Generic placeholder image

CNS & Neurological Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

Research Article

The Use of Midazolam as an Antiseizure Medication in Neonatal Seizures: Single Center Experience and Literature Review

Author(s): Raffaele Falsaperla, Ausilia Desiree Collotta*, Vincenzo Sortino, Simona Domenica Marino, Silvia Marino, Francesco Pisani and Martino Ruggieri

Volume 23, Issue 10, 2024

Published on: 30 October, 2023

Page: [1285 - 1294] Pages: 10

DOI: 10.2174/1871527322666230608105206

Price: $65

conference banner
Abstract

Background: Existing therapeutic alternatives for neonatal crises have expanded in recent decades, but no consensus has been reached on protocols based on neonatal seizures. In particular, little is known about the use of midazolam in newborns.

Aim: The aim of our study is to evaluate the response to midazolam, the appearance of side effects, and their impact on therapeutic decisions.

Methods: This is a STROBE-conformed retrospective observational study of 10 patients with neonatal seizures unresponsive to common antiseizure drugs, admitted to San Marco University Hospital’s neonatal intensive care (Catania, Italy) from September 2015 to October 2022. In our database search, 36 newborns were treated with midazolam, but only ten children met the selection criteria for this study.

Results: Response was assessed both clinically and electrographic. Only 4 patients at the end of the treatment showed a complete electroclinical response; they were full-term infants with a postnatal age greater than 7 days. Non-responders and partial responders are all premature (4/10) or full-term neonates who started therapy in the first days of life (< 7th day) (2/10).

Conclusion: Neonatal seizures in preterm show a lower response rate to midazolam than seizures in full-term infants, with poorer prognosis. Liver and renal function and central nervous system development are incomplete in premature infants and the first days of life. In this study, we show that midazolam, a short-acting benzodiazepine, appears to be most effective in full-term infants and after 7 days of life.

