Use Of Neuromuscular Blocking Agents Research Articles

Improving the safety of neuromuscular blocking agents: A statement from the USP Safe Medication Use Expert Committee

Recommendations of the interdisciplinary Safe Medication Use Expert Committee of the United States Pharmacopeia (USP) to assist health care professionals, manufacturers, and organizations in handling neuromuscular blocking agents (NMBAs) safely and effectively are discussed. Review and analysis of the USP Medication Errors Reporting Program and MEDMARX program databases showed a continuing risk of patient harm or death due to errors with NMBAs. Medication errors involving wrong concentrations, wrong doses, wrong drugs, look-alike packaging, and sound-alike names, combined with lack of monitoring and communication, have been associated with the use of NMBAs in health care institutions. Serious adverse events occur when NMBAs are used without adequate safeguards. Recommendations for improving safety were developed through review and discussion of root causes and areas of concern with these medications. Medical errors with NMBAs continue to result in patient morbidity and mortality. Increased awareness and action on the part of all parties involved are needed to improve the safety of this class of medications.

The Use of Neuromuscular Blocking Agents to Facilitate Prehospital Intubation Does Not Impair Outcome after Traumatic Brain Injury

Several studies have demonstrated that the success rate of prehospital intubation is improved by the use of neuromuscular blocking agents (NMBAs). However, a recent study has reported that prehospital intubation with NMBAs worsens outcome after traumatic brain injury (TBI). We sought to determine the effect of the use of NMBAs to facilitate prehospital intubation on outcome after TBI. All patients admitted to our Level I trauma center with a head Abbreviated Injury Scale score >/= 3 were identified by the trauma registry (January 1998-June 2003). Patient records were matched with prehospital databases. Patients were further stratified on the basis of prehospital Glasgow Coma Scale (GCS) score into mild (GCS score of 14/15), moderate (GCS score of 9-13), and severe (GCS score < 9) TBI. Outcome included mortality and good outcome (survival to discharge with a GCS score of 14/15). There were 3,052 patients who were identified as having been transported directly from the field. Complete prehospital data were available for 2,012 patients (66%). Of these, 920 were mild TBI (intubation rate, 17.4%), 293 moderate TBI (intubation rate, 57.7%), and 799 severe TBI (intubation rate, 95%). Overall, 72% of intubated patients received NMBAs. There were no significant differences in demographics or injury severity between the groups. Patients not receiving NMBAs were more likely to be hypotensive and have prehospital cardiopulmonary resuscitation (p = 0.001). The unadjusted mortality for the patients intubated with NMBAs was 25% versus 37% for those not receiving NMBAs (p < 0.001). When adjusted for confounding variables, patients intubated with NMBAs were more likely to survive (odds ratio, 0.63; 95% confidence interval, 0.41-0.97; p = 0.04) and have a good outcome (odds ratio, 1.7; 95% confidence interval, 1.2-2.6; p = 0.006) than those in the no-NMBA group. The use of NMBAs to facilitate prehospital intubation improves outcome for patients with TBI. The value of prehospital intubation for TBI remains to be determined; however, any trial evaluating nonintubation for TBI must be compared with NMBA-facilitated intubation to be valid.

Sedation, analgesia, and neuromuscular blockade for high-frequency oscillatory ventilation

To provide a comprehensive review of the issue related to the administration of sedative, analgesic, and neuromuscular blocking agents (NMBA) to patients who are receiving ventilatory support for acute respiratory distress syndrome (ARDS) with high-frequency oscillatory ventilation. Sedative, analgesic, and NMBA are used with great frequency in patients with severe ARDS who are undergoing high-frequency oscillatory ventilation. In particular, the use of NMBA has been higher than for other ARDS populations. Important considerations for effective treatment include careful patient evaluation, patient-based medication selection, identification of treatment goals with periodic re-assessment, titration of medications to objective parameters such as sedation scales and peripheral nerve stimulation, use of intermittent therapy when feasible, implementation of drug interruption strategies, and discontinuation of medications at the earliest possible time. It is important to recognize that patients evolve from severe ARDS through phases of recovery to the resolution of respiratory failure and that ventilatory management, as well as sedative and related medication requirements, will vary markedly over the course of this process. A multidisciplinary, structured approach that is based on the considerations described should help achieve optimal results in this challenging patient population.

