Quantitative Neuromuscular Monitoring Permits Early Diagnosis of Abnormal Butyrylcholinestrase: Two Case Studies Demonstrating Prevention of Awareness from Premature Awakening.

Administration of succinylcholine to patients with a variant in the butyrylcholinesterase (BChE) gene increases the risk of anesthesia emergence prior to recovery from neuromuscular blockade (NMB). Application of quantitative neuromuscular monitoring (NMM) can identify residual NMB. We present two patients with abnormal BChE gene variants. In the first case, quantitative monitoring was applied too late to prevent awareness, but allowed diagnosis and prevented admission to the intensive care unit. In the second case, monitoring was applied prior to NMB, which enabled early diagnosis and prevented premature awakening from anesthesia. These cases illustrate the importance of quantitative NMM, even in short cases and with short-acting depolarizing agents such as succinylcholine. The clinical implications of this report include a more consistent use of NMM to identify and manage patients with undiagnosed abnormal BChE and to prevent premature anesthesia emergence.

Drug and pro-drug substrates and pseudo-substrates of human butyrylcholinesterase.

Butyrylcholinesterase (BChE) is present in plasma and numerous cells and organs. Its physiological function(s) is(are) still unclear. However, this enzyme is of pharmacological and toxicological importance. It displays a broad specificity and is capable of hydrolyzing a wide range of substrates with turnovers differing by several orders of magnitude. Nowaday, these substrates include more than two dozen carboxyl-ester drugs, numerous acetylated prodrugs, and transition state analogues of acetylcholine. In addition, BChE displays a promiscuous hydrolytic activity toward amide bonds of arylacylamides, and slowly hydrolyzes carbamyl- and phosphoryl-esters. Certain pseudo-substrates like carbamates and organophosphates are major drugs of potential medical interest. The existence of a large genetic poly-allelism, affecting the catalytic properties of BChE is at the origin of clinical complications in the use of certain drugs catabolized by BChE. The number of drugs and prodrugs hydrolyzed by BChE is expected to increase in the future. However, very few quantitative data (Km, kcat) are available for most marketed drugs, and except for myorelaxants like succinylcholine and mivacurium, the impact of BChE genetic mutations on catalytic parameters has not been evaluated for most of these drugs.

Risk Factors for Postoperative Urinary Retention After Lumbar Fusion Surgery: Anesthetics and Surgical Approach.

INTRODUCTION: Postoperative urinary retention (POUR) after lumbar fusion surgery can lead to longer hospital stays and thus increased risk of developing other postoperative complications. Therefore, we aimed to determine the relationship between POUR and (1) surgical approach and (2) anesthetic agents, including sugammadex and glycopyrrolate. METHODS: After institutional review board approval, L4-S1 single-level lumbar fusion surgeries between 2018 and 2021 were identified. A 3:1 propensity match of patients with POUR to those without was conducted, controlling for patient age, sex, diabetes status, body mass index, smoking status, history of benign prostatic hyperplasia, and the number of levels decompressed. POUR was defined as documented straight catheterization yielding >400 mL. We compared patient demographic, surgical, anesthetic, and postoperative characteristics. A bivariant analysis and backward multivariable stepwise logistic regression analysis ( P -value < 0.200) were performed. Significance was set to P < 0.05. RESULTS: Of the 899 patients identified, 51 met the criteria for POUR and were matched to 153 patients. No notable differences were observed between groups based on demographic or surgical characteristics. On bivariant analysis, patients who developed POUR were more likely to have been given succinylcholine (13.7% vs. 3.92%, P = 0.020) as an induction agent. The independent predictors of POUR identified by multivariable analysis included the use of succinylcholine {odds ratio (OR), 4.37 (confidence interval [CI], 1.26 to 16.46), P = 0.022} and reduced postoperative activity (OR, 0.99 [CI, 0.993 to 0.999], P = 0.049). Factors protective against POUR included using sugammadex as a reversal agent (OR, 0.38 [CI, 0.17 to 0.82], P = 0.017). The stepwise regression did not identify an anterior surgical approach as a notable predictor of POUR. CONCLUSION: We demonstrate that sugammadex for anesthesia reversal was protective against POUR while succinylcholine and reduced postoperative activity were associated with the development of POUR. In addition, we found no difference between the anterior or posterior approach to spinal fusion in the development of POUR.

