Traumatic brain injury and RSI is rocuronium or succinylcholine preferred?

PURPOSE OF REVIEW: Traumatic brain injury is widespread and has significant morbidity and mortality. Patients with severe traumatic brain injury often necessitate intubation. The paralytic for rapid sequence induction and intubation for the patient with traumatic brain injury has not been standardized. RECENT FINDINGS: Rapid sequence induction is the standard of care for patients with traumatic brain injury. Historically, succinylcholine has been the agent of choice due to its fast onset and short duration of action, but it has numerous adverse effects such as increased intracranial pressure and hyperkalemia. Rocuronium, when dosed appropriately, provides neuromuscular blockade as quickly and effectively as succinylcholine but was previously avoided due to its prolonged duration of action which precluded neurologic examination. However, with the widespread availability of sugammadex, rocuronium is able to be reversed in a timely manner. SUMMARY: In patients with traumatic brain injury necessitating intubation, rocuronium appears to be safer than succinylcholine.

Does Sugammadex Suppress Allergic Inflammation Due to Rocuronium in Animal Model of Rat?

Introduction and Objectives: There are a few reports in the literature about the successful use of sugammadex in the treatment of hypersensitivity reactions caused by rocuronium; however, the pathophysiological mechanism is still unknown. This study aims to investigate the changes caused by rocuronium in the lung and the effect of sugammadex on these changes with biochemical, light microscopic and immunohistochemical parameters on a rat model. Materials and Methods: For the study, 28-male Sprague-Dawley rats were randomly divided, seven of each, into four groups. Group C (control) received only 0. 9 % NaCl without any drug. Group R received rocuronium alone 1mg/kg. Group S received sugammadex alone 96 mg/kg. Group RS received rocuronium 1mg/kg and sugammadex 96 mg/kg. After 24 h later, the animals were sacrificed and their tissues were removed. Biochemical (IgE/CRP), light microscopic and immunohistochemical findings were recorded. Results: Immunoglobulin E and CRP levels, peribronchial, alveolar septal lymphocytic infiltration, thickening of the alveolar membranes and bleeding sites in Group R were significantly higher than all the other groups. In Group RS, while these parameters were significantly lower than that of Group R and Group S, it was significantly higher than that of Group C. Total mast cells and tryptase-positive mast cells counts were significantly higher in Group R than in all other groups. In Group RS, these parameters were statistically lower than that of Group R and Group S, but higher than that of Group C. Conclusions: This study shows that allergic inflammatory changes due to rocuronium in the lungs of rats are reduced with sugammadex. These results support cases of anaphylaxis due to rocuronium which improved with sugammadex (AU)

Rapid Sequence Induction With a Standard Intubation Dose of Rocuronium After Magnesium Pretreatment Compared With Succinylcholine: A Randomized Clinical Trial.

BACKGROUND: Succinylcholine remains the muscle relaxant of choice for rapid sequence induction (RSI) but has many adverse effects. High-dose rocuronium bromide may be an alternative to succinylcholine for RSI but recovery times are nearly doubled compared with a standard intubating dose of rocuronium. Magnesium sulfate significantly shortens the onset time of a standard intubating dose of rocuronium. We set out to investigate whether intravenous (IV) pretreatment with MgSO4 followed by a standard intubating dose of rocuronium achieved superior intubation conditions compared with succinylcholine. METHODS: Adults were randomized to receive a 15-minute IV infusion of MgSO4 (60 mg·kg-1) immediately before RSI with propofol 2 mg·kg-1, sufentanil 0.2 µg·kg-1 and rocuronium 0.6 mg·kg-1, or a matching 15-minute IV infusion of saline immediately before an identical RSI, but with succinylcholine 1 mg·kg-1. Primary end point was the rate of excellent intubating conditions 60 seconds after administration of the neuromuscular blocking agent and compared between groups using multivariable log-binomial regression model. Secondary end points were blood pressure and heart rate before induction, before and after intubation, and adverse events up to 24 hours postoperatively. RESULTS: Among 280 randomized patients, intubating conditions could be analyzed in 259 (133 MgSO4-rocuronium and 126 saline-succinylcholine). The rate of excellent intubating conditions was 46% with MgSO4-rocuronium and 45% with saline-succinylcholine. The analysis adjusted for gender and center showed no superiority of MgSO4-rocuronium compared with saline-succinylcholine (relative risk [RR] 1.06, 95% confidence interval [CI], 0.81-1.39, P = .659). The rate of excellent intubating conditions was higher in women (54% [70 of 130]) compared with men (37% [48 of 129]; adjusted RR 1.42, 95% CI, 1.07-1.91, P = .017). No significant difference between groups was observed for systolic and diastolic blood pressures. Mean heart rate was significantly higher in the MgSO4-rocuronium group. The percentage of patients with at least 1 adverse event was lower with MgSO4-rocuronium (11%) compared with saline-succinylcholine (28%) (RR 0.38, 95% CI, 0.22-0.66, P < .001). With saline-succinylcholine, adverse events consisted mainly of postoperative muscle pain (n = 26 [19%]) and signs of histamine release (n = 13 [9%]). With MgSO4-rocuronium, few patients had pain on injection, nausea and vomiting, or skin rash during the MgSO4-infusion (n = 5 [4%]). CONCLUSIONS: IV pretreatment with MgSO4 followed by a standard intubating dose of rocuronium did not provide superior intubation conditions to succinylcholine but had fewer adverse effects.

