Table 1.

Summary of randomized trials and interventions included in the network meta-analysis

Study, year [reference]	N	Intervention	Control	Delirium occurrence	Duration of mechanical ventilation	Length of stay—ICU	Length of stay—hospital	Mortality	Arrhythmia	Risk of bias*
Abbasi 2018 [34]	137	Melatonin PO	Placebo PO	+	+	+	+	+		Low
Abdelgalel 2016 [35]	90	Dexmedetomidine IV infusion with optional LD	Placebo IV intermittent	+		+	+	+	+	Low
Al-Qadheeb 2016 [36]	68	Haloperidol IV intermittent	Placebo IV intermittent	+		+		+		Low
Azeem 2018 [38]	60	Dexmedetomidine IV LD + infusion	Morphine IV + midazolam IV	+	+	+				Low
vanden Boogaard 2018 [40]	1789	Haloperidol IV intermittent	Placebo IV intermittent	+	+	+	+	+		Low
Chang 2018 [43]	60	Dexmedetomidine IV infusion	Propofol IV infusion	+			+			High
Chanques 2017 [44]	137	IV sedation interruption	Usual sedation	+	+	+	+	+		High
DeJonghe 2018 [49]	1174	IV sedation protocol	Usual sedation	+				+		High
Devlin 2014 [50]	33	Dexmedetomidine IV infusion	Placebo IV infusion	+	+	+		+		Low
Djaiani 2016 [51]	183	Dexmedetomidine IV LD + infusion	Propofol IV infusion	+	+	+	+	+		Low
Gandolfi 2020 [55]	203	Melatonin PO	Placebo PO		+	+	+	+		Low
Girard 2008 56]	336	IV sedation interruption	Usual sedation	+		+		+		High
Hakim 2012 [59]	101	Risperidone PO	Placebo PO	+		+	+	+		Low
Hu 2015 [60]	76	Intervention 1: dexmedetomidine IV infusion + propofol IV infusion Intervention 2: propofol IV infusion	Midazolam IV infusion		+					High
Huang 2014 [61]	108	Dexmedetomidine IV infusion	Propofol IV infusion	+	+					High
Hughes 2021 [62]	432	Dexmedetomidine IV infusion	Propofol IV infusion					+		Low
Javaherforooh Zadeh 2021 [63]	60	Melatonin PO	Placebo PO		+	+				High
Kawazoe 2017 [67]	201	Dexmedetomidine IV infusion	Sedation IV infusion without dexmedetomidine	+	+	+	+	+	+	High
Khan 2018 [69]	135	Haloperidol IV intermittent dose	Placebo IV intermittent dose	+	+	+	+	+		Low
Li 2016 [71]	70	3 groups of dexmedetomidine, propofol or combination IV infusion to circadian clock	Sedation IV infusion without regulation to circadian clock	+	+	+				High
Liu 2017 [73]	105	Intervention 1: remifentanil IV + midazolam IV infusions Intervention 2: fentanyl + midazolam IV infusions	Placebo + midazolam IV infusion	+	+	+		+		Low
Lyu 2015 [74]	140	Remifentanil + midazolam IV infusion	Midazolam IV infusion	+	+	+		+		High
Mehta 2012 [76]	423	Protocolized sedation + daily interruption	Protocolized sedation	+	+	+	+	+		High
Mokhtari 2020 [79]		Aripiprazole PO	Placebo PO	+		+				High
Nassar 2014 [81]		Daily IV sedation interruption	Intermittent IV sedation	+		+	+	+		High
Nishikimi 2018 [82]	88	Ramelteon PO	Placebo PO	+		+		+		Low
Pandharipande 2007 [85]	103	Dexmedetomidine IV LD + infusion	Lorazepam IV LD + infusion	+		+		+		Low
Park 2014 [86]	142	Dexmedetomidine IV LD + infusion	Remifentanil IV infusion	+			+			High
Prakanrattana 2007[89]	126	Risperidone PO	Placebo PO	+		+	+		+	Low
Priye 2015 [90]	64	Dexmedetomidine IV infusion	Placebo IV infusion	+						Low
Rubino 2010 [93]	30	Clonidine IV LD + infusion	Placebo IV infusion	+	+	+				Moderate
Ruokonen 2009 [94]	85	Dexmedetomidine IV infusion	Propofol or midazolam IV infusion	+						Low
Shehabi 2009 [97]	299	Dexmedetomidine IV infusion	Morphine IV infusion	+	+	+	+	+	+	Low
Shehabi 2013 [98]	37	Early goal directed sedation Dexmedetomidine IV infusion	Propofol or midazolam IV infusion	+		+	+	+		High
Shehabi 2019 [99]	4000	Dexmedetomidine IV infusion	Propofol or midazolam IV infusion	+		+	+	+	+	High
Shu 2019 [100]	80	Dexmedetomidine IV LD + infusion	Midazolam IV infusion	+						High
Skrobik 2018 [102]	100	Dexmedetomidine IV infusion	Placebo IV infusion		+	+	+	+		Low
Song 2015 [103]	90	Dexmedetomidine IV infusion	Midazolam IV infusion	+	+	+				High
Spies 2011 [105]	60	Remifentanil IV infusion	Fentanyl IV infusion	+			+			Low
Strom 2010 [106]	113	No sedation; analgesia with opioid	Analgesia with opioid + propofol IV infusion	+			+			High
Su 2016 [107]	700	Dexmedetomidine IV infusion	Placebo IV infusion	+	+	+	+	+	+	Low
Wan 2011 [112]	200	Dexmedetomidine IV infusion	Midazolam IV infusion	+	+					High
Wang 2012 [113]	457	Haloperidol IV infusion	Placebo IV infusion	+	+	+	+	+	+	Low

See supplementary eTables 2 and 3 for detailed description of included studies and risk of bias assessment

IV intravenous, LD loading dose, PO per os

^*The overall risk of bias was the lowest for any domain in the risk of bias tool (i.e., sequence generation, allocation concealment, incomplete outcome data, selective reporting, or other bias)