Publications by authors named "David Drover"

Background: Postoperative cognitive decline (POCD) is the predominant complication affecting patients over 60 years old following major surgery, yet its prediction and prevention remain challenging. Understanding the biological processes underlying the pathogenesis of POCD is essential for identifying mechanistic biomarkers to advance diagnostics and therapeutics. This study aimed to provide a comprehensive analysis of immune cell trajectories differentiating patients with and without POCD and to derive a predictive score enabling the identification of high-risk patients during the preoperative period.

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Unlabelled: Postoperative cognitive decline (POCD) is the predominant complication affecting elderly patients following major surgery, yet its prediction and prevention remain challenging. Understanding biological processes underlying the pathogenesis of POCD is essential for identifying mechanistic biomarkers to advance diagnostics and therapeutics. This longitudinal study involving 26 elderly patients undergoing orthopedic surgery aimed to characterize the impact of peripheral immune cell responses to surgical trauma on POCD.

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Background: Intraoperative hypotension is common during noncardiac surgery and is associated with postoperative myocardial infarction, acute kidney injury, stroke, and severe infection. The Hypotension Prediction Index software is an algorithm based on arterial waveform analysis that alerts clinicians of the patient's likelihood of experiencing a future hypotensive event, defined as mean arterial pressure < 65 mmHg for at least 1 min.

Methods: Two analyses included (1) a prospective, single-arm trial, with continuous blood pressure measurements from study monitors, compared to a historical comparison cohort.

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Background: Fentanyl is widely used for analgesia and sedation in neonates, but pharmacokinetic (PK) analysis in this population has been limited by the relatively large sample volumes required for plasma-based assays.

Methods: In this multicenter observational study of fentanyl kinetics in neonates up to 42 weeks of postmenstrual age (PMA) who received fentanyl boluses and continuous infusions, dried blood spots were used for small-volume sampling. A population PK analysis was used to describe fentanyl disposition in term and preterm neonates.

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Introduction: Dexmedetomidine is one of the anesthetics of choice for drug induced sleep endoscopy (DISE), with advantages including limited respiratory depression, analgesia, and decreased incidence of emergence delirium. However, challenges with determining sedation levels and prolonged recovery have limited its usage. An improved understanding of the effect of dexmedetomidine on the level of sedation and the corresponding electroencephalographic (EEG) changes could help overcome these barriers.

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Multiple electroencephalographic (EEG) monitors and their associated EEG markers have been developed to aid in assessing the level of sedation in the operating room. While many studies have assessed the response of these markers to propofol sedation and anesthetic gases, few studies have compared these markers when using dexmedetomidine, an alpha-2 agonist. Fifty-one patients underwent drug induced sleep endoscopy with dexmedetomidine sedation.

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Objective: To determine if treatment with a 5-HT3 antagonist (ondansetron) reduces need for opioid therapy in infants at risk for neonatal opioid withdrawal syndrome (NOWS).

Study Design: A multicenter, randomized, placebo controlled, double blind clinical trial of ninety (90) infants. The intervention arms were intravenous ondansetron or placebo during labor followed by a daily dose of ondansetron or placebo in infants for five days.

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Objective: Ampicillin is used for multiple peripartum indications including prevention of neonatal group B streptococcus (GBS) and treatment of chorioamnionitis. Despite its widespread use in obstetrics, existing pharmacokinetic data for ampicillin do not address contemporary indications or dosing paradigms for this population. We sought to characterize the pharmacokinetic profile of ampicillin administered to laboring women.

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Background: Several devices record and interpret patient brain activity via electroencephalogram (EEG) to aid physician assessment of anaesthetic effect. Few studies have compared EEG monitors on data from the same patient. Here, we describe a set-up to simultaneously compare the performance of three processed EEG monitors using pre-recorded EEG signals from older surgical patients.

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Background: Theophylline, a non-selective adenosine receptor antagonist, improves renal perfusion in the setting of hypoxia-ischemia and may offer therapeutic benefit in neonates with hypoxic-ischemic encephalopathy (HIE) undergoing hypothermia. We evaluated the pharmacokinetics and dose-exposure relationships of theophylline in this population to guide dosing strategies.

Methods: A population pharmacokinetic analysis was performed in 22 neonates with HIE undergoing hypothermia who were part of a prospective study or retrospective chart review.

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Objectives: Little is known on the impact of continuous renal replacement therapy on antimicrobial dose requirements in children. In this study, we evaluated the pharmacokinetics of commonly administered antimicrobials in an ex vivo continuous renal replacement therapy model.

Design: An ex vivo continuous renal replacement therapy circuit was used to evaluate drug-circuit interactions and determine the disposition of five commonly used antimicrobials (meropenem, piperacillin, liposomal amphotericin B, caspofungin, and voriconazole).

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Background: Although few studies have used ketamine for induction and maintenance of pediatric anesthesia, official dosage recommendations are lacking. This study evaluates the outcomes of adult anesthetic doses in a pediatric population through pharmacokinetic modeling and computer simulations in an attempt to recommend an adequate ketamine dosing regimen.

