The effect of sugammadex on patient morbidity and quality of recovery after general anaesthesia: a systematic review and meta-analysis.

BACKGROUND: Residual neuromuscular block is associated with increased patient morbidity. Therefore prevention of residual neuromuscular block is an important component of general anaesthesia where neuromuscular blocking agents are used. Whereas sugammadex improves reversal based on neuromuscular twitch monitoring parameters, there have been no prospective, adequately powered definitive studies demonstrating that sugammadex is also associated with less patient morbidity. METHODS: We performed a systematic review of randomised trials comparing sugammadex with anticholinesterase-based reversal or placebo reversal that reported important patient outcomes beyond the postanaesthesia care unit. RESULTS: We identified 43 articles, including 5839 trial participants. Only one trial reported days alive and out of hospital to 30 days (DAOH-30), which showed that the number of DAOH-30 was similar in those allocated to sugammadex compared with neostigmine-based reversal (25 days [19-27] vs 24 days [21-27], median difference 0.00 [-2.15 to 2.15]). Pooled analyses of data from 16 trials showed an estimated odds ratio (OR) for postoperative pulmonary complications of 0.67 (95% confidence interval 0.47-0.95) with sugammadex use. Pooled analysis showed that pneumonia (eight trials OR 0.51 [0.24-1.01] with sugammadex use), hospital length of stay (23 trials, mean difference -0.31 [-0.84 to 0.22] with sugammadex use), and patient-reported quality of recovery (11 trials, varied depending on metric used) are similar in those allocated to sugammadex vs control. The difference seen in mortality (11 trials, OR 0.39 [0.15-1.01] with sugammadex use) would be considered to be clinically significant and warrants further investigation, however, the rarity of these events precludes drawing definitive conclusions. CONCLUSION: Although few trials reported on DAOH-30 or important patient outcomes, sugammadex is associated with a reduction in postoperative pulmonary complications, however, this might not translate to a difference in hospital length of stay, patient-reported quality of recovery, or mortality. CLINICAL TRIAL REGISTRATION: PROSPERO database (CRD42022325858).

Comparison of the effects of neostigmine and sugammadex on postoperative residual curarization and postoperative pulmonary complications by means of diaphragm and lung ultrasonography: a study protocol for prospective double-blind randomized controlled trial.

BACKGROUND: Postoperative residual curarization (PORC) may be a potential risk factor of postoperative pulmonary complications (PPCs), and both of them will lead to adverse consequences on surgical patient recovery. The train-of-four ratio (TOFr) which is detected by acceleromyography of the adductor pollicis is thought as the gold standard for the measurement of PORC. However, diaphragm function recovery may differ from that of the peripheral muscles. Recent studies suggested that diaphragm ultrasonography may be useful to reveal the diaphragm function recovery, and similarly, lung ultrasound was reported for the assessment of PPCs in recent years as well. Sugammadex reversal of neuromuscular blockade is rapid and complete, and there appear to be fewer postoperative complications than with neostigmine. This study aims to compare the effects of neostigmine and sugammadex, on PORC and PPCs employing diaphragm and lung ultrasonography, respectively. METHODS/DESIGN: In this prospective, double-blind, randomized controlled trial, patients of the American Society of Anesthesiologists Physical Status I-III, aged over 60, will be enrolled. They will be scheduled to undergo arthroplasty under general anesthesia. All patients will be allocated randomly into two groups, group NEO (neostigmine) and group SUG (sugammadex), using these two drugs for reversing rocuronium. The primary outcome of the study is the incidence of PPCs in the NEO and SUG groups. The secondary outcomes are the evaluation of diaphragm ultrasonography and lung ultrasound, performed by an independent sonographer before anesthesia, and at 10 min and 30 min after extubation in the post-anesthesia care unit, respectively. DISCUSSION: Elimination of PORC is a priority at the emergence of anesthesia, and it may be associated with reducing postoperative complications like PPCs. Sugammadex was reported to be superior to reverse neuromuscular blockade than neostigmine. Theoretically, complete recovery of neuromuscular function should be indicated by TOFr > 0.9. However, the diaphragm function recovery may not be the same matter, which probably harms pulmonary function. The hypothesis will be proposed that sugammadex is more beneficial than neostigmine to reduce the incidence of PPCs and strongly favorable for the recovery of diaphragm function in our study setting. TRIAL REGISTRATION: ClinicalTrials.gov NCT05040490 . Registered on 3 September 2021.

Half-Dose Sugammadex After Neostigmine Versus Neostigmine as a Routine Reversal Agent: A Pilot Randomized Trial.

