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 effectAcetazolamidePlaceboRisk of side effectEffect modification by total daily dose (<400 mg/day vs 400–600 mg/day vs >600 mg/day)
YesNoYesNoOR (95% CI)I2 (%)NPOR=1Quality*Beta(95% CI)PEMxTDDc
Primary outcomes
Paraesthesia5426138194812.3 (9.3 to 16)1639<0.01⊕⊕⊕◯
1.8(1.1 to 2.9)0.01
 <400 mg22127649384.58.4 (5.6 to 12.5)1013<0.01
 400–600 mg1942422240914.5 (9.3 to 23)1120<0.01
 >600 mg1279510154.527.3 (12 to 63)06<0.01
Dysgeusia84729106254.2 (2.5 to 7.1)022<0.01⊕⊕◯◯
3.1(1.2 to 8.2)0.02
 <400 mg3125285.50.8 (0.18 to 3.4)050.75
 400–600 mg3832763153.6 (1.8 to 7.1)012<0.01
 >600 mg432772224.59.7 (3.3 to 29)05<0.01
Polyuria157683546631.9 (1.3 to 2.8)022<0.01⊕⊕◯◯
1.3(0.7 to 2.4)0.46
Fatigue5834273756.5 (3.4 to 12.4)014<0.01⊕⊕◯◯
2.6(0.7 to 9.4)0.14
Secondary outcomes
 Nausea52326183502.8 (1.6 to 4.7)1012<0.010.8(0.2 to 3.5)0.77
 GERD3018971822.8 (1.2 to 6.3)060.022.2(0.6 to 8.2)0.16
 Diarrhoea‡2716141745.3 (2.1 to 13)05<0.011.6(0.01 to 397)0.81
 Depression1814731534.2 (1.5 to 11.6)050.012.1(0.04 to 108)0.58
 Dizziness18266152671.2 (0.6 to 2.3)0100.650.8(0.13 to 5.2)0.82
 Rash1643363591.7 (0.75 to 3.8)080.211.8(0.3 to 10.4)0.43
 Drowsiness7911914.2 (0.86 to 21)030.08Na†
 Tinnitus1611661202.5 (0.99 to 6.2)030.053Na†
 Dyspnoea1211141122.7 (0.9 to 8)040.07Na†
 Dry mouth510911424.8 (0.91 to 25)030.07Na†
  • *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; PEMxTDDc, P value for the test for effect modification by total daily dose categories; POR=1, P value for the odds ratio.