Clinical experience with phenytoin prophylaxis in severe preeclampsia

Ryan, Greg; Lange, Ian; Naugler, Mary Anne K.

doi:10.1016/0020-7292(90)90403-8

Cited by 6 publications

(15 citation statements)

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“…The method we used to adjust total serum phenytoin concentrations for changes in albumin has been shown to correlate closely with actual free levels, although all such adjustments are relatively imprecise (Beck et al 1987). Transformation of the data in this way also allowed comparison with the results of Ryan et al (1989). However, this adjustment may not be applicable to women in late pregnancy since the method takes no account of changes in volume of distribution or clearance, and much of the original data from which they were derived came from hypoalbuminaemic patients in renal failure, in whom increases in free phenytoin may also arise from a reduction in drug‐albumin affinity (Rowland & Tozer 1989).…”

Section: Discussionmentioning

confidence: 99%

“…The initial choice of a 15 mg/kg loading dose for this study was based on the work of Ryan et al (1989). They reported therapeutic levels in 94% of women studied at 12 h after completion of the loading dose.…”

Section: Discussionmentioning

confidence: 99%

“…No arrhythmias were recorded during electrocardiographic monitoring, and it is now our policy to continue the electrocardiogram only during the loading infusions. Ryan et al (1989) reported pain at the infusion site in 70% of cases when phenytoin was diluted in 100 ml normal saline. This side effect is due to the alkalinity of the injection vehicle, which is buffered to pH 12 to maintain phenytoin sodium in solution at 50 mg/ml.…”

Section: Discussionmentioning

confidence: 99%

“…A 22 μm filter was placed in‐line to prevent any risk of microprecipitates being infused. The first 29 women received a total dose of 15 mg/kg, given as 10 mg/kg and then 5 mg/kg 2 h later (Ryan et al 1989). Analysis of plasma levels suggested that a significant number were subtherapeutic prior to the first maintenance dose.…”

Section: Methodsmentioning

confidence: 99%

“…The drug has a stabilising effect on neuronal membranes and rapidly crosses the blood‐brain barrier after intravenous infusion (Wilder et al 1977). Slater et al (1987) and Ryan et al (1989) reported encouraging results with phenytoin in severe pre‐eclampsia and a few cases of eclampsia. No major side effects were encountered and no seizures occurred following administration of the advocated dose.…”

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confidence: 99%

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Phenytoin prophylaxis in severe pre‐eclampsia and eclampsia

Robson

Redfern

Seviour³

et al. 1993

BJOG

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Objective To determine plasma phenytoin levels and seizure outcome in women given phenytoin for seizure prophylaxis in severe pre‐eclampsia and eclampsia. Design Prospective observational study comparing two phenytoin loading regimens. Setting Two UK teaching hospitals. Subjects Sixty‐seven consecutive women with severe pre‐eclampsia and five with eclampsia. Interventions The first 29 women were given a 15 mg/kg intravenous loading dose of phenytoin. The next 43 received 17.5 mg/kg. All were given 500 mg phenytoin 12 h after completion of the loading dose and then 250 mg every 12 h for four doses. Main outcome measures Total plasma phenytoin levels at 30 min, 6 h and 12 h after loading dose, 6 h after first maintenance dose and on days 2 and 3 of maintenance therapy; eclamptic seizures after starting phenytoin. Results Mean plasma phenytoin levels were higher at 30 min and 6 h after the 17.5 mg/kg loading dose. Nine of 29 (31%) phenytoin levels 30 min after the loading dose were above the therapeutic range in the 15 mg/kg group compared with 26/38 (68%) in the 17.5 mg/kg group (P<0.01). Six of 27 (22%) phenytoin levels 12 h after the loading dose were subtherapeutic in the 15 mg/kg group compared with 2/38 (5%) in the 17.5 mg/kg group (P<0.05). Three women, two in the 17.5 mg/kg group, developed seizures after starting phenytoin. All three had plasma levels within the therapeutic range. Conclusions Compared with a loading dose of 17.5 mg/kg, loading with 15 mg/kg phenytoin was associated with a lower incidence of high plasma levels at 30 min but a higher incidence of subtherapeutic levels at 12 h. Seizures occur in 2 to 3% of pre‐eclamptics despite apparently therapeutic phenytoin levels.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Phenytoin prophylaxis in severe pre‐eclampsia and eclampsia

Robson

Redfern

Seviour³

et al. 1993

BJOG

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A Simplified Phenytoin Regimen for Preeclampsia

Lucas¹,

DePalma²,

Peters³

et al. 1994

Amer J Perinatol

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The objective of this study was to assess the feasibility of giving phenytoin to a group of mild preeclamptic women in a universal dosing scheme comparable to that typical of magnesium sulfate administration. Serum phenytoin levels were measured at regular intervals for 32 hours following a 1 g intravenous loading dose in 14 patients. A second group of 14 women received 500 mg orally to supplement the 1 g initial dose and had serum levels similarly measured. The resultant serum levels are described, and the effect of maternal weight analyzed. The average serum phenytoin level in the first 14 women given the 1 g loading dose fell to 10 micrograms/mL approximately 12 hours after treatment. Serum levels plateaued above this threshold in the 14 women given 500 mg of additional medication orally 10 hours after treatment initiation and were maintained for an additional 14 hours before decline was observed. The serum levels resulting from the initial 1 g loading dose were analyzed 8 hours after treatment initiation in the entire group of 28 women according to body weight, and a clinically significant effect of weight on serum level was observed only at the extremes of weight. We conclude that a universal dosing scheme comparable to that typically used for magnesium sulfate is feasible for phenytoin administration to preeclamptic women.

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Phenytoin Versus Magnesium Sulfate in Preeclampsia: A Pilot Study

et al. 2008

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A randomized clinical trial was designed to determine whether there are clinically demonstrable advantages of phenytoin over magnesium sulfate in preeclamptic patients because of the latter drug's uterine relaxant properties. An intravenous infusion, immediately after randomization, of either phenytoin or magnesium sulfate, with subsequent measurement of serum concentrations and maintenance of therapeutic levels was given to 103 preeclamptic and two eclamptic women. Observed were the rate of cervical dilation during active labor and change in hematocrit between predelivery and 24-hour postdelivery values and the incidence of side effects ascertained by interview. Compared with those receiving magnesium sulfate, patients receiving phenytoin had more rapid cervical dilation (3.3 cm/hr versus 1.5 cm/hr, p = 0.016) and a smaller fall in hematocrit after delivery (-4.7% versus -7.6%, p = 0.034). A significantly lower incidence of hot flushes (15% versus 46%, p < 0.005) and a trend toward less dyspnea and weakness were reported by phenytoin-treated patients. Our phenytoin regimen produced acceptable serum phenytoin levels (10 to 25 micrograms/ml) in 96% of patients.

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Clinical experience with phenytoin prophylaxis in severe preeclampsia

Cited by 6 publications

References 0 publications

Phenytoin prophylaxis in severe pre‐eclampsia and eclampsia

Phenytoin prophylaxis in severe pre‐eclampsia and eclampsia

A Simplified Phenytoin Regimen for Preeclampsia

Phenytoin Versus Magnesium Sulfate in Preeclampsia: A Pilot Study

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