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R Phillip Dellinger

Publications and source records attributed to R Phillip Dellinger.

36 records · Page 2Linked to original sources
PubMed2004

Low-dose inhaled nitric oxide in patients with acute lung injury: a randomized controlled trial.

CONTEXT: Inhaled nitric oxide has been shown to improve oxygenation in acute lung injury. OBJECTIVE: To evaluate the clinical efficacy of low-dose (5-ppm) inhaled nitric oxide in patients with acute lung injury. DESIGN AND SETTING: Multicenter, randomized, placebo-controlled study, with blinding of patients, caregivers, data collectors, assessors of outcomes, and data analysts (triple blind), conducted in the intensive care units of 46 hospitals in the United States. Patients were enrolled between March 1996 and September 1999. PATIENTS: Patients (n = 385) with moderately severe acute lung injury, a modification of the American-European Consensus Conference definition of acute respiratory distress syndrome (ARDS) using a ratio of PaO2 to FiO2 of < or =250, were enrolled if the onset was within 72 hours of randomization, sepsis was not the cause of the lung injury, and the patient had no significant nonpulmonary organ system dysfunction at randomization. INTERVENTIONS: Patients were randomly assigned to placebo (nitrogen gas) or inhaled nitric oxide at 5 ppm until 28 days, discontinuation of assisted breathing, or death. MAIN OUTCOME MEASURES: The primary end point was days alive and off assisted breathing. Secondary outcomes included mortality, days alive and meeting oxygenation criteria for extubation, and days patients were alive following a successful unassisted ventilation test. RESULTS: An intent-to-treat analysis revealed that inhaled nitric oxide at 5 ppm did not increase the number of days patients were alive and off assisted breathing (mean [SD], 10.6 [9.8] days in the placebo group and 10.7 [9.7] days in the inhaled nitric oxide group; P =.97; difference, -0.1 day [95% confidence interval, -2.0 to 1.9 days]). This lack of effect on clinical outcomes was seen despite a statistically significant increase in PaO2 that resolved by 48 hours. Mortality was similar between groups (20% placebo vs 23% nitric oxide; P =.54). Days patients were alive following a successful 2-hour unassisted ventilation trial were a mean (SD) of 11.9 (9.9) for placebo and 11.4 (9.8) for nitric oxide patients (P =.54). Days alive and meeting criteria for extubation were also similar: 17.0 placebo vs 16.7 nitric oxide (P =.89). CONCLUSION: Inhaled nitric oxide at a dose of 5 ppm in patients with acute lung injury not due to sepsis and without evidence of nonpulmonary organ system dysfunction results in short-term oxygenation improvements but has no substantial impact on the duration of ventilatory support or mortality.

Administration, Inhalation↗
PubMed2004

Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock.

OBJECTIVE: To develop management guidelines for severe sepsis and septic shock that would be of practical use for the bedside clinician, under the auspices of the Surviving Sepsis Campaign, an international effort to increase awareness and improve outcome in severe sepsis. DESIGN: The process included a modified Delphi method, a consensus conference, several subsequent smaller meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. The modified Delphi methodology used for grading recommendations built upon a 2001 publication sponsored by the International Sepsis Forum. We undertook a systematic review of the literature graded along 5 levels to create recommendation grades from A-E, with A being the highest grade. Pediatric considerations were provided to contrast adult and pediatric management. PARTICIPANTS: Participants included 44 critical care and infectious disease experts representing 11 international organizations. RESULTS: A total of 46 recommendations plus pediatric management considerations. CONCLUSIONS: Evidence-based recommendations can be made regarding many aspects of the acute management of sepsis and septic shock that will hopefully translate into improved outcomes for the critically ill patient. The impact of these guidelines will be formally tested and guidelines updated annually, and even more rapidly when some important new knowledge becomes available.

Adult↗
PubMed2004

Inhaled nitric oxide: another weapon in our armamentarium in the battle against acute hypoxic respiratory failure in preterm infants.