Malignant hyperthermia susceptibility: utilization of genetic results in an electronic medical record to increase safety.

Aim: This manuscript describes implementation of clinical decision support for providers concerned with perioperative complications of malignant hyperthermia susceptibility. Materials & methods: Clinical decision support for malignant hyperthermia susceptibility was implemented in 2018 based around our pre-emptive genotyping platform. We completed a brief descriptive review of patients who underwent pre-emptive testing, focused particularly on RYR1 and CACNA1S genes. Results: To date, we have completed pre-emptive genetic testing on more than 10,000 patients; 13 patients having been identified as a carrier of a pathogenic or likely pathogenic variant of RYR1 or CACNA1S. Conclusion: An alert system for malignant hyperthermia susceptibility - as an extension of our pre-emptive genomics platform - was implemented successfully. Implementation strategies and lessons learned are discussed herein.

Succinylcholine and postoperative pulmonary complications: a retrospective cohort study using registry data from two hospital networks.

BACKGROUND: Neuromuscular blocking agents (NMBAs) with a non-depolarising mechanism of action carry the risk of postoperative residual paralysis and are associated with postoperative pulmonary complications (POPC). Owing to the shorter duration of action, the depolarising NMBA succinylcholine may be associated with less postoperative residual paralysis, and hence fewer POPC. We tested the association of succinylcholine administration during anaesthesia and POPC. METHODS: In a retrospective cohort study of registry data from two large US academic medical centres, 244 850 adult noncardiac surgical patients undergoing general anaesthesia were included. The primary outcome was POPC, defined as post-extubation haemoglobin oxygen de-saturation to <90%, or re-intubation requiring intensive care unit admission within 7 days after surgery. The association between succinylcholine and POPC and its dose-dependency were tested in a hierarchical fashion using a multivariable logistic regression model. RESULTS: A total of 13 206 patients (5.4%) experienced POPC. Use of succinylcholine was associated with increased risk of POPC (adjusted odds ratio [ORAdj]=1.11; 95% confidence interval [CI], 1.06-1.16; P<0.001; adjusted risk=5.18%; 95% CI, 5.06-5.30 without and 5.69%; 95% CI, 5.53-5.85 with succinylcholine), with a dose-dependent relationship (ORAdj=1.08; 95% CI, 1.05-1.11 per mg kg-1; P<0.001). In patients receiving non-depolarising NMBAs, succinylcholine further increased the risk of POPC (ORAdj=1.08; 95% CI, 1.03-1.14; P=0.001). The association between succinylcholine and POPC was modified (P=0.03 for interaction) by the duration of surgery with higher odds of POPC in patients undergoing surgeries of <2 vs ≥2 h (ORAdj=1.24; 95% CI, 1.15-1.33 and 1.05; 95% CI, 1.00-1.10, respectively). CONCLUSIONS: In contrast to our prediction, succinylcholine administration was associated with an increased risk of POPC. This association was dose-dependent and magnified in surgeries of shorter duration.

A Paralyzing Case of Myalgias.

