An Assessment of the Practice of Neuromuscular Blockade and the Association Between Its Prophylactic Use and Outcomes Among Postoperative Pediatric Cardiac Patients.

OBJECTIVES: The authors investigated the management of neuromuscular blocking agents (NMBAs) for pediatric patients after cardiac surgery, and compared the outcomes of patients who received prophylactic NMBA (pNMBA) infusions and patients without pNMBA infusions. DESIGN: A retrospective cohort study. SETTING: At a tertiary teaching hospital. PARTICIPANTS: Patients younger than 18, with congenital heart disease, who underwent cardiac surgery. INTERVENTIONS: Commencement of NMBA infusion in the first 2 hours after surgery MEASUREMENTS AND MAIN RESULTS: The primary endpoint was a composite of one or more of the following major adverse events (MAEs) that occurred within 7 days after surgery: death from any cause, a circulatory collapse that needed cardiopulmonary resuscitation, and requirement for extracorporeal membrane oxygenation. The secondary endpoints included the total duration of mechanical ventilation for the first 30 days after surgery. A total of 566 patients were included in this study. The MAEs occurred in 13 patients (2.3%). An NMBA was commenced within 2 hours after surgery in 207 patients (36.6%). There were significant differences in the incidence of postoperative MAEs between the pNMBA group and the non-pNMBA group (5.3% v 0.6%; p < 0.001). In multivariate regression models, pNMBA infusion was not significantly associated with the incidence of MAEs (odds ratio: 1.79, 95% CI: 0.23-13.93, p = 0.58), but was significantly associated with prolonged mechanical ventilation by 3.85 days (p < 0.001). CONCLUSIONS: Postoperative prophylactic neuromuscular blockade after cardiac surgery can be associated with prolonged mechanical ventilation, but has no association with MAEs among pediatric patients with congenital heart disease.

Comparison of the effects of sugammadex versus neostigmine for reversal of neuromuscular block on hospital costs of care.

BACKGROUND: Sugammadex reversal of neuromuscular block facilitates recovery of neuromuscular function after surgery, but the drug is expensive. We evaluated the effects of sugammadex on hospital costs of care. METHODS: We analysed 79 474 adult surgical patients who received neuromuscular blocking agents and reversal from two academic healthcare networks between 2016 and 2021 to calculate differences in direct costs. We matched our data with data from the Healthcare Cost and Utilization Project-National Inpatient Sample (HCUP-NIS) to calculate differences in total costs in US dollars. Perioperative risk profiles were defined based on ASA physical status and admission status (ambulatory surgery vs hospitalisation). RESULTS: Based on our registry data analysis, administration of sugammadex vs neostigmine was associated with lower direct costs (-1.3% lower costs; 95% confidence interval [CI], -0.5 to -2.2%; P=0.002). In the HCUP-NIS matched cohort, sugammadex use was associated with US$232 lower total costs (95% CI, -US$376 to -US$88; P=0.002). Subgroup analysis revealed that sugammadex was associated with US$1042 lower total costs (95% CI, -US$1198 to -US$884; P<0.001) in patients with lower risk. In contrast, sugammadex was associated with US$620 higher total costs (95% CI, US$377 to US$865; P<0.001) in patients with a higher risk (American Society of Anesthesiologists physical status ≥3 and preoperative hospitalisation). CONCLUSIONS: The effects of using sugammadex on costs of care depend on patient risk, defined based on comorbidities and admission status. We observed lower costs of care in patients with lower risk and higher costs of care in hospitalised surgical patients with severe comorbidities.

Neuromuscular Blockade Monitoring in Acute Respiratory Distress Syndrome: Randomized Controlled Trial of Clinical Assessment Alone or With Peripheral Nerve Stimulation.

