Soluble Fms-Like Tyrosine Kinase-1 Associates With Risk of Acute Respiratory Distress Syndrome and Mortality in Sepsis.

Importance: The vascular endothelial growth factor (VEGF) signaling pathway is important in the pathogenesis of acute respiratory distress syndrome (ARDS) with supportive genetic and proteomic evidence. Genetic polymorphisms within FLT1, which encodes VEGF receptor 1, associate with risk of ARDS in sepsis. Soluble Fms-like tyrosine kinase-1 (sFlt-1) is a secreted splice variant of FLT1 that acts as a potent antagonist to circulating VEGF.

Propofol: A Medication That Changed Pediatric Anesthesia Practice.

The introduction of propofol changed our understanding of pediatric anesthesia pharmacology, research approaches for intravenous drug study, and led to infusion pump development for the maintenance phase of anesthesia. The story of propofol development provides a blueprint for other intravenous drug development. The introduction of the target concentration strategy based on pharmacokinetic-pharmacodynamic and covariate understanding is central to total intravenous anesthesia techniques and is best exemplified by propofol.

Intravenous Dabigatran for Anticoagulation for Cardiopulmonary Bypass in a Sheep Model.

Background: Heparin is the standard anticoagulant used during cardiopulmonary bypass (CPB). However, there are problems with heparin, including immunogenicity and variability of effect, that make a search for an alternative desirable. Dabigatran anticoagulation has been reported to provide adequate conditions for CPB in a rabbit model.

Identifying a unique signature of sepsis in patients with pre-existing cirrhosis.

Background: The pre-existing diagnosis of cirrhosis is a complicating factor in the progression and prognosis of sepsis; however, the unique epidemiology, sepsis characteristics, and underlying mechanisms of immune dysregulation in sepsis among patients with cirrhosis remain incompletely understood. Our primary objective was to identify clinical outcomes and biological characteristics that differ between patients with and without cirrhosis among critically ill patients with sepsis.

Methods: We analyzed data from a prospective cohort of critically ill patients presenting to single center with sepsis.

Pharmacokinetics of Intraperitoneal Lidocaine for Sustained Postoperative Analgesia in Adults.

Background And Objective: Intraperitoneal lidocaine is an emerging strategy for analgesia following abdominal surgery but its pharmacokinetics are poorly quantified. We aimed to develop a pharmacokinetic model for unbound and total lidocaine by intraperitoneal and intravenous routes.

Methods: Unbound and total lidocaine concentrations, and pain scores (visual analogue score 0-10) were from a published randomized control trial of adults (n = 56) undergoing laparoscopic colon resection.

Pharmacokinetics of Methadone in Adult Patients Undergoing Cardiac Surgery With Cardiopulmonary Bypass.

Background: Cardiopulmonary bypass (CPB) induces profound physiological changes that may alter the pharmacokinetics of methadone. We aimed to describe the pharmacokinetics of an intravenous bolus of methadone racemate in adult patients undergoing heart surgery with CPB.

Methods: We prospectively studied 29 patients aged 45 to 75 years scheduled for cardiac surgery with CPB who received methadone 0.

Absorption pharmacokinetics and feasibility of intranasal dexmedetomidine in patients under general anaesthesia.

Background: The use of intranasal dexmedetomidine is hampered by a limited understanding of its absorption pharmacokinetics.

Methods: We examined the pharmacokinetics and feasibility of intranasal dexmedetomidine administered in the supine position to adult patients undergoing general anaesthesia. Twenty-eight patients between 35 and 80 years of age, ASA 1-3 and weight between 50 and 100 kg, who underwent elective unilateral total hip or knee arthroplasty under general anaesthesia were recruited.

A pharmacokinetic framework describing antibiotic adsorption to cardiopulmonary bypass devices.

Cardiopulmonary bypass (CPB) can alter pharmacokinetic (PK) parameters and the drug may adsorb to the CPB device, altering exposure. Cefazolin is a beta-lactam antibiotic used for antimicrobial prophylaxis during cardiac surgery supported by CPB. Adsorption of cefazolin could result in therapeutic failure.

