Neuromuscular Blockade Agents Research Articles

Frequency of inadequate neuromuscular blockade during general anesthesia

Study ObjectiveWe used electronic health record data to define frequency of inadequate intraoperative neuromuscular blockade (NMB). DesignRetrospective observational study using electronic health record data. SettingOperating room in a tertiary care academic hospital. PatientsA total of 129,209 adult patients with American Society of Anesthesiologists physical status 1 to 5 undergoing general anesthesia in an outpatient or inpatient setting who received nondepolarizing NMB. We excluded patients intubated before arrival to the operating room, patients undergoing a liver transplant or cardiac surgery, and patients who remained intubated at the end of the operation. InterventionsNone. MeasurementsThe primary outcomes were inadequate NMB defined by (1) documentation of patient movement and (2) documentation of surgical request for additional NMB, followed by NMB agent administration. Main ResultsA total of 1261 patients (1.0%) demonstrated either intraoperative movement (369 or 0.29%) or prompted surgical request for additional NMB agent (921 or 0.71%). Trend analysis showed a variation in the annual rate of inadequate NMB, with an increase from 2004 to 2013 for criteria 1 and 2. ConclusionsNearly 1% of all general anesthetic procedures involving NMB exhibit inadequate relaxation resulting in procedural interruption. These data suggest that current use of neuromuscular blocking drugs and NMB monitoring expose patients to inadequate blockade. The risk of this phenomenon warrants further study.

Observational study on patterns of neuromuscular blockade reversal.

BackgroundUsing electronic health record data, we hypothesized that larger reversal doses are used for patients with deeper levels of neuromuscular blockade (NMB) as evidenced by the last recorded TOF measurement. We also examined if dosing regimens reflect current practice guidelines of using ideal body weight (IBW) for NMB agents and total body weight (TBW) for neostigmine.MethodsThis is a retrospective observational study of adult, ASA 1–4 patients who underwent general anaesthesia and received non-depolarizing NMB agents between 01/01/2004 and 12/31/2013. For the primary outcome, percentages of cases receiving neostigmine and median doses administered for each subjective train-of-four (TOF) category were calculated. Secondary analyses evaluated associations between NMB dosing and neostigmine administration based on Body Mass Index (BMI) categories.ResultsA total of 135,633 cases met inclusion criteria for the study. There was no clinically significant difference in median neostigmine dosing based on last TOF count prior to reversal administration: 37.5 mcg/kg for TOF of 4/4 vs. 37.9 mcg/kg for TOF of 0/4 for the total neostigmine dose. Significantly higher number of patients with lower TOF counts received additional neostigmine administration: 5.7 % for 0/4 vs. 1.5 % for 4/4 TOF counts. The median times to extubation following neostigmine administration were clinically similar across TOF count categories. The median doses for neostigmine based on TBW decreased with higher BMI categories and were significantly different between the lowest and highest categories: 42.8 mcg/kg vs 30.8 mcg/kg for total doses (p < .0001) respectively. The percentages of cases requiring reversal in addition to the initial dose increased with increasing BMI categories and were 2.1 % for BMI < 18 vs. 3.3 % for BMI ≥ 40. The total median dose of NMB agents in ED95 equivalents per IBW increased from 2.9 in the Underweight category to 4.2 in the Class III Obese category. The majority of patients in the pancuronium subgroup received very low ED95 equivalent dose of 0.1 and did not require reversal. Patients receiving cisatracurium were given significantly higher median ED95 equivalent dose of 5.6 vs 2.8–3.9 compared to other intermediate acting NMB agents, while receiving clinically similar doses of neostigmine.ConclusionsNeither neostigmine dosing nor times to extubation were affected by the depth of the neuromuscular blockade prior to reversal. The need for additional reversal, or rescue, correlated strongly with the depth of NMB. There was significant variability in neostigmine dosing across the BMI categories. Underweight patients received relatively lower NMB doses while simultaneously receiving relatively higher reversal doses, and the opposite was true for patients with BMI >40.

