Risk factors for recurrence after repair of enterocutaneous fistula.

OBJECTIVES: To assess outcomes after repair of enterocutaneous fistulae (ECF) and identify factors that predict mortality and recurrence. DESIGN: Retrospective study. SETTING: University hospital. PATIENTS: One hundred thirty-five patients undergoing ECF repair between 1989 and 2005. MAIN OUTCOME MEASURES: Mortality and recurrence of ECF. RESULTS: Definitive operation for ECF was attempted in 135 patients. Mortality was 8%, recurrence was 17%, and 84% of patients eventually survived with a closed fistula. The primary determinant of mortality was ECF recurrence (odds ratio [OR], 6.7; 95% confidence interval [CI], 1.9-23.4). Factors independently associated with ECF recurrence by multivariate logistic regression included the presence of inflammatory bowel disease (OR, 4.9; 95% CI, 1.5-16.1), interval between diagnosis and operation of 36 weeks or longer (OR, 5.4; 95% CI, 1.8-16.4), location of fistulae in the small intestine (OR, 9.8; 95% CI, 1.7-57.6), and resection with stapled anastomosis (OR, 4.1; 95% CI, 1.3-13.2). Recurrence of ECF was 35% with resection and stapled anastomosis, 22% with simple oversew, and 11% with resection and hand-sewn anastomosis. Recurrence of ECF was 12% when operation was performed prior to 36 weeks from diagnosis, compared with 36% if performed at or beyond 36 weeks. CONCLUSIONS: The primary determinant of mortality after ECF repair is a failed operation leading to recurrence of the fistula. Risk factors for ECF recurrence include inflammatory bowel disease, fistula located in the small intestine, an interval of 36 weeks or longer between diagnosis and operation, and resection with stapled anastomosis.

Patient volume per surgeon does not predict survival in adult level I trauma centers.

BACKGROUND: The 1999 American College of Surgeons resources for optimal care document added the requirement that Level I trauma centers admit over 240 patients with Injury Severity Score (ISS) > 15 per year or that trauma surgeons care for at least 35 patients per year. The purpose of this study was to test the hypothesis that high volume of patients with ISS > 15 per individual trauma surgeon is associated with improved outcome. METHODS: Data were obtained from the trauma registry of the five American College of Surgeons-verified adult Level I trauma centers in our mature trauma system between January 1, 1998, and March 31, 1999. Data abstracted included age, sex, Glasgow Coma Scale (GCS) score, intensive care unit length of stay, hospital length of stay, probability of survival (Ps), mechanism of injury, number of patients per each trauma surgeon and institution, and mortality. Multiple logistic regression was performed to select independent variables for modeling of survival. RESULTS: From the five Level I centers there were 11,932 trauma patients in this time interval; of these, 1,754 patients (14.7%) with ISS > 15 were identified and used for analysis. Patients with ISS > 15 varied from 173 to 625 per institution; trauma surgeons varied from 8 to 25 per institution; per-surgeon patient volume varied from 0.8 to 96 per year. Logistic regression analysis revealed that the best independent predictors of survival were Ps, GCS score, age, mechanism of injury, and institutional volume (p < 0.01). Age and institutional volume correlated negatively with survival. Analysis of per-surgeon patient caseload added no additional predictive value (p = 0.44). CONCLUSION: The significant independent predictors of survival in severely injured trauma patients are Ps, GCS score, age, mechanism of injury, and institutional volume. We found no statistically meaningful contribution to the prediction of survival on the basis of per-surgeon patient volume. Since this volume criterion for surgeon enpanelment and trauma center designation would not be expected to improve outcome, such a requirement should be justified by other measures or abandoned.

Prehospital intubation in patients with severe head injury.