Acute hypoxic respiratory failure (AHRF) remains a significant cause of death in intensive care units. With the realization that pathophysiologic abnormalities in AHRF involve surfactant abnormalities as well as inflammatory and vascular changes, it is not surprising that nitric oxide (NO) has been investigated as an adjunct to the multiple ventilatory strategies adopted in the management of this disorder. Since the enthusiastic reports of Roussaint in 1993 showing improved survival with inhaled NO in the management of AHRF, several well-designed studies have been published, all designed to investigate the utility of NO in neonatal, pediatric and adult patients. Michael Schreiber and colleagues evaluated 207 preterm infants with AHRF in a randomized, double-blind placebo-controlled study. Inhaled NO was administered at a constant low dose for up to 6 days in the NO group. Patients were further randomized to conventional ventilation and to high-frequency oscillatory ventilation. The patients showed a statistically significant improvement in their primary endpoint of the incidence of chronic lung injury and death in the inhaled NO group. There was no increase in the incidence of intraventricular hemorrhage between the study and placebo groups. Schreiber and colleagues concluded that early treatment with inhaled NO would improve long-term pulmonary outcomes in premature infants with respiratory distress syndrome, decreasing the incidence of chronic lung disease and death. Prior to this study no prospective randomized trial had demonstrated any benefits in clinical outcomes such as the length of hospital stay or death. This study supports the belief that the majority of patients will experience, at a minimum, a short-term benefit from inhaled NO therapy, but also suggests that inhaled NO may influence clinical outcomes as well. The recognition that AHRF is often the result of a multifactorial process makes it unlikely that one treatment modality will have a major beneficial effect on mortality and morbidity.

Administration, Inhalation↗
PubMed2004

Infections and severe sepsis in solid-organ transplant patients admitted from a university-based ED.

The objective was to provide a descriptive analysis of infectious processes in transplant patients admitted from the emergency department (ED). A database of all adult transplant patients at a university medical center was cross-referenced with a computerized record of all ED visits over an 18-month period. ED charts, inpatient records, and microbiology data were retrospectively reviewed. Final diagnoses and outcomes were analyzed. There were 352 ED visits by transplant patients (kidney 66%, kidney/pancreas 15%, liver 13%, lung 3%, heart 3%). Infections were the most common indications for admission (77/217, 35%). Urinary tract infection and pneumonia were the most common infections. Nine of 77 patients (11.7%) with documented infections developed severe sepsis, which was the most common reason for ICU utilization. Thirty-five percent of transplant patients admitted from the ED had acute infections, and 11.7% of these patients had severe sepsis. The emergency physician must have a high index of suspicion for infections when evaluating organ transplant recipients.

Adult↗
PubMed2004

Shock overview.

Despite improved understanding of the pathophysiology of shock and significant advances in technology, it remains a serious problem associated with high morbidity and mortality. Early treatment is essential but is hampered by the fact that signs and symptoms of shock appear only after the shock state is well established and the body's compensatory mechanisms have started to fail. Although the causes of shock are varied, the basic abnormality in all varieties is tissue and cellular dysoxia. In this overview we discuss the definition, classification and pathogenesis of shock in light of the recent advances in our understanding of its mechanisms. The epidemiology, diagnosis, and management of the various types of shock are also briefly discussed.

Journal Article↗
PubMed2004

Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock.

