Erythropoietin plus iron versus control treatment including placebo or iron for preoperative anaemic adults undergoing non‐cardiac surgery

Lutz Kaufner; Christian von Heymann; Anne Henkelmann; Nathan L Pace; Stephanie Weibel; Peter Kranke; Joerg J Meerpohl; Ravi Gill

doi:10.1002/14651858.CD012451.pub2

Scolaris Content Display Scolaris Content Display

Contenido relacionado

Ir a:

Revisiones y protocolos relacionados
Guías
Temas

Revisiones y protocolos relacionados

Topics

Temas

Figure 1

Study flow diagram.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 2

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

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 3

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 4

Funnel plot of comparison: 1 rHuEPO versus control treatment, outcome: 1.1 Transfusion.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 5

Forest plot of comparison: 1 rHuEPO versus control treatment, outcome: 1.1 Transfusion.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 6

Forest plot of comparison: 1 rHuEPO versus control treatment with or without iron, outcome: 1.2 Haemoglobin concentration immediately prior to surgery (g/dL).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 7

Forest plot of comparison: 1 rHuEPO versus control treatment with or without iron, outcome: 1.3 Number of RBC units transfused per participant (intraoperative to 5 days postoperative).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 8

Forest plot of comparison: 1 rHuEPO versus control treatment with or without iron, outcome: 1.4 Mortality (within 30 days after surgery).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 9

Forest plot of comparison: 1 rHuEPO versus control treatment with or without iron, outcome: 1.5 Adverse events (number of participants with any adverse event).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 10

Forest plot of comparison: 1 rHuEPO versus control treatment with or without iron, outcome: 1.6 Length of hospital stay.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.1

Comparison 1: rHuEPO versus control treatment with or without iron, Outcome 1: Transfusion (measured in participants during or up to 5 days after operation)

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.2

Comparison 1: rHuEPO versus control treatment with or without iron, Outcome 2: Haemoglobin concentration immediately prior to surgery (g/dL)

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.3

Comparison 1: rHuEPO versus control treatment with or without iron, Outcome 3: Number of RBC units transfused per participant (intraoperative to 5 days postoperative)

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.4

Comparison 1: rHuEPO versus control treatment with or without iron, Outcome 4: Mortality (within 30 days after surgery)

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.5

Comparison 1: rHuEPO versus control treatment with or without iron, Outcome 5: Adverse events (number of participants with any adverse event)

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.6

Comparison 1: rHuEPO versus control treatment with or without iron, Outcome 6: Length of hospital stay

Ir a la figura de la revisiónAbrir en una pestaña nueva

Summary of findings 1. rHuEPO with iron compared to control treatment with or without iron in preoperative anaemic adults undergoing non‐cardiac surgery

