Caution for psychiatrists: malignant hyperthermia risks with the anesthetic agent succinylcholine (Suxamethonium) during electroconvulsive therapy.

BACKGROUND: Malignant hyperthermia is a potentially lethal condition triggered by specific anesthetic drugs, especially a depolarizing muscle relaxant of succinylcholine (Suxamethonium). Despite the frequent use of succinylcholine with electroconvulsive therapy (ECT), there has been no reported case of potentially lethal malignant hyperthermia following ECT. In addition, the time interval between the administration of succinylcholine and the onset of malignant hyperthermia has not been outlined in the context of ECT. CASE PRESENTATION: We present the case of a 79-year-old woman suffering from severe depression, who experienced severe malignant hyperthermia due to succinylcholine administration during an ECT session. She presented with a high fever of 40.2 °C, tachycardia of 140/min, hypertension with a blood pressure exceeding 200 mmHg, significant muscle rigidity, and impaired consciousness. These symptoms emerged two hours after ECT, which occurred in a psychiatric ward rather than an operating room, and reached their peak in less than 24 h. She was given 60 mg of dantrolene, which quickly reduced the muscular rigidity. Subsequently, she received two additional doses of 20 mg and 60 mg of dantrolene, which brought her fever down to 36.2 °C and completely eased her muscle rigidity within two days after ECT. CONCLUSIONS: This is the first reported case of potentially lethal malignant hyperthermia after ECT. In addition, it highlights the delayed onset of malignant hyperthermia following an ECT procedure, emphasizing the necessity for psychiatrists to recognize its onset even after the treatment. In the light of potentially lethal consequences of malignant hyperthermia, it is critically important for psychiatrists to closely monitor both intraoperative and postoperative patient's vital signs and characteristic physical presentations, promptly identify any symptomatic emergence, and treat it immediately with dantrolene.

Pregabalina preoperatoria previene las fasciculaciones y mialgias inducidas por succinilcolina: metaanálisis de ensayos aleatorizados / Preoperative pregabalin prevents succinylcholine-induced fasciculations and myalgias: A meta-analysis of randomized trials

La succinilcolina es el bloqueador neuromuscular de referencia para la inducción de secuencia rápida. Sin embargo, su uso se asocia a fasciculaciones y mialgias. Se realizó una revisión sistemática y un metaanálisis. Se incluyeron ensayos clínicos controlados aleatorizados comparando gabapentinoides frente a placebo, para la prevención de fasciculaciones y mialgias inducidas por succinilcolina. Se incluyeron seis estudios clínicos aleatorizados. El número total de pacientes fue de 481, de los cuales 241 se incluyeron en el grupo de intervención y 240 en el grupo de placebo. Los gabapentinoides redujeron la incidencia de mialgia inducida por succinilcolina (RR=0,69; IC95%: 0,56-0,84; p<0,001), que siguió siendo estadísticamente significativa para pregabalina (RR=0,71; IC95%: 0,54-0,93; p=0,013) y gabapentina (RR=0,61; IC95%: 0,45-0,82; p=0,001) por separado. No hubo diferencia entre los grupos en cuanto a fasciculaciones (RR=0,92; IC95%: 0,82-1,03; p=0,148). El uso preoperatorio de gabapentinoides se asocia a una menor incidencia de mialgias inducidas por succinilcolina dentro de las primeras 24horas posteriores al procedimiento. (AU)

Succinylcholine is the gold standard neuromuscular blocker for rapid sequence induction, however, its use is associated with fasciculations and myalgias. A systematic review and meta-analysis including randomized controlled clinical trials was performed comparing gabapentinoids versus placebo for the prevention of fasciculations and succinylcholine-induced myalgias. Six randomized clinical studies were included. The total number of patients was 481, of which 241 were in the intervention group and 240 in the placebo group. Gabapentinoids reduced the incidence of succinylcholine-induced myalgia (RR=.69; 95%CI: .56-.84; P<.001), which remained statistically significant for pregabalin (RR=.71; 95%CI: .54-.93; P=.013) and gabapentin (RR=.61; 95%CI: .45-.82; P=.001) separately. There was no difference between the groups in fasciculations (RR=.92; 95%CI: .82-1.03; P=.148). Preoperative use of gabapentinoids is associated with lower incidence of succinylcholine-induced myalgias within the first 24hours after the procedure. (AU)

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.

Prolonged duration of action of suxamethonium in pregnant and postpartum patients: A registry study.

BACKGROUND: Suxamethonium is hydrolysed by butyrylcholinesterase (BChE) and a low BChE activity can result in a prolonged duration of action of suxamethonium. The BChE activity is reduced during pregnancy and postpartum period by up to 33%. However, it can also be reduced by mutations in the BChE gene. In this study, we assessed BChE activity and mutations in the BChE gene in pregnant and postpartum patients with prolonged duration of action of suxamethonium. It was hypothesised that at least 30% of patients with a low BChE activity did not have a mutation in the BChE gene. METHODS: In this registry study we focused on pregnant and postpartum patients with a history of prolonged duration of action of suxamethonium referred to the Danish Cholinesterase Research Unit (DCRU) between March 2007 and January 2023. Primary outcome was the proportion of patients without a mutation among patients with a low BChE activity. Secondary outcomes were the proportion of patients with a low BChE activity and the proportion of patients with a mutation out of the total number of patients. RESULTS: A total of 40 patients were included and among patients with a low BChE activity, 6% (95% CI: 1%-21%) did not have a mutation. Out of the total number of included patients referred to the DCRU, 90% (95% CI: 76%-97%) had a mutation and 94% (95% CI: 80%-99%) had a low BChE activity. CONCLUSION: Among pregnant and postpartum patients with a history of prolonged duration of action of suxamethonium and a low BChE activity, 6% did not have a mutation in the BChE gene. Our findings suggest that during pregnancy and postpartum clinically relevant prolonged duration of action of suxamethonium rarely occurs in genotypically normal patients.

Rapid sequence induction of anesthesia: works in progress and steps forward with focus to oxygenation and monitoring techniques.

The description of the main scientifically consolidated innovations in recent years on Rapid Sequence Induction have been the subject of this narrative review. Data sources were PubMed, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials, and ClinicaTrials.gov, searched up to March 21st, 2023; rapid sequence induction and anesthesia were used as key word for the research. In recent years at least three significant innovations which have improved the procedure: firstly the possibility of using drugs which rapidly reverse the action of the myorelaxants and which have made it possible to give up the use of succinylcholine, replaced by rocuronium; secondly, the possibility of using much more effective pre-oxygenation methods than in the past, also through apneic oxygenation techniques which allow longer apnea time, and finally new monitoring systems much more effective than pulse oximetry in identifying and predicting periprocedural hypoxemia and indicating the need for ventilation in patients at risk of hypoxemia and preventing it. The description of three main scientifically consolidated innovations in recent years, in pharmacology, oxygen method of administration and monitoring, have been the subject of this narrative review.

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.

Patient suspected susceptibility to malignant hyperthermia: impact of the disease

Abstract 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.

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.

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.

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.