Background
Methods
Protocol and guidance
Study selection
Inclusion criteria
Exclusion criteria
Missing data
Duplicate publications
Information sources and search strategy
Study selection
Data collection process
Outcomes and prioritization
Subgroup and sensitivity analyses
Risk of bias and quality of evidence
Data synthesis
Results
Search results and characteristics of included studies
Author | Year | Size (n) | Centers (n) | Country | Setting | Age, median (IQR) | |
---|---|---|---|---|---|---|---|
Tight control | Usual control | ||||||
Vlasselaers et al. [12] | 2009 | 700 | 1 | Belgium | Mixed with 75% cardiac surgery | 1.4 (0.3–5.5) | 1.3 (0.3–4.6) |
Jeschke et al. [27] | 2010 | 239 | 1 | USA | Burns | 7.7 (5.2)a | 10.8 (5.4)a |
Agus et al. [14] | 2012 | 980 | 2 | USA | Cardiac surgery | 0.4 (0.2–0.8) | 0.4 (0.2–0.9) |
Alsweiler et al. [17] | 2012 | 88 | 1 | New Zealand | Preterm | Preterm babies | |
Macrae et al. [13] | 2014 | 1369 | 13 | UK | Mixed with 60% cardiac surgery | 0.5 (0.1–2.7) | |
Agus et al. [15] | 2017 | 713 | 35 | USA | Mixed without cardiac surgery | 5.5 (1.4–12.5) | 6.7 (1.7–12.8) |
Risk of bias and quality of evidence
Outcome | Number of children (studies) | Effect | Qualitya | Importance | |
---|---|---|---|---|---|
Relative effect, OR (95% CI) | Absolute risk (95% CI) | ||||
Hospital mortality | 4021 (6 studies) | 0.95 (0.62–1.45) | 3 fewer per 1000 (from 20 fewer to 23 more) | ⊕ ⊕ ⊕⊝ moderateb | Critical |
Severe hypoglycemia (glucose < 40 ml/dl) | 3835 (5 studies) | 4.11 (2.67–6.32) | 42 more per 1000 (from 23 more to 69 more)b | ⊕ ⊕ ⊕ ⊕ high | Critical |
Any hypoglycemia (glucose < 60 mg/dl) | 3747 (4 studies) | 4.57 (2.24–9.33) | 157 more per 1000 (from 61 more to 299 more) | ⊕ ⊕ ⊕ ⊕ highb | Critical |
Dialysis | 3049 (3 studies) | 0.63 (0.45–0.86) | 24 fewer per 1000 (from 9 fewer to 36 fewer) | ⊕ ⊕ ⊕ ⊕ highb | Important |
Seizures | 3047 (3 studies) | 0.98 (0.59–1.63) | 0 fewer per 1000 (from 8 fewer to 12 more) | ⊕ ⊕ ⊝⊝ lowb,c | Important |
Sepsis | 4021 (6 studies) | 0.83 (0.63–1.08) | 20 fewer per 1000 (from 45 fewer to 9 more) | ⊕ ⊕ ⊕ ⊕ high | Important |
Primary outcome: hospital mortality
Secondary outcomes: hypoglycemia, sepsis, new need for dialysis, seizures
Subgroup analyses
Subgroup of trialsa | Number of trials | Event number/total number (%) | OR (95% CI) | I2 (%) | |
---|---|---|---|---|---|
Tight control | Usual control | ||||
Mortality | |||||
Very tight control | 2 | 12/392 (3.1) | 19/369 (5.1) | 1.11 (0.12–10.60) | 73 |
Moderately tight control | 4 | 98/1582 (6.2) | 94/1651 (5.7) | 1.10 (0.81–1.49) | 0 |
