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Biomedical subjects

R Phillip Dellinger

Publications and source records attributed to R Phillip Dellinger.

At least 19 recordsLinked to original sources

Early microcirculatory perfusion derangements in patients with severe sepsis and septic shock: relationship to hemodynamics, oxygen transport, and survival.

STUDY OBJECTIVE: To study early microcirculatory perfusion indices in patients with severe sepsis/septic shock, compare early microcirculatory indices in sepsis survivors versus nonsurvivors, and identify systemic hemodynamic/oxygen transport variables that correlate with early microcirculatory perfusion indices. METHODS: This prospective observational study used orthogonal polarization spectral imaging to directly visualize the sublingual microcirculation in patients with severe sepsis/septic shock treated with early goal-directed therapy. We performed initial imaging within 6 hours of early goal-directed therapy initiation and late follow-up studies at 24-hour intervals until death or resolution of organ dysfunction. We imaged 5 sublingual sites and analyzed the data offline in a blinded fashion. We calculated 3 microcirculatory perfusion indices: flow velocity score, flow heterogeneity index, and capillary density. We analyzed early data to compare survivors versus nonsurvivors and examine correlations with systemic hemodynamic measurements. We used a linear mixed-effects model for longitudinal analyses. RESULTS: We performed 66 orthogonal polarization spectral studies in 26 sepsis patients. Early microcirculatory indices were more markedly impaired (lower flow velocity and more heterogeneous perfusion) in nonsurvivors compared with survivors. These same early indices, flow velocity and heterogeneity, were also more markedly impaired with increasing severity of systemic cardiovascular dysfunction (lower arterial pressure or increasing vasopressor requirement). CONCLUSION: Early microcirculatory perfusion indices in severe sepsis and septic shock are more markedly impaired in nonsurvivors compared with survivors and with increasing severity of global cardiovascular dysfunction.

Aged↗

Current treatment of severe sepsis.

The treatment of severe sepsis includes three essential principles: eradication of the inciting infection using source control measures and empiric antibiotics, hemodynamic resuscitation of hypoperfusion to avoid acute life-threatening organ dysfunction, and sustained support of organ system dysfunction using interventions that minimize organ injury. Therapy can be divided into immediate steps taken to stabilize the patient, followed by more definitive therapeutic intervention. The evidence for best clinical practice for resuscitation, management of infection, and intensive care unit supportive care has recently been synthesized by the Surviving Sepsis Campaign and published as evidence-based guidelines for the management of severe sepsis and septic shock.

Journal Article↗

Controversies in sepsis clinical trials: proceedings of a meeting of the International Sepsis Forum, Lausanne, Switzerland, September 29, 2001.

Despite some recent success with clinical trials studying innovative therapies in sepsis, the field remains predominantly one of failure despite compounds with significant preclinical activity. Preclinical animal experimentation remains an important component of drug development, and a portfolio approach is recommended. Failure in animals is more likely to predict failure in humans; however, success in animals often does not predict success in humans. Because the signal with innovative therapy of sepsis is likely to be low, an oncology model clinical trial approach, in which studies start with a high-risk homogeneous population and look for a large treatment effect with smaller numbers of patients, is likely to be more relevant than the commonly used cardiology model, in which studies search for a small treatment effect using large, heterogeneous, low-risk populations. With certain rules in place, improvement in organ function may be a worthwhile alternative to mortality as a clinical end point. Once a therapy is approved, adopting less stringent but still appropriate criteria for the use of that therapy in clinical practice may be appropriate.

Animals↗

Guidelines for severe infections: are they useful?

PURPOSE OF REVIEW: The large variability in clinical practice plus the increasing awareness that certain processes of care are associated with improved medical outcomes has led to the development of clinical practice guidelines in serious infection. The evolution of guidelines and their impact on delivery of care in severe infection is reviewed. RECENT FINDINGS: Guidelines development has centered around community- and hospital-acquired pneumonia as well as sepsis. The Institute of Healthcare Improvement has emerged as an international leader in changing healthcare professional behavior to be consistent with clinical recommendations in infection-related morbidity. These educational programs are designed to increase awareness of guidelines recommendations and to optimize their implementation. Change bundles are selected sets of interventions or processes distilled from evidence-based practice guidelines that are likely to improve outcome. As new evidence is published, and as experts ponder how the guidelines should best be expressed in the bundles, the bundles will be adapted to optimize their utility. SUMMARY: The change bundle approach to performance improvement (guidelines-based) is the key to change in practice. The Surviving Sepsis Campaign/Institute of Healthcare Improvement sepsis change bundles are an excellent example of progress along these lines.

