Effects and safety of natriuretic peptides as treatment of cirrhotic ascites: A systematic review and meta-analysis

Table 1 Main characteristics of the 22 included studies [34 subgroups; receiving bolus injection (n = 8) or continuous infusion (n = 26)]. Atrial natriuretic peptide was tested in 19 studies (215 patients), B-type natriuretic peptide in one study (7 patients), and urodilatin in two studies (21 patients)

Ref.	Country	Study type	Patient n	Drug	Comparator	Adm	Dose (ng/kg/min or ng/kg)	Duration (min)	Post-infusion follow-up (min)	Age (mean)	Male (%)	Ascites severity: Mild/moderate/ severe/refractory	S- or P-sodium (mmol/L) mean ± SE	Quality assessments (risk of bias)
														NOS	RoB2
Abraham et al[31], 1995	United States	Non-random	6	ANP	None	Cont	150	180	180	44.5	67	6/0/0/0	NR	Low	-
			6	ANP	None	Cont	150	180	180	49.5	100	1/3/2/0
Ando[32], 1991	Japan	Non-random	10	ANP	None	Bolus	1000	NA	90	57.1	80	0/5/5/0	138.3 ± 0.7	Low	-
			6	ANP	None	Bolus	1000	NA	90	58.7	67	0/3/3/0	134.2 ± 0.2
Badalamenti et al[33], 1992	Italy	Non-random	9	ANP	None	Bolus	1000	NA	90	57.8	78	0/5/4/0	134.7 ± 1.6	Low	-
			4	ANP	None	Cont	20	60	0	63.3	75	0/3/1/0		Moderate
Carstens et al[36], 1998	Denmark	RCT	15	Urodilatin	Placebo	Cont	20	60	60	50.6	60	15/0/0/0	137.0 ± 0.5	-	Low
Carstens et al[37], 2007	Denmark	RCT	6	Urodilatin	Placebo	Cont	20	90	90	54.0	67	0/0/0/6	133.3 ± 2.0	-	Low
Ferrier et al[14], 1989	Switzerland	Non-random	7	ANP	None	Cont	36	60	60	54.3	57	0/7/0/0	NR	Moderate	-
Fried et al[34], 1990	United States/Switzerland	RCT	11	ANP	Placebo	Cont	15	120	90	NR	82	11/0/0/0	NR	-	Moderate
		RCT	8	ANP	Placebo	Cont	30	120	90	NR	88	8/0/0/0
		RCT	9	ANP	Placebo	Cont	60	120	90	NR	89	9/0/0/0
Gerbes et al[35], 1988	Germany	Non-random	4	ANP	None	Cont	50	30	90	NR	NR	NR	NR	Moderate	-
Ginès et al[22], 1992	Spain	Non-random	5	ANP	None	Cont	50	60	0	57.0	60	0/5/0/0	NR	Moderate	-
			11	ANP	None	Cont	50	60	0		73	0/11/0/0
Heim et al[23], 1990	Germany	Non-random	8	ANP	None	Bolus	500	NA	60	54.5	75	0/8/0/0	NR	Low	-
Jespersen et al[12], 1995	Denmark	Non-random	9	ANP	None	Bolus	2000	NA	120	49.0	89	0/7/2/0	NR	Low	-
Laffi et al[15], 1989	Italy	Non-random	8	ANP	None	Bolus	1000	NA	900	56.4	75	0/0/0/8	131.8 ± 2.6	Low	-
Laffi et al[24], 1989	Italy	Non-random	5	ANP	None	Cont	100	45	75	58.0	60	0/5/0/0	NR	Low	-
			4	ANP	None	Cont	100	45	75	56.4	25	0/4/0/0
			6	ANP	None	Cont	100	45	75	54.0	83	0/6/0/0
La Villa et al[16], 1995	Italy	Non-random	7	BNP	None	Cont	13.861	60	60	56.0	57	0/7/0/0	135.0 ± 1.0	Low	-
Legault et al[25], 1993	Canada	Non-random	5	ANP	None	Cont	15	120	120	NR	80	5/0/0/0	139.0 ± 2.0	Low	-
			7	ANP	None	Cont	15	120	120	NR	71	7/0/0/0	133.0 ± 1.0
Miyase et al[26], 1990	Japan	Non-random	6	ANP	None	Bolus	500	NA	90	58.0	NR	6/0/0/0	NR	Low	-
Morali et al[13], 1991	Canada	Non-random	5	ANP	None	Cont	15	120	60	54.0	80	5/0/0/0	133.0 ± 1.0	Low	-
			12	ANP	None	Cont	15	120	60	53.0	67	0/0/0/12	138.0 ± 1.0
Morali et al[11], 1992	Canada	Non-random	6	ANP	None	Cont	15	120	0	56.8	100	0/0/0/6	NR	Low	-
			4	ANP	None	Cont	15	120	0	64.3	100	0/0/0/4
Salerno et al[27], 1988	Italy	Non-random	7	ANP	Placebo	Bolus	1000	NA	60	56.6	100	0/2/5/0	NR	Low	-
Tobe et al[28], 1993	Canada	Non-random	8	ANP	None	Cont	15	120	0	52.4	100	8/0/0/0	NR	Low	-
Tobe et al[29], 1993	Canada	Non-random	6	ANP	None	Cont	15	120	0	58.0	67	0/0/0/6	NR	Low	-
Wong et al[30], 1993	Canada	RCT	3	ANP	Albumin	Cont	15	120	60	58.0	67	3/0/0/0	135.0 ± 5.0	-	Low
			10	ANP	Albumin	Cont	15	120	60	54.0	70	0/0/0/10	134.0 ± 1.0

¹The continuous infusion of B-type natriuretic peptide (BNP) was administered with 4 pmol/kg/min. The dose was converted to ng/kg/min using the molar mass of BNP.

RCT: Randomised controlled trial; Non-random: Non-randomised trial; ANP: Atrial natriuretic peptide; BNP: B-type natriuretic peptide; NOS: Newcastle-Ottawa-Scale; ROB2: Risk of bias tool version 2; Adm: Mode of administration; Cont: Continuous infusion; S- or P-sodium: Serum or plasma sodium; NR: Not reported; NA: Not applicable.