National survey on the use of sedatives and neuromuscular blocking agents in the pediatric intensive care unit.

OBJECTIVES: To describe the sedative and neuromuscular blocking agents (NMBA) that are currently used in pediatric intensive care units across the country and to assess the use of written protocols for their use, criteria used for selecting these agents, monitoring practices, and clinicians responsible for making therapeutic decisions in the pediatric intensive care units. DESIGN: A questionnaire was mailed to pediatric attending physician members of the Society of Critical Care Medicine practicing in the United States in January 1997. A cover letter was also enclosed that explained the purpose of the survey and asked the respondent to forward the questionnaire to a colleague if unable to complete. RESULTS: A total of 176 questionnaires were returned, which represented 145 pediatric institutions across the country, for a response rate of 51%. The agents reported to be used most often for sedation were the opioids and benzodiazepines, which were used for >72 hrs. The NMBA used were vecuronium and pancuronium, which were used for >48 hrs. Newer agents such as propofol and cisatracurium were being used by some clinicians as well. Respondents primarily use the intravenous route of administration as either intermittent bolus or continuous infusion. Frequently cited indications for sedatives were anxiety, fear, and amnesia and facilitation of intubation and maintenance of mechanical ventilation for NMBA. Only 13.4% indicated using written protocols for sedatives and 26.1% for NMBA. Decisions regarding the choice of agent were usually based on clinician preference and experience and the duration of action of the agent. Respondents most often reported using clinical assessment (57%) or the Glasgow Coma Scale (47.3%) to monitor the depth or adequacy of sedation. Over 80% of those surveyed use a peripheral nerve stimulator to monitor NMBA activity. CONCLUSION: Clinicians continue to use the opioids and benzodiazepines most often for sedation in the pediatric intensive care units, but newer agents are being used more often and warrant further investigation. The use of written protocols is very low, possibly because of the lack of guidelines in the literature on pediatric intensive care unit sedation and neuromuscular blockade. Development and implementation of protocols for the selection, use, and monitoring of sedatives and NMBA through a multidisciplinary team approach may be a beneficial way to provide safe and cost-effective therapy to critically ill pediatric patients.

Prospective documentation of sedative, analgesic, and neuromuscular blocking agent use in infants and children in the intensive care unit: A multicenter perspective.

OBJECTIVE: To describe the use of neuromuscular blocking agents (NMBA) in critically ill children. DESIGN: Prospective cohort study. SETTING: Two pediatric intensive care units (ICUs). PATIENTS: All children who received NMBA in the ICUs during the study year. INTERVENTIONS: None Measurements: Data on use of NMBA agents and concurrent use of narcotic and sedative agents were collected. Demographic and outcome information was also obtained. MAIN RESULTS: NMBAs were used for either short-term (<6 hrs) or long-term neuromuscular blockade in 6%-9% of patient ICU days and for long-term blockade in 14%-16% of ventilatory support days. The overall mortality rate among ICU patients who received NMBA was 18%. Choice of agent varied between ICUs; however, succinyl choline was used in only 1% of cases for short-term neuromuscular blockade. The most frequent indication for long-term NMBA use was facilitation of mechanical ventilatory support (49%). Among these children, 46% received high frequency oscillatory ventilation. Long-term neuromuscular blockade was most frequently monitored by clinical examination rather than peripheral nerve stimulation. Paralysis for >6 hrs after discontinuation of NMBA was significantly more common when the agent was administered as an infusion instead of as bolus doses. Myopathy after long-term use of NMBA was seen in only 1 patient (0.4%). Doses (mg/kg) of NMBA did not significantly vary by patient age, but they did increase over time. CONCLUSIONS: Use of NMBA is more common in critically ill children than in reported studies of critically ill adults. Use of NMBA in critically ill children is associated with high severity of illness and mortality rates. Choice of NMBA and method of administration varies among providers. Concurrent use of narcotic and sedative agents with NMBA is frequent, but medication choice also varies among medical providers.

