Opioid and benzodiazepine requirements in critically ill post-surgical children with down syndrome: a systematic review and meta-analysis

Abstract

Background: Down syndrome (DS), or Trisomy 21, is defined by the existence of an additional chromosome 21. Various physiological considerations in DS patients might lead to challenges in adequate pain management and sedation after surgery. The aim of this systematic review and meta-analysis is to evaluate the variations of the requirement needed for pain management and sedation in patients with DS who have undergone surgery compared to patients without DS.

Methods: A systematic review and meta-analysis of studies were conducted, focusing on critically ill patients with DS who were admitted to Intensive care units (ICUs) post-surgery and received opioids and/or benzodiazepines. Searches were conducted in four databases from their inception to November 18, 2023 (Pubmed, Scopus, Cochrane Library, and Web of Science). The primary outcome measured was the dosage of Oral Morphine Equivalent (OME) administered in the days following surgery. Fixed-effect models were used, an approach advisable when only a limited number of studies are available.

Results: Out of the 992 studies initially screened, the systematic review included ten studies, encompassing 730 patients, while the meta-analysis consisted of seven studies, encompassing 533 patients. Of the seven studies included in the analysis, 298 patients were identified to have DS, and 235 patients served as controls. Patients with DS showed a slight increase in OME needs on the first day, but this increase was not statistically significant (mean difference [MD] = 0.09; 95% Confidence Interval [CI]: [-0.02, 0.20]; P = 0.11). There was also no significant difference in the requirement for Midazolam on the first day among DS patients (MD = 0.01; CI [-0.16, 0.19]; P = 0.88). In addition, the duration of mechanical ventilation was not statistically significant in patients with DS compared with the control group (MD = -1.46 hours; 95% CI [-9.74, 6.82]; P = 0.73).

Conclusion: Patients with Down syndrome did not require more sedation or analgesia in the first three days after surgery than patients without Down syndrome. Additionally, the two groups showed no significant difference in the duration of mechanical ventilation.

Keywords: Analgesia; Critical care; Down syndrome; Post surgery; Sedation; Trisomy 21.

Fig. 1

PRISMA flow diagram of the study selection process

Fig. 2

Forest plot comparing the DS and the control groups regarding the OME at day 1

Fig. 3

Forest plot comparing the DS and the control groups regarding the OME at day 2

Fig. 4

Forest plot comparing the DS and the control groups regarding the OME at day 3

Fig. 5

Forest plot comparing the DS and the control groups regarding the cumulative OME for the first two days

Fig. 6

Forest plot comparing the DS and the control groups regarding the cumulative OME for the first two days after resolving the heterogeneity

Fig. 7

Forest plot comparing the DS and the control groups regarding the cumulative OME for the first three days

Fig. 8

Forest plot comparing the DS and the control groups regarding the midazolam at day 1

Fig. 9

Forest plot comparing the DS and the control groups regarding the midazolam at day 2

Fig. 10

Forest plot comparing the DS and the control groups regarding the midazolam at day 3

Fig. 11

Forest plot comparing the DS and the control groups regarding the total cumulative dose of Midazolam for the first two days

Fig. 12

Forest plot comparing the DS and the control groups regarding the mechanical ventilation duration