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Quality of the evidence (GRADE)
rHuEPO with iron compared to control treatment with or without iron in preoperative anaemic adults undergoing non‐cardiac surgery
Patient or population: adult participants, irrespective of gender and type of non‐cardiac surgery, with mild or severe preoperative anaemia Setting: hospital (Europe, Canada, and South Korea) Intervention: rHuEPO subcutaneously or intravenously with iron supplementation (enteral or parenteral) Comparison: control treatment
Outcomes	Risk with control treatment	Risk with rHuEPO + iron	Relative effect (95% CI)	№ of participants (studies)	Quality of the evidence (GRADE)
Transfusion (measured in participants during or up to 5 days after operation)	444 per 1000	231 per 1000 (200 to 262)	RR 0.55 (0.38 to 0.80)	1880 (12 RCTs)	⊕⊕⊕⊝ MODERATE ¹
Subgroup Hb concentration immediately prior to surgery (g/dL) rHuEPO high (500 to 600 IU/kg BW)	The mean Hb ‐ rHuEPO high 500 to 600 IU/kg BW ranged across control groups from 10.7 to 12.4 g/dL.	MD 1.87 (1.26 higher to 2.49 higher)	‐	852 (3 RCTs)	⊕⊕⊝⊝ LOW^{1 2}
Subgroup Hb concentration immediately prior to surgery (g/dL) rHuEPO low (150 to 300 IU/kg BW)	The mean Hb ‐ rHuEPO low 150 to 300 IU/kg BW ranged across control groups from 11.9 to 12.1 g/dL.	MD 0.11 (0.46 lower to 0.69 higher)	‐	334 (4 RCTs)	⊕⊕⊝⊝ LOW^{1 2}
Number of RBC units transfused per participant (intraoperative to 5 days postoperative)	The mean number of RBC units ranged across control groups from 1.28 to 2.69.	MD 0.09 lower (0.23 lower to 0.05 higher)	‐	1420 (6 RCTs)	⊕⊕⊕⊝ MODERATE³
Mortality (within 30 days after surgery)	45 per 1000	54 per 1000 (18 to 165)	RR 1.18 (0.39 to 3.63)	230 (2 RCTs)	⊕⊕⊕⊝ MODERATE⁴
Adverse events (number of participants with any adverse event)	88 per 1000	81 per 1000 (59 to 111)	RR 0.93 (0.68 to 1.28)	1722 (10 RCTs)	⊕⊕⊕⊝ MODERATE⁴
Length of hospital stay	The mean length of hospital stay ranged across control groups from 7 to 13.	MD 1.07 lower (4.12 lower to 1.98 higher)	‐	293 (3 RCTs)	⊕⊝⊝⊝ LOW^{1 4}
*The risk in the intervention group (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). BW: body weight; CI: confidence interval; Hb: haemoglobin; IU: international unit; MD: mean difference; RBC: red blood cells; RCT: randomized controlled trial; rHuEPO: recombinant human erythropoietin; RR: risk ratio
GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate quality: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low quality: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low quality: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.
¹Downgraded 1 level due to inconsistency. Unexplained inconsistency, with widely different point estimates. ²Downgraded 1 level due to risk of bias (study limitations) (sensitivity analysis). ³Downgraded 1 level due to differences between studies regarding counting units (imprecision). ⁴Downgraded 1 level due to imprecision: the 95% CI is consistent with both important benefit and harm.

Summary of findings 1. rHuEPO with iron compared to control treatment with or without iron in preoperative anaemic adults undergoing non‐cardiac surgery

Ir a la tabla de la revisión

Table 1. Sensitivity analysis, risk of bias

Outcome	Statistical method	All studies		Trials with low risk of bias for random sequence generation, blinding, incomplete outcome data
Outcome	Statistical method	Studies	Effect estimate (95% CI)	Studies	Effect estimate (95% CI)
Transfusion (measured in participants during or up to 5 days after operation)	Risk ratio (MH Random 95% CI)	12	RR 0.55 (0.38; 0.80)	5	RR 0.79 (0.61; 1.01)
Hb concentration preoperatively (directly before surgery)	Mean difference (IV Random 95% CI)	7	MD 0.97 (0.07; 1.87)	2	MD −0.31 (−0.69; 0.08)
Subgroup Hb concentration immediately prior to surgery (g/dL) rHuEPO high (500 to 600 IU/kg BW)	Mean difference (IV Random 95% CI)	3	MD 1.87 (1.26; 2.49)	0	‐
Subgroup Hb concentration immediately prior to surgery (g/dL) rHuEPO low (150 to 300 IU/kg BW)	Mean difference (IV Random 95% CI)	4	MD 0.11 (−0.46; 0.69)	2	MD 0.15 (−1.28; 1.58)
Number of RBC units transfused per participant (intraoperative to 5 days postoperative)	Mean difference (IV Random 95% CI)	6	MD −0.09 (−0.23; 0.05)	3	MD −0.09 (−0.27; 0.09)
Mortality (within 30 days after surgery)	Risk ratio (MH Random 95% CI)	2	RR 1.18 (0.39; 3.63)	1	RR 1.25 (0.35; 4.52)
Adverse events (number of participants with any adverse event)	Risk ratio (MH Random 95% CI)	10	RR 0.97 (0.70; 1.34)	5	RR 0.92 (0.63; 1.33)
Length of hospital stay	Mean difference (IV Random 95% CI)	3	MD −1.07 (−4.12; 1.98)	2	MD 0.65 (0.05; 1.25)
BW: body weight; CI: confidence interval; Hb: haemoglobin; IU: international unit; IV: inverse variance; MD: mean difference; MH: Mantel‐Haenszel; RBC: red blood cells; rHuEPO: recombinant human erythropoietin; RR: risk ratio

