Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016

OBJECTIVE: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012". DESIGN: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy wasdeveloped at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroupsand among the entire committee served as an integral part of the development. METHODS: The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. RESULTS: The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. CONCLUSIONS: Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.(AU)

A randomized trial of the effects of nebulized albuterol on pulmonary edema in brain-dead organ donors.

Donor lung utilization rates are persistently low primarily due to donor lung dysfunction. We hypothesized that a treatment that enhances the resolution of pulmonary edema by stimulating the rate of alveolar fluid clearance would improve donor oxygenation and increase donor lung utilization. We conducted a randomized, blinded, placebo-controlled trial of aerosolized albuterol (5mg q4h) versus saline placebo during active donor management in 506 organ donors.The primary outcome was change in oxygenation arterial partial pressure of oxygen/fraction of inspired oxygen [PaO2/FiO2] from enrollment to organ procurement.The albuterol (n»260) and placebo (n»246)groups were well matched for age, gender, ethnicity,smoking, and cause of brain death. The change in PaO2/FiO2 from enrollment to organ procurement did not differ between treatment groups (p»0.54) nor did donor lung utilization (albuterol 29% vs. placebo 32%,p»0.44). Donors in the albuterol versus placebo groups were more likely to have the study drug dose reduced (13% vs. 1%, p<0.001) or stopped (8% vs. 0%,p<0.001) for tachycardia. In summary, treatment with high dose inhaled albuterol during the donor management period did not improve donor oxygenation or increase donor lung utilization but did cause tachycardia.High dose aerosolized albuterol should not be used in donors to enhance the resolution of pulmonary edema.

Long-term cognitive impairment after critical illness.

BACKGROUND: Survivors of critical illness often have a prolonged and disabling form of cognitive impairment that remains inadequately characterized. METHODS: We enrolled adults with respiratory failure or shock in the medical or surgical intensive care unit (ICU), evaluated them for in-hospital delirium, and assessed global cognition and executive function 3 and 12 months after discharge with the use of the Repeatable Battery for the Assessment of Neuropsychological Status (population age-adjusted mean [±SD] score, 100±15, with lower values indicating worse global cognition) and the Trail Making Test, Part B (population age-, sex-, and education-adjusted mean score, 50±10, with lower scores indicating worse executive function). Associations of the duration of delirium and the use of sedative or analgesic agents with the outcomes were assessed with the use of linear regression, with adjustment for potential confounders. RESULTS: Of the 821 patients enrolled, 6% had cognitive impairment at baseline, and delirium developed in 74% during the hospital stay. At 3 months, 40% of the patients had global cognition scores that were 1.5 SD below the population means (similar to scores for patients with moderate traumatic brain injury), and 26% had scores 2 SD below the population means (similar to scores for patients with mild Alzheimer's disease). Deficits occurred in both older and younger patients and persisted, with 34% and 24% of all patients with assessments at 12 months that were similar to scores for patients with moderate traumatic brain injury and scores for patients with mild Alzheimer's disease, respectively. A longer duration of delirium was independently associated with worse global cognition at 3 and 12 months (P=0.001 and P=0.04, respectively) and worse executive function at 3 and 12 months (P=0.004 and P=0.007, respectively). Use of sedative or analgesic medications was not consistently associated with cognitive impairment at 3 and 12 months. CONCLUSIONS: Patients in medical and surgical ICUs are at high risk for long-term cognitive impairment. A longer duration of delirium in the hospital was associated with worse global cognition and executive function scores at 3 and 12 months. (Funded by the National Institutes of Health and others; BRAIN-ICU ClinicalTrials.gov number, NCT00392795.).

Beyond single-marker analyses: mining whole genome scans for insights into treatment responses in severe sepsis.

Management of severe sepsis, an acute illness with high morbidity and mortality, suffers from the lack of effective biomarkers and largely empirical predictions of disease progression and therapeutic responses. We conducted a genome-wide association study using a large randomized clinical trial cohort to discover genetic biomarkers of response to therapy and prognosis utilizing novel approaches, including combination markers, to overcome limitations of single-marker analyses. Sepsis prognostic models were dominated by clinical variables with genetic markers less informative. In contrast, evidence for gene-gene interactions were identified for sepsis treatment responses with genetic biomarkers dominating models for predicting therapeutic responses, yielding candidates for replication in other cohorts.

