The impact of sugammadex dosing and administration practices on potential cost savings for pharmacy departments.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: Neuromuscular blocking agents (NMBAs) are commonly used during surgery, and restoring neuromuscular function at the end of surgery is vital in preventing complications of residual paralysis. Recent guidelines from the American Society of Anesthesiology recommend using sugammadex over neostigmine; however, sugammadex is significantly more expensive than neostigmine and may increase drug expenditure for pharmacy departments. This review summarizes evidence evaluating sugammadex dose adjustments and the potential of these dose adjustments to lead to cost savings for pharmacy departments. SUMMARY: We found evidence suggesting that the manufacturer-recommended sugammadex dose may not be needed in many patients and that dosing based on an adjusted body weight or based on depth of neuromuscular blockade may lead to lower sugammadex usage. Combining sugammadex with neostigmine could also decrease the dose of sugammadex required. We have highlighted the importance of objective neuromuscular monitoring to guide sugammadex dosing and evaluation for residual neuromuscular blockade. Cost savings for pharmacy departments may be realized by these alternative dosing strategies and/or vial-splitting practices. CONCLUSION: Implementing practices related to sugammadex vial splitting and dose adjustment based on body weight and depth of neuromuscular blockade shows potential benefits in terms of sugammadex cost savings.

Assessing pain in paralyzed critically ill patients receiving neuromuscular blocking agents: A monocenter prospective cohort.

INTRODUCTION: Given the absence of established recommendations for pain assessment in pharmacologically paralyzed Intensive-Care-Units (ICU) patients under Neuro-Muscular-Blocking Agents (NMBA), this study assessed the validity of various parameters for evaluating pain in this specific population. PATIENTS AND METHODS: Four electrophysiological parameters (instant-Analgesia-Nociception-Index (ANI), Bispectral index (BIS), Heart Rate (HR) and Mean Arterial Blood Pressure (ABP)) and one clinical parameter (Behavioural-Pain-Scale (BPS)) were recorded during tracheal-suctioning in all consecutive ICU patients who required a continuous infusion of cisatracurium, before and just after paralysis recovery measured by Train-of-Four ratio. The validity of the five pain-related parameters was assessed by comparing the values recorded during different situations (before/during/after the nociceptive procedure) (discriminant-validity, primary outcome), and the effect of paralysis was assessed by comparing values obtained during and after paralysis (reliability, secondary outcome). RESULTS: Twenty patients were analyzed. ANI, BIS, and HR significantly changed during the nociceptive procedure in both paralysis and recovery, while BPS changed only post-recovery. ANI and HR were unaffected by paralysis, unlike BIS and BPS (mixed-effect model). ANI exhibited the highest discriminant-validity, with values (min 0/max 100) decreasing from 71 [48-89] at rest to 41 [25-72] during tracheal suctioning in paralyzed patients, and from 71 [53-85] at rest to 40 [31-52] in non-paralyzed patients. CONCLUSIONS: ANI proves the most discriminant parameter for pain detection in both paralyzed and non-paralyzed sedated ICU patients. Its significant and clinically relevant decrease during tracheal suctioning remains unaltered by NMBA use. Pending further studies on analgesia protocols based on ANI, it could be used to assess pain during nociceptive procedures in ICU patients receiving NMBA.

Onset time, duration of action, and intubating conditions after mivacurium in elderly and younger patients.

