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.

Compared efficacy and tolerance of the neuromuscular blockade induced by brand-name (Nimbex®) and generic (Cisatrex®) of cisatracurium in mechanically ventilated critically ill patients: a crossover double-blind randomized study.

INTRODUCTION: use of generic drugs is common. However, there is still concern among patients and physicians that brand name drugs are more efficient. The aim of the study was to compare efficacy and tolerance between two forms of cisatracurium: brand name versus generic name. METHODS: it´s a crossover, randomized, double-blind physiological trial. Patients admitted for hypoxemic acute respiratory failure with PaO2/FIO2 < 200mmHg despite optimized ventilation and sedation thus requiring non-depolarizing neuromuscular blocking agents (NMBAs), were enrolled. Patients received consecutively, in a random order, cisatracurium brand name (Nimbex®) and generic (Cisatrex®) over two-hour period separated by one-hour washout period. Neuromuscular function was monitored by a calibrated train-of-four (TOF) stimulation device. Paralysis time delay to reach TOF of 2/4, recovery kinetics and tolerance were monitored. The number needed to demonstrate a significant difference in time delays to reach a TOF of 2/4 between the two forms of cisatracurium was estimated at 22 patients. RESULTS: twenty-two patients were included. Eight (36.4%) had acute respiratory distress syndrome; 8(36.4%), acute exacerbation of chronic obstructive pulmonary disease and 3(13.6%), status asthmaticus. Median [IQR] SAPS II at admission, 28.5 [22, 41]. PaO2/FIO2, 121 [81, 156] mmHg. Paralysis time delays were respectively, 80 [50, 112] vs. 87 [65, 115] minutes, in Nimbex® group and Cisatrex® group; (p=0.579). Within the recovery period, the between two-studied drugs´ difference in TOF was at 0.25±0.96; p=0.64. There were no significant hemodynamic differences. CONCLUSION: the present study revealed no significant differences in efficacy nor in tolerance between cisatracurium brand name Nimbex® and generic name Cisatrex® in hypoxemic ventilated patients.

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.

Cost analysis and safety comparison of Cisatracurium and Atracurium in patients undergoing general anesthesia.

BACKGROUND: Non-depolarizing neuromuscular blocking agents (NMB) differ in pharmacokinetic and pharmacodynamic parameters. An anesthesiologist according to these similarities and differences is able to choose the least costly one if the same safety profile and same clinical benefit achieved with the different alternatives. AIM: The main objective of this study is to evaluate the economic and adverse drug reactions prevalence and differences between cisatracurium and atracurium the two non-depolarizing NMB drugs, which are widely used in adult patients undergoing surgery with general anesthesia in a teaching Hospital in Iran. MATERIALS AND METHODS: A cost analysis and adverse drug reactions (ADR) monitoring were performed. Only direct costs were considered and data were collected through a prospective randomized study. Regardless of the type of surgery, 100 patients were randomly divided into two equal groups to receive either cisatracurium or atracurium by anesthesiologists. ADRs prevalence and cost differences between patients receiving one of the two non-depolarizing NMB agents were evaluated by independent sample t-test and Chi-square test respectively. RESULTS: No significant difference was observed between the two groups of patients in demographic data. There was no statistical difference in the ADR prevalence in both groups. The numbers of ADR within atracurium group was higher than cisatracurium group, but this distinction was not statistically significant (p > 0.05). It was significant difference in cost between the two neuromuscular blocking drugs (p < 0.05). CONCLUSIONS: According to our study it seems that atracurium and cisatracurium had similar safety profile and atracurium had a cost benefit relative to cisatracurium in initial loading doses. In patients with instability in hemodynamic parameters the cisatracurium was the appropriate choice.  

[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?

Economic aspects of different muscle relaxant regimens.

OBJECTIVE: At a time of cost reduction in medical care efforts to manage the ever-increasing costs of new pharmaceutical drugs become increasingly important. Costs of four different muscle relaxant regimens including the new intermediate-acting neuromuscular blocking drugs (NMBD) cisatracurium and rocuronium will be analyzed. METHODS: Eighty patients undergoing laparoscopic cholecystectomy were prospectively studied. All patients received standardized general anaesthesia with desflurane/fentanyl. Muscle relaxation was achieved with atracurium, cisatracurium, vecuronium, or rocuronium with 20 patients in each group. Intraoperatively muscle relaxants were added to maintain two twitches of the train-of-four (TOF) assessment. RESULTS: There were no differences among the four groups regarding biometric data, duration of surgery and anesthesia, number of patients with reversal of neuromuscular blockade, and time of extubation. Length of stay in the postanesthesia care unit (PACU) and the incidence of side effects were similar in all groups. Total costs of used drugs were significantly lowest in the atracurium-treated patients (per patient: 18.27 Euro) and significantly highest in the cisatracurium group (26.71 Euro) compared with the other groups (vecuronium: 22.61 Euro; rocuronium: 22.63 Euro). CONCLUSION: It is summarized that the use of cisatracurium was associated with higher costs compared to a standard muscle relaxant regimen using atracurium, whereas patient outcome was the same in all study groups. The routine use of the newer NMBDs can only be justified economically, if considerable improvements to clinical practice can be demonstrated.