BACKGROUND: Whether train-of-four (TOF) monitoring is more effective than clinical monitoring to guide neuromuscular blockade (NMB) in patients with acute respiratory distress syndrome (ARDS) is unclear. We compared clinical monitoring alone or with TOF monitoring to guide atracurium dosage adjustment with respect to drug dose and respiratory parameters. METHODS: From 2015 to 2016, we conducted a randomized controlled trial comparing clinical assessments every 2 hours with or without corrugator supercilii TOF monitoring every 4 hours in patients who developed ARDS (Pao2/Fio2 <150 mm Hg) in a cardiothoracic intensive care unit. The primary outcome was the cumulative atracurium dose (mg/kg/h). Secondary outcomes included respiratory parameters during the neuromuscular blockade. RESULTS: A total of 38 patients in the clinical + TOF (C + TOF) group and 39 patients in the clinical (C) group were included in an intention-to-treat (ITT) analysis. The cumulative atracurium dose was higher in the C + TOF group (1.06 [0.75-1.30] vs 0.65 [0.60-0.89] mg/kg/h in the C group; P < .001) compared to C group, as well as the atracurium daily dose (C + TOF - C group mean difference = 0.256 mg/kg/h [95% confidence interval {CI}, 0.099-0.416], P = .026). Driving pressures during neuromuscular blocking agent (NMBA) administration did not differ between groups (P = .653). Intensive care unit (ICU) mortality was 22% in the C group and 27% in the C + TOF group (P = .786). Days on ventilation were 17 (8-26) in the C group and 16 (10-35) in the C + TOF group. CONCLUSIONS: In patients with ARDS, adding TOF to clinical monitoring of neuromuscular blockade did not change ICU mortality or days on mechanical ventilation (MV) but did increase atracurium consumption when compared to clinical assessment alone. TOF monitoring may not be needed in all patients who receive neuromuscular blockade for ARDS.

Sugammadex versus neostigmine for routine reversal of rocuronium block in adult patients: A cost analysis.

STUDY OBJECTIVE: This report analyzes the comparative costs, efficacy and side effects of a newer, more expensive reversal drug, sugammadex, with its generic counterpart, neostigmine combined with glycopyrrolate, or no reversal agent when used routinely to reverse rocuronium-induced neuromuscular blockade in adult patients. DESIGN: Cost analysis. METHODS: We constructed a decision model to analyze the costs associated with the choice of reversal drug and differences in reversal time, occurrence of postoperative nausea or vomiting (PONV), and residual blockade requiring unplanned postoperative mechanical ventilation (UPMV). We selected variables that demonstrated meaningful differences in meta-analyses of published studies and/or had significant associated costs. We used data from local hospital system information, meta-analysis of published studies, and the general literature to construct base-case scenarios and sensitivity analyses. We performed the analysis from the perspective of a single hospital system. Costs were in 2019 U.S. dollars. RESULTS: Cost analysis suggested that reversal with sugammadex is preferable to neostigmine or no reversal drug when operating room (OR) time was valued at ≥$8.60/min (base case $32.49/min). Net costs of sugammadex were less than no treatment or neostigmine reversal when the probability of UPMV exceeded 0.019 and 0.036, respectively. Neither sugammadex nor neostigmine reversal was preferable to no treatment in a base-case analysis that considered the effect of the reversal agent on only drug and PONV costs, disregarding costs of OR time or UPMV. CONCLUSIONS: Routine reversal with sugammadex is preferable to choosing neostigmine or no reversal drug when accounting for potential savings in OR time. Sugammadex might also be a reasonable choice for patients at high risk of UPMV. If the cost of OR time is not considered, the analysis does not support the routine use of sugammadex in patients with perceived increased risk or solely to reduce PONV.

The Effects of Postoperative Residual Neuromuscular Blockade on Hospital Costs and Intensive Care Unit Admission: A Population-Based Cohort Study.

