Pathogenesis of pulmonary edema associated with the adult respiratory distress syndrome.

Pulmonary edema is common cause of acute respiratory failure and can be seen in not only cardiac but also noncardiac diseases. The pathophysiologic mechanism for the development of acute pulmonary edema in any clinical situation can usually be explained alterations in the forces governing the transvascular flux of fluid in the pulmonary microvasculature, according to the Starling equation. "Cardiac" pulmonary edema is primarily due to an increase in the capillary hydrostatic pressure of sufficient magnitude to overcome the forces maintaining fluid within the vessel and the ability of the lymphatics to drain the transudated fluid. On the other hand, pulmonary edema occurring in association with noncardiac disease (e.g., sepsis, aspiration or shock) is secondary to an increase in the permeability of the pulmonary microvasculature and is referred to as noncardiogenic pulmonary edema or the adult respiratory distress syndrome. This article examines the mechanisms for the development of pulmonary edema and discusses the differences between the cardiac and noncardiac types.     

Antibiotic dosing in the 'at risk' critically ill patient: Linking pathophysiology with pharmacokinetics/pharmacodynamics in sepsis and trauma patients

Background

Critical illness, mediated by trauma or sepsis, can lead to physiological changes that alter the pharmacokinetics of antibiotics and may result in sub-therapeutic concentrations at the sites of infection. The first aim of this project is to identify the clinical characteristics of critically ill patients with significant trauma that have been recently admitted to ICU that may predict the dosing requirements for the antibiotic, cefazolin. The second aim of this is to identify the clinical characteristics of critically ill patients with sepsis that may predict the dosing requirements for the combination antibiotic, piperacillin-tazobactam.

Methods/Design

This is an observational pharmacokinetic study of patients with trauma (cefazolin) or with sepsis (piperacillin-tazobactam). Participants will have samples from blood and urine, collected at different intervals. Patients will also have a microdialysis catheter inserted into subcutaneous tissue to measure interstitial fluid penetration of the antibiotic. Participants will be administered sinistrin, indocyanine green and sodium bromide as well as have cardiac output monitoring performed and tetrapolar bioimpedance to determine physiological changes resulting from pathology. Analysis of samples will be performed using validated liquid chromatography tandem mass-spectrometry. Pharmacokinetic analysis will be performed using non-linear mixed effects modeling to determine individual and population pharmacokinetic parameters of antibiotics.

Discussion

The study will describe cefazolin and piperacillin-tazobactam concentrations in plasma and the interstitial fluid of tissues in trauma and sepsis patients respectively. The results of this study will guide clinicians to effectively dose these antibiotics in order to maximize the concentration of antibiotics in the interstitial fluid of tissues.