Pediatric anesthesia in Australia and New Zealand and health inequity among First Nations and Māori children.

Australia and New Zealand are two countries in the Southern Pacific region. They share many pediatric anesthesia similarities in terms of medical organizational systems, education, training, and research, however there are important differences between the two nations in relation to geography, the First Nations populations and the history of colonization. While the standards for pediatric anesthesia and the specialty training requirements are set by the Australian and New Zealand College of Anesthetists and the Society for Pediatric Anesthesia in New Zealand and Australia, colonization has created distinct challenges that each nation now faces in order to improve the anesthetic care of its pediatric population.

Time-Varying Clearance in Milrinone Pharmacokinetics from Premature Neonates to Adolescents.

Background And Objectives: Milrinone is an inotrope and vasodilator used for prophylaxis or treatment of low cardiac output syndrome after weaning from cardiopulmonary bypass (CPB). It is renally eliminated and has an acceptable therapeutic range of 100-300 μg/L, but weight-based dosing alone is associated with poor target attainment. We aimed to develop a population pharmacokinetic model for milrinone from premature neonates to adolescents, and to evaluate how age, renal function and recovery from CPB may impact dose selection.

Feasibility and Acceptability of Using Wireless Limited Polysomnography to Capture Sleep Before, During, and After Hospitalization for Patients With Planned Cardiothoracic Surgery.

Background: Sleep disruption, a common symptom among patients requiring cardiovascular surgery, is a potential risk factor for the development of postoperative delirium. Postoperative delirium is a disorder of acute disturbances in cognition associated with prolonged hospitalization, cognitive decline, and mortality.

Objective: The aim of this study was to evaluate the feasibility and acceptability of using polysomnography (PSG) to capture sleep in patients with scheduled cardiothoracic surgery.

Dabigatran pharmacokinetic-pharmacodynamic in sheep: Informing dose for anticoagulation during cardiopulmonary bypass.

Background: The effect of the anticoagulant, dabigatran, and its antagonist, idarucizumab, on coagulation remains poorly quantified. There are few pharmacokinetic-pharmacodynamic data available to determine dabigatran dose in humans or animals undergoing cardiopulmonary bypass.

Methods: Five sheep were given intravenous dabigatran 4 mg/kg.

Preliminary pharmacokinetics and patient experience of jet-injected dexmedetomidine in healthy adults.

Jet injection is a drug delivery system without a needle. A compressed liquid drug formulation pierces the skin, depositing the drug into the subcutaneous or intramuscular tissues. We investigated the pharmacokinetics and patient experience of dexmedetomidine administered using jet injection in six healthy adult study participants.

Exposure to ambient air pollutants and acute respiratory distress syndrome risk in sepsis.

Purpose: Exposures to ambient air pollutants may prime the lung enhancing risk of acute respiratory distress syndrome (ARDS) in sepsis. Our objective was to determine the association of short-, medium-, and long-term pollutant exposures and ARDS risk in critically ill sepsis patients.

Methods: We analyzed a prospective cohort of 1858 critically ill patients with sepsis, and estimated short- (3 days), medium- (6 weeks), and long- (5 years) term exposures to ozone, nitrogen dioxide (NO), sulfur dioxide (SO), carbon monoxide (CO), particulate matter < 2.

Perioperative Acetaminophen Dosing in Obese Children.

Acetaminophen is a commonly used perioperative analgesic drug in children. The use of a preoperative loading dose achieves a target concentration of 10 mg/L associated with a target analgesic effect that is 2.6 pain units (visual analogue scale 1-10).

Causes, Consequences, and Treatments of Sleep and Circadian Disruption in the ICU: An Official American Thoracic Society Research Statement.

Sleep and circadian disruption (SCD) is common and severe in the ICU. On the basis of rigorous evidence in non-ICU populations and emerging evidence in ICU populations, SCD is likely to have a profound negative impact on patient outcomes. Thus, it is urgent that we establish research priorities to advance understanding of ICU SCD.