« Previous
Graphical Abstract

[1]
Keene JC, Morgan LA, Abend NS, et al. Treatment of neonatal seizures: Comparison of treatment pathways from 11 neonatal intensive care units. Pediatr Neurol 2022; 128: 67-74.
[http://dx.doi.org/10.1016/j.pediatrneurol.2021.10.004] [PMID: 34750046]
[2]
Lacroix D, Sonnier M, Moncion A, Cheron G, Cresteil T. Expression of CYP3A in the human liver-evidence that the shift between CYP3A7 and CYP3A4 occurs immediately after birth. Eur J Biochem 1997; 247(2): 625-34.
[http://dx.doi.org/10.1111/j.1432-1033.1997.00625.x] [PMID: 9266706]
[3]
Kaminiów K, Kozak S, Paprocka J. Neonatal seizures revisited. Children 2021; 8(2): 155.
[http://dx.doi.org/10.3390/children8020155] [PMID: 33670692]
[4]
Padiyar S, Nusairat L, Kadri A, Abu-Shaweesh J, Aly H. Neonatal seizures in the U.S. National inpatient population: Prevalence and outcomes. Pediatr Neonatol 2020; 61(3): 300-5.
[http://dx.doi.org/10.1016/j.pedneo.2019.12.006] [PMID: 31937508]
[5]
Spagnoli C, Falsaperla R, Deolmi M, Corsello G, Pisani F. Symptomatic seizures in preterm newborns: A review on clinical features and prognosis. Ital J Pediatr 2018; 44(1): 115.
[http://dx.doi.org/10.1186/s13052-018-0573-y] [PMID: 30382869]
[6]
Bassan H, Bental Y, Shany E, et al. Neonatal seizures: Dilemmas in workup and management. Pediatr Neurol 2008; 38(6): 415-21.
[http://dx.doi.org/10.1016/j.pediatrneurol.2008.03.003] [PMID: 18486824]
[7]
Scher MS. Neonatal seizure classification: A fetal perspective concerning childhood epilepsy. Epilepsy Res 2006; 70 (Suppl. 1): 41-57.
[http://dx.doi.org/10.1016/j.eplepsyres.2005.11.020] [PMID: 16889942]
[8]
Volpe JJ. Brain injury in premature infants: A complex amalgam of destructive and developmental disturbances. Lancet Neurol 2009; 8(1): 110-24.
[http://dx.doi.org/10.1016/S1474-4422(08)70294-1] [PMID: 19081519]
[9]
Glass HC, Soul JS, Chu CJ, et al. Response to antiseizure medications in neonates with acute symptomatic seizures. Epilepsia 2019; 60(3): e20-4.
[http://dx.doi.org/10.1111/epi.14671] [PMID: 30790268]
[10]
Painter MJ, Scher MS, Stein AD, et al. Phenobarbital compared with phenytoin for the treatment of neonatal seizures. N Engl J Med 1999; 341(7): 485-9.
[http://dx.doi.org/10.1056/NEJM199908123410704] [PMID: 10441604]
[11]
Pacifici GM. Clinical pharmacology of midazolam in neonates and children: Effect of disease-a review. Int J Pediatr 2014; 2014: 1-20.
[http://dx.doi.org/10.1155/2014/309342] [PMID: 24696691]
[12]
World Health Organization. Guidelines on neonatal seizures. 2011. Available from: https://apps.who.int/iris/handle/10665/77756
[13]
El-Dib M, Soul JS. The use of phenobarbital and other anti-seizure drugs in newborns. Semin Fetal Neonatal Med 2017; 22(5): 321-7.
[http://dx.doi.org/10.1016/j.siny.2017.07.008] [PMID: 28811085]
[14]
Donovan MD, Griffin BT, Kharoshankaya L, Cryan JF, Boylan GB. Pharmacotherapy for neonatal seizures: Current knowledge and future perspectives. Drugs 2016; 76(6): 647-61.
[http://dx.doi.org/10.1007/s40265-016-0554-7] [PMID: 26943929]
[15]
Soul JS. Acute symptomatic seizures in term neonates: Etiologies and treatments. Semin Fetal Neonatal Med 2018; 23(3): 183-90.
[http://dx.doi.org/10.1016/j.siny.2018.02.002] [PMID: 29433814]
[16]
Samanta D. Recent advances in the diagnosis and treatment of neonatal seizures. Neuropediatrics 2021; 52(2): 073-83.
[http://dx.doi.org/10.1055/s-0040-1721702] [PMID: 33291160]
[17]
Sheth RD, Buckley DJ, Gutierrez AR, Gingold M, Bodensteiner JB, Penney S. Midazolam in the treatment of refractory neonatal seizures. Clin Neuropharmacol 1996; 19(2): 165-70.