Table 1. Sensitivity analysis, risk of bias

Ir a la tabla de la revisión

Table 2. Sensitivity analysis (random‐effects model/fixed‐effect model)

Outcome	Statistical heterogeneity (I²)	Fixed‐effect (95% CI)	Random‐effects (95% CI)
Transfusion (measured in participants during or up to 5 days after operation)	84%	RR 0.52 (0.45, 0.59)	RR 0.55 (0.38, 0.45)
Hb concentration preoperatively (directly before surgery)	97%	MD 1.58 (1.47, 1.70)	MD 0.97 (0.07, 1.87)
Subgroup Hb concentration immediately prior to surgery (g/dL) rHuEPO high (500 to 600 IU/kg BW)	69%	MD −0.11 (−0.39, 0.17)	MD 0.11 (−0.46, 0.69)
Subgroup Hb concentration immediately prior to surgery (g/dL) rHuEPO low (150 to 300 IU/kg BW)	89%	MD 1.94 (1.81, 2.07)	MD 1.87 (1.26, 2.49)
Number of RBC units transfused per participant (intraoperative to 5 days postoperative)	0%	MD −0.09 (−0.23, 0.05)	MD −0.09 (−0.23, 0.05)
Mortality (within 30 days after surgery)	0%	RR 1.19 (0.39, 3.63)	RR 1.18 (0.39, 3.63)
Adverse events (number of participants with any adverse event)	0%	RR 0.93 (0.68, 1.28)	RR 0.97 (0.70, 1.34)
Length of hospital stay	87%	MD 0.59 (−0.00, 1.18)	MD −1.07 (−4.12, 1.98)
BW: body weight; CI: confidence interval; Hb: haemoglobin; IU: international unit; MD: mean difference; RBC: red blood cells; rHuEPO: recombinant human erythropoietin; RR: risk ratio

Table 2. Sensitivity analysis (random‐effects model/fixed‐effect model)

Ir a la tabla de la revisión

Comparison 1. rHuEPO versus control treatment with or without iron

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1.1 Transfusion (measured in participants during or up to 5 days after operation) Show forest plot	12	1880	Risk Ratio (M‐H, Random, 95% CI)	0.55 [0.38, 0.80]

1.2 Haemoglobin concentration immediately prior to surgery (g/dL) Show forest plot	7	1186	Mean Difference (IV, Random, 95% CI)	0.97 [0.07, 1.87]

1.2.1 rHuEPO low 150 to 300 IU/kg body weight	4	334	Mean Difference (IV, Random, 95% CI)	0.11 [‐0.46, 0.69]
1.2.2 rHuEPO high 500 to 600 IU/kg body weight	3	852	Mean Difference (IV, Random, 95% CI)	1.87 [1.26, 2.49]
1.3 Number of RBC units transfused per participant (intraoperative to 5 days postoperative) Show forest plot	6	1420	Mean Difference (IV, Fixed, 95% CI)	‐0.09 [‐0.23, 0.05]

1.4 Mortality (within 30 days after surgery) Show forest plot	2	230	Risk Ratio (M‐H, Fixed, 95% CI)	1.19 [0.39, 3.63]

1.5 Adverse events (number of participants with any adverse event) Show forest plot	10	1722	Risk Ratio (M‐H, Fixed, 95% CI)	0.93 [0.68, 1.28]

1.6 Length of hospital stay Show forest plot	3	293	Mean Difference (IV, Random, 95% CI)	‐1.07 [‐4.12, 1.98]

Comparison 1. rHuEPO versus control treatment with or without iron

Ir a la tabla de la revisión

The Cochrane Library

Scolaris Language Selector Scolaris Language Selector

Idioma de la Revisión Cochrane

Idioma de la web

Scolaris Content Language Banner Portlet Scolaris Content Language Banner Portlet