Impact of proning with and without inhaled pulmonary vasodilators and neuromuscular blocking agents in COVID acute respiratory distress syndrome

doi:10.5492/wjccm.v14.i3.101327

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World Journal of Critical Care Medicine

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World J Crit Care Med. Sep 9, 2025; 14(3): 101327
Published online Sep 9, 2025. doi: 10.5492/wjccm.v14.i3.101327

Table 1 Demographics and comorbidities, n (%)

Characteristic	All	Control	Prone position ventilation ± rescue therapy	P value
n	114	25	89	-
Age (years) (mean ± SD)	58.32 ± 13.44	62.48 ± 14.84	57.18 ± 12.89	0.081
Sex
Female	25 (21.55)	14 (56.0)	35 (38.46)	0.116
Male	91 (78.45)	11 (44.0)	56 (61.54)	0.116
Race
African American	73 (69.93)	19 (76.0)	54 (59.34)	0.208
White	6 (5.17)	0 (0.00)	6 (6.59)
Other	37 (31.9)	6 (24.0)	31 (34.07)
Ethnicity
Hispanic or Latino	30 (25.86)	2 (8.0)	28 (30.77)	0.021^a
Non-Hispanic or Latino	86 (74.14)	23 (92.0)	63 (69.23)	0.021^a
Body mass index (median, interquartile range)	30.7 (27.5, 39.2)	28.3 (24.3, 33.0)	32.8 (28.4, 40.0)	0.012^a
Comorbidities
Immune disorders	11 (9.48)	1 (4.0)	10 (10.99)	0.291
Kidney disease	13 (11.21)	1 (4.0)	12 (13.19)	0.197
Liver disease	17 (14.66)	4 (16.0)	13 (14.29)	0.830
Diabetes	72 (62.07)	15 (60.0)	57 (62.64)	0.830
Heart disease	70 (60.34)	14 (56.0)	56 (61.54)	0.616
Hypertension	78 (67.24)	16 (64.00)	62 (68.13)	0.697
Discharge status
Expired	59 (50.86)	12 (48.0)	47 (51.65)	0.722
Inpatient rehab	10 (8.77)	1 (4.0)	9 (9.89)
Acute Care Hospital	16 (14.0)	4 (16.0)	12 (13.19)
Skilled nursing facility, long-term acute care	5 (4.31)	1 (4.0)	4 (4.40)
Home	23 (19.82)	7 (28.0)	16 (17.58)
Other	3 (2.58)	0 (0.00)	3 (3.30)

^aStatistically significant value (P < 0.05).

Table 2 Clinical features, baseline ventilator settings and hard outcomes of patients that received either intervention in combination with prone position ventilation compared to controls, n (%)

Characteristic	All	Control	Prone position ventilation ± rescue therapy	P value
n	114	25	89	-
Highest Sequential Organ Failure Assessment score (mean ± SD)	13.8 ± 3.2	11.7 ± 3.5	14.4 ± 2.9	< 0.001^a
Baseline respiratory parameters (mean ± SD)
FiO₂	73.6 ± 21.4	55 ± 15.6	80.2 ± 19.2	< 0.001^a
PaO₂	85.9 ± 35.0	105.7 ± 45.7	80.3 ± 29.2	0.002^a
PaO₂/FiO₂	121.6 ± 58.8	175.7 ± 75.0	105.3 ± 41.4	< 0.001^a
SpO₂	94.8 ± 4.5	97.2 ± 3.5	94.0 ± 4.5	0.001^a
Baseline ventilator parameters, median (interquartile range)
Positive end expiratory pressure (cm H₂O)	11.1 ± 6.3	10.8 ± 7.9	11.2 ± 4.9	0.771
Tidal volume (mL)	425.7 ± 64.8	418.4 ± 65.6	429.2 ± 64.8	0.496
Plateau pressure (cm H₂O)	25.2 ± 5.5	24.3 ± 6.1	25.6 ± 5.1	0.360
Driving pressure (cm H₂O)	14.6 ± 4.4	15.2 ± 4.8	14.3 ± 4.2	0.470
Tidal compliance (mL/cm H₂O)	32.4 ± 10.1	31.0 ± 9.0	33.1 ± 10.6	0.478
Peak inspiratory pressure (cm H₂O)	31.0 ± 7.3	28.0 ± 6.1	32.6 ± 7.4	0.009^a
O₂ index	14.0 ± 9.0	9.7 ± 11.2	16.4 ± 6.6	0.002^a
Average number of times patient was proned during hospitalization	-	-	1.3	-
Average time from intubation to first prone (hours)	-	-	25.7	-
Average duration of first proning session (days) (n = 89)	-	-	2.5	-
Average duration of second proning session (days) (n = 44)	-	-	2.6	-
Average duration of third proning session (days) (n = 12)	-	-	1.5	-
Primary outcomes
Mortality	59 (50.8)	12 (48.0)	47 (51.65)	0.747
Venovenous extracorporeal membrane oxygenation	21.9 (25)	8 (2.0)	76 (19)	0.052^a
Intensive care unit LOS (mean ± SD)	15.2 ± 12.8	7.4 ± 7.0	17.3 ± 13.2	< 0.001^a
Hospital LOS (mean ± SD)	20.2 ± 15.7	12.6 ± 14.1	22.3 ± 15.6	0.003^a

