A Practical Dosing Algorithm for Deep Neuromuscular Blockade During Total Intravenous Anesthesia: ROCURITHM.

BACKGROUND: The number of trials investigating the effects of deep neuromuscular blockade (NMB) on surgical conditions and patient outcomes is steadily increasing. Consensus on which surgical procedures benefit from deep NMB (a post tetanic count of 1-2) and how to implement it has not been reached. The ESAIC does not advise routine application but recommends use of deep NMB to improve surgical conditions on indication. This study investigates the optimal dosing strategy to reach and maintain adequate deep NMB during total intravenous anesthesia. METHODS: Data from three trials investigating deep NMB during laparoscopic surgery with TIVA (n=424) was pooled to analyze the required rocuronium dose, when to start continuous infusion and how to adjust. The resulting algorithm was validated (n=32) and compared to the success rate in ongoing studies where the algorithm was not used (n=180). RESULTS: The mean rocuronium dose based on actual bodyweight for PTC 1-2 was 1.0 ± 0.27 mg.kg -1.h -1 in the trials where mean duration of surgery was ±2 hours (116 minutes). An induction dose of 0.6 mg.kg -1 lead to a PTC of 1-5 in a quarter of patients after a mean of 11 minutes. The remaining patients were equally divided over too shallow (additional bolus and direct start of continuous infusion) or too deep; a ±15-minute wait after PTC 0 for return of PTC to ≥1. Using the proposed algorithm, a mean 76% of all 5-minute measurements throughout surgery were on target PTC 1-2 in the validation cohort. The algorithm performed significantly better than anesthesiology residents without the algorithm, even after a learning curve from 0-20 patients (42% on target, P≤.001, Cohen's d=1.4 [95% CI 0.9, 1.8]) to 81-100 patients (61% on target, P≤.05, Cohen's d=0.7 [95% CI 0.1, 1.2]). CONCLUSIONS: We propose a dosing algorithm for deep NMB with rocuronium in patients receiving TIVA.

Muscle Ultrasound Abnormalities in Individuals with RYR1-Related Malignant Hyperthermia Susceptibility.

BACKGROUND: Variants in RYR1, the gene encoding the ryanodine receptor-1, can give rise to a wide spectrum of neuromuscular conditions. Muscle imaging abnormalities have been demonstrated in isolated cases of patients with a history of RYR1-related malignant hyperthermia (MH) susceptibility. OBJECTIVE: To provide insights into the type and prevalence of muscle ultrasound abnormalities and muscle hypertrophy in patients carrying gain-of-function RYR1 variants associated with MH susceptibility and to contribute to delineating the wider phenotype, optimizing the diagnostic work-up and care for MH susceptible patients. METHODS: We performed a prospective cross-sectional observational muscle ultrasound study in patients with a history of RYR1-related MH susceptibility (n = 40). Study procedures included a standardized history of neuromuscular symptoms and a muscle ultrasound assessment. Muscle ultrasound images were analyzed using a quantitative and qualitative approach and compared to reference values and subsequently subjected to a screening protocol for neuromuscular disorders. RESULTS: A total of 15 (38%) patients had an abnormal muscle ultrasound result, 4 (10%) had a borderline muscle ultrasound screening result, and 21 (53%) had a normal muscle ultrasound screening result. The proportion of symptomatic patients with an abnormal result (11 of 24; 46%) was not significantly higher compared to the proportion of asymptomatic patients with an abnormal ultrasound result (4 of 16; 25%) (P = 0.182). The mean z-scores of the biceps brachii (z = 1.45; P < 0.001), biceps femoris (z = 0.43; P = 0.002), deltoid (z = 0.31; P = 0.009), trapezius (z = 0.38; P = 0.010) and the sum of all muscles (z = 0.40; P < 0.001) were significantly higher compared to 0, indicating hypertrophy. CONCLUSIONS: Patients with RYR1 variants resulting in MH susceptibility often have muscle ultrasound abnormalities. Frequently observed muscle ultrasound abnormalities include muscle hypertrophy and increased echogenicity.

