Martina Richtsfeld

Succinylcholine -induced hyperkalemia in acquired pathologic states : Etiologic factors and molecular mechanisms

Lethal hyperkalemic response to succinylcholine continues to be reported, but the molecular mechanisms for the hyperkalemia have not been completely elucidated. In the normal innervated mature muscle, the acetylcholine receptors (AChRs) are located only in the junctional area. In certain pathologic states, including upper or lower motor denervation, chemical denervation by muscle relaxants, drugs, or toxins, immobilization, infection, direct muscle trauma, muscle tumor, or muscle inflammation, and/or burn injury, there is up-regulation (increase) of AChRs spreading throughout the muscle membrane, with the additional expression of two new isoforms of AChRs. The depolarization of these AChRs that are spread throughout the muscle membrane by succinylcholine and its metabolites leads to potassium efflux from the muscle, leading to hyperkalemia. The nicotinic (neuronal) α7 acetylcholine receptors, recently described to be expressed in muscle also, can be depolarized not only by acetylcholine and succinylcholine but also by choline, persistently, and possibly play a critical role in the hyperkalemic response to succinylcholine in patients with up-regulated AChRs.

Long-term Effects of Botulinum Toxin on Neuromuscular Function

Background:Recent reports indicate increased incidence of Clostridium botulinum infections, particularly among drug abusers and tissue allograft recipients. Botulinum toxin also has potential application in biochemical warfare. The neurotoxin-induced paralysis often requires mechanical ventilation with and without muscle relaxants. The authors investigated the long-term effects of botulinum toxin on muscle function, expression of nicotinic acetylcholine receptors (nAChRs), and their interaction with muscle relaxant, atracurium. Methods:Rats (n = 30) were injected with varying doses (0.625, 2.5, and 10 U) of botulinum toxin into the tibialis muscle. Control animals (n = 9) received an equivalent volume of saline. At 128 days after injection, neuromuscular function, pharmacodynamics of atracurium, and nAChRs were evaluated. Results:Nerve-evoked tensions, including tetanic tension and muscle mass, were decreased on the toxin-injected side in a dose-dependent manner relative to saline-injected controls as well as the contralateral side. Specific muscle tension and specific tetanic muscle tension (tensions/muscle mass) were not reduced. The ED10 of atracurium was reduced, the ED50 was unchanged, and the ED90 was increased in the highest (10-U) dose of toxin group. The atracurium plasma concentration to maintain a steady state 50% paralysis was significantly reduced in the 10-U toxin group. The nAChR concentrations in the tibialis muscle were significantly increased in a dose-dependent manner in all experimental groups. Conclusion:Botulinum toxin causes dose-dependent long-term neuromuscular changes. The loss of tension generating capacity is almost exclusively related to muscle atrophy, because the specific tension did not change. The decreased ED10, unaltered ED50, and increased ED90 to atracurium suggest its interactions with different isoforms of receptors having varying sensitivity to atracurium. The absence of fade, despite the persistent botulinum toxin-induced denervation (increased nAChRs), suggests that the up-regulated nAChRs may have compensated for the prejunctional effects of botulinum toxin.

Transgenic Alzheimer mice have a larger minimum alveolar anesthetic concentration of isoflurane than their nontransgenic littermates.

