Exploring the pharmacokinetics of oral ketamine in children undergoing burns procedures

Brunette, Katharine E.J.; Anderson, Brian J.; Thomas, Jennifer; Wiesner, Lubbe; Herd, David; Schulein, S.

doi:10.1111/j.1460-9592.2011.03548.x

Cited by 39 publications

(25 citation statements)

References 42 publications

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“…As a result, estimation of CL from a pediatric cohort that includes infants <3 months would be expected to yield lower values, as was the case in our study and the study of infants recovering from cardiac surgery . An estimate of CL in an older pediatric cohort should in turn result in higher CL values, as was the case in the report from the emergency department and a subsequent reanalysis of the same data set …”

Section: Discussionmentioning

confidence: 67%

“…Ketamine is an N‐methyl D‐aspartate receptor antagonist increasingly used “off label” to facilitate a dissociative anesthesia in children undergoing invasive procedures . Commercial preparations of ketamine are a racemic mixture of R‐ and S‐enantiomers approved for use in adults as the sole anesthetic agent for diagnostic and surgical procedures and for the induction of anesthesia .…”

mentioning

confidence: 99%

“…Ketamine V ss decreases with age, ranging from 242 L/70 kg in infants <3 months to 53 L/70 kg by adulthood. Subsequent analyses of pediatric data have contributed valuable information on optimal sampling times, oral bioavailability (45%), and absorption half‐time following oral administration (59 minutes, 95%CI 29.4‐109.2 minutes) . Ketamine was also found to have a 36% bioavailability following intranasal administration in children ≥10 kg .…”

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confidence: 99%

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Population Pharmacokinetics of Intramuscular and Intravenous Ketamine in Children

Hornik

González

Anker

et al. 2018

The Journal of Clinical Pharma

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Ketamine is an N-methyl D-aspartate receptor antagonist used off-label to facilitate dissociative anesthesia in children undergoing invasive procedures. Available for both intravenous and intramuscular administration, ketamine is commonly used when vascular access is limited. Pharmacokinetic (PK) data in children are sparse, and the bioavailability of intramuscular ketamine in children is unknown. We performed 2 prospective PK studies of ketamine in children receiving either intramuscular or intravenous ketamine and combined the data to develop a pediatric population PK model using nonlinear mixed-effects methods. We applied our model by performing dosing simulations targeting plasma concentrations previously associated with analgesia (>100 ng/mL) and anesthesia awakening (750 ng/mL). A total of 113 children (50 intramuscular and 63 intravenous ketamine) with a median age of 3.3 years (range 0.02 to 17.6 years), and median weight of 14 kg (2.4 to 176.1) contributed 275 plasma samples (149 after intramuscular, 126 after intravenous ketamine). A 2-compartment model with first-order absorption following intramuscular administration and first-order elimination described the data best. Allometrically scaled weight was included in the base model for central and peripheral volume of distribution (exponent 1) and for clearance and intercompartmental clearance (exponent 0.75). Model-estimated bioavailability of intramuscular ketamine was 41%. Dosing simulations suggest that doses of 2 mg/kg intravenously and 8 mg/kg or 6 mg/kg intramuscularly, depending on age, provide adequate sedation (plasma ketamine concentrations >750 ng/mL) for procedures lasting up to 20 minutes.

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Section: Discussionmentioning

confidence: 67%

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confidence: 99%

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confidence: 99%

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Population Pharmacokinetics of Intramuscular and Intravenous Ketamine in Children

Hornik

González

Anker

et al. 2018

The Journal of Clinical Pharma

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“…After oral administration, peak ketamine and norketamine levels are seen at around 60 minutes, so a delay of 45-50 minutes between oral administration and a planned painful procedure is recommended. Oral pharmacokinetics in children have been recently reviewed (21). Although the literature includes individual oral and intramuscular dosing regimes, there is no recommended dosing guidance for procedural pain from recent published guidelines (9), or from the British National Formulary for Children (BNFC).…”

Section: 3mentioning

confidence: 99%

Procedural Pain Management in Neonates, Infants and Children

Wilson-Smith

2011

Reviews in Pain

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• Neonates, infants and children all feel pain and require analgesia for painful procedures. • Many painful procedures are associated with medical interventions, including immunisation, heel lance, venesection, IV cannulation and dressing change. • Untreated pain can have short and long term effects, including sensitisation to pain episodes in later life. • A range of non-pharmacological and pharmacological interventions have been shown to be effective for procedural pain management in infants and children, and are most effective when used in combination. • Developmental changes in pain responses, analgesic response and drug pharmacokinetics need to be taken into account when planning procedural pain management for neonates. • Comprehensive evidence based guidelines are available to guide effective procedural pain management in neonates, infants and older children.

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“…After the acute phase of a severe burn, the blood flow volumes in the liver and kidneys increase with the presence of hypermetabolism and increasing cardiac output, which leads to enhanced drug clearance. The recovery of hepatic and renal functions varies according to the individual Kaneda and Han, 2009;Yamashita et al, 2010;Brunette et al, 2011). The combination of remifentanil and propofol for intravenous targetcontrolled infusion (TCI) has been extensively used for various types of surgical anesthesia.…”

Section: Introductionmentioning

confidence: 99%

Bispectral index for monitoring anesthetic depth in patients with severe burns receiving target-controlled infusion of remifentanil and propofol

et al. 2015

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ABSTRACT. This study evaluated the feasibility and effectiveness of using the bispectral index (BIS) to monitor anesthetic depth in patients with severe burns receiving intravenous target-controlled infusion (TCI) of remifentanil and propofol. We randomly assigned 80 patients undergoing elective escharectomy (<1 week) to BIS (A) and control (B) groups. All patients received remifentanil and propofol as intravenous TCI anesthesia. Clinical data were recorded at different time points. The time from drug withdrawal to eye opening upon the patient hearing his/ her name called and upon reaching an Aldrete score of 9 points was also recorded. During anesthesia maintenance, the target concentrations of remifentanil and propofol in group A were significantly lower than that in group B (2.12 ± 0.35 vs 2.50 ± 0.21 ng/mL and 2.54 ± 0.22 vs 2.86 ± 0.31 μg/mL, respectively; P < 0.01). The time from drug withdrawal to eye opening upon the patient hearing his/her name called and reaching an Aldrete score of 9 points in group A was considerably shorter than Z.G. Guo et al. 7598©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (3): 7597-7604 (2015) that in group B (7.90 ± 0.58 vs 8.35 ± 0.66 min and 9.15 ± 0.69 vs 11.13 ± 0.96 min, respectively; P < 0.01). In both groups, mean arterial pressure and heart rate values at each time point after loss of consciousness were significantly lower than the baseline values (P < 0.05), with the exception of 2 min after intubation. The use of BIS to monitor anesthetic depth in patients with severe burns receiving TCI of remifentanil and propofol during the perioperative period reduces propofol consumption and shortens the consciousness recovery time in patients.

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Exploring the pharmacokinetics of oral ketamine in children undergoing burns procedures

Cited by 39 publications

References 42 publications

Population Pharmacokinetics of Intramuscular and Intravenous Ketamine in Children

Population Pharmacokinetics of Intramuscular and Intravenous Ketamine in Children

Procedural Pain Management in Neonates, Infants and Children

Bispectral index for monitoring anesthetic depth in patients with severe burns receiving target-controlled infusion of remifentanil and propofol

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