Functional analysis of RYR1 variants in patients with confirmed susceptibility to malignant hyperthermia.

BACKGROUND: A major bottleneck to the introduction of noninvasive presymptomatic diagnostic tests for the pharmacogenetic disorder malignant hyperthermia is the lack of functional data for associated variants. METHODS: We screened 50 genes having a potential role in skeletal muscle calcium homeostasis using the HaloPlex™ (Agilent Technologies, Santa Clara, CA, USA) target enrichment system and next-generation sequencing. Twenty-one patients with a history of a clinical malignant hyperthermia reaction together with a positive in vitro contracture test were included. Eight variants in RYR1 were subsequently introduced into the cDNA for the human ryanodine receptor gene and tested in cultured human embryonic kidney (HEK293) cells for their effect on calcium release from intracellular stores in response to the ryanodine receptor-1 agonist 4-chloro-m-cresol using fura-2 as calcium indicator. Each variant was subjected to in silico curation using the European Malignant Hyperthermia Group scoring matrix and ClinGen RYR1 variant curation expert panel guidelines. RESULTS: Potentially causative RYR1 variants were identified in 15 patients. Of these, two families carried two RYR1 variants, five variants had been previously reported as 'pathogenic', two variants had been previously reported as 'likely benign', and eight were of 'uncertain significance'. Of these eight variants, four showed hypersensitivity to 4-chloro-m-cresol. Three variants were reclassified as either 'pathogenic' or 'likely pathogenic'. Two were classified as 'benign', whilst three remained of 'uncertain significance'. CONCLUSIONS: Three (p.Tyr1711Cys, p.Val2280Ile, and p.Arg4737Gln) additional variants can be added to the list of RYR1 disease-associated variants managed by the European Malignant Hyperthermia Group. These can therefore be used diagnostically in the future. Three variants (p.Glu2348Gly, p.Asn2634Lys, and p.Arg3629Trp) that remained classified as of uncertain significance require further family studies or a different functional test to determine clinical relevance in malignant hyperthermia.

European Neuromuscular Centre consensus statement on anaesthesia in patients with neuromuscular disorders.

BACKGROUND AND PURPOSE: Patients with neuromuscular conditions are at increased risk of suffering perioperative complications related to anaesthesia. There is currently little specific anaesthetic guidance concerning these patients. Here, we present the European Neuromuscular Centre (ENMC) consensus statement on anaesthesia in patients with neuromuscular disorders as formulated during the 259th ENMC Workshop on Anaesthesia in Neuromuscular Disorders. METHODS: International experts in the field of (paediatric) anaesthesia, neurology, and genetics were invited to participate in the ENMC workshop. A literature search was conducted in PubMed and Embase, the main findings of which were disseminated to the participants and presented during the workshop. Depending on specific expertise, participants presented the existing evidence and their expert opinion concerning anaesthetic management in six specific groups of myopathies and neuromuscular junction disorders. The consensus statement was prepared according to the AGREE II (Appraisal of Guidelines for Research & Evaluation) reporting checklist. The level of evidence has been adapted according to the SIGN (Scottish Intercollegiate Guidelines Network) grading system. The final consensus statement was subjected to a modified Delphi process. RESULTS: A set of general recommendations valid for the anaesthetic management of patients with neuromuscular disorders in general have been formulated. Specific recommendations were formulated for (i) neuromuscular junction disorders, (ii) muscle channelopathies (nondystrophic myotonia and periodic paralysis), (iii) myotonic dystrophy (types 1 and 2), (iv) muscular dystrophies, (v) congenital myopathies and congenital dystrophies, and (vi) mitochondrial and metabolic myopathies. CONCLUSIONS: This ENMC consensus statement summarizes the most important considerations for planning and performing anaesthesia in patients with neuromuscular disorders.