BACKGROUND: More than 12% of all people older than 65 yr have Alzheimers disease. Because nothing is known about changes in demand of volatile anesthetics in this disease, we determined minimum alveolar anesthetic concentration (MAC) values of isoflurane in young and aged transgenic mice at risk of developing Alzheimers disease (heterozygote APP23 mice with the “Swedish double mutation”). To differentiate between unspecific effects of the transgenic model and specific Alzheimer effects, we additionally evaluated MAC values in mice with the same genetic construct but without the Alzheimers disease-causing Swedish double mutation (heterozygote APP51/16 mice). METHODS: MAC was determined in 60 mice (10 per group): heterozygote APP23 mice and their wild type littermates at the age of 4 and 18 mo, respectively, and heterozygote APP51/16 mice and their wild type littermates at the age of 18 mo. Anesthesia was induced with isoflurane in oxygen/air. The concentration of inhaled isoflurane varied between 1.0 and 2.0 Vol%, and the motor reaction to toeclamping was recorded. Means of the MAC values were compared with an unpaired t-test. RESULTS: The MAC of 18-mo-old heterozygote APP23 mice was 1.67 ± 0.09, i.e., 9% larger than the MAC of their wild type littermates (1.53 ± 0.14; P = 0.020). Heterozygote APP51/16 mice had a lower MAC than their wild type littermates (1.32 ± 0.14 vs 1.48 ± 0.13; P = 0.037). All wild type groups and young heterozygote APP23 mice had comparable MAC values. CONCLUSIONS: The increased MAC value in aged heterozygote APP23 mice seems to be attributable to changes related to Alzheimers disease.

The efficacy of GlideScope ® videolaryngoscopy compared with direct laryngoscopy in children who are difficult to intubate: An analysis from the paediatric difficult intubation registry

Background We analysed data from the Paediatric Difficult Intubation Registry examining the use of direct laryngoscopy and GlideScope® videolaryngoscopy. Methods Data collected by a multicentre, paediatric difficult intubation registry from 1295 patients were analysed. Rates of success and complications between direct laryngoscopy and GlideScope videolaryngoscopy were analysed. Results Initial (464/877 = 53% vs 33/828 = 4%, Z-test = 22.2, P < 0.001) and eventual (720/877 = 82% vs. 174/828 = 21%, Z-test = 25.2, P < 0.001) success rates for GlideScope were significantly higher than direct laryngoscopy. Children weighing <10 kg had lower success rates with the GlideScope than the group as a whole. There were no differences in complication rates per attempt between direct laryngoscopy and GlideScope. The direct laryngoscopy group had more complications associated with the greater number of attempts needed to intubate. There were no increased risks of hypoxia or trauma with GlideScope use. Each additional attempt at intubation with either device resulted in a two-fold increase in complications (odds ratio: 2.0, 95% confidence interval: 1.5-2.5, P < 0.001). Conclusions During difficult tracheal intubation in children, direct laryngoscopy is an overly used technique with a low chance of success. GlideScope use was associated with a higher chance of success with no increased risk of complications. GlideScope use in children with difficult tracheal intubation has a lower success rate than in adults with difficult tracheal intubation. Children weighing less than 10 kilograms had lower success rates with either device. Attempts should be minimized with either device to decrease complications.

Prolonged administration of pyridostigmine impairs neuromuscular function with and without down-regulation of acetylcholine receptors

Background:The acetylcholinesterase inhibitor, pyridostigmine, is prophylactically administered to mitigate the toxic effects of nerve gas poisoning. The authors tested the hypothesis that prolonged pyridostigmine administration can lead to neuromuscular dysfunction and even down-regulation of acetylcholine receptors. Methods:Pyridostigmine (5 or 25 mg·kg−1·day−1) or saline was continuously administered via osmotic pumps to rats, and infused for either 14 or 28 days until the day of neuromuscular assessment (at day 14 or 28), or discontinued 24 h before neuromuscular assessment. Neurotransmission and muscle function were examined by single-twitch, train-of-four stimulation and 100-Hz tetanic stimulation. Sensitivity to atracurium and acetylcholine receptor number (quantitated by 125I-&agr;-bungarotoxin) provided additional measures of neuromuscular integrity. Results:Specific tetanic tensions (Newton [N]/muscle weight [g]) were significantly (P < 0.05) decreased at 14 (10.3 N/g) and 28 (11.1 N/g) days of 25 mg·kg−1·day−1 pyridostigmine compared with controls (13.1–13.6 N/g). Decreased effective dose (0.81–1.05 vs. 0.16–0.45 mg/kg; P < 0.05) and decreased plasma concentration (3.02–3.27 vs. 0.45–1.37 &mgr;g/ml; P < 0.05) of atracurium for 50% paralysis (controls vs. 25 mg·kg−1·day−1 pyridostigmine, respectively), irrespective of discontinuation of pyridostigmine, confirmed the pyridostigmine-induced altered neurotransmission. Pyridostigmine (25 mg·kg−1·day−1) down-regulated acetylcholine receptors at 28 days. Conclusions:Prolonged administration of pyridostigmine (25 mg·kg−1·day−1) leads to neuromuscular impairment, which can persist even when pyridostigmine is discontinued 24 h before assessment of neuromuscular function. Pyridostigmine has the potential to down-regulate acetylcholine receptors, but induces neuromuscular dysfunction even in the absence of receptor changes.