Effect of neuromuscular blockade on oxygen consumption and energy expenditure in sedated, mechanically ventilated children.

OBJECTIVE: To quantify the effects of neuromuscular blockade (NMB) on energy expenditure for intubated, mechanically ventilated, critically ill children. DESIGN: A prospective, unblinded clinical study. Each subject was studied twice, before and after establishment of NMB. SETTING: A tertiary care pediatric intensive care unit. PATIENTS: Critically ill children undergoing mechanical ventilation and receiving ongoing sedation were eligible, if they had a cuffed endotracheal tube and were physiologically stable. INTERVENTIONS: A total of 20 children (age, 1 to 15 yrs) were studied in an unblinded, crossover fashion. All were mechanically ventilated via a cuffed endotracheal tube, with ventilator rate and tidal volume adequate to provide complete ventilation, and F(IO2) <0.6. Absence of gas leak around the endotracheal tube was assured, and all patients were sedated using continuous infusions of midazolam and/or fentanyl; no changes in ventilator settings, nutritional input, or inotropic drug dose were permitted during the study period. Each patient underwent indirect calorimetry immediately before establishment of NMB. NMB was then induced, and indirect calorimetry was repeated. Complete blockade was verified using a peripheral nerve stimulator. In each case, the two sets of measurements were completed within a 1-hr period. MEASUREMENTS AND MAIN RESULTS: Data analyzed included identifying and diagnostic information, oxygen consumption, and carbon dioxide production. Energy expenditure was calculated using standard formulas. Oxygen consumption and energy expenditure values obtained before and after the establishment of NMB were compared by using paired Student's t-test. NMB reduced oxygen consumption from 6.54+/-0.49 mL/kg/min to 5.90+/-0.40 ml/kg/min, and energy expenditure was reduced from 46.5+/-3.7 kcal/kg/24 hrs to 41.0+/-2.8 kcal/kg/24 hrs (p < .001 in each case). The reduction in oxygen consumption was 8.7+/-1.7%, and that in energy expenditure 10.3+/-1.8%, of pre-NMB values, respectively. CONCLUSION: NMB significantly reduces oxygen consumption and energy expenditure in critically ill children who are sedated and mechanically ventilated; the degree of reduction is small.

The impact of implementation of neuromuscular blockade monitoring standards in a surgical intensive care unit.

The purpose was to determine whether implementation of standards for peripheral nerve monitoring could decrease the incidence of neuromuscular dysfunction related to the administration of paralytic agents. Over a 2-year period, consecutive patients admitted to a surgical intensive care unit who received continuously-infused or >6 daily doses of neuromuscular blocking agents were subjected to train-of-four (TOF) monitoring of the adductor pollicis. Therapy was titrated to the maintenance of one to two twitches at all times. The incidence of prolonged (>12 h) paralysis after drug discontinuation was documented in these patients and compared to that in patients treated in the previous 12 months. The presence of electrolyte abnormalities, organ dysfunction, and concomitant medications was also recorded. Chi-square analysis with Yates correction was employed. Before implementation of routine TOF monitoring, there were five instances of paralytic-associated neuromuscular dysfunction (5/43). After implementation of the TOF protocol, no instances of paralytic-associated neuromuscular dysfunction occurred (0/90), despite the same incidence of risk factors (100%) (P < 0.05). A protocol for neuromuscular blockade monitoring is efficacious in preventing paralytic-associated neuromuscular dysfunction. This can be a cost-effective measure, minimizing the prolonged mechanical ventilation and intensive rehabilitation required secondary to unmonitored use of neuromuscular blocking agents.

A retrospective analysis of long-term use of nondepolarizing neuromuscular blocking agents in the intensive care unit, and guidelines for drug selection.

Nondepolarizing neuromuscular blocking agents (NNMBAs) are frequently administered to patients in the intensive care unit (ICU). We conducted a retrospective study of patients in intensive care who received infusions (> 48 hrs) of commonly used NNMBAs. The goals were to describe NNMBA use in our ICUs, determine patient characteristics, and assess the cost of the individual drugs. We found that atracurium was prescribed for 68% of study patients; 68% of the patients did not have renal, hepatic, or cardiovascular disease; dosages of NNMBAs varied; a statistically significant increase in dosage requirements over time occurred with atracurium; assessment of neuromuscular blockade was 100% subjective; and 41% and 17% of patients receiving atracurium and vecuronium, respectively, experienced prolonged neuromuscular weakness documented subjectively. As a result of this study, guidelines for agent selection were developed to facilitate cost effective use of NNMBA in our ICUs. Using these guidelines would potentially significantly decrease drug expenditures in this setting.