Interventions for non-oliguric hyperkalaemia in preterm neonates.
BACKGROUND
Non-oliguric hyperkalaemia of the newborn is defined as a plasma potassium level > 6.5 mmol/L in the absence of acute renal failure. Hyperkalaemia is a common complication in the first 48 hours of life in very low birth weight (birth weight < 1500 g) and/or very preterm newborns (< 32 weeks gestational age).


OBJECTIVE
To determine the effectiveness and safety of interventions for non-oliguric hyperkalaemia [for the purpose of this review defined as serum potassium > 6.0 mmol/L ( the clinical setting in which interventions would likely be introduced prior to reaching a grossly abnormal level) and a urine output > 0.5 ml/kg/hour] in preterm or very low birth weight (VLBW) infants during their first 72 hours of life.


METHODS
The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2006) was searched to identify relevant randomised and quasi-randomised controlled trials. The following data bases were searched in June 2006; MEDLINE from 1966, EMBASE from 1980, CINAHL from 1982.


METHODS
Randomised or quasi-randomised controlled trials conducted in preterm and/or VLBW neonates with a diagnosis of non-oliguric hyperkalaemia. The interventions included were those aimed at redistributing serum potassium (sodium bicarbonate or insulin and glucose) or increasing the elimination of potassium from the body [diuretics (any type) or ion exchange resins (any type), or exchange transfusion, or peritoneal dialysis, or salbutamol, or albuterol] or counteracting potential arrhythmias from hyperkalaemia (calcium) vs. placebo or no intervention; or comparing any two of these interventions. The primary outcome measure was 'All cause mortality during initial hospital stay'. Secondary outcomes included common adverse outcomes seen in infants born preterm.


METHODS
The standard review methods of the Cochrane Neonatal Review Group were used. All studies identified as potentially relevant by the literature search were assessed for inclusion in the review by the two authors. The statistical methods included relative risk (RR), risk difference (RD), number needed to treat to benefit (NNTB) or number needed to treat to harm (NNTH) for dichotomous and weighed mean difference (WMD) for continuous outcomes reported with 95% confidence intervals (CI). A fixed effects model was used for meta-analysis. Heterogeneity was assessed using the I squared (I(2 )) statistic.


RESULTS
Three randomized trials, enrolling 74 preterm infants (outcome data available on 71 infants) evaluated interventions for hyperkalemia. Urine output was ascertained only in one study (Hu 1999). In none of the trials could we ascertain that allocation to the comparison groups was concealed. The sample sizes of the three trials were very small with 12 (Malone 1991), 19 (Singh 2002) and 40 infants enrolled (Hu 1999). The intervention and the outcomes assessments could not be blinded to the clinical staff in two trials (Hu 1999; Malone 1991). In one study (Malone 1991), glucose and insulin, compared to cation-exchange resin, caused a reduction in all cause mortality that was of borderline statistical significance: RR 0.18 (95% CI 0.03, 1.15); RD -0.66 (95% CI -1.09, -0.22); NNTB 2 (95% CI 1, 5)]. In the study of Hu (Hu 1999), the incidence of intraventricular haemorrhage > grade 2 was significantly reduced [RR 0.30 (95% CI; 0.10, 0.93); RD -0.35 (95% CI; -0.62, -0.08); NNTB 3 (95% CI; 2, 13). Albuterol inhalation vs. saline inhalation changed serum K+ from baseline at 4 hours [WMD -0.69 mmol/L (95% CI; -0.87, -0.51)] and at 8 hours [WMD -0.59 mmol/L (95% CI; -0.78, -0.40)] after initiation of treatment. No differences were noted in mortality or other clinical outcomes (Singh 2002). No serious side effects were noted with either the combination of insulin and glucose or albuterol inhalation. Other interventions that we listed in our objectives have not been studied to date.


CONCLUSIONS
In view of the limited information from small studies of uncertain quality, no firm recommendations for clinical practice can be made. It appears that the combination of insulin and glucose is preferred over treatment with rectal cation-resin for hyperkalaemia in preterm infants. Both the combination of insulin and glucose and albuterol inhalation deserve further study. The two interventions could possibly be tested against each other. The effectiveness of other potentially effective interventions for non-oliguric hyperkalaemia (diuretics, exchange transfusion, peritoneal dialysis and calcium) have not been tested in randomized controlled trials.
Vemgal
P
P
Ohlsson
A
A
D000420:Albuterol / Q000627:therapeutic use; D005947:Glucose / Q000627:therapeutic use; D006801:Humans; D006947:Hyperkalemia / Q000628:therapy*; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000628:therapy*; D019102:Infant, Very Low Birth Weight; D007328:Insulin / Q000627:therapeutic use; D011137:Polystyrenes / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic
D007328:Insulin; D011137:Polystyrenes; C003321:polystyrene sulfonic acid; D005947:Glucose; D000420:Albuterol