^aStatistically significant value (P < 0.05).

FiO₂: Fractional inspired oxygen; LOS: Length of stay; PaO_2: Arterial oxygen partial pressure.

Table 3 Logistical and linear regression of primary outcomes adjusted for baseline Sequential Organ Failure Assessment score and age

Primary outcomes	Control vs treatment subgroup	Odds ratio (95%CI)	P value	SE
Mortality	PPV	0.82 (0.19-3.36)	0.78	-
	PPV and IVd	0.57 (0.15-2.04)	0.39	-
	PPV and NMBA	0.8 (0.07-7.28)	0.84	-
	PPV, IVd and NMBA	2.15 (0.51-9.40)	0.3	-
Venovenous extracorporeal membrane oxygenation	PPV	2.33 (0.03-22.63)	0.43	-
	PPV and IVd	1.03 (0.12-10.36)	0.98	-
	PPV and NMBA	8 (0.55-139.75)	0.13	-
	PPV, IVd and NMBA	1.04 (0.17-8.90)	0.97	-
Intensive care unit LOS	PPV	-	0.028	0.24
	PPV and IVd	-	< 0.001^a	0.23
	PPV and NMBA	-	< 0.001^a	0.38
	PPV, IVd and NMBA	-	< 0.001^a	0.24
Hospital LOS	PPV	-	0.04	0.25
	PPV and IVd	-	< 0.001^a	0.23
	PPV and NMBA	-	0.007	0.4
	PPV, IVd and NMBA	-	< 0.001^a	0.03

^aStatistically significant value (P < 0.05).

IVd: Inhaled vasodilators; LOS: Length of stay; NMBA: Neuromuscular blocking agents; PPV: Prone position ventilation.

Table 4 Clinical features, ventilator settings and outcomes of treatment sub-group analysis