BACKGROUND: Postoperative residual neuromuscular blockade continues to be a frequent occurrence with a reported incidence rate of up to 64%. However, the effect of postoperative residual neuromuscular blockade on health care utilization remains unclear. We conducted a retrospective cohort study to investigate the effects of postoperative residual neuromuscular blockade on hospital costs (primary outcome), intensive care unit admission rate, and hospital length of stay (secondary outcomes). METHODS: We performed a prespecified secondary analysis of data obtained in 2233 adult patients undergoing surgery under general anesthesia. Postoperative residual neuromuscular blockade was defined as a train-of-four ratio <0.9 in the postanesthesia care unit (PACU). Our confounder model adjusted for a variety of patient, surgical, and anesthesia-related factors. We fitted truncated negative binomial regression models for hospital cost and hospital length of stay analyses and a logistic regression model for our intensive care unit admission analysis. RESULTS: Overall, 457 (20.5%) patients in our cohort had residual neuromuscular blockade on admission to the PACU. Postoperative residual neuromuscular blockade was not independently associated with increased hospital costs (adjusted incidence rate ratio, 1.04, CI, 0.98-1.11; P = .22). There were significantly higher odds of intensive care unit admission in those with postoperative residual neuromuscular blockade compared to those without (adjusted odds ratio, 3.03, CI, 1.33-6.87; P < .01). Further, we found a trend toward increased hospital length of stay in patients with postoperative residual neuromuscular blockade (adjusted incidence rate ratio, 1.09; P = .06). Sensitivity analysis using the same model in the day of surgery admissions and ambulatory surgery confirmed our findings. CONCLUSIONS: Postoperative residual neuromuscular blockade at PACU admission was not significantly associated with increased hospital costs, but was associated with higher rates of intensive care unit admission. These findings support the view that clinicians should continue to work to reduce the rate of postoperative residual neuromuscular blockade.

Do we really need sugammadex as an antagonist of muscle relaxants in anesthesia?

PURPOSE OF REVIEW: Sugammadex is a selective relaxant-binding agent that is designed to encapsulate rocuronium and chemically similar steroidal muscle relaxants such as vecuronium. This review summarizes recent information on the use of sugammadex in clinical practice. RECENT FINDINGS: The main advantages of sugammadex when compared with conventional anticholinesterase agents are a much faster recovery time and its unique ability to reverse rapidly and efficiently, for the first time, deep levels of neuromuscular blockade. However, there is paucity of evidence-based studies on the benefit of deep neuromuscular block, and then routine administration of sugammadex to reverse any level of block, for example, during laparoscopic surgery. It appears that reduction of costs depends mainly on organizational factors. Finally it must be remembered that sugammadex only works with steroidal nondepolarizing muscle relaxants; therefore neostigmine should not be withdrawn because it is the only reversal agent effective against atracurium or cisatracurium. SUMMARY: Sugammadex offers a significantly faster and more predictable recovery profile than neostigmine. It is now possible to reverse rapidly and efficiently any level of neuromuscular blockade and to avoid the risk of adverse events because of residual paralysis such as critical respiratory events during recovery from anesthesia.

[Sugammadex: something new to improve patient safety or simply a gadget?]. / Le sugammadex : une nouveauté qui s'inscrit dans le cadre de l'amélioration de la sécurité des patients ou un simple gadget ?

The launch on the market of a new compound is always an important event for a specialty, particularly when the mechanism of action is completely new. It is the case with sugammadex, a cyclodextrin able to encapsulate specifically and only nondepolarizing steroidal muscles relaxant, rocuronium or vecuronium. The clinical trials which have been performed for sugammadex approval have demonstrated promising results. Sugammadex is able to rapidly reverse (2-5 min) different levels of neuromuscular blockade: moderate (e.g., T2 recovery), deep (e.g., PTC 1-2 recovery) and also few minutes (3-15) after rocuronium administration. Thus, the sugammadex's onset time is about 10 times more rapid than neostigmine without the need of concomitantly atropine administration. Sugammadex has only been tested in small sample size of patients. Therefore, the exact place in the anesthetic practice, the potential indications, the safety profile on a large-scale, thus remain to determine. In particular, how it will modify our current practices characterized to date by 1) under-use of neuromuscular monitoring, 2) a marginal practice of reversal and 3) a wide use of benzylisoquinolines : atracurium and cis-atracurium? Finally, what will be the medical strategies to justify an additional cost when compared to neostigmine?

A case of pseudocholinesterase deficiency in the PACU.