Quality of Recovery and Innate Immune Homeostasis in Patients Undergoing Low-pressure Versus Standard-pressure Pneumoperitoneum During Laparoscopic Colorectal Surgery (RECOVER): A Randomized Controlled Trial.

OBJECTIVE: To study the effects of intra-abdominal pressure on the quality of recovery and innate cytokine production capacity after laparoscopic colorectal surgery within the enhanced recovery after surgery program. BACKGROUND: There is increasing evidence for the safety and advantages of low-pressure pneumoperitoneum facilitated by deep neuromuscular blockade (NMB). Nonetheless, there is a weak understanding of the relationship between clinical outcomes, surgical injury, postoperative immune dysfunction, and infectious complications. METHODS: Randomized controlled trial of 178 patients treated at standard-pressure pneumoperitoneum (12 mm Hg) with moderate NMB (train-of-four 1-2) or low pressure (8 mm Hg) facilitated by deep NMB (posttetanic count 1-2). The primary outcome was the quality of recovery (Quality of Recovery 40 questionnaire) on a postoperative day 1 (POD1). The primary outcome of the immune substudy (n=100) was ex vivo tumor necrosis factor α production capacity upon endotoxin stimulation on POD1. RESULTS: Quality of Recovery 40 score on POD1 was significantly higher at 167 versus 159 [mean difference (MD): 8.3 points; 95% confidence interval (CI): 2.5, 14.1; P =0.005] and the decline in cytokine production capacity was significantly less for tumor necrosis factor α and interleukin-6 (MD: -172 pg/mL; 95% CI: -316, -27; P =0.021 and MD: -1282 pg/mL; 95% CI: -2505, -59; P =0.040, respectively) for patients operated at low pressure. Low pressure was associated with reduced surgical site hypoxia and inflammation markers and circulating damage-associated molecular patterns, with a less impaired early postoperative ex vivo cytokine production capacity. At low pressure, patients reported lower acute pain scores and developed significantly less 30-day infectious complications. CONCLUSIONS: Low intra-abdominal pressure during laparoscopic colorectal surgery is safe, improves the postoperative quality of recovery and preserves innate immune homeostasis, and forms a valuable addition to future enhanced recovery after surgery programs.

Pre-operative exercise and pyrexia as modifying factors in malignant hyperthermia (MH).

Malignant hyperthermia (MH) is a life-threatening reaction triggered by volatile anesthetics and succinylcholine. MH is caused by mutations in the skeletal muscle ryanodine receptor (RYR1) gene, as is rhabdomyolysis triggered by exertion and/or pyrexia. The discrepancy between the prevalence of risk genotypes and actual MH incidence remains unexplained. We investigated the role of pre-operative exercise and pyrexia as potential MH modifying factors. We included cases from 5 MH referral centers with 1) clinical features suggestive of MH, 2) confirmation of MH susceptibility on Contracture Testing (IVCT or CHCT) and/or RYR1 genetic testing, and a history of 3) strenuous exercise within 72 h and/or pyrexia >37.5 °C prior to the triggering anesthetic. Characteristics of MH-triggering agents, surgery and succinylcholine use were collected. We identified 41 cases with general anesthesias resulting in an MH event (GA+MH, n = 41) within 72 h of strenuous exercise and/or pyrexia. We also identified previous general anesthesias without MH events (GA-MH, n = 51) in the index cases and their MH susceptible relatives. Apart from pre-operative exercise and/or pyrexia, trauma and acute abdomen as surgery indications, emergency surgery and succinylcholine use were also more common with GA+MH events. These observations suggest a link between pre-operative exercise, pyrexia and MH.

Referral Indications for Malignant Hyperthermia Susceptibility Diagnostics in Patients without Adverse Anesthetic Events in the Era of Next-generation Sequencing.

