Anticonvulsant Effectiveness and Hemodynamic Safety of Midazolam in Full-Term Infants Treated with Hypothermia

Broek, Marcel P. H. van den; Straaten, H.L.M. van; Huitema, Alwin D. R.; Egberts, Toine C. G.; Toet, Mona C.; Vries, Linda S. de; Rademaker, Karin J; Groenendaal, Floris

doi:10.1159/000368180

Cited by 33 publications

(19 citation statements)

References 32 publications

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“…This adverse effect has already been documented (with midazolam) and was often associated with rapid injection, co-administration of opioids or phenobarbital, 7 at higher doses or in combination with hypothermia. 8,9 The other adverse effects occurred in neonates with severe conditions (multiple malfomations, grade IV brain hemorrhage) that can contribute to lower tolerability. Compared with the two classical AED used for the Neonatal seizure of unknown origin, n = 6; seizure secondary to opioid withdrawal, n = 1; burst suppression encephalopathy, n = 1; and ornithine transcarbamylase deficiency, n = 1.…”

Section: Discussionmentioning

confidence: 99%

Midazolam as a first‐line treatment for neonatal seizures: Retrospective study

Dao

Giannoni

Diezi

et al. 2018

Pediatrics International

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Midazolam is commonly used to treat refractory seizures in newborns and as a first-line anti-epileptic drug in children. Its use as first-line treatment of neonatal seizures has not been investigated so far. We retrospectively studied the tolerability of midazolam in 72 newborn infants who received i.v. or i.n. midazolam as first-line treatment for seizures. No major side-effect exclusively due to midazolam was reported. The i.n. route was used for 20 patients (27.8%). Effectiveness could not be formally evaluated due to the absence of systematic electroencephalogram recording while midazolam was administered. In conclusion, midazolam was well-tolerated as a first-line abortive emergency treatment of neonatal seizure. The i.n. route offers a useful alternative to i.v. phenobarbital or phenytoin in emergency settings.

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Section: Discussionmentioning

confidence: 99%

Midazolam as a first‐line treatment for neonatal seizures: Retrospective study

Dao

Giannoni

Diezi

et al. 2018

Pediatrics International

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“…[8][9][10][11][12][13][14][15][16][17][19][20][21][22][23][24][25] Phenobarbital is still the most widely used first-line drug, 7 with a response rate of 21.4-50%. 8,21,24 For refractory neonatal seizures, phenytoin (response rate 26.7-53.1%), 22,24 midazolam (response rate 0-100%), 8,15,22,26,27 lidocaine (response rate 40-53.3%), 8,11,15 clonazepam (response rate 0%), 8 and levetiracetam (response rate 28.6-32%) 20,23 have been studied as second-line AEDs and midazolam (response rate 50-73.3%) 15,25,26 and lidocaine (response rate 62.5-91%) 10,[12][13][14]16,17 as third-line AEDs. Phenytoin, midazolam, and lidocaine show the most promising results.…”

Section: Discussionmentioning

confidence: 99%

Lidocaine response rate in aEEG‐confirmed neonatal seizures: Retrospective study of 413 full‐term and preterm infants

et al. 2015

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SUMMARYObjective: To investigate the seizure response rate to lidocaine in a large cohort of infants who received lidocaine as second-or third-line antiepileptic drug (AED) for neonatal seizures. Methods: Full-term (n = 319) and preterm (n = 94) infants, who received lidocaine for neonatal seizures confirmed on amplitude-integrated EEG (aEEG), were studied retrospectively (January 1992-December 2012). Based on aEEG findings, the response was defined as good (>4 h no seizures, no need for rescue medication); intermediate (0-2 h no seizures, but rescue medication needed after 2-4 h); or no clear response (rescue medication needed <2 h). Results: Lidocaine had a good or intermediate effect in 71.4%. The response rate was significantly lower in preterm (55.3%) than in full-term infants (76.1%, p < 0.001). In full-term infants the response to lidocaine was significantly better than midazolam as second-line AED (21.4% vs. 12.7%, p = 0.049), and there was a trend for a higher response rate as third-line AED (67.6% vs. 57%, p = 0.086). Both lidocaine and midazolam had a higher response rate as third-line AED than as second-line AED (p < 0.001). Factors associated with a good response to lidocaine were the following: higher gestational age, longer time between start of first seizure and administration of lidocaine, lidocaine as third-line AED, use of new lidocaine regimens, diagnosis of stroke, use of digital aEEG, and hypothermia. Multivariable analysis of seizure response to lidocaine included lidocaine as second-or third-line AED and seizure etiology. Significance: Seizure response to lidocaine was seen in~70%. The response rate was influenced by gestational age, underlying etiology, and timing of administration. Lidocaine had a significantly higher response rate than midazolam as second-line AED, and there was a trend for a higher response rate as third-line AED. Both lidocaine and midazolam had a higher response rate as third-line compared to second-line AED, which could be due to a pharmacologic synergistic mechanism between the two drugs.

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“…In clinical conditions, hypothermia, which is the most effective treatment of neonatal encephalopathy, alters clearance of PHB and MDZ to different degrees, shortening their efficacy 19 . MDZ has hypotensive effects that alter pharmacokinetics and has poor efficacy as a first‐ or second‐line AED after PHB 20 . This contrasts with the efficacy of MDZ administered before or after the insult in rodents 2 .…”

Section: Phb Mdz and Neonatal Seizures: Less Than Idealmentioning

confidence: 99%

Phenobarbital, midazolam, bumetanide, and neonatal seizures: The devil is in the details

Ben-Ari

Delpire

2021

Epilepsia

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Kaila, Löscher, and colleagues report that phenobarbital (PHB) and midazolam (MDZ) attenuate neonatal seizures following birth asphyxia, but the former only when applied before asphyxia and the latter before or after the triggering insult. In contrast, the NKCC1 chloride importer antagonist bumetanide (BUM) had no effect whether applied alone or with PHB. The observations are compelling and in accord with earlier studies. However, there are several general issues that deserve discussion. What is the clinical relevance of these data and the validity of animal models of encephalopathic seizures? Why is it that although they act on similar targets, these agents have different efficacy? Are both PHB and MDZ actions restricted to γ‐aminobutyric acidergic (GABAergic) mechanisms? Why is BUM inefficient in attenuating seizures but capable of reducing the severity of other brain disorders? We suggest that the relative failure of antiepileptic drugs (AEDs) to treat this severe life‐threatening condition is in part explicable by the recurrent seizures that shift the polarity of GABA, thereby counteracting their effects on their target. AEDs might be efficient after a few seizures but not recurrent ones. In addition, PHB and MDZ actions are not limited to GABA signals. BUM efficiently attenuates autism symptomatology notably in patients with tuberous sclerosis but does not reduce the recurrent seizures, illustrating the uniqueness of epilepsies. Therefore, the efficacy of AEDs to treat babies with encephalopathic seizures will depend on the history and severity of the seizures prior to their administration, challenging a universal common underlying mechanism.

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Anticonvulsant Effectiveness and Hemodynamic Safety of Midazolam in Full-Term Infants Treated with Hypothermia

Cited by 33 publications

References 32 publications

Midazolam as a first‐line treatment for neonatal seizures: Retrospective study

Midazolam as a first‐line treatment for neonatal seizures: Retrospective study

Lidocaine response rate in aEEG‐confirmed neonatal seizures: Retrospective study of 413 full‐term and preterm infants

Phenobarbital, midazolam, bumetanide, and neonatal seizures: The devil is in the details

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