[http://dx.doi.org/10.1097/00002826-199619020-00005] [PMID: 8777770]
[18]
Dao K, Giannoni E, Diezi M, Roulet-Perez E, Lebon S. Midazolam as a first-line treatment for neonatal seizures: Retrospective study. Pediatr Int 2018; 60(5): 498-500.
[http://dx.doi.org/10.1111/ped.13554] [PMID: 29878631]
[19]
Abushanab D, Abounahia FF, Alsoukhni O, Abdelaal M, Al-Badriyeh D. Clinical and economic evaluation of the impact of midazolam on morphine therapy for pain relief in critically Ill ventilated infants with respiratory distress syndrome. Paediatr Drugs 2021; 23(2): 143-57.
[http://dx.doi.org/10.1007/s40272-020-00432-0] [PMID: 33354750]
[20]
Arya V, Ramji S. Midazolam sedation in mechanically ventilated newborns: A double blind randomized placebo controlled trial. Indian Pediatr 2001; 38(9): 967-72.
[PMID: 11568372]
[21]
Yakıncı C, Müngen B, Şahın S, Karabıber H, Durmaz Y. Midazolam in treatment of various types of seizures in children. Brain Dev 1997; 19(8): 571-2.
[http://dx.doi.org/10.1016/S0387-7604(97)00090-9] [PMID: 9440805]
[22]
Kulkarni A. Midazolam sedation in mechanically ventilated newborns. Indian Pediatr 2002; 39(3): 316.
[PMID: 11910152]
[23]
McPherson C. Premedication for endotracheal intubation in the neonate. Neonatal Netw 2018; 37(4): 238-47.
[http://dx.doi.org/10.1891/0730-0832.37.4.238] [PMID: 30567922]
[24]
Jacqz-Aigrain E, Burtin P, Daoud P, Desplanques L, Beaufils F. Placebo-controlled trial of midazolam sedation in mechanically ventilated newborn babies. Lancet 1994; 344(8923): 646-50.
[http://dx.doi.org/10.1016/S0140-6736(94)92085-0] [PMID: 7915348]
[25]
Baleine J, Milési C, Mesnage R, et al. Intubation in the delivery room: Experience with nasal midazolam. Early Hum Dev 2014; 90(1): 39-43.
[http://dx.doi.org/10.1016/j.earlhumdev.2013.10.007] [PMID: 24331827]
[26]
Glass HC, Kan J, Bonifacio SL, Ferriero DM. Neonatal seizures: Treatment practices among term and preterm infants. Pediatr Neurol 2012; 46(2): 111-5.
[http://dx.doi.org/10.1016/j.pediatrneurol.2011.11.006] [PMID: 22264706]
[27]
Neonatal Formulary. (6th ed.), West Sussex, UK: John Wiley & Sons 2011.
[28]
de Wildt SN, Kearns GL, Sie SD, Hop WCJ, van den Anker JN. Pharmacodynamics of intravenous and oral midazolam in preterm infants. Clin Drug Investig 2003; 23(1): 27-38.
[http://dx.doi.org/10.2165/00044011-200323010-00004] [PMID: 23319091]
[29]
Young TE, Neofax MB. A Manual of Drugs Used in Neonatal Care. (23rd ed.), Montvale, NJ, USA: Thomson Reuters 2010.
[30]
Ng E, Taddio A, Ohlsson A. Intravenous midazolam infusion for sedation of infants in the neonatal intensive care unit. Cochrane Database Syst Rev 2017; 1(1): CD002052.
[http://dx.doi.org/10.1002/14651858.CD002052.pub3]
[31]
Shellhaas RA, Chang T, Tsuchida T, et al. The American Clinical Neurophysiology Society’s guideline on continuous electroencephalography monitoring in neonates. J Clin Neurophysiol 2011; 28(6): 611-7.
[http://dx.doi.org/10.1097/WNP.0b013e31823e96d7] [PMID: 22146359]
[32]
Stevenson NJ, Tataranno ML, Kaminska A, et al. Reliability and accuracy of EEG interpretation for estimating age in preterm infants. Ann Clin Transl Neurol 2020; 7(9): 1564-73.
[http://dx.doi.org/10.1002/acn3.51132] [PMID: 32767645]
[33]
Völler S, Flint RB, Beggah F, et al. Recently registered midazolam doses for preterm neonates do not lead to equal exposure: A population pharmacokinetic model. J Clin Pharmacol 2019; 59(10): 1300-8.
[http://dx.doi.org/10.1002/jcph.1429] [PMID: 31093992]
[34]
Pressler RM, Cilio MR, Mizrahi EM, et al. The ILAE classification of seizures and the epilepsies: Modification for seizures in the neonate. Position paper by the ILAE Task Force on Neonatal Seizures. Epilepsia 2021; 62(3): 615-28.
