Treatment of non-oliguric hyperkalaemia with inhaled salbutamol in premature infants with severe respiratory distress syndrome

Non-oliguric hyperkalaemia (NOHK) in neonates is defined as a plasma potassium level > 6.5 mmol/L in the presence of urine output ≥ 1 mL/kg/h during the first 72 hours of life. It is characterized by a rapid rise of serum potassium to excessively high values, a high risk of cardiac arrhythmias and no occurrence after 72 hours of birth. NOHK commonly occurs in premature neonates, especially in those with a gestational age <28 weeks, with only a few reports of this entity in moderate or late preterm neonates. The effectiveness and safety of different treatments for NOHK is uncertain and currently there is no firm treatment recommendation. We describe the case of a moderately premature neonate (32+ 2 weeks gestation), with severe neonatal respiratory distress syndrome, who developed NOHK that was treated with inhaled salbutamol. When salbutamol is used for the treatment of NOHK, an initial paradoxical rise in potassium levels should always be taken into account to avoid cardiac arrhythmias.


INTRODUCTION
Non-oliguric hyperkalaemia (NOHK) is a common and serious complication in premature neonates, especially in those with very low birth weight (<1500g) and/or very preterm (≤28 weeks gestational age).
(1,2) The reported incidence of NOHK is 11% to 52%.(3)(4)(5) With increased survival of premature neonates, NOHK is becoming more common.(5) Reversible hyperkalaemia in premature neonates was first reported in 1959 by Usher.(6) Characteristics of NOHK as we know it today were described by Perkkiö and Räihä (7) in 1977.NOHK is defined as a serum potassium ≥ 6.5mmol/L during the first 72 hours of life in a non-haemolysed arterial or venous blood sample in the presence of urine output ≥ 1 mL/kg/h.(2) It is characterized by a rapid rise in serum potassium to excessively high values after birth in premature neonates, a high risk of cardiac arrhythmias and no occurrence after 72 hours of birth.The pathophysiology of NOHK is not completely understood.Current evidence suggests that it is mainly due to a shift in potassium from the intra-into the extracellular spaces because of immature function of the Na+/K+ ATPase in premature neonates.(5,(8)(9)(10) More than 80% of neonates with NOHK are extremely low birth weight (ELBW) infants with gestational age below 28 weeks.(4) Few cases have been reported in moderate to late preterm neonates.(1,4) The effectiveness and safety of different treatment options for NOHK is uncertain and currently there is no firm treatment recommendation.(2) We describe a case of a moderately premature neonate (32+2 weeks gestation) with severe neonatal respiratory distress syndrome, who developed NOHK that was treated with inhaled salbutamol.

CASE REPORT
A premature girl was admitted to the interdisciplinary neonatal and paediatric intensive care unit (ICU) of the Department of Paediatric Surgery and Intensive Care, University Medical Centre Ljubljana, Slovenia because of respiratory distress.Due to incipient premature labour, the mother received a course of antenatal steroids (betamethasone) 16 days before delivery.The girl was delivered at 32 weeks and 2 days gestational age at the regional maternity hospital by caesarean section after minor antepartum haemorrhage because of placenta praevia and persistent foetal tachycardia.The girl weighed 1900 g and appeared vigorous, with spontaneous respirations; the 1-minute and 5-minute Apgar scores were 8 and 9, respectively.Haemoglobin level at birth was 126 g/L, which was an indicator that she suffered some blood loss because of placenta praevia.Shortly after birth she developed tachypnoea with shallow respirations and retractions.Features of severe hyaline membrane disease were found on chest X-ray.Endotracheal intubation was performed and assisted  1).Urinary output was monitored closely and was high -early polyuria (first day: 3.5 ml/kg/h, second day 6.3 ml/kg/h, third day 5.6 ml/kg/h, fourth day 7.8 ml/kg/h, fifth day 7 ml/kg/h).There was hyperphosphataemia, hypocalcaemia and hypomagnesaemia.Due to early hyperglycaemia she received an insulin infusion for 7 h during the first day of life.After discontinuation of the insulin infusion, glucose levels were below 10 mmol/L.At 42 hours of age K+ rose to 5.8 mmoL/L.She was receiving only potassium-free infusions.As seen in figure 1, a further increase in K+ occurred with the maximum level reached at 53 hours of age (7.9 mmol/L).When the K+ level reached 7.8 mmol/L, tall peaked T waves were noticed on the ECG.The baby was already receiving supplementation with calcium gluconate every 6 hours due to low levels of ionized calcium.Despite this, an additional dose of calcium gluconate 10% 100 mg (1ml)/kg was administered and shortly thereafter the ECG normalized.When the K+ level reached 7.8 mmol/L, salbutamol was given by nebulizer (400 μg = 200 μg/ kg).The dose was repeated every 2 hours until the K+ level fell below 5 mmol/L, thereafter the dose was repeated every 4 hours for another 12 hours.The potassium level slightly increased after the first inhalation of salbutamol (figure 1), but declined rapidly thereafter and reached 6.0 mmol/L within 6 hours following the first inhalation.Changes in heart rate and blood pressure after salbutamol inhalation are shown in table 2.

DISCUSSION
Even though NOHK is most common in ELBW infants with a gestational age < 28 weeks (4) and there are only a few reports of this entity in late preterm infants, (1,4) our report emphasizes that NOHK can oc-

SIGNA VITAE 2018; 14(1): 88-91
Laboratory parameters were regularly checked after birth (table 1).Potassium serum concentrations (K+) were in the low normal range for the first 36 hours of life, despite rather low pH values (table 1, figure

Table 1 .
Blood gas, electrolytes, urea, creatinine and glucose levels at different times after birth.Samples at postnatal age of 4 minutes and 1h are umbilical venous blood, all other samples are arterial.
(5)+, calcium ion; creat., creatinine; glu., glucose; HCO3, hydrogen carbonate; iCa, ionized calcium; K+, potassium ion; Mg++, magnesium ion; P, phosphate; PCO2, partial pressure of carbon dioxide.cur in more mature preterm infants.The characteristic feature of NOHK is a rapid rise in serum K+ to high values during the first 72 h of life.(5)Inourinfant, as seen in Figure1, K+ increased steeply between 42 and 52 hours of age.Low to normal K+ levels during the first 36 h of life in our

Table 2 .
Difference in blood pressure and heart rate before and after salbutamol inhalation ) after the first dose of salbutamol followed by a significant decrease in K+.The early paradoxical increase in K+ may be the result of K+ release from skeletal muscle after β2 adrenoceptor stimulation.Whether this increase in K+ in already hyperkalaemic infants may provoke cardiac arrhythmias, especially as salbutamol also facilitates cardiac excitability through β1 adrenoceptor stimulation, is unknown.To conclude, this report underscores the need to recognize the possibility of NOHK in moderately and late preterm infants as well as in very preterm infants.Even in the face of low or normal K+ during the first 24 h of life, K+ should be checked every six hours during the first days of life as K+ can quickly rise and lead to rhythm disturbances.As seen in our case, salbutamol inhalation can effectively and rapidly lower K+ in NOHK, but the paradoxical increase in K+ during the first minutes following administration needs to be taken into account.It seems reasonable to administer calcium first to stabilize the myocardium and then commence salbutamol inhalation.With no absolute treatment recommendation, and in view of the limited information from small studies, the effectiveness of potentially beneficial interventions should be tested in further studies.