Anti-Infective Agents↗

Care of critically ill surgical patients using the 80-hour Accreditation Council of Graduate Medical Education work-week guidelines: a survey of current strategies.

As a result of the recently mandated work-hour restrictions, it has become more difficult to provide 24-hour intensive care unit (ICU) in-house coverage by the general surgical residents. To assess the current state of providing appropriate continuous care to surgical critical care patients during the era of resident work-hour constraints, a national survey was conducted by the Association of Program Directors of Surgery. The results revealed that 37 per cent of programs surveyed have residents other than general surgery housestaff providing cross-coverage and writing orders for surgical ICU patients. Residents in emergency medicine, anesthesia, family medicine, otorhinolaryngology, obstetrics/gynecology, internal medicine, urology, and orthopedic surgery have provided this cross-coverage. Some found it necessary to use physician extenders (i.e., nurse practitioners or physician assistants), thereby decreasing the burden of surgical housestaff coverage. The results indicated that 30 per cent use physician extenders to help cover the ICU during daytime hours and 11 per cent used them during nighttime hours. In addition, 24 per cent used a "night-float" system in an attempt to maintain continuous care, yet still adhere to the mandated guidelines. In conclusion, our survey found multiple strategies, including the use of physician extenders, a "night-float" system, and the use of nongeneral surgical residents in an attempt to provide continuous coverage for surgical ICU patients. The overall outcome of these new strategies still needs to be assessed before any beneficial results can be demonstrated.

Accreditation↗

Recombinant activated protein C: the key is clinical assessment of risk of death, not subset analysis.

The PROWESS (Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis) trial demonstrated a 6.1% absolute decrease in mortality with a p value of 0.005. Despite the impressive results of this trial, criticism of the study has targeted various aspects of design, analysis and interpretation. Additional studies of recombinant activated protein C (rhAPC) have added to our understanding about this drug and to controversy as well. So how do we deal with rhAPC use in our clinical practice?

Humans↗

Hemodynamic optimization of sepsis-induced tissue hypoperfusion.

Sepsis is associated with cardiovascular changes that may lead to development of tissue hypoperfusion. Early recognition of sepsis and tissue hypoperfusion is critical to implement appropriate hemodynamic support and prevent irreversible organ damage. End points for resuscitation need to be defined and invasive hemodynamic monitoring is usually required. Targets for hemodynamic optimization should include intravascular volume, blood pressure, and cardiac output. Therapeutic interventions aimed at optimizing hemodynamics in patients with sepsis include aggressive fluid resuscitation, the use of vasopressor agents, inotropic agents and in selected cases transfusions of blood products. This review will cover the most important aspects of hemodynamic optimization for treatment of sepsis induced tissue-hypoperfusion.

Biomarkers↗

Translating research to clinical practice: a 1-year experience with implementing early goal-directed therapy for septic shock in the emergency department.

OBJECTIVE: Early goal-directed therapy (EGDT) has been shown to decrease mortality in patients with severe sepsis and septic shock. Consensus guidelines now advocate EGDT for the first 6 h of sepsis resuscitation. However, EGDT has not yet been widely adopted in practice. A need for effective collaboration between emergency medicine and critical care medicine services has been identified as an obstacle for implementation. We aimed to determine if EGDT end points could reliably be achieved in real-world clinical practice. METHODS: EGDT was implemented as a collaborative emergency medicine/critical care quality improvement initiative. EGDT included the following: i.v. fluids (IVF) targeting central venous pressure > or = 8 mm Hg, vasopressors targeting mean arterial pressure > or = 65 mm Hg, and (if necessary) packed RBCs (PRBCs) and/or dobutamine targeting central venous oxygen saturation > or = 70%. A retrospective analysis was performed of emergency department (ED) patients with persistent sepsis-induced hypotension (systolic BP < 90 mm Hg despite 1.5 L of IVF) treated with EGDT during the first year of the initiative. Primary outcome measures included successful achievement of EGDT end points and time to achievement. A secondary analysis was performed comparing EGDT cases to historical control cases (nonprotocolized control subjects without invasive monitoring). RESULTS: All end points were achieved in 20 of 22 cases (91%). The median time to reach each end point was < or = 6 h. In the secondary analysis, patients (n = 38; EGDT, n = 22; pre-EGDT, n = 16) had similar age, do-not-resuscitate status, severity scores, hypotension duration, and vasopressor requirement (p = not significant). In the ED, EGDT used more IVF and included PRBC/dobutamine utilization, without any impact on the overall use of these therapies through the first 24 h in the ICU. EGDT was associated with decreased ICU pulmonary artery catheter (PAC) utilization (9.1% vs 43.7%, p = 0.01). CONCLUSIONS: With effective emergency medicine/critical care collaboration, we demonstrate that EGDT end points can reliably be achieved in real-world sepsis resuscitation. ED-based EGDT appears to decrease ICU PAC utilization.