Post-intubation analgesia and sedation following succinylcholine vs. rocuronium in the emergency department.

BACKGROUND: Succinylcholine and rocuronium are the most commonly utilized neuromuscular blocker agents (NMBAs) for rapid sequence intubation (RSI) in the emergency department (ED). The duration of action of rocuronium is significantly longer (∼30 min) compared to succinylcholine (∼10 min) and previous studies have shown that patients receiving rocuronium are more likely to have longer time to sedation initiation following RSI. Furthermore, patients receiving rocuronium may be more likely to experience awareness with paralysis than those receiving succinylcholine. The primary goal for this study was to evaluate the association between NMBA use during RSI and post-intubation sedation and analgesia practices in the ED. METHODS: This was a retrospective, multicenter cohort study including patients 18 years and older that received succinylcholine or rocuronium during RSI in the ED between September 1, 2020 and August 31, 2021. Patients were excluded if they were intubated prior to ED arrival, experienced an out-of-hospital or in ED cardiac arrest, or received sugammadex within 60 min of rocuronium administration. Patients were screened in reverse chronological order until the targeted sample size was achieved and all data was abstracted from the electronic health record. The primary outcome was the time to initiation of analgesia or sedation. Secondary outcomes included dose of sedatives or analgesia administered at 30- and 60 min, and medications administered for post-intubation sedation or analgesia. FINDINGS: A total of 200 ED patients were included of which 100 received succinylcholine and 100 received rocuronium. There was no difference in the median time to initiation of analgesia or sedation between the succinylcholine and rocuronium groups (10 vs 8.5 min, p = 0.82) or in Kaplan-Meier cumulative probabilities (p = 0.17). At 60 min post-RSI, those receiving succinylcholine received significantly higher median doses of propofol (20 µg/kg/min vs. 10 µg/kg/min; p = 0.02) and fentanyl [100 µg vs. 84.2 µg; p = 0.02]. CONCLUSION: While no differences were observed in the time to initiation of post-intubation sedation or analgesia in ED patients receiving succinylcholine compared to rocuronium, differences in the intensity of post-intubation regimens was observed. Further investigation is needed to evaluate the adequacy of sedation following RSI in the ED.

Pharmacotherapy optimization for rapid sequence intubation in the emergency department.

PURPOSE: Rapid-sequence intubation (RSI) is the process of administering a sedative and neuromuscular blocking agent (NMBA) in rapid succession to facilitate endotracheal intubation. It is the most common and preferred method for intubation of patients presenting to the emergency department (ED). The selection and use of medications to facilitate RSI is critical for success. The purpose of this review is to describe pharmacotherapies used during the RSI process, discuss current clinical controversies in RSI medication selection, and review pharmacotherapy considerations for alternative intubation methods. SUMMARY: There are several steps to the intubation process requiring medication considerations, including pretreatment, induction, paralysis, and post-intubation sedation and analgesia. Pretreatment medications include atropine, lidocaine, and fentanyl; but use of these agents in clinical practice has fallen out of favor as there is limited evidence for their use outside of select clinical scenarios. There are several options for induction agents, though etomidate and ketamine are the most used due to their more favorable hemodynamic profiles. Currently there is retrospective evidence that etomidate may produce less hypotension than ketamine in patients presenting with shock or sepsis. Succinylcholine and rocuronium are the preferred neuromuscular blocking agents, and the literature suggests minimal differences between succinylcholine and high dose rocuronium in first-pass success rates. Selection between the two is based on patient specific factors, half-life and adverse effect profiles. Finally, medication-assisted preoxygenation and awake intubation are less common methods for intubation in the ED but require different considerations for medication use. AREAS FOR FUTURE RESEARCH: The optimal selection, dosing, and administration of RSI medications is complicated, and further research is needed in several areas. Additional prospective studies are needed to determine optimal induction agent selection and dosing in patients presenting with shock or sepsis. Controversy exists over optimal medication administration order (paralytic first vs induction first) and medication dosing in obese patients, but there is insufficient evidence to significantly alter current practices regarding medication dosing and administration. Further research examining awareness with paralysis during RSI is needed before definitive and widespread practice changes to medication use during RSI can be made.

