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Biomedical subjects

R P Dellinger

Publications and source records attributed to R P Dellinger.

At least 19 recordsLinked to original sources
PubMed2001

Other supportive therapies in sepsis.

Patients who survive the circulatory and organ deficits in sepsis may still fall victim to complications such as pulmonary embolism and stress ulcer bleeding. Although there is no clearcut evidence to quantitate the impact of such complications on mortality, the anticipated impact is grave when considering the compromised physiological reserve of these patients. For this reason it is important to institute effective prophylaxis to minimize the impact. In addition, catabolism associated with sepsis likely influences the recovery of patients with sepsis and moreover can compromise the response of the immune system against an infectious insult. Early and adequate nutritional support therefore appears important. There is much controversy and lack of prospective research regarding effect of supportive therapies on outcome in patients with severe sepsis. This research is needed.

Enteral Nutrition↗
PubMed2001

Innovative therapies for sepsis.

Sepsis and septic shock continue to be a major cause of morbidity and mortality. Despite numerous advances in the supportive care of patients with sepsis, the overall mortality has changed little in the past 20 years. Many innovative therapies have been attempted in the field of sepsis, primarily aimed at stopping the cycle of cytokine activation which is part of the systemic inflammatory response. Therapies have also targeted other molecular mediators of inflammation and coagulation. Despite encouraging preliminary preclinical results, most of the early trials in sepsis research have failed to offer hope of improving survival with the use of these innovative therapies. Postulated reasons for the failure of clinical trials include the disparity between animal models and clinical reality, the heterogeneous nature of patient populations and sepsis, and the complexity of the inflammatory cascade. On a more hopeful note, three recent trials assessing corticosteroids, anti-tumour necrosis factor strategy and drotrecogin alfa (rhAPC), respectively, have proclaimed positive results. However, only the drotrecogin alfa trial has been peer reviewed and published.

Animals↗
PubMed2000

Pharmacologic issues in the management of septic shock.

Despite our increased understanding of the biochemistry and physiology of sepsis, the treatment of septic shock remains a challenge. Initial management of septic shock entails urgent and emergent stabilization of the patient followed by broad-spectrum, empiric antibiotic therapy. After volume resuscitation, vasopressors or inotropic therapy or both may be necessary to restore perfusion. Adjunctive therapies and monitoring strategies may be helpful in preventing complications in the intensive care setting. Additional research and clinical trials are needed to identify supportive interventions that may affect the outcome of the septic patient.

Adrenal Cortex Hormones↗
PubMed2000

Phase I trial of the recombinant soluble complement receptor 1 in acute lung injury and acute respiratory distress syndrome.

OBJECTIVE: To determine the safety, pharmacokinetics, biological effects, and immunogenicity of recombinant soluble complement receptor 1 (TP10) in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). DESIGN: Open label, ascending dosage, phase I trial. SETTING: Two academic teaching hospitals. PATIENTS: A total of 24 patients diagnosed with ALI/ARDS. INTERVENTION: A single, 30-min intravenous infusion of 0.1, 0.3, 1, 3, or 10 mg/kg TP10. MEASUREMENTS AND MAIN RESULTS: Serum levels of TP10 increased in proportion to the dose. Mean variable estimates (+/-SD) were half-life of disposition 69.7 +/- 39.7 hrs, plasma clearance 2.39 +/- 1.32 mL/hr/kg, and volume of distribution 190.6 +/- 135.0 mL/kg. Inhibition of complement activity, measured by CH50, was significant for the interaction of dose and time (p = .024). The C3a levels demonstrated a trend for dose which did not reach statistical significance (p = .090) and soluble C5b-9 levels were significant only for dose (p = .023). As expected by the proposed physiologic mechanism, C4a levels were not affected by TP10, dose, or time. The overall mortality rate was 33%. Neither the type nor the frequency rate of specific adverse events were substantially different between dose groups. Seven adverse events in four patients were thought to be possibly related to TP10. CONCLUSIONS: TP10 has a half-life of approximately 70 hrs and at doses > or =1 mg/kg, significantly inhibits complement activity at the levels of C3 and C5 in patients with ALI/ARDS. Complement inhibition was more prolonged over time with TP10 doses of 3 and 10 mg/kg. TP10 appears to be safe at the doses tested. Further studies will be required to completely assess the impact of TP10 on pathophysiology and clinical outcome in patients with ALI/ARDS.

Adult↗
PubMed2000

Noncardiac surgery: postoperative arrhythmias.

Postoperative arrhythmias are common and represent a major source of morbidity after both cardiac and noncardiac surgical procedures. Postoperative dysrhythmias are most likely to occur in patients with structural heart disease. The initiating factor for an arrhythmia in a given patient after surgery is usually a transient insult, such as hypoxemia, cardiac ischemia, catecholamine excess, or electrolyte abnormality. Management includes correction of these imbalances and medical therapy directed at the arrhythmia itself. The physiologic impact of arrhythmias depends on arrhythmia duration, ventricular response rate, and underlying cardiac function. Similarly, urgency and type of treatment is determined by the physiologic impact of the arrhythmia, as well as by underlying clinical status. The purpose of this review is to provide current concepts of diagnosis and acute management of arrhythmias after noncardiac surgery. A systematic approach to arrhythmia diagnosis and evaluation of predisposing factors is presented, followed by consideration of specific bradyarrhythmias and tachyarrhythmias in the postoperative setting.

