Diuretic combinations in critically ill patients with respiratory failure: A systematic review and meta-analysis

Table 2 Safety events and change in serum creatinine and electrolytes at 24-h for all included studies

Ref.	Treatment group	24-h biochemical changes1				Safety events, n (%)
		Creatinine, μmol/L	Sodium, mmol/L	Potassium, mmol/L	Bicarbonate, mmol/L	Hypona-tremia	Hypo-kalemia
Mineralocortocoid-antagonist
Apte et al[21], 2008	Spironolactone + Furosemide (n = 10)	+4.8 (4.1-6.9)	-1.0 (?)	+0.13 (?)	-	-	-
	Furosemide (n = 10)	+23 (-4.4-39)	+3.0 (?)	+0.13 (?)	-	-	-
Thiazides
Bihari et al[22], 2016	Indapamide + Furosemide (n = 20)	-5.2 ± 38	0 ± 0	-0.4 ± 1.8	+1.4 ± 6.3	0 (0)	0 (0)
	Furosemide (n = 20)	-2.3 ± 14	+2.0 ± 4.0	-0.2 ± 0.6	+0.9 ± 2.5	0 (0)	0 (0)
Bohn et al[27], 2019	CTZ + Furosemide (n = 34)	-	-	-	-	-	8 (24)
	MTZ + Furosemide (n = 16)	-	-	-	-	-	3 (19)
Michaud and Mintus[23], 2017	CTZ + Furosemide (n = 58)	-18 ± 57	+0.5 ± 5.6	-0.4 ± 0.6	+3.3 ± 5.1	15 (26)	10 (17)
	MTZ + Furosemide (n = 64)	-18 ± 73	-1.2 ± 5.3	-0.3 ± 0.6	+2.6 ± 5.6	25 (39)	11 (17)
Ng et al[28], 2013	MTZ + Furosemide (n = 42)	+2.7 ± 28	-	-	-	18 (43)	15 (35)
Shulenberger et al[29], 2016	CTZ + Furosemide (n = 40)	+8.8 ± 27	+0.1 ± 2.3	-	-	2 (5)2	34 (85)3
	MTZ + Furosemide (n = 38)	+18 ± 35	-0.7 ± 3.1	-	-	2 (5)2	27 (71)3
Vánky et al[26], 1997	HCTZ + Amiloride + Furosemide (n = 20)	-2.0 ± 7.1	-	-	-	-	-
	Furosemide (n = 57)	-2.0 ± 7.6	-	-	-	-	-
Carbonic anhydrase inhibitor
Heming et al[24], 2011	Acetazo + Furosemide (n = 29)	+4.3 ± 9.4	-	-0.3 ± 0.4	-3.6 ± 5.1	-	9 (31)
Imiela and Budaj[25], 2017	Acetazo + Furosemide (n = 10)	-	-	-	-	-	-
	Furosemide (n = 10)	-	-	-	-	-	-

¹Results are presented in median (IQR), or mean ± SD change within 24-h, from baseline.

²Only severe hyponatremia event (Na⁺ < 125 mmol/L) were reported.

³Hypokalemia was defined as K⁺ < 4.0 mmol/L, instead of 3.5 mmol/L for all other studies.

CTZ: Chlorothiazide; MTZ: Metolazone; HCTZ: Hydrochlorothiazide; Acetazo: Acetazolamide.