A 39-year-old patient with unrecognized atypical pseudocholinesterase was given succinylcholine during the rapid-sequence induction process and subsequently had a prolonged neuromuscular blockade. The patient was reassured, sedated, and ventilated in the postanesthesia care unit (PACU). The primary nursing interventions included airway clearance, communication, comfort, and patient education. Several important learning experiences occurred for the nurses in the PACU related to identifying possible causes, ordering the pseudocholinesterase and dibucaine inhibition test, interpreting the results, and developing and delivering patient education. This article will provide the perianesthesia nurse with the fundamental understanding of the physiology, laboratory diagnostic interpretation, and nursing interventions needed to deliver evidence-based, high-quality care to patients diagnosed with pseudocholinesterase deficiency.

A Markov computer simulation model of the economics of neuromuscular blockade in patients with acute respiratory distress syndrome.

BACKGROUND: Management of acute respiratory distress syndrome (ARDS) in the intensive care unit (ICU) is clinically challenging and costly. Neuromuscular blocking agents may facilitate mechanical ventilation and improve oxygenation, but may result in prolonged recovery of neuromuscular function and acute quadriplegic myopathy syndrome (AQMS). The goal of this study was to address a hypothetical question via computer modeling: Would a reduction in intubation time of 6 hours and/or a reduction in the incidence of AQMS from 25% to 21%, provide enough benefit to justify a drug with an additional expenditure of $267 (the difference in acquisition cost between a generic and brand name neuromuscular blocker)? METHODS: The base case was a 55 year-old man in the ICU with ARDS who receives neuromuscular blockade for 3.5 days. A Markov model was designed with hypothetical patients in 1 of 6 mutually exclusive health states: ICU-intubated, ICU-extubated, hospital ward, long-term care, home, or death, over a period of 6 months. The net monetary benefit was computed. RESULTS: Our computer simulation modeling predicted the mean cost for ARDS patients receiving standard care for 6 months to be $62,238 (5%-95% percentiles $42,259-$83,766), with an overall 6-month mortality of 39%. Assuming a ceiling ratio of $35,000, even if a drug (that cost $267 more) hypothetically reduced AQMS from 25% to 21% and decreased intubation time by 6 hours, the net monetary benefit would only equal $137. CONCLUSION: ARDS patients receiving a neuromuscular blocker have a high mortality, and unpredictable outcome, which results in large variability in costs per case. If a patient dies, there is no benefit to any drug that reduces ventilation time or AQMS incidence. A prospective, randomized pharmacoeconomic study of neuromuscular blockers in the ICU to asses AQMS or intubation times is impractical because of the highly variable clinical course of patients with ARDS.

A prospective randomized comparison of train-of-four monitoring and clinical assessment during continuous ICU cisatracurium paralysis.

STUDY PURPOSE: Train-of-four (TOF) monitoring is often recommended during the continuous use of neuromuscular blockade (NMB) [paralysis] in the ICU. Prior study results are conflicting regarding the benefits of TOF monitoring. DESIGN: Thirty patients in the medical ICU were randomized to TOF monitoring (n = 16) or to clinical assessment (n = 14) during continuous cisatracurium infusion. TOF monitoring was done at least every 4 h, with the goal being maintenance of one to two twitches. Statistical analysis was performed by two-tailed, unpaired t test (with Bonferroni correction for multiple comparisons), chi(2), and Fisher exact test, with p < 0.05 considered significant. Given a power of 80%, and the variance seen in the two groups, we estimate that the sample size used is sufficient to detect a change of > or = 60 min between groups for recovery time. RESULTS: The mean recovery time after cessation of paralytics was no different between TOF and clinical assessment (45 +/- 7 min vs 38 +/- 10 min, respectively [mean +/- SEM]). No differences were noted for mean APACHE (acute physiology and chronic health evaluation) II entry scores, glomerular filtration rates, or use of corticosteroids. No significant differences were noted between TOF monitoring and clinical assessment in mean total paralysis time (4,118 +/- 1,012 min vs 3,188 +/- 705 min, respectively), mean total cisatracurium dose (920 +/- 325 mg vs 715 +/- 167 mg), or dosage (2.3 +/- 0.2 microg/kg/min vs 2.9 +/- 0.2 microg/kg/min). CONCLUSIONS: TOF monitoring does not lead to improved recovery time or lower cisatracurium dosing compared with monitoring by clinical assessment. We conclude that TOF monitoring is unnecessary, and careful titration of the neuromuscular blocking agent by clinical assessment alone is sufficient in patients undergoing continuous cisatracurium NMB.