BACKGROUND: Prehospital intubation and airway control is routinely performed by paramedics in critically injured patients. Despite the advantages provided by this procedure, numerous potential risks exist when this is performed in the field. We reviewed the outcome of patients with severe head injury, to determine whether prehospital intubation is associated with an improved outcome. METHODS: A retrospective review of registry data of patients admitted to an urban trauma center with severe head injury (field Glasgow Coma Scale score of < or =8 and head Abbreviated Injury Scale score of > or =3) was performed. Patients were stratified by methods of airway control performed by prehospital personnel: not intubated, intubated, or unsuccessful intubation. Mortality was determined for each group. To control for significant variables between these populations, matching and multivariate analysis were performed. RESULTS: Patients requiring prehospital intubation or in whom intubation was attempted had an increased mortality (81% and 77%, respectively) when compared with nonintubated patients (43%). The mortality for patients who had prehospital intubation performed did not demonstrate an improved survival using matching. In fact, intubated patients had a significantly higher relative risk (RR) of mortality when compared with nonintubation (RR = 1.74,p < 0.001) and unsuccessful intubation patients (RR = 1.53, p = 0.008) CONCLUSION: For patients with severe head injury, prehospital intubation did not demonstrate an improvement in survival. Further prospective randomized trials are necessary to confirm these results.

Cyclooxygenase 2 (COX-2) gene activation is regulated by cyclic adenosine monophosphate.

Prostaglandin E2 production by tissue-fixed macrophages (Mphi) after severe injury contributes to an enhanced susceptibility to infection and sepsis. The purpose of this study was to investigate the effect of cyclic adenosine monophosphate (cAMP) on prostaglandin (PGE2) production and cyclooxygenase II (COX-2) gene activation in LPS-stimulated macrophages (Mphi). RAW264.7 cells, a mouse Mphi cell line, were exposed to various concentrations of dibutyryl cAMP +/- lipopolysaccharide (10 microg/mL) stimulation. Total Mphi ribonucleic acid (RNA) was harvested for the determination of COX-2 messenger RNA (mRNA) with mouse complementary deoxyribonucleic acid (cDNA) by Northern blot assay. Mphi supernatant was collected for the measurement of tumor necrosis factor (TNF) by L929 bioassay and PGE2 by enzyme-linked immunosorbent assay (ELISA), respectively. Mphi NFkappaB activity was determined by electrophoretic mobility shift assays (EMSA). Dibutyryl cAMP significantly inhibited TNF production by LPS-stimulated Mphi. Dibutyryl cAMP (1 mM) alone induced PGE2 production. Dibutyryl cAMP (100 microM and 1 mM) also augmented PGE2 production by LPS-stimulated Mphi. Dibutyryl cAMP had similar effect on Mphi COX-2 mRNA expression and NFkappaB activity. Our data demonstrate that cAMP modulates Mphi TNF production and upregulates COX-2 gene and PGE2 production.

Advances in the understanding of multiple organ failure.

Multiple organ failure (MOF) is currently the most common cause of late death after injury and surgery. The pathogenesis of MOF remains incompletely understood but in all likelihood results from a combination of dysregulated balance between inflammatory response and immune function, maldistribution of microcirculatory blood flow, and ischemia/reperfusion injury. Advances in the understanding of the pathogenesis of MOF have been hampered by a lack of precise animal models, accurate definitions of disease, consistent means to qualitatively and quantitatively diagnose disease, and a definable at-risk group of patients for study. Several recent advances in critical care and proposed new therapies hold promise for improving the outcome of patients with multiple injuries who are at risk for MOF. However, as recent clinical trials have shown, studies demonstrating an improvement in outcome from use of these therapeutic agents are difficult to design. The purpose of this article is to discuss the evolution, clinical course, and pathogenesis of MOF, to attempt to better define and quantitate MOF, and to describe recent studies aimed at identifying an at-risk study population for improved treatment and prevention strategies for MOF.

Macrophage TNF mRNA expression induced by LPS is regulated by sphingomyelin metabolites.

Metabolism of macrophage (MO) membrane phospholipids produces key mediators of inflammation and major second messengers that modulate inflammatory responses during sepsis. Sphingomyelin is a major class of phospholipid that releases ceramide and sphingosine. This study was designed to investigate the involvement of sphingomyelin metabolites in MO activation by lipopolysaccharide (LPS). Rabbit alveolar MO were obtained by bronchoalveolar lavage and exposed to C6-ceramide, a cell-permeable analogue of natural ceramide, or sphingosine in the presence of Escherichia coli LPS (100 ng/mL). Tumor necrosis factor (TNF) mRNA expression was measured by Northern blot assays. Total nuclear extract was harvested for the measurement of nuclear factor KB (NFkappaB) with electrophoretic mobility shift assays. MO TNF production was measured by L929 bioassays. C-6 ceramide did not have any effects on MO TNF production or TNF mRNA expression with or without LPS stimulation. Inhibition of ceramide metabolism with 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP), or N-oleoyl-ethanolamine (NOE) also did not induce TNF mRNA or TNF production. In comparison, sphingosine inhibited TNF mRNA expression as well as TNF production of LPS-stimulated MO. LPS-induced MO NFkappaB activity was also reduced by sphingosine. Our data indicate that ceramide alone has no effect on macrophage activity, but its metabolite sphingosine down-regulates MO activation induced by LPS stimulation. Therefore, the sphingomyelin pathway is involved in the regulation of MO activation.

