Use Of Neuromuscular Blocking Agents Research Articles

Validation of neuromuscular blocking agent use in acute respiratory distress syndrome: a meta-analysis of randomized trials

BackgroundWe aimed to synthesize up-to-date trials to validate the effects of neuromuscular blocking agent (NMBA) use in patients with moderate-to-severe acute respiratory distress syndrome (ARDS).MethodsSeveral databases including PubMed, EMBASE, Web of Science, and Cochrane Central Register were searched up to November 14, 2019. All randomized trials investigating the use of NMBAs in patients with moderate-to-severe ARDS and reporting mortality data were included in the meta-analysis. The primary outcome was mortality, and the secondary outcomes were clinical outcomes, including respiratory physiological parameters, incidence of barotrauma, ICU-free days, and ventilation-free days.ResultsA total of 7 trials enrolling 1598 patients were finally included in this meta-analysis. The results revealed that the use of NMBAs in moderate-to-severe ARDS could significantly decrease the mortality truncated to day 28 (RR 0.74, 95% CI 0.56 to 0.98, P = 0.03) and day 90 (RR 0.77, 95% CI 0.60 to 0.99, P = 0.04). NMBA use could significantly decrease the incidence of barotrauma (RR 0.56, 95% CI 0.36 to 0.87, P = 0.009). No significant difference was observed in ICU-free days or ventilation-free days between the NMBA and control groups.ConclusionThe use of NMBAs could significantly decrease mortality in moderate-to-severe ARDS patients and decrease the incidence of barotrauma during mechanical ventilation. However, more large-scale randomized trials are needed to further validate the effect of NMBA use in ARDS.

Neuromuscular blocking agents for acute respiratory distress syndrome: an updated meta-analysis of randomized controlled trials

BackgroundsThe aim of this study is investigating the benefits and harms of neuromuscular blocking agents (NMBAs) in patients with acute respiratory distress syndrome (ARDS).MethodsWe comprehensively searched PubMed, EMBASE, and Cochrane library for randomized controlled trials comparing NMBAs to any other comparator. We pooled data using relative risk (RR) for dichotomous outcomes and weighted mean difference (WMD) for continuous outcomes, with 95% confidence intervals. We assessed the quality of included studies using the Cochrane tool and levels of evidence using the GRADE method.ResultsFinally, six RCTs (n = 1557 patients) were eligible for analysis. The results showed NMBAs use was not associated with reduced 28 days mortality (RR 0.78; 95% CI, 0.58 to 1.06; P = 0.11), 90 days mortality (RR, 0.92; 95% CI, 0.81 to 1.04; P = 0.16), and intensive care unit (ICU) mortality (RR, 0.90; 95% CI, 0.79 to 1.03; P = 0.13) in patients with ARDS. However, 21–28 days mortality was slightly lower in patients received NMBAs (RR 0.73; 95% CI, 0.54 to 0.99; P = 0.04; I2 = 53%). Besides, NMBAs use could improve the PaO2/FiO2 ratio at 48 and 72 h, decrease plateau pressure and PEEP at 72 h. Additionally, NMBAs had no significant effects on days free of ventilation at day 28 (WMD, 0.55; 95% CI, − 0.46 to 1.57; P = 0.29), days not in ICU at day 28 (WMD, 0.12; 95% CI, − 0.85 to 1.08; P = 0.82), ICU-acquired weakness (RR, 1.23; 95% CI, 0.99 to 1.93; P = 0.06). Finally, NMBAs use was associated with a lower risk of barotrauma (RR, 0.55; 95% CI, 0.35 to 0.85; P = 0.007).ConclusionIn patients with respiratory distress syndrome, NMBAs may be beneficial in reverse refractory hypoxemia and may be associated with reduced short-term mortality and incidence of barotrauma. However, there is no significant effects of NMBAs on mid-term and long-term mortality, and further studies are required.

How to optimize neuromuscular blockade in ambulatory setting?