BACKGROUND: The introduction of next-generation sequencing into the diagnosis of neuromuscular disorders has resulted in an increased number of newly identified RYR1 variants. The hypothesis was that there is an increased referral of patients to malignant hyperthermia units without a personal/family history of adverse anesthetic events suspected to be malignant hyperthermia. This retrospective multicenter cohort study evaluates patient referral indications and outcomes for those without a history of an adverse anesthetic event. METHODS: Patients referred between 2010 and 2019 to the malignant hyperthermia units in Antwerp, Belgium; Lund, Sweden; Nijmegen, The Netherlands; and Toronto, Ontario, Canada were included. Previously tested patients and relatives of previously tested patients were excluded. Data collection included demographics, referral details, muscle contracture, and genetic testing results including Rare Exome Variant Ensemble Learner scores. Referral indications were categorized into those with a personal/family history of adverse anesthetic event and other indications including exertional and/or recurrent rhabdomyolysis, RYR1 variant(s) detected in diagnostic testing in the neuromuscular clinic without a specific diagnosis (in a family member), diagnosed RYR1-related myopathy (in a family member), idiopathically elevated resting creatine kinase values, exertional heat stroke, and other. RESULTS: A total of 520 medical records were included, with the three most frequent referral indications as follows: personal history of an adverse anesthetic event (211 of 520; 40.6%), family history of an adverse anesthetic event (115 of 520; 22.1%), and exertional and/or recurrent rhabdomyolysis (46 of 520; 8.8%). The proportion of patients referred without a personal/family history of an adverse anesthetic event increased to 43.6% (133 of 305) between 2015 and 2019 compared to 28.4% (61 of 215) in 2010 to 2014 (P < 0.001). Patients with a personal/family history of an adverse anesthetic event were more frequently diagnosed as malignant hyperthermia-susceptible (133 of 220; 60.5%) than those without (47 of 120; 39.2%; P < 0.001). Due to missing data, 180 medical records were excluded. CONCLUSIONS: The proportion of patients referred to malignant hyperthermia units without a personal/family history of an adverse anesthetic event has increased, with 39.2% (47 of 120) diagnosed as malignant hyperthermia-susceptible.

Mapping the current evidence on the anesthetic management of adult patients with neuromuscular disorders-a scoping review.

PURPOSE: Patients with neuromuscular disorders (NMDs) are at increased risk of perioperative complications. The objective of this scoping review was to examine emerging evidence from published studies, case reports, and review articles on anesthetic management of patients with NMDs, following the methodological frame for scoping reviews. SOURCES: We searched PubMed and EMBASE for articles published between 1 January 2000 and 14 July 2021. PRINCIPAL FINDINGS: Three prospective and 21 retrospective studies on altered pharmacokinetics and pharmacodynamics of neuromuscular blocking agents (NMBA) in NMD patients were included. Furthermore, 168 case reports/series reporting 212 anesthetics in 197 patients were included. These studies showed that preanesthetic neuromuscular monitoring can be used for precise NMBA dosing in myasthenia gravis patients. Sugammadex was associated with fewer postoperative myasthenic crises. Perioperative complications were not associated with specific anesthetic agents. Case reports/series showed that in 32% (67/212) of anesthetics, at least one complication was reported. Unexpected intensive care unit admission was a frequently reported complication. Patients with a complicated disease course may have had a higher use of succinylcholine (unadjusted relative risk, 0.13; 95% confidence interval [CI], 0.20 to 0.86) and volatile anesthetics (adjusted odds ratio [OR], 0.38; 95% CI, 0.20 to 0.73; P = 0.004). CONCLUSION: Evidence on the anesthetic management and perioperative complications of patients with NMDs is mainly based on small retrospective studies and case reports. Further clinical trials or large retrospective studies are required to investigate the choice of safe anesthetic agents. Main areas of interest are the potential benefits of neuromuscular monitoring and sugammadex and the risks possibly associated with volatile anesthetics and succinylcholine.