BACKGROUND Myalgia, which describes muscle pain or soreness, is a common presenting complaint encountered in the Emergency Department, in inpatient settings and in outpatient settings. Its differential diagnosis is broad and includes benign as well as more serious clinical entities. Some of the common causes of myalgias include viral infections, strenuous exercise, and medications. Succinylcholine is a well-known neuromuscular blockade agent that is frequently used for rapid sequence intubation and short surgeries. CASE REPORT We present the case of a 70-year-old male who presented to the Emergency Department with a chief complaint of acute, severe onset diffuse myalgia leading to the inability to mobilize. He was being investigated for recent onset generalized lymphadenopathy and had undergone a diagnostic lymph node biopsy under general anesthesia 2 days prior to his presentation. He was diagnosed with presumed succinylcholine-induced myalgias after other etiologies were deemed less likely with thorough history, physical examination, and laboratory investigations. Succinylcholine binds nicotinic acetylcholine receptors of the neuromuscular junction and produces prolonged depolarization during which activation of the muscle is blocked. Initial depolarization of the neuromuscular junction induces hectic fasciculation of the muscle fibers, which in turn may be responsible for the occurrence of post-operative myalgias (POM). This entity can be severe and debilitating and is self-limited. CONCLUSIONS Succinylcholine remains a commonly used agent in anesthesia and succinylcholine-induced myalgia should remain in the differential diagnosis of acute, non-inflammatory myalgia. Its recognition can help avoid unwarranted, possibly invasive investigations and their associated additional healthcare costs.

Succinylcholine-Induced Rhabdomyolysis in Adults: Case Report and Review of the Literature.

PURPOSE: A case of succinylcholine (SCh) and sevoflurane as a probable cause of rhabdomyolysis in an adult is presented, along with a review of the relevant literature and strategies for prevention. SUMMARY: A nondiabetic, morbidly obese 32-year-old female developed rhabdomyolysis after administration of SCh and sevoflurane for diagnostic procedures of 30 minutes' duration. Thirty-three hours following anesthesia, the patient developed diffuse muscle tenderness and progressive weakness with a creatinine kinase (CK) of 4319 U/L. Urinalysis findings indicated contamination, a white blood cells of 12.1 × 103/µL was stress induced, while all other labs were normal. Following 26 hours of intravenous fluids, the patient's CK decreased to 1243 U/L, with pain responsive to acetaminophen and improved mobility, resulting in discharge. With a lack of reasonable alternative causes and a temporal association of symptoms, procedural medication-induced rhabdomyolysis was suspected. Based on Naranjo scale evaluation, SCh and sevoflurane were probable causes of rhabdomyolysis. We reviewed the literature for SCh-induced rhabdomyolysis among adults and found 10 cases. The majority of patients received halogenated anesthesia (HA) and prophylaxis for SCh myopathy, with no known personal or family history of neuromuscular disorders (NMD) reported. CONCLUSION: Rhabdomyolysis was observed in a woman following the administration of SCh and sevoflurane for diagnostic procedures lasting 30 minutes. While avoidance is possible in adults with histories of NMDs, a high index of suspicion for occurrence of rhabdomyolysis is needed whenever combining SCh with HA in all adults.

A Chronology for the Identification and Disclosure of Adverse Effects of Succinylcholine.

BACKGROUND: New therapies are created to address specific problems and enjoy popularity as they enter widespread clinical use. Broader use can reveal unknown adverse effects and impact the life cycle significantly. Succinylcholine, a depolarizing neuromuscular blocker, was the product of decades of research surrounding the ancient compound, curare. It was introduced into practice in the 1950s by Burroughs Wellcome and Company (BW Co) and was welcomed due to its rapidly acting muscle relaxation effects. Global clinical use revealed adverse effects, both minor and major, in particular, hyperkalemia and malignant hyperthermia. We investigated when practitioners and the manufacturer became aware of these adverse effects, how information about these side effects was disseminated, and whether the manufacturer met the regulatory requirements of the time, specifically regarding the timely reporting of adverse effects. SOURCES: Primary literature search using online and archived documents was conducted at the Wood Library-Museum of Anesthesiology, Schaumburg, IL. We consulted documents submitted by BW Co to federal authorities, through the Freedom of Information Act (FOIA), Food and Drug Administration (FDA) reports, promotional advertisements, package inserts, published articles, and textbooks. RESULTS: Initial clinical testing in humans in 1952 found no adverse effects on cardiovascular or respiratory systems. Fasciculations and myalgia were early side effects described in case reports in 1952. Large-scale clinical trials in 1953 found abnormally long recovery times among some patients; the discovery of abnormal pseudocholinesterase enzyme activity was not fully demonstrated until the early 1960s. Bradycardia was first reported in 1957 in children, and in 1959 in adults. In 1960, animal studies reported a transient increase in plasma potassium; further experiments in 1969 clearly demonstrated succinylcholine-induced hyperkalemia in burn patients. Malignant hyperthermia was first described in 1966. Similar cases of elevated temperatures and muscle rigidity were described globally but the underlying mechanism was not elucidated until the 1990s. Standard anesthesia textbooks did not report major side effects of succinylcholine until 1960 and included newly documented side effects with each edition. BW Co's packaging contained warnings as early as the 1950s but were later updated in 1962 and beyond to reflect the newly discovered hyperkalemia and malignant hyperthermia. CONCLUSION: Particularly given the regulatory environment of the time, BW Co appropriately reported the adverse effects of succinylcholine after market entry; it updated promotional and packaging material in a timely manner to reflect newly discovered adverse effects. The toxicity, though alarming and put clinicians on alert, did not seem to heavily impact succinylcholine's use, given its various desirable properties. It is still a choice muscle relaxant used today, although there are efforts to develop superior agents to replace succinylcholine.