Assessment of a simple artificial neural network for predicting residual neuromuscular block.

BACKGROUND: Postoperative residual curarization (PORC) after surgery is common and its detection has a high error rate. Artificial neural networks are being used increasingly to examine complex data. We hypothesized that a neural network would enhance prediction of PORC. METHODS: In 40 previously reported patients, neuromuscular function, neuromuscular block/antagonist usage and time intervals were recorded throughout anaesthesia until tracheal extubation by an observer uninvolved in patient care. PORC was defined as significant 'fade' (train of four <0.7) at extubation. Neuromuscular function was classified as PORC (value=1) or no PORC (value=0). A back-propagation neural network was trained to assign similar values (0, 1) for prediction of PORC, by examining the impact of (i) the degree of spontaneous recovery at reversal, and (ii) the time since pharmacological reversal, using the jackknife method. Successful prediction was defined as attainment of a predicted value within 0.2 of the target value. RESULTS: Twenty-six patients (65%) had PORC at tracheal extubation. Clinical detection of PORC had a sensitivity of 0 and specificity of 1, with an indeterminate positive predictive value and a negative predictive value of 0.35. Using the artificial neural network, one patient with residual block and one with adequate neuromuscular function were incorrectly classified during the test phase, with no indeterminate predictions, giving an artificial neural network sensitivity of 0.96 (chi(2)=44, P<0.001) and specificity of 0.92 (P=1), with a positive predictive value of 0.96 and a negative predictive value of 0.93 (chi(2)=12, P<0.001). CONCLUSIONS: Neural network-based prediction, using readily available clinical measurements, is significantly better than human judgement in predicting recovery of neuromuscular function.

Equi-lasting doses of rocuronium, compared to mivacurium, result in improved neuromuscular blockade in patients undergoing gynecological laparoscopy : [Des doses de durée équivalente de rocuronium, comparé au mivacurium, améliorent la curarisation chez des patientes qui subissent une laparoscopie gynécologique].

PURPOSE: To compare equi-lasting doses of a short-acting (mivacurium) to an intermediate-acting (rocuronium) neuromuscular relaxant, with regard to intubating conditions, efficacy, number of maintenance doses, hemodynamic alterations, adverse events and costs, in patients undergoing laparoscopic gynecological surgery. METHODS: Sixty patients were randomly allocated to receive either 0.2 mg*kg(-1) (3 x ED(95)) mivacurium or 0.5 mg*kg(-1) (1.7 x ED(95)) rocuronium, under propofol/fentanyl anesthesia. T1, first twitch of the train-of-four (TOF) and TOF ratio (T4:T1) were used to evaluate neuromuscular block using the Relaxometer(R) mechanomyograph. The trachea was intubated when T1 was maximally suppressed. Neuromuscular block was maintained at 25% T1 with equi-lasting doses of 0.075 mg*kg(-1) mivacurium or 0.15 mg*kg(-1) rocuronium. RESULTS: Mean (min) +/- SD mivacurium onset time (1.9 +/- 0.4) was longer than that of rocuronium (1.3 +/- 0.3). This did not yield a statistical difference in intubating conditions between the two groups. Interval 25-75% T1 recovery and time to 0.8 TOF recovery were prolonged following rocuronium (11.9 +/- 3.9, 52.6 +/- 15.5 respectively) compared to mivacurium (6.7 +/- 2.3, 39.2 +/- 8.1 respectively). More patients, 22/30, required mivacurium maintenance doses compared to 14/30 patients in the rocuronium group. Arterial blood pressure declined and 13/30 patients manifested erythema following mivacurium administration. The acquisition costs of rocuronium (6.93 Euro/patient) were 23% lower compared to mivacurium (8.96 Euro/patient). CONCLUSION: Equi-lasting doses of rocuronium resulted in favourable intubating conditions more rapidly, improved hemodynamic stability, required less frequent administration of maintenance doses and were not associated with erythema, compared to mivacurium.