Operational implementation of prospective genotyping for personalized medicine: the design of the Vanderbilt PREDICT project.

The promise of "personalized medicine" guided by an understanding of each individual's genome has been fostered by increasingly powerful and economical methods to acquire clinically relevant information. We describe the operational implementation of prospective genotyping linked to an advanced clinical decision-support system to guide individualized health care in a large academic health center. This approach to personalized medicine entails engagement between patient and health-care provider, identification of relevant genetic variations for implementation, assay reliability, point-of-care decision support, and necessary institutional investments. In one year, approximately 3,000 patients, most of whom were scheduled for cardiac catheterization, were genotyped on a multiplexed platform that included genotyping for CYP2C19 variants that modulate response to the widely used antiplatelet drug clopidogrel. These data are deposited into the electronic medical record (EMR), and point-of-care decision support is deployed when clopidogrel is prescribed for those with variant genotypes. The establishment of programs such as this is a first step toward implementing and evaluating strategies for personalized medicine.

Pharmacogenetic treatment of acute respiratory distress syndrome.

Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) occur due to systemic inflammatory disorders or direct injury to the lung. The occurrence of ALI/ARDS is sporadic and is not reliably predicted by the type or severity of injury. A combination of patient characteristics and mechanism of injury are responsible for the sporadic nature of ALI/ARDS and its observed phenotypic variability. Research on the pathophysiology and genetics of ALI/ARDS continues to advance, revealing critical molecular pathways in disease development and specific genetic factors that alter the expression of disease. Despite these advances, pharmacologic therapies have yet to be developed for the prevention or treatment of disease. We anticipate that continued improvement of our understanding of the genetic and pathophysiologic mechanisms underlying ALI/ARDS combined with future clinical trials will allow pharmacogenetic therapies for ALI/ARDS to be developed.

Development of a large-scale de-identified DNA biobank to enable personalized medicine.

Our objective was to develop a DNA biobank linked to phenotypic data derived from an electronic medical record (EMR) system. An "opt-out" model was implemented after significant review and revision. The plan included (i) development and maintenance of a de-identified mirror image of the EMR, namely, the "synthetic derivative" (SD) and (ii) DNA extracted from discarded blood samples and linked to the SD. Surveys of patients indicated general acceptance of the concept, with only a minority ( approximately 5%) opposing it. As a result, mechanisms to facilitate opt-out included publicity and revision of a standard "consent to treatment" form. Algorithms for sample handling and procedures for de-identification were developed and validated in order to ensure acceptable error rates (<0.3 and <0.1%, respectively). The rate of sample accrual is 700-900 samples/week. The advantages of this approach are the rate of sample acquisition and the diversity of phenotypes based on EMRs.

Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM-ICU).