Abstract PR272

Background & Objectives: Sugammadex was introduced to anesthetic practice for the reversal of neuromuscular blockade by chemical encapsulation. The study is to evaluate the efficacy and safety of sugammadex on reversal of neuromuscular blockade in pediatric patients under general anesthesia. Materials & Methods: The protocol of this study was registered in PROSPERO 2015 (CRD42015032448). The authors searched databases including the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and ISI Web of Science. Randomized clinical trials were included if they compared sugammadex with neostigmine or placebo in pediatric patients undergoing surgery using rocuronium or vecuronium. The primary outcome of this study was time from the reversal of neuromuscular blockade to train-of-four > 0.9. Incidences of any drug-related adverse events were analyzed as secondary outcome. Data of primary outcome was continuous, and mean difference was used as summary measures with random effects models. The secondary outcome, drugs-related AEs, was binary and relative risk was used as summary measures. The I2 test was used to measure heterogeneity. If strong heterogeneity (I2≥75%) was present and could not be explained by subgroup analyses, the authors would gave up meta-analysis. Results: Seven studies with 388 participants were included, which all used rocuronium as neuromuscular blockade agents. With considerable heterogeneity (I2 = 98.5%) in primary outcome, a qualitative analysis was performed. The results suggested that, compared with placebo or neostigmine, sugammadex can reduce the time from administration of agents to train-of-four > 0.9 (from 1.51 min to 23.76 min). Sugammadex did not increase the incidences of adverse events. Conclusion: Compared with neostigmine or placebo, sugammadex can reverse rocuronium-induced neuromuscular blockade rapidly and safely in pediatrics.

Does pharmacological activation of 5-HT1A receptors improve urine flow rate in female rats?

The role of 5-HT1A receptors in regulating voiding functions remains unclear, particularly regarding the urine flow rate (UFR) during voiding. This study examined the effects of 5-HT1A receptors on regulating urethral functions in female rats and investigated underlying modulatory mechanisms. Intravesical pressure (IVP), external urethral sphincter-electromyography (EUS-EMG), and UFR were simultaneously recorded during continuous transvesical infusion to examine the effects of a 5-HT1A receptor agonist (8-OH-DPAT) and antagonist (WAY-100635) on bladder and urethral functions. In addition, this study evaluated the independent roles of urethral striated and smooth muscles in the UFR in rats after a neuromuscular blockade (NMB) treatment and bilateral hypogastric nerve transection. Our results revealed that 8-OH-DPAT significantly increased the maximal UFR but reduced the mean UFR. This discrepancy may be because 8-OH-DPAT markedly increased the maximal UFR during the initial segment of the flow duration and subsequently induced an approximately zero level of long oscillatory waves during the remaining flow duration. Thus the mean UFR was reduced because of the prolonged approximately zero level of the UFR. However, paralyzing the EUS with an NMB agent, 8-OH-DPAT, significantly increased the maximal and mean UFRs because the prolonged zero level of the oscillatory UFR did not continue. These results support the hypothesis that the increased UFR in female rats during voiding is due to the induction of urethral smooth muscle relaxation by 8-OH-DPAT. This paper provides a detailed understanding of the role of 5-HT1A receptors in controlling the UFR in female rats.

Outcomes following neuromuscular blockade in patients receiving tracheostomies

ObjectiveThe purpose of this study is to determine whether the use of neuromuscular blockade agents (NMBAs) in pediatric patients following tracheostomy is associated with increased rates of complications or a prolonged length of stay. MethodsThis was a single-center retrospective chart review of pediatric patients undergoing tracheostomy placement between 2010 and 2013 who were admitted to the pediatric or neonatal intensive care units and did or did not receive NMBA within 7 days post-procedure. ResultsOut of 114 included patients, 26 (23%) received NMBAs during the postoperative period. Patients receiving NMBAs were more likely to have cardiac disease and preoperative respiratory failure but less likely to have neurologic disease. Patients receiving NMBAs had a longer median postoperative length of stay (33 vs. 23 days, p=0.043) and were more likely to have postoperative ileus (12% vs. 3%, p=0.037). ConclusionIn patients undergoing tracheostomy placement, use of NMBAs is associated with prolonged postoperative hospital courses. NMBAs are not associated with a higher likelihood of postoperative complications.