Characteristic	PPV		PPV + IVd		PPV + NMBA	PPV + NMBA + IVd		P value
Total	36		36		5	12		-
Highest Sequential Organ Failure Assessment score pre-ICU (mean ± SD)	14.0 ± 2.7		15.2 ± 2.4		12.2 ± 2.9	14.2 ± 4.2		0.089
Respiratory parameters < 24 hours prior to the first proning session (mean ± SD)
FiO₂	76.6 ± 20.0		85.3 ± 18.5		70.0 ± 7.0	81.2 ± 21.6		0.237
PaO₂	82.4 ± 31.3		73.6 ± 21.4		73.6 ± 21.4	73.6 ± 21.4		0.701
PaO₂/FiO₂	112.0 ± 68.1		101.3 ± 58.5		101.0 ± 9.3	61.6 ± 55.1		0.241
SpO₂	94.0 ± 4.6		93.9 ± 4.8		95.6 ± 3.5	93.9 ± 3.4		0.896
Ventilator parameters < 24 hours prior to the first proning session (mean ± SD)
positive end expiratory pressure, cm H₂O	10.7 ± 2.2		12.6 ± 8.8		8.7 ± 2.5	12.8 ± 2.2		0.528
Tidal volume (mL)	413.5 ± 65.0		440.5 ± 70.3		428.7 ± 44.0	443.3 ± 64.0		0.570
Plateau pressure (cm H₂O)	24.5 ± 6.1		25.9 ± 4.1		26.5 ± 4.9	27.8 ± 5.8		0.643
Driving pressure (cm H₂O)	13.2 ± 12.3		14.3 ± 3.9		18.0 ± 0.0	15.8 ± 4.7		0.373
Tidal compliance (mL/cm H₂O)	34.8 ± 12.3		35.5 ± 9.0		29.5 ± 10.60	24.0 ± 6.7		0.185
Peak inspiratory pressure	32.7 ± 7.0		33.5 ± 5.8		24.2 ± 9.9	35.1 ± 9.6		0.111
O₂ index	16.8 ± 8.3		15.6 ± 5.5		14.2 ± 2.0	20.5 ± 3.1		0.537
Average duration of intervention
First proning session duration (days)	2.3		3.1		1.0	2.0		-
Total duration of IVd (days)	-		2.9		-	3.7		-
Total duration of NMBA (days)	-	-		3.4		2.7	-
Average time from intubation to first prone (hour)	23.2	18.8		23.5		43.4	-
Primary outcomes
Mortality	21 (58.33)		20 (55.56)		2 (40.00)	4 (33.33)		0.439
Total LOS (mean ± SD)	15.2 ± 10.7		15.8 ± 10.8		32.2 ± 34.2	17.4 ± 8.0		0.618
ICU LOS (mean ± SD)	19.5 ± 11.8		20.6 ± 13.1		34.2 ± 20.0	34.2 ± 34.1		0.737

FiO₂: Fractional inspired oxygen; ICU: Intensive care unit; IVd: Inhaled vasodilators; LOS: Length of stay; NMBA: Neuromuscular blocking agents; PaO_2: Arterial oxygen partial pressure; PPV: Prone position ventilation.

Table 5 Secondary outcomes from day 0 to day 7 after initiation of intervention per treatment subgroup

Intervention	Day	Arterial oxygen partial pressure/fractional inspired oxygen Ratio			Plateau pressure			Compliance			Driving pressure			Oxygen index
Intervention	Day	Mean	∆ From day 0	P value	Mean	∆ From day 0	P value	Mean	∆ From day 0	P value	Mean	∆ From day 0	P value	Mean	∆ From day 0	P value
PPV	0	121.6	-	-	23.4	-	-	39.4	-	-	12.0	-	-	13.1	-	-
	1	141.5	16.3	0.00^a	24.3	0.9	0.31	39.1	-0.3	0.88	12.7	0.7	0.42	10.4	-2.6	0.04^a
	2	150.4	23.7	0.00^a	24.0	0.6	0.56	37.8	-1.7	0.55	12.8	0.8	0.43	10.3	-2.7	0.09
	3	139.8	15.0	0.05^a	23.9	0.5	0.66	35.2	-4.3	0.16	13.2	1.2	0.30	11.9	-1.1	0.53
	4	142.2	16.9	0.05^a	24.3	0.9	0.45	36.2	-3.3	0.30	13.6	1.7	0.16	11.4	-1.7	0.39
	5	142.4	17.1	0.07	24.2	1.8	0.17	35.3	-4.1	0.19	14.5	2.5	0.04^a	12.7	-0.3	0.87
	6	140.1	15.2	0.12	24.7	1.2	0.34	35.1	-4.4	0.18	14.9	2.9	0.02^a	12.2	-0.8	0.69
	7	140.9	15.9	0.12	24.8	1.4	0.29	35.0	-4.4	0.18	15.1	3.1	0.01^a	11.6	-1.1	0.61
PPV and IVd	0	109.3	-	-	25.0	-	-	36.3	-	-	13.6	-	-	11.5	-	-
	1	124.9	14.4	0.01^a	26.3	1.2	0.13	38.1	1.8	0.49	13.1	-0.5	-	14.0	2.6	0.05
	2	136.1	24.6	0.00^a	26.1	1.1	0.26	38.1	1.8	0.55	12.2	-1.3	0.51	13.4	2	0.22
	3	133.3	22.0	0.01^a	26.9	1.9	0.08	34.3	-2	0.52	14.2	0.6	0.18	13.5	2.1	0.25
	4	129.8	18.8	0.03^a	27.7	2.6	0.02^a	34.2	-2.1	0.51	15.2	1.7	0.55	13.8	2.4	0.22
	5	136.1	24.5	0.01^a	27.1	2.0	0.09	36.6	0.3	0.92	15.1	1.6	0.14	13.0	1.6	0.44
	6	134.2	22.8	0.02^a	27.8	2.7	0.03^a	32.7	-3.6	0.28	16.3	2.8	0.18	13.6	2.2	0.30
	7	138.5	26.8	0.01^a	27.4	2.3	0.07	32.5	-3.8	0.26	16.0	2.4	0.02^a	12.6	1.2	0.58
PPV and NMBA	0	108.3	-	-	25.9	-	-	35.9	-	-	-	-	-	11.8	-	-
	1	115.6	6.8	0.54	29.7	3.8	0.13	29.2	-6.7	0.33	18.7	2.3	0.40	12.3	0.5	0.86
	2	115.6	6.8	0.65	27.7	1.8	0.54	32.3	-3.7	0.66	18.3	1.9	0.53	10.2	-1.7	0.65
	3	115.6	6.8	0.70	27.1	1.2	0.71	23.1	-12.8	0.15	18.6	2.2	0.50	12.0	0.2	0.96
	4	119.5	10.3	0.61	26.8	0.9	0.79	34.9	-1.1	0.91	19.4	3	0.38	9.7	-2.2	0.64
	5	120.4	11.3	0.60	24.8	-1.0	0.77	35.8	-0.1	0.99	16.8	0.6	0.86	11.2	-0.6	0.91
	6	130.6	20.6	0.40	24.6	-1.2	0.74	36.4	0.5	0.96	16.8	0.6	0.86	10.2	-1.6	0.75
	7	127.6	17.8	0.47	24.6	-1.2	0.74	36.4	0.5	0.96	17.0	0.8	0.82	11.0	-0.8	0.87
PPV, IVd and NMBA	0	119.5	-	-	25.9	-	-	28.8	-	-	14.7	-	-	14.4	-	-
	1	102.0	-3.0	0.78	27.6	1.7	0.28	36.7	7.9	0.06	14.4	-0.3	0.86	18.0	3.6	0.19
	2	98.6	-6.2	0.64	25.8	-0.1	0.97	40.1	11.3	0.02^a	12.9	-1.8	0.32	18.9	4.4	0.19
	3	119.5	-10.9	0.46	26.4	0.6	0.78	38.0	9.2	0.08	13.2	-1.6	0.43	20.5	6	0.11
	4	119.5	23.8	0.21	24.6	-1.3	0.55	35.5	6.6	0.22	12.9	-1.8	0.40	14.7	0.3	0.95
	5	122.7	16.8	0.39	24.4	-1.4	0.52	37.1	8.3	0.13	13.7	-1	0.63	13.4	-1	0.81
	6	123.9	18.0	0.40	25.7	-0.2	0.94	37.4	8.6	0.12	15.0	-0.1	0.96	11.6	-2.8	0.52
	7	127.2	21.1	0.34	23.4	-2.4	0.29	37.7	8.9	0.12	13.0	-2.1	0.34	11.0	-3.5	0.44

^aStatistically significant value (P < 0.05).

IVd: Inhaled vasodilators; NMBA: Neuromuscular blocking agents; PPV: Prone position ventilation.

Citation: Cabrera M, Bharil S, Chin M, Yohannes S, Clark P. Impact of proning with and without inhaled pulmonary vasodilators and neuromuscular blocking agents in COVID acute respiratory distress syndrome. World J Crit Care Med 2025; 14(3): 101327
URL: https://www.wjgnet.com/2220-3141/full/v14/i3/101327.htm
DOI: https://dx.doi.org/10.5492/wjccm.v14.i3.101327