BACKGROUND: The neuromuscular blocking agent mivacurium can be used during anesthesia to facilitate tracheal intubation. Data on onset time, duration of action, and effect on intubating conditions in patients 80 years and older are however limited. We hypothesized that onset time and duration of action of mivacurium would be longer in elderly patients than in younger adults. METHODS: This prospective observational study included 35 elderly (≥80 years) and 35 younger (18-40 years) patients. Induction of anesthesia comprised fentanyl 1-3 µg kg-1 and propofol 1.5-2.5 mg kg-1 and propofol and remifentanil for maintenance. Acceleromyography was used for monitoring neuromuscular blockade. The primary outcome was onset time defined as time from injection of mivacurium 0.2 mg kg-1 to a train-of-four (TOF) count of zero. Other outcomes included duration of action (time to TOF ratio ≥0.9), intubating conditions using the Fuchs-Buder scale and the intubating difficulty scale (IDS), and occurrence of hoarseness and sore throat postoperatively. RESULTS: No difference was found in onset time comparing elderly with younger patients; 219 s (SD 45) versus 203 s (SD 74) (difference: 16 s (95% CI: -45 to 14), p = .30). Duration of action was significantly longer in elderly patients compared with younger patients; 52 min (SD 17) versus 30 min (SD 8) (difference: 22 min [95% CI: 15 to 28], p < .001). No difference was found in the proportion of excellent intubating conditions (Fuchs-Buder); 31/35 (89%) versus 26/35 (74%) (p = .12) or IDS score (p = .13). A larger proportion of younger patients reported sore throat 24 h postoperatively; 34% versus 0%, p = .0002. No difference was found in hoarseness. CONCLUSION: No difference in onset time of mivacurium 0.2 mg kg-1 was found comparing elderly and younger patients. However, elderly patients had significantly longer duration of action. No difference was found in intubating conditions.

Design, synthesis, and biological evaluation of new bis-benzylisoquinoline-based analogues as potential neuromuscular blocking agents.

Neuromuscular blocking agents (NMBAs) are widely used in anesthesia for intubation and surgical muscle relaxation. Novel atracurium and mivacurium derivatives were developed, with compounds 18c, 18d, and 29a showing mivacurium-like relaxation at 27.27 nmol/kg, and 15b, 15c, 15e, and 15h having a shorter duration at 272.7 nmol/kg. The structure-activity and configuration-activity relationships of these derivatives and 29a's binding to nicotinic acetylcholine receptors were analyzed through molecular docking. Rabbit trials showed 29a has a shorter duration compared to mivacurium. This suggests that linker properties, ammonium group substituents, and configuration are crucial for NMBA activity and duration, with compound 29a emerging as a potential ultra-short-acting NMBA.

Neuromuscular blocking agents during targeted temperature management for out-of-hospital cardiac arrest patients.

BACKGROUND: Neuromuscular blocking agents (NMBAs) can control shivering during targeted temperature management (TTM) of patients with cardiac arrest. However, the effectiveness of NMBA use during TTM on neurologic outcomes remains unclear. We aimed to evaluate the association between NMBA use during TTM and favorable neurologic outcomes after out-of-hospital cardiac arrest (OHCA). MATERIALS AND METHODS: A multicenter, prospective, observational cohort study from 2019 to 2021. It included OHCA patients who received TTM after hospitalization. We conducted overlap weight propensity-score analyses after multiple imputation to evaluate the effect of NMBAs during TTM. The primary outcome was a favorable neurological outcome, defined as a cerebral performance category of 1 or 2 at discharge. Subgroup analyses were conducted based on initial monitored rhythm and brain computed tomography findings. RESULTS: Of the 516 eligible patients, 337 received NMBAs during TTM. In crude analysis, the proportion of patients with favorable neurological outcome was significantly higher in the NMBA group (38.3% vs. 16.8%; risk difference (RD): 21.5%; 95% confidence interval (CI): 14.0% to 29.1%). In weighted analysis, a significantly higher proportion of patients in the NMBA group had a favorable neurological outcome compared to the non-NMBA group (32.7% vs. 20.9%; RD: 11.8%; 95% CI: 1.2% to 22.3%). In the subgroup with an initial shockable rhythm and no hypoxic encephalopathy, the NMBA group showed significantly higher proportions of favorable neurological outcomes. CONCLUSIONS: The use of NMBAs during TTM was significantly associated with favorable neurologic outcomes at discharge for OHCA patients. NMBAs may have benefits in selected patients with initial shockable rhythm and without poor prognostic computed tomography findings.