PURPOSE: The use of sugammadex at a lower dose after a routine reversal dose of neostigmine may prevent residual neuromuscular blockade (rNMB). Our goal was to investigate the effects of the use of half-dose sugammadex for reversing rNMB after administration of neostigmine, and compare these effects to a routine full-dose of neostigmine. DESIGN: Prospective, single-blinded, randomized trial. METHODS: Ninety-eight patients having lower abdominal tumor resection surgery under general anesthesia were randomized into two groups. Group N (Neostigmine) (n = 48) patients received standard reversal dose of intravenous neostigmine 0.05 mg/kg and atropine 0.02 mg/kg before extubationl Group N + S (Neostigmine + Sugammadex) (n = 50) patients received 1 mg/kg of intravenous sugammadex three minutes after a standard neostigmine reversal dose. The primary end-point was the incidence of a train-of-four (TOF) ratio less than 0.9 at tracheal extubation. Secondary end-points were periods between the start of administration of reversal agents and extubation or operating room discharge in minutes to achieve recovery of TOF ratio < 0.9 to 0.7 and TOF ratio ≥ 0.9. FINDINGS: The demographic data were not different between the two groups (P > .005). The incidence of rNMB presented as TOF ratio < 0.9 to 0.7 was present in 52% of Group N patients compared to 8% in Group N + S patients (P < .0001). The time to recovery between administering reversal and extubation as well as operating room discharge in Group N were; 18.52 ± 6.34 minutes and 23.27 ± 6.95 minutes, respectively, whereas; in Group N + S, they were; 12.86 ± 5.05 and 17.82 ± 4.99 minutes, respectively. (P < .0001, P < .0001, respectively). Adverse events were similar between groups (P > .05). CONCLUSIONS: A half-dose sugammadex (1 mg/kg) after full-dose reversal of neostigmine provides a lower incidence of rNMB and shorter recovery times as compared to full-dose neostigmine reversal agent. This practice is safe and effective in case of rNMB.

Prehabilitative exercise hastens recovery from isoflurane in diabetic and non-diabetic rats.

Diabetes has been demonstrated to be one of the strongest predictors of risk for postoperative delirium and functional decline in older patients undergoing surgery. Exercise is often prescribed as a treatment for diabetic patients and regular physical activity is hypothesized to decrease the risk of postoperative cognitive impairments. Prior studies suggest that anesthetic emergence trajectories and recovery are predictive of risk for later postoperative cognitive impairments. Therapeutic strategies aimed at improving emergence and recovery from anesthesia may therefore be beneficial for diabetic patients. Wistar (n = 32) and Goto-Kakizaki (GK) type 2 diabetic (n = 32) rats between 3-4 months old underwent treadmill exercise for 30 min/day for ten days or remained inactive. Pre-anesthesia spontaneous alternation behavior was recorded with a Y-maze. Rats then received a 2-h exposure to 1.5-2 % isoflurane or oxygen only. The time to reach anesthetic emergence and post-anesthesia recovery behaviors was recorded for each rat. Postsynaptic density protein-95 (PSD-95), an important scaffolding protein required for synaptic plasticity, protein levels were quantified from hippocampus using western blot. Spontaneous alternation behavior (p = 0.044) and arm entries (p < 0.001) were decreased in GK rats. There was no difference between groups in emergence times from isoflurane, but exercise hastened the recovery time (p = 0.008) for both Wistar and GK rats. Following 10 days of exercise, both Wistar and GK rats show increased levels of PSD-95 in the hippocampus. Prehabilitation with moderate intensity exercise, even on a short timescale, is beneficial for recovery from isoflurane in rats, regardless of metabolic disease status.

Elevated preoptic brain activity in zebrafish glial glycine transporter mutants is linked to lethargy-like behaviors and delayed emergence from anesthesia.

Delayed emergence from anesthesia was previously reported in a case study of a child with Glycine Encephalopathy. To investigate the neural basis of this delayed emergence, we developed a zebrafish glial glycine transporter (glyt1 - / -) mutant model. We compared locomotor behaviors; dose-response curves for tricaine, ketamine, and 2,6-diisopropylphenol (propofol); time to emergence from these anesthetics; and time to emergence from propofol after craniotomy in glyt1-/- mutants and their siblings. To identify differentially active brain regions in glyt1-/- mutants, we used pERK immunohistochemistry as a proxy for brain-wide neuronal activity. We show that glyt1-/- mutants initiated normal bouts of movement less frequently indicating lethargy-like behaviors. Despite similar anesthesia dose-response curves, glyt1-/- mutants took over twice as long as their siblings to emerge from ketamine or propofol, mimicking findings from the human case study. Reducing glycine levels rescued timely emergence in glyt1-/- mutants, pointing to a causal role for elevated glycine. Brain-wide pERK staining showed elevated activity in hypnotic brain regions in glyt1-/- mutants under baseline conditions and a delay in sensorimotor integration during emergence from anesthesia. Our study links elevated activity in preoptic brain regions and reduced sensorimotor integration to lethargy-like behaviors and delayed emergence from propofol in glyt1-/- mutants.

Cholinergic Chemotransmission and Anesthetic Drug Effects at the Carotid Bodies.

General anesthesia is obtained by administration of potent hypnotics, analgesics and muscle relaxants. Apart from their intended effects (loss of consciousness, pain relief and muscle relaxation), these agents profoundly affect the control of breathing, in part by an effect within the peripheral chemoreflex loop that originates at the carotid bodies. This review assesses the role of cholinergic chemotransmission in the peripheral chemoreflex loop and the mechanisms through which muscle relaxants and hypnotics interfere with peripheral chemosensitivity. Additionally, consequences for clinical practice are discussed.