Aged↗

Treatment options for severe sepsis and septic shock.

Despite significant advances in the understanding of the pathophysiology of sepsis, severe sepsis and septic shock continue to be associated with high morbidity and mortality. Eradication of infection, with appropriate antibiotics and source control, remains the cornerstone of sepsis management, but does not ensure survival. Aggressive supportive care, such as fluid resuscitation, vasoactive agents or mechanical ventilation, is often required. With the exception of drotrecogin alfa, attempts to modulate the inflammatory response in sepsis have generally been unsuccessful. Early goal-directed therapy targeting adequate central venous oxygen saturation appears to improve outcome. Recently, there has been renewed interest in the use of corticosteroids, not as anti-inflammatory agents, but as replacement therapy. There is also some evidence to suggest that tight glucose control may improve outcome in these patients.

Adrenal Cortex Hormones↗

The Surviving Sepsis Campaign sepsis change bundles and clinical practice.

The Surviving Sepsis Campaign (SSC) is an international effort to reduce mortality in severe sepsis and septic shock. The campaign included the creation of evidence-based guidelines sponsored and endorsed by 11 international organizations. From these guidelines, sepsis change bundles for initial resuscitation (6 hours) and management (24 hours) were created as a performance improvement tool. In this issue of Critical Care, Gao et al. have evaluated performance at their institution by using a close adaptation of the two SSC bundle sets and demonstrated an association between 100% compliance with the bundle elements and clinical outcome. The next step will be to demonstrate that the use of education and feedback for performance improvement will increase compliance and decrease mortality in the patient population in general.

Clinical Protocols↗

Critical care medicine training and certification for emergency physicians.

Demand for critical care services is increasing. Unless the supply of intensivists increases, critically ill patients will not have access to intensivists. Recent critical care society recommendations include increased graduate medical education support and expansion of the J-1 visa waiver program for foreign medical graduates. This article proposes additional recommendations, based on strengthening the relationship between emergency medicine and critical care medicine. Critical care is a continuum that includes out-of-hospital, emergency department (ED), and ICU care teams. Both emergency medicine and critical care medicine require expertise in treating life-threatening acute illness, with many critically ill patients often presenting first to the ED. Increased patient volumes and acuity have resulted in longer ED lengths of stay and more critical care delivery in the ED. However, the majority of critical care medicine fellowships do not accept emergency medicine residents, and those who do successfully complete a fellowship do not have access to a US certification examination in critical care medicine. Despite these barriers, interest in critical care medicine training among emergency physicians is increasing. Dual emergency medicine- and critical care medicine-trained physicians will not only help alleviate the intensivist shortage but also strengthen critical care delivery in the ED and facilitate coordination at the ED-ICU interface. We therefore propose that all accreditation bodies work cooperatively to create a route to critical care medicine certification for emergency physicians who complete a critical care fellowship.

Certification↗

Critical care medicine training and certification for emergency physicians.