RéSUMé: OBJECTIF: Les patients atteints de maladies neuromusculaires (MNM) courent un risque accru de développer des complications périopératoires. L'objectif de cette étude de portée est de résumer les connaissances émergentes tirées des études, présentations de cas et comptes rendus publiés portant sur l'anesthésie des patients atteints de MNM, tout en suivant le cadre méthodologique d'une étude de portée. CONSTATATIONS PRINCIPALES: ont été incluses trois études prospectives et 21 études rétrospectives comprenant des patients atteints de MNM chez lesquels les myorelaxants ont eu des propriétés pharmacocinétiques et pharmacodynamiques modifiées. En outre, 168 présentations / séries de cas portant sur 212 gestes d'anesthésie chez 197 patients ont été incluses. Ces études ont démontré qu'un suivi neuromusculaire peut être utilisé en pré-anesthésie pour ajuster les doses de myorelaxant chez les patients atteints de myasthénie grave. En postopératoire, un taux plus faible de crises de myasthénie grave a été observé avec le sugammadex. Aucune relation entre les anesthésiques et les complications périopératoires n'a été détectée. Dans les présentations / séries de cas, les patients ayant eu au moins une complication représentaient 67 (32 %) des cas. L'admission non programmée en réanimation est une complication fréquemment rapportée. Les patients dont la maladie s'est dégradée plus rapidement ont possiblement reçu des doses plus fortes de succinylcholine (risque relatif non ajusté 0,13, intervalle de confiance [IC] 95 %, 0,20 à 0,86) et d'agents volatils (rapport de cotes [RC] ajusté, 0,38 (IC 95 %, 0,20 à 0,73), P = 0.004). SOURCES: Les articles sont issus des bases de données PubMed et EMBASE (articles publiés entre le 1er janvier 2000 et le 14 juillet 2021). CONCLUSION: Les données probantes sur la prise en charge anesthésique et les complications périopératoires affectant les patients atteints de MNM sont principalement fondées sur de petites études rétrospectives et des cas cliniques. Des études cliniques ou rétrospectives d'envergure sont nécessaires pour orienter le choix de la technique d'anesthésie optimale. Les principaux domaines d'intérêt sont les bienfaits potentiels du monitorage neuromusculaire et de l'utilisation de sugammadex ainsi que les effets indésirables possibles des anesthésiques volatils et de la succinylcholine.

Neuromuscular symptoms in patients with RYR1-related malignant hyperthermia and rhabdomyolysis.

Malignant hyperthermia and exertional rhabdomyolysis have conventionally been considered episodic phenotypes that occur in otherwise healthy individuals in response to an external trigger. However, recent studies have demonstrated a clinical and histopathological continuum between patients with a history of malignant hyperthermia susceptibility and/or exertional rhabdomyolysis and RYR1-related congenital myopathies. We hypothesize that patients with a history of RYR1-related exertional rhabdomyolysis or malignant hyperthermia susceptibility do have permanent neuromuscular symptoms between malignant hyperthermia or exertional rhabdomyolysis episodes. We performed a prospective cross-sectional observational clinical study of neuromuscular features in patients with a history of RYR1-related exertional rhabdomyolysis and/or malignant hyperthermia susceptibility (n = 40) compared with healthy controls (n = 80). Patients with an RYR1-related congenital myopathy, manifesting as muscle weakness preceding other symptoms as well as other (neuromuscular) diseases resulting in muscle weakness were excluded. Study procedures included a standardized history of neuromuscular symptoms, a review of all relevant ancillary diagnostic tests performed up to the point of inclusion and a comprehensive, standardized neuromuscular assessment. Results of the standardized neuromuscular history were compared with healthy controls. Results of the neuromuscular assessment were compared with validated reference values. The proportion of patients suffering from cramps (P < 0.001), myalgia (P < 0.001) and exertional myalgia (P < 0.001) was higher compared with healthy controls. Healthcare professionals were consulted because of apparent neuromuscular symptoms by 17/40 (42.5%) patients and 7/80 (8.8%) healthy controls (P < 0.001). Apart from elevated creatine kinase levels in 19/40 (47.5%) patients and mild abnormalities on muscle biopsies identified in 13/16 (81.3%), ancillary investigations were normal in most patients. The Medical Research Council sum score, spirometry and results of functional measurements were also mostly normal. Three of 40 patients (7.5%) suffered from late-onset muscle weakness, most prominent in the proximal lower extremity muscles. Patients with RYR1 variants resulting in malignant hyperthermia susceptibility and/or exertional rhabdomyolysis frequently report additional neuromuscular symptoms such as myalgia and muscle cramps compared with healthy controls. These symptoms result in frequent consultation of healthcare professionals and sometimes in unnecessary invasive diagnostic procedures. Most patients do have normal strength at a younger age but may develop muscle weakness later in life.

