Failure of Phenobarbitone to Prevent Intraventricular Haemorrhage in Small Preterm Infants

Hope, P L; Stewart, Ann; Thorburn, RosalindJ.; Whitehead, M D; Reynolds, E. O. R.; Lowe, Derek

doi:10.1016/s0140-6736(82)91639-7

Cited by 18 publications

(12 citation statements)

References 14 publications

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“…However, LOWESS regression suggested that the CBF from the controls dropped as the arterial pressure de-LOWESS, locally weighted regression and smoothing scatter plots TX, thromboxane Some clinical studies have reported that the incidence and/or severity of PIVH in preterm infants decreases when anticonvulsant dosages of PhS are given either antenatally or early in the postnatal period (1)(2)(3)(4)(5). Other studies have questioned the effectiveness of PhS in preventing PIVH (6)(7)(8)(9)(10). It has been shown that PhS in anticonvulsant concentrations lowers CBF during hypertension in newborn beagles and pigs, which may explain its protective effect against PIVH (1 1, 12).…”

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confidence: 99%

Phenobarbital and Cerebral Blood Flow during Hypotension in Newborn Pigs

et al. 1993

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ABSTRACT. Phenobarbital sodium (PhS) has been used in anticonvulsant concentrations in premature newborns in attempts to prevent peri-and intraventricular hemorrhages (PIVH). Its effectiveness in preventing PIVH in clinical situations is still uncertain; however, PhS has reduced PIVH after hypertension in newborn beagles, and it has lowered cerebral blood flow (CBF) during hypertension in newborn beagles and piglets. We hypothesized that PhS might reduce CBF during systemic hypotension. Twelve control and 12 PhS-treated piglets (1 to 2 d old) were used for microsphere determinations of CBF during 1 ) steady state; 2) 30 min after PhS (treatment group) or saline infusion (controls); and 3 and 4) during two levels of graded hypotension. Mean arterial blood pressure (MABP) was 61 f 13 (SD) mm Hg (controls) and 57 f 13 (SD) mm Hg (PhS) during steady state. Thirty min after the PhS or saline infusion, MABP and CBF remained unchanged in both groups. CBF during hypotension at MABP of 41 f 5 (SD) mm Hg was significantly higher in controls than was CBF at MABP of 39 + 6 (SD) mm Hg in the PhS-treated group (p = 0.044); CBF in the two groups during the second hypotensive phase was not significantly different.

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Phenobarbital and Cerebral Blood Flow during Hypotension in Newborn Pigs

et al. 1993

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“…Phenobarbital and indomethacin have been tested separately and at varying ages in the immediate neonatal period for IVH prophylaxis, with conflicting results. [4][5][6][7]11,12,[15][16][17]19 The Cochrane Collaborative has provided excellent reviews on this topic based on available studies in the literature. 27,32 However, those trials included newborns as old as 34 weeks GA and with BW up to 1499 g--infants at minimal risk of developing SIVH.…”

Section: Discussionmentioning

confidence: 99%

“…It is unclear why this medication was chosen for a protocol, given that its efficacy had been discredited prior to 1994. [12][13][14] In June 1998, a second medication, indomethacin, was added to phenobarbital for IVH prophylaxis at a dose of 0.1 mg/kg/d for a total of five doses, although for undocumented reasons, some patients continued to receive phenobarbital alone or did not receive prophylaxis at all. Consequently, there were three treatment groups and we were interested in determining whether there was some previously undetermined protective effect of combining phenobarbital with indomethacin on the neonatal outcomes of interest.…”

Section: Methodsmentioning

confidence: 99%

“…failed to corroborate those findings. [12][13][14] Although some investigators have suggested that indomethacin may have a place in IVH prophylaxis, 15,16 there is limited evidence that it significantly lowers SIVH rates in VLBW infants, 4,7,17 especially among the most susceptible group of infants, the ELBW. [5][6][7] There is ample evidence that neither phenobarbital nor indomethacin improves cognitive/motor developmental outcomes or survival of the VLBW infant, 5,13,[18][19][20][21][22] and that their routine use may be associated with adverse neurological outcomes, [23][24][25][26] prolonged mechanical ventilation, 27 and intestinal perforation or necrosis (necrotizing enterocolitis [NEC]), 16,28,29 respectively.…”