Methods: Ketamine plasma concentration-time data in 19 children (age 8 months to 16 years; weight 5.

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Background: Some practitioners "prime" small IV angiocatheter needles with 0.9% sodium chloride-claiming this modification speeds visual detection of blood in the angiocatheter flash chamber on vessel cannulation.

Methods: We compared the time required for human blood to travel the length of saline-primed and saline-unprimed 24- and 22-gauge angiocatheter needles (Introcan Safety IV Catheter; B.

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While geriatric patients have a high likelihood of requiring anesthesia, they carry an increased risk for adverse cognitive outcomes from its use. Previous work suggests this could be mitigated by better intraoperative monitoring using indexes defined by several processed electroencephalogram (EEG) measures. Unfortunately, inconsistencies between patients and anesthetic agents in current analysis techniques have limited the adoption of EEG as standard of care.

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Background: Dexmedetomidine (DEX) is a sedative and analgesic medication that is frequently used postoperatively in children after liver transplantation. Hepatic dysfunction, including alterations in drug clearance, is common immediately after liver transplantation. However, the pharmacokinetics (PK) of DEX in this population is unknown.

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Nitrous oxide (NO) and remifentanil (remi) are used along with other anesthetic and adjuvant agents for routine surgical anesthesia, yet the electroencephalogram (EEG) changes produced by this combination are poorly described. NO administered alone produces EEG spectral characteristics that are distinct from most hypnotics. Furthermore, EEG frequency-derived trends before and after clinically relevant time points vary depending on NO concentration.

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Purpose Of Review: Electroencephalography (EEG) was introduced into anesthesia practice in the 1990s as a tool to titrate anesthetic depth. However, limitations in current analysis techniques have called into question whether these techniques improve standard of care, or instead call for improved, more ubiquitously applicable measures to assess anesthetic transitions and depth. This review highlights emerging analytical approaches and techniques from neuroscience research that have the potential to better capture anesthetic transitions to provide better measurements of anesthetic depth.

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OBJECTIVE MR-guided laser interstitial thermal therapy (MRgLITT) is a minimally invasive method for thermal destruction of benign or malignant tissue that has been used for selective amygdalohippocampal ablation for the treatment of temporal lobe epilepsy. The authors report their initial experience adopting a real-time MRI-guided stereotactic platform that allows for completion of the entire procedure in the MRI suite. METHODS Between October 2014 and May 2016, 17 patients with mesial temporal sclerosis were selected by a multidisciplinary epilepsy board to undergo a selective amygdalohippocampal ablation for temporal lobe epilepsy using MRgLITT.

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The aim of the study was to identify the optimal therapeutic maternal magnesium drug exposure and maternal serum concentration to prevent cerebral palsy in the extremely preterm fetus. We applied a previously constructed pharmacokinetic model adjusted for indication to a large cohort of pregnant women receiving magnesium sulfate to prevent cerebral palsy in their preterm offspring at 20 different US academic centers between December 1997 and May 2004. We simulated the population-based individual maternal serum magnesium concentration at the time of delivery and the total magnesium dose for each woman who received magnesium sulfate to determine the relationship between maternal serum magnesium level at the time of delivery and the development of cerebral palsy.

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Background: The influence of obesity on the pharmacokinetic (PK) behavior of remifentanil is incompletely understood. The aim of the current investigation was to develop a new population PK model for remifentanil that would adequately characterize the influence of body weight (among other covariates, e.g.

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Background: In the perioperative period, anesthesiologists and postanesthesia care unit (PACU) nurses routinely prepare and administer small-volume IV injections, yet the accuracy of delivered medication volumes in this setting has not been described. In this ex vivo study, we sought to characterize the degree to which small-volume injections (≤0.5 mL) deviated from the intended injection volumes among a group of pediatric anesthesiologists and pediatric postanesthesia care unit (PACU) nurses.

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Morphine is commonly used in neonates with hypothermic ischemic encephalopathy (HIE) during therapeutic hypothermia to provide comfort and analgesia. However, pharmacokinetic data to support morphine dosing in this vulnerable population are lacking. A prospective, 2-center clinical pharmacokinetic study of morphine was conducted in 20 neonates (birthweight, 1.

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Objective: The aim of this study was to characterize the relationship between morphine plasma concentration and repeated time to postoperative remedication events in children undergoing cardiac surgery.

Methods: Data from our previously published study of morphine pharmacokinetics were utilized in this pharmacodynamic study. A population survival analysis based on hazard functions was undertaken in NONMEM(®).

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Objective: To compare VOTE classification findings (velum, oropharyngeal-lateral walls, tongue base, and epiglottis) for drug-induced sleep endoscopy (DISE) among patients with obstructive sleep apnea (OSA) using 2 sedation protocols.

Study Design: Case series with chart review.

Setting: Single tertiary institution.

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