Letter to the Editor: Neonatal intraventricular hemorrhage

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To The Editor: We found the article by Alan et al.1 very interesting (Alan N, Manjila S, Minich N, et al: Reduced ventricular shunt rate in very preterm infants with severe intraventricular hemorrhage: an institutional experience. Clinical article. J Neurosurg Pediatr 10:357–364, November 2012). This study reported a decline in the need for surgery in very preterm infants with intraventricular hemorrhage and hydrocephalus, with suggestions about the probable reasons for this decrease. These authors have treated symptomatic hydrocephalus with serial lumbar punctures (LPs). Surgical intervention was limited to ventriculosubgaleal shunt

To The Editor: We found the article by Alan et al.1 very interesting (Alan N, Manjila S, Minich N, et al: Reduced ventricular shunt rate in very preterm infants with severe intraventricular hemorrhage: an institutional experience. Clinical article. J Neurosurg Pediatr 10:357–364, November 2012). This study reported a decline in the need for surgery in very preterm infants with intraventricular hemorrhage and hydrocephalus, with suggestions about the probable reasons for this decrease. These authors have treated symptomatic hydrocephalus with serial lumbar punctures (LPs). Surgical intervention was limited to ventriculosubgaleal shunt insertion as a temporary intervention whenever serial LPs failed, and in case of active hydrocephalus this shunt was changed to a standard ventriculoperitoneal shunt at a later age.

Prolonged symptomatic hydrocephalus is a potentially destructive pathology that impairs normal development of the CNS. The literature is full of studies related to conservative management for neonates with prematurity and posthemorrhagic hydrocephalus. This treatment included LP, diuretic therapy, and also acetazolamide. Serial LPs have been accepted in most studies as a mainstay of conservative treatment, but there is no agreement about acetazolamide and diuretics. Some reviews and original articles found acetazolamide useful, and others reported it to be useless and even harmful for management of hydrocephalus. The prescribed dosage for acetazolamide with or without furosemide was 100 mg/kg/day in most previous studies. Nephrocalcinosis has been reported in neonates who received acetazolamide as a conservative treatment.3–5

Some studies have claimed that they could decrease the risk of shunt surgery with conservative treatment and some have rejected it. What we can conclude from the published series is that conservative treatment helps protect the premature neonates from high intracranial hypertension consequences and to postpone shunt surgery to a later time at which the child can tolerate physiologically the anesthesia and surgical intervention with fewer complications.

With this philosophy in mind, the proposed protocol for management of hydrocephalus in premature neonates with posthemorrhagic hydrocephalus in our department is acetazolamide and serial LPs, with daily measurement of head circumference and fontanel in addition to serial brain ultrasonography studies.2 To decrease the metabolic complications of acetazolamide we use it at a dosage of 20 mg/kg/day, which is lower than the dose that causes nephrocalcinosis. To decrease metabolic acidosis the child is checked clinically for tachypnea and by laboratory tests for venous blood gas. In case of acidosis the medication is stopped. If conservative treatment fails, ventriculosubgaleal shunt insertion is a good alternative to control hydrocephalus until the child can successfully tolerate a ventriculoperitoneal shunt surgery.

Disclosure

The authors report no conflict of interest.

References

  • 1

    Alan NManjila SMinich NBass NCohen ARWalsh M: Reduced ventricular shunt rate in very preterm infants with severe intraventricular hemorrhage: an institutional experience. Clinical article. J Neurosurg Pediatr 10:3573642012

  • 2

    Behjati SEmami-Naeini PNejat FEl Khashab M: Incidence of hydrocephalus and the need to ventriculoperitoneal shunting in premature infants with intraventricular hemorrhage: risk factors and outcome. Childs Nerv Syst 27:9859892011

  • 3

    Kennedy CRAyers SCampbell MJElbourne DHope PJohnson A: Randomized, controlled trial of acetazolamide and furosemide in posthemorrhagic ventricular dilation in infancy: follow-up at 1 year. Pediatrics 108:5976072001

  • 4

    Poca MASahuquillo J: Short-term medical management of hydrocephalus. Expert Opin Pharmacother 6:152515382005

  • 5

    Shinnar SGammon KBergman EW JrEpstein MFreeman JM: Management of hydrocephalus in infancy: use of acetazolamide and furosemide to avoid cerebrospinal fluid shunts. J Pediatr 107:31371985

Response

We read with interest the thoughtful letter to the editor submitted by Nejat and colleagues regarding our article in the Journal of Neurosurgery: Pediatrics on the declining need for surgical intervention for extremely preterm infants with symptomatic hydrocephalus from intraventricular hemorrhage. We agree that nonoperative strategies such as serial LPs can sometimes delay or avoid the need for surgical intervention, and that older and larger preterm infants suffer fewer perioperative complications than younger and smaller infants. Nejat et al. suggest a combination of serial LPs and acetazolamide (20 mg/kg/day) as a temporizing measure for symptomatic hydrocephalus prior to surgical intervention, with daily head circumference measurements and serial head ultrasonography studies to assess efficacy. They recommend screening for metabolic acidosis by checking for tachypnea and serial venous blood gas measurements.

