What is the value of bicarbonate in correcting acidosis during newborn resuscitation?


Primary Reviewers: Opiyo Newton, Mike English 1     Secondary Reviewer:W James Tibballs 2

1 KEMRI / Wellcome Trust, Nairobi, Kenya
2 Royal Children’s Hospital, Melbourne

Date posted: 19th April 2006

The World Health Organization has produced guidelines for the management of common illnesses in hospitals with limited resources. This series reviews the scientific evidence behind WHO's recommendations. The WHO guidelines, and more reviews are available at
http://www.who.int/child-adolescent-health/publications/CHILD_HEALTH/PB.htm

This review addresses the question: What is the value of bicarbonate in correcting acidosis during newborn resuscitation?

The WHO Pocketbook of Hospital Care for Children currently makes no recommendation regarding the use of bicarbonate in neonatal resuscitation.


Introduction

Drugs have traditionally been used in newborns who do not respond to adequate ventilation and chest compressions. However, in newborn resuscitation, the emphasis is on adequate ventilation and compressions as drugs will be useless unless the primary problems of hypoxaemia/ischaemia are overcome and there is some degree of circulation. There is still no firm evidence for or against sodium bicarbonate in neonatal resuscitation.


Methods

Articles were identified through Medline searches by use of Pubmed clinical queries.

Using the terms acidosis AND (sodium bicarbonate OR bicarbonate) AND (newborn OR infant OR neonat*) and searching under the clinical filter for systematic reviews, 6 articles were found, 2 of which were relevant. Using the terms (bicarbonate OR acidosis) AND newborn resuscitation under therapy, broad, sensitive (Limits: Publication Date from 1980 to 2005), 85 articles were retrieved, 2 of which were relevant.

The title and abstract of each retrieved study was read by two independent reviewers to assess eligibility; those on the use of bicarbonate in correcting newborn acidosis were selected. The methodological quality of the selected articles were assessed using the Oxford Centre for Evidence Based Medicine Levels of Evidence (CEBM LOE) [1].

Overall, 2 systematic reviews (SRs), 2 randomised control trials (RCTs) and 1 Guideline were identified; 2 were level 1a evidence while two had a LOE of 1b (Table1).

Results

Mortalityas an outcome was reported by one SR [2] and one study [3]; the SR did not find evidence of an effect on mortality (RR 1.39, 95% CI 0.72 to 2.67), RD 0.12, 95% CI -0.12 to 0.36), although only one small RCT measured this effect. Similarly, the composite primary outcome of death or abnormal neurological examination at discharge was similar in both groups (52% vs 54%, p=0.88)[3].

The incidence of intra/peri-ventricular haemorrhage was reported by 2 studies [2][3] one SR [2] did not find evidence of an effect in this outcome (RR 1.24 95% CI 0.47 to 3.28; RD 0.05, 95% CI -0.16 to 0.25). The same SR noted that sodium bicarbonate may cause hypernatraemia and has been associated with intra-ventricular haemorrhage when given rapidly and in large quantities. In one study [3]the incidence of intraventricular haemorrhage (IVH) was similar between groups, 11% vs 10.7%. All the intraventricular bleeds were seen in the preterm neonates.

Arterial blood pH/ excess was reported by one SR [2]and two studies [3][4]. The SR did not find any statitistically significant difference in the rate at which pH was corrected or in the mean arterial blood pH levels after commencing the intervention. The same SR reported failure to improve pH >7.25 and base excess to <-6mmol/litre within 4 hours of treatment. However, this difference was of borderline statistical significant: RR 0.28, 95% CI 0.07-1.11). In the two studies[3][4] the mean pH was between the groups.

There were no significant differences in the other outcomes; encephalopathy, cerebral edema, need for ventilation, duration of respiratory distress, seizures [4] and need for inotropic support, multiple-organ dysfunction [3].

One SR [5] found no studies meeting the criteria for inclusion and concluded that there is no evidence available from RCTs to support or refute the rapid correction of metabolic acidaemia in low birth weight infants as compared with slow or no correction.



Discussion

The findings of this review demonstrate that bicarbonate administration in preterm infants with metabolic acidosis is of no value; mortality was similar between the groups. Similarly, there were no significant differences in abnormal neurological examination, arterial blood pH/base excess, encephalopathy, cerebral edema and need for ventilation.

The use of bicarbonate has potential risks; rapid administration of large quantities of sodium bicarbonate may cause hypernatremia and intra-ventricular haemorrhage. Furthermore, the hyperosmolarity and CO2 generating properties of sodium bicarbonate may be detrimental to myocardial or cerebral function.

The small number of studies found may, however, limit the strengths of the above findings.


Summary

Based on the available evidence (from the current review), bicarbonate administration does not help to improve survival or immediate neurological outcome. Bicarbonate infusion has potential risks. Thus, consideration should be given to revision of current recommendations. The above notwithstanding, there is need for larger studies to confirm the above findings.



Table1: Characteristics of included studies
Please click here to view table in new window


References

  1. http://www.cebm.net/levels_of_evidence.asp#levels. [URL]

  2. Lawn CJ, Weir FJ, McGuire, W. Base Administration or Fluid Bolus for preventing Morbidity and Mortality in Preterm infants with Metabolic Acidosis (Review). The Cochrane Database of Systematic Reviews 2005. [Medline]

  3. Lokesh L, Kumar P, Murki S et al. A Randomized Controlled Trial of Sodium Bicarbonate in Neonatal Resuscitation-Effect on Immediate Outcome. Resuscitation 2004; 60: 219-223. [Medline]

  4. Murki S, Kumar P, Lingappa L, et al. Effect of a Single Dose of Sodium Bicarbonate Given during Neonatal Resuscitation at Birth on the Acid -Base Status on First Day of Life. Journal of Perinatology 2004; 24:696-699. [Medline]

  5. Kecskes Z, Davis MW. Rapid Correction of Early Metabolic Acidaemia in Comparison with Placebo, No Intervention or Slow Correction in LBW Infants (Review). The Cochrane Database of Systematic Reviews. 2001. [Medline]