What are the anesthetic implications of Duchenne Muscular Dystrophy?

1.

Segura LG, Lorenz JD, Weingarten TN, et al. Paediatric Anaesthesia. 2013;23(9):855-64. doi:10.1111/pan.12248.

Publish date: September 0, 2013.

BACKGROUND: Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are associated with life-threatening perioperative complications, including rhabdomyolysis, hyperkalemia, and hyperthermia. Current recommendations contraindicate use of succinylcholine and volatile anesthetics; however, the latter recommendation remains controversial. OBJECTIVE: To review the perioperative outcomes of patients with DMD and BMD. METHODS: We reviewed records of patients with DMD or BMD who underwent anesthetic management at our institution from January 1990 through December 2011. RESULTS: We identified 47 patients (DMD, 37; BMD, 10) who underwent 117 anesthetic exposures (DMD, 101; BMD, 16). Volatile anesthetic agents were used 66 times (DMD, 59; BMD, 7). One patient with undiagnosed BMD received succinylcholine and developed acute rhabdomyolysis and hyperkalemic cardiac arrest. All other major complications were attributed to the procedure (i.e., large bleeding), to preexisting comorbidities (i.e., respiratory failure, cardiac disease), or to both. CONCLUSIONS: Use of succinylcholine in children with dystrophinopathy is contraindicated. These patients have significant comorbidities and are frequently undergoing extensive operations; complications related to these factors can develop, as evidenced by our series. These complications may occur with use of volatile and nonvolatile anesthetics. However, because most of our patients were older than 8 years at the time of surgery, our observation cannot be generalized to younger dystrophin-deficient children.

2.

Elsevier ClinicalKey Drug Monograph

Content last updated: May 3, 2024.

Contraindications And Precautions Use of inhaled anesthetic agents has been associated with rare increases in serum potassium concentrations that have resulted in cardiac arrhythmias and death in pediatric patients during the postoperative period. Patients with latent as well as overt neuromuscular disease, particularly Duchenne muscular dystrophy, appear to be most vulnerable. Concomitant use of succinylcholine has been associated with most, but not all, of these cases.

Adverse Reactions Use of inhaled anesthetic agents, such as isoflurane, has been associated with rare cases of hyperkalemia that have resulted in cardiac arrhythmias and death in pediatric patients during the postoperative period. Patients with latent as well as overt neuromuscular disease, particularly Duchenne muscular dystrophy, appear to be most vulnerable. Concomitant use of succinylcholine has been associated with most, but not all, of these cases. These patients also experienced significant elevations in serum creatine kinase concentrations and changes in urine consistent with myoglobinuria in some cases. Despite the similarity in presentation to malignant hyperthermia, none of these patients exhibited signs or symptoms of muscle rigidity or hypermetabolic state. Early and aggressive intervention to treat the hyperkalemia and resistant arrhythmias is recommended. Subsequent evaluation for latent neuromuscular disease is also recommended.

Warnings WARNINGS Perioperative Hyperkalemia Use of inhaled anesthetic agents has been associated with rare increases in serum potassium levels that have resulted in cardiac arrhythmias and death in pediatric patients during the postoperative period. Patients with latent as well as overt neuromuscular disease, particularly Duchenne muscular dystrophy, appear to be most vulnerable. Concomitant use of succinylcholine has been associated with most, but not all, of these cases. These patients also experienced significant elevations in serum creatinine kinase levels and, in some cases, changes in urine consistent with myoglobinuria. Despite the similarity in presentation to malignant hyperthermia, none of these patients exhibited signs or symptoms of muscle rigidity or hypermetabolic state. Early and aggressive intervention to treat the hyperkalemia and resistant arrhythmias is recommended, as is subsequent evaluation for latent neuromuscular disease. Malignant Hyperthermia In susceptible individuals, isoflurane anesthesia may trigger a skeletal muscle hypermetabolic state leading to high oxygen demand and the clinical syndrome known as malignant hyperthermia. The syndrome includes nonspecific features such as muscle rigidity, tachycardia, tachypnea, cyanosis, arrhythmias and unstable blood pressure. (It should also be noted that many of these nonspecific signs may appear with light anesthesia, acute hypoxia, etc.) An increase in overall metabolism may be reflected in an elevated temperature (which may rise rapidly early or late in the case, but usually is not the first sign of augmented metabolism) and an increased usage of the CO 2 absorption system (hot cannister). PaO 2 and pH may decrease, and hyperkalemia and a base deficit may appear.

3.

Elsevier ClinicalKey Drug Monograph

Content last updated: May 3, 2024.

Contraindications And Precautions Inhaled anesthetics, such as desflurane, have been associated with rare cases of hyperkalemia. These increases in serum potassium concentrations have resulted in cardiac arrhythmias and death in pediatric patients during the post-operative period. These patients also experienced significant increases in serum creatinine kinase and myoglobinuria. Patients appearing to be most vulnerable include those with latent or overt neuromuscular disease, such as Duchenne muscular dystrophy. In many, but not all cases, succinylcholine was administered concurrently. Aggressive treatment of hyperkalemia and resistant arrhythmias is recommended.

