A retrospective cohort study of children with spinal muscular atrophy type 2 receiving anesthesia for intrathecal administration of nusinersen

Abstract

Summary Introduction Spinal muscular atrophy is characterized by loss of motor neurons in the anterior horn of the spinal cord with resultant proximal muscle weakness. Intrathecal nusinersen has revolutionized the treatment of spinal muscular atrophy. We reviewed the perioperative care of 61 anesthetics performed on eight patients with spinal muscular atrophy type 2 who received nusinersen over 30 months in conjunction with nusinersen's phase 3 clinical trials. Methods Anesthesia was induced in all patients with sevoflurane, nitrous oxide, and oxygen (30%) via facemask. A peripheral intravenous line was placed after the loss of consciousness in all but three procedures. General anesthesia was maintained in 58 anesthetics with a propofol infusion at 250‐300 μg/kg/min, while the remainder was maintained with inhalational anesthetics. The airway was managed via facemask or nasal cannula in all but two procedures, in whom a laryngeal mask airway was placed. We analyzed patient demographics, duration of anesthesia and of postanesthesia care unit stay, discharge destination, preprocedure oxygen saturation (SaO2), postanesthesia care unit discharge oxygen saturation, and occurrence of unanticipated admission or postdischarge hospitalization. Results Eight American Society of Anesthesiologists physical status three patients (3 male: 5 female) with a median age of 4.1 (2.1‐7.8) years and median weight of 13.2 (10‐24.7) kg, underwent 61 anesthetics for nusinersen administration or sham procedure. There were no intraoperative anesthetic complications of unanticipated cardiovascular instability, major neurologic events, respiratory failure, or death. Anesthesiologists performed 83% of the procedures. Conclusion Nusinersen has revolutionized the care of patients with spinal muscular atrophy type 2 and anesthesiologists will be involved in its administration. We found that routine anesthetic care was safe and effective.

Anesthetic management of pediatric patients with Niemann‐Pick disease type C for intrathecal 2‐hydroxypropyl‐β‐cyclodextrin injection

“…The retrospective cohort study of anesthetic outcomes for eight pediatric American Society of Anesthesiologists three physical status patients receiving serial intrathecal injections of nusinersen (Spinraza™) for Spinal Muscular Atrophy demonstrated no adverse cardiovascular anesthesia‐related events for 61 unique anesthetic encounters and only 16% of encounters demonstrated a respiratory complication defined as desaturation of SpO 2 to <90%. This patient population was safely anesthetized utilizing inhalational induction and postinduction peripheral IV placement with majority having total intravenous general anesthesia and supplemental oxygen provided by nasal cannula or mask in all but two encounters in which a supraglottic airway was placed 8 . Although the pathophysiology and genetic origins of Spinal Muscular Atrophy are unrelated to the Niemann‐Pick population, the required serial administration of nusinersen is similar to although less frequent than that of intrathecal 2‐hydroxypropyl‐beta‐cyclodextrin administration.…”

Long-term follow-up of patients with type 2 and non-ambulant type 3 spinal muscular atrophy (SMA) treated with olesoxime in the OLEOS trial

“…Although generally well tolerated, the procedure itself is not without side-effects, which occur more frequently in older patients [16] . The procedure may need to be conducted under general anesthesia in younger children who cannot lie still throughout the procedure, and although generally safe [17] , it is not yet fully understood how cumulative exposure to anesthesia affects the developing brain [18 , 19] . ITC procedures may also be challenging in patients with a complex spine and severe scoliosis [20] .…”

Anesthetic management of pediatric patients undergoing intrathecal nusinersen administration for treatment of spinal muscular atrophy: A single‐center experience

“…SMA type I (Werdnig‐Hoffman disease) has an onset before the age of 6 months and is the most common form of the disease. Patients exhibit severe muscle weakness, delayed attainment of motor milestones, swallowing difficulties, and respiratory dysfunction often leading to tracheostomy and ventilator dependence 1,2 . While often fatal before age 2 years, aggressive ventilator support can allow these patients to survive into adolescence.…”

“…While often fatal before age 2 years, aggressive ventilator support can allow these patients to survive into adolescence. SMA type II symptoms usually present between the ages of 6 months to 2 years 1,2 . After previously normal development, milestones become delayed.…”

“…In our case series, anesthetic management varied from monitored care with no drugs, sedation with spontaneous ventilation, or general anesthesia for children undergoing this procedure. In the analysis from Bielsky et al, general anesthesia was shown to be safe and effective for SMA II patients undergoing Nusinersen injections during the Nusinersen phase three clinical trials 1 . Their analysis included no SMA I patients.…”