Bridget B. Swindell

The effects of ibuprofen on the physiology and survival of patients with sepsis

BACKGROUND In patients with sepsis the production of arachidonic acid metabolites by cyclooxygenase increases, but the pathophysiologic role of these prostaglandins is unclear. In animal models, inhibition of cyclooxygenase by treatment with ibuprofen before the onset of sepsis reduces physiologic abnormalities and improves survival. In pilot studies of patients with sepsis, treatment with ibuprofen led to improvements in gas exchange and airway mechanics. METHODS From October 1989 to March 1995, we conducted a randomized, double-blind, placebo-controlled trial of intravenous ibuprofen (10 mg per kilogram of body weight [maximal dose, 800 mg], given every six hours for eight doses) in 455 patients who had sepsis, defined as fever, tachycardia, tachypnea, and acute failure of at least one organ system. RESULTS In the ibuprofen group, but not the placebo group, there were significant declines in urinary levels of prostacyclin and thromboxane, temperature, heart rate, oxygen consumption, and lactic acidosis. With ibuprofen therapy there was no increased incidence of renal dysfunction, gastrointestinal bleeding, or other adverse events. However, treatment with ibuprofen did not reduce the incidence or duration of shock or the acute respiratory distress syndrome and did not significantly improve the rate of survival at 30 days (mortality, 37 percent with ibuprofen vs 40 percent with placebo). CONCLUSIONS In patients with sepsis, treatment with ibuprofen reduces levels of prostacyclin and thromboxane and decreases fever, tachycardia, oxygen consumption, and lactic acidosis, but it does not prevent the development of shock or the acute respiratory distress syndrome and does not improve survival.

Hypoproteinemia predicts acute respiratory distress syndrome development, weight gain, and death in patients with sepsis.

ObjectiveStarling’s equation indicates that reduced oncotic pressure gradients will favor edema formation, and the current consensus definition of acute respiratory distress syndrome (ARDS) excludes only the hydrostatic pressure contribution. We hypothesized that low serum total protein levels might correlate with the likelihood of ARDS in at-risk patients because serum total protein is the chief determinant of oncotic pressure in humans. DesignRegression analysis to compare outcomes in patients with low serum total protein levels with outcomes in patients with normal serum total protein levels with respect to weight change, development of ARDS, and mortality. SettingIntensive care units (ICUs) of seven clinical centers in North America. PatientsA total of 455 ICU patients who met consensus criteria for severe sepsis (178 of whom developed ARDS) from a recently completed prospective clinical trial. InterventionNone. Measurements and Main ResultsWe found that 92% of the patients developing ARDS had low or borderline serum total protein levels (<6 g/dL). Logistic and multiple regression analyses confirmed that of 18 clinical variables, initial serum total protein level and protein change over time were the most statistically significant predictors of weight gain, prolonged mechanical ventilation, ARDS development, and mortality in the study population. This correlation remained significant after adjustment for the other major predictors of outcome present at baseline (ie, Acute Physiology and Chronic Health Evaluation II score). ConclusionsHypoproteinemia is significantly correlated with fluid retention and weight gain, development of ARDS and poor respiratory outcome, and mortality in patients with sepsis. Prospective, randomized trials of serum protein manipulation are needed to establish whether there is a cause-effect relationship to this association.

Diagnosis and therapy of acute respiratory distress syndrome in adults: an international survey.

In an attempt to identify the range of opinions influencing the diagnosis and therapy of patients with the adult respiratory distress syndrome (ARDS), a postal survey was mailed to 3,164 physician members of the American Thoracic Society Critical Care Assembly. The questionnaire asked opinions regarding the factors important in the diagnosis of ARDS and its treatment. Thirty-one percent of physicians surveyed responded within 4 weeks, the vast majority of which were board certified or eligible in Internal Medicine, Pulmonary Disease, and/or Critical Care Medicine. A known predisposing cause, measure of oxygenation efficiency, and a chest radiograph depicting pulmonary edema were reported to be the most important criteria for a clinical and research diagnosis of ARDS. Lung compliance and bronchoalveolar lavage neutrophil or protein content were reportedly less important. The initial treatment of patients with ARDS was reported to be most commonly accomplished using volume-cycled ventilation in the assist/control mode. Nearly half the responders reported using lower tidal volumes (5 to 9 mL/kg) than the traditionally recommended 10 to 15 mL/kg. Most respondents indicated they have intentionally allowed CO2 retention. On average, oxygen toxicity was thought to begin at an FIO2 between 0.5 and 0.6. It was reported that modest levels of positive end-expiratory pressure (PEEP) were used in incremental fashion as FiO2 requirements increased. Perceived indications for insertion of pulmonary artery catheters and compensation of the effects of PEEP on the pulmonary artery occlusion pressure varied widely among the responders. We conclude that reported practice patterns regarding the care of ARDS patients vary widely even within a relatively homogenous group of critical care practitioners.

CommLog/spl copy/: A communication log system for clinical trials

Thanks to the advent of information technologies, the emergence of commercial products for electronic clinical trials has improved many aspects of conducting clinical trials. While there are many new options available to facilitate the collection of patient data, little advancements have been made in the way in which information generated from the coordination of a clinical trial is managed. The coordination of a clinical trial has proven to have a significant impact on the quality and economy of clinical trials. The Vanderbilt Coordinating Center has designed and implemented a communication log system (CommLog/spl copy/) to streamline the coordination of clinical trials in order to improve the quality and economy of clinical trials. The CommLog/spl copy/ has been operational for several industry-sponsored phase II/III clinical trails and has provided a knowledge base for the studies and repository for useful study information.

Prototyping A Workstation-based Icu Charting System

ARSTRACT We describe a prototype ICU charting system based on workstation technology. The system is designed to provide a natural, paper-style user interface. Significant graphical capabilities are included. The prototypc is implemented using Microsoft Excel running under MS Windows. We discuss the issues and methods involved in the creation of the prototype. INTRODUCTION AND RACKGROUND The explosion of data acquired through intcnsive care monitoring of critically ill patients has posed a major problem for physicians and nurses for the past 10-15 years. Several serious attcmpts have bcen madc, both commercially and by individual medical centers to develop systems capable of handling these data in a manner not intimidating to non- computer competent mcdical personnel. These attempts have gcnerally been less than fully successful because sufficient skills wcrc not ablc to be maintained across a wide range of personncl. Further, most commcrcially available systems are extremely cumbersome to use (command driven or multiple level menu systems), are relatively slow due to hardware constraints, and support only relatively low resolution graphics output with small viewing areas. However, new computing technology, namcly, high performance workstations with high resolution bit-mapped displays promise to provide a development and user environmcnt capablc of addressing the problems described above. Only rcccntly havc conimcrcial products been announced that begin to address the ICU data problem utilizing workstation technology. Our goal is to prototype an ICU workstation meeting local design requirements. Thcse dcsign requirements include automation of the data collection process, improving tk quality of charted data, increasing the effcctiveness of interpretation of charted data through new visualization tcchniques, crcating a ncw research tool through the creation of research data bases, decreasing the workload of nursing staff, creating a more uniform charting cnvironment, and creating a charting environment that is natural to use. The system is developed around the concept of rcplicating the functions of the ICU chart, a large, two dimensional spreadsheet, whcrc rows reprcscnt itcms and columns represent timc. Typically, the flow sheet represents one full day of patient data. On this flowshcct the nurse records all vital information related to the patient including viral signs, medication, fluid balance, lab results, interventions, etc.