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confidence: 99%

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Combining Phenobarbital and Indomethacin to Improve Early Neonatal Outcomes in the Extremely Low Birth Weight Infant

Okah¹,

Mundy²,

Ekekezie³

2005

Am J Perinatol

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In this retrospective study, we tested the following hypotheses: rates of severe intraventricular hemorrhage (SIVH) and early neonatal survival are similar among extremely low birth weight (ELBW) infants treated with combination prophylaxis of phenobarbital and indomethacin compared with phenobarbital alone or no prophylaxis; and rates of patent ductus arteriosus (PDA) and necrotizing enterocolitis (NEC) are similar among indomethacin-exposed and nonexposed ELBW infants. Data were abstracted on 265 ELBW infants admitted into a level 3 neonatal intensive care unit from 1994 through 2002. Combination prophylaxis neither reduced the odds ratio (OR) of SIVH (OR = 1.53; 95% confidence interval [CI], 0.43 to 1.16) versus phenobarbital (OR = 2.91; 95% CI, 0.91 to 9.27 versus none (OR = 1; 95% CI, reference) nor increased the odds of early neonatal survival (OR = 0.72; 95% CI, 0.17 to 3.09 for combination prophylaxis versus OR = 0.66; 95% CI, 0.16 to 2.67 for phenobarbital versus OR = 1; 95% CI, reference for none). Indomethacin exposure reduced the odds of PDA (OR = 0.35; 95% CI, 0.17 to 0.75) without increasing the risk of NEC (OR = 1.37; 95% CI, 0.60 to 3.12). In conclusion, combination prophylaxis does not improve SIVH and early neonatal survival outcomes. Early exposure to indomethacin offers some benefits without any added risks.

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“…In another study, prophylactic phenobarbital did indeed suppress overall motor activity, but the incidence of intraventricular hemorrhage may have actually increased.21 A larger prospective study of 280 low-birth-weight infants also found a higher incidence of periventricular/ intraventricular hemorrhage in phenobarbital-treated infants.22 Several other investigators also failed to find phenobarbital to be neuroprotective. [23][24][25][26][27] Some studies have assessed the ability of phenobarbital given antenatally to prevent intraventricular hemorrhage in premature infants. In one randomized prospective study, 28 an intravenous loading dose of phenobarbital was given to women shortly before delivery if gestation had been less than 32 weeks.…”

Section: Pharmacologic Prophylaxis Of Periventricularlintravent?iculamentioning

confidence: 99%

Topical Review Article: Pharmacologic Management of Neonatal Cerebral Ischemia and Hemorrhage: Old and New Directions

Miller

1993

J Child Neurol

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New developments in pharmacologic management of cerebral ischemia and hemorrhage are reviewed. A number of agents with diverse modes of action have now been shown to be neuroprotective in adult and neonatal animal models when administered either before or after a hypoxic-ischemic insult. As experience improves with these agents in hypoxic-ischemic injury and periventricular-intraventricular hemorrhage in human neonates, there is reason to be optimistic that effective neuroprotective strategies will soon be clinically available.

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Failure of Phenobarbitone to Prevent Intraventricular Haemorrhage in Small Preterm Infants

Cited by 18 publications

References 14 publications

Phenobarbital and Cerebral Blood Flow during Hypotension in Newborn Pigs

Phenobarbital and Cerebral Blood Flow during Hypotension in Newborn Pigs

Combining Phenobarbital and Indomethacin to Improve Early Neonatal Outcomes in the Extremely Low Birth Weight Infant

Topical Review Article: Pharmacologic Management of Neonatal Cerebral Ischemia and Hemorrhage: Old and New Directions

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