F AILED P REHOSPITAL I NTUBATIONS : A N A NALYSIS OF E MERGENCY D EPARTMENT C OURSES AND O UTCOMES

Objective. To examine the reasons for failed prehospital endotracheal intubation (ETI) and to identify how the airway was subsequently managed in the emergency department (ED). Methods. Data were collected from January to December 1998 for a county-wide paramedic system. Failed prehospital ETIs and perceived reasons for failure were identified. Subsequent ED airway management was reviewed. Results. During the study period there were 13,112 patient contacts resulting in ETI attempts on 592 patients, of whom 536 (90.5%) were successfully intubated. Of the 56 failed field intubations, 49 (87.5%) had ED charts available for review. Endotracheal intubation failure was associated with inadequate relaxation in 24 (49%), difficult anatomy in ten (20%), and obstruction in five (10%). Successful ETI was achieved in the ED in 42 cases (86%). Twenty cases (41%) were facilitated by rapid-sequence intubation (RSI) in the ED. For those with incomplete relaxation in the field, 13 of 24 (54%) were intubated in the ED using RSI. Factors associated with the use of ED RSI include attempted prehospital nasotracheal intubation or attempted prehospital midazolam-facilitated intubation (p < 0.001). The predicted need for RSI in this prehospital system is approximately 3.9%. In eight cases, three or more ETI attempts or the use of rescue airways was required in the ED. The predicted minimum incidence of “truly difficult” intubation in this system is approximately 0.8–1.6%. Conclusions. Paramedic intubation failures result from a variety of factors. Less than half of field intubation failures were remedied in the ED by the use of neuromuscular-blocking agents. A similar number were intubated without the use of RSI. A fraction of failed field ETIs may have resulted from inadequate operator training or experience. A small percentage of field patients were “truly difficult” and required advanced resources in the ED to facilitate airway management. Medical directors should be cognizant of the numerous factors affecting intubation performance when designing and implementing approaches to difficult prehospital airways.

The pharmacoeconomics of neuromuscular blocking drugs.

The pharmacoeconomics of neuromuscular blocking drugs.

Monitoring neuromuscular blockade in the intensive care unit: The peripheral nerve stimulator

Traditionally, neuromuscular blocking agents (NMBAs) have been administered in the operating room as an adjunct to anesthetics. Recent studies in the United States have indicated that 98% of the anesthesiologists and critical care nurses surveyed use NMBAs at least occasionally. When monitoring the use of NMBAs, a combination of clinical monitoring and peripheral nerve stimulator monitoring has been recommended. However, the most effective techniques have yet to be described. Understanding the complexities of NMBAs and the absolute need for accurate monitoring techniques is imperative for clinicians. The purpose of this literature review is to evaluate current literature regarding monitoring techniques of NMBAs and to guide the advanced practice nurse’s role in critical care. (Heart Lung® 1999;28:352-62)

