Selective ß2-Adrenoceptor Agonists and Relevant Hyperlactatemia: Systematic Review and Meta-Analysis

Figures

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  Figure 1. Flowchart of the literature search process.

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  Figure 2. l-lactic acid level in 47 individual cases with relevant l-hyperlactatemia (≥5.0 mmol/L) after taking either an intravenous or a nebulized ß2-agonist (red color; ●) and with a decrease (blue color, ●) in l-lactate level by ≥3.0 mmol/L or to ≤2.5 mmol/L, 3 to 56, median 13 h after discontinuing, reducing or without modifying the dosage of the ß2-agonist. The results are given as ‘box and whisker plot’: bottom and top of box 25th and 75th centile, respectively, middle of box 50th centile (the median), ends of whiskers 5th and 95th centile, respectively.

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  Figure 3. Forest plot of observational studies and clinical trials and pooled prevalence (dotted line) of relevant hyperlactatemia (≥5.0 mmol/L) associated with ß2-agonists, including 95% confidence intervals (95% CI). The size of the squares is related to the weight of each study. The horizontal lines indicate the 95% CI values for each study, whereas the horizontal diameter of the rhombus indicates the 95% CI value for the pooled prevalence. One clinical trial reported the results both on healthy volunteers (Kirkpatrick (1) et al., 1980) and on females with premature labor (Kirkpatrick (2) et al., 1980).

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  Figure 4. Forest plot of the 12 clinical trials (upper panel) and the two observational studies (lower panel) and pooled prevalence (dotted line) of relevant hyperlactatemia (≥5.0 mmol/L) associated with ß2-agonists in the two types of study design, including 95% confidence intervals (95% CI). The size of the squares is related to the weight of each study. The horizontal lines indicate the 95% CI values for each study, whereas the horizontal diameter of the rhombus indicates the 95% CI value for the pooled prevalence. One clinical trial reported the results both on healthy volunteers (Kirkpatrick (1) et al., 1980) and on females with premature labor (Kirkpatrick (2) et al., 1980).

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  Figure 5. Forest plots of pooled prevalence including 95% confidence interval (95% CI) values of relevant hyperlactatemia (≥5.0 mmol/L) associated with selective ß2-agonists, in the different study populations: (a) healthy volunteers; (b) adults with asthma; (c) children with asthma; and (d) females with premature labor. The size of the squares is related to the weight of each study. The horizontal lines indicate the 95% CI values for each study, whereas the horizontal diameter of the rhombus indicates the 95% CI value for the pooled prevalence.

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  Figure 6. Forest plots of pooled prevalence including 95% confidence interval (95% CI) values of relevant hyperlactatemia (≥5.0 mmol/L) associated with selective ß2-agonists, according to the various routes of drug administration: (a) intravenous or subcutaneous; (b) nebulized; (c) both intravenous and nebulized. The size of the squares is related to the weight of each study. The horizontal lines indicate the 95% CI values for each study, whereas the horizontal diameter of the rhombus indicates the 95% CI value for the pooled prevalence. The Egger’s test did not detect a significant publication bias (p > 0.05).