Descriptive Analysis of Combat-Associated Aspiration Pneumonia.

BACKGROUND: Airway obstruction is the second leading cause of potentially preventable death on the battlefield. The treatment for airway obstruction is intubation or advanced airway adjunct, which has a known risk of aspiration. We sought to describe the variables associated with aspiration pneumonia after prehospital airway intervention. METHODS: This is a sub-analysis of previously described data from the Department of Defense Trauma Registry (DoDTR) from 2007 to 2020. We included casualties that had at least one prehospital airway intervention with documentation of subsequent aspiration pneumonia or pneumonia within three days of the intervention. We used a generalized linear model with Firth bias estimates to test for associations. RESULTS: There were 1,509 casualties that underwent prehospital airway device placement. Of these, 41 (2.7%) met inclusion criteria into the aspiration pneumonia cohort. The demographics had no statistical difference between the groups. The non-aspiration cohort had fewer median ventilator days (2 versus 6, p < 0.001), intensive care unit days (2 versus 7, p < 0.001, and hospital days [3 versus 8, p < 0.001]). Survival was lower in the non-aspiration cohort (74.2% versus 90.2%, p = 0.017). The administration of succinylcholine was higher in the non-aspiration cohort (28.0% versus 12.2%, p = 0.031). In our multivariable model, only the administration of succinylcholine was significant and was associated with lower probability of aspiration pneumonia (odds ratio 0.56). CONCLUSION: Overall, the incidence of aspiration pneumonia was low in our cohort. The administration of succinylcholine was associated with a lower odds of developing aspiration pneumonia.

Comparison of etomidate and methohexital as anesthetic agents for continuation and maintenance electroconvulsive therapy: A retrospective analysis of seizure quality and safety.

BACKGROUND: The ideal hypnotic agent for electroconvulsive therapy (ECT) is still under debate and previous studies comparing etomidate and methohexital have produced conflicting results. This retrospective study compares etomidate and methohexital as anesthetic agents in continuation and maintenance (m)ECT with regard to seizure quality and anesthetic outcomes. METHODS: All subjects undergoing mECT at our department between October 1st, 2014 and February 28th, 2022 were included in this retrospective analysis. Data for each ECT session were obtained from the electronic health records. Anesthesia was performed with either methohexital/succinylcholine or etomidate/succinylcholine. Standard seizure quality parameters, anesthesiological monitoring data, pharmacological interventions and side-effects were recorded. RESULTS: 573 mECT treatments in 88 patients were included (methohexital n = 458, etomidate n = 115). Seizures lasted significantly longer after using etomidate (electroencephalography: +12.80 s [95 %-CI:8.64-16.95]; electromyogram +6.59 s [95 %-CI:4.14-9.04]). Time to maximum coherence was significantly longer with etomidate (+7.34 s [95 %-CI:3.97-10.71]. Use of etomidate was associated with longer procedure duration (+6.51 min [95 %-CI:4.84-8.17]) and higher maximum postictal systolic blood pressure (+13.64 mmHg [95 %-CI:9.33-17.94]). Postictal systolic blood pressure > 180 mmHg, the use of antihypertensives, benzodiazepines and clonidine (for postictal agitation), as well as the occurrence of myoclonus was significantly more common under etomidate. CONCLUSIONS: Due to longer procedure duration and an unfavorable side effect profile, etomidate appears inferior to methohexital as an anesthetic agent in mECT despite longer seizure durations.