The RECITE Study: A Canadian Prospective, Multicenter Study of the Incidence and Severity of Residual Neuromuscular Blockade.

Postoperative residual neuromuscular blockade (NMB), defined as a train-of-four (TOF) ratio of <0.9, is an established risk factor for critical postoperative respiratory events and increased morbidity. At present, little is known about the occurrence of residual NMB in Canada. The RECITE (Residual Curarization and its Incidence at Tracheal Extubation) study was a prospective observational study at 8 hospitals in Canada investigating the incidence and severity of residual NMB. Adult patients undergoing open or laparoscopic abdominal surgery expected to last <4 hours, ASA physical status I-III, and scheduled for general anesthesia with at least 1 dose of a nondepolarizing neuromuscular blocking agent for endotracheal intubation or maintenance of neuromuscular relaxation were enrolled in the study. Neuromuscular function was assessed using acceleromyography with the TOF-Watch SX. All reported TOF ratios were normalized to the baseline values. The attending anesthesiologist and all other observers were blinded to the TOF ratio (T4/T1) results. The primary and secondary objectives were to determine the incidence and severity of residual NMB (TOF ratio <0.9) just before tracheal extubation and at arrival at the postanesthesia care unit (PACU). Three hundred and two participants were enrolled. Data were available for 241 patients at tracheal extubation and for 207 patients at PACU arrival. Rocuronium was the NMB agent used in 99% of cases. Neostigmine was used for reversal of NMB in 73.9% and 72.0% of patients with TE and PACU data, respectively. The incidence of residual NMB was 63.5% (95% confidence interval, 57.4%-69.6%) at tracheal extubation and 56.5% (95% confidence interval, 49.8%-63.3%) at arrival at the PACU. In an exploratory analysis, no statistically significant differences were observed in the incidence of residual NMB according to gender, age, body mass index, ASA physical status, type of surgery, or comorbidities (all P > 0.13). Residual paralysis is common at tracheal extubation and PACU arrival, despite qualitative neuromuscular monitoring and the use of neostigmine. More effective detection and management of NMB is needed to reduce the risks associated with residual NMB.

Predicting Survival after Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Failure. The Respiratory Extracorporeal Membrane Oxygenation Survival Prediction (RESP) Score

Increasing use of extracorporeal membrane oxygenation (ECMO) for acute respiratory failure may increase resource requirements and hospital costs. Better prediction of survival in these patients may improve resource use, allow risk-adjusted comparison of center-specific outcomes, and help clinicians to target patients most likely to benefit from ECMO. To create a model for predicting hospital survival at initiation of ECMO for respiratory failure. Adult patients with severe acute respiratory failure treated by ECMO from 2000 to 2012 were extracted from the Extracorporeal Life Support Organization (ELSO) international registry. Multivariable logistic regression was used to create the Respiratory ECMO Survival Prediction (RESP) score using bootstrapping methodology with internal and external validation. Of the 2,355 patients included in the study, 1,338 patients (57%) were discharged alive from hospital. The RESP score was developed using pre-ECMO variables independently associated with hospital survival on logistic regression, which included age, immunocompromised status, duration of mechanical ventilation before ECMO, diagnosis, central nervous system dysfunction, acute associated nonpulmonary infection, neuromuscular blockade agents or nitric oxide use, bicarbonate infusion, cardiac arrest, PaCO2, and peak inspiratory pressure. The receiver operating characteristics curve analysis of the RESP score was c = 0.74 (95% confidence interval, 0.72-0.76). External validation, performed on 140 patients, exhibited excellent discrimination (c = 0.92; 95% confidence interval, 0.89-0.97). The RESP score is a relevant and validated tool to predict survival for patients receiving ECMO for respiratory failure.

