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Adverse reaction to ceftriaxone in a 28-day-old infant undergoing urgent craniotomy due to epidural hematoma: review of neonatal biliary pseudolithiasis

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      The debate as to whether to administer ceftriaxone to neonates is likely to continue. Ceftriaxone has numerous advantages for critically ill pediatric patients. However, it is also known to contribute substantially to the development of biliary pseudolithiasis. Although pediatric patients rarely develop gallbladder disorders, this complication may lead to adverse events in high-risk patients with predisposing factors, particularly in neonates and infants treated with ceftriaxone. In this paper we present an interesting case report of a 28-day-old neonate with spontaneous severe epidural hematoma who developed biliary pseudolithiasis related to the use of ceftriaxone. We also discuss the efficacy of ceftriaxone in neonates and infants. Neonatologists and pediatric intensivists should be aware of the higher risk of co-existence of hyperbilirubinemia and gallbladder disorders while using ceftriaxone in pediatric settings.

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        Clinical pharmacology of midazolam in infants and children.

        Midazolam is a parenteral benzodiazepine with sedative, amnesic, anxiolytic, muscle relaxant and anticonvulsant properties. The drug exerts its clinical effect by binding to a receptor complex which facilitates the action of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Midazolam has a faster onset and shorter duration of action than other benzodiazepines such as diazepam and lorazepam. The most serious adverse events associated with midazolam in children include hypoventilation, decreased oxygen saturation, apnoea and hypotension. It is water soluble in the commercially prepared formulation but becomes lipid soluble at physiological pH and can then cross the blood brain barrier. It is metabolised in the liver by the cytochrome P450 system, and its chief metabolite is 1-hydroxymethyl midazolam. The latter is conjugated to the glucuronide form, and it has only minimal biological activity. Midazolam is excreted primarily by the kidney. Its half-life in children over 12 months is reported to be 0.8 to 1.8 hours, with a clearance of 4.7 to 19.7 ml/min/kg. Doses given to children must be calculated on a mg/kg basis. For children 6 months to 5 years of age the initial dose is 0.05 to 0.1 mg/kg. A total dose up to 0.6 mg/kg titrated slowly may be necessary to achieve the desired endpoint. For children 6 to 12 years of age the initial dose is 0.025 to 0.05 mg/kg with a total dose up to 0.4 mg/kg to achieve the desired end-point.
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          Reversible ceftriaxone-associated biliary pseudolithiasis in children.

          Serial abdominal ultrasonography was performed in 37 children being treated with ceftriaxone for serious infections. Biliary concrements developed in 16 patients, causing symptoms in 3, one of whom also had urolithiasis with renal colic and obstructive ureteropyelectasia. After cessation of ceftriaxone treatment, ultrasound abnormalities and symptoms gradually disappeared, with complete sonographic resolution after 2 to 63 days.

            Author and article information

            [1 ]Department of Pediatric Anesthesiology and Intensive Therapy, Poznan University of Medical Sciences, Poznan, Poland
            [2 ]Department of Pediatric Radiology, Poznan University of Medical Sciences, Poznan, Poland
            [3 ]Department of Anesthesiology and Intensive Care, Pediatric Intensive Care Unit, Wroclaw Medical University, Wroclaw, Poland
            Author notes
            Correspondence: Alicja Bartkowska-Śniatkowska, Department of Pediatric Anesthesiology and Intensive Therapy, Poznan University of Medical Sciences, Szpitalna, Street 27/33, Poznan 60-572, Poland, Tel +48 61 849 1478, Fax +48 61 849 1486, Email asniatko@
            Ther Clin Risk Manag
            Ther Clin Risk Manag
            Therapeutics and Clinical Risk Management
            Therapeutics and Clinical Risk Management
            Dove Medical Press
            02 July 2015
            : 11
            : 1035-1041
            4494631 10.2147/TCRM.S79419 tcrm-11-1035
            © 2015 Bartkowska-Śniatkowska et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

            The full terms of the License are available at Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.



            efficacy, pseudolithiasis, neonate, pharmacodynamics, ceftriaxone


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