Skeletal and Dental Fractures Associated With Electroconvulsive Therapy.

During the motor seizure associated with electroconvulsive therapy (ECT), the muscles of the trunk and limbs contract forcefully and repetitively, predisposing to injuries to muscles, joints, teeth, and bones. This motor seizure is irrelevant to the therapeutic action of the treatment. It is therefore modified by the administration of an intravenous muscle relaxant, such as succinylcholine, after the administration of the anesthesia in the ECT premedication. Well-modified ECT is associated with markedly diminished skeletal muscle contractions and hence with minimal skeletal and dental risks. In this context, anecdotal reports across a range of skeletal disorders testify to the safety of well-modified ECT in ultrahigh-risk patients. Population-based data suggest that the fracture risk with modified ECT is 2 events per 100,000 ECTs; if only recent data are examined, the risk may be as low as 0.36 events per 100,000 ECTs. Population-based data also suggest that the dental fracture risk with modified ECT is 0.02% per ECT and 0.17% per ECT course. The overall magnitude of skeletal and dental fracture risk depends on patient factors and on how well the ECT procedure is performed. Preexisting bone and dental disease increase the risk; good seizure modification, proper use of bite blocks, and effective jaw immobilization during ECT reduce the risk. Careful assessment of preexisting risk and good ECT practice can minimize the risk of skeletal and dental complications during ECT.

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.

Severe Postictal Confusion After Electroconvulsive Therapy: A Retrospective Study.

OBJECTIVES: Severe postictal confusion (sPIC) is an important but poorly investigated adverse effect of electroconvulsive therapy (ECT). In this retrospective study, prevalence of sPIC and potential risk factors were explored. METHODS: Medical charts of 295 ECT patients (mean ± SD age, 57 ± 15 years; male, 36%) were scrutinized for occurrence of sPIC, as well as demographic, clinical, and treatment characteristics. Patients showing sPIC were compared with patients who did not, using univariate statistics. Multivariate analyses with a split-sample validation procedure were used to assess whether predictive models could be developed using independent data sets. RESULTS: O 295 patients, 74 (25.1%) showed sPIC. All patients showing sPIC needed extra medication, 9% (n = 7) required physically restraints, and 5% (n = 4) had to be secluded. Univariate analyses showed several trends: patients with sPIC were more often males (P = 0.05), had more often history of cerebrovascular incident (P = 0.02), did not use concomitant selective serotonin reuptake inhibitors (P = 0.01), received higher median dosage of succinylcholine (P = 0.02), and received pretreatment with flumazenil more often (P = 0.07), but these associations did not remain significant after correction for multiple comparisons. Multiple logistic regression analysis did not result in a model that could predict sPIC in the holdout data set. CONCLUSIONS: In this retrospective naturalistic study in 295 ECT patients, the prevalence of sPIC appeared to be 25%. Patients showing sPIC were characterized by male sex, history of cerebrovascular incident, use of higher-dose succinylcholine, and pretreatment with flumazenil. However, multivariate analysis revealed no significant model to predict sPIC in independent data.

Modulation of Cerebral Function by Muscle Afferent Activity, with Reference to Intravenous Succinylcholine.