The use of curare-like agents in resuscitation

To analyse current data on use of neuromuscular blocking agents (NBA) in the intensive therapy unit (ITU) patients and to propose practice guidelines. We did a Medline search of French and English language articles on NBA administration in ITU patients from 1960 to 1998. Data were also selected from our own collection of articles and books. Original articles, clinical cases, letters to the editor and review articles were considered. Data on pharmacology of NBA in the ITU patient were extracted, as well as data on administration patterns and cost. The indications for myorelaxation in ITU patients include either short term use, as in anaesthesia, or long term administration for facilitation of mechanical ventilation, control of increased intracranial pressure, status epilepticus, tetanus and oxygen demand in case of muscular hyperactivity, diagnostic and therapeutic procedures facilitation. A beneficial effect of NBA on the prognosis of the disease for which these agents have been used is not yet proven. Suxamethonium, because for its short onset time and duration of action, is the agent of choice for endotracheal intubation if myorelaxation is required. Among the benzylisoquinolines, atracurium and besilate of cisatracurium are convenient agents in ITU patients, whereas mivacurium is of no special interest. Among the aminosteroids, pancuronium and vecuronium are the most often used agents in the ITU. Rocuronium has not yet been extensively assessed. Myorelaxants carry risks for morbidity and mortality. The difficulty to assess the neurological status and the level of sedation is a recognised adverse effect. An accidental disconnection from the circuit and the resulting asphyxia is nowadays recognised without delay by the ventilator. NBAs increase the rate of bronchopulmonary infections. Cardiovascular complications include extreme bradycardia or sinus arrest following vecuronium administration, and cardiac arrest after suxamethonium injection mainly in burned or traumatised patients. Conversely to anaesthesia, NBAs do not carry a significant risk for anaphylactic or anaphylactoid complications in the ITU. Tachyphylaxis occurs mainly in burns and other pathologies modifying acetylcholine receptors. Neuromuscular complications include myopathy from steroids, postparalytic syndrome, deconditioning syndrome and intensive care polyneuropathy. Prolonged curarisation after discontinuation of NBA administration has a multifactorial origin and must be differentiated from neuromuscular complications. For prolonged neuromuscular blockade, pancuronium, vecuronium and atracurium are the agents of choice. The association with an adequate sedation is essential. Assessment of depth of neuromuscular blockade is not based on clinical symptoms but on train-of-four (TOF) twitch monitoring. A convenient basic relaxation is usually obtained with the suppression of the two last responses to TOF. The use of NBA in ITU patient should result from a rational decision making procedure, the blockade titrated with a TOF monitor and maintained as superficially and shortly as possible.

Use of sedatives, analgesics and neuromuscular blocking agents in Danish ICUs 1996/97. A national survey.

To assess the use of sedatives, analgesics and neuromuscular blocking agents (NMBAs) in patients requiring mechanical ventilation in Danish Intensive Care Units (ICUs). Questionnaires were mailed in December 1996 to all Departments of Anaesthesiology listed in the Annual Directory of Danish Hospitals. The questionnaires asked about the use of sedatives, analgesics and NMBAs in patients on mechanical ventilation in the ICU. Forty-nine questionnaires were received from a possible 53 ICUs with ventilators (response rate 92.5%). Sedatives and analgesics were given to patients on mechanical ventilation at virtually all the ICUs surveyed (60% used the combination routinely). The frequency of use was influenced by both the level of ventilatory support and the type of underlying disease. Opioids, benzodiazepines and propofol were employed most commonly, in particular by continuous infusion. NMBAs were used in 65% of the ICUs surveyed in less than 20% of the total number of patients in the respective ICU. Overall 98% of the ICUs reported the occurrence of some kind of side effect secondary to the sedative treatment, but in most ICUs they were reported to occur in less than 20% of the patients. Sedatives and analgesics are widely used in patients requiring mechanical ventilation in Danish ICUs. NMBAs are only used in a few patients. The frequency of use is correlated to the level of ventilatory support required and to the kind of respiratory disease.

The Clinical Use of Neuromuscular Blocking Agents as an Interpretive Aid to the EEG in Suspected Status Epilepticus

ABSTRACT.Generalized convulsive status epilepticus can evolve into a condition of coma with subtle clinical signs. These subtle signs are often indistinguishable from those of a different etiology. The EEG must be used to assess the ongoing electrical activity of the brain and how that is related to the observed clinical features. Determination of status epilepticus must be done as swiftly as possible since abnormal cerebral potentials can permanently damage the cortex. Movement and electromyogenic artifacts from the patient can obscure interpretation of the recording. Temporary pharmaceutical paralysis with non-depolarizing neuromuscular blocking agents can effectively help distinguish artifact from cerebral potentials and guide patient care. Examples are given of cases in which pharmaceutical paralysis helped in the evaluation of the state of the brain in patients with suspected status epilepticus.

