Hemodynamic Effects of Halothane in the Newborn Piglet

Boudreaux, J Philip; Schieber, Richard A.; Cook, David

doi:10.1213/00000539-198408000-00005

Cited by 30 publications

(7 citation statements)

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“…Pigs are a suitable animal model for comparison of cardiovascular physiology with man and were used in this study because of their anatomical and physiological similarity to the human system. In this regard, the first 2.5 weeks of a piglet's life corresponds to the first six months of a newborn infant's life (Boudreaux et al 1984). Previous studies have shown that distribution of drugs into the CNS of neonatal pigs correlates with drug disposition in human neonates (Abdel-Rahman et al 2000).…”

Section: Introductionmentioning

confidence: 99%

Disposition of morphine in plasma and cerebrospinal fluid varies during neonatal development in pigs

Rai

Bhalla

Rebello

et al. 2005

Journal of Pharmacy and Pharmacology

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The pharmacological effects of morphine are mediated via the central nervous system (CNS) but its clearance from the CNS in neonates has not been investigated. We have proposed that neonatal development of the blood-brain barrier affected CNS clearance mechanisms and CNS exposure to morphine. Male piglets (n = 5) aged one, three and six weeks were given morphine sulfate (0.5 mg kg(-1), i.v.). Serial blood and cerebrospinal fluid (CSF) samples were withdrawn over 360 min after morphine administration. Morphine concentration was measured by radioimmunoassay. A three-compartment model was fitted to individual data. Estimated parameters were reported as median and range. The peak morphine concentrations in plasma were not significantly different in the one-, three- or six-week-old piglets. Plasma clearance at one week (4.5, 3.8-8.6 mL min(-1) kg(-1)) was significantly lower than at three weeks (30.0, 19.1- 39.0 mL min(-1) kg(-1)) and six weeks (37.0, 29.7-82.8 mL min(-1) kg(-1)). The peak morphine concentration in CSF at one week (59.84, 31-67 ng mL(-1)) was higher than at three weeks (18.8, 17.7-25 ng mL(-1)) and six weeks (24.51, 16.5-84 ng mL(-1)), while CSF clearance was lower at one week (1.0, 0.18-9 mL min(-1) kg(-1)) compared with three weeks (6.2, 2.3-9.3 mL min(-1) kg(-1)) and six weeks (3.95, 1.3-85.7 mL min(-1) kg(-1)). Apparent plasma:CSF transfer ratio at one week was greater than at three and six weeks. The reduced plasma and CSF morphine clearance in early infancy resulted in elevated systemic and central morphine exposure in neonatal pigs.

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Section: Introductionmentioning

confidence: 99%

Disposition of morphine in plasma and cerebrospinal fluid varies during neonatal development in pigs

Rai

Bhalla

Rebello

et al. 2005

Journal of Pharmacy and Pharmacology

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“…Cardiovascular depression by halothane in infants and neonatal mammals has been shown by echocardiographic studies to be primarily due to depression of cardiac contractility ( 2,4,5,28). The developing mammalian heart has been extensively studied by Friedman, who demonstrated significant functional and histological differences that might predispose the neonate to be sensitive to depression by halothane ( 11).…”

Section: Discussionmentioning

confidence: 99%

Haemodynamic depression by halothane is age‐related in paediatric patients

Friesen

Wurl

Charlton

2000

Pediatric Anesthesia

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The hypothesis that young infants are more sensitive to the haemodynamic depressant effects of halothane compared with older children was tested. One hundred and sixty unpremedicated, ASA physical status I or II paediatric patients without cardiac or pulmonary disease were divided into five age groups: term neonates, 1-6 months, 6-24 months, 2-6 years and 6-12 years. Anaesthetic induction was achieved with halothane in oxygen and air via mask. Vecuronium 0.1 mg.kg-1 was administered intravenously. During normocapnic manual ventilation by mask, endtidal halothane concentration was maintained at either 2xage-specific MAC (Method I) or 1.7% (Method II) in 20 patients in each age group for 10 min. In both Method I and Method II, systolic and mean blood pressure of term neonates and infants aged 1-6 months decreased significantly (P < 0.01) compared with other age groups. The results of this study demonstrate that neonates and young infants are more susceptible to haemodynamic depression during halothane anaesthesia than are older children, confirming clinical experience.

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“…18 4 Defined the pharmacokinetic and pharmacodynamics effects of volatile anesthetics in pediatric patients. 30 6,7,[11][12][13] They helped define the dose response, duration, pharmacokinetics, and clinical side effects of these agents in neonates, infants, and children. They identified the sensitivity of infants to nondepolarizing neuromuscular blockers 12 and the relative resistance to children (larger ED 95 ) when compared to adults.…”

Section: During Dr Cook's Third Year Of Medical School He Was Hired mentioning

confidence: 99%

The advancement of pediatric anesthesia pharmacology: David Ryan Cook (scions, serendipity, and six degrees of separation)

Cladis

Christine

Yaster

et al. 2018

Pediatric Anesthesia

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Summary Dr David Ryan Cook, Professor Emeritus of Anesthesiology and Pharmacology at the University of Pittsburgh and Chief of Anesthesiology at Children's Hospital of Pittsburgh (1977‐1999), is a pioneer in the field of pediatric anesthesiology and pharmacology. Dr Cook contributed significantly to the understanding of pharmacologic differences among infants, children, and adults. His work as a clinician‐scientist, educator, and mentor defined the pharmacology of many of the anesthetic agents we continue to use today. He brought science to the art of anesthesia and enhanced the safety of pediatric perioperative care. Based on a 2017 interview with Dr Cook, this article outlines the development of his career and his contributions to the field of anesthesiology and pharmacology.

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Hemodynamic Effects of Halothane in the Newborn Piglet

Cited by 30 publications

References 0 publications

Disposition of morphine in plasma and cerebrospinal fluid varies during neonatal development in pigs

Disposition of morphine in plasma and cerebrospinal fluid varies during neonatal development in pigs

Haemodynamic depression by halothane is age‐related in paediatric patients

The advancement of pediatric anesthesia pharmacology: David Ryan Cook (scions, serendipity, and six degrees of separation)

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