Randomised controlled trial of sugammadex or neostigmine for reversal of neuromuscular block on the incidence of pulmonary complications in older adults undergoing prolonged surgery.

BACKGROUND: Residual neuromuscular block has been associated with postoperative pulmonary complications. We hypothesised that sugammadex reduces postoperative pulmonary complications in patients aged ≥70 yr having surgery ≥3 h, compared with neostigmine. METHODS: Patients were enrolled in an open-label, assessor-blinded, randomised, controlled trial. At surgical closure, subjects were equally randomised to receive sugammadex 2 mg kg-1 or neostigmine 0.07 mg kg-1 (maximum 5 mg) for rocuronium reversal. The primary endpoint was incidence of postoperative pulmonary complications. Secondary endpoints included residual paralysis (train-of-four ratio <0.9 in the PACU) and Phase 1 recovery (time to attain pain control and stable respiratory, haemodynamic, and neurological status). The analysis was by intention-to-treat. RESULTS: Of the 200 subjects randomised, 98 received sugammadex and 99 received neostigmine. There was no significant difference in the primary endpoint of postoperative pulmonary complications despite a signal towards reduced incidence for sugammadex (33% vs 40%; odds ratio [OR]=0.74; 95% confidence interval [CI]=[0.40, 1.37]; P=0.30) compared with neostigmine. Sugammadex decreased residual neuromuscular block (10% vs 49%; OR=0.11, 95% CI=[0.04, 0.25]; P<0.001). Phase 1 recovery time was comparable between sugammadex (97.3 min [standard deviation, sd=54.3]) and neostigmine (110.0 min [sd=62.0]), difference -12.7 min (95% CI, [-29.2, 3.9], P=0.13). In an exploratory analysis, there were fewer 30 day hospital readmissions in the sugammadex group compared with the neostigmine group (5% vs 15%; OR=0.30, 95% CI=[0.08, 0.91]; P=0.03). CONCLUSIONS: In older adults undergoing prolonged surgery, sugammadex was associated with a 40% reduction in residual neuromuscular block, a 10% reduction in 30 day hospital readmission rate, but no difference in the occurrence of postoperative pulmonary complications. Based on this exploratory study, larger studies should determine whether sugammadex may reduce postoperative pulmonary complications and 30 day hospital readmissions. CLINICAL TRIAL REGISTRATION: NCT02861131.

Unrecognised postoperative residual curarisation in developing countries remains a common problem.

BACKGROUND: Postoperative residual curarisation (PORC) is a potentially life-threatening complication of non-depolarising muscle relaxant use in anaesthesia. Quantitative neuromuscular monitoring has the potential to reduce the risk of PORC, but many anaesthetists rely on clinical assessment of neuromuscular function alone. OBJECTIVES: To investigate the occurrence of PORC in the recovery room at an academic hospital in Gauteng, South Africa. Additionally, this prospective, cross-sectional study aimed to determine the extent of intraoperative neuromuscular monitoring and to assess clinical factors that may influence the risk of PORC. METHODS: Patient characteristics and clinical information, including whether neuromuscular monitoring had been conducted, were recorded. Patients were evaluated by clinical assessment and determination of a quantitative train-of-four ratio (TOFR). PORC assessment methods were compared and clinical characteristics were analysed for association with TOFR status. RESULTS: The incidence of PORC (TOFR <0.9) in the study group was 45.5%; however, 78% passed the clinical assessment. The specificity of clinical assessment to detect residual paralysis was 24%. Notably, only 3 patients (6%) were monitored intraoperatively for neuromuscular function. Advanced age (p=0.011, r=-0.34) and female gender (p=0.001) were shown to be associated with a TOFR <0.7. CONCLUSIONS: PORC is more common in practice than currently recognised. This deduction is supported by the low rate of intraoperative neuromuscular monitoring conducted and the high pass rate on clinical assessment. Routine use of quantitative monitoring of neuromuscular function should be encouraged to minimise the risk of this serious yet preventable condition.

[Algorithm-based preventive strategies for avoidance of residual neuromuscular blocks]. / Algorithmusbasierte Präventionsstrategien zur Vermeidung neuromuskulärer Restblockaden.

