piperidines and Muscle-Weakness

Aspiration is a significant cause of anesthetic morbidity, occurring most commonly during the induction of anesthesia. For patients with a high likelihood of aspiration, rapid sequence intubation (RSI) techniques may minimize this risk by reducing the time between the loss of protective airway reflexes and the placement of a cuffed endotracheal tube. Although RSI frequently involves the administration of a neuromuscular-blocking agent (NMBA) such as succinylcholine or rocuronium, there are times when the administration of an NMBA is contraindicated or undesirable. We present an 11-year-old boy who presented with vomiting, papilledema, and a history concerning for an undiagnosed neuromuscular disorder. Deep sedation or anesthesia was required during an emergent lumbar puncture to evaluate his symptoms. Rapid sequence intubation was successfully performed with propofol and remifentanil without the use of an NMBA. We highlight the anesthetic considerations in such a clinical scenario and review the literature regarding the combination of remifentanil and propofol for RSI.

Topics: Anesthesia, Inhalation; Child; Contraindications; Deep Sedation; Emergencies; Headache; Humans; Hypnotics and Sedatives; Intracranial Hypertension; Intubation, Intratracheal; Laryngoscopy; Male; Methyl Ethers; Muscle Weakness; Neuromuscular Depolarizing Agents; Neuromuscular Diseases; Piperidines; Propofol; Remifentanil; Respiratory Aspiration of Gastric Contents; Risk; Sevoflurane; Spinal Puncture; Succinylcholine; Vision Disorders; Vomiting

Amyotrophic lateral sclerosis (ALS) is a lethal and incurable neurodegenerative disease due to the loss of upper and lower motor neurons, which leads to muscle weakness, atrophy, and paralysis. Sigma-1 receptor (σ-1R) is a ligand-operated protein that exhibits pro-survival and anti-apoptotic properties. In addition, mutations in its codifying gene are linked to development of juvenile ALS pointing to an important role in ALS. Here, we investigated the disease-modifying effects of pridopidine, a σ-1R agonist, using a delayed onset SOD1 G93A mouse model of ALS. Mice were administered a continuous release of pridopidine (3.0 mg/kg/day) for 4 weeks starting before the appearance of any sign of muscle weakness. Mice were monitored weekly and several behavioural tests were used to evaluate muscle strength, motor coordination and gait patterns. Pridopidine-treated SOD1 G93A mice showed genotype-specific effects with the prevention of cachexia. In addition, these effects exhibited significant improvement of motor behaviour 5 weeks after treatment ended. However, the survival of the animals was not extended. In summary, these results show that pridopidine can modify the disease phenotype of ALS-associated cachexia and motor deficits in a SOD1 G93A mouse model.

Topics: Amyotrophic Lateral Sclerosis; Animals; Cachexia; Disease Models, Animal; Mice; Mice, Transgenic; Muscle Weakness; Neurodegenerative Diseases; Phenotype; Piperidines; Superoxide Dismutase; Superoxide Dismutase-1

Topics: Antirheumatic Agents; Biopsy; Disease Progression; Drug Resistance, Multiple; Electromyography; Female; Humans; Janus Kinase Inhibitors; Medication Therapy Management; Middle Aged; Monitoring, Immunologic; Muscle Strength; Muscle Weakness; Piperidines; Polymyositis; Pyrimidines; Pyrroles; Treatment Outcome

Topics: Abdominal Pain; Aged; Anesthesia; Anesthetics, Inhalation; Anesthetics, Intravenous; Aortic Aneurysm, Abdominal; Atracurium; Desflurane; Fentanyl; Follow-Up Studies; Gait Disorders, Neurologic; Guillain-Barre Syndrome; Humans; Incidental Findings; Isoflurane; Male; Monitoring, Intraoperative; Muscle Weakness; Neuromuscular Nondepolarizing Agents; Piperidines; Propofol; Radiography, Abdominal; Remifentanil; Tomography, X-Ray Computed; Treatment Outcome