Demand for critical care services is increasing. Unless the supply of intensivists increases, critically ill patients will not have access to intensivists. Recent critical care society recommendations include increased graduate medical education support and expansion of the J-1 visa waiver program for foreign medical graduates. This article proposes additional recommendations, based on strengthening the relationship between emergency medicine and critical care medicine. Demand for critical care services is increasing. Unless the supply of intensivists increases, critically ill patients will not have access to intensivists. Recent critical care society recommendations include increased graduate medical education support and expansion of the J-1 visa waiver program for foreign medical graduates. This article proposes additional recommendations, based on strengthening the relationship between emergency medicine (EM) and critical care medicine (CCM). Critical care is a continuum that includes prehospital, emergency department (ED), and intensive care unit (ICU) care teams. Both EM and CCM require expertise in treating life-threatening acute illness, with many critically ill patients often presenting first to the ED. Increased patient volumes and acuity have resulted in longer ED lengths of stay and more critical care delivery in the ED. However, the majority of CCM fellowships do not accept EM residents, and those who successfully complete a fellowship do not have access to a U.S. certification exam in CCM. Despite these barriers, interest in CCM training among EM physicians is increasing. Dual EM/CCM-trained physicians not only will help alleviate the intensivist shortage but also will strengthen critical care delivery in the ED and facilitate coordination at the ED-ICU interface. We therefore propose that all accreditation bodies work cooperatively to create a route to CCM certification for emergency physicians who complete a critical care fellowship.

Certification↗

Inclusion criteria for clinical trials in sepsis: did the American College of Chest Physicians/Society of Critical Care Medicine consensus conference definitions of sepsis have an impact?

BACKGROUND: Over the last 25 years, a growing number of clinical trials have evaluated novel sepsis therapies. To promote uniformity in inclusion criteria for patient enrollment, the American College of Chest Physicians and Society of Critical Care Medicine first published consensus conference definitions for sepsis in 1992. STUDY OBJECTIVES: To characterize (1) the utilization of specific criteria for patient enrollment in sepsis clinical trials and (2) the impact that the consensus conference definitions have had on these criteria. DESIGN: We used MEDLINE to identify clinical trials in sepsis from 1976 to 2001. Clinical trials published after the consensus conference (ACC; from 1993 to 2001) were compared with trials published before the consensus conference (BCC; from 1976 to 1992). RESULTS: We identified 176 clinical trials (ACC, 119 trials; BCC, 57 trials). Clinical trials published ACC were more likely to utilize or reference a previously published standard for inclusion criteria (65% vs 11%, respectively; p < 0.001). The consensus conference definitions were the standards used in 69% of these trials. The utilization of specified values for WBC count, temperature (T), heart rate (HR), and respiratory rate (RR) was significantly increased in the ACC group compared to the BCC group, as follows: WBC count, 62% vs 26%, respectively (p < 0.001); T, 89% vs 56%, respectively (p < 0.001); HR, 77% vs 26%, respectively (p < 0.001); and RR, respectively 76% vs 28% (p < 0.001). ACC, clinical trials were less likely to require blood culture positivity (4 of 119 trials [3%] vs 9 of 57 trials [16%], respectively; p < 0.006) and were more likely to incorporate markers of acute organ dysfunction (81 of 119 trials [68%] vs 28 of 57 trials [49%], respectively; p < 0.03) in the inclusion criteria. CONCLUSIONS: (1) Since 1992 there has been a significant increase in the utilization of predefined sepsis criteria for patient enrollment in clinical trials, and this increase can be attributed to the existence of consensus conference definitions. (2) Compared to inclusion criteria BCC, inclusion criteria ACC were less reliant on blood culture positivity and were more likely to incorporate markers of organ dysfunction.

Clinical Trials as Topic↗

Diagnostic and prognostic implications of endotoxemia in critical illness: results of the MEDIC study.

A novel assay for endotoxin, based on the ability of antigen-antibody complexes to prime neutrophils for an augmented respiratory burst response, was studied in a cohort study of 857 patients admitted to an intensive-care unit (ICU). On the day of ICU admission, 57.2% of patients had either intermediate (>or=0.40 endotoxin activity [EA] units) or high (>or=0.60 units) EA levels. Gram-negative infection was present in 1.4% of patients with low EA levels, 4.9% with intermediate levels, and 6.9% with high levels; EA had a sensitivity of 85.3% and a specificity of 44.0% for the diagnosis of gram-negative infection. Rates of severe sepsis were 4.9%, 9.2%, and 13.2%, and ICU mortality was 10.9%, 13.2%, and 16.8% for patients with low, intermediate, and high EA levels, respectively. Stepwise logistic regression analysis showed that elevated Acute Physiology and Chronic Health Evaluation II score, gram-negative infection, and emergency admission status were independent predictors of EA.

APACHE↗