BACKGROUND: Postoperative residual neuromuscular block (train of four ratio <0.9) is an outcome-relevant problem in balanced anesthesia, which increases postoperative morbidity and mortality. Implementation of medium and short-acting muscle relaxants, quantitative neuromuscular monitoring and pharmacological reversal of muscle relaxation reduce the incidence of residual neuromuscular block. The question arises whether this is suitable to create a pragmatic algorithm integrating these three individual methods to reduce paralysis-associated complications? METHODS: A selective literature search was carried out in PubMed and guidelines of national specialist societies were searched using special terms. RESULTS: The incidence of residual neuromuscular block varied among the studies but was as high as 93%. Using calibrated acceleromyography it is possible to identify a residual relaxation with a negative predictive value of 97% (95% confidence interval, CI 83-100%). Reversal by administration of the acetylcholinesterase inhibitor neostigmine reduces the incidence of residual neuromuscular block to 15.4%, in combination with calibrated acceleromyography to 3.3%. Reversal with sugammadex can nearly completely eliminate residual neuromuscular block. Quantitative neuromuscular monitoring and pharmacological reversal can be suitably integrated into a stage-based, pragmatic treatment algorithm. CONCLUSION: The algorithm-based concept of quantitative neuromuscular monitoring and pharmacological reversal using neostigmine and sugammadex enables residual neuromuscular block to be treated within 10 min before extubation of the patient. Ongoing educational programs are essential for implementation of modern muscle relaxant management concepts. Quantitative neuromuscular monitoring should be mandatory for all patients receiving neuromuscular blocking drugs. It would be desirable that German-speaking societies for anesthesiology make appropriate recommendations in guidelines.

Comparison of rocuronium requirement in children with continuous infusion versus intermittent bolus: A randomised controlled trial.

BACKGROUND: Minimising rocuronium administration during paediatric surgery helps to reduce the incidence of residual muscular blockade. OBJECTIVE: To determine whether intermittent bolus injection (Bolus group) or continuous infusion (group) requires the lesser amount of rocuronium. DESIGN: A randomised, single-blind controlled trial. SETTING: A single university hospital from March to June 2017. PATIENTS: Sixty-six children undergoing general anaesthesia. INTERVENTIONS: Dose of rocuronium for maintenance of muscle relaxation in either Bolus or continuous infusion group. Train-of-four (TOF) count of two was maintained during surgery. When TOF count reached three, 0.1 mg kg of rocuronium was administered in Bolus group or infused at an increased rate of 0.1 mg kg h in continuous infusion group. MAIN OUTCOME MEASURES: Primary outcome was the dose of rocuronium given (µg kg min). The recovery time from the TOF count four to TOF 0.7 (RT0.7), and 0.9 (RT0.9) were recorded. All adverse events were recorded up to 30 min after extubation. RESULTS: Mean (SD) rocuronium dose in the Bolus group was 6.1 (0.9), [95% confidence interval (95% CI) 5.7 to 6.4] µg kg min and 4.9 (1.0), (95% CI 4.6 to 5.3) µg kg min in the continuous infusion group (P = 0.001). RT0.7 was 24.0 (13.7), 95% CI 19.3 to 28.7) min in the Bolus group, and 25.7 (16.0), (95% CI 20.2 to 31.2) min in the continuous infusion group (P = 0.73). RT0.9 was 30.7 (17.1), (95% CI 24.9 to 36.5) min in the Bolus group, and 30.0 (17.6), (95% CI 24.0 to 36.0) min in the continuous infusion group (P = 0.91). The incidence of adverse events was not significantly different between two groups. CONCLUSION: In children undergoing general anaesthesia, the dose of rocuronium given by continuous administration was less than that with intermittent bolus. TRIAL REGISTRATION: ClinicalTrials.gov (identifier: NCT03060707).

Incidence, risk factors, and consequences of residual neuromuscular block in the United States: The prospective, observational, multicenter RECITE-US study.

STUDY OBJECTIVE: To determine the incidence burden and associated risk factors of residual neuromuscular block (rNMB) during routine U.S. hospital care. DESIGN: Blinded multicenter cohort study. SETTING: Operating and recovery rooms of ten community and academic U.S. hospitals. PATIENTS: Two-hundred fifty-five adults, ASA PS 1-3, underwent elective abdominal surgery with general anesthesia and ≥1 dose of non-depolarizing neuromuscular blocking agent (NMBA) for endotracheal intubation and/or maintenance of NMB between August 2012 and April 2013. INTERVENTIONS: TOF measurements using acceleromyography were performed on patients already receiving routine anesthetic care for elective open or laparoscopic abdominal surgery. Measurements allowed assessment of the presence of residual neuromuscular block (rNMB), defined as a train-of-four (TOF) ratio <0.9 at tracheal extubation. We recorded patient and procedural characteristics and assessed TOF ratios (T4/T1) at various times throughout the procedure and at tracheal extubation. Differences in patient and clinical characteristics were compared using Fisher's exact test for categorical variables and t-test for continuous variables. Multivariate logistic regression assessed risk factors associated with rNMB at extubation. MAIN RESULTS: Most of the study population, 64.7% (n = 165) had rNMB (TOF ratio < 0.9), among them, 31.0% with TOF ratio <0.6. Among those receiving neostigmine and/or qualitative peripheral nerve stimulation per clinical decision, 65.0% had rNMB. After controlling for confounders, we observed male gender (odds ratio: 2.60, P = 0.008), higher BMI (odds ratio: 1.04/unit, P = 0.043), and surgery at a community hospital (odds ratio: 3.15, P = 0.006) to be independently associated with increased odds of rNMB. CONCLUSIONS: Assessing TOF ratios blinded to the care team, we found that the majority of patients (64.7%) in this study had rNMB at tracheal extubation, despite neostigmine administration and qualitative peripheral nerve stimulation used for routine clinical care. Qualitative neuromuscular monitoring and clinical judgement often fails to detect rNMB after neostigmine reversal with potential severe consequences to the patient. Our data suggests that clinical care could be improved by considering quantitative neuromuscular monitoring for routine care.