[http://dx.doi.org/10.1111/epi.16815] [PMID: 33522601]
[35]
Komatsu T, Singh PK, Kimura T, Nishiwaki K, Bando K, Shimada Y. Differential effects of ketamine and midazolam on heart rate variability. Can J Anaesth 1995; 42(11): 1003-9.
[http://dx.doi.org/10.1007/BF03011073] [PMID: 8590488]
[36]
van den Broek MPH, van Straaten HLM, Huitema ADR, et al. Anticonvulsant effectiveness and hemodynamic safety of midazolam in full-term infants treated with hypothermia. Neonatology 2015; 107(2): 150-6.
[http://dx.doi.org/10.1159/000368180] [PMID: 25572061]
[37]
Bernet V, Latal B, Natalucci G, Doell C, Ziegler A, Wohlrab G. Effect of sedation and analgesia on postoperative amplitude-integrated EEG in newborn cardiac patients. Pediatr Res 2010; 67(6): 650-5.
[http://dx.doi.org/10.1203/PDR.0b013e3181da44ba] [PMID: 20496474]
[38]
Shany E, Benzaquen O, Friger M, Richardson J, Golan A. Influence of antiepileptic drugs on amplitude-integrated electroencephalography. Pediatr Neurol 2008; 39(6): 387-91.
[http://dx.doi.org/10.1016/j.pediatrneurol.2008.08.005] [PMID: 19027583]
[39]
Sirsi D, Nangia S, LaMothe J, Kosofsky BE, Solomon GE. Successful management of refractory neonatal seizures with midazolam. J Child Neurol 2008; 23(6): 706-9.
[http://dx.doi.org/10.1177/0883073807313041] [PMID: 18539997]
[40]
Hu KC, Chiu NC, Ho CS, Lee ST, Shen EY. Continuous midazolam infusion in the treatment of uncontrollable neonatal seizures. Acta Paediatr Taiwan 2003; 44(5): 279-81.
[PMID: 14964983]
[41]
Castro Conde JR, Hernández Borges AA, Martínez ED, Campo CG, Soler RP. Midazolam in neonatal seizures with no response to phenobarbital. Neurology 2005; 64(5): 876-9.
[http://dx.doi.org/10.1212/01.WNL.0000152891.58694.71] [PMID: 15753426]
[42]
Mihi SJ, Harris RA. Hypnotic and sedatives. In: Brunton L, Chabner B, Knollman B, Eds. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. (12th ed.), New York, NY, USA: McGraw Hill 2011.
[43]
Ben-Ari Y. Excitatory actions of gaba during development: The nature of the nurture. Nat Rev Neurosci 2002; 3(9): 728-39.
[http://dx.doi.org/10.1038/nrn920] [PMID: 12209121]
[44]
Mueller AL, Taube JS, Schwartzkroin PA. Development of hyperpolarizing inhibitory postsynaptic potentials and hyperpolarizing response to gamma-aminobutyric acid in rabbit hippocampus studied in vitro. J Neurosci 1984; 4(3): 860-7.
[http://dx.doi.org/10.1523/JNEUROSCI.04-03-00860.1984] [PMID: 6707735]
[45]
Ben-Ari Y, Cherubini E, Corradetti R, Gaiarsa JL. Giant synaptic potentials in immature rat CA3 hippocampal neurones. J Physiol 1989; 416(1): 303-25.
[http://dx.doi.org/10.1113/jphysiol.1989.sp017762] [PMID: 2575165]
[46]
Holmes GL, Riviello JJ Jr. Midazolam and pentobarbital for refractory status epilepticus. Pediatr Neurol 1999; 20(4): 259-64.
[http://dx.doi.org/10.1016/S0887-8994(98)00155-6] [PMID: 10328273]
[47]
Dzhala VI, Talos DM, Sdrulla DA, et al. NKCC1 transporter facilitates seizures in the developing brain. Nat Med 2005; 11(11): 1205-13.
[http://dx.doi.org/10.1038/nm1301] [PMID: 16227993]
[48]
Rivera C, Voipio J, Payne JA, et al. The K+/Cl− co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation. Nature 1999; 397(6716): 251-5.
[http://dx.doi.org/10.1038/16697] [PMID: 9930699]
[49]
Ben-Ari Y, Holmes GL. The multiple facets of γ-aminobutyric acid dysfunction in epilepsy: Review. Curr Opin Neurol 2005; 18(2): 141-5.
[http://dx.doi.org/10.1097/01.wco.0000162855.75391.6a] [PMID: 15791144]
[50]
Yamada J, Okabe A, Toyoda H, Kilb W, Luhmann HJ, Fukuda A. Cl− uptake promoting depolarizing GABA actions in immature rat neocortical neurones is mediated by NKCC1. J Physiol 2004; 557(3): 829-41.