Intubation success rates improve for an air medical program after implementing the use of neuromuscular blocking agents

To determine whether the success rate for endotracheal intubation improves after implementing the use of neuromuscular blocking (NMB) agents in an air medical program, this retrospective study analyzed all patients requiring endotracheal intubation at two air medical programs (nurse/paramedic crews) over a 5-year period. Air medical program A, the control group, had employed NMB agents throughout the entire study period. Air medical program B, which did not use NMB agents from July 1, 1989 through June 30, 1992, implemented their use starting July 1, 1992. For program A, the overall intubation success rate was 93.5% (202 successful intubations in 216 patients) and the successful intubations/total attempts ratio was 0.67 (202 of 301). For program B, the overall intubation success rate improved from 66.7% (46 successful intubations in 69 patients) before NMB agent use to 90.5% (57 in 63) after NMB agent use ( P = .001). The successful intubations/total attempts ratio increased from 0.36 (51 of 141) prior to NMB agent use to 0.48 (63 of 132) after NMB agent use ( P = NS). In comparing the 92 patients who did not receive NMB agents to the 40 patients who did, the intubation success rate increased from 69.6% (64 of 92) to 97.5% (39 of 40) ( P < .001) and the successful intubation/total attempts ratio increased from 0.36 (73 of 202) to 0.58 (41 of 71) ( P = .007). With the use of NMB agents, program B's overall intubation success rate increased significantly, matching the results of program A.

Out-of-hospital use of neuromuscular-blocking agents in the united states

Objective. A national survey was mailed to state EMS directors to assess the current status of use of neuromuscular-blocking agents (NMBAs) by EMS systems across the United States. Methods. Initial and second mailings were completed in early 1996 and 1997, respectively. Results. Replies were received from all 50 (100%) states following the second mailing. Twenty-nine (58%) states use NMBAs. Eleven (22%) of the 29 use paralytic drugs only in aeromedical programs. Of the 18 states that use NMBAs in ground-based EMS systems, 11 (22%) use paramedic ambulance staffing exclusively. Registered nurses (RNs) or RN-paramedic teams comprised the majority of the remaining states' staffing configurations. The first reported date of implementation of use of NMBAs was 1985, and there has been a steady trend of additional states launching paralytic drug use over the last 12 years. Conclusion. This trend suggests that use of paralytic drugs by paramedics is becoming standard of care in many out-of-hospital systems.

The use of neuromuscular-blocking agents in children.

The use of neuromuscular-blocking agents in children.

Acute myopathy associated with combined use of corticosteroids and neuromuscular blocking agents.

To review the occurrence and pathophysiology of myopathy associated with combined use of neuromuscular blocking agents (NMBAs) and systemic corticosteroids. A MEDLINE search (1985 to July 1995, English language) yielded case reports and clinical studies involving myopathy or weakness associated with the use of NMBAs and/or corticosteroids. References cited in those articles were reviewed. Prolonged muscle weakness has been reported in intubated patients in the intensive care unit (ICU) who were receiving NMBAs and/or corticosteroids. Many cases involved the use of both agents in individuals with no underlying risk factors. The term "blocking agent-corticosteroid myopathy" (BACM) has been used to describe this myopathy when it develops following combined use of these agents. Features common to BACM include prolonged weakness, elevated creatine kinase concentrations, myopathic features on electromyography, normal nerve conduction and sensation, and reduced deep tendon reflexes. Muscle biopsy results vary, but tend to show type 1 and/or 2 fiber atrophy without inflammation. Some recently reported cases revealed thick myosin myofilament loss, which is consistent with findings in denervated rat muscle after exposure to corticosteroids. Two small prospective studies reported that 36-50% of mechanically ventilated patients receiving either one or both drugs developed prolonged weakness. NMBAs and corticosteroids alone have both been reported to cause myopathy in patients in the ICU. When coadministered, these agents appear to confer an even greater risk of myopathy; the exact pathology is not understood. Concomitant use of NMBAs and corticosteroids should be avoided if possible. Guidelines for cautious use and careful monitoring are suggested when combined use is deemed necessary.

A method to produce sedation in critically ill patients.