Atypical reaction to anesthesia in Duchenne/Becker muscular dystrophy / Reação atípica à anestesia em distrofia muscular de Duchenne/Becker

Abstract Background and objectives Duchenne/Becker muscular dystrophy affects skeletal muscles and leads to progressive muscle weakness and risk of atypical anesthetic reactions following exposure to succinylcholine or halogenated agents. The aim of this report is to describe the investigation and diagnosis of a patient with Becker muscular dystrophy and review the care required in anesthesia. Case report Male patient, 14 years old, referred for hyperCKemia (chronic increase of serum creatine kinase levels - CK), with CK values of 7,779-29,040 IU.L-1 (normal 174 IU.L-1). He presented with a discrete delay in motor milestones acquisition (sitting at 9 months, walking at 18 months). He had a history of liver transplantation. In the neurological examination, the patient showed difficulty in walking on one's heels, myopathic sign (hands supported on the thighs to stand), high arched palate, calf hypertrophy, winged scapulae, global muscle hypotonia and arreflexia. Spirometry showed mild restrictive respiratory insufficiency (forced vital capacity: 77% of predicted). The in vitro muscle contracture test in response to halothane and caffeine was normal. Muscular dystrophy analysis by Western blot showed reduced dystrophin (20% of normal) for both antibodies (C and N-terminal), allowing the diagnosis of Becker muscular dystrophy. Conclusion On preanesthetic assessment, the history of delayed motor development, as well as clinical and/or laboratory signs of myopathy, should encourage neurological evaluation, aiming at diagnosing subclinical myopathies and planning the necessary care to prevent anesthetic complications. Duchenne/Becker muscular dystrophy, although it does not increase susceptibility to MH, may lead to atypical fatal reactions in anesthesia.

Resumo Justificativa/objetivos Distrofia muscular de Duchenne/Becker afeta a musculatura esquelética e leva a fraqueza muscular progressiva e risco de reações atípicas anestésicas após exposição à succinilcolina ou halogenados. O objetivo do presente relato é descrever investigação e diagnóstico de paciente com distrofia muscular de Becker e revisar os cuidados necessários na anestesia. Relato de caso Paciente masculino, 14 anos, encaminhado por hiperCKemia (aumento crônico dos níveis séricos de creatinoquinase - CK), com valores de CK de 7.779-29.040 UI.L-1 (normal 174 UI.L-1). Apresentou discreto atraso da aquisição de marcos motores (sentou aos nove meses, andou aos 18). Antecedente de transplante hepático. No exame neurológico apresentava dificuldade para andar nos calcanhares, levantar miopático (apoiava mãos nas coxas para ficar de pé), palato arqueado alto, hipertrofia de panturrilhas, escápulas aladas, hipotonia muscular global e arreflexia. Havia insuficiência respiratória restritiva leve na espirometria (capacidade vital forçada: 77% do previsto). O teste de contratura muscular in vitro em resposta ao halotano e à cafeína foi normal. Estudo da distrofina muscular por técnica de Western blot mostrou redução da distrofina (20% do normal) para ambos os anticorpos (C e N-terminal), e permitiu o diagnóstico de distrofia muscular de Becker. Conclusão Na avaliação pré-anestésica, história de atraso do desenvolvimento motor, bem como sinais clínicos e/ou laboratoriais de miopatia, deve motivar avaliação neurológica, com o objetivo de diagnosticar miopatias subclínicas e planejar cuidados necessários para prevenir complicações anestésicas. Distrofia muscular de Duchenne/Becker, apesar de não conferir suscetibilidade aumentada à HM, pode levar a reações atípicas fatais na anestesia.

Dexamethasone concentration affecting rocuronium-induced neuromuscular blockade and sugammadex reversal in a rat phrenic nerve-hemidiaphragm model: An ex vivo study.

BACKGROUND: The concentration range of dexamethasone that inhibits neuromuscular blockade (NMB) and sugammadex reversal remains unclear. OBJECTIVE: To evaluate the effects of dexamethasone on rocuronium-induced NMB and sugammadex reversal. DESIGN: Ex vivo study. SETTING: Asan Institute for Life Sciences, Asan Medical Center, Korea, from July 2015 to November 2015. ANIMALS: One hundred sixty male Sprague-Dawley rats. INTERVENTIONS: We assessed the effect of four concentrations of dexamethasone [0, 0.5, 5 (clinical concentrations) and 50 µg ml (experimental concentration)] on partial NMB on 40 phrenic nerve-hemidiaphragm preparations (n=10 per concentration). Once the first twitch of train-of-four (TOF) had been depressed by 50% with rocuronium, dexamethasone was administered. To assess the effect of dexamethasone on sugammadex reversal, 120 phrenic nerve-hemidiaphragm preparations were used in three subexperiments (n=40 per experiment), using three administration regimens of rocuronium-equimolar sugammadex: a single dose, a split-dose (split and ) and a reduced split-dose (split and ). After complete NMB was achieved, dexamethasone and sugammadex were administered. MAIN OUTCOME MEASURES: The change in the first twitch height, the recovery time to a TOF ratio at least 0.9, and the TOF ratio at 30 min were evaluated. RESULTS: There were no significant differences in the first twitch height among groups (P = 0.532). With a single dose of sugammadex, dexamethasone did not affect the recovery time to a TOF ratio at least 0.9 (P = 0.070). After using a split-dose of sugammadex, the recovery time to a TOF ratio at least 0.9 was delayed only at a concentration of 50 µg ml of dexamethasone. With a reduced split-dose of sugammadex, the TOF ratio at 30 min was lowered only by a concentration of 50 µg ml of dexamethasone (P < 0.010). CONCLUSION: Acute bolus administration of dexamethasone at clinical concentrations had no effect on NMB or on sugammadex reversal.