Multiple organ failure: by the time you predict it, it's already there.

OBJECTIVE: Validate an at-risk population to study multiple organ failure and to determine the importance of organ dysfunction 24 hours after injury in determining the ultimate severity of multiple organ failure. METHODS: We evaluated 105 patients admitted to five academic trauma centers during a 1-year period who survived for more than 24 hours with Injury Severity Scores > or = 25 and who received 6 or more units of blood. Organ dysfunction was scored daily with a modified multiple organ failure scoring system made up of individual adult respiratory distress syndrome score, renal dysfunction, hepatic dysfunction, and cardiac dysfunction scores. Multiple organ failure (MOF) severity was quantitated using the maximum daily multiple organ failure score and the cumulative sum of daily multiple organ failure scores for the first 7 days (MOF 7) and 10 days (MOF 10). Independent variables included markers of tissue injury, shock, host factors, physiologic response, therapeutic factors, and organ dysfunction within the first 24 hours after admission. Data were subjected to a conditional stepwise multiple regression analysis, first excluding and then including 24-hour MOF as an independent variable. RESULTS: Of the 105 high-risk patients, 69 (66%) developed a maximum daily multiple organ failure score > or = 1; 50 (72%) did so on day 1 one and 60 (87%) did so by day 2. In multiple regression models, the multiple correlation coefficient increased from 0.537 to 0.720 when maximum MOF was the dependent variable, from 0.449 to 0.719 when maximum daily MOF was the dependent variable, from 0.519 to 0.812 when MOF 7 was the dependent variable, and from 0.514 to 0.759 when MOF 10 was the dependent variable. CONCLUSION: We have confirmed that the population of patients with Injury Severity Scores > or = 25 who received 6 or more units of blood represent a high-risk group for the development of multiple organ failure. Our data also indicate that multiple organ failure after trauma is established within 24 hours of injury in the majority of patients who develop it. It appears that multiple organ failure is already present at the time when most published models are trying to predict whether or not it will occur.

Interleukin 10 inhibits alveolar macrophage production of inflammatory mediators involved in adult respiratory distress syndrome.

BACKGROUND: Adult respiratory distress syndrome (ARDS) causes severe morbidity and mortality in trauma patients. One potential method to attenuate the lung injury is to inhibit alveolar macrophage production of proinflammatory mediators. The purpose of this study was to investigate the cellular mechanism of interleukin 10 (IL-10) inhibition on LPS-stimulated macrophage (Mphi). We hypothesized that IL-10 inhibited phospholipase C signal pathways in Mphi. IL-10 inhibition would be restored by calcium ionophores and protein kinase C (PKC) activation. METHODS: Rabbit alveolar Mphi were obtained by bronchoalveolar lavage. Mphi were treated with Escherichia coli LPS (10 ng/ml) in the presence of various concentrations of human IL-10. Cell lysates and supernatant were analyzed for proagulants (PCA) and tumor necrosis factor (TNF), respectively. TNF mRNA expression of alveolar Mphi was also measured by Northern Blot assay. Macrophage PGE2 production was measured by ELISA. RESULTS: IL-10 inhibited the production of both TNF and PCA by LPS-stimulated Mphi. In addition, IL-10 also reduced TNF mRNA expression. Similarly, PGE2 production by LPS-stimulated Mphi was also attenuated by IL-10. An increase in the intracellular [Ca2+] induced by A23187 failed to reverse this IL-10-mediated inhibition. In comparison, phorbol myristate acetate, a protein kinase C (PKC) activator, restored TNF and PCA production despite the presence of IL-10. CONCLUSIONS: IL-10 inhibits Mphi production of inflammatory mediators. This inhibition is, at least in part, mediated by modulating the PKC activity.