[http://dx.doi.org/10.1113/jphysiol.2004.062471] [PMID: 15090604]
[51]
Carrasco M, Stafstrom CE. How early can a seizure happen? pathophysiological considerations of extremely premature infant brain development. Dev Neurosci 2018; 40(5-6): 417-36.
[http://dx.doi.org/10.1159/000497471] [PMID: 30947192]
[52]
Nardou R, Ferrari DC, Ben-Ari Y. Mechanisms and effects of seizures in the immature brain. Semin Fetal Neonatal Med 2013; 18(4): 175-84.
[http://dx.doi.org/10.1016/j.siny.2013.02.003] [PMID: 23702158]
[53]
Brussee JM, Yu H, Krekels EHJ, et al. First-Pass CYP3A-mediated metabolism of midazolam in the gut wall and liver in preterm neonates. CPT Pharmacometrics Syst Pharmacol 2018; 7(6): 374-83.
[http://dx.doi.org/10.1002/psp4.12295] [PMID: 29745466]
[54]
Mansoor N, Ahmad T, Alam Khan R, Sharib SM, Mahmood I. Prediction of clearance and dose of midazolam in preterm and term neonates: A comparative study between allometric scaling and physiologically based pharmacokinetic modeling. Am J Ther 2019; 26(1): e32-7.
[http://dx.doi.org/10.1097/MJT.0000000000000506] [PMID: 27574923]
[55]
Van Donge T, Mian P, Tibboel D, Van Den Anker J, Allegaert K. Drug metabolism in early infancy: Opioids as an illustration. Expert Opin Drug Metab Toxicol 2018; 14(3): 287-301.
[http://dx.doi.org/10.1080/17425255.2018.1432595] [PMID: 29363349]
[56]
de Wildt SN, Kearns GL, Murry DJ, Koren G, van den Anker JN. Ontogeny of midazolam glucuronidation in preterm infants. Eur J Clin Pharmacol 2010; 66(2): 165-70.
[http://dx.doi.org/10.1007/s00228-009-0741-5] [PMID: 19838691]
[57]
Ancora G, Garetti E, Pirelli A, et al. Analgesic and sedative drugs in newborns requiring respiratory support. J Matern Fetal Neonatal Med 2012; 25(sup4)(Suppl. 4): 80-2.
[http://dx.doi.org/10.3109/14767058.2012.715036] [PMID: 22958030]
[58]
Girard T. Dosing of midazolam in neonates. J Clin Pharm Ther 2005; 30(5): 423-4.
[http://dx.doi.org/10.1111/j.1365-2710.2005.00679.x] [PMID: 16164486]
[59]
Luhmann HJ, Prince DA. Postnatal maturation of the GABAergic system in rat neocortex. J Neurophysiol 1991; 65(2): 247-63.
[60]
Owens DF, Boyce LH, Davis MBE, Kriegstein AR. Excitatory GABA responses in embryonic and neonatal cortical slices demonstrated by gramicidin perforated-patch recordings and calcium imaging. J Neurosci 1996; 16(20): 6414-23.
[http://dx.doi.org/10.1523/JNEUROSCI.16-20-06414.1996] [PMID: 8815920]
[61]
Altamimi MI, Sammons H, Choonara I. Inter-individual variation in midazolam clearance in children. Arch Dis Child 2015; 100(1): 95-100.
[http://dx.doi.org/10.1136/archdischild-2013-305720] [PMID: 25281734]
[62]
Burtin P, Jacqz-Aigrain E, Girard P, et al. Population pharmacokinetics of midazolam in neonates. Clin Pharmacol Ther 1994; 56(6): 615-25.
[http://dx.doi.org/10.1038/clpt.1994.186] [PMID: 7995003]
[63]
Jacqz-Aigrain E, Wood C, Robieux I. Pharmacokinetics of midazolam in critically ill neonates. Eur J Clin Pharmacol 1990; 39(2): 191-2.
[http://dx.doi.org/10.1007/BF00280059] [PMID: 2253674]
[64]
van den Anker JN, Sauer PJJ. The use of midazolam in the preterm neonate. Eur J Pediatr 1992; 151(2): 152.
[http://dx.doi.org/10.1007/BF01958970] [PMID: 1537365]
[65]
Waisman D, Weintraub Z, Rotschild A, Bental Y. Myoclonic movements in very low birth weight premature infants associated with midazolam intravenous bolus administration. Pediatrics 1999; 104(3): 579.
[http://dx.doi.org/10.1542/peds.104.3.579] [PMID: 10515771]
[66]
Ozcan B, Kavurt S, Yucel H, Bas AY, Demirel N. Rhythmic myoclonic jerking induced by midazolam in a preterm infant. Pediatr Neurol 2015; 52(6): e9.