Emergence times and airway reactions during general anaesthesia with remifentanil and a laryngeal mask airway: A multicentre randomised controlled trial.

BACKGROUND: Avoidance of airway complications and rapid emergence from anaesthesia are indispensable for the use of a laryngeal mask airway (LMA). Evidence from adequately powered randomised studies with a low risk of bias for the optimal anaesthetic in this context is limited. OBJECTIVE: We tested the hypothesis that when using remifentanil-based intra-operative analgesia, desflurane would be the most suitable anaesthetic: with noninferiority in the occurrence of upper airway complications and superiority in emergence times compared with sevoflurane or propofol. DESIGN: A randomised, multicentre, partially double-blinded, three-arm, parallel-group study. SETTING: Two university and two regional German hospitals, from February to October 2015. PATIENTS: A total of 352 patients (age 18 to 75 years, ASA physical status I to III, BMI less than 35 kg m and fluent in German) were enrolled in this study. All surgery was elective with a duration of 0.5 to 2 h, and general anaesthesia with a LMA was feasible. INTERVENTION: The patients were randomised to receive desflurane, sevoflurane or propofol anaesthesia. MAIN OUTCOME MEASURES: This study was powered for the primary outcome 'time to state date of birth' and the secondary outcome 'intra-operative cough'. Time to emergence from anaesthesia and the incidence of upper airway complications were assessed on the day of surgery. RESULTS: The primary outcome was analysed for 343 patients: desflurane (n=114), sevoflurane (n=111) and propofol (n=118). The desflurane group had the fastest emergence. The mean (± SD) times to state the date of birth following desflurane, sevoflurane and propofol were 8.1 ±â€Š3.6, 10.1 ±â€Š4.0 and 9.8 ±â€Š5.1 min, respectively (P < 0.01). There was no difference in upper airway complications (cough and laryngospasm) across the groups, but these complications were less frequent than in previous studies. CONCLUSION: When using a remifentanil infusion for intra-operative analgesia in association with a LMA, desflurane was associated with a significantly faster emergence and noninferiority in the incidence of intra-operative cough than either sevoflurane or Propofol. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02322502; EudraCT identifier: 2014-003810-96.

Effect of creatine phosphate sodium on bispectral index and recovery quality during the general anaesthesia emergence period in elderly patients: A randomized, double-blind, placebo-controlled trial.

Objective To evaluate the effect of creatine phosphate sodium on bispectral index (BIS) and recovery quality during the general anaesthesia emergence period in elderly patients. Methods This randomized, double-blind, placebo-controlled study enrolled patients undergoing transabdominal cholecystectomy under general anaesthesia. Patients were randomly assigned to receive either creatine phosphate sodium (1.0 g/100 ml 0.9% saline; group P) or 100 ml 0.9% saline (group C) over 30 minutes during surgical incision. The BIS values were recorded at anaesthesia induction (T0), skin incision (T1), cutting the gallbladder (T2), suturing the peritoneum (T3), skin closure (T4), sputum suction (T5), extubation (T6) and 1 min (T7), 5 min (T8), 10 min (T9), and 15 min (T10) after extubation. The anaesthesia duration, operation time, waking time, extubation time, consciousness recovery time, time in the postanaesthesia care unit (PACU), and the Steward recovery scores at T7, T8, T9 and T10 were recorded. Results A total of 120 elderly patients were randomized equally to the two groups. Compared with group C, the BIS values were significantly higher in group P at T5, T6, T7 and T8; and the Steward recovery scores at T7 and T8 were significantly higher in group P. The waking time, extubation time, consciousness recovery time and time in the PACU were significantly shorter in group P compared with group C. Conclusion Creatine phosphate sodium administered during transabdominal cholecystectomy can improve BIS values and recovery following general anaesthesia in elderly patients.

Neostigmine-based reversal of intermediate acting neuromuscular blocking agents to prevent postoperative residual paralysis: A systematic review.