The purpose of this review is to discuss the optimal use of neuromuscular blocking agents (NMBA) during ambulatory surgery, and to provide an update on the routine use of neuromuscular monitoring and the prevention of residual paralysis. The number of major surgical procedures performed in ambulatory patients is likely to increase in the coming years, following the development of laparoscopic and thoracoscopic procedures. To successfully complete these procedures, the proper use of NMBA is mandatory. The use of NMBA not only improves intubating conditions but also ventilation. Recent studies demonstrate that NMBA are much more the solution rather than the cause of airway problems. There is growing evidence that the paralysis of the diaphragm and the abdominal wall muscles, which are resistant to NMBA is of importance during laparoscopic surgery. Further studies are still required to determine when deep neuromuscular block [posttetanic count (PTC) < 5] is required perioperatively. There is now a consensus to use perioperatively neuromuscular monitoring and particularly objective neuromuscular monitoring in combination with reversal agents to avoid residual paralysis and its related morbidity (e.g. respiratory complications in the PACU). Recent data suggest that it is now possible to obtain a tight control of neuromuscular block to maintain optimal relaxation tailored to the surgical requirements and to obtain a rapid and reliable recovery at the end of the procedure.

Current Use of Neuromuscular Blocking Agents in Intensive Care Units.

Neuromuscular blocking agents can be used for purposes such as eliminating ventilator-patient dyssynchrony, facilitating gas exchange by reducing intra-abdominal pressure and improving chest wall compliance, reducing risk of lung barotrauma, decreasing contribution of muscles to oxygen consumption by preventing shivering and limiting elevations in intracranial pressure caused by airway stimulation in patients supported with mechanical ventilation in intensive care units. Adult Respiratory Distress Syndrome (ARDS), status asthmaticus, increased intracranial pressure and therapeutic hypothermia following ventricular fibrillation-associated cardiac arrest are some of clinical conditions that can be sustained by neuromuscular blockade. Appropriate indication and clinical practice have gained importance considering side effects such as ICU-acquired weakness, masking seizure activity and longer durations of hospital and ICU stays. We mainly aimed to review the current literature regarding neuromuscular blockade in up-to-date clinical conditions such as improving oxygenation in early ARDS and preventing shivering in the therapeutic hypothermia along with summarising the clinical practice in adult ICU in this report.

Utilisation of medications among elderly patients in intensive care units: a cross-sectional study using a nationwide claims database

ObjectivesClinical practice guidelines for the management of pain and sedation in critically ill patients have been developed and applied; however, there is limited data on medication use among elderly patients....

Effect of Neuromuscular Blocking Agents on Sedation Requirements in Trauma Patients with an Open Abdomen.

The appropriate level of sedation in patients with an open abdomen following damage control laparotomy (DCL) is debated. Chemical paralysis with neuromuscular blocking agents (NMBAs) has been used to decrease time to abdominal closure. We sought to evaluate the effect of NMBA use on sedation requirements in patients with an open abdomen and to determine the effect of sedation on patient outcomes. A retrospective cohort study was conducted at an American College of Surgeons' verified level 1 trauma center. Adult trauma patients who underwent DCL between 2009 and 2015 were included. Patients with an intensive care unit length of stay of less than 48hours and those who died before abdominal closure were excluded. The NMBA+ group received continuous NMBA within 24hours of DCL; the NMBA- group did not. The primary outcome was cumulative sedation dose during the 7days following DCL. Secondary outcomes included Richmond Agitation-Sedation Scale (RASS) score, mechanical ventilation-free days, and delirium-coma-free days. Delirium-coma-free days were analyzed with linear regression. A total of 222 patients were included (NMBA+ 125; NMBA- 97). Demographics were similar between groups including age, Injury Severity Score, and mechanism of injury. The median time to closure in the overall cohort was 2days (interquartile range [IQR] 1-2days). Propofol and fentanyl were the primary sedatives used. The NMBA+ group received higher cumulative doses of propofol (NMBA+ 5405mg, IQR 3103-10,573mg; NMBA- 3601mg, IQR 1605-6887mg; p=0.007), but not of fentanyl. Time to abdominal closure, but not NMBA use, was associated with a higher cumulative propofol dose on multivariate analysis. The NMBA+ group had significantly lower RASS scores on the first 3days following DCL. Mechanical ventilation-free days (NMBA+ 20days vs NMBA- 18days, p=0.960) and delirium-coma-free days (NMBA+ 18days vs NMBA- 18days, p=0.610) were similar between the groups. On linear regression, cumulative propofol dose was associated with fewer delirium-coma-free days (β-coefficient -0.007, 95% confidence interval -0.015 to -0.003). In trauma patients managed with DCL, higher cumulative sedative doses were administered in patients who received adjunctive NMBA, although NMBA therapy was not associated with a higher cumulative propofol dose on multivariate analysis. Consideration must be given to the potential effect of sedation on delirium and awakening following DCL.

