An Observational Study of the Efficacy of Cisatracurium Compared with Vecuronium in Patients with or at Risk for Acute Respiratory Distress Syndrome.

RATIONALE: The neuromuscular blocking agent cisatracurium may improve mortality for patients with moderate-to-severe acute respiratory distress syndrome (ARDS). Other neuromuscular blocking agents, such as vecuronium, are commonly used and have different mechanisms of action, side effects, cost, and availability in the setting of drug shortages. OBJECTIVES: To determine whether cisatracurium is associated with improved outcomes when compared with vecuronium in patients at risk for and with ARDS. METHODS: Using a nationally representative database, patients who were admitted to the ICU with a diagnosis of ARDS or an ARDS risk factor, received mechanical ventilation, and were treated with a continuous infusion of neuromuscular blocking agent for at least 2 days within 2 days of hospital admission were included. Patients were stratified into two groups: those who received cisatracurium or vecuronium. Propensity matching was used to balance both patient- and hospital-specific factors. Outcomes included hospital mortality, duration of mechanical ventilation, ICU and hospital duration, and discharge location. MEASUREMENTS AND MAIN RESULTS: Propensity matching successfully balanced all covariates for 3,802 patients (1,901 per group). There was no significant difference in mortality (odds ratio, 0.932; P = 0.40) or hospital days (-0.66 d; P = 0.411) between groups. However, patients treated with cisatracurium had fewer ventilator days (-1.01 d; P = 0.005) and ICU days (-0.98 d; P = 0.028) but were equally likely to be discharged home (odds ratio, 1.19; P = 0.056). CONCLUSIONS: When compared with vecuronium, cisatracurium was not associated with a difference in mortality but was associated with improvements in other clinically important outcomes. These data suggest that cisatracurium may be the preferred neuromuscular blocking agent for patients at risk for and with ARDS.

Sugammadex efficacy for reversal of rocuronium- and vecuronium-induced neuromuscular blockade: A pooled analysis of 26 studies.

STUDY OBJECTIVE: To summarize and compare efficacy of sugammadex with neostigmine or placebo for reversal of rocuronium- or vecuronium-induced neuromuscular blockade (NMB), and to demonstrate consistency of sugammadex results across various patient populations. DESIGN: Pooled analysis on data from 26 multicenter, randomized, Phase II and III studies. SETTING: Operating room. PATIENTS: 1855 adults undergoing surgery under general anesthesia and receiving rocuronium or vecuronium for NMB. INTERVENTIONS: Sugammadex (2.0mg/kg at second twitch reappearance [T2; moderate NMB], 4.0mg/kg at 1-2 post-tetanic counts [PTC; deep NMB] or 16.0mg/kg at 3min after rocuronium 1.2mg/kg), neostigmine or placebo. MEASUREMENTS: Time to recovery of the train-of-four (TOF) ratio to 0.9. MAIN RESULTS: Geometric mean (95% CI) times to recovery to TOF ratio of 0.9 were 1.9 (1.8-2.0) min following sugammadex 2.0mg/kg and 10.6 (9.8-11.6) min following neostigmine administration at T2 after rocuronium, and 2.9 (2.5-3.4) min and 17.4 (13.4-22.6) min, respectively, after vecuronium. Recovery times were 2.2 (2.1-2.3) min following sugammadex 4.0mg/kg and 19.0 (14.8-24.6) min following neostigmine administered at a target of 1-2 PTC after rocuronium, and 3.8 (3.0-5.0) min and 67.6 (56.3-81.2) min after vecuronium. Sugammadex administered 3min after rocuronium 1.2mg/kg resulted in rapid recovery (1.7 [1.5-2.0] min). Modest increases in mean recovery time were associated with vecuronium use (+1.6min [78%; (61%-98%)] versus rocuronium), mild-to-moderate renal impairment (+0.4min [20%; (9%-32%)] versus normal renal function) and geographic location (+1.0min [38%; (25%-52%)] in subjects in USA/Canada versus Europe/Japan). CONCLUSIONS: Sugammadex administered at recommended doses provides rapid and predictable reversal of rocuronium and vecuronium-induced moderate and deep NMB, and effective reversal 3min after rocuronium 1.2mg/kg. Robust recovery was seen across various patient factors, providing further confirmation of labeled dose recommendations.

