Effects of Continuous Infusion of Fentanyl Citrate (Fc) on CSF and Cerebrovascular Prostanoid Concentrations in Newborn Piglets. † 1370

Modanlou, Houchang D.; Pan, Ting; Riaz, Hassan; Samson, Tom; Sheikh, Rizwan; Beharry, Kay D.

doi:10.1203/00006450-199604001-01393

Cited by 4 publications

(8 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Fentanyl has also been shown to produce cerebral vasoconstriction in piglets which resulted in a dosedependent decrease in cerebral blood flow [19]. Local production of vasoconstrictor prostanoids may play a role in cerebral vasoconstrictor effect of fentanyl [15,25].…”

Section: Discussionmentioning

confidence: 99%

“…Newborn animal models have been previously used to study the respiratory effects, and cardiovascular and cerebral hemodynamic responses to fentanyl administration [15,16,[18][19][20]. Doses of 10-12 Ìg/kg provide adequate anesthesia and prevent surgical stress responses in neonates [7,18].…”

Section: Discussionmentioning

confidence: 99%

“…Fourteen newborn Yorkshire piglets (1-3 days old) were anesthetized with 1.5-2.0% halothane and oxygen for catheterization of the blood vessels. The surgical procedure was carried out as previously described [15].…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Pharmacodynamic Effects and Pharmacokinetic Profile of Continuous Infusion Fentanyl in Newborn Piglets

Rajan

Beharry²,

Williams³

et al. 1998

Neonatology

View full text Add to dashboard Cite

The objective of this study was to determine hemodynamic effects and pharmacokinetic profiles of fentanyl with continuous infusion in 1- to 3-day-old newborn piglets. The piglets (n = 6) were administered a loading dose of fentanyl at 30 µg/kg i.v. over 15 min followed by a continuous i.v. infusion at 10 µg/kg/h for 6 h. The control group (n = 8) received equivalent volume bolus and infusion of 5% dextrose. Blood samples were obtained serially from systemic circulation and sagittal sinus vein for measurement of plasma fentanyl, pH and blood gases. Plasma fentanyl achieved steady state levels by 30 min of infusion both in the systemic (202.7 ± 39.1 ng/ml) and sagittal sinus vein (136.7 ± 20.7 ng/ml). Fentanyl caused a transient increase in respiratory rate at 2 h. Heart rate was significantly elevated at 30 min and 6 h during infusion but systemic and sagittal sinus vein blood pressure remained unchanged. Systemic and sagittal sinus vein PO₂ were significantly decreased from 2 through 6 h of infusion. Compared to the control group, there was a 56% (p < 0.01) decrease in sagittal sinus vein O₂ content at 30 min of infusion, an effect which lasted up to 6 h (47%, p < 0.01). Fractional O₂ extraction by the brain increased significantly at 30 min (26%, p < 0.01) and remained elevated throughout the infusion time (22%, p < 0.05 at 6 h). Brain fractional O₂ extraction increased as a function of brain fractional fentanyl extraction (r² = 0.40, p < 0.001). Mean clearance was estimated as 56.2 ± 13.7 ml/kg/h (range 43.5–76.9 ml/kg/h), mean volume of distribution at steady state was 1.29 ± 0.6 liters/kg (range 0.78–2.15 liters/kg) and the mean half-life was 15.7 ± 5.7 h (range 9.4–22.5 h). These data suggest that increased systemic oxygen may be necessary to maintain normal cerebral oxygen extraction during fentanyl anesthesia/analgesia.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Pharmacodynamic Effects and Pharmacokinetic Profile of Continuous Infusion Fentanyl in Newborn Piglets

Rajan

Beharry²,

Williams³

et al. 1998

Neonatology

View full text Add to dashboard Cite

show abstract

“…Up to date, two single reports have been found in scientific literature describing this relationship in experimental animal models, but they refer to the administration of doses far higher than the ones concerned herein. The first one was performed in dogs injected tritium‐labeled 3 H‐FEN (10 or 100 µg/kg), and the second one applied HPLC‐UV to the quantification of FEN only at steady state conditions in piglets administered 30 µg/kg bolus followed by infusion at 10 µg/kg/h …”