CONTEXT: Delirium is a common problem in the intensive care unit (ICU). Accurate diagnosis is limited by the difficulty of communicating with mechanically ventilated patients and by lack of a validated delirium instrument for use in the ICU. OBJECTIVES: To validate a delirium assessment instrument that uses standardized nonverbal assessments for mechanically ventilated patients and to determine the occurrence rate of delirium in such patients. DESIGN AND SETTING: Prospective cohort study testing the Confusion Assessment Method for ICU Patients (CAM-ICU) in the adult medical and coronary ICUs of a US university-based medical center. PARTICIPANTS: A total of 111 consecutive patients who were mechanically ventilated were enrolled from February 1, 2000, to July 15, 2000, of whom 96 (86.5%) were evaluable for the development of delirium and 15 (13.5%) were excluded because they remained comatose throughout the investigation. MAIN OUTCOME MEASURES: Occurrence rate of delirium and sensitivity, specificity, and interrater reliability of delirium assessments using the CAM-ICU, made daily by 2 critical care study nurses, compared with assessments by delirium experts using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. RESULTS: A total of 471 daily paired evaluations were completed. Compared with the reference standard for diagnosing delirium, 2 study nurses using the CAM-ICU had sensitivities of 100% and 93%, specificities of 98% and 100%, and high interrater reliability (kappa = 0.96; 95% confidence interval, 0.92-0.99). Interrater reliability measures across subgroup comparisons showed kappa values of 0.92 for those aged 65 years or older, 0.99 for those with suspected dementia, or 0.94 for those with Acute Physiology and Chronic Health Evaluation II scores at or above the median value of 23 (all P<.001). Comparing sensitivity and specificity between patient subgroups according to age, suspected dementia, or severity of illness showed no significant differences. The mean (SD) CAM-ICU administration time was 2 (1) minutes. Reference standard diagnoses of delirium, stupor, and coma occurred in 25.2%, 21.3%, and 28.5% of all observations, respectively. Delirium occurred in 80 (83.3%) patients during their ICU stay for a mean (SD) of 2.4 (1.6) days. Delirium was even present in 39.5% of alert or easily aroused patient observations by the reference standard and persisted in 10.4% of patients at hospital discharge. CONCLUSIONS: Delirium, a complication not currently monitored in the ICU setting, is extremely common in mechanically ventilated patients. The CAM-ICU appears to be rapid, valid, and reliable for diagnosing delirium in the ICU setting and may be a useful instrument for both clinical and research purposes.

Safety and dose relationship of recombinant human activated protein C for coagulopathy in severe sepsis.

OBJECTIVES: To assess the safety and effect on coagulopathy of a range of doses of recombinant human activated protein C (rhAPC). To determine an effective dose and duration of rhAPC for use in future clinical trials. DESIGN: Double-blind, randomized, placebo-controlled, multicenter, dose-ranging (sequential), phase II clinical trial. SETTING: Forty community or academic medical institutions in United States and Canada. PATIENTS: One hundred thirty-one adult patients with severe sepsis. INTERVENTIONS: Intravenous infusion of rhAPC (12, 18, 24, or 30 microg/kg/hr) or placebo for 48 or 96 hrs. MEASUREMENTS AND MAIN RESULTS: No significant differences in incidence of serious bleeding events (4% rhAPC, 5% placebo, p >.999) or incidence of serious adverse events (39% rhAPC, 46% placebo, p = 0.422) between rhAPC- and placebo-treated patients were observed. One of 53 rhAPC-treated patients with suitable immunogenicity samples had a low level, transient, non-neutralizing anti-APC antibody response not associated with any clinical adverse event. Significant dose-dependent decreases in both D-dimer (p <0.001) and end of infusion interleukin 6 levels (p =.021) were demonstrated. No statistically significant effects on fibrinogen or platelet counts were observed. A nonstatistically significant 15% relative risk reduction in 28-day all-cause mortality was observed between rhAPC- and placebo-treated patients. CONCLUSIONS: rhAPC was safe and well-tolerated and demonstrated a dose-dependent reduction in D-dimer and interleukin 6 levels relative to placebo. The dose of 24 microg/kg/hr for 96 hrs was selected for use in future clinical studies.

Low levels of protein C are associated with poor outcome in severe sepsis.

STUDY OBJECTIVE: To investigate whether protein C levels predict 30-day mortality rate, shock status, duration of ICU stay, and ventilator dependence in patients with sepsis. DESIGN: Retrospective analysis of a subset of a previously published, prospective, randomized, double-blind, placebo-controlled trial ("Effects of Ibuprofen on the Physiology and Survival of Patients With Sepsis" [ISS]). SETTING: A multicenter study performed in the United States and Canada (seven sites). PATIENTS: Seventy hospitalized patients with acute severe sepsis and failure in one or more organs at entry into the ISS trial. MEASUREMENTS AND MAIN RESULTS: Blood samples were obtained from all patients at baseline and at 20, 44, 72, and 120 h after the initiation of study drug (ibuprofen or placebo) infusion. Data obtained at these times included platelet count, prothrombin time, and partial thromboplastin time. The results described in this article are based on a subset of the total ISS population for whom additional coagulation assays were performed on the blood samples obtained at baseline and 44 h. These assays included protein C antigen, D-dimer, and fibrinogen levels. A total of 63 of the 70 patients (90%) studied in this report had acquired protein C deficiency at entry to the ISS trial (baseline). The presence and severity of acquired protein C deficiency were associated with poor clinical outcome, including lower survival rate, higher incidence of shock, and fewer ICU-free and ventilator-free days. CONCLUSIONS: Acquired protein C deficiency may be useful in predicting clinical outcome in patients with sepsis. Clinical studies are warranted to determine whether the replacement of protein C in sepsis patients may improve outcome.