Tolerance to preoperative placement of electrodes for neuromuscular monitoring using the Tetragraph™.

Background: Quantitative train-of-four (TOF) monitoring has recently been shown to be feasible in infants and children using a novel electromyography (EMG)-based monitor with a pediatric-sized self-adhesive sensor. However, placement of the sensor and initiation of TOF monitoring may require additional time in the operating room (OR), delaying workflow and the time to induction of anesthesia. The current study evaluates the feasibility of placing the self-adhesive sensor in the preoperative holding area in pediatric patients before arrival to the OR. Methods: Consented pediatric patients undergoing inpatient surgery requiring the administration of NMBAs were enrolled. The EMG electrode was placed along the ulnar nerve on the volar aspect of the distal forearm to provide neurostimulation. After the induction of anesthesia, monitoring was initiated and TOF recording started before the administration of the NMBA. A Likert score (0-10) was used to assess ease of placement, tolerability of the monitor during the preoperative period, and its ability to generate a recorded response in the OR. Results: The final study cohort included 40 patients with a median age of 3.7 years. Fourteen patients (35%) pulled off the sensor before arrival to the OR and 26 patients (65%) arrived at the OR with the sensor intact and functioning. Older children were more likely to maintain the sensor until arrival to the OR compared to younger patients (median age of 5.24 versus 1 year, P = 0.0521). A median age of 3.7 years correlated with an 80% chance of arriving in the OR with the sensor intact. Application ease and tolerance of the sensor were higher in the group that maintained the sensor until OR arrival. Conclusion: In patients more than 4 years of age, placement of the self-adhesive sensor for EMG-based TOF monitoring may be feasible. However, in younger patients, additional interventions may be required to achieve a similar success rate.

Basophil activation test in the diagnostic workup of perioperative anaphylaxis due to neuromuscular blocking agents: A case series and implications for practice.

In Australia, neuromuscular blocking agents are the leading cause of perioperative anaphylaxis. Current investigation of suspected anaphylaxis includes tryptase levels, serum immunoglobulin E (IgE) levels, and skin testing, including intradermal testing and skin prick testing. The gold standard for the diagnosis of a hypersensitivity reaction is a challenge test, but this poses a risk to patient safety. An alternative test, known as the basophil activation test (BAT) is a form of cellular in vitro testing using flow cytometry to measure the degree of basophil degranulation within a sample of blood following exposure to an allergen. This acts as a surrogate marker for mast cell and basophil activation, thereby identifying IgE-mediated allergy. It is most commonly used to supplement equivocal findings from initial in vitro testing to assist in confirming the diagnosis of a hypersensitivity reaction and identify the causative agent. We present a case series in which five patients with suspected anaphylaxis underwent a BAT, demonstrating its role and limitations in allergy testing within Australia.

Association between reversal agents (sugammadex vs. neostigmine) for neuromuscular block and postoperative pulmonary complications: A retrospective analysis.

AIMS: Residual neuromuscular blockade has been linked to pulmonary complications in the postoperative period. This study aimed to determine whether sugammadex was associated with a lower risk of postoperative pulmonary complications (PPCs) compared with neostigmine. METHODS: This retrospective cohort study was conducted in a tertiary academic medical center. Patients ≥18 year of age undergoing noncardiac surgical procedures with general anesthesia and mechanical ventilation were enrolled between January 2019 and September 2021. We identified all patients receiving rocuronium and reversal with neostigmine or sugammadex via electronic medical record review. The primary endpoint was a composite of PPCs (including pneumonia, atelectasis, respiratory failure, pulmonary embolism, pleural effusion, or pneumothorax). The incidence of PPCs was compared using propensity score analysis. RESULTS: A total of 1786 patients were included in this study. Among these patients, 976 (54.6%) received neostigmine, and 810 (45.4%) received sugammadex. In the whole sample, PPCs occurred in 81 (4.54%) subjects (7.04% sugammadex vs. 2.46% neostigmine). Baseline covariates were well balanced between groups after overlap weighting. Patients in the sugammadex group had similar risk (overlap weighting OR: 0.75; 95% CI: 0.40 to 1.41) compared to neostigmine. The sensitivity analysis showed consistent results. In subgroup analysis, the interaction P-value for the reversal agents stratified by surgery duration was 0.011. CONCLUSION: There was no significant difference in the rate of PPCs when the neuromuscular blockade was reversed with sugammadex compared to neostigmine. Patients undergoing prolonged surgery may benefit from sugammadex, which needs to be further investigated.