[http://dx.doi.org/10.1016/j.pediatrneurol.2015.02.019] [PMID: 25896869]
[67]
Khazipov R, Khalilov I, Tyzio R, Morozova E, Ben-Ari Y, Holmes GL. Developmental changes in GABAergic actions and seizure susceptibility in the rat hippocampus. Eur J Neurosci 2004; 19(3): 590-600.
[http://dx.doi.org/10.1111/j.0953-816X.2003.03152.x] [PMID: 14984409]
[68]
Rheims S, Minlebaev M, Ivanov A, et al. Excitatory GABA in rodent developing neocortex in vitro. J Neurophysiol 2008; 100(2): 609-19.
[http://dx.doi.org/10.1152/jn.90402.2008] [PMID: 18497364]
[69]
Kirmse K, Kummer M, Kovalchuk Y, Witte OW, Garaschuk O, Holthoff K. GABA depolarizes immature neurons and inhibits network activity in the neonatal neocortex in vivo. Nat Commun 2015; 6: 7750.
[http://dx.doi.org/10.1038/ncomms8750]
[70]
Ben-Ari Y, Tyzio R, Nehlig A. Excitatory action of GABA on immature neurons is not due to absence of ketone bodies metabolites or other energy substrates. Epilepsia 2011; 52(9): 1544-58.
[http://dx.doi.org/10.1111/j.1528-1167.2011.03132.x] [PMID: 21692780]
[71]
Wells JE, Porter JT, Agmon A. GABAergic inhibition suppresses paroxysmal network activity in the neonatal rodent hippocampus and neocortex. J Neurosci 2000; 20(23): 8822-30.
[http://dx.doi.org/10.1523/JNEUROSCI.20-23-08822.2000] [PMID: 11102490]
[72]
Wolff M, Brunklaus A, Zuberi SM. Phenotypic spectrum and genetics ofSCN 2A ‐related disorders, treatment options, and outcomes in epilepsy and beyond. Epilepsia 2019; 60(S3) (Suppl. 3): S59-67.
[http://dx.doi.org/10.1111/epi.14935] [PMID: 31904126]
[73]
Numis AL, Angriman M, Sullivan JE, et al. KCNQ2 encephalopathy: Delineation of the electroclinical phenotype and treatment response. Neurology 2014; 82(4): 368-70.
[http://dx.doi.org/10.1212/WNL.0000000000000060] [PMID: 24371303]
[74]
Okan MA, Büyükkayhan D, Karatekin G. The effect of midazolam on oxidative stress and apoptosis in preterm infants. Fetal Pediatr Pathol 2021; 40(5): 423-9.
[http://dx.doi.org/10.1080/15513815.2020.1721627] [PMID: 32000555]
[75]
Magny JF, d’Allest AM, Nedelcoux H, Zupan V, Dehan M. Midazolam and myoclonus in neonate. Eur J Pediatr 1994; 153(5): 389-90.
[http://dx.doi.org/10.1007/BF01956430] [PMID: 8033934]
[76]
Jennekens W, Dankers F, Janssen F, et al. Effects of midazolam and lidocaine on spectral properties of the EEG in full-term neonates with stroke. Eur J Paediatr Neurol 2012; 16(6): 642-52.
[http://dx.doi.org/10.1016/j.ejpn.2012.03.005] [PMID: 22464455]
[77]
Leuven K, Groenendaal F, Toet MC, et al. Midazolam and amplitude-integrated EEG in asphyxiated full-term neonates. Acta Paediatr 2004; 93(9): 1221-7.
[http://dx.doi.org/10.1111/j.1651-2227.2004.tb02753.x] [PMID: 15384888]
[78]
Endo M, Hirano R, Shibasaki H, et al. Midazolam intoxication in a premature neonate. Clin Ther 2020; 42(5): 946-51.
[http://dx.doi.org/10.1016/j.clinthera.2020.03.013] [PMID: 32354497]
[79]
Hellström-Westas L. Midazolam and amplitude-integrated EEG. Acta Paediatr 2004; 93(9): 1153-4.
[http://dx.doi.org/10.1111/j.1651-2227.2004.tb02739.x] [PMID: 15384874]
[80]
van Alfen-van der Velden AAEM, Hopman JCW, Klaessens JHGM, Feuth T, Sengers RCA, Liem KD. Effects of midazolam and morphine on cerebral oxygenation and hemodynamics in ventilated premature infants. Neonatology 2006; 90(3): 197-202.
[http://dx.doi.org/10.1159/000093489] [PMID: 16717443]
[81]
Burtin P, Daoud P, Jacqz-Aigrain E, Mussat P, Moriette G. Hypotension with midazolam and fentanyl in the newborn. Lancet 1991; 337(8756): 1545-6.
[http://dx.doi.org/10.1016/0140-6736(91)93235-2] [PMID: 1675391]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy