Table 2

Risk of side effects (based on OR). Dose dependency was assessed by checking for effect modification by total daily dose and was only significant for paraesthesias and dysgeusia. There was a trend towards higher odds for fatigue, but this relationship did not reach statistical significance. ORs were chosen a priori as the effect measure for primary analyses due to the favourable mathematical properties, but to aid interpretation table 4 shows results translated into risk ratios and numbers need to treat

Side effect	Acetazolamide		Placebo		Risk of side effect					Effect modification by total daily dose (<400 mg/day vs 400–600 mg/day vs >600 mg/day)
Side effect	Yes	No	Yes	No	OR (95% CI)	I² (%)	N	P_OR=1	Quality*	Beta	(95% CI)	P_EMxTDDc
Primary outcomes
Paraesthesia	542	613	81	948	12.3 (9.3 to 16)	16	39	<0.01	⊕⊕⊕◯ Moderate	1.8	(1.1 to 2.9)	0.01
<400 mg	221	276	49	384.5	8.4 (5.6 to 12.5)	10	13	<0.01
400–600 mg	194	242	22	409	14.5 (9.3 to 23)	11	20	<0.01
>600 mg	127	95	10	154.5	27.3 (12 to 63)	0	6	<0.01
Dysgeusia	84	729	10	625	4.2 (2.5 to 7.1)	0	22	<0.01	⊕⊕◯◯ Low	3.1	(1.2 to 8.2)	0.02
<400 mg	3	125	2	85.5	0.8 (0.18 to 3.4)	0	5	0.75
400–600 mg	38	327	6	315	3.6 (1.8 to 7.1)	0	12	<0.01
>600 mg	43	277	2	224.5	9.7 (3.3 to 29)	0	5	<0.01
Polyuria	157	683	54	663	1.9 (1.3 to 2.8)	0	22	<0.01	⊕⊕◯◯ Low	1.3	(0.7 to 2.4)	0.46
Fatigue	58	342	7	375	6.5 (3.4 to 12.4)	0	14	<0.01	⊕⊕◯◯ Low	2.6	(0.7 to 9.4)	0.14
Secondary outcomes
Nausea	52	326	18	350	2.8 (1.6 to 4.7)	10	12	<0.01		0.8	(0.2 to 3.5)	0.77
GERD	30	189	7	182	2.8 (1.2 to 6.3)	0	6	0.02		2.2	(0.6 to 8.2)	0.16
Diarrhoea‡	27	161	4	174	5.3 (2.1 to 13)	0	5	<0.01		1.6	(0.01 to 397)	0.81
Depression	18	147	3	153	4.2 (1.5 to 11.6)	0	5	0.01		2.1	(0.04 to 108)	0.58
Dizziness	18	266	15	267	1.2 (0.6 to 2.3)	0	10	0.65		0.8	(0.13 to 5.2)	0.82
Rash	16	433	6	359	1.7 (0.75 to 3.8)	0	8	0.21		1.8	(0.3 to 10.4)	0.43
Drowsiness	7	91	1	91	4.2 (0.86 to 21)	0	3	0.08			Na†
Tinnitus	16	116	6	120	2.5 (0.99 to 6.2)	0	3	0.053			Na†
Dyspnoea	12	111	4	112	2.7 (0.9 to 8)	0	4	0.07			Na†
Dry mouth	5	109	1	142	4.8 (0.91 to 25)	0	3	0.07			Na†

*Quality of Evidence Assessment based on Grading of Recommendations Assessment, Development and Evaluation; only performed for primary outcomes (for details see online supplementary e-Table 4).
†Dose dependence was only assessed for outcomes with pooled effect estimates based on at least five studies.
‡Primary analysis for diarrhoea had a high degree of heterogeneity (OR 2.3; 95% CI 1.2 to 4.4; I²=55%, n=6, p=0.01) which was entirely driven by one study15 in which there were many cases of diarrhoea in the placebo group thought to be due to infectious aetiology in the setting of mountain sojourn; for the final analysis (results reported earlier) this study was excluded resulting in similar results without evidence of heterogeneity (thus final analysis is based on fixed model).
GERD, gastro-oesophageal reflux disease; OR, Odds ratio; P_EMxTDDc, P value for the test for effect modification by total daily dose categories; P_OR=1, P value for the odds ratio.