Pharmacokinetics of S‐ketamine during prolonged sedation at the pediatric intensive care unit

Flint, Robert B.; Brouwer, Carole N. M.; Kränzlin, Anne S. C.; Lie‐A‐Huen, Loraine; Bos, Albert P.; Mathôt, Ron A. A.

doi:10.1111/pan.13239

Cited by 14 publications

(10 citation statements)

References 37 publications

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“…Twenty-five percent received a concomitant infusion of neuromuscular-blocking agent. The median length of the PICU stay was 17 days (IQR, [12][13][14][15][16][17][18][19][20][21][22][23][24]. The mortality rate at the time of PICU discharge was 12%.…”

Section: Resultsmentioning

confidence: 99%

Ketamine Prolonged Infusions in the Pediatric Intensive Care Unit: a Tertiary-Care Single-Center Analysis

Sperotto¹,

Giaretta²,

Mondardini³

et al. 2021

The Journal of Pediatric Pharmacology and Therapeutics

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OBJECTIVE Ketamine is commonly used as an anesthetic and analgesic agent for procedural sedation, but there is little evidence on its current use as a prolonged continuous infusion in the PICU. We sought to analyze the use of ketamine as a prolonged infusion in critically ill children, its indications, dosages, efficacy, and safety. METHODS We retrospectively reviewed the clinical charts of patients receiving ketamine for ≥24 hours in the period 2017–2018 in our tertiary care center. Data on concomitant treatments pre and 24 hours post ketamine introduction and adverse events were also collected. RESULTS Of the 60 patients included, 78% received ketamine as an adjuvant of analgosedation, 18% as an adjuvant of bronchospasm therapy, and 4% as an antiepileptic treatment. The median infusion duration was 103 hours (interquartile range [IQR], 58–159; range, 24–287), with median dosages between 15 (IQR, 10–20; range, 5–47) and 30 (IQR, 20–50; range, 10–100) mcg/kg/min. At 24 hours of ketamine infusion, dosages/kg/hr of opioids significantly decreased (p < 0.001), and 81% of patients had no increases in dosages of concomitant analgosedation. For 27% of patients with bronchospasm, the salbutamol infusions were lowered at 24 hours after ketamine introduction. Electroencephalograms of epileptic patients (n = 2) showed resolution of status epilepticus after ketamine administration. Adverse events most likely related to ketamine were hypertension (n = 1), hypersalivation (n = 1), and delirium (n = 1). CONCLUSIONS Ketamine can be considered a worthy strategy for the analgosedation of difficult-to-sedate patients. Its use for prolonged sedation allows the sparing of opioids. Its efficacy in patients with bronchospasm or status epilepticus still needs to be investigated.

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Section: Resultsmentioning

confidence: 99%

Ketamine Prolonged Infusions in the Pediatric Intensive Care Unit: a Tertiary-Care Single-Center Analysis

Sperotto¹,

Giaretta²,

Mondardini³

et al. 2021

The Journal of Pediatric Pharmacology and Therapeutics

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“…Study 24. Flint et al 34 (2017) studied the pharmacokinetics of S-ketamine in a pediatric population requiring long-term sedation in the pediatric intensive care unit. S-Ketamine combined with lorazepam was administered for 5 days to 25 children as part of a sedation rotation schedule.…”

Section: Description Of Studiesmentioning

confidence: 99%

“…As described above, Brunette et al, 24 Herd et al, 22 and Goldberg et al 26 were excluded because of the mixed pediatric and adult populations or lacking standard errors. 22,24,26 The study by Flint et al 34 was excluded from the volume of distribution analysis because the norketamine volume of compartment 1 (V1) was fixed at 1. The weighted mean volume of distribution equaled 142 l/70 kg (95% CI, 87 to 298 l/70 kg).…”

Section: Meta-analysesmentioning

confidence: 99%

Ketamine Pharmacokinetics

Kamp¹,

Olofsen²,

Henthorn³

et al. 2020

Anesthesiology

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Background Several models describing the pharmacokinetics of ketamine are published with differences in model structure and complexity. A systematic review of the literature was performed, as well as a meta-analysis of pharmacokinetic data and construction of a pharmacokinetic model from raw data sets to qualitatively and quantitatively evaluate existing ketamine pharmacokinetic models and construct a general ketamine pharmacokinetic model. Methods Extracted pharmacokinetic parameters from the literature (volume of distribution and clearance) were standardized to allow comparison among studies. A meta-analysis was performed on studies that performed a mixed-effect analysis to calculate weighted mean parameter values and a meta-regression analysis to determine the influence of covariates on parameter values. A pharmacokinetic population model derived from a subset of raw data sets was constructed and compared with the meta-analytical analysis. Results The meta-analysis was performed on 18 studies (11 conducted in healthy adults, 3 in adult patients, and 5 in pediatric patients). Weighted mean volume of distribution was 252 l/70 kg (95% CI, 200 to 304 l/70 kg). Weighted mean clearance was 79 l/h (at 70 kg; 95% CI, 69 to 90 l/h at 70 kg). No effect of covariates was observed; simulations showed that models based on venous sampling showed substantially higher context-sensitive half-times than those based on arterial sampling. The pharmacokinetic model created from 14 raw data sets consisted of one central arterial compartment with two peripheral compartments linked to two venous delay compartments. Simulations showed that the output of the raw data pharmacokinetic analysis and the meta-analysis were comparable. Conclusions A meta-analytical analysis of ketamine pharmacokinetics was successfully completed despite large heterogeneity in study characteristics. Differences in output of the meta-analytical approach and a combined analysis of 14 raw data sets were small, indicative that the meta-analytical approach gives a clinically applicable approximation of ketamine population parameter estimates and may be used when no raw data sets are available. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

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“…The purpose of this case report was not to describe ketamine-induced side effects during PICU hospitalization, but rather to pose questions regarding the long-term consequences of ketamine use in the sedation and analgesia of infants. In particular, the present case prompts questions as to whether the therapeutic use of ketamine for sedation is beneficial considering its long-lasting behavioral consequences in the immature brain, and whether the difficulty in controlling ketamine and the pharmacokinetic profile of its active metabolites induces behavioral alterations in pediatric patients (10).…”

Section: Discussionmentioning

confidence: 94%

Long-lasting neurocognitive disorders: a case report of previously undescribed adverse effects after ketamine sedation and analgesia in a pediatric patient

Machado-Ferraro¹,

Soriano-de-Mello²,

Moura³

et al. 2022

Ann Transl Med

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Pharmacokinetics of S‐ketamine during prolonged sedation at the pediatric intensive care unit

Abstract: Substantial interpatient variability in pharmacokinetics in children complicates the development of adequate dosage regimen for continuous sedation.

Cited by 14 publications

References 37 publications

Ketamine Prolonged Infusions in the Pediatric Intensive Care Unit: a Tertiary-Care Single-Center Analysis

Ketamine Prolonged Infusions in the Pediatric Intensive Care Unit: a Tertiary-Care Single-Center Analysis

Ketamine Pharmacokinetics

Long-lasting neurocognitive disorders: a case report of previously undescribed adverse effects after ketamine sedation and analgesia in a pediatric patient

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