Overall | 6 | 110/1974 (2.9) | 113/2047 (5.5) | 0.95 (0.62–1.45) | 40 |
Any hypoglycemia (< 60 mg/dl) | |||||
Very tight control | 2 | 112/392 (28.6) | 17/396 (4.3) | 9.35 (1.49–58.83) | 88 |
Moderately tight control | 3 | 259/1533 (16.9) | 99/1514 (6.5) | 3.00 (2.07–4.34) | 54 |
Overall | 5 | 371/1925 (19.3) | 116/1910 (6.1) | 4.39 (2.39–8.06) | 83 |
Severe hypoglycemia (< 40 mg/dl) | |||||
Very tight control | 2 | 24/392 (6.1) | 5/396 (8.7) | 5.23 (1.95–14.00) | 0 |
Moderately tight control | 3 | 85/1533 (5.5) | 22/1514 (1.5) | 3.88 (2.41–6.26) | 0 |
Overall | 5 | 109/1925 (18.4) | 27/1910 (5.8) | 4.11 (2.67–6.32) | 0 |
Sepsis | |||||
Very tight control | 2 | 121/392 (30.9) | 143/396 (36.1) | 1.01 (0.43–2.41) | 73 |
Moderately tight control | 4 | 95/1582 (6.0) | 132/1651 (8.0) | 0.81 (0.59–1.12) | 18 |
Overall | 6 | 216/1947 (11.1) | 275/2047 (13.4) | 0.83 (0.63–1.08) | 32 |
Dialysis | |||||
Very tight control | 1 | 2/349 (0.6) | 6/351 (1.7) | 0.33 (0.07–1.65) | NA |
Moderately tight control | 2 | 67/1184 (5.7) | 97/1165 (8.3) | 0.64 (0.46–0.89) | 0 |
Overall | 3 | 69/1533 (4.5) | 103/1516 (6.8) | 0.63 (0.45–0.86) | 0 |
Seizures | |||||
Very tight control | 0 | NA | NA | NA | NA |
Moderately tight control | 3 | 31/1533 (2.0) | 31/1514 (2.0) | 0.98 (0.59–1.63) | 51 |
Overall | 3 | 31/1533 (2.0) | 31/1514 (2.0) | 0.98 (0.59–1.63) | 51 |
Subgroup of trials | Number of trials | Event number/total number (%) | OR (95% CI) | I2 (%) | |
---|---|---|---|---|---|
Tight control | Usual control | ||||
Mortality | |||||
Noncardiac surgery | 3 | 57/441 (12.9) | 45/394 (9.2) | 1.29 (0.52–3.23) | 29 |
Cardiac surgery | 3 | 53/1533 (3.5) | 64/1516 (4.2) | 0.79 (0.50–1.26) | 26 |
Overall | 6 | 110/1974 (5.6) | 113/2047 (5.0) | 0.95 (0.62–1.45) | 40 |
Any hypoglycemia (< 60 mg/dl) | |||||
Noncardiac surgery | 2 | 104/342 (30.4) | 45/394 (11.4) | 2.97 (2.01–4.41) | 0 |
Cardiac surgery | 3 | 267/1533 (17.4) | 71/1516 (4.7) | 5.72 (1.95–16.73) | 91 |
Overall | 5 | 371/1925 (19.3) | 116/1910 (6.1) | 4.39 (2.39–8.06) | 83 |
Severe hypoglycemia (< 40 mg/dl) | |||||
Noncardiac surgery | 2 | 25/392 (6.4) | 9/394 (2.3) | 2.95 (1.35–6.42) | 0 |
Cardiac surgery | 3 | 84/1533 (5.5) | 18/1516 (1.2) | 4.76 (2.84–7.97) | 91 |
Overall | 5 | 109/1925 (18.4) | 27/1910 (5.8) | 4.11 (2.67–6.32) | 0 |
Sepsis | |||||
Noncardiac surgery | 3 | 52/441 (11.8) | 79/531 (14.9) | 0.82 (0.55–1.22) | 67 |
Cardiac surgery | 3 | 164/1633 (10.0) | 196/1516 (19.2) | 0.79 (0.62–1.00) | 0 |