Sexually dimorphic urethral activity in response to pharmacological activation of 5-HT1A receptors in the rat

In this study, we examined the possibility that 5-HT1A receptors may underlie sexually dimorphic mechanisms affecting the regulation of urethral functions in anesthetized rats. Simultaneous recordings of intravesical pressure under isovolumetric conditions, external urethral sphincter-electromyography, and urethral perfusion pressure were used to examine the effects of a 5-HT1A receptor agonist [8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT)] and antagonist (WAY-100635) on bladder and urethral functions. This research also evaluated the effects of 8-OH-DPAT and α-bungarotoxin (a neuromuscular blockade agent) on urethral continence using leak point pressure testing, and the distribution of 5-HT1A receptors in the lower urinary tract was assessed by immunohistochemistry. The serotonergic mechanism that controls the urinary bladder and external urethral sphincter-electromyography activity showed no significant sexual differences, but urethral activity in urethral perfusion pressure and leak point pressure values exhibited some sexual differences. 8-OH-DPAT enhanced urethral pressure during continence in rats of both sexes, but the drug elevated the pressure during voiding in male rats and reduced it in female rats. The distribution of 5-HT1A receptors in the spinal cord also showed some sexual differences. The present study contributes to our understanding of the role of 5-HT1A receptors in physiological and immunohistochemical properties of urethral smooth muscle in rats of different sexes. These findings may be a basis for the future development of pharmacotherapies for stress urinary incontinence in men.

Emergency tracheal intubation immediately following traumatic injury

The ABCs of trauma resuscitation begin with the airway evaluation, and effective airway management is imperative in the care of a patient with critical injury. The Eastern Association for the Surgery of Trauma Practice Management Guidelines committee aimed to update the guidelines for emergency tracheal intubation (ETI) published in 2002. These guidelines were made to assist clinicians with decisions regarding airway management for patients immediately following traumatic injury. The goals of the work group were to develop evidence-based guidelines to (1) characterize patients in need of ETI and (2) delineate the most appropriate procedure for patients undergoing ETI. A search of the National Library of Medicine and the National Institutes of Health MEDLINE database was performed using PubMed (www.pubmed.gov). The search retrieved English-language articles published from 2000 to 2012 involving patients who had sustained blunt trauma, penetrating trauma, or heat-related injury and had developed respiratory system insufficiency or required ETI in the immediate period after injury (first 2 hours after injury). Sixty-nine articles were used to construct this set of practice management guidelines. The data supported the formation of six Level 1 recommendations, four Level 2 recommendations, and two Level 3 recommendations. In summary, the decision to intubate a patient following traumatic injury is based on multiple factors, including the need for oxygenation and ventilation, the extent and mechanism of injury, predicted operative need, or progression of disease. Rapid sequence intubation with direct laryngoscopy continues to be the recommended method for ETI, although the use of airway adjuncts such as blind insertion supraglottic devices and video laryngoscopy may be useful in facilitating successful ETI and may be preferred in certain patient populations. There is no pharmacologic induction agent of choice for ETI; however, succinylcholine is the neuromuscular blockade agent recommended for rapid sequence intubation.

Incidence of Residual Neuromuscular Blockade in a Post-Anaesthetic Care Unit

We conducted a prospective observational study to assess the incidence of residual neuromuscular blockade (RNMB) in a post-anaesthetic care unit (PACU) of a tertiary hospital. The subjects were 102 patients undergoing general anaesthesia with neuromuscular blockade (NMB). The procedural anaesthetists were unaware of their patients' inclusion in the study, and the choice of muscle relaxant and use of reversal agents were at the anaesthetists' discretion. On arrival to the PACU, the train-of-four ratio was assessed using electromyography, repeated every five minutes until the train-of-four ratio exceeded 0.9. RNMB was defined as a train-of-four ratio < 0.9. The requirement for airway support, incidence of desaturation while in the PACU and time to eligibility for PACU discharge were recorded. The mean interval between the last dose of relaxant and arrival in the PACU for patients with RNMB was 81 minutes. An intermediate-acting muscle relaxant had been used for most patients. Despite this, RNMB was observed in 31% (95% confidence interval 25 to 47%) of patients. Our findings suggest that RNMB in the PACU is common. As RNMB may predispose to postoperative complications, anaesthetists should utilise quantitative monitoring to assess neuromuscular blockade and optimise reversal use. Anaesthetists should be aware that intervals between the last dose of relaxant of well over one hour do not exclude the possibility of RNMB, even when using intermediate-acting neuromuscular blockade agents.