Improved Reliability of Electromyography-Based Neuromuscular Monitoring During Laparoscopic Surgery Achieved by the Modified Attachment Method for Nihon-Kohden NM-345Y™ Stimulating Electrodes: A Case Report.

Neuromuscular monitoring is crucial during the administration of neuromuscular blocking agents owing to individual variations in their effects. In electromyography (EMG)-based neuromuscular monitoring using the EMG electrodes (NM-345Y™, Nihon-Kohden Corporation, Tokyo, Japan) following the manufacturer-recommended attachment method, the accuracy of neuromuscular monitoring may be reduced when forearm limb position is changed. We previously devised a novel attachment method for NM-345Y™ stimulating electrodes in adult volunteers to maintain stable monitoring accuracy despite changes in forearm position. Its effectiveness in clinical practice was evaluated by conducting a descriptive study on a 52-year-old woman undergoing laparoscopic uterine surgery. NM-345Y™ electrodes were attached to each forearm following the manufacturer's recommendations (Pattern N) and our novel method (Pattern C). In Pattern C, NM-345Y™ was attached without ultrasound guidance so that the ulnar nerve crossed the line connecting the centers of the anode and cathode of the stimulating electrode. Pattern C exhibited consistent EMG-based monitoring accuracy even with changes in forearm position despite a smaller stimulus current value at calibration. Additionally, Pattern C displayed reliable recovery of the train-of-four (TOF) response after sugammadex administration in the original forearm position, with no observed adverse events. In contrast, Pattern N showed unstable monitoring accuracy after forearm position changes, highlighting the danger of imprecise EMG-based neuromuscular monitoring during the administration of neuromuscular blocking agents. The study's strength lies in identifying Pattern C, where the ulnar nerve crosses the line connecting the anode and cathode, significantly enhancing monitoring accuracy. This novel attachment method holds promise to improve EMG-based neuromuscular monitoring precision in surgery involving forearm limb position changes, although further research is required to assess its utility comprehensively.

Trends in the use of neuromuscular blocking agents, reversal agents and neuromuscular transmission monitoring: a single-centre retrospective cohort study.