Regulation of macrophage eicosanoid generation is dependent on nuclear factor kappaB.

BACKGROUND: Prostaglandin E2 (PGE2) is a major contributor to the production and maintenance of immunosuppression after overwhelming injury, leading to increased infectious morbidity and mortality in trauma patients. Elucidation of the cellular pathways involved in PGE2 production could lead to potential therapeutic interventions. The purpose of this study was to determine the role of cyclooxygenase II (COX-2) in PGE2 production by Mphi and to investigate the cellular mechanism of COX-2 gene activation. METHODS: Mouse macrophages (Mphi), RAW 264.7, were exposed to Escherichia coli lipopolysaccharide (LPS) in the presence of cyclooxygenase inhibitors (ibuprofen or NS398). COX-1 and COX-2 mRNA expression and PGE2 production were measured by Northern blot assay and enzyme-linked immunosorbent assay, respectively. Nuclear factor kappaB (NFkappaB) activity was measured by electrophoretic mobility shift assay. To elucidate the role of NFkappaB in LPS-induced COX-2 gene activation, Mphi were exposed to LPS in the presence of an NFkappaB inhibitor, TPCK. RESULTS: LPS increased Mphi COX-2 mRNA expression but had no effect on COX-1 mRNA expression. Both ibuprofen and NS398 inhibited COX-2 mRNA as well as PGE2 production by LPS-stimulated Mphi. In addition, LPS-induced NFkappaB activity was attenuated by these agents. Inhibition of NFkappaB with TPCK reduced COX-2 but not COX-1 gene expression and decreased PGE2 production by LPS-stimulated Mphi. CONCLUSION: Our data indicate that COX-2 gene expression by LPS-stimulated Mphi is dependent on NFkappaB. Cyclooxygenase inhibitors reduced PGE2 production by inhibiting both COX-2 mRNA expression and preventing NFkappaB activation.

Endotoxin-induced macrophage gene expression depends on platelet-activating factor.

BACKGROUND: The development of multiple organ failure in septic patients is due to a systemic inflammation orchestrated by macrophages (Mphi). Elucidation and control of the mechanism involved in Mphi activation in sepsis is crucial to improving survival. An early event of Mphi activation involves the hydrolysis of membrane phospholipid by phospholipase A2 (PLA2) and subsequent generation of platelet-activating factor (PAF). OBJECTIVE: We designed this study to test the hypothesis that Mphi gene expression depends on PAF. DESIGN: Rabbit alveolar Mphi were obtained by bronchoalveolar lavage and were stimulated with 10 ng/mL of Escherichia coli endotoxin lipopolysaccharide (LPS), PAF (1 micromol/L), LPS+/-CV3988 (10 micromol/L), a PAF receptor antagonist, or LPS+/-PLA2 inhibitors: AACOCF3 (50 micromol/L) or manoalide (10 micromol/L). After 4 hours of incubation, Mphi tumor necrosis factor (TNF) messenger RNA (mRNA) expression was assessed by Northern blot analyses. The TNF production in the Mphi supernatant was measured by L929 bioassays. RESULTS: The LPS-stimulated Mphi expressed increased levels of TNF mRNA and produced an enormous amount of TNF. CV3988, a PAF antagonist, inhibited LPS-induced TNF mRNA. Furthermore, inhibiting PAF production with AACOCF3, or manoalide, also inhibited LPS-induced Mphi TNF mRNA expression. The effect of PAF depends on changes in intracellular calcium concentration. Inhibitors of calcium flux attenuated the PAF effects on LPS-stimulated Mphi. CONCLUSIONS: Our data suggest that LPS-induced Mphi gene expression is mediated by PAF. It is likely that modulation of PAF production or activity may be beneficial in down-regulating the overactivity of Mphi in sepsis.

Therapeutic approaches for clinical ischemia and reperfusion injury.

