What are the risks of anesthesia in a patient with Trisomy 21?

1.

Elsevier ClinicalKey Drug Monograph

Content last updated: May 3, 2024.

Contraindications And Precautions Early and aggressive intervention to treat the hyperkalemia and resistant arrhythmias is recommended as is subsequent evaluation for latent neuromuscular disease. Avoid induction and maintenance of anesthesia using sole agents that decrease systemic vascular resistance or diastolic blood pressure, such as sevoflurane, in pediatric patients with acid alpha-glucosidase deficiency (Pompe disease). Life-threatening arrhythmias, including severe bradycardia, torsade de pointes, and fatal ventricular fibrillation have been reported in pediatric patients with infantile-onset Pompe disease. Severe bradycardia and cardiac arrest, unrelated to underlying congenital heart disease, have been reported in pediatric persons with Down syndrome during anesthesia induction with sevoflurane. Closely monitor heart rate and consider incremental increases in inspired sevoflurane concentration during anesthesia induction in this patient population; consider having epinephrine and an anticholinergic medication available for use. Bradycardia improved with decreasing sevoflurane concentration, airway manipulation, or administration of an anticholinergic or epinephrine in most reported cases.

Contraindications And Precautions Repeated or lengthy use of general anesthetic and sedation drugs during surgeries or procedures in neonates, infants, and children younger than 3 years, including in utero exposure during the third trimester, may have negative effects on brain development. Consider the benefits of appropriate anesthesia in young children against the potential risks, especially for procedures that may last more than 3 hours or if multiple procedures are required during the first 3 years of life. It may be appropriate to delay certain procedures if doing so will not jeopardize the health of the child. No specific anesthetic or sedation drug has been shown to be safer than another. Human studies suggest that a single short exposure to a general anesthetic in young pediatric patients is unlikely to have negative effects on behavior and learning; however, further research is needed to fully characterize how anesthetic exposure affects brain development. Sevoflurane's minimal alveolar concentration (MAC) is higher in children than adults; it is highest in very young children and decreases with increasing age. The MAC in premature neonates has not been established. The use of sevoflurane has been associated with seizures. The majority of these have occurred in infants older than 2 months, children, and young adults, most of whom had no predisposing risk factors. Clinical judgment should be exercised when using sevoflurane in patients with a seizure disorder or who are at risk for seizures. Use of inhaled anesthetics 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. Concomitant use of succinylcholine has been associated with most, but not all, of these cases. Patients with latent or overt neuromuscular disease, particularly Duchenne muscular dystrophy, appear to be most vulnerable. Early and aggressive intervention to treat the hyperkalemia and resistant arrhythmias is recommended as is subsequent evaluation for latent neuromuscular disease.

2.

Food and Drug Administration (DailyMed).

Publish date: January 1, 2024.

Warnings Early and aggressive intervention to treat the hyperkalemia and resistant arrhythmias is recommended as is subsequent evaluation for latent neuromuscular disease. Pediatric Neurotoxicity Published animal studies demonstrate that the administration of anesthetic and sedation drugs that block NMDA receptors and/or potentiate GABA activity increase neuronal apoptosis in the developing brain and result in long-term cognitive deficits when used for longer than 3 hours. The clinical significance of these findings is not clear. However, based on the available data, the window of vulnerability to these changes is believed to correlate with exposures in the third trimester of gestation through the first several months of life, but may extend out to approximately three years of age in humans (see PRECAUTIONS – Pregnancy, PRECAUTIONS – Pediatric Use, ANIMAL TOXICOLOGY AND/OR PHARMACOLOGY ). Some published studies in children suggest that similar deficits may occur after repeated or prolonged exposures to anesthetic agents early in life and may result in adverse cognitive or behavioral effects. These studies have substantial limitations, and it is not clear if the observed effects are due to the anesthetic/sedation drug administration or other factors such as the surgery or underlying illness. Anesthetic and sedation drugs are a necessary part of the care of children needing surgery, other procedures, or tests that cannot be delayed, and no specific medications have been shown to be safer than any other. Decisions regarding the timing of any elective procedures requiring anesthesia should take into consideration the benefits of the procedure weighed against the potential risks. Bradycardia in Down Syndrome Episodes of severe bradycardia and cardiac arrest, not related to underlying congenital heart disease, have been reported during anesthesia induction with Sojourn (sevoflurane) in pediatric patients with Down syndrome. In most cases, bradycardia improved with decreasing the concentration of Sojourn (sevoflurane), manipulating the airway, or administering an anticholinergic or epinephrine. During induction, closely monitor heart rate, and consider incrementally increasing the inspired Sojourn (sevoflurane) concentration until a suitable level of anesthesia is achieved.