BACKGROUND: Residual neuromuscular blockade (rNMB) remains a persistent and preventable problem, with serious risks. METHODS: Our objective was to describe and assess patterns in the use of neuromuscular blocking agents (NMBAs), neuromuscular transmission (NMT) monitoring, and factors associated with the use of sugammadex. We performed a retrospective, observational cohort study based on electronic medical records in a large teaching hospital in the Netherlands that introduced an integrated NMT monitoring module with automatic recording in 2017. A total of 22,000 cases were randomly selected from all surgeries between January 2015 and December 2019 that required endotracheal intubation with the use of an NMBA. A total of 14,592 cases fulfilled all the inclusion criteria for complete analyses. RESULTS: Relative NMBA usage remained the same over time. For rocuronium, spontaneous reversal decreased from 86 to 81%, sugammadex reversal increased from 12 to 18%. There was a decline in patients extubated in the operating room (OR) with neither documented NMT monitoring nor sugammadex-mediated reversal from 46 to 31%. The percentage of patients extubated in the OR without a documented train-of-four ratio ≥ 0.9, decreased from 77 to 56%. Several factors were independently associated with the use of sugammadex, including BMI > 30 kg/m2 (odds ratio: 1.41; 95% CI: 1.24-1.60), ASA class 3 or 4 (1.20; 1.07-1.34), age > 60 years (1.37; 1.23-1.53), duration of surgery < 120 min (3.01; 2.68-3.38), emergency surgery (1.83; 1.60-2.09), laparoscopic surgery (2.01; 1.71-2.36), open abdominal/thoracic surgery (1.56; 1.38-1.78), NMT monitoring used (5.31; 4.63-6.08), total dose of rocuronium (1.99; 1.76-2.25), and (inversely) use of inhalational anaesthetics (0.88; 0.79-0.99). CONCLUSION: Our data demonstrate that the implementation of NMT monitoring with automatic recording coincides with a gradual increase in the (documented) use of NMT monitoring and an increased use of sugammadex with a more precise dose. Factors associated with sugammadex use include higher age, ASA score, BMI, abdominal and thoracic surgery, higher rocuronium doses, emergency surgery and the use of NMT monitoring. Trial registration N/A. KEY POINTS: • Introduction of NMT monitoring with automatic recording coincides with an increase in (documented) use of NMT monitoring. • Sugammadex is more frequently used in patients with a presumed higher a priori risk of pulmonary complications. • Despite increased NMT monitoring and use of sugammadex a significant percentage of patients remain at potential risk of rNMB.

Effect of Different Doses of Sugammadex on Recovery and Hemodynamic Parameters in Reversing Neuromuscular Blockade in Patients Undergoing Electroconvulsive Therapy.

Objective: This retrospective observational study aimed to investigate the effect of different doses of sugammadex used in reversing neuromuscular blockade in electroconvulsive therapy (ECT) procedures on patient recovery and hemodynamic measurements. Methods: Anesthesia induction was performed using propofol (1 mg/kg) and rocuronium (0.4 mg/kg). Patients were classified into group 2 (2 mg/kg) and group 3 (3 mg/kg) according to the dose of sugammadex used to reverse neuromuscular blockade. The patient's spontaneous breathing time, eye-opening time, time to comply with voluntary commands, time to reach Modified Aldrete score (MAS) 9, complications, and hemodynamic data were analyzed. Results: In total, 314 ECT sessions were performed on 46 patients. The average age of the patients was 38.3±12.6 years, and 56.6% (n=26) were male. While the average number of ECTs applied to the patients was 6.8±2.8, the average seizure duration was 28.2±12.7 seconds. The most common diagnosis (32.7%) in patients who underwent ECT was bipolar disorder. The average time to recovery of spontaneous breathing, eyeopening time, time to comply with voluntary commands, and time to reach MAS 9 were found to be significantly lower in group 3 (p<0.001, p<0.001, p<0.001, and p=0.002, respectively). Tooth damage was observed in 0.3% (n=1) and tongue abrasion in 0.6% (n=2) of the cases. Hemodynamic measurements were similar between groups (p>0.05). Conclusions: Sugammadex used at a dose of 3 mg/kg in ECT procedures significantly reduces recovery times compared with 2 mg/kg. However, both doses can be safely and cost-effectively used to reverse the neuromuscular blockade provided by 0.4 mg/kg rocuronium.

Management of Neuromuscular Blocking Agents in Critically Ill Patients with Lung Diseases.