Clinical effects of low-stretch ventilation on acute respiratory distress syndrome

To investigate the effectiveness of low-stretch as compared with low-tidal-volume strategy in the treatment of acute respiratory distress syndrome (ARDS). Eighty-five cases of ARDS patients were randomly divided into low-stretch group (42 cases) and low-tidal-volume group (43 cases). The former group of patient received pressure assist control mode with not higher than 35 cm H(2)O (1 cm H(2)O=0.098 kPa) of peak pressure or pressure support mode ventilation with not higher than 30 cm H(2)O of Pplateau, while in low-tidal-volume group tidal volume of no more than 6 ml/kg of predicted body weight was given. The mortality rate within 28 days, the incidence of hypercapnia, the duration of using sedatives and neuromuscular blockade agents, the time of ventilation and the length of intensive care unit (ICU) stay were compared between two groups. According to the monitored expiratory tidal volume (V(T)e), the low-stretch group was divided into low-tidal-volume subgroup (V(T)e < or =6 ml/kg, 11 cases) and non-low-tidal-volume subgroup (V(T)e >6 ml/kg, 31 cases). The mortality within 28 days and the incidence of hypercapnia were compared between two subgroups. There was no significant difference in the 28-day mortality rate between two groups (34.0% vs. 37.0%, P>0.05), but patients of low-stretch group had lower incidence of hypercapnia than low-tidal-volume group (10.6% vs. 40.7%, P<0.05), and also the duration of using sedatives [(4.5+/-1.2) days vs. (8.7+/-2.3) days] and neuromuscular blockade agents [(8.4+/-2.1) days vs. (10.7+/-1.2) days], and the length of ventilation and ICU stay [(10.2+/-2.2) days vs. (13.7+/-3.1) days, all P<0.05] were less. Low tidal volume occurred in 26.2% of low-stretch group, and the low-tidal-volume subgroup had higher 28-day mortality rate (40.8%) and incidence of hypercapnia (65.7%) than non-low-tidal-volume subgroup (13.2% and 8.6%, both P<0.05). Compared with low-tidal-volume strategy, low-stretch strategy can reduce the incidence of hypercapnia, the length of ventilation and ICU stay for ARDS patients, but have similar mortality rate. When low-stretch strategy is exercised, an inappropriate low tidal volume may be associated with poor outcome of ARDS.

Monitorización de la sedación profunda. El monitor BIS ®

Adequate monitoring of analgesia and sedation should be one of the main goals in the Intensive Care Units. Once the analgesia is assured, the correct dosage of the sedatives will depend on the correct monitoring of the sedation level. For years, clinical scales have been used to evaluate the sedation level. These scales are appropriate for the evaluation of mild sedation but they cannot correctly evaluate deeply sedated patients or those patients who require continuous intravenous administration of neuromuscular blockade agents. In this chapter, we review the most used monitor to control the adequate level of sedation in the Intensive Care Units as well as the BIS® Monitor, which is the one recommended by the Analgesia and Sedation Work Group of the Spanish Society of Critical Care Medicine (SEMICYUC).

Controversies in rapid sequence intubation in children

Rapid sequence intubation is the method of choice for intubation of the emergency department patient. The purpose of the present review is to address several controversies pertaining to emergency department rapid sequence intubation of children. The topics covered in this review include the determination of the appropriate clinician to perform emergency department intubation, the use of atropine and lidocaine as premedications, the choice of sedative agents depending upon the clinical scenario, and the choice of neuromuscular blockade agent. Concerning these topics: The literature supports that emergency department physicians, with appropriate training, successfully perform intubation in most patients. Limited data exist to determine the appropriate use of atropine and lidocaine for rapid sequence intubation. Etomidate has clearly become a preferred sedative for rapid sequence intubation with a low risk of cardiovascular side effects. Thiopental and propofol may more readily provide adequate sedation as compared with etomidate but both have the potential to reduce blood pressure. Succinylcholine arguably remains the preferred neuromuscular blockade agent for rapid sequence intubation in most children. The side effects of succinylcholine occur in relatively predictable circumstances. Rocuronium is a commonly used nondepolarizing paralytic agent but its prolonged duration of action must be weighed against the risk of side effects associated with succinylcholine. Though more research is needed, the available data allow for the development of protocols that will result in a rational, scenario-based approach to rapid sequence intubation in children.

