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Table 1 Characteristics of published cases between 1977 and 2014 by survival statusc

From: Serum lactate level and mortality in metformin-associated lactic acidosis requiring renal replacement therapy: a systematic review of case reports and case series

Variable

Total

Alive

Deceased

p-value

[N, proportion of total study population, 253 patients]

[n, proportion of total N] 212 patients

[n, proportion of total N] 41 patients

Demographics

 Age (yr)

64 (52.5–72.5) [252, 99.6%]

64 (54–72.5) [212, 84.1%]

60.5 (42.5–73) [40, 15.9%]

0.40

 Sex (male)

41.8% [249, 98.4%]

38.5% [208, 83.5%]

58.5% [41, 16.5%]

0.02

 Diabetes

91.3% [231, 96.9%]

91.0% [210, 83.0%]

93.0% [43, 17.0%]

0.76

Medical history

 Metformin use

[232, 91.7%]

[196, 84.5%]

[36, 15.5%]

0.11

  Regular medication

76.7%

79.1%

63.9%

 

  Suicidal

22.8%

20.4%

36.1%

 

  Accidental

0.4%

0.5%

0.0%

 

 Estimated metformin dosage at MALAa (g)

2.6 (1.7–5.1) [181, 72.0%]

2.6 (1.7–4.0) [154, 85.0%]

2.6 (1.0–24.5) [27, 14.9%]

0.79

 Predisposing medicationb

97.7% [83, 32.8%]

97.4% [76, 91.6%]

100% [7, 8.2%]

0.67

 Other anti-diabetic agents

95.7% [47, 18.6%]

97.5% [40, 85.1%]

85.7% [7, 14.9%]

0.15

Appropriateness of metformin use

 Creatinine criteria

28.8% [80, 31.6%]

25.0% [68, 85%]

50.0% [12, 15%]

0.08

 eGFR-dosing criteria

57.5% [73, 28.9%]

59.0% [61, 83.6%]

50.0% [12, 16.4%]

0.56

Symptoms & Signs

 Hypothermia

63.4% [93, 36.8%]

64.5% [76, 81.7%]

58.8% [17, 18.3%]

0.66

 Hypotension

50.0% [162, 64.0%]

49.3% [136, 84.0%]

53.9% [26, 16.1%]

0.67

 Abdominal pain

35.6% [149, 59.0%]

37.3% [134. 89.9%]

20.0% [15, 10.1%]

0.18

 Upper GI discomfort

77.4% [155, 61.3%]

78.4% [139, 90.0%]

68.8% [16, 10.3%]

0.38

 Lower GI discomfort

43.7% [151, 59.7%]

44.1% [136, 90.1%]

40.0% [15, 9.9%]

0.76

 Conscious disturbance

56.9% [202, 79.8%]

56.3% [174, 86.1%]

60.7% [28, 13.9%]

0.66

Severity

 Respiratory failure

60.1% [168, 66.4%]

55.1% [138, 82.1%]

83.3% [30, 17.9%]

<0.01

Kidney Injury Profile

[203, 80.2%]

[175, 86.2%]

[28, 13.8%]

0.66

 Acute kidney injury

94.6%

94.9%

92.9%

 

 ESRD

5.4%

5.1%

7.1%

 

Biochemical profile

 Baseline creatinine (mg/dL)

1.2 (1.0–1.5) [104, 41.1%]

1.2 (0.9–1.5) [88, 84.6%]

1.3 (1.1–1.8) [16, 15.4%]

0.26

 Baseline eGFR (ml/min/1.73m2)

50.0 (38.7–71.5) [102, 40.3%]

52.0 (39.6–71.5) [86, 84.3%]

43.5 (37.4–73.4) [16, 15.7%]

0.56

 Peak creatinine (mg/dL)

7.0 (3.3–9.5) [211, 83.4%]

7.2 (4.2–9.7) [183, 86.7%]

3.2 (1.8–7.2) [28, 13.3%]

<0.01

 Trough eGFR (ml/min/1.73m2)

6.1 (4.5–16.4) [207, 81.8%]

5.6 (4.3–11.2) [179, 86.4%]

19.2 (6.1–27.4) [28, 13.5%]

<0.01

 Metformin (mg/L)

45 (27.0–74.4) [85, 33.6%]

43.9 (27.0–71.0) [71, 83.5%]

58 (16–150) [14, 16.5%]

0.61

 Lactate (mmol/L)

18.0 (12.7–23) [234, 92.5%]

17 (12.5–21.2) [198, 84.6%]

22 (14.7–28.4) [36, 15.4%]

<0.01

 Bicarbonate (mmol/L)

5.0 (3.1–8.0) [170, 67.1%]

5.0 (3.0–8.0) [146, 85.9%]

5.6 (4.2–8.5) [24, 14.1%]

0.19

 pH

6.9 (6.8–7.1) [241, 95.3%]

6.9 (6.8–7.1) [203, 84.2%]

6.9 (6.8–7.1) [38, 15.8%]

0.56

 Glucose (mg/dL)

120.9 (36–22 [118, 46.6%]

105.4 (34.3–219.5) [105, 88.1%]

198.5 (72–270) [14, 11.9%]

0.22

 MALA criteria

95.7% [253, 100%]

96.2% [212, 83.8%]

92.7% [41, 16.2%]

0.31

Renal replacement therapy (RRT) profile

 Type of RRT

[251, 99.2%]

[210, 83.7%]

[41, 16.3%]

0.03

  IRRT

33.9%

36.7%

19.5%

 

  PIRRT

13.2%

13.3%

12.2%

 

  CRRT

50.6%

48.6%

61.0%

 

  PD

2.3%

1.4%

7.3%

 

 RRT dose intensification

11.2% [214, 84.6%]

9.8% [184, 86.0%]

20.0% [30, 14.0%]

0.10

 RRT duration (day)

2.0 (1.0–3.0) [162, 64.0%]

2.0 (1.0–4.0) [140, 86.4%]

1.5 (1.0–2.0) [22, 13.6%]

0.11

 Post-event ESRD

3.9% [156, 61.7%]

3.3% [154, 98.7%]

50.0% [2, 1.3%]

<0.01

  1. Abbreviations: CRRT continuous renal replacement therapy, eGFR estimated glomerular filtration rate, IRRT intermittent renal replacement therapy, MALA metformin-associated lactic acidosis, PD peritoneal dialysis, PIRRT prolonged intermittent renal replacement therapy
  2. aDaily metformin dosage (g/day) for patient on regular metformin; total dosage (g) for patients with suicidal or accidental metformin exposure
  3. bMedication that may predispose the development of MALA included nonsteroidal anti-inflammatory drugs, angiotensin-converting-enzyme inhibitors, angiotensin II receptor blockers, diuretics, aspirin, and statins
  4. cCharacteristics of MALA patients are given as percentage in each categorical variable (e.g., male) or median (interquartile range) (e.g., age) in each continuous variable; p-values for categorical and continuous variables are derived from Pearson Chi-squared and Wilcoxon signed rank test, respectively