[A Case of Rocuronium Anaphylaxis in which Anesthesia was Safely Performed after Selection of an Alternative Drug after a Skin Test].

We report our experience of a patient with a history of anaphylactic shock suspected to be caused by rocuronium who was scheduled to undergo hepatic tumor resection. The patient was a 17-year-old female (height : 166 cm, weight : 46 kg). During general anesthesia at another hospital several years ago, she had an anaphylactic shock, and rocuronium was suspected to be the offending drug. To collect information and search for the cause, skin tests were performed for rocuronium, vecuronium and suxamethonium. She was positive for rocuronium, and negative for other drugs. At anesthesia induction, we administered vecuronium and confirmed no development of anaphylaxis before commencement of surgery. In the perioperative period, she had no symptoms that indicated anaphylaxis. Since there is potential high cross-reactivity among muscle relaxants, it is important to perform a test for alternative drugs when a muscle relaxant may be a cause of anaphylaxis. Selection and administration of an alternative drug should be carefully performed, even when a skin test is negative for the alternative drug.

Influence of Tumor Location and Other Variables on Predictive Value of Intraoperative myogenic Motor-Evoked Potentials in Spinal Cord Tumor Surgery.

OBJECTIVE: To study the influence of tumor location (cervical vs. thoracic; extramedullary vs. intramedullary) on predictive value of intraoperative myogenic motor-evoked potentials (iMEP) changes in patients undergoing surgery for spinal cord tumors. METHODS: Three hundred patients retrospective data (91 intramedullary) and 209 (intradural extramedullary) with successful iMEP recordings were analyzed. Responses to transcranial electrical stimulation were recorded from the lower limb muscles. Preoperative clinical variables, iMEPs changes, and postoperative neurologic deficits were noted. Associations between categorical variables and outcome were analyzed with the Fisher exact test. RESULTS: Of the 300 patients 28 (9.3%) had significant intraoperative worsening of iMEPs. New postoperative deficits occurred in 23 of these 28 patients. False-positive decreases in iMEPs were observed in 5 patients. There was a significant association between changes in iMEP and postoperative new motor deficits (P ≤ 0.0001). Multivariate analysis showed that patients with changes in iMEP undergoing surgery for thoracic segment tumors, with longer duration of symptoms (>12 months) and older age (≥21.5 years) were more likely to suffer postoperative neurological decline (odds ratio 4.1, P ≤ 0.001 and odds ratio 5.4 P ≤ 0.0001, respectively). The sensitivity of iMEPs was 100% and specificity 98.2%. The positive and negative predictive values were 82% and 100%; however, the sensitivity and specificity is similar in thoracic intramedullary (TIM) (n = 53) and cervical intramedullary tumors (n = 38) (both were 100% and 97%). The positive predictive value was significantly greater for TIM tumors (93% vs. 50%). CONCLUSIONS: A strong association was observed between worsening of iMEPs and postoperative new neurological deficits in patients with TIM tumor.

Volume guarantee ventilation during surgical closure of patent ductus arteriosus.

BACKGROUND: Surgical closure of patent ductus arteriosus (PDA) is associated with adverse outcomes. Surgical exposure requires retraction of the lung, resulting in decreased aeration and compliance. Optimal respiratory support for PDA surgery is unknown. Experience with volume guarantee (VG) ventilation at our institution led us to hypothesize that surgery would be better tolerated with automatic adjustment of pressure by VG to maintain tidal volume (VT) during retraction. OBJECTIVE: The objective of this study was to describe ventilator support, VT, and oxygenation of infants supported with VG during PDA surgery. DESIGN/METHODS: Ventilator variables, oxygen saturation, and heart rate were recorded during PDA surgery in a convenience sample of infants during PDA closure on VG. Pressure limit increased 11% and set VT was 26% lower during lung retraction. Fentanyl and pancuronium/vecuronium were used for anesthesia/muscle relaxation. Longitudinal data were analyzed by analysis of variance for repeated measures. RESULTS: Seven infants, 25.4 ± 1.5 weeks and 723 ± 141 g, underwent closure of PDA on VG at a mean age 29.9 days. No air leak, bradycardia, or death occurred. Target VT was maintained with a modest increase in inflation pressure. Oxygenation remained adequate. CONCLUSIONS: VG avoided hypoxemia and maintained adequate VT with only a modest increase in peak inflation pressure and thus may be a useful mode during PDA surgery.