Feasibility of an alternative, physiologic, individualized open-lung approach to high-frequency oscillatory ventilation in children

BackgroundHigh-frequency oscillatory ventilation (HFOV) is a common but unproven management strategy in paediatric critical care. Oscillator settings have been traditionally guided by patient age and/or weight rather than by lung mechanics, thereby potentially negating any beneficial effects. We have adopted an open-lung HFOV strategy based on a corner frequency approach using an initial incremental–decremental mean airway pressure titration manoeuvre, a high frequency (8–15 Hz), and high power to initially target a proximal pressure amplitude (∆Pproximal) of 70–90 cm H2O, irrespective of age or weight.MethodsWe reviewed prospectively collected data on patients < 18 years of age who were managed with HFOV for acute respiratory failure. We measured metrics for oxygenation, ventilation, and haemodynamics as well as the use of sedative-analgesic medications and neuromuscular blocking agents.ResultsData from 115 non-cardiac patients were analysed, of whom 53 had moderate-to-severe paediatric acute respiratory distress syndrome (PARDS). Sixteen patients (13.9%) died. Frequencies≥ 8 Hz and high ∆Pproximal were achieved in all patients irrespective of age or PARDS severity. Patients with severe PARDS showed the greatest improvement in oxygenation. pH and PaCO2 normalized in all patients. Haemodynamic parameters, cumulative amount of fluid challenges, and daily fluid balance did not deteriorate after transitioning to HFOV in any age or PARDS severity group. We observed a transient increase neuromuscular blocking agent use after switching to HFOV, but there was no increase in the daily cumulative amount of continuous midazolam or morphine in any age or PARDS severity group. No patients experienced clinically apparent barotrauma.ConclusionsThis is the first study reporting the feasibility of an alternative, individualized, physiology-based open-lung HFOV strategy targeting high F and high ∆Pproximal. No adverse effects were observed with this strategy. Our findings warrant further systematic evaluation.

Effects of the use of neuromuscular blocking agents on acute respiratory distress syndrome outcomes: A systematic review.

Acute respiratory distress syndrome (ARDS) is a high-mortality disease with limited treatment options. Optimization of gas exchange while limiting damage to the lungs is key. The use of neuromuscular blocking agents may limit hypoxemia while preventing ventilator-induced lung injury. A literature search was conducted using Ovid Medline and the exploded MeSH terms ARDS, acute respiratory distress syndrome, neuromuscular blockade, neuromuscular blocking agents, and paralytics. With limitations applied, three original randomized controlled trials investigating the use of neuromuscular blocking agents (NMBAs) in severe ARDS were identified and reviewed. Two of the three trials demonstrated improved primary outcomes with the use of NMBA. The third trial was underpowered (due to unanticipated low mortality in the control group) and did not show a statistically significant improvement in the primary outcome. As all the original research was conducted by the same group, further investigation is necessary to assess generalizability and confirm results. Currently, additional research is underway, focusing on early enrollment and narrow inclusion criteria. Secondary analysis from two separate groups concluded the improved outcomes, with no evidence of increased risk of critical illness polyneuropathy or myopathy, suggest that the use of NMBAs in severe ARDS is appropriate.

Abstract P-474: NEUROMUSCOLAR BLOCKING AGENTS IN PEDIATRIC INTENSIVE CARE UNITS: A MULTICENTER REPORT OF THE ITALIAN NETWORK OF PEDIATRIC INTENSIVE CARE UNIT STUDY GROUP (TIPNET)

Aims & Objectives: In the past 20 years, the use of neuromuscular blocking agents (NMBAs) in pediatric intensive care units (PICUs) is decreased, but still described in mechanically ventilated (MV) patients, often without definite indications. Our aim was to evaluate the NMBAs use and its associated factors in MV children. Methods We performed a retrospective observational multicenter study using a prospective compiled electronic web-based-national registry (TIPNet) of patients admitted to 18 Italians’ PICUs (January 2010-October 2017). We included all MV children (<18 years-of-age) and compared patients who received NMBA (Cur+) with a control group who did not receive this therapy (Cur-). Results A total of 7957 patients were included, 800 (10%) of them were Cur+ (Figure-1). There were no significant differences about race, gender and comorbidities between the two populations. Cur+ patients had a significantly lower age at admission (21months [interquartile range (IQR) 5–69] vs 30months [IQR 7–93],p<0.001), lower weight (10kg [IQR 6–19] vs 12kg [IQR 7–24]),p<0.001), and higher PIM3 (0.02 [IQR 0.01–0.07] vs 0.01 [IQR 0.01–0.04],p< 0.001). Cur+ patients showed longer ventilation duration (4days [IQR 1–10] vs 1day [IQR 0–4],p<0.001) and length of PICU stay (8days [IQR 2–17] vs 3days [IQR 1–9],p<0.001), as well as a significantly higher mortality rate (15%vs 6%,p<0.001). Conclusions A non-negligible proportion of MV children in PICUs received NMBAs. Their use is more frequent in younger age and more critically ill patients. Prolonged MV, longer PICU stay and higher mortality rate were statistically associated. Further studies are needed to clarify the specific indications, patients’ clinical features and the concomitant pharmacological management.