Supramolecular therapeutics to treat the side effects induced by a depolarizing neuromuscular blocking agent.

Succinylcholine (Sch) is the only depolarizing neuromuscular blocking agent widely used for rapid sequence induction in emergency rooms. Unfortunately, a variety of (sometimes lethal) adverse effects, such as hyperkalemia and cardiac arrest, are associated with its use, and currently there are no specific antidotes to reverse Sch or to treat these side-effects. Methods: The binding behaviors of Sch and several synthetic receptors, including cucurbit[7]uril, sulfo-calix[4]arene and water-soluble carboxylatopillar[6]arene (WP[6]), were first investigated. With a mouse model, a leathal dose of Sch was selected for evaluation of the antidotal effects of these synthetic receptors on Sch induced mortality. The antidotal effects of a selected synthetic receptor, WP[6], on Sch induced cardiac arrhythmias, hyperkalemia, rhabdomyolysis and paralysis were subsequently evaluated with rat and mouse models. The reversal mechanism was also investigated at a cellular level. Results: All of these macrocyclic molecules exhibited relatively high binding affinities with Sch in vitro. In a Sch-overdosed mouse model, immediate injection of these synthetic receptors right after Sch administration increased the overall survival rate, with WP[6] standing out with the most effective antidotal effects. In addition, administration of WP[6] also reversed the paralysis induced by Sch in a mouse model. Moreover, infusion of WP[6] to Sch-overdosed rats reduced the incidence of cardiac arrhythmia, inhibited the otherwise abnormally high serum potassium levels, and relieved the muscular damage. At the cellular level, WP[6] reversed the Sch induced depolarization and reduced the efflux of intracellular potassium. Conclusion: Synthetic receptors, particularly WP[6], exhibited high binding affinities towards Sch, and presented a significant potential as supramolecular therapeutics to treat the various side effects of Sch by specifically sequestering Sch in vivo.

Malignant Hyperthermia.

Malignant Hyperthermia (MH) is a life-threatening pharmacogenetic disorder which results from exposure to volatile anesthetic agents and depolarizing muscle relaxants. It manifests as a hypermetabolic response resulting in tachycardia, tachypnea, hyperthermia, hypercapnia, acidosis, muscle rigidity and rhabdomyolysis. An increase in the end-tidal carbon dioxide is one of the earliest diagnostic signs. Dantrolene sodium is effective in the management of MH, and should be available whenever general anesthesia is administered. This review also aims to highlight the genetics and pathology of MH, along with its association with various inherited myopathy syndromes like central core disease, multi-mini core disease, Native-American myopathy, and King-Denborough syndrome.

A suspected case of anesthesia-induced rhabdomyolysis in a child undergoing strabismus surgery.

We report a case of acute rhabdomyolysis following general anesthesia for strabismus surgery in a previously healthy 11-year-old girl. The patient received a depolarizing muscle relaxant (succinylcholine) and halogenated volatile anesthetic agent (sevoflurane) during surgery. In rare cases, these classes of drugs can trigger malignant hyperthermia (MH) or anesthesia-induced rhabdomyolysis (AIR), which can cause significant morbidity and mortality if not recognized and treated promptly. Pathophysiology, early recognition, and special considerations in strabismus patients are discussed.

Succinylcholine Use and Dantrolene Availability for Malignant Hyperthermia Treatment: Database Analyses and Systematic Review.