Anesthetic management of bronchial rupture following extraction of a fishbone from the bronchus after 5 months.

Bronchial rupture occurred during bronchoscopic visualization and extraction of a fishbone from the bronchus in a 2-year-old male patient with a 5-month history of foreign body aspiration. Emergency thoracotomy was scheduled for examination and surgical repair of the bronchus. The pressure of the airway and circuit fell sharply and ventilation could not be maintained after muscle relaxants were injected and spontaneous respiration ceased. Oxygenation worsened rapidly with the peripheral oxygen saturation level decreasing below 60%. An endotracheal tube was inserted into one of the main bronchi. Peripheral oxygen saturation improved from 60% to 90%, and subsequent surgery was performed without complications.

Long-acting neuromuscular blocker use during prehospital transport of trauma patients.

INTRODUCTION: The purpose of this study was to determine the rate of long-acting neuromuscular blocker (LA-NMB) use and evaluate the concurrent use of sedatives during prehospital care. SETTING: Prehospital patients who were brought to a single emergency department in the United States. METHODS: This was a retrospective cohort study of trauma patients who were intubated in the prehospital setting. The primary outcome measure was to determine the rate of LA-NMB use. The use of postintubation sedatives and the time to the administration of sedative agents was compared between patients who received an LA-NMB and those who did not. RESULTS: A total of 51 patients were included in the final analyses. Overall, 82% (n = 42) of patients received an LA-NMB during transport. There was no difference in the rate of postintubation sedative use during transport between the LA-NMB and no LA-NMB groups (79% vs. 67%, respectively, P = .42). The LA-NMB group received sedatives less promptly after intubation compared with those who did not receive LA-NMBs (16 vs. 7 minutes, respectively; P = .04). CONCLUSION: The use of LA-NMB is common during the prehospital transport of trauma patients. Some of these patients may not be given sedatives or may have delays in receiving sedatives after intubation.

Multichannel intraluminal impedance to study gastroesophageal reflux in mechanically ventilated children in the first 48 h after PICU admission.

OBJECTIVE: The aim of this study was to determine the incidence, characteristics, related factors, and clinical implications of gastroesophageal reflux (GER) in critically ill children using esophageal pH monitoring and multichannel intraluminal impedance. METHODS: A prospective observational clinical study was performed including 36 non-enterally fed critically ill children with mechanical ventilation, aged 1 mo to 7 y, in the first 48 h after admission in the pediatric intensive care unit (PICU). Esophageal pH monitoring and multichannel intraluminal impedance were used. RESULTS: Multichannel intraluminal impedance detected 352 episodes of GER (20.1% acid, 53.8% weak acid, 26% alkaline), whereas pH monitoring detected 171 episodes (100% acid). There were no differences in the type of reflux according to age and no differences in the number or type of reflux according to the administration of inotropic or sedatives drugs or the duration of mechanical ventilation. Patients treated with vecuronium had fewer episodes of GER than those without muscle relaxant drugs. CONCLUSIONS: The incidence of GER in non-enterally fed critically ill children with mechanical ventilation is high in the first 48 h after admission to the PICU. Multichannel intraluminal impedance is more sensitive than pH monitoring for establishing the diagnosis of GER because the refluxate is alkaline or weak acid in the majority of episodes. Patients who received muscle relaxants had a lower frequency of GER.

[Rocuronium vs vecuronium for neuromuscular block during transsternal thymectomy in the patient with myasthenia gravis]. / Rocuronio frente a vecuronio para el bloqueo neuromuscular en la timectomía transesternal del paciente miasténico.