Prolonged (more than ten hours) neuromuscular blockade after cardiac surgery: report of two cases

We examine two cases of prolonged neuromuscular blockade (NMB) after cardiac surgery. To the best of our knowledge, these are the first reported cases of complete paralysis lasting more than ten hours after surgery. We attribute the extended durations of NMB (more than ten hours) to high doses of NMB drugs in combination with magnesium sulphate and moderate renal failure. Advanced age, hepatic disease, aminoglycoside exposure, hypocalcemia, and possible interaction between rocuronium and pancuronium may have played minor roles. We should avoid administering large doses of NMB agents, even in the context of planned postoperative ventilation. If NMB is not monitored intraoperatively in patients who are at risk of prolonged NMB, then train-of-four response should be measured in the intensive care unit. Adequate sedation should be provided until proper recovery of neuromuscular function is documented.

Handbook of Pediatric Intensive Care, 3rd Edition.

Handbook of Pediatric Intensive Care, 3rd Edition.

Monitoring the administration of neuromuscular blockade in critical care.

The future direction of neuromuscular blockade (NMB) in critical care will be characterized by prudent utilization and quality monitoring. With the potential for persistent paralysis and less than optimal outcomes, this direction makes sense. Prudent utilization can be further defined as exhausting other therapies prior to NMB utilization. When NMB is necessary, the agents should be titrated consistently according to a protocol, using the minimally effective dose to produce the least amount of NMB in order to facilitate patient management. Quality monitoring requires that peripheral nerve stimulator (PNS) monitoring become the standard for monitoring the administration of NMB agents and also that monitoring be accurate. Inherent to prudent utilization and quality monitoring is an adequate knowledge related to all aspects of NMB. The purpose of this article is to provide the necessary knowledge base for practitioners to understand normal and altered neuromuscular junction function, perform accurate PNS monitoring, and titrate NMB therapy according to the individual and desired response.

Pharmacology of Neuromuscular Blocking Agents in the Intensive Care Unit

In critically ill patients, organ function, blood flow, and caregiving personnel change constantly. The risks inherent in paralyzing a patient, such as those of positioning (nerve injuries, stasis injuries) and ventilator disconnection are compounded by the duration of paralysis in the ICU. When used with attention to the pharmacologic properties, patient organ function, and cost, however, muscle relaxants are a useful adjunct to ICU management.

An evaluation of mivacurium chloride in an air medical service

Abstract Introduction: Neuromuscular blockade (NMB) has become popular in the emergency department and even in some ground prehospital systems. A majority of air medical services use NMB following intubation, but far fewer services use NMB as an adjunct to intubation. Mivacurium chloride is a nondepolarizing NMB agent of short-to-intermediate duration. We studied the use of this agent in an air medical service. Setting: Dayton CareFlight is a community hospital-based, rotor-wing program that flies more than 800 flights per year, using a medical team of flight nurses cross-trained as paramedics. Sixty-two percent of the flights are trauma-related. At the time of the study, CareFlight policy allowed the discretionary use of NMB only after airway control had been achieved. NMB could be used to assist in intubation with the permission of the medical-control physician. Methods: Twenty-five patients (age range of 3 to 68 years old) were entered into the study over a six-month period. The program protocol for the discretionary use of NMB requires establishment of a secure airway, followed by hyperventilation with 100% oxygen. Twenty-four patients then were given mivacurium chloride (0.15 mg/kg) intravenously over 60 seconds. A single patient received the same dose of mivacurium chloride to assist in intubation. The onset and duration of NMB as well as any adverse reactions were recorded. Results: Neuromuscular blockade was achieved in a mean of 1.25 minutes (range of one to three minutes), and lasted for 19 minutes (range of five to 35 minutes). No definite or probable adverse reactions due to the drug were noted. Conclusion: Mivacurium chloride can be used safely and effectively by an experienced air medical team to achieve NMB.