Scoliosis Research Society Response to FDA Med Watch
December 14, 2016
The United States Food and Drug Administration has released a warning that “repeated or lengthy use of general anesthesia and sedation drugs during surgeries or procedures in children younger than 3 years... may affect the development of children’s brains” (1). Warnings will be added to the labels of anesthetic drugs (inhaled anesthetics, ketamine, propofol, midazolam, and lorazepam) and apply specifically to patients undergoing 3 or more hours of anesthesia. For the SRS membership, this development has the greatest potential impact on the treatment of patients with early onset scoliosis. Young children with severe spinal and thoracic deformity may require procedures under sedation/anesthesia including MRI, serial Mehta casting, hemivertebra resection, or growing spine instrumentation for example. These procedures and the anesthetic exposure may be multiple and at times prolonged.
Initial concerns regarding early childhood exposure to anesthetic agents were based on animal studies with multiple classes of drugs, including both IV and inhaled anesthetics. Observational clinical studies have shown a higher rate of learning delays in school children who had two or more anesthetics compared to patients with one or no anesthetic exposure (2,3). One short anesthetic likely is safe(4,5) and a prospective randomized controlled trial showed no learning differences in children undergoing regional vs. inhaled anesthesia for one-time inguinal hernia repair(5). One study found that patients with 2 or more anesthetic exposures had a 18% rate of attention-deficit/hyperactivity disorder compared to 7-11% in patients with one or fewer exposures with an adjusted hazard ratio of 1.95(3). Longer anesthetic exposure is associated with a higher rate of learning disorders. This association has held up in multiple studies that have controlled for associated comorbidities and other exposures that may contribute to learning delay.
Infantile scoliosis is a life-threatening condition associated with higher than expected mortality(6,7). Early intervention is thought to prevent severe deformity and worsening pulmonary function, which may compromise lifetime health-related quality of life(8,9). For infantile idiopathic scoliosis, Mehta casting has found to be curative in up to ½ the cases, eliminating or delaying the need for spinal surgery. Casting at a younger age (<18 months) is associated with a higher cure rate. If intervention is delayed until over age 3, larger curves may require more aggressive procedures such as vertebral column osteotomy which hold higher neurologic risk or prolonged treatments such as halo gravity traction. Thus, we know young children with severe spinal deformity benefit from early treatment with casting and surgery. These benefits must be weighed against the FDA warning and potential risk of early childhood exposure to anesthetics.
We are supportive of future work on this topic to identify protocols in children 3 and under to reduce potential anesthetic effects on the developing brain. Early onset scoliosis patients are at high risk for pulmonary compromise and lifetime disability without appropriate and early treatment. Thus, surgeons must take a balanced approach and discuss with families both the known and unknown risks as well as benefits of a procedure requiring repeated or lengthy anesthesia prior to age 3 years.
1) FDA Med Watch December 14, 2016 (http://www.fda.gov/Drugs/DrugSafety/ucm532356.htm)
2) Wilder RT, Flick RP, Sprung J, et al. Early exposure to anesthesia and learning disabilities in a population-based birth cohort. Anesthesiology. 2009;110:796–804.
3) Sprung J, Flick RP, Katusic SK, et al. Attention-deficit/hyperactivity disorder after early exposure to procedures requiring general anesthesia. Mayo Clin Proc. 2012;87:120–129.
4) Sun LS, Li G, Miller TKL, et al. Association Between a Single General Anesthesia Exposure Before Age 36 Months and Neurocognitive Outcomes in Later Childhood. JAMA. 2016;315(21):2312-2320.
5) Davidson AJ, Disma N, de Graaff JC, et al. Neurodevelopmental outcome at 2 years of age after general anaesthesia and awake regional anaesthesia in infancy (GAS): an international multicentre, randomised controlled trial. Lancet. 2016;387:239–250.
6) Pehrsson K, Larsson S, Oden A, Nachemson A. Long-term follow-up of patients with untreated scoliosis. A study of mortality, causes of death, and symptoms. Spine (Phila Pa 1976). 1992 Sep;17(9):1091-6.
7) Pehrsson K, Nachemson A, Olofson J, Ström K, Larsson S. Respiratory failure in scoliosis and other thoracic deformities. A survey of patients with home oxygen or ventilator therapy in Sweden. Spine (Phila Pa 1976). 1992 Jun;17(6):714-8.
8) Goldberg CJ, Gillic I, Connaughton O, Moore DP, Fogarty EE, Canny GJ, Dowling FE. Respiratory function and cosmesis at maturity in infantile-onset scoliosis. Spine (Phila Pa 1976). 2003 Oct 15;28(20):2397-406.
9) Karol LA, Johnston C, Mladenov K, Schochet P, Walters P, Browne RH. Pulmonary function following early thoracic fusion in non-neuromuscular scoliosis. J Bone Joint Surg Am. 2008 Jun;90(6):1272-81.