Recombinant human growth hormone for treating burns and donor sites

Roelf S Breederveld; Wim E Tuinebreijer

doi:10.1002/14651858.CD008990.pub3

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Figure 1

'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.

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Figure 2

Study flow diagram.

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Analysis 1.1

Comparison 1 Comparison of rhGH with placebo, Outcome 1 Healing time of burn wounds in days for adults.

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Analysis 1.2

Comparison 1 Comparison of rhGH with placebo, Outcome 2 Donor site healing time in days for adults.

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Analysis 1.3

Comparison 1 Comparison of rhGH with placebo, Outcome 3 Donor site healing time in days for children.

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Analysis 1.4

Comparison 1 Comparison of rhGH with placebo, Outcome 4 Length of hospital stay.

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Analysis 1.5

Comparison 1 Comparison of rhGH with placebo, Outcome 5 Mortality.

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Analysis 1.6

Comparison 1 Comparison of rhGH with placebo, Outcome 6 Adverse events.

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Analysis 1.7

Comparison 1 Comparison of rhGH with placebo, Outcome 7 Adverse event: Septicaemia in adults.

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Analysis 2.1

Comparison 2 Comparison of rhGH with oxandrolone, Outcome 1 Donor site healing in days.

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Analysis 2.2

Comparison 2 Comparison of rhGH with oxandrolone, Outcome 2 Hyperglycaemia (blood glucose > 225 mg/dl).

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Summary of findings for the main comparison. Recombinant human growth hormone compared with placebo for treating burns and donor sites

Recombinant human growth hormone compared with placebo for treating burns and donor sites
Patient or population: Settings: burn centres Intervention: recombinant human growth hormone Comparison:
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
		Recombinant human growth hormone
Healing time of burn wounds in days for adults		The mean healing time of burn wounds in days for adults in the intervention groups was 9.07 lower (4.39 to 13.76 lower)		36 (2 studies)	⊕⊕⊝⊝ low^1,2,3,4
Donor site healing time in days for adults		The mean donor site healing time in days for adults in the intervention groups was 3.15 lower (1.54 to 4.75 lower)		36 (2 studies)	⊕⊕⊝⊝ low^1,2,3,4
Donor site healing time in days for children		The mean donor site healing time in days for children in the intervention groups was 1.70 lower (0.87 to 2.53 lower)		73 (2 studies)	⊕⊕⊝⊝ low¹³
Mortality in adults and children	Study population⁵		RR 0.53 (0.22 to 1.29)	324 (5 studies)	⊕⊕⊝⊝ low^5,6,7
	7 per 100	4 per 100 (2 to 9)
	Low⁵
	5 per 100	3 per 100 (1 to 6)
	High⁵
	13 per 100	7 per 100 (3 to 17)
Septicaemia in adults	Study population⁸		RR 0.61 (0.31 to 1.22)	267 (4 studies)	⊕⊕⊝⊝ low^1,8,9
	13 per 100	8 per 100 (4 to 16)
	Low⁸
	4 per 100	2 per 100 (1 to 5)
	High⁸
	13 per 100	8 per 100 (4 to 16)
Hyperglycaemia in adults and children	Study population¹⁰		RR 2.65 (1.68 to 4.16)	340 (5 studies)	⊕⊕⊝⊝ low^2,10,11
	11 per 100	30 per 100 (19 to 48)
	Low¹⁰
	0 per 100	0 per 100 (0 to 0)
	High¹⁰
	19 per 100	50 per 100 (32 to 79)
Length of hospital stay in days for adults		The mean length of hospital stay in days for adults in the intervention groups was 12.55 lower (8 to 17.09 lower)		99 (4 studies)	⊕⊕⊝⊝ low^1,12
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio;
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. 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.
¹ Method of randomisation, allocation concealment and blinding not reported. ² Small sample sizes of studies and wide confidence interval of estimate. ³ Patients in study of Sun 1998 had larger and deeper burns. ⁴ In the studies of Sun 1998 and Luo 2000 the way of assessment of the healing time was not reported. ⁵ The low and high risk values are the two extreme numbers of mortality in the control groups from two studies. ⁶ Method of randomisation and blinding in four studies and allocation concealment in five studies not reported. ⁷ Mortality is a rare outcome and the number of included patients in three studies was small. ⁸ The low and high risk values are the two extreme numbers of septicaemia in the control groups from two studies. ⁹ Septicaemia is a rare outcome and the number of included patients in three studies was small. ¹⁰ The low and high risk values are the two extreme numbers of hyperglycaemia in the control groups from two studies. Small sample sizes in four studies and wide confidence interval of estimate. ¹¹ Method of randomisation and blinding in three studies and allocation concealment in five studies not reported. ¹² Small sample sizes in four studies and wide confidence interval of estimate. Patients in control group of study of Lu 2004 received glutamine orally and no placebo injections. ¹³ Method of randomisation in one study and allocation concealment in two studies not reported.

Summary of findings for the main comparison. Recombinant human growth hormone compared with placebo for treating burns and donor sites

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Comparison 1. Comparison of rhGH with placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Healing time of burn wounds in days for adults Show forest plot	2	36	Mean Difference (IV, Fixed, 95% CI)	‐9.07 [‐13.76, ‐4.39]

2 Donor site healing time in days for adults Show forest plot	2	36	Mean Difference (IV, Fixed, 95% CI)	‐3.15 [‐4.75, ‐1.54]

3 Donor site healing time in days for children Show forest plot	2	73	Mean Difference (IV, Fixed, 95% CI)	‐1.70 [‐2.53, ‐0.87]

4 Length of hospital stay Show forest plot	5		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

4.1 Adults	4	99	Mean Difference (IV, Fixed, 95% CI)	‐12.55 [‐17.09, ‐8.00]
4.2 Children	1	28	Mean Difference (IV, Fixed, 95% CI)	‐7.0 [‐29.94, 15.94]
5 Mortality Show forest plot	5	324	Risk Ratio (M‐H, Fixed, 95% CI)	0.53 [0.22, 1.29]

5.1 Adults	4	296	Risk Ratio (M‐H, Fixed, 95% CI)	0.48 [0.19, 1.25]
5.2 Children	1	28	Risk Ratio (M‐H, Fixed, 95% CI)	1.15 [0.08, 16.67]
6 Adverse events Show forest plot	5	340	Risk Ratio (M‐H, Fixed, 95% CI)	2.65 [1.68, 4.16]

6.1 Hyperglycaemia (adults)	4	300	Risk Ratio (M‐H, Fixed, 95% CI)	2.43 [1.54, 3.85]
6.2 Hyperglycaemia (children)	1	40	Risk Ratio (M‐H, Fixed, 95% CI)	10.74 [0.65, 178.65]
7 Adverse event: Septicaemia in adults Show forest plot	4	267	Risk Ratio (M‐H, Fixed, 95% CI)	0.61 [0.31, 1.22]

Comparison 1. Comparison of rhGH with placebo

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Comparison 2. Comparison of rhGH with oxandrolone

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Donor site healing in days Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

2 Hyperglycaemia (blood glucose > 225 mg/dl) Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 2. Comparison of rhGH with oxandrolone

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