Anti-Arrhythmia Agents↗
PubMed1999

Current therapy for sepsis.

The treatment of severe sepsis and septic shock remains a challenge as we approach the next millennium. Although more attention is being given to guidelines and care pathways for sepsis, these are unfortunately based primarily on consensus opinion. Additional research into supportive interventions in this potentially devastating disease is needed. Priorities in the management of sepsis include rapid reversal of hypotension and hypoperfusion, followed by empiric antibiotic therapy and definitive localization and treatment of infection nidus. A wide variety of adrenergic agents may be useful in sepsis. Initial therapy for hypoperfusion, however, should be targeted toward establishing adequate intravascular volume and left ventricular preload. Adjunctive therapy to prevent complications during the intensive care unit stay is important.

Adrenergic Agents↗
PubMed1999

The laboratory-clinical interface: point-of-care testing.

POC testing provides an opportunity for clinicians and laboratorians to work together to consider how best to serve the patients within an individual institution. Each health system has unique characteristics relative to patient population, as well as a unique laboratory structure. If physicians, nurses, laboratorians, and pathologists work collaboratively, the best interests of patients will be served. In some institutions that cater to specific patient groups, POC testing may offer clear and distinct advantages. In other institutions with sophisticated transport systems and established rapid response capabilities, the quality resulting from central laboratory testing may outweigh any advantages of bedside testing. Clearly, attention to regulatory issues, QC issues, the importance of proper documentation, proficiency testing, performance enhancement, and cost-effectiveness is requisite. As the technology for diagnostic testing advances through more microcomputerization, microchemistry, and enhanced test menus, the concept of POC testing will need perpetual revisiting. We hope that the information provided here will aid clinicians, laboratorians, and administrators in their quest to best serve their patients.

Costs and Cost Analysis↗
PubMed1998

Effects of inhaled nitric oxide in patients with acute respiratory distress syndrome: results of a randomized phase II trial. Inhaled Nitric Oxide in ARDS Study Group.

OBJECTIVES: To evaluate the safety and physiologic response of inhaled nitric oxide (NO) in patients with acute respiratory distress syndrome (ARDS). In addition, the effect of various doses of inhaled NO on clinical outcome parameters was assessed. DESIGN: Prospective, multicenter, randomized, double-blind, placebo-controlled study. SETTING: Intensive care units of 30 academic, teaching, and community hospitals in the United States. PATIENTS: Patients with ARDS, as defined by the American-European Consensus Conference, were enrolled into the study if the onset of disease was within 72 hrs of randomization. INTERVENTIONS: Patients were randomized to receive placebo (nitrogen gas) or inhaled NO at concentrations of 1.25, 5, 20, 40, or 80 ppm. MEASUREMENTS AND MAIN RESULTS: Acute increases in PaO2, decreases in mean pulmonary arterial pressure, intensity of mechanical ventilation, and oxygenation index were examined. Clinical outcomes examined were the dose effects of inhaled NO on mortality, the number of days alive and off mechanical ventilation, and the number of days alive after meeting oxygenation criteria for extubation. A total of 177 patients were enrolled over a 14-month period. An acute response to treatment gas, defined as a PaO2 increase > or =20%, was seen in 60% of the patients receiving inhaled NO with no significant differences between dose groups. Twenty-four percent of placebo patients also had an acute response to treatment gas during the first 4 hrs. The initial increase in oxygenation translated into a reduction in the FIO2 over the first day and in the intensity of mechanical ventilation over the first 4 days of treatment, as measured by the oxygenation index. There were no differences among the pooled inhaled NO groups and placebo with respect to mortality rate, the number of days alive and off mechanical ventilation, or the number of days alive after meeting oxygenation criteria for extubation. However, patients receiving 5 ppm inhaled NO showed an improvement in these parameters. In this dose group, the percentage of patients alive and off mechanical ventilation at day 28 (a post hoc analysis) was higher (62% vs. 44%) than the placebo group. There was no apparent difference in the number or type of adverse events reported among those patients receiving inhaled NO compared with placebo. Four patients had methemoglobin concentrations >5%. The mean inspired nitrogen dioxide concentration in inhaled NO patients was 1.5 ppm. CONCLUSIONS: From this placebo-controlled study, inhaled NO appears to be well tolerated in the population of ARDS patients studied. With mechanical ventilation held constant, inhaled NO is associated with a significant improvement in oxygenation compared with placebo over the first 4 hrs of treatment. An improvement in oxygenation index was observed over the first 4 days. Larger phase III studies are needed to ascertain if these acute physiologic improvements can lead to altered clinical outcome.

Acute Disease↗