Recent clinical applications of strategies derived from microcirculation and shock research directed at preventing the sequelae of ischemia and reperfusion syndromes are successfully decreasing mortality in a variety of human diseases. The most commonly applied principle remains early reperfusion, which has been most successfully applied in the treatment of myocardial infarction with balloon angioplasty and employed with moderate success in the recent treatment of stroke with fibrinolytic agents. This strategy is designed to prevent reperfusion injury before it occurs and has limited applicability. A more commonly used principle to clinically treat the reperfusion injury component of ischemia and reperfusion syndromes is controlled reperfusion, which is now routinely applied in transplant and experimentally applied in the treatment of peripheral artery occlusion, stroke, and myocardial infarction. Strategies to control the microcirculatory environment during ischemia are employed successfully in transplantation and cardiopulmonary bypass. These techniques have been recently modified for use in a combined fashion with controlled reperfusion in experimental clinical studies in heart surgery, limb ischemia, and transplantation. Future strategies that have indirect support but have not yet been tested in clinical studies include anticytokine therapy and ischemic preconditioning. In conclusion, the successes in the treatment of ischemia reperfusion injury in experimental animals have slowly been integrated into clinical practice. Marked gains have been made in the treatment of myocardial infarction, peripheral artery occlusion, and transplantation. On the other hand, in areas such as stroke and hemorrhagic shock, we have a long way to go.

Improving pain management in critical care.

BACKGROUND: In April 1994 at the University of California at Los Angeles Medical Center the Surgical Intensive Care Unit's (SICU's) Quality Improvement Council unanimously agreed on pain management as one of the major factors that negatively affect outcomes for their patient population. Using the FOCUS-PDCA (plan-do-check-act) model for quality improvement (QI), the council chartered a subcommittee to improve the pain management in their ICUs. METHODOLOGY: The subcommittee first measured the pain assessment scores of patients at transfer from the ICU. After ascertaining that these scores were greater than the goal of 2, the process of providing pain relief was examined with the assistance of process control statistics, which showed a process barely capable of meeting the goal of pain score of 2 or less on a 0-5 scale. The process factors that affected this outcome were examined and changes were made where appropriate. One of these changes was development of a guideline for acute pain management based on the Agency for Health Care Policy Research's Acute Pain Management Clinical Practice Guideline. Reassessment of the pain scores and the process was then conducted. RESULTS: The pain assessment scores at transfer from the ICU decreased significantly. Thirty-five percent of patients in the preguideline survey rated their scores as greater than 2, compared with only 21% at the postguideline survey. Pain assessment and documentation also improved significantly. CONCLUSION: The Quality Improvement Council felt that improvements in pain management were due largely to their having provided staff with the right tools to use in assessing, documenting, and controlling pain. Gains in pain management continue to be made.

Fluid-percussion brain injury adversely affects control of vascular tone during hemorrhagic shock.

To test the hypothesis that brain injury impairs control of vascular tone during compensation from hemorrhagic shock, Sprague-Dawley rats underwent fluid-percussion brain injury (or sham injury control) followed by a stepwise hemorrhage period to 1/2 baseline mean arterial pressure (1/2 MAP), a shock period holding at 1/2 MAP for 30 min, and a resuscitation period. Aortic blood flow (ABF) was measured and vascular conductance (ABF/MAP) was calculated. No differences occurred between groups during the stepwise hemorrhage period. During the 30 min shock period, controls decreased conductance from .2 +/- .07 to .16 +/- .04 and required repeated additional hemorrhage (3.4 +/- 1.3 cc) to maintain 1/2 MAP. In contrast, brain-injured animals increased conductance from .21 +/- .07 to .24 +/- .06 (p < .05) during the shock period and required repeated fluid replacements (3.0 +/- 1.3 cc lactated Ringer's (LR), p < .05) to maintain 1/2 MAP. Following resuscitation, conductance appropriately increased to .31 +/- .05 in controls but did not change (.25 +/- .04, p < .05) in brain-injured animals. We conclude that brain injury adversely affects control of vascular tone during shock and resuscitation in this model.

Continuous use of standard process audit filters has limited value in an established trauma system.

OBJECTIVE: To evaluate the ability of five quality assurance/ quality improvement audit filters to identify opportunities for improvement in patient care in a mature trauma system. DESIGN: Retrospective analysis of prospectively collected data. MATERIALS AND METHODS: Total patient population at risk and audit filter fallouts were evaluated for the following audit filters: patients with (1) Glasgow Coma Scale (GCS) score < 14