The use of neuromuscular blocking agents (NMBAs) is common in the intensive care unit (ICU). NMBAs have been used in critically ill patients with lung diseases to optimize mechanical ventilation, prevent spontaneous respiratory efforts, reduce the work of breathing and oxygen consumption, and avoid patient-ventilator asynchrony. In patients with acute respiratory distress syndrome (ARDS), NMBAs reduce the risk of barotrauma and improve oxygenation. Nevertheless, current guidelines and evidence are contrasting regarding the routine use of NMBAs. In status asthmaticus and acute exacerbation of chronic obstructive pulmonary disease, NMBAs are used in specific conditions to ameliorate patient-ventilator synchronism and oxygenation, although their routine use is controversial. Indeed, the use of NMBAs has decreased over the last decade due to potential adverse effects, such as immobilization, venous thrombosis, patient awareness during paralysis, development of critical illness myopathy, autonomic interactions, ICU-acquired weakness, and residual paralysis after cessation of NMBAs use. The aim of this review is to highlight current knowledge and synthesize the evidence for the effects of NMBAs for critically ill patients with lung diseases, focusing on patient-ventilator asynchrony, ARDS, status asthmaticus, and chronic obstructive pulmonary disease.

Investigational pharmacological agents for the treatment of ARDS.

INTRODUCTION: Acute Respiratory Distress Syndrome (ARDS) is a heterogeneous form of lung injury with severe hypoxemia and bilateral infiltrates after an inciting event that results in diffuse lung inflammation with a high mortality rate. While research in COVID-related ARDS has resulted in several pharmacotherapeutic agents that have undergone successful investigation, non-COVID ARDS studies have not resulted in many widely accepted pharmacotherapeutic agents despite exhaustive research. AREAS COVERED: The aim of this review is to discuss adjuvant pharmacotherapies targeting non-COVID Acute Lung Injury (ALI)/ARDS and novel therapeutics in COVID associated ALI/ARDS. In ARDS, variable data may support selective use of neuromuscular blocking agents, corticosteroids and neutrophil elastase inhibitors, but are not yet universally used. COVID-ALI/ARDS has data supporting the use of IL-6 monoclonal antibodies, corticosteroids, and JAK inhibitor therapy. EXPERT OPINION: Although ALI/ARDS modifying pharmacological agents have been identified in COVID-related disease, the data in non-COVID ALI/ARDS has been less compelling. The increased use of more specific molecular phenotyping based on physiologic parameters and biomarkers, will ensure equipoise between groups, and will likely allow more precision in confirming pharmacological agent efficacy in future studies.

Current Practices and Safety of Medication Use During Pediatric Rapid Sequence Intubation.

OBJECTIVES: This study aimed to characterize medication-related practices during and immediately -following rapid sequence intubation (RSI) in pediatric care units across the United States and to evaluate adverse drug events. METHODS: This was a multicenter, observational study of medication practices surrounding intubation in pediatric and neonatal intensive care unit (NICU) and emergency department patients across the United States. RESULTS: A total of 172 patients from 13 geographically diverse institutions were included. Overall, 24%, 69%, and 50% received preinduction, induction, and neuromuscular blockade, respectively. Induction and neuromuscular blocking agent (NMBA) use was low in NICU patients (52% and 23%, respectively), whereas nearly all patients intubated outside of the NICU received both (98% and 95%, respectively). NICU patients who received RSI medications were older and weighed more. Despite infrequent use of atropine (21%), only 3 patients developed bradycardia after RSI. Of the 119 patients who received an induction agent, fentanyl (67%) and midazolam (34%) were administered most frequently. Hypotension and hypertension occurred in 23% and 24% of patients, respectively, but were not associated with a single induction agent. Etomidate use was low and not associated with development of adrenal insufficiency. Rocuronium was the most used NMBA (78%). Succinylcholine use was low (11%) and administered despite hyperkalemia in 2 patients. Postintubation sedation and analgesia were not used or inadequate based on timing of initiation in many patients who received a non-depolarizing NMBA. CONCLUSIONS: Medication practices surrounding pediatric RSI vary across the United States and may be influenced by patient location, age, and weight.

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).