Mechanical hemolysis in pediatric patients associated with rapid transfusion and one-way valve: MECHANICAL HEMOLYSIS WITH ONE-WAY VALVE

Four similar transfusion reactions involving infants were reported in less than 1 year. After transfusion of red blood cells (RBCs) via syringe in the operating room, each patient experienced discolored urine, laboratory evidence of hemolysis, and acute kidney injury. Clerical and serologic investigations were unremarkable. Mechanical hemolysis was considered.

Management and Anesthetic Considerations for Patients With Anomalous Aortic Origin of a Coronary Artery

The term “coronary artery anomalies” encompasses a large and heterogeneous group of disorders that may affect origin, intrinsic anatomy, course, location, and termination of the coronary arteries. With these different anatomies, presentation, symptoms, and outcomes are heterogeneous as well. While significant efforts are directed toward improving diagnosis and risk-stratification, best evidence-guided practices remain in evolution. Data about anesthetic management of patients with coronary anomalies are lacking as well. This review aims to provide the anesthesiologist with a better understanding of an important subgroup of coronary artery anomalies: anomalous aortic origin of a coronary artery. We will discuss classification, pathophysiology, incidence, evaluation, management, and anesthetic implications of this potentially fatal disease group.

Anesthesiology and the difficult airway - Where do we currently stand?

© 2017 Annals of Cardiac Anaesthesia | Published by Wolters Kluwer Medknow Anesthesiology has made a significant advance in airway care since the introduction of the facemask and then followed by endotracheal tubes for assisted ventilation.[1] The need for assisted ventilation for the advancement of anesthesia care has resulted in significant improvements in health care for patients needing surgical, diagnostic, and intensive care. Practitioners involved in the care of patients requiring sedation and general anesthesia have recognized that jaw‐lift, proper neck positioning, use of continuous positive airway pressure, recognizing the difficult upper airway before sedation, and meeting as a group of experts to establish the difficult airway algorithm have led to significant progress in successfully establishing an airway and decreasing airway‐related morbidity.[2,3] For decades, the facemask, an oral airway, curved and straight‐bladed laryngoscopes for performing endotracheal intubation, along with proper training for their use, were the mainstay of upper airway care. This then led to the introduction of the gum‐elastic bougie for accessing minimally visible laryngeal inlets even after applying significant externally applied downward and upward laryngeal pressure. The bougie is then serving as a guide for advancing the endotracheal tube. Until the availability of bedside capnography became available for confirming successful endotracheal intubation, practitioners relied on clinical signs that included observing chest expansion, auscultating for bilateral breath sounds, and the use of an esophageal detector device.[4] Currently, bedside capnography is a requirement for documenting successful endotracheal intubation. Dr. Archie Brain from the United Kingdom realized that facemask ventilation requires significant expertise and skill to prevent stomach distension and often required not only jaw‐lift but also an oral airway for effective lung ventilation. After several prototypes, he successfully introduced the laryngeal mask airway (LMA).[5] This was a significant contribution of the 20th century to upper airway care. Along with the use of fiberscope devices, practitioners became increasingly comfortable in providing care for patients with a difficult upper airway.