Pharmacological interventions for preventing acute mountain sickness: a network meta-analysis and trial sequential analysis of randomized clinical trials

Figures & data

Figure 1. PRISMA flow diagram. A total of 114 studies were obtained with the search strategy of which finally 24 were included.

Figure 2. Forest plot of mixed treatment comparison estimates for the incidence of AMS. Acetazolamide 375 mg twice daily, dexamethasone, ibuprofen, acetazolamide 125 mg twice daily, combined acetazolamide with Ginkgo biloba and acetazolamide 250 mg twice daily were observed with significantly lower incidence of AMS compared to placebo.

Table 1. Mixed treatment comparison pooled estimates {odds ratio [95% confidence interval]} for the key comparisons for incidence of AMS.

Comparator intervention	Reference intervention
	Acetazolamide 375 mg twice daily		Dexamethasone		Ibuprofen		Acetazolamide 125 mg twice daily		Acetazolamide 250 mg twice daily		Acetazolamide+Ginkgo biloba		Placebo
	D	M	D	M	D	M	D	M	D	M	D	M	D	M
Acetazolamide 375 mg twice daily			–	0.5 [0.1, 1.8]	–	0.4 [0.1, 1.3]	–	0.4 [0.1, 1.3]	–	0.4 [0.1, 1.1]	–	0.2 [0.1, 1]	0.1* [0.1, 0.4]	0.1* [0.1, 0.4]
Dexamethasone					–	1 [0.3, 2.6]	–	0.9 [0.3, 2.5]	–	0.8 [0.3, 2.1]	–	0.4 [0.1, 2]	0.3* [0.1, 0.7]	0.3* [0.1, 0.7]
Ibuprofen							–	1 [0.5, 1.8]	–	0.8 [0.5, 1.5]	–	0.5 [0.1, 1.7]	0.3* [0.2, 0.5]	0.3* [0.2, 0.5]
Acetazolamide 125 mg twice daily									–	0.8 [0.5, 1.6]	–	0.5 [0.1, 1.8]	0.3* [0.2, 0.5]	0.3* [0.2, 0.5]
Acetazolamide 250 mg twice daily											–	0.6 [0.1, 2.1]	0.4* [0.2, 0.6]	0.4* [0.2, 0.6]
Acetazolamide+Ginkgo biloba													0.3* [0.2, 0.6]	0.3* [0.2, 0.6]
Placebo

* Statistically significant (p ≤ .05); high degree of consistency was observed between the direct and indirect pooled estimates wherever available.

Figure 3. Forest plot of mixed treatment comparison estimates for incidence of severe AMS. Acetazolamide at 125, 250 and 375 mg twice daily, dexamethasone and combined acetazolamide with Ginkgo biloba showed a significant reduction in the incidence of severe AMS compared to placebo.

Table 2. Grading the evidence for key interventions compared to placebo for the incidence of AMS.

Comparisons	Illustrative comparative risks (95% confidence intervals)		Effect estimate and quality ofevidence for directcomparisons	Effect estimate andquality of evidence for mixedtreatment comparisons
	Assumed risk^a	Corresponding risk
Acetazolamide 375 mg twice daily	583 per 1000	124 per 1000 (124–359)	0.1 [0.1, 0.4] ⊕⊝⊝⊝ Very low^b^,^c^,^d	0.1 [0.1, 0.4] ⊕⊝⊝⊝ Very low^b^,^c^,^d
Dexamethasone	583 per 1000	292 per 1000 (124–492)	0.3 [0.1, 0.7] ⊕⊝⊝⊝ Very low^b^,^c^,^d	0.3 [0.1, 0.7] ⊕⊝⊝⊝ Very low^b^,^c^,^d
Ibuprofen	583 per 1000	292 per 1000 (220–411)	0.3 [0.2, 0.5] ⊕⊕⊝⊝ Low^b^,^c	0.3 [0.2, 0.5] ⊕⊕⊝⊝ Low^b^,^c
Acetazolamide 125 mg twice daily	583 per 1000	292 per 1000 (220–411)	0.3 [0.2, 0.5] ⊕⊕⊕⊝ Moderate^b	0.3 [0.2, 0.5] ⊕⊕⊕⊝ Moderate^b
Acetazolamide 250 mg twice daily	583 per 1000	359 per 1000 (220–454)	0.4 [0.2, 0.6] ⊕⊕⊕⊝ Moderate^b	0.4 [0.2, 0.6] ⊕⊕⊕⊝ Moderate^b

Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate; very low quality: we are very uncertain about the estimate.

^a Assumed risk was the median control group risk (score value) across the studies.

^b Downgraded one level for imprecision of the estimates.

^c Downgraded one level as publication bias could not be assessed.

^d Downgraded one level due to small number of study participants.