Cerebral Function and Muscle Afferent Activity Following Intravenous Succinylcholine in Dogs Anesthetized with Halothane: The Effects of Pretreatment with a Defasciculating Dose of Pancuronium. By WL Lanier, PA Iaizzo, and JH Milde. Anesthesiology 1989; 71:87-95. Reprinted with permission. By the mid-1980s, it was widely assumed that if the depolarizing muscle relaxant, succinylcholine, given IV, produced increases in intracranial pressure, it did so because fasciculations produced increases in intrathoracic and central venous pressures that were transferred to the brain; however, there was no direct evidence that this was true. In contrast, we explored the possibility that the succinylcholine effect on the brain was explained by the afferentation theory of cerebral arousal, which predicts that agents or maneuvers that stimulate muscle stretch receptors will tend to stimulate the brain. Our research in tracheally intubated, lightly anesthetized dogs discovered that IV succinylcholine (which does not cross the blood-brain barrier) produced a doubling of cerebral blood flow that lasted for 30 min and corresponded to activation of the electroencephalogram and increases in intracranial pressure. Later, in our Classic Paper, we were able to assess simultaneously cerebral physiology and afferent nerve traffic emanating from muscle stretch receptors (primarily muscle spindles). We affirmed that the cerebral arousal response to succinylcholine was indeed driven by muscle afferent traffic and was independent of fasciculations or increases in intrathoracic or central venous pressures. Later research in complementary models demonstrated that endogenous movement (e.g., coughing, hiccups) produced a cerebral response very similar to IV succinylcholine, apparently as a result of the same muscle afferent mechanisms, independent of intrathoracic and central venous pressures. Thus, the importance of afferentation theory as a driver of the cerebral state of arousal and cerebral physiology during anesthesia was affirmed.

The Nonirritating Concentrations of Neuromuscular Blocking Agents and Related Compounds.

BACKGROUND: Skin testing (ST) concentrations of neuromuscular blocking agents (NMBAs), NMBA-reversal agents, and the sugammadex-rocuronium inclusion complex (S-R-Cx) vary widely among reports. OBJECTIVE: To determine maximal ST nonirritant concentrations (NICs) of NMBAs (cisatracurium, rocuronium, succinylcholine, and vecuronium), NMBA-reversal agents (neostigmine and sugammadex), and S-R-Cx in NMBA-tolerant and NMBA-naïve participants. METHODS: A single-center, prospective study between October 2019 and November 2021 of adult participants with or without a planned surgical procedure. The reference standard was tolerance of medication tested during a procedure (NMBA-tolerant group) before ST. Participants received skin prick testing (SPT) and intradermal test (IDT) injections at 5-7 increasing concentrations of 1 or more medications. All medications were reconstituted according to package insert instructions and diluted with 0.9% saline. A concentration was considered irritant when more than 5% of participants had a positive test per ST positivity criteria (wheal ≥3 mm than initial wheal and associated erythema of the same size or greater than wheal). We also compared our results with current guidelines. RESULTS: A total of 187 participants (78% NMBA-tolerant) underwent 7812 skin tests. All undiluted SPT concentrations were nonirritant. We found the following maximal IDT NICs (mg/mL): cisatracurium (0.02), rocuronium (0.05), succinylcholine (0.8), vecuronium (0.01), neostigmine (0.2), sugammadex (50), and S-R-Cx (sugammadex 7.14 + rocuronium 2). CONCLUSION: Our results suggest that SPT may be performed with undiluted stock concentrations. We confirm maximal IDT NICs for cisatracurium and rocuronium. We also propose that currently recommended maximal IDT NICs of succinylcholine, neostigmine, sugammadex, and S-R-Cx could be increased, whereas the maximal IDT NIC of vecuronium could be decreased compared with current guidelines and prior reports.

Patient suspected susceptibility to malignant hyperthermia: impact of the disease.

INTRODUCTION: Malignant Hyperthermia (MH) is an inherited hypermetabolic syndrome triggered by exposure to halogenated anesthetics/succinylcholine. The lack of knowledge regarding this condition might be associated with the rare occurrence of MH reaction and symptoms. METHODS: This observational study evaluated 68 patients from 48 families with confirmed or suspected MH susceptibility due to medical history of MH reaction or idiopathic increase of creatine kinase or MH-related myopathies. Participants were assessed by a standardized questionnaire and submitted to physical/neurological examination to assess the characteristics of patients with MH, their knowledge about the disease, and the impact suspected MH had on their daily lives. RESULTS: Suspected MH impacted the daily life of 50% of patients, creating difficulties in performing surgical/clinical/dental treatment and problems related to their family life/working/practicing sports. The questionnaire on MH revealed a correct answer score of 62.1 ± 20.8 (mean ± standard deviation) on a scale 0 to 100. Abnormal physical/neurological examination findings were detected in 92.6% of susceptible patients. CONCLUSIONS: Suspected MH had impacted the daily lives of most patients, with patients reporting problems even before MH investigation with IVCT. Patients showed a moderate level of knowledge about MH, suggesting the need to implement continuing education programs. MH susceptible patients require regular follow-up by a health team to detect abnormalities during physical and neurological examination.

