Table 2.

GRADE certainty assessment of evidence for esketamine versus placebo/control drug for postoperative delirium and secondary outcomes.

Outcome	Certainty assessment							No. of patients		Effect		Certainty
	No. of studies	Study design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Esketamine	Placebo/control drug	Relative (95% CI)	Absolute (95% CI)
POD incidence	22	Randomized trials	Not serious	Seriousa	Seriousb	Not serious	None	243/1432 (17.0%)	337/1428 (23.6%)	RR 0.57 (0.43 to 0.75)	101 fewer per 1,000	⨁⨁◯◯ Lowa,b
dNCR incidence	3	Randomized trials	Not serious	Not serious	Seriousb	Seriousc	None	45/189 (23.8%)	72/182 (39.6%)	RR 0.60 (0.44 to 0.82)	158 fewer per 1,000	⨁⨁◯◯ Lowb,c
MMSE score	4	Randomized trials	Not serious	Seriousa	Seriousb	Seriousc	None	148	147	-	mean 0.79 higher (−0.16 to 1.74)	⨁◯◯◯ Very lowa,b,c
QoR-15 score	4	Randomized trials	Not serious	Seriousa	Seriousb	Seriousc	None	312	303	-	MD 4.8 higher (1.06 to 8.55)	⨁◯◯◯ Very lowa,b,c
Adverse events	16	Randomized trials	Seriousd	Not serious	Seriousb	Not serious	None			RR 0.93 (0.85 to 1.03)	1 fewer per 1,000	⨁⨁◯◯ Lowb,d

POD, postoperative delirium; dNCR, Delayed neurocognitive recovery; MMSE, Mini-Mental State Examination; QoR-15, 15-item Quality of Recovery questionnaire; CI, confidence interval; MD, mean difference; RR, risk ratio.

^aThere was notable inconsistency in effect estimates between different eligible RCTs.

^bAll trials originated from China, limiting the generalizability of our results to international clinical settings.

^cThe number of included studies was relatively limited.

^dMultiple studies lacked consistent definitions and assessment standards for adverse events.