OBJECTIVE: In 2003, critical care and infectious disease experts representing 11 international organizations developed management guidelines for severe sepsis and septic shock that would be of practical use for the bedside clinician, under the auspices of the Surviving Sepsis Campaign, an international effort to increase awareness and improve outcome in severe sepsis. DESIGN: The process included a modified Delphi method, a consensus conference, several subsequent smaller meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. METHODS: We used a modified Delphi methodology for grading recommendations, built on a 2001 publication sponsored by the International Sepsis Forum. We undertook a systematic review of the literature graded along five levels to create recommendation grades from A to E, with A being the highest grade. Pediatric considerations were provided to contrast adult and pediatric management. RESULTS: Key recommendations, listed by category and not by hierarchy, include early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition; appropriate diagnostic studies to ascertain causative organisms before starting antibiotics; early administration of broad-spectrum antibiotic therapy; reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate; a usual 7-10 days of antibiotic therapy guided by clinical response; source control with attention to the method that balances risks and benefits; equivalence of crystalloid and colloid resuscitation; aggressive fluid challenge to restore mean circulating filling pressure; vasopressor preference for norepinephrine and dopamine; cautious use of vasopressin pending further studies; avoiding low-dose dopamine administration for renal protection; consideration of dobutamine inotropic therapy in some clinical situations; avoidance of supranormal oxygen delivery as a goal of therapy; stress-dose steroid therapy for septic shock; use of recombinant activated protein C in patients with severe sepsis and high risk for death; with resolution of tissue hypoperfusion and in the absence of coronary artery disease or acute hemorrhage, targeting a hemoglobin of 7-9 g/dL; appropriate use of fresh frozen plasma and platelets; a low tidal volume and limitation of inspiratory plateau pressure strategy for acute lung injury and acute respiratory distress syndrome; application of a minimal amount of positive end-expiratory pressure in acute lung injury/acute respiratory distress syndrome; a semirecumbent bed position unless contraindicated; protocols for weaning and sedation/analgesia, using either intermittent bolus sedation or continuous infusion sedation with daily interruptions/lightening; avoidance of neuromuscular blockers, if at all possible; maintenance of blood glucose <150 mg/dL after initial stabilization; equivalence of continuous veno-veno hemofiltration and intermittent hemodialysis; lack of utility of bicarbonate use for pH > or =7.15; use of deep vein thrombosis/stress ulcer prophylaxis; and consideration of limitation of support where appropriate. Pediatric considerations included a more likely need for intubation due to low functional residual capacity; more difficult intravenous access; fluid resuscitation based on weight with 40-60 mL/kg or higher needed; decreased cardiac output and increased systemic vascular resistance as the most common hemodynamic profile; greater use of physical examination therapeutic end points; unsettled issue of high-dose steroids for therapy of septic shock; and greater risk of hypoglycemia with aggressive glucose control. CONCLUSION: Evidence-based recommendations can be made regarding many aspects of the acute management of sepsis and septic shock that are hoped to translate into improved outcomes for the critically ill patient. The impact of these guidelines will be formally tested and guidelines updated annually and even more rapidly as some important new knowledge becomes as available.

Adult↗
PubMed2004

Critical care medicine as a distinct product line with substantial financial profitability: the role of business planning.

OBJECTIVE: As academic health centers face increasing financial pressures, they have adopted a more businesslike approach to planning, particularly for discrete "product" or clinical service lines. Since critical care typically has been viewed as a service provided by a hospital, and not a product line, business plans have not historically been developed to expand and promote critical care. The major focus when examining the finances of critical care has been cost reduction, not business development. We hypothesized that a critical care business plan can be developed and analyzed like other more typical product lines and that such a critical care product line can be profitable for an institution. DESIGN: In-depth analysis of critical care including business planning for critical care services. SETTING: Regional academic health center in southern New Jersey. SUBJECTS: None. INTERVENTIONS: As part of an overall business planning process directed by the Board of Trustees, the critical care product line was identified by isolating revenue, expenses, and profitability associated with critical care patients. MEASUREMENTS AND MAIN RESULTS: We were able to identify the major sources ("value chain") of critical care patients: the emergency room, patients who are admitted for other problems but spend time in a critical care unit, and patients transferred to our intensive care units from other hospitals. The greatest opportunity to expand the product line comes from increasing the referrals from other hospitals. A methodology was developed to identify the revenue and expenses associated with critical care, based on the analysis of past experience. With this model, we were able to demonstrate a positive contribution margin of dollar 7 million per year related to patients transferred to the institution primarily for critical care services. This can be seen as the profit related to the product line segment of critical care. There was an additional positive contribution margin of dollar 5.8 million attributed to the critical care portion of the hospital stay of patients admitted primarily through other product lines or the emergency room. This can be seen as the profit related to the "hospital service" segment of critical care. This represented a total contribution margin of dollar 12.8 million, approximately 24% of the institution's entire contribution margin. This information was subsequently used to develop strategic plans to promote this product line. CONCLUSIONS: We were able to define the critical care product line, and we were able to demonstrate profitability through an analysis of revenue and expenses related to critical care services. Our experience suggests that the concept of critical care as a product line, in addition to a hospital service, may lead to a useful analysis of this new discipline. This plan provided a rational foundation for development of the operating and capital budgets for the health system.

Academic Medical Centers↗
PubMed2004

Other supportive therapies in sepsis: an evidence-based review.