Overall | 6 | 216/1947 (11.0) | 275/2047 (13.4) | 0.83 (0.63–1.08) | 32 |
Dialysis | |||||
Noncardiac surgery | 3 | 69/1533 (4.5) | 103/1516 (6.8) | 0.63 (0.45–0.86) | 0 |
Cardiac surgery | 0 | NA | NA | NA | NA |
Overall | 3 | 69/1533 (4.5) | 103/1516 (6.8) | 0.63 (0.45–0.86) | 0 |
Seizures | |||||
Noncardiac surgery | 1 | 5/349 (1.4) | 10/349 (2.9) | 0.49 (0.17–1.46) | NA |
Cardiac surgery | 2 | 26/1533 (1.7) | 21/1165 (1.8) | 1.22 (0.68–2.18) | 50 |
Overall | 3 | 31/1533 (2.0) | 31/1514 (2.0) | 0.98 (0.59–1.63) | 51 |
Subgroup of trials | Number of trials | Event number/total number (%) | OR (95% CI) | I2 (%) | |
---|---|---|---|---|---|
Tight control | Usual control | ||||
Mortality | |||||
Using CGM | 3 | 97/1553 (12.9) | 86/1514 (9.2) | 1.13 (0.83–1.53) | 0 |
Not using CGM | 3 | 13/441 (3.5) | 27/533 (4.2) | 0.70 (0.18–2.69) | 49 |
Overall | 6 | 110/1974 (5.6) | 113/2047 (5.0) | 0.95 (0.62–1.45) | 40 |
Any hypoglycemia (< 60 mg/dl) | |||||
Using CGM | 3 | 259/1533 (30.4) | 99/1514 (11.4) | 3.00 (2.07–4.36) | 54 |
Not using CGM | 2 | 24/392 (6.1) | 5/396 (4.7) | 5.23 (1.95–4.00) | 0 |
Overall | 5 | 371/1925 (19.3) | 116/1910 (6.1) | 4.39 (2.39–8.06) | 83 |
Severe hypoglycemia (< 40 mg/dl) | |||||
Using CGM | 2 | 85/1533 (30.4) | 22/1514 (11.4) | 3.88 (2.41–6.26) | 0 |
Not using CGM | 3 | 112/392 (28.6) | 17/396 (4.7) | 9.35 (1.49–58.83) | 88 |
Overall | 5 | 109/1925 (18.4) | 27/1910 (5.8) | 4.11 (2.67–6.32) | 0 |
Sepsis | |||||
Using CGM | 3 | 91/1553 (12.9) | 101/1514 (9.2) | 0.88 (0.66–1.18) | 0 |
Not using CGM | 3 | 125/441 (3.5) | 174/533 (4.2) | 0.76 (0.18–2.69) | 69 |
Overall | 6 | 216/1947 (11.0) | 275/2047 (13.4) | 0.83 (0.63–1.08) | 32 |
Dialysis | |||||
Using CGM | 2 | 67/1184 (4.5) | 97/1165 (6.8) | 0.64 (0.46–0.89) | 0 |
Not using CGM | 1 | 2/349 (4.5) | 6/351 (6.8) | 0.33 (0.07–1.65) | NA |
Overall | 3 | 69/1533 (4.5) | 103/1516 (6.8) | 0.63 (0.45–0.86) | 0 |
Seizures | |||||
Using CGM | 3 | 31/1533 (2.0) | 31/1514 (2.0) | 0.98 (0.59–1.63) | 51 |
Not using CGM | 0 | NA | NA | NA | NA |
Overall | 3 | 31/1533 (2.0) | 31/1514 (2.0) | 0.98 (0.59–1.63) | 51 |
Discussion
Findings and interpretations
Compared with other studies
Strengths and limitations
Conclusions
-
Tight glycemic control does not appear to improve mortality in critically ill children.
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Tight glycemic control reduces a new need for dialysis in critically ill children.
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Tight glycemic control greatly increases the risk of hypoglycemia in critically ill children.