Evaluation of the classifications of severity in acute respiratory distress syndrome in childhood by the Berlin Consensus and the Pediatric Acute Lung Injury Consensus Conference / Avaliação das classificações de gravidade na síndrome do desconforto respiratório agudo na infância pelo Consenso de Berlim e pelo Pediatric Acute Lung Injury Consensus Conference

ABSTRACT Objective To compare two methods for defining and classifying the severity of pediatric acute respiratory distress syndrome: the Berlin classification, which uses the relationship between the partial pressure of oxygen and the fraction of inspired oxygen, and the classification of the Pediatric Acute Lung Injury Consensus Conference, which uses the oxygenation index. Methods This was a prospective study of patients aged 0 - 18 years with a diagnosis of acute respiratory distress syndrome who were invasively mechanically ventilated and provided one to three arterial blood gas samples, totaling 140 valid measurements. These measures were evaluated for correlation using the Spearman test and agreement using the kappa coefficient between the two classifications, initially using the general population of the study and then subdividing it into patients with and without bronchospasm and those with and without the use of neuromuscular blockers. The effect of these two factors (bronchospasm and neuromuscular blocking agent) separately and together on both classifications was also assessed using two-way analysis of variance. Results In the general population, who were 54 patients aged 0 - 18 years a strong negative correlation was found by Spearman's test (ρ -0.91; p < 0.001), and strong agreement was found by the kappa coefficient (0.62; p < 0.001) in the comparison between Berlin and Pediatric Acute Lung Injury Consensus Conference. In the populations with and without bronchospasm and who did and did not use neuromuscular blockers, the correlation coefficients were similar to those of the general population, though among patients not using neuromuscular blockers, there was greater agreement between the classifications than for patients using neuromuscular blockers (kappa 0.67 versus 0.56, p < 0.001 for both). Neuromuscular blockers had a significant effect on the relationship between the partial pressure of oxygen and the fraction of inspired oxygen (analysis of variance; F: 12.9; p < 0.001) and the oxygenation index (analysis of variance; F: 8.3; p = 0.004). Conclusion There was a strong correlation and agreement between the two classifications in the general population and in the subgroups studied. Use of neuromuscular blockers had a significant effect on the severity of acute respiratory distress syndrome.

RESUMO Objetivo Comparar dois métodos para definição e classificação de gravidade na síndrome do desconforto respiratório agudo pediátrica: a classificação de Berlim, que utiliza a relação entre pressão parcial de oxigênio e fração inspirada de oxigênio e a classificação do Pediatric Acute Lung Injury Consensus Conference, que utiliza o índice de oxigenação. Métodos Estudo prospectivo com pacientes de 0 - 18 anos com diagnóstico de síndrome do desconforto respiratório agudo e ventilados mecanicamente de forma invasiva, que forneceram de uma a três amostras de gasometria arterial, totalizando 140 medidas válidas. Essas medidas foram avaliadas quanto à correlação pelo teste de Spearman e à concordância pelo coeficiente kappa entre as duas classificações, inicialmente usando a população geral do estudo e, depois, subdividindo-a em pacientes com e sem broncoespasmo e com e sem o uso do bloqueador neuromuscular. Também foi verificado o efeito desses dois fatores (broncoespasmo e bloqueador neuromuscular) de forma separada e conjunta sobre ambas as classificações por meio da análise de variância para dois fatores. Resultados Na população geral, composta de 54 pacientes com idades de 0 - 18 anos, foi encontrada forte correlação negativa pelo teste de Spearman (ρ -0,91; p < 0,001) e forte concordância pelo coeficiente kappa (0,62; p < 0,001) na comparação entre Berlim e Pediatric Acute Lung Injury Consensus Conference. Nas populações com e sem broncoespasmo e com e sem o uso do bloqueador neuromuscular, os coeficientes de correlação mantiveram valores semelhantes aos da população geral. Entretanto, para os pacientes sem uso do bloqueador neuromuscular, houve maior concordância entre as classificações em relação aos pacientes com uso do bloqueador neuromuscular (kappa 0,67 versus 0,56 com p < 0,001 em ambos). Acrescenta-se ainda o efeito significativo do uso do bloqueador neuromuscular sobre a relação entre pressão parcial de oxigênio e fração inspirada de oxigênio (análise de variância; F: 12,9; p < 0,001) e o índice de oxigenação (análise de variância; F: 8,3; p = 0,004). Conclusão Houve forte correlação e concordância entre as duas classificações na população geral e nos subgrupos estudados, entretanto, há efeito significativo do uso do bloqueador neuromuscular sobre as classificações de gravidade da síndrome do desconforto respiratório agudo.