Malignant Hyperthermia During Cardiac Surgery Successfully Treated by Deep Hypothermia Using Cardiopulmonary Bypass: A Case Report.

Malignant hyperthermia (MH) is a life-threatening hypermetabolic disorder triggered by volatile anesthetics and/or succinylcholine. We report a case of a 58-year-old patient with a type-A aortic dissection. After induction of general anesthesia, a hypermetabolic reaction was successfully treated by deep hypothermia using cardiopulmonary bypass. Dantrolene became available in theater after the hypermetabolism was already treated successfully by hypothermia. Because of a low suspicion of MH, dantrolene was not administered when it became available. The patient fully recovered, and MH susceptibility was confirmed. Cardiopulmonary bypass should be considered to treat MH in case dantrolene and conservative therapy are unavailable or insufficient.

Anaesthesia and neuromuscular disorders: what a neurologist needs to know.

Neurologists are often asked for specific advice regarding patients with neuromuscular disease who require general anaesthesia. However, guidelines on specific neuromuscular disorders do not usually include specific guidelines or pragmatic advice regarding (regional and/or general) anaesthesia or procedural sedation. Furthermore, the medical literature on this subject is mostly limited to publications in anaesthesiology journals. We therefore summarise general recommendations and specific advice for anaesthesia in different neuromuscular disorders to provide a comprehensive and accessible overview of the knowledge on this topic essential for clinical neurologists. A preoperative multidisciplinary approach involving anaesthesiologists, cardiologists, chest physicians, surgeons and neurologists is crucial. Depolarising muscle relaxants (succinylcholine) should be avoided at all times. The dose of non-depolarising muscle relaxants must be reduced and their effect monitored. Patients with specific mutations in RYR1 (ryanodine receptor 1) and less frequently in CACNA1S (calcium channel, voltage-dependent, L type, alpha 1S subunit) and STAC3 (SH3 and cysteine rich domain 3) are at risk of developing a life-threatening malignant hyperthermia reaction.

[Exertional heat stroke in athletes and soldiers]. / Inspanningsgebonden hitteberoerte bij sporters en militairen.

Exertional heat stroke (EHS) is a medical emergency characterized by life-threatening hyperthermia and central nerve system dysfunction during or directly after exercise. Early recognition and aggressive cooling reduces morbidity and mortality of patients with EHS. Therefore, all health care professionals involved in acute care should immediately recognise EHS and start cooling with cold water immersion as soon as possible. Most EHS occur in young and healthy individuals without a medical history, such as athletes or soldiers. We report the case of EHS in a 26-year-old man without a medical history. He suffered from EHS during a military admission test. A few years later he had a second EHS during military training. This time, the EHS was complicated by compartment syndrome, rhabdomyolysis, acute kidney injury and epilepsy. He fully recovered from both EHS episodes. Muscle histology, whole exome sequencing and heat tolerance tests did not show any abnormalities.

The effect of low- versus normal-pressure pneumoperitoneum during laparoscopic colorectal surgery on the early quality of recovery with perioperative care according to the enhanced recovery principles (RECOVER): study protocol for a randomized controlled study.