Section: Resultsmentioning

confidence: 99%

“…The first one was performed in dogs injected tritium-labeled 3 H-FEN (10 or 100 μg/kg), [49] and the second one applied HPLC-UV to the quantification of FEN only at steady state conditions in piglets administered 30 μg/kg bolus followed by infusion at 10 μg/kg/h. [38] In this sense, there also seems to be a paucity of published data on methods of analysis using HPLC-MS/MS for the quantification of FEN in CSF or cerebral microdialysis samples, despite the importance of determining the drug levels in the CNS with a sufficient degree of sensitivity. Even though in the present study only one CSF sample was obtained from each animal, the low volume of CSF needed (50 μL) allows the applicability of the method in future and more specific pharmacokinetic studies aimed to further evaluate the CSF distribution of FEN in larger preclinical populations and/or under different dosing protocols.…”

Section: Analysis Of Samples From Pk/pd Experimental Studymentioning

confidence: 99%

Quantitative determination of fentanyl in newborn pig plasma and cerebrospinal fluid samples by HPLC‐MS/MS

Blanco

Encinas

González

et al. 2015

Drug Testing and Analysis

View full text Add to dashboard Cite

In this study, a selective and sensitive high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method requiring low sample volume (≤100 μL) was developed and validated for the quantitative determination of the opioid drug fentanyl in plasma and cerebrospinal fluid (CSF). A protein precipitation extraction with acetonitrile was used for plasma samples whereas CSF samples were injected directly on the HPLC column. Fentanyl and (13) C6 -fentanyl (Internal Standard) were analyzed in an electrospray ionization source in positive mode, with multiple reaction monitoring (MRM) of the transitions m/z 337.0/188.0 and m/z 337.0/105.0 for quantification and confirmation of fentanyl, and m/z 343.0/188.0 for (13) C6 -fentanyl. The respective lowest limits of quantification for plasma and CSF were 0.2 and 0.25 ng/mL. Intra- and inter-assay precision and accuracy did not exceed 15%, in accordance with bioanalytical validation guidelines. The described analytical method was proven to be robust and was successfully applied to the determination of fentanyl in plasma and CSF samples from a pharmacokinetic and pharmacodynamic study in newborn piglets receiving intravenous fentanyl (5 µg/kg bolus immediately followed by a 90-min infusion of 3 µg/kg/h).

show abstract

Evaluation of Fentanyl Disposition and Effects in Newborn Piglets as an Experimental Model for Human Neonates

et al. 2014

View full text Add to dashboard Cite

BackgroundFentanyl is widely used off-label in NICU. Our aim was to investigate its cerebral, cardiovascular and pulmonary effects as well as pharmacokinetics in an experimental model for neonates.MethodsFentanyl (5 µg/kg bolus immediately followed by a 90 minute infusion of 3 µg/kg/h) was administered to six mechanically ventilated newborn piglets. Cardiovascular, ventilation, pulmonary and oxygenation indexes as well as brain activity were monitored from T = 0 up to the end of experiments (T = 225–300 min). Also plasma samples for quantification of fentanyl were drawn.ResultsA “reliable degree of sedation” was observed up to T = 210–240 min, consistent with the selected dosing regimen and the observed fentanyl plasma levels. Unlike cardiovascular parameters, which were unmodified except for an increasing trend in heart rate, some of the ventilation and oxygenation indexes as well as brain activity were significantly altered. The pulmonary and brain effects of fentanyl were mostly recovered from T = 210 min to the end of experiment.ConclusionThe newborn piglet was shown to be a suitable experimental model for studying fentanyl disposition as well as respiratory and cardiovascular effects in human neonates. Therefore, it could be extremely useful for further investigating the drug behaviour under pathophysiological conditions.

show abstract

Effects of Continuous Infusion of Fentanyl Citrate (Fc) on CSF and Cerebrovascular Prostanoid Concentrations in Newborn Piglets. † 1370

Cited by 4 publications

References 0 publications

Pharmacodynamic Effects and Pharmacokinetic Profile of Continuous Infusion Fentanyl in Newborn Piglets

Pharmacodynamic Effects and Pharmacokinetic Profile of Continuous Infusion Fentanyl in Newborn Piglets

Quantitative determination of fentanyl in newborn pig plasma and cerebrospinal fluid samples by HPLC‐MS/MS

Evaluation of Fentanyl Disposition and Effects in Newborn Piglets as an Experimental Model for Human Neonates

Contact Info

Product

Resources

About