BACKGROUND: Neostigmine is widely used to antagonise residual paralysis. Over the last decades, the benchmark of acceptable neuromuscular recovery has increased progressively to a train-of-four (TOF) ratio of at least 0.9. Raising this benchmark may impact on the efficacy of neostigmine. OBJECTIVE(S): The systematic review evaluates the efficacy of neostigmine to antagonise neuromuscular block to attain a TOF ratio of at least 0.9. DESIGN: We performed a systematic search of the literature from January 1992 to December 2015. DATA SOURCES OR SETTING: PubMed, EMBASE and the Cochrane Controlled Clinical Trials database were searched for randomised controlled human studies. Search was performed without language restrictions, using the following free text terms: 'neostigmine', 'sugammadex', 'edrophonium' or 'pyridostigmine' AND 'neuromuscular block', 'reversal' or 'reverse'. ELIGIBILITY CRITERIA: Studies were accepted for inclusion if they used quantitative neuromuscular monitoring and neostigmine as the reversal agent. Selected trials were checked by two of the authors for data integrity. Trials relevant for inclusion had to report the number of patients included, the type of anaesthetic maintenance, the type of neuromuscular blocking agent used, the reversal agent and dose used, the depth of neuromuscular block when neostigmine was administered and the reversal time (time from injection of neostigmine until a TOF ratio ≥0.9 was attained). RESULTS: 19 trials were eligible for quantitative analysis. In patients with deep residual block [T1 (first twitch height) <10%] 70 µg kg neostigmine was used (five trials, 118 patients), and the mean reversal time was 17.1 min (95% confidence interval (CI) [12.4 to 21.8]). In patients with moderate residual block (T1 10% to <25%) the mean neostigmine dose was 56 µg kg (seven trials, 342 patients), and the mean reversal time was 11.3 min (95% CI [9.2 to 13.4]). In patients with a shallow residual block (T1 ≥ 25%) the mean neostigmine dose was 40 µg kg (13 trials, 535 patients), and the mean reversal time was 8.0 min (95% CI [6.8 to 9.2]). CONCLUSION: Based on the findings of this systematic review, we recommend that the administration of neostigmine be delayed until an advanced degree of prereversal recovery has occurred (i.e. a T1 >25% of baseline), or that a recovery time longer than 15 min be accepted.

Development of an algorithm using clinical tests to avoid post-operative residual neuromuscular block.

BACKGROUND: Quantitative neuromuscular monitoring is the gold standard to detect postoperative residual curarization (PORC). Many anesthesiologists, however, use insensitive, qualitative neuromuscular monitoring or unreliable, clinical tests. Goal of this multicentre, prospective, double-blinded, assessor controlled study was to develop an algorithm of muscle function tests to identify PORC. METHODS: After extubation a blinded anesthetist performed eight clinical tests in 165 patients. Test results were correlated to calibrated electromyography train-of-four (TOF) ratio and to a postoperatively applied uncalibrated acceleromyography. A classification and regression tree (CART) was calculated developing the algorithm to identify PORC. This was validated against uncalibrated acceleromyography and tactile judgement of TOF fading in separate 100 patients. RESULTS: After eliminating three tests with poor correlation, a model with four tests (r = 0.844) and uncalibrated acceleromyography (r = 0.873) were correlated to electromyographical TOF-values without losing quality of prediction. CART analysis showed that three consecutively performed tests (arm lift, head lift and swallowing or eye opening) can predict electromyographical TOF. Prediction coefficients reveal an advantage of the uncalibrated acceleromyography in terms of specificity to identify the EMG measured train-of-four ratio < 0.7 (100% vs. 42.9%) and <0.9 (89.7% vs. 34.5%) compared to the algorithm. However, due to the high sensitivity of the algorithm (100% vs. 94.4%), the risk to overlook an awake patient with a train-of-four ratio < 0.7 was minimal. Tactile judgement of TOF fading showed poorest sensitivity and specifity at train of four ratio < 0.9 (33.7%, 0%) and <0.7 (18.8%, 16.7%). CONCLUSIONS: Residual neuromuscular blockade can be detected by uncalibrated acceleromyography and if not available by a pathway of four clinical muscle function tests in awake patients. The algorithm has a discriminative power comparable to uncalibrated AMG within TOF-values >0.7 and <0.3. TRIAL REGISTRATION: Clinical Trials.gov (principal investigator's name: CU, and identifier: NCT03219138) on July 8, 2017.

Effects of calcium chloride coadministered with neostigmine on neuromuscular blockade recovery: A double-blind randomised study.