BACKGROUND AND OBJECTIVES: Myasthenia gravis is an autoimmune disease marked by high titers of immunoglobulin G antibodies, which accelerate destruction of cholinergic receptors and interfere with neuromuscular transmission. This study aimed to determine whether neuromuscular function under a rocuronium block is different from function under a vecuronium block patients with myasthenia gravis and to describe extubation conditions in the operating room or the intensive care unit. MATERIAL AND METHODS: Randomized, single-blind clinical trial enrolling patients with myasthenia gravis type IIa and IIb according to the classification of Osserman. The patients were randomized to groups receiving a vecuronium or rocuronium block. We recorded arterial oxygen saturation, capnogram, heart rate, noninvasive blood pressure, electrocardiogram, and neuromuscular function by accelerometry. During surgery 25% of the total dose of the neuromuscular blocking agent was administered. Maintenance was with a continuous infusion of propofol and fentanyl. All patients were extubated according to clinical criteria, confirmed by train-of-four ratio (T4/T1). RESULTS: The mean (SD) time elapsed before recovery of 25% of neuromuscular function was 53.1 (1.9) min in the rocuronium group and 56.2 (0.8) min in the vecuronium group (P = .01). Time elapsed before recovery of 90% of function was 71.3 (2.7) min in the rocuronium group and 96.3 (1.2) min in the vecuronium group (P = .001). Twenty-eight of the 30 patients in the rocuronium group (93.3%) were extubated with recovery of 89.1% (0.5%) of twitch response and a T4/T1 ratio of 0.83. The difference between groups was statistically significant (P = .01). In no case was it necessary to administer a maintenance dose or reverse the block. CONCLUSIONS: The rocuronium block had a better profile than the vecuronium block in this study. With this blocking agent we were able to circumvent respiratory depression, with its immediate consequences, and thus meet the main clinical criterion when anesthetizing patients with myasthenia gravis.

[Muscle relaxants in the ICU]. / Anwendung bei Intensivpatienten--Indikationen und Risiken.

Neuromuscular blockade in ICU patients has become less popular, in particular since non-invasive methods of artificial respiration have been introduced. Succinylcholine has numerous side effects. Due to its short onset, Rocuronium may be an alternative. The advantage of Atracurium and Cis-Atracurium is a largely organ-independent metabolism. In ICU patients, neuromuscular monitoring should be applied. Prolonged action and critical illness neuropathy are the most prominent side effects of neuromuscular blockade.

Neuromuscular blockade, reversal agent use, and operating room time: retrospective analysis of US inpatient surgeries.

PURPOSE: Reducing operating room (OR) time is of interest to hospital administrators because of high costs of OR utilization. Neuromuscular blocking agents (NMBAs) induce muscle relaxation during surgery. Several acetylcholinesterase inhibitors are used to reverse neuromuscular blockade to shorten recovery time. This study explored the relationship between elapsed OR time and the use of specific NMBAs and reversal agents among patients undergoing selected surgeries based on data from two large hospitals. Specifically, this study sought to test the hypothesis that the application of reversal agents in surgeries using a neuromuscular block would be associated with a decrease in elapsed OR time. METHODS: This retrospective cohort study used clinical data from two large hospitals. The authors selected seven types of surgical cases involving thoracic, cardiac, vascular, abdominal, peripheral, urological, and neurological systems. Eligible cases were elective surgeries performed under general anesthesia and using one or more NMBAs (including rocuronium, vecuronium, cisatracurium, and/or pancuronium). Multivariate linear regressions were conducted to examine the relationships among neuromuscular blockade, reversal agent use (including neostigmine, pyridostigmine, and edrophonium), and elapsed OR time by controlling for age, gender, and patient comorbidities. RESULTS: A total of 9670 surgeries were included in this analysis. The mean elapsed OR time across all surgeries was 227 min, and vecuronium was the most commonly used NMBA. Approximately 67% of all surgeries used a reversal agent. After controlling for confounding factors, use of a reversal agent was shown to be associated with the reduction of elapsed OR time in six of seven types of surgery. The magnitude of this effect ranged from 12 to 46 min of OR time saved. The exception was thoracic surgeries, for which use of a reversal agent was shown to be associated with longer OR time (approximately 26 min). Multivariate regression analyses revealed that the type of NMBA used was also a significant predictor of elapsed time for all surgeries (except cardiac). CONCLUSIONS: This analysis has shown that use of selected neuromuscular blockade reversal agents may lead to more efficient OR resource use.

[Medicinal management of pain and symptoms following the withdrawal of treatment in babies and children]. / Medicamenteuze pijn- en symptoombestrijding bij het staken van de behandeling bij pasgeborenen en kinderen.