Evaluation of delirium in critically ill patients: validation of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU).

OBJECTIVE: To develop and validate an instrument for use in the intensive care unit to accurately diagnose delirium in critically ill patients who are often nonverbal because of mechanical ventilation. DESIGN: Prospective cohort study. SETTING: The adult medical and coronary intensive care units of a tertiary care, university-based medical center. PATIENTS: Thirty-eight patients admitted to the intensive care units. MEASUREMENTS AND MAIN RESULTS: We designed and tested a modified version of the Confusion Assessment Method for use in intensive care unit patients and called it the CAM-ICU. Daily ratings from intensive care unit admission to hospital discharge by two study nurses and an intensivist who used the CAM-ICU were compared against the reference standard, a delirium expert who used delirium criteria from the Diagnostic and Statistical Manual of Mental Disorders (fourth edition). A total of 293 daily, paired evaluations were completed, with reference standard diagnoses of delirium in 42% and coma in 27% of all observations. To include only interactive patient evaluations and avoid repeat-observer bias for patients studied on multiple days, we used only the first-alert or lethargic comparison evaluation in each patient. Thirty-three of 38 patients (87%) developed delirium during their intensive care unit stay, mean duration of 4.2 +/- 1.7 days. Excluding evaluations of comatose patients because of lack of characteristic delirium features, the two critical care study nurses and intensivist demonstrated high interrater reliability for their CAM-ICU ratings with kappa statistics of 0.84, 0.79, and 0.95, respectively (p <.001). The two nurses' and intensivist's sensitivities when using the CAM-ICU compared with the reference standard were 95%, 96%, and 100%, respectively, whereas their specificities were 93%, 93%, and 89%, respectively. CONCLUSIONS: The CAM-ICU demonstrated excellent reliability and validity when used by nurses and physicians to identify delirium in intensive care unit patients. The CAM-ICU may be a useful instrument for both clinical and research purposes to monitor delirium in this challenging patient population.

New strategies for clinical trials in patients with sepsis and septic shock.

OBJECTIVE: The difficulty in identifying new treatment modalities that significantly reduce the mortality and morbidity rates associated with sepsis has highlighted the need to reevaluate the approach to clinical trial design. The United Kingdom Medical Research Council convened an International Working Party to address these issues. DATA SOURCES: The subject areas that were to be the focus of discussion were identified by the co-chairs, and group leaders were nominated. Preconference reading material was circulated to group members. STUDY SELECTION AND DATA EXTRACTION: Small-group discussion fed into an iterative process of feedback from plenary sessions, followed by the formulation of recommendations. Finally, each working group prepared a summary of its recommendations and these are reported herein. DATA SYNTHESIS: There were five key recommendations. First, investigators should no longer rely solely on the American College of Chest Physicians/Society of Critical Care Medicine definitions of sepsis or sepsis syndrome as the basis of trial entry. Entry criteria should be based on three principles: a) All patients should have infection; b) there should be evidence of a pathologic process that represents a biologically plausible target for the proposed intervention, for example, an abnormal circulating level of a biological marker pertinent to the study drug; and c) patients should fall into an appropriate category of severity (usually severe sepsis). Second, investigators should use a scoring system for organ dysfunctions that has been validated and that can be incorporated into all sepsis studies; agreement on the use of a single system would simplify comparisons between studies. Third, the primary outcome measure generally should be mortality rates, but under appropriate circumstances major morbidities could be considered as primary end points. Regardless of choice of the duration to primary end point, patients should be followed for > or =90 days. Fourth, sample size needs to be based on a realistic assessment of achievable effect size based on knowledge of the at-risk population. Fifth, subgroups should be few in number and should be defined a priori on the basis of variables present before randomization. CONCLUSIONS: Important changes in several aspects of trial design may improve the quality of clinical studies in sepsis and maximize the chance of identifying effective therapeutic agents.