3.

Food and Drug Administration (DailyMed).

Publish date: August 4, 2022.

Warnings Decisions regarding the timing of any elective procedures requiring anesthesia should take into consideration the benefits of the procedure weighed against the potential risks. Bradycardia in Down Syndrome Episodes of severe bradycardia and cardiac arrest, not related to underlying congenital heart disease, have been reported during anesthesia induction with Ultane (sevoflurane) in pediatric patients with Down syndrome. In most cases, bradycardia improved with decreasing the concentration of Ultane (sevoflurane), manipulating the airway, or administering an anticholinergic or epinephrine. During induction, closely monitor heart rate, and consider incrementally increasing the inspired Ultane (sevoflurane) concentration until a suitable level of anesthesia is achieved. Consider having an anticholinergic and epinephrine available when administering Ultane (sevoflurane) for induction in this patient population. Risk of Driving and Operating Machinery Performance of activities requiring mental alertness, such as driving or operating machinery, may be impaired after Ultane (sevoflurane) anesthesia.

4.

Food and Drug Administration (DailyMed).

Publish date: May 3, 2023.

Warnings Decisions regarding the timing of any elective procedures requiring anesthesia should take into consideration the benefits of the procedure weighed against the potential risks. Bradycardia in Down Syndrome Episodes of severe bradycardia and cardiac arrest, not related to underlying congenital heart disease, have been reported during anesthesia induction with sevoflurane, USP in pediatric patients with Down syndrome. In most cases, bradycardia improved with decreasing the concentration of sevoflurane, USP manipulating the airway, or administering an anticholinergic or epinephrine. During induction, closely monitor heart rate, and consider incrementally increasing the inspired sevoflurane, USP concentration until a suitable level of anesthesia is achieved. Consider having an anticholinergic and epinephrine available when administering sevoflurane, USP for induction in this patient population. Risk of Driving and Operating Machinery Performance of activities requiring mental alertness, such as driving or operating machinery, may be impaired after sevoflurane, USP anesthesia.

5.

Zur, Karen B. (2025). In Nelson Textbook of Pediatrics (pp. 2562). DOI: 10.1016/B978-0-323-88305-4.00431-4

Swelling of the tongue and uvula can lead to acute airway obstruction and globus sensation in the first few hours after surgery. Children with underlying hypotonia (trisomy 21) or craniofacial anomalies are at greater risk for suffering this complication. Rare complications include anesthesia-related issues (malignant hyperthermia, arrhythmias, intubation trauma, aspiration), velopharyngeal insufficiency, nasopharyngeal or oropharyngeal stenosis, torticollis, and, very rarely, death from uncontrolled bleeds. Visit Elsevier eBooks+ ateBooks.Health.Elsevier.comfor Bibliography.

6.

Graber TJ, Baskin PL, Soria C, et al. Paediatric Anaesthesia. 2021;31(4):410-418. doi:10.1111/pan.14138.

Publish date: April 4, 2021.