BACKGROUND: There is increasing evidence for the use of lower insufflation pressures during laparoscopic surgery. Deep neuromuscular blockade allows for a safe reduction in intra-abdominal pressure without compromising the quality of the surgical field. While there is considerable evidence to support superior surgical conditions during deep neuromuscular blockade, there is only a limited amount of studies investigating patient outcomes. Moreover, results are not always consistent between studies and vary between different types of laparoscopic surgery. This study will investigate the effect of low-pressure pneumoperitoneum facilitated by deep NMB on quality of recovery after laparoscopic colorectal surgery. METHODS: The RECOVER study is a multicenter double-blinded randomized controlled trial consisting of 204 patients who will be randomized in a 1:1 fashion to group A, low-pressure pneumoperitoneum (8 mmHg) facilitated by deep neuromuscular blockade (post tetanic count of 1-2), or group B, normal-pressure pneumoperitoneum (12 mmHg) with moderate neuromuscular blockade (train-of-four response of 1-2). The primary outcome is quality of recovery on postoperative day 1, quantified by the Quality of Recovery-40 questionnaire. DISCUSSION: Few studies have investigated the effect of lower insufflation pressures facilitated by deep neuromuscular blockade on patient outcomes after laparoscopic colorectal procedures. This study will identify whether low pressure pneumoperitoneum and deep neuromuscular blockade will enhance recovery after colorectal laparoscopic surgery and, moreover, if this could be a valuable addition to the Enhanced Recovery After Surgery guidelines. TRIAL REGISTRATION: EudraCT 2018-001485-42. Registered on April 9, 2018. Clinicaltrials.govNCT03608436. Registered on July 30, 2018.

[Overactive muscles: it can be more serious than common myalgia or cramp]. / Overactieve spieren: soms meer dan gewone spierpijn of kramp.

Positive muscle phenomena are due to muscle overactivity. Examples are cramp, myalgia, and stiffness. These manifestations have mostly acquired causes, e.g. side-effects of medication, metabolic disorders, vitamin deficiency, excessive caffeine intake or neurogenic disorders. We report on three patients with various positive muscle phenomena, to illustrate the clinical signs that indicate an underlying myopathy. Patient A, a 56-year-old man, was diagnosed with muscle cramp in the context of excessive coffee use and previous lumbosacral radiculopathy. Patient B, a 71-year-old man, was shown to have RYR1-related myopathy. Patient C, a 42-year-old man, suffered from Brody myopathy. We propose for clinicians to look out for a number of 'red flags' that can point to an underlying myopathy, and call for referral to neurology if indicated. Red flags include second wind phenomenon, familial occurrence of similar complaints, marked muscle stiffness, myotonia, muscle weakness, muscle hypertrophy, and myoglobinuria. Establishing a correct diagnosis is important for proper treatment. Certain myopathies call for cardiac or respiratory screening.

[Ultrasound-guided anterior approach to sciatic nerve block]. / Blokkade van de N. ischiadicus via echogeleide anterieure benadering.

Ultrasound guidance has made it possible to carry out an anterior approach to sciatic nerve block. This technique can be performed as fast and as successfully as the posterior or subgluteal approach. A major advantage of this technique is that the patient can remain comfortable in a neutral supine position.

Prolonged neuromuscular blockade following succinylcholine administration to a patient with a reduced butyrylcholinesterase activity.

This case is about a 48-year-old woman known with a reduced butyrylcholinesterase activity, who developed prolonged neuromuscular blockade following the unintentional administration of succinylcholine. We took the opportunity to monitor the development of neuromuscular function during this period and blood samples were taken for molecular genetic analysis and for quantitative and qualitative analysis since not all causative mutations are functionally characterized. Reduced butyrylcholinesterase activity is discussed in many aspects. Clinical considerations are suggested concerning genetic counselling.