BACKGROUND: Ionised calcium plays an important role in neuromuscular transmission, but its effects on the reversal of nondepolarising neuromuscular blockade have not been fully evaluated. OBJECTIVE: We examined whether calcium chloride coadministered with neostigmine could enhance the rate of neuromuscular recovery. DESIGN: Randomised double-blind trial. SETTING: A tertiary teaching hospital. PATIENTS: In total, 53 patients undergoing elective surgery under general anaesthesia with neuromuscular monitoring by acceleromyography using a TOF-Watch SX monitor. INTERVENTIONS: Patients were randomly allocated to receive either 5 mg kg of calcium chloride (calcium group, n = 26) or the same volume of normal saline (control group, n = 27) coadministered with 25 µg kg of neostigmine and 15 µg kg of atropine at the end of surgery. MAIN OUTCOME MEASURES: The primary end point was the neuromuscular recovery time [time from neostigmine administration to recovery of the TOF ratio (TOFr) to 0.9]. Secondary end points included the TOFr at 5, 10 and 20 min after neostigmine administration and the incidence of postoperative residual curarisation (PORC), defined as a TOFr less than 0.9 at each time point. RESULTS: The neuromuscular recovery time was significantly faster in the calcium group than in the control group (median [Q1 to Q3]; 5.0 [3.0 to 7.0] vs. 6.7 [5.7 to 10.0] min, respectively; P = 0.007). At 5 min after neostigmine administration, the TOFr was higher [87 (74 to 100) vs. 68 (51 to 81)%, respectively; P = 0.002] and the incidence of PORC was lower (50.0 vs. 81.5%, respectively; P = 0.016) in the calcium group than in the control group. There were no differences between the two groups with respect to the TOFr or incidence of PORC at 10 and 20 min after neostigmine administration. CONCLUSION: Calcium chloride coadministered with neostigmine enhanced neuromuscular recovery in the early period of nondepolarising neuromuscular blockade reversal.

Caffeine accelerates recovery from general anesthesia via multiple pathways.

Various studies have explored different ways to speed emergence from anesthesia. Previously, we have shown that three drugs that elevate intracellular cAMP (forskolin, theophylline, and caffeine) accelerate emergence from anesthesia in rats. However, our earlier studies left two main questions unanswered. First, were cAMP-elevating drugs effective at all anesthetic concentrations? Second, given that caffeine was the most effective of the drugs tested, why was caffeine more effective than forskolin since both drugs elevate cAMP? In our current study, emergence time from anesthesia was measured in adult rats exposed to 3% isoflurane for 60 min. Caffeine dramatically accelerated emergence from anesthesia, even at the high level of anesthetic employed. Caffeine has multiple actions including blockade of adenosine receptors. We show that the selective A2a adenosine receptor antagonist preladenant or the intracellular cAMP ([cAMP]i)-elevating drug forskolin, accelerated recovery from anesthesia. When preladenant and forskolin were tested together, the effect on anesthesia recovery time was additive indicating that these drugs operate via different pathways. Furthermore, the combination of preladenant and forskolin was about as effective as caffeine suggesting that both A2A receptor blockade and [cAMP]i elevation play a role in caffeine's ability to accelerate emergence from anesthesia. Because anesthesia in rodents is thought to be similar to that in humans, these results suggest that caffeine might allow for rapid and uniform emergence from general anesthesia in humans at all anesthetic concentrations and that both the elevation of [cAMP]i and adenosine receptor blockade play a role in this response.NEW & NOTEWORTHY Currently, there is no method to accelerate emergence from anesthesia. Patients "wake" when they clear the anesthetic from their systems. Previously, we have shown that caffeine can accelerate emergence from anesthesia. In this study, we show that caffeine is effective even at high levels of anesthetic. We also show that caffeine operates by both elevating intracellular cAMP levels and by blocking adenosine receptors. This complicated pharmacology makes caffeine especially effective in accelerating emergence from anesthesia.

Recommendations on the use of deep neuromuscular blockade by anaesthesiologists and surgeons. AQUILES (Anestesia QUIrúrgica para Lograr Eficiencia y Seguridad) Consensus. / Recomendaciones sobre el uso de bloqueo neuromuscular profundo por parte de anestesiólogos y cirujanos. Consenso AQUILES (Anestesia QUIrúrgica para Lograr Eficiencia y Seguridad).

INTRODUCTION: Neuromuscular blockade enables airway management, ventilation and surgical procedures. However there is no national consensus on its routine clinical use. The objective was to establish the degree of agreement among anaesthesiologists and general surgeons on the clinical use of neuromuscular blockade in order to make recommendations to improve its use during surgical procedures. METHODS: Multidisciplinary consensus study in Spain. Anaesthesiologists experts in neuromuscular blockade management (n=65) and general surgeons (n=36) were included. Delphi methodology was selected. A survey with 17 final questions developed by a dedicated scientific committee was designed. The experts answered the successive questions in two waves. The survey included questions on: type of surgery, type of patient, benefits/harm during and after surgery, impact of objective neuromuscular monitoring and use of reversal drugs, viability of a multidisciplinary and efficient approach to the whole surgical procedure, focussing on the level of neuromuscular blockade. RESULTS: Five recommendations were agreed: 1) deep neuromuscular blockade is very appropriate for abdominal surgery (degree of agreement 94.1%), 2) and in obese patients (76.2%); 3) deep neuromuscular blockade maintenance until end of surgery might be beneficial in terms of clinical aspects, such as as immobility or better surgical access (86.1 to 72.3%); 4) quantitative monitoring and reversal drugs availability is recommended (89.1%); finally 5) anaesthesiologists/surgeons joint protocols are recommended. CONCLUSIONS: Collaboration among anaesthesiologists and surgeons has enabled some general recommendations to be established on deep neuromuscular blockade use during abdominal surgery.