INTRODUCTION: Several prior studies have demonstrated an association between trisomy 21 and airway-related anesthetic complications. However, there is a paucity of large clinical studies characterizing the airway challenges associated with trisomy 21. In this analysis, we examine anesthetic-related airway complications in children with trisomy 21 and compare our findings to well-matched controls. METHODS: A chart review of all general anesthetics occurring between 2011 and 2017 at a single pediatric hospital was performed. Children with trisomy 21 were identified. Matched controls were created using a 1:1 propensity score and controlling for patient sex, patient age, surgical specialty, airway management, and anesthetic induction technique. The primary outcomes were the numbers of difficult intubations and perioperative respiratory adverse events. Secondary outcomes included the number of intubation attempts and the Cormack-Lehane grade in each cohort. RESULTS/DATA ANALYSIS: A total of 2702 anesthetic records were reviewed. Propensity score matching resulted in adequately matched control groups as indicated by a standard mean difference below 0.2 in each case. Logistic regression analysis between trisomy 21 patients and matched controls demonstrated that the trisomy 21 cohort had a higher incidence of perioperative respiratory adverse events (OR 2.04, 95% CI 1.34-3.09, p = .0008) due largely to a higher incidence of airway obstruction (1.7% vs. 0.2%, p = .0005). The trisomy 21 group had a lower rate of difficult intubation (OR 0.26, 95% CI 0.07-0.91, p = .034).

7.

Roach, E. Steve (2024). In Goldman-Cecil Medicine (pp. 2545). DOI: 10.1016/B978-0-323-93038-3.00385-3

No targeted therapy currently exists for Down syndrome. Nevertheless, the prognosis for these individuals has improved considerably owing to improved recognition and management of conditions such congenital heart disease, spine defects, and leukemia.Screening for cervical spine instability is recommended before general anesthesia and before allowing participation in activities that might aggravate atlantoaxial instability. It is important to eliminate potentially treatable causes of cognitive change, particularly hypothyroidism (Chapter 207). Appropriate educational programs, good medical care, and a supportive environment allow most patients to lead enjoyable lives.

8.

Pipan, Mary (2025). In Nelson Textbook of Pediatrics (pp. 362). DOI: 10.1016/B978-0-323-88305-4.00057-2

Individuals with DS have short stature across the life span and stop growing sooner than typical peers, the mechanism of which is unclear. Growth hormone is rarely deficient. Ligamentous laxity is common, especially in the ankles and feet. Inflammatory arthritis is underrecognized, and scoliosis is more common. Joint instability is most apparent in the neck (atlantoaxial instability [AAI]), hips, and knees. Joint pain and impaired mobility can contribute to motor skills deficits, impede independence, and add to behavioral difficulties. Radiographic screening for AAI is not recommended because flexion/extension neck x-rays are not predictive for future neurologic risk. Signs and symptoms of AAI occur because of compression of the spinal cord from slippage of the C1 or C2 vertebrae, which can occur after an injury or anesthesia but can also be seen spontaneously. Neck pain, stiffness, and/or myelopathic signs and symptoms (e.g., change in gait, bowel, or bladder pattern or weakness) should prompt referral to orthopedics or neurosurgery. Universal neck precautions are recommended for all children with DS, assuming that all are at risk for injury from AAI, including limited participation in any activities that would be associated with forcible neck movement such as contact sports, diving, and universal cervical precautions with intubation procedures/surgery. Children with DS should be secured in rear-facing car seats until 40 pounds and may need harness-style car restraints over 40 pounds. Hip instability resulting in recurrent (often painless and voluntary) hip dislocation and patellar instability can impair ambulation and may require surgical interventions.

9.

Elsevier ClinicalKey Drug Monograph

Content last updated: May 4, 2024.

Contraindications And Precautions Repeated or lengthy use of general anesthetic and sedation drugs during surgeries or procedures in neonates, infants, and children younger than 3 years, including in utero exposure during the third trimester, may have negative effects on brain development. Consider the benefits of appropriate anesthesia in young children against the potential risks, especially for procedures that may last more than 3 hours or if multiple procedures are required during the first 3 years of life. It may be appropriate to delay certain procedures if doing so will not jeopardize the health of the child. No specific anesthetic or sedation drug has been shown to be safer than another. Human studies suggest that a single short exposure to a general anesthetic in young pediatric patients is unlikely to have negative effects on behavior and learning; however, further research is needed to fully characterize how anesthetic exposure affects brain development.