BACKGROUND: Although dantrolene effectively treats malignant hyperthermia (MH), discrepant recommendations exist concerning dantrolene availability. Whereas Malignant Hyperthermia Association of the United States guidelines state dantrolene must be available within 10 min of the decision to treat MH wherever volatile anesthetics or succinylcholine are administered, a Society for Ambulatory Anesthesia protocol permits Class B ambulatory facilities to stock succinylcholine for airway rescue without dantrolene. The authors investigated (1) succinylcholine use rates, including for airway rescue, in anesthetizing/sedating locations; (2) whether succinylcholine without volatile anesthetics triggers MH warranting dantrolene; and (3) the relationship between dantrolene administration and MH morbidity/mortality. METHODS: The authors performed focused analyses of the Multicenter Perioperative Outcomes Group (2005 through 2016), North American MH Registry (2013 through 2016), and Anesthesia Closed Claims Project (1970 through 2014) databases, as well as a systematic literature review (1987 through 2017). The authors used difficult mask ventilation (grades III and IV) as a surrogate for airway rescue. MH experts judged dantrolene treatment. For MH morbidity/mortality analyses, the authors included U.S. and Canadian cases that were fulminant or scored 20 or higher on the clinical grading scale and in which volatile anesthetics or succinylcholine were given. RESULTS: Among 6,368,356 queried outcomes cases, 246,904 (3.9%) received succinylcholine without volatile agents. Succinylcholine was used in 46% (n = 710) of grade IV mask ventilation cases (median dose, 100 mg, 1.2 mg/kg). Succinylcholine without volatile anesthetics triggered 24 MH cases, 13 requiring dantrolene. Among 310 anesthetic-triggered MH cases, morbidity was 20 to 37%. Treatment delay increased complications every 10 min, reaching 100% with a 50-min delay. Overall mortality was 1 to 10%; 15 U.S. patients died, including 4 after anesthetics in freestanding facilities. CONCLUSIONS: Providers use succinylcholine commonly, including during difficult mask ventilation. Succinylcholine administered without volatile anesthetics may trigger MH events requiring dantrolene. Delayed dantrolene treatment increases the likelihood of MH complications. The data reported herein support stocking dantrolene wherever succinylcholine or volatile anesthetics may be used.

Pseudocholinesterase Deficiency: What the Proceduralist Needs to Know.

Pseudocholinesterase deficiency is a rare genetic as well as an acquired disorder that affects the body's ability to metabolize choline esters such as succinylcholine and mivacurium. It can be inherited as an autosomal recessive trait, occurring in approximately 1 in 3,200 to 1 in 5,000 people. In most cases of pseudocholinesterase deficiency, no signs or symptoms of the condition exist. It is first suspected after a prolonged recovery from paralysis following general anesthesia in which succinylcholine or mivacurium are administered. We emphasize the importance of obtaining a detailed history prior to any endoscopic intervention or surgery requiring monitored anesthesia care or general anesthesia. In addition, a family history of anesthesia complications may help identify patients at risk. This article examines a case of a patient who underwent a successful endoscopic pneumatic dilation under general anesthesia for the treatment of achalasia, but was subsequently admitted to the intensive care unit, requiring mechanical ventilator support, for 18 hours. The patient made a complete recovery and was discharged home with no further complications. This case stimulated a review of this entity and we provide recommendations relevant to all proceduralist and anesthesia staff, as well as all personnel involved in procedures.

Comparing The Functional Outcome Of Different Dose Regimes Of Succinylcholine When Used For Rapid Induction And Intubation.

BACKGROUND: This study was conducted to compare outcomes of different doses of succinylcholine, in terms of intubation condition, onset of action, duration of action and abdominal fasciculation. METHODS: Thus, randomized control trial was conducted in the department of anaesthesia and ICU, Nishter Hospital Multan from April 2016 to November 2016. A total number of 60 patients with ASA status I and II were enrolled. All patients were divided into three groups by lottery method. Data was entered and analysed by computer software SPSS version 23.2. Descriptive variables like age and onset of action were presented as mean and SD and continues statistics like gender, abdominal fasciculation and incubation condition were presented as frequency and percentages. Chi square test and one-way ANOVA was applied to see effect modification and significance of results. The p-value 0.05 was considered as significant. RESULTS: A Total number of 60 patients included in this study and all were female. The mean age of the patients was 28.15±4.5 years. The main outcome variables of this study were the fasciculation, satisfactory intubation, onset time (seconds) and duration of action (in minutes). In group (A) 1mg, abdominal fasciculation was found 80%, 85% and 75% in group A, B, C respectively. It was also observed that satisfactory intubation was found 90%, 80% and 30% in three groups respectively. The mean onset time was 50.95±4.6, 70.7±5.66 and 94.15±8.73 seconds in three groups respectively. Similarly, the mean duration of action was 16.1±3.76, 13.55±3.01 and 8±2.05 minutes respectively. CONCLUSIONS: Results of our clinical trial suggest that succinylcholine in low doses shorter duration of action and low rate of abdominal fasciculation which is desirable for rapid induction but onset of action is prolonged and intubation conditions were not satisfactory predominantly. So, we concluded that low doses of succnylcholine are not so much beneficial that I can replace full doses of succinylcholine when used for rapid induction and intubation.