Efficacy and safety of recombinant human activated protein C for severe sepsis.

BACKGROUND: Drotrecogin alfa (activated), or recombinant human activated protein C, has antithrombotic, antiinflammatory, and profibrinolytic properties. In a previous study, drotrecogin alfa activated produced dose-dependent reductions in the levels of markers of coagulation and inflammation in patients with severe sepsis. In this phase 3 trial, we assessed whether treatment with drotrecogin alfa activated reduced the rate of death from any cause among patients with severe sepsis. METHODS: We conducted a randomized, double-blind, placebo-controlled, multicenter trial. Patients with systemic inflammation and organ failure due to acute infection were enrolled and assigned to receive an intravenous infusion of either placebo or drotrecogin alfa activated (24 microg per kilogram of body weight per hour) for a total duration of 96 hours. The prospectively defined primary end point was death from any cause and was assessed 28 days after the start of the infusion. Patients were monitored for adverse events; changes in vital signs, laboratory variables, and the results of microbiologic cultures; and the development of neutralizing antibodies against activated protein C. RESULTS: A total of 1690 randomized patients were treated (840 in the placebo group and 850 in the drotrecogin alfa activated group). The mortality rate was 30.8 percent in the placebo group and 24.7 percent in the drotrecogin alfa activated group. On the basis of the prospectively defined primary analysis, treatment with drotrecogin alfa activated was associated with a reduction in the relative risk of death of 19.4 percent (95 percent confidence interval, 6.6 to 30.5) and an absolute reduction in the risk of death of 6.1 percent (P=0.005). The incidence of serious bleeding was higher in the drotrecogin alfa activated group than in the placebo group (3.5 percent vs. 2.0 percent, P=0.06). CONCLUSIONS: Treatment with drotrecogin alfa activated significantly reduces mortality in patients with severe sepsis and may be associated with an increased risk of bleeding.

Acute respiratory distress syndrome: innovative therapies.

Since its description in 1967, the acute respiratory distress syndrome (ARDS) has become one of the most studied pathophysiological processes in intensive care units worldwide. The current state of knowledge about this severe illness and its associated mediators has come from the study of relevant animal models. In the mid-1970s, the development of the sheep model of ARDS and later, the porcine model, led to the discovery of a wide variety of inflammatory lipid mediators, cytokines, and proteases, to name but a few. Recognition of the presence of such highly toxic mediators associated with the development of ARDS has led to numerous potential targets for drug development toward therapeutic intervention. Through implementation of a standardized definition for ARDS and its less severe sibling acute lung injury (ALI), growth in patient-oriented research has been possible. Substantial numbers of new therapies have been brought forth and examined in recent years, many of which remain controversial. This article is a critical appraisal of the potential therapeutic options investigated in recent years for the management of ALI/ARDS.

Changing pattern of organ dysfunction in early human sepsis is related to mortality.

