anaesthesia including suxamethonium and halothane suffered cardiac arrest on two occasions. Clinical and laboratory examination subsequently showed that the patient had suffered from acute rhabdomyolysis. The eventual recovery was satisfactory.

Background Muscle relaxants are prescribed routinely for patients undergoing general anesthesia, but the requirement for paralysis in spinal surgery is unclear. This study compared the operating conditions of general anesthesia with and without a muscle relaxant on spinal surgery patients. Methods Eighty-six adults who underwent elective spinal surgery were randomly assigned to a relaxant group (group R) or a no-relaxant group (group NR). All patients were induced with intravenous midazolam (0.05 mg/kg), fentanyl (4 µg/kg), propofol (1.0 mg/kg), and succinylcholine (2 mg/kg) and then atracurium was used in group R but not in group NR. The operating conditions, including muscle tone, body movements, airway pressure, anesthetics consumption, eye-opening time, extubation time, and the Observer's Assessment of the Alertness/Sedation (OAA/S) score 20 minutes after the extubation were compared between the 2 groups. Results The operating conditions including muscle tone scales, body movements, and airway pressure did not differ between the 2 groups. Eye-opening time (9.35±2.34 vs. 11.02±2.50 min; P=0.002) and extubation time (13.95±3.41 vs. 16.72±3.67 min; P=0.001) were shorter in group NR than in group R. The BIS score at extubation (87.2±5.0 vs. 83.3±5.7; P=0.001) and the OAA/S score 20 minutes after extubation (5 [3 to 5] vs. 4 [3 to 5]; P=0.005) were significantly higher in group NR than in group R. Propofol consumption was higher in group NR than in group R (4206.10±415.80 vs. 3900.60±365.40 μg/kg, respectively; P=0.001). Conclusions General anesthesia without muscle relaxant provides similar working conditions to those observed with muscle relaxant, and it is associated with earlier eye opening and extubation and higher level of consciousness on emergence from spinal surgery.