Warnings And Cautions Patients with latent as well as overt neuromuscular disease, particularly Duchenne muscular dystrophy, appear to be most vulnerable. Concomitant use of succinylcholine has been associated with most, but not all, of these cases. These patients also experienced significant elevations in serum creatinine kinase levels and, in some cases, changes in urine consistent with myoglobinuria. Despite the similarity in presentation to malignant hyperthermia, none of these patients exhibited signs or symptoms of muscle rigidity or hypermetabolic state. Early and aggressive intervention to treat the hyperkalemia and resistant arrhythmias is recommended, as is subsequent evaluation for latent neuromuscular disease. 5.3 Respiratory Adverse Reactions in Pediatric Patients Desflurane is not approved for maintenance of anesthesia in non-intubated children due to an increased incidence of respiratory adverse reactions, including coughing, laryngospasm and secretions [See Clinical Studies (14.5) ] . Children, particularly if 6 years old or younger, who are under an anesthetic maintenance of desflurane delivered via laryngeal mask airway (LMA™ mask) are at increased risk for adverse respiratory reactions, e.g., coughing and laryngospasm, especially with removal of the laryngeal mask airway under deep anesthesia [See Clinical Studies (14.5) ] . Therefore, closely monitor these patients for signs and symptoms associated with laryngospasm and treat accordingly. When desflurane is used for maintenance of anesthesia in children with asthma or a history of recent upper airway infection, there is an increased risk for airway narrowing and increases in airway resistance. Therefore, closely monitor these patients for signs and symptoms associated with airway narrowing and treat accordingly . 5.4 QTc Prolongation QTc prolongation, associated with torsade de pointes, has been reported [See Adverse Reactions ( 6.2 )]. Carefully monitor cardiac rhythm when administering desflurane to susceptible patients (e.g., patients with congenital Long QT Syndrome or patients taking drugs that can prolong the QT interval).

4.

Elsevier ClinicalKey Drug Monograph

Content last updated: May 3, 2024.

Adverse Reactions Use of inhaled anesthetic agents such as sevoflurane has been associated with rare cases of hyperkalemia that have resulted in cardiac arrhythmias and death in pediatric patients during the postoperative period. Patients with latent as well as overt neuromuscular disease, particularly Duchenne muscular dystrophy, appear to be most vulnerable. Concomitant use of succinylcholine has been associated with most, but not all, of these cases. These patients also experienced significant elevations in serum creatine kinase concentrations and changes in urine consistent with myoglobinuria in some cases. Despite the similarity in presentation to malignant hyperthermia, none of these patients exhibited signs or symptoms of muscle rigidity or hypermetabolic state. Early and aggressive intervention to treat the hyperkalemia and resistant arrhythmias is recommended. Subsequent evaluation for latent neuromuscular disease is also recommended.

5.

Food and Drug Administration (DailyMed).

Publish date: February 4, 2023.

Warnings And Cautions Patients with latent as well as overt neuromuscular disease, particularly Duchenne muscular dystrophy, appear to be most vulnerable. Concomitant use of succinylcholine has been associated with most, but not all, of these cases. These patients also experienced significant elevations in serum creatinine kinase levels and, in some cases, changes in urine consistent with myoglobinuria. Despite the similarity in presentation to malignant hyperthermia, none of these patients exhibited signs or symptoms of muscle rigidity or hypermetabolic state. Early and aggressive intervention to treat the hyperkalemia and resistant arrhythmias is recommended, as is subsequent evaluation for latent neuromuscular disease. 5.3 Respiratory Adverse Reactions in Pediatric Patients Suprane (desflurane) is not approved for maintenance of anesthesia in non-intubated children due to an increased incidence of respiratory adverse reactions, including coughing, laryngospasm and secretions [ See Clinical Studies (14.5) ]. Children, particularly if 6 years old or younger, who are under an anesthetic maintenance of Suprane (desflurane) delivered via laryngeal mask airway (LMA™ mask) are at increased risk for adverse respiratory reactions, e.g., coughing and laryngospasm, especially with removal of the laryngeal mask airway under deep anesthesia [ See Clinical Studies (14.5) ]. Therefore, closely monitor these patients for signs and symptoms associated with laryngospasm and treat accordingly. When Suprane (desflurane) is used for maintenance of anesthesia in children with asthma or a history of recent upper airway infection, there is an increased risk for airway narrowing and increases in airway resistance. Therefore, closely monitor these patients for signs and symptoms associated with airway narrowing and treat accordingly. 5.4 QT Prolongation QT prolongation, associated with torsade de pointes, has been reported [see Adverse Reactions (6.2)]. Carefully monitor cardiac rhythm when administering Suprane (desflurane) to susceptible patients (e.g., patients with congenital Long QT Syndrome or patients taking drugs that can prolong the QT interval).

6.

Elsevier ClinicalKey Derived Clinical Overview

Formal evaluation by anesthetist is recommended before any operation with general anesthesia in patients with dystrophinopathy.

7.

Auerbach, Andrew D. (2024). In Goldman-Cecil Medicine (pp. 2659). DOI: 10.1016/B978-0-323-93038-3.00399-3

Neuromuscular diseases (Chapters 386to390) have diverse underlying pathophysiologies but present with similar symptoms in terms of muscularweakness or limited respiratory reserve. Some neuromuscular diseases involve other organs involvement (e.g., cardiac involvement Duchenne muscular dystrophy) that require specific monitoring. The complexity of these illnesses and the relationships among choices of anesthetics, the surgical approach, and the patient’s baseline level of function require careful preoperative planning linked to postoperative monitoring, particularly for respiratory status.