OBJECTIVE: We examined the pattern of organ system dysfunction, the evolution of this pattern over time, and the relationship of these features to mortality in patients who had sepsis syndrome. DESIGN: Prospective, multicenter, observational study. SETTING: Intensive care units in tertiary referral teaching hospitals. PATIENTS: A total of 287 patients who had sepsis syndrome were prospectively identified in intensive care units. MATERIALS AND MEASUREMENTS: Cardiovascular, pulmonary, neurologic, coagulation, renal, and hepatic dysfunction were assessed at onset and on day 3 of sepsis syndrome. Organ dysfunction was classified as normal, mild, moderate, severe, and extreme dysfunction. We calculated the occurrence rate and associated 30-day mortality rate of organ dysfunction at the onset of sepsis syndrome. We then measured the change in organ dysfunction from onset to day 3 of sepsis syndrome and determined, for individual organ systems, the associated 30-day mortality rate. RESULTS: At the onset of sepsis syndrome, clinically significant pulmonary dysfunction was the most common organ failure, but was not related to 30-day mortality. Clinically significant cardiovascular, neurologic, coagulation, renal, and hepatic dysfunction were less common at the onset of sepsis syndrome but were significantly associated with the 30-day mortality rate. Worsening neurologic, coagulation, and renal dysfunction from onset to day 3 of sepsis syndrome were associated with significantly higher 30-day mortality than with improvement or no change in organ dysfunction. CONCLUSIONS: Increased mortality rate in sepsis syndrome is associated with a pattern characterized by failure of nonpulmonary organ systems and, in particular, worsening neurologic, coagulation, and renal dysfunction over the first 3 days. Although initial pulmonary dysfunction is common in patients with sepsis syndrome, it is not associated with an increased mortality rate.

Acute respiratory distress syndrome. Potential pharmacologic interventions.

Remarkable progress has been made in the past 10 years with regard to understanding the interplay of potent physiologic mediators in patients with acute lung injury. Because there are so many mediators and the interaction of these agents is complex, true insight into the process has been slow in coming. Clinical studies in ARDS, as well as sepsis, the leading cause of ARDS, have increased in number, size, and quality over this same period. Although none of these studies has produced an accepted new therapy for ARDS, each has laid the groundwork for more efficient and more elegant studies of the problem. The stage is now set for the real advances to be brought forward and put to rigorous, efficient clinical testing.

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

OBJECTIVE: Starling'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. DESIGN: Regression 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. SETTING: Intensive care units (ICUs) of seven clinical centers in North America. PATIENTS: A total of 455 ICU patients who met consensus criteria for severe sepsis (178 of whom developed ARDS) from a recently completed prospective clinical trial. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: We 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). CONCLUSIONS: Hypoproteinemia 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.

Pulmonary artery catheterization and clinical outcomes: National Heart, Lung, and Blood Institute and Food and Drug Administration Workshop Report. Consensus Statement.

OBJECTIVE: The efficacy and safety of the pulmonary artery catheter are under scrutiny because of its association with increased morbidity and mortality in observational studies. In response, the National Heart, Lung, and Blood Institute (NHLBI) and the US Food and Drug Administration (FDA) conducted the Pulmonary Artery Catheterization and Clinical Outcomes workshop in Alexandria, Va, on August 25 and 26, 1997, to develop recommendations regarding actions to improve pulmonary artery catheter utility and safety. PARTICIPANTS: The NHLBI and FDA planning task force selected a workshop chairperson, subcommittee chairs, and participants. Approximately 85 participants were selected for their collective expertise in critical care, pulmonary medicine, cardiovascular medicine and surgery, pediatrics, nursing, biostatistics, and medical economics. The meeting was open to industry representatives and other government and lay observers. This workshop was funded by the NHLBI and the FDA's Division of Devices. EVIDENCE: Published reports relating to the efficacy and safety of the pulmonary artery catheter, especially consensus documents developed by professional societies. CONSENSUS PROCESS: The planning task force disseminated materials, held teleconferences, and developed draft position papers prior to the workshop. These were modified during the workshop and thereafter in the course of several teleconferences, and presented to the entire group for final modifications and approval. CONCLUSIONS: A need exists for collaborative education of physicians and nurses in performing, obtaining, and interpreting information from the use of pulmonary artery catheters. This effort should be led by professional societies, in collaboration with federal agencies, with the purpose of developing and disseminating standardized educational programs. Areas given high priority for clinical trials were pulmonary artery catheter use in persistent/refractory congestive heart failure, acute respiratory distress syndrome, severe sepsis and septic shock, and low-risk coronary artery bypass graft surgery. JAMA. 2000;283:2568-2572