Neuromuscular Blockade Monitoring: Having It but Knowing When Not to Trust It.

Butyrylcholinesterase (BChE) is an enzyme involved in the degradation of depolarizing and non-depolarizing neuromuscular blocking agents (NMBA), such as succinylcholine and mivacurium, respectively. Its deficiency is inherited or acquired, and results in paralysis of skeletal muscles after NMBA administration. We report a case of a 32-year-old pregnant woman proposed for cesarean section. General anesthesia (GA) was induced using propofol and succinylcholine. The surgical procedure was uneventful but after 40 minutes, there was no reversal of neuromuscular block (NMB). Other differential diagnoses were excluded and a deficit of BChe was assumed. When the train-of-four ratio (TOFr) achieved 40%, neostigmine/atropine led to the slow recovery of NMB up to TOFr 88%. The patient was extubated, but ventilation proved ineffective, so GA was induced and the patient was reintubated. A new measurement found a TOFr of 60%. Sedation and ventilatory support were maintained until the complete reversal of NMB (4 hours after succinylcholine). Prolonged block is a rare but serious complication of the use of succinylcholine in patients with BChE deficiency. This report not only highlights the importance of intraoperative NMB monitoring in homozygotic patients for atypical cholinesterase but also raises awareness for its careful interpretation.

Association between neuromuscular blocking agent use and outcomes among out-of-hospital cardiac arrest patients treated with extracorporeal cardiopulmonary resuscitation and target temperature management: A secondary analysis of the SAVE-J II study.

Background: Neuromuscular blocking agents are used to control shivering in cardiac arrest patients treated with target temperature management. However, their effect on outcomes in patients treated with extracorporeal cardiopulmonary resuscitation is unclear. Methods: This study was a secondary analysis of the SAVE-J II study, a retrospective multicenter study of 2175 out-of-hospital cardiac arrest patients treated with extracorporeal cardiopulmonary resuscitation in Japan. We classified patients into those who received neuromuscular blocking agents and those who did not and compared in-hospital mortality and incidence rates of favorable neurological outcome and in-hospital pneumonia between the groups using multivariable regression models and stabilized inverse probability weighting with propensity scores. Results: Six hundred sixty patients from the SAVE-J II registry were analyzed. Neuromuscular blocking agents were used in 451 patients (68.3%). After adjusting for potential confounders, neuromuscular blocking agents use was not significantly associated with in-hospital mortality (aHR 0.88; 95% CI, 0.67-1.14), favorable neurological outcome (aOR 0.85; 95% CI, 0.60-1.11), or pneumonia (aOR 1.52; 95% CI, 0.85-2.71). The results for in-hospital mortality (aHR 0.89; 95% CI, 0.64-1.25), favorable neurological outcome (aOR 0.94; 95% CI, 0.59-1.48) and pneumonia (aOR 1.59; 95% CI, 0.74-3.41) were similar after weighting was performed. Conclusions: Although data on the rationale for using neuromuscular blocking agents were unavailable, their use was not significantly associated with outcomes in out-of-hospital cardiac arrest patients treated with extracorporeal cardiopulmonary resuscitation and targeted temperature management. Neuromuscular blocking agents should be used based on individual clinical indications.