We present three cases to illustrate the end-of-life care after withdrawal of mechanical ventilation. In a one-year-old girl with meningococcal septic shock, muscle relaxants were continued when mechanical ventilation was withdrawn. In a 10-day-old girl with perinatal asphyxia a high dose of fentanyl was given before mechanical ventilation was withdrawn. A 6-week-old girl in a vegetative state was fighting for breath after detubation. At the request of the parents to end this condition, vecuronium bromide was given. In these three cases death was probably brought forward by a maximum of 12-24 hours. Three arguments can be presented to justify this: the relief of suffering, the perceptions of the parents and the fact that death was expected within a very short time. The administration of these medicines cannot, however, be considered normal medical practice. Therefore we argue that these cases should be reviewed by the national expert review committee and guidelines should be developed for appropriate palliative care after the withdrawal ofmechanical ventilation.

Acute effects of vecuronium on pulmonary function and hypoxemic episodes in preterm infants.

BACKGROUND: Varying effects of pancuronium on neonatal pulmonary mechanics have been documented, including a decrease in pulmonary compliance or no significant change in compliance; but measurements of respiratory mechanics or quantification of episodes of hypoxemia in preterm newborns receiving vecuronium (Norcuron, Bedford Labs, Bedford, OH, USA) have not been reported. The objective of the present study was to quantify the short-term effects of vecuronium on pulmonary mechanics and episodes of hypoxemia in preterm infants receiving mechanical ventilation. METHODS: A total of 15 preterm infants (birthweight 610-1560 g, gestational age 25-32 weeks, postnatal age 0.2-22 days) was studied. The initial dose of vecuronium used for the study was 0.2 mg/kg i.v. Measurements of respiratory mechanics were obtained 1 h prior to and 1 h after the initial dose of vecuronium at comparable ventilator settings and fractional inspired oxygen concentration (FiO(2)). Dynamic respiratory compliance and respiratory resistance were calculated by two-factor least mean square analysis. Pulse oximeter oxygen saturation (SpO(2)) was measured during both 1 h intervals with the Nellcor N-200 oximeter, a computer, and a software program for quantification of episodes of hypoxemia. Heart rate and blood pressure were also monitored. RESULTS: There were no significant differences in tidal volume, respiratory compliance, or respiratory resistance when comparing measurements obtained before and after vecuronium administration. However, fewer episodes of hypoxemia (SpO(2) < 85%, P = 0.025; and SpO(2) < 80%, P = 0.04) were observed during muscle relaxation. No significant changes in heart rate or blood pressure were noted. CONCLUSIONS: The preliminary data indicate: (i) a single dose of vecuronium does not significantly change respiratory compliance or respiratory resistance in preterm infants and (ii) during muscle relaxation fewer episodes of desaturation (hypoxemia) are observed.

Ototoxic drugs and sensorineural hearing loss following severe neonatal respiratory failure.

AIM: To determine relationships between ototoxic drugs and 4-y sensorineural hearing loss (SNHL) in near-term and term survivors of severe neonatal respiratory failure. METHODS: All 81 survivors of the Canadian arm of the Neonatal Inhaled Nitric Oxide Study (mortality 32, loss to follow-up 9) received loop diuretics, aminoglycosides, and neuromuscular blockers (NMB), and 50 received vancomycin as neonates. Prospective, longitudinal secondary outcome using audiological tests diagnosed late-onset, progressive SNHL in 43 (53%); not flat (sloping) in 29, flat (severe to profound) in 14. Risk for SNHL was determined. RESULTS: A combination of duration of diuretic use of >14 d and average NMB dose of >0.96 mg/kg/d contributed to SNHL among survivors (odds ratio 5.2; 95% CI 1.6, 16.7). Markers of illness severity did not contribute. Dosage or duration of aminoglycosides use did not relate to SNHL. Cumulative dosages and duration of use of diuretics; NMB; use of vancomycin; and overlap of diuretics with NMB, aminoglycosides, and vancomycin individually linked to SNHL (p<0.001). CONCLUSION: Overuse of loop diuretics and/or NMB contributes to SNHL after neonatal respiratory failure; markers of illness severity or the appropriate administration of aminoglycosides do not.