As recently discussed in 2 reviews of the management of neonatal posthemorrhagic hydrocephalus from prematurity,3,4 a large randomized controlled trial of acetazolamide (100 mg/kg/day) and furosemide (1 mg/kg/day) across 55 centers demonstrated no improvement with the addition of these agents to standard therapy, which included CSF removal with LPs.2 At 1 year, infants treated with acetazolamide and furosemide did not require fewer shunt insertions and had poorer neurological outcomes than those infants who received only standard therapy. Adverse effects were attributed to the drug intervention in 43% of the treatment group and resulted in treatment cessation in 26%. The acetazolamide dose suggested by Nejat and colleagues is much lower than the dose used in the controlled trial. Given that the high dose was ineffective in lowering the need for surgical intervention, it seems unlikely that a lower dose would be effective in altering the need for surgical intervention. Both acetazolamide and furosemide probably have unanticipated side effects on neurological development, which may have contributed to the inferior neurological outcomes observed in infants treated with the regimen. For example, furosemide is a nonspecific inhibitor of the potassium chloride cotransporter (KCC2) found primarily on neurons, and KCC2 regulates key components of neuronal development.1

In summary, although we agree with Nejat that aggressive treatment of symptomatic hydrocephalus in this population is essential, and that a trial of nonoperative intervention is warranted given the relatively high complication rate associated with early surgical procedures, we cannot at this time endorse the use of acetazolamide in these infants without further support from high-quality preclinical studies.

References

  • 1

    Blaesse PAiraksinen MRivera CKaila K: Cation-chloride transporters and neuronal function. Neuron 61:8208382009

  • 2

    Kennedy CRAyers SCampbell MJElbourne DHope PJohnson A: Randomized, controlled trial of acetazolamide and furosemide in posthemorrhagic ventricular dilatation in infancy: follow-up at 1 year. Pediatrics 108:5976072001

  • 3

    Robinson S: Neonatal posthemorrhagic hydrocephalus from prematurity: pathophysiology and current treatment concepts. A review. J Neurosurg Pediatr 9:2422582012

  • 4

    Whitelaw AAquilina K: Management of posthaemorrhagic ventricular dilatation. Arch Dis Child Fetal Neonatal Ed 97:F229F2332012

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Article Information

Please include this information when citing this paper: published online September 20, 2013; DOI: 10.3171/2012.11.PEDS12559.

© AANS, except where prohibited by US copyright law.

Headings

References

1

Alan NManjila SMinich NBass NCohen ARWalsh M: Reduced ventricular shunt rate in very preterm infants with severe intraventricular hemorrhage: an institutional experience. Clinical article. J Neurosurg Pediatr 10:3573642012

2

Behjati SEmami-Naeini PNejat FEl Khashab M: Incidence of hydrocephalus and the need to ventriculoperitoneal shunting in premature infants with intraventricular hemorrhage: risk factors and outcome. Childs Nerv Syst 27:9859892011

3

Kennedy CRAyers SCampbell MJElbourne DHope PJohnson A: Randomized, controlled trial of acetazolamide and furosemide in posthemorrhagic ventricular dilation in infancy: follow-up at 1 year. Pediatrics 108:5976072001

4

Poca MASahuquillo J: Short-term medical management of hydrocephalus. Expert Opin Pharmacother 6:152515382005

5

Shinnar SGammon KBergman EW JrEpstein MFreeman JM: Management of hydrocephalus in infancy: use of acetazolamide and furosemide to avoid cerebrospinal fluid shunts. J Pediatr 107:31371985

1

Blaesse PAiraksinen MRivera CKaila K: Cation-chloride transporters and neuronal function. Neuron 61:8208382009

2

Kennedy CRAyers SCampbell MJElbourne DHope PJohnson A: Randomized, controlled trial of acetazolamide and furosemide in posthemorrhagic ventricular dilatation in infancy: follow-up at 1 year. Pediatrics 108:5976072001

3

Robinson S: Neonatal posthemorrhagic hydrocephalus from prematurity: pathophysiology and current treatment concepts. A review. J Neurosurg Pediatr 9:2422582012

4

Whitelaw AAquilina K: Management of posthaemorrhagic ventricular dilatation. Arch Dis Child Fetal Neonatal Ed 97:F229F2332012

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