Malignant hyperthermia in maxillofacial surgery: Literature review supported by case presentation.

OBJECTIVE: Malignant hyperthermia (MH) is characterized by a state of hypermetabolism after exposure to halogenated inhalational anesthetics or succinylcholine. The aims of this study were to carry out an updated review on the subject and report an illustrative case of MH in urgent maxillofacial surgery. MATERIAL AND METHODS: A search of the PubMed/MEDLINE database using the keyword "malignant hyperthermia" was performed including articles published over the last 11 years in English, Spanish or Portuguese. Exclusion criteria were similar presentations but not associated with MH and cases not related to the use of anesthetic drugs as a trigger of the condition. CASE REPORT: A 45-year-old man (75 kg, ASA status IE) with a negative family history for neuromuscular diseases, victim of a car accident with a facial fracture, underwent surgery under balanced general anesthesia and developed signs of MH 4 h after anesthesia induction. In our patient, the causative agent was sevoflurane and the diagnosis of MH was confirmed, subsequently, by muscle biopsy. RESULTS/DISCUSSION: Overall, 44 cases of MH were found. According to the recent literature, MH shows a male predilection (3:1) and the mean age of patients is 32.2 ± 22.2 years. The most frequently cited causative agents were sevoflurane (30.5%), isoflurane (22.2%), and sevoflurane + succinylcholine (13.8%). The most common clinical indicators included hypercarbia (88.8%), hyperthermia (86.1%), and tachycardia (63.8%). Dantrolene was administered in 24 cases. The outcome was favorable in 31 cases (86.1%). The in vitro muscle contracture test (IVCT) was performed in only 15 patients and all of them tested positive. In our patient, the causative agent was sevoflurane and the diagnosis of MH was confirmed by muscle biopsy. CONCLUSION: The mortality from MH is still high and an early clinical diagnosis and specific treatment with dantrolene are necessary for a favorable outcome. A complete understanding will allow better management of patients with MH. At present, the best management is to identify susceptible patients and to avoid triggering agents, combined with vigilant monitoring.

Should rocuronium and sugammadex replace succinylcholine for airway emergencies in class B ambulatory anesthesia settings?

INTRODUCTION: In class B surgical facilities, where only oral or intravenous (IV) sedation is employed without the administration of volatile anesthetics, laryngospasm is among the most common airway complications. However, these facilities generally do not stock succinylcholine to avoid the cost of storing dantrolene for the treatment of malignant hyperthermia (MH). High dose IV rocuronium with sugammadex reversal has been suggested as an alternative to succinylcholine for airway emergencies. The aim of this paper was to evaluate the clinical utility, patient safety, and financial implications of replacing succinylcholine with rocuronium and sugammadex in lieu of stocking dantrolene in class B facilities. EVIDENCE ACQUISITION: A systematic review of the literature concerning neuromuscular blockade for airway emergencies in class B settings in adult patients was conducted. The MEDLINE and EMBASE databases were searched for published studies from January 1, 1990, to October 1, 2021. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system was used to assess the certainty of evidence. EVIDENCE SYNTHESIS: The search strategy yielded 1124 articles. After review, 107 articles were included, with 49 graded as "strong" evidence to provide recommendations for the posed questions. CONCLUSIONS: The use of succinylcholine in isolation without volatile agents has a low incidence of triggering MH. Laryngospasm is a common airway emergency that requires immediate treatment to avoid morbidity and mortality. Both succinylcholine and rocuronium-sugammadex provide adequate treatment of airway emergencies and rapid return of spontaneous ventilation, but succinylcholine has a superior economic and clinical profile.