To evaluate a protocol based on continuous infusion of a benzodiazepine and morphine to produce apnea/decreased respiratory effort as an adjunct to complex mechanical ventilation in patients with respiratory failure. Observational report of consecutive patients. University medical intensive care unit. Seventeen consecutive patients with acute respiratory failure requiring high levels of sedation and/or paralysis to facilitate mechanical ventilation were studied. Patients were started on a continuous infusion of a benzodiazepine and morphine soon after mechanical ventilation was instituted. The dosages of the benzodiazepine and morphine were increased to the end point of diminished respiratory effort or apnea depending on the clinical status of the patient and ventilatory mode. This regimen was supplemented with single doses of neuromuscular blocking agents (NMBAs) only as the dosages of benzodiazepine/narcotic were being titrated. The benzodiazepine/narcotic agents were then gradually reduced as the patient's condition improved, often using an oral route of administration. The benzodiazepine/morphine combination produced apnea and diminished respiratory effort in patients requiring sedation from 2 to 50 days, including those with hemodynamic instability, hepatic dysfunction, renal dysfunction, and sepsis. The combination allowed the use of NMBAs to be minimized. There was no evidence of worsened hemodynamic instability as a result of the administration of these agents. The gastrointestinal tract could be used for nutrition in 8 of the 17 patients. Continuous infusion of a benzodiazepine and morphine controlled the respiratory rate in patients with severe respiratory failure requiring complex mechanical ventilatory support.

Neurologic function and neuromuscular blocking agents in critical care.

Neuromuscular blocking agent (NMBA) use in critical care units is generally reserved for life threatening situations. The goal of any life-support effort, including efficient mechanical ventilation, maintenance of hemodynamic stability, and NMBA use, is to optimize cerebral preservation. Yet, although all other organ systems are aggressively monitored, very little is done to assess neurologic stability during NMBA therapy. This article addresses the neurologic issues associated with NMBA use: identification of those patients at risk for a neurologic event; rationale for monitoring cerebral changes during paralytic therapy; and potential means of assessing and intervening before, during, and after chemical paralysis.

Neuromuscular blocking agents in the critically ill patient: neither sedating nor pain relieving.

Although neuromuscular blocking agents (NMBAs), such as pancuronium bromide and succinylcholine, are widely used in the management of critically ill patients, many misconceptions regarding the agents' clinical effects and indications persist. This article will discuss these misconceptions and review the indications for the use of NMBAs in the critically ill patient, how these potent agents work, and strategies to effectively manage critically ill patients who are receiving NMBAs as a part of their treatment regimen.

Points: Prescription for a better British diet

<h3>Objectives</h3> Clinical practice guidelines for the management of pain and sedation in critically ill patients have been developed and applied; however, there is limited data on medication use among elderly patients. This study identifies current practice patterns for analgo-sedative use in mechanically ventilated elderly patients in Korea using a national claims database. <h3>Design</h3> Cross-sectional study. <h3>Setting and participants</h3> Ventilated elderly patients aged 65 years or older in intensive care units (ICUs) from an aged patients’ national claims database in Korea <h3>Primary outcome measures</h3> Use of sedatives including benzodiazepines, opioids and non-opioid analgesics, neuromuscular blocking agents (NMBAs) and antipsychotic drugs were analysed by the duration of mechanical ventilation (MV), age and time. <h3>Results</h3> From 2012 to 2016, 22 677 elderly patients underwent MV in 267 general or tertiary ICUs. Mean age was 77.2 (±6.9) years and the median duration of MV was 4.1 days; 77.2% of patients received sedatives, 65.0% analgesics, 29.1% NMBAs and 19.6% antipsychotics. Midazolam (62.0%) was the most commonly prescribed medication. The proportions of sedatives, analgesics and NMBAs increased, whereas the percentages of person-days decreased with longer MV duration (p&lt;0.01). With advanced age, the prevalence and duration of sedative, analgesic and NMBA use decreased (adjusted OR (95% CI) 0.98 (0.97 to 0.98) in all three classes) while antipsychotic did not (adjusted OR 1.00 (1.00–1.01)). Annually, benzodiazepines showed reduced administration (76.2% in 2012 and 71.4% in 2016, p&lt;0.01), while daily opioid dose increased (21.6 in 2012 vs 30.0 mg in 2016, p&lt;0.01). <h3>Conclusions</h3> The prevalence of sedative, analgesic and NMBAs use and daily opioid doses were lower, whereas antipsychotic use was higher compared with those in previous studies in adult patients. The findings warrant further studies investigating appropriateness and safety of medication use that consider clinical severity scores with a focus on elderly patients in ICUs.