Neuromuscular blocking agents in acute respiratory distress syndrome: updated systematic review and meta-analysis of randomized trials

Tarazan, Nehal; Alshehri, Moayad; Sharif, Sameer; Al Duhailib, Zainab; Møller, Morten Hylander; Belley-Cote, Emilie; Alshahrani, Mohammed; Centofanti, John; McIntyre, Lauralyn; Baw, Bandar; Meade, Maureen; Alhazzani, Waleed

doi:10.1186/s40635-020-00348-6

Intensive Care Medicine Experimental

Table 1 Characteristics of included studies

From: Neuromuscular blocking agents in acute respiratory distress syndrome: updated systematic review and meta-analysis of randomized trials

Study	Population	Agent/Dose	NMBA PRN	PEEP	Prone ventilation	Sedation target	Sedative	Ventilation Protocol	Steroids
Gainnier 2004 [18]	ARDS PaO₂/FiO₂ < 150 PEEP ≥ 5 Eligible < 36 h Exclude prior NMBA	cisatracurium bolus of 50mg then infusion at 5 mcg/kg/min	NR	11.1±2.8	14.3%	Deep Ramsay score 6	Midazolam Sufentanil	Yes	7.1%
Gainnier 2004 [18]		Placebo (0.9% NS)	48 h: 7.1%	10.9±2.4	14.3%	Deep Ramsay score 6	Midazolam Sufentanil	Yes	14.3%
Forel 2006 [19]	ARDS Intubated < 48 h PaO₂/FiO₂ < 200 Exclude recent steroids or NMBA	cisatracurium bolus of 0.2 mg/kg then infusion at 5 mcg/kg/min Titrated (increase of 20% if TOF >1) to obtain no response on TOF	48 h: NR ICU stay: 5.6%	9±2.3	-	Deep Ramsay score 6	Midazolam Sufentanil	Yes Same protocol for the first 5 days	5.5%
Forel 2006 [19]		Placebo (0.9%NS)	48 h: 0% ICU stay: 5.6%	9.9±2.9	-	Deep Ramsay score 6	Midazolam Sufentanil	Yes	0%
Papazian 2010 [8]	ARDS PaO₂/FiO₂ < 150 Eligible < 48 h Exclude prior NMBA	cisatracurium 15 mg bolus then infusion of 37.5 mg/h for 48h	48 h: 10% ICU stay: 50%	9.2±3.2	28%	Deep Ramsay score 6	Sufentanil Midazolam Ketamine Propofol	Yes	39.5%
Papazian 2010 [8]	ARDS PaO₂/FiO₂ < 150 Eligible < 48 h Exclude prior NMBA	Placebo	48 h: 22% ICU stay: 56%	9.2±3.5	29%	Deep Ramsay score 6	Sufentanil Midazolam Ketamine Propofol	Yes	45.1%
Lyu 2014 [20]	Severe sepsis and moderate to severe ARDS by Berlin criteria	Vecuronium	-	-	-	Deep	-	-	-
Lyu 2014 [20]		No placebo	-	-	-	Deep	-	-	-
Rao 2016 [22]	ARDS by Berlin criteria	Vecuronium	-	-	-	-	-	-	-
Rao 2016 [22]	ARDS by Berlin criteria	No placebo	-	-	-	-	-	-	-
Guervilly 2016 [21]	ARDS; PaO₂/FiO₂ < 150 with PEEP at least 5 within 48 hours of ARDS onset	cisatracurium 15 mg bolus then infusion of 37.5 mg/h for 48h	-	10 (9; 12)	-	Deep Ramsay score 6	Sufentanil Midazolam Ketamine	ARDSnet protocol	-
Guervilly 2016 [21]		No infusion, but severe ARDS received PRN NMBA	-	11(10;11.5)	-	Deep Ramsay score 6	Sufentanil Midazolam Ketamine	ARDSnet protocol	-
ROSE 2019 [11]	ARDS with PaO₂/FiO₂ <150 + PEEP>8cmH2O	cisatracurium 15 mg bolus then infusion of 37.5 mg/h for 48h	48 h: 0.9% After 48h: 16.0%	12.6±3.6	16.8%	Deep RASS -5 or Ramsay 5-6	-	ARDSNet	Day 7: 17.0%
ROSE 2019 [11]	ARDS with PaO₂/FiO₂ <150 + PEEP>8cmH2O	Usual care	48h:17.0% After 48h: 7.9%	12.5±3.6	14.9%	Light RASS: 0 to -1, Riker: 3 to 4, or Ramsay: 2-3	-	ARDSNet	Day 7: 16.4%

ARDS acute respiratory distress syndrome, ARMA the Acute Respiratory Distress Syndrome Network, ICU intensive care unit, NMBA neuromuscular blocking agents, NS normal saline, PaO₂/FiO₂ ratio of partial arterial pressure of oxygen to fraction of inspired oxygen, PEEP positive end expiratory pressure, RASS Richmond Agitation-Sedation Scale, TOF train of four

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