Low versus high haemoglobin concentration threshold for blood transfusion for preventing morbidity and mortality in very low birth weight infants
Low versus high haemoglobin concentration threshold for bloodtransfusion for preventing morbidity andmortality in very low birth weight infants: a Cochrane Review Clinical www.cochranejournalclub.com
Clinical question• When should we transfuse low birthweight babies for anemia of prematurity? Source: Whyte R, Kirpalani H. Low versus high haemoglobin concentration threshold for blood transfusion for preventing morbidity and mortality in very low birth weight infants. Cochrane Database of Systematic Reviews 2011, Issue 11. Art. No.: CD000512. DOI: 10.1002/14651858.CD000512.pub2. www.cochranejournalclub.com 2
Context• Haemoglobin levels fall after birth but this is greatly accelerated in very low birthweight babies.• In some parts of the world, nearly all babies that weigh under 1000g at birth receive a blood transfusion, and most receive several.• Ideally, blood transfusions should be given when the baby’s haemoglobin reaches the lowest level compatible with health, safety, and good growth and development. However, this value is unknown and, so, different strategies are used to decide when to transfuse.• Maintaining a high haemoglobin level (liberal strategy) may lead to excessive repeated transfusion and its complications.• Maintaining a low haemoglobin level (restrictive strategy) may lead to cardiac failure, death or neurodevelopmental impairment. www.cochranejournalclub.com 3
Methods• Searches were conducted in 2010 and 2011 of the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and Science Citation Index. Prospectively registered trials were searched for in the U.S. National Institutes of Health’s Clinicaltrials.gov and conference proceedings were checked for unpublished trials.• Data were extracted on the inclusiveness of the population, masking of allocation, masking of intervention, completeness of follow-up and masking of outcome assessment.• Meta-analyses used the random effects model because of marked clinical and, often, statistical heterogeneity. www.cochranejournalclub.com 4
PICO(S) to assess eligible studies• Participants: Infants of <1500 g birthweight or <32 weeks gestational age; who were less than 1 week old and receiving any level of intensive care.• Comparison 1: Restrictive versus liberal transfusion protocols (i.e. low haemoglobin threshold versus high haemoglobin threshold for transfusion).• Comparison 2: Restrictive versus liberal strategy (i.e. withhold transfusion until clinical signs of anaemia versus administer earlier transfusion at a set level of haemoglobin or haematocrit).• Primary outcomes: Death before a defined time, composite of death or severe morbidity, and composite of death or severe adverse neurosensory outcome at age 18 months.• Studies: Randomized and quasi-randomized trials. www.cochranejournalclub.com
Description of eligible studies• Four studies with a total of 651 infants were included in comparison 1 (restrictive versus liberal transfusion protocols), with three reporting a primary outcome of numbers of transfusions (a secondary outcome for this review) and one reporting a primary outcome of death or serious adverse outcome.• One study (56 infants) was included in comparison 2 (restrictive versus liberal strategy). It reported clinical events up to discharge, but did not report death or serious morbidity. www.cochranejournalclub.com
Results: comparison 1• There were no significant differences between the transfusion protocols on death (see slide), death or severe morbidity at hospital discharge, or death or impaired neurodevelopmental outcome at 18-21 months.• Restrictive transfusion protocols led to a small decrease in transfusion frequency and haemoglobin levels compared to liberal transfusion protocols. The relative risk for transfusion was 0.95 (95% confidence interval: 0.91-1.00, p=0.041) and the mean number of transfusions per baby was 1.12 lower (95% CI: 0.49-1.75, p<0.001). www.cochranejournalclub.com 7
Comparison 1: Death before discharge www.cochranejournalclub.com 8
Results: comparison 1 Cognitive function• In the one study that reported neurosensory impairment at 18-21 months of age, the effect on cognitive function was close to favoring the liberal strategy in an unadjusted analysis of the originally planned outcome (RR: 1.39; 0.90-2.13), and statistically significantly better when a less severe definition cognitive function was used (RR: 1.32; 1.00-1.74).• This apparent benefit of the liberal strategy was strengthened when the original researchers adjusted their analysis for gestational age (RR: 1.28; 0.84-1.94 and 1.37; 1.07-1.76, respectively). www.cochranejournalclub.com 9
Results: comparison 2 • There were no significant differences in short-term health outcomes, when clinical findings rather than haemoglobin levels were used to drive transfusions. Topped up at Clinical Effect (95% Cl) 100 g/l signsDeath or death / morbidity Not reportedInfants with apnea 17/26 19/30 RR 0.97 (0.66 to1.43)Time to regain birthweight 26 days 27 days MD 1 (-5 to 6)Length of hospitalization 51 days 49 days MD -2 (-13 to 9)Hospital costs $3430 $3642 MD $212 (446 to 870)Discharge haemoglobin 118 g/l 91 g/l MD -26 g/l (-35 to -17) www.cochranejournalclub.com 11
Conclusions• The use of restrictive as compared to liberal haemoglobin transfusion thresholds in very low birthweight infants results in modest reductions in exposure to transfusion and in haemoglobin levels.• There is no evidence that using a lower haemoglobin transfusion threshold (using the limits tested in these trials) has an effect on mortality, major morbidities or on survival without major morbidity in very low birth weight infants.• As the restrictive levels used were more similar among trials, a summarised approximation of the lower thresholds evaluated is presented in the following table. Safety at haemoglobin levels below these lower limits has not been evaluated and these should be maintained until further evidence is available. www.cochranejournalclub.com 12
Approximate lower limits for haemoglobin andhaematocrit thresholds evaluated in this review Postnatal age Respiratory No respiratory support support Haemoglobin g/l (Haematocrit %) <7 days 115 (35%) 100 (30%) 7-14 days 100 (30%) 85 (25%) 14-21 days 85 (25%) 75 (23%) www.cochranejournalclub.com 13
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