OBJECTIVE: In 2003, critical care and infectious disease experts representing 11 international organizations developed management guidelines for other supportive therapies in sepsis that would be of practical use for the bedside clinician, under the auspices of the Surviving Sepsis Campaign, an international effort to increase awareness and improve outcome in severe sepsis. DESIGN: The process included a modified Delphi method, a consensus conference, several subsequent smaller meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. METHODS: The modified Delphi methodology used for grading recommendations built on a 2001 publication sponsored by the International Sepsis Forum. We undertook a systematic review of the literature graded along five levels to create recommendation grades from A to E, with A being the highest grade. Pediatric considerations to contrast adult and pediatric management are in the article by Parker et al. on p. S591. CONCLUSION: Patients with severe sepsis should be treated with deep-vein thrombosis prophylaxis. Low-dose unfractionated heparin or low molecular weight heparin is preferred. Use of graduated compression devices is recommended in septic patients with contraindication to the use of heparin or combined with heparin in very high-risk patients. Stress ulcer prophylaxis should be given to all patients with severe sepsis. Histamine-2 receptor antagonists are more effective than sucralfate in decreasing bleeding risk and transfusion requirements. Proton pump inhibitors have not been assessed in a direct comparison with histamine-2 receptor antagonists but do demonstrate equivalency and ability to increase gastric pH.

Consensus Statements as Topic↗
PubMed2003

Inflammation and coagulation: implications for the septic patient.

Sepsis with acute organ dysfunction (severe sepsis) is common, frequently fatal, and associated with a significant national health/economic burden. In addition to standard care, investigators have focused on interrupting the inflammatory and anti-inflammatory cascade associated with this disease. Unfortunately, despite promising preclinical results, interventions directed at the inflammatory elements have not reduced the morbidity and mortality associated with this disease. Inflammation and coagulation are tightly linked. In fact, sepsis-associated coagulopathy is almost universal in patients with severe sepsis. Preclinical observations indicate that antithrombotic-targeted therapy has the potential to reduce morbidity and mortality in patients with this disease. Treatment with recombinant human activated protein C (drotrecogin alpha [activated]) was the first antithrombotic-targeted therapy to significantly reduce 28-day all-cause mortality in patients with severe sepsis. The pathophysiological and clinical significance of this evidence and the relationship of coagulation to inflammation are discussed, as are positive and negative results of clinical trials of antithrombotic therapy.

Adrenal Cortex Hormones↗
PubMed2003

Recent developments in the treatment of sepsis.

Despite advances in supportive care, septic shock remains a major cause of morbidity and mortality. With the identification of the systemic inflammatory response as a major component in the pathogenesis of the septic shock syndrome, much of the recent work has focused on modulating this response. This includes antiendotoxin therapies in patients with Gram-negative sepsis, and therapies to modulate the pro-inflammatory mediators produced in response to infection, such as TNF-alpha, platelet-activating factor and complement. High-flow haemofiltration has the potential advantage of clearing both endotoxin and pro-inflammatory mediators. Antithrombotic strategies have been investigated and have yielded the first major success in the treatment of sepsis with activated protein C. Nitric oxide produces the cardiovascular features of sepsis and investigators have looked at both reducing its production and mopping up the excess. Attempts to reduce apoptosis have been a new focus in the treatment of sepsis. There have also been recent developments in supportive care suggesting a role for vasopressin and replacement corticosteroid therapy.

Animals↗
PubMedDate not supplied

Drotrecogin alfa (activated) in an infant with gram-negative septic shock.

The authors observed the effect of drotrecogin alfa (activated) in a case of pediatric severe sepsis. A 4-month-old male infant with Serratia marcescens septic shock, multiple organ dysfunction syndrome (MODS), and consumptive coagulopathy was admitted. The safety and efficacy of drotrecogin alfa (activated) has not yet been established for patients younger than 18 years of age. This is the first published report of the use of drotrecogin alfa (activated) in an infant with severe sepsis. Within 6 hours of starting therapy, there was a significant improvement in hemodynamics, which was not maintained after the drotrecogin alfa (activated) infusion was temporarily discontinued. No significant bleeding complications occurred during the infusion. A brain MRI on day 22 after drotrecogin alfa (activated) infusion showed bilateral small occipital hemorrhages. Drotrecogin alfa (activated) in this infant was temporally related to significant improvement. It is unknown whether the MRI brain lesions are related to severe sepsis with disseminated intravascular coagulation or drotrecogin alfa (activated) infusion. The authors believe that drotrecogin alfa (activated) should be considered in select children with life-threatening severe sepsis.

Disseminated Intravascular Coagulation↗