Profound Neuromuscular Blockade: Advantages and Challenges for Patients, Anesthesiologists, and Surgeons

Rarely has the introduction of an anesthetic agent or adjunct been as anticipated or needed as that of sugammadex. Residual paralysis after neuromuscular blockade (NMB) occurs frequently and is associated with a range of adverse effects ranging from patient discomfort to respiratory complications and death. Residual neuromuscular block is due to a number of factors that include overdosing of neuromuscular blocking agents (NMBAs), inadequate monitoring of the effect of NMBAs, and the limitations of anticholinesterses to antagonize neuromuscular block (relatively slow onset of effect and inability to antagonize deep levels of NMB. Sugammadex, a selective relaxant binding agent, will, when dosed appropriately, rapidly and completely reverse the effects of vecuronium and rocuronium, steroidal NMBAs, from any depth of NMB. While this approach has the potential to increase safety in the perioperative use of NMBAs, it also allows clinicians to revise dosing paradigms to improve surgical conditions and, importantly, patient outcome.

Sedation and neuromuscular blocking agents in acute respiratory distress syndrome.

Mechanical ventilation (MV) is the cornerstone of acute respiratory distress syndrome (ARDS) management. The use of protective ventilation is a priority in this acute phase of lung inflammation. Neuromuscular blocking agents (NMBAs) induce reversible muscle paralysis. Their use in patients with ARDS remains controversial but occurs frequently. NMBAs are used in 25-45% of ARDS patients for a mean period of 1±2 days. The main indications of NMBAs are hypoxemia and facilitation of MV. For ethical reasons, NMBA use is inseparable from sedation in the management of early ARDS. During paralysis, sedation monitoring seems to be necessary to avoid awareness with recall. Three randomized controlled trials (RCTs) have demonstrated that the systematic use of NMBAs in the early management of ARDS patients improves oxygenation. Furthermore, the most recent trial reported a reduction of mortality at 90 days when NMBAs were infused over 48 hours. Spontaneous ventilation (SV) during MV at the acute phase of ARDS could improve oxygenation and alveolar recruitment, but it may not allow protective ventilation. The major risk is an increase in ventilator-induced lung injury. However, the adverse effects of NMBAs are widely discussed, particularly the occurrence of intensive care unit (ICU)-acquired weakness. This review analyses the recent findings in the literature concerning sedation and paralysis in managing ARDS.

Avoidance versus use of neuromuscular blocking agents for improving conditions during tracheal intubation or direct laryngoscopy in adults and adolescents.

Avoidance versus use of neuromuscular blocking agents for improving conditions during tracheal intubation or direct laryngoscopy in adults and adolescents.

Clinical Practice Guidelines for Sustained Neuromuscular Blockade in the Adult Critically Ill Patient.

Clinical Practice Guidelines for Sustained Neuromuscular Blockade in the Adult Critically Ill Patient.

Early Paralysis for the Management of ARDS.

The use of neuromuscular blocking agents (NMBAs) early in the development of ARDS has been a strategy of interest for many years. The use of NMBAs with a concomitant deep sedation strategy can increase oxygenation and possibly decrease mortality when used in the early stages of ARDS. The mechanism by which this occurs is unclear but probably involves a combination of factors, such as improving patient-ventilator synchrony, decreasing oxygen consumption, and decreasing the systemic inflammatory response associated with ARDS. The use of NMBA and deep sedation for these patients is not without consequence. This discussion describes the rationale and evidence behind the use of NMBAs in the setting of ARDS.

Anaesthesia for thymectomy in adult and juvenile myasthenic patients.

Myasthenia gravis, a chronic disease of the neuromuscular junction, is associated with an interaction with neuromuscular blocking agents (NMBAs). As thymectomy is often the method of choice for its treatment, anaesthetic management requires meticulous preoperative evaluation, careful monitoring, and adequate dose titration. The frequency of video-assisted thoracoscopic extended thymectomy (VATET) is also increasing, making the use of NMBA obligatory. The number of cases of the juvenile form has also increased over years; airway management in juvenile one-lung ventilation is another challenge. Sugammadex appears to be a safe choice to avoid prolonged action of NMBA also in patients with myasthenia gravis, although this information has to be confirmed in further series. The number of VATETs is increasing so that the experience with sugammadex will also increase in time. In non-VATET operations, use of NMBA should and can be avoided as much as possible. New scoring systems are defined to predict a postoperative myasthenic crisis. For VATET in juvenile cases, blockers can be a good option for the airway management. Anaesthetic management of thymectomy in myasthenia gravis requires experience concerning different approaches. Sugammadex should be considered as a possible further step toward postoperative safety.

Acute Physiology and Chronic Health Evaluation II score of ≥15: A risk factor for sepsis-induced critical illness polyneuropathy.

Critical illness polyneuropathy (CIP) is a common complication of severe sepsis and systemic inflammatory response syndrome (SIRS). The risk factors for sepsis-induced CIP have not been well established. The aim of this study was to find out the risk factors of sepsis-induced CIP, especially its relationship with the severity of illness. A cohort of 100 patients with sepsis defined as SIRS of proven or presumed microbial etiology were followed up with nerve conduction studies (NCS) performed within the first 14 days of admission. If the assessment was normal then the study was repeated between day 21 and 28. The two groups (with and without neuropathy) were compared. The following risk factors were evaluated for the development of sepsis-related CIP: Duration of symptoms, stay in Intensive Care Unit, and mechanical ventilation; use of neuromuscular blocking agents (NMBAs), steroids, insulin infusion, and inotropes. The following laboratory parameters recorded in the first 24 h of admission were included: Hemoglobin (Hb), total leukocyte count, serum urea, creatinine, aminotransaminases (aspartate aminotransferase and alanine aminotransferase), total protein, albumin, potassium, creatinine kinase, plasma glucose, HbA1C, and Acute Physiology and Chronic Health Evaluation II (APACHE II) score at admission or within 24 h. Thirty-seven patients had features of neuropathy. Among these 37 patients, 30 patients (81%) developed it in the first 14 days. Multivariate analysis using linear regression showed the APACHE II score and use of NMBAs to be significant factors in its development. An APACHE II score of ≥15 was associated with a significant risk of developing CIP (relative risk: 11.6, 95% confidence interval: 4.9-27.2, P < 0.0001). Critically ill patients with sepsis and APACHE II score at admission or within 24 h of ≥15 are at risk for the development of CIP.

Neuromuscular blocking effects of cisatracurium and its antagonism with neostigmine in a canine model of autosomal-recessive centronuclear myopathy

Centronuclear myopathy (CNM) is a rare congenital condition associated with skeletal muscle weakness. Patients with CNM may have decreased acetylcholine receptor expression and a reduced number of releasable quanta. Such perturbations could affect the time-course of neuromuscular blocking agents (NMBAs) and their antagonism with cholinesterase inhibitors. As a result of the rarity of CNM, prospective data regarding NMBA use in this subpopulation is scarce. We evaluated the neuromuscular blocking effects of cisatracurium and its antagonism with neostigmine in a canine model of CNM. Six dogs with congenital autosomal-recessive CNM and six controls received cisatracurium 0.15 mg kg(-1) i.v. under general anaesthesia and intermittent positive pressure ventilation. Neuromuscular function was monitored with acceleromyography.When the second response (T2) to train-of-four (TOF) stimulation returned, neostigmine 0.04 mg kg(-1) (with glycopyrrolate) were administered i.v. The onset time, time to spontaneous return of T2, and the time to reach a TOF ratio ≥0.9 after neostigmine administration were recorded. Onset time was no different between groups. Median (interquartile range) time to return of T2 was 27 (24-31) min for control dogs and 26 (22-31) min for CNM dogs (P=0.93).After neostigmine administration, a TOF ratio ≥0.9 was reached in 12 (10-15) min and 17 (16-19) min in control and CNM, respectively (P=0.005). The spontaneous return of T2 was not different between groups. However, neostigmine-facilitated recovery was significantly slower in dogs with CNM. Canine autosomal-recessive CNM does not preclude the use of cisatracurium or its antagonism with neostigmine.

Intensive Care Nurses' Knowledge About Use of Neuromuscular Blocking Agents in Patients With Respiratory Failure.

The recent increase in use of neuromuscular blocking agents (NMBAs) in patients with acute respiratory distress syndrome is set against a backdrop of concerns about harm associated with use of these high-risk drugs. Bedside nurses play a pivotal role in the safe and effective use of these agents. To describe critical care nurses' knowledge of the therapeutic properties, adverse effects, and monitoring parameters associated with NMBAs. A prospective, multicenter survey of medical intensive care unit nurses between July 2012 and May 2013. The web-based survey instrument was designed, pretested, and administered under the direction of a multidisciplinary group of individuals. Responses from 160 nurses (22% of eligible nurses) were analyzed. Most respondents were able to identify NMBAs correctly as nonanalgesic (93%) and nonanxiolytic (83%). The perceived durations of action of NMBAs varied widely, and few nurses were familiar with patient-specific considerations related to drug elimination. Most (70%) recognized the independent associations between NMBAs and footdrop, muscle breakdown, and corneal ulceration. Pressure ulcers and a history of neuromuscular disease were the characteristics of patients perceived to most heighten the risk of NMBA use. Critical care nurses are knowledgeable about the importance of concurrent analgesia and sedation during use of NMBAs. Routes of elimination, duration of action, and adverse effects were less commonly known and represent areas for focused education and quality improvement surrounding use of NMBAs in the intensive care unit.

Muscle Relaxation in Laparoscopic Surgery: What is the Evidence for Improved Operating Conditions and Patient Outcome? A Brief Review of the Literature.

When neuromuscular blocking agents (NMBA) were introduced into clinical practice in 1942, the event was called the "second revolution in anesthesia." Despite some significant side effects, NMBAs have remained in the anesthetists' repertoire, not at least because muscle relaxation has been claimed to allow or facilitate many surgical procedures. Aim of this literature review was to investigate the evidence for the use of NMBA as well as the optimum depth of neuromuscular blockade during laparoscopic surgery. Muscle relaxation may optimize laparoscopic operating conditions by preventing patient movement and achieving more intra-abdominal space for a given intra-abdominal insufflation pressure. In this context, deeper than normally maintained levels of neuromuscular blockade appear to be superior. However, the decision to utilize deeper than standard muscle relaxation should currently be based on a risk-benefit analysis for each individual patient. Thus good communication between surgeon and anesthetist remains crucial to achieve best outcomes.

Dose-dependent Association between Intermediate-acting Neuromuscular-blocking Agents and Postoperative Respiratory Complications.

Duration of action increases with repeated administration of neuromuscular-blocking agents, and intraoperative use of high doses of neuromuscular-blocking agent may affect respiratory safety. In a hospital-based registry study on 48,499 patients who received intermediate-acting neuromuscular-blocking agents, the authors tested the primary hypothesis that neuromuscular-blocking agents are dose dependently associated with the risk of postoperative respiratory complications. In the secondary analysis, the authors evaluated the association between neostigmine dose given for reversal of neuromuscular-blocking agents and respiratory complications. Post hoc, the authors evaluated the effects of appropriate neostigmine reversal (neostigmine ≤ 60 μg/kg after recovery of train-of-four count of 2) on respiratory complications. The authors controlled for patient-, anesthesia-, and surgical complexity-related risk factors. High doses of neuromuscular-blocking agents were associated with an increased risk of postoperative respiratory complications (n = 644) compared with low doses (n = 205) (odds ratio [OR], 1.28; 95% CI, 1.04 to 1.57). Neostigmine was associated with a dose-dependent increase in the risk of postoperative respiratory complications (OR, 1.51; 95% CI, 1.25 to 1.83). Post hoc analysis revealed that appropriate neostigmine reversal eliminated the dose-dependent association between neuromuscular-blocking agents and respiratory complications (for neuromuscular-blocking agent effects with appropriate reversal: OR, 0.98; 95% CI, 0.63 to 1.52). The use of neuromuscular-blocking agents was dose dependently associated with increased risk of postoperative respiratory complications. Neostigmine reversal was also associated with a dose-dependent increase in the risk of respiratory complications. However, the exploratory data analysis suggests that the proper use of neostigmine guided by neuromuscular transmission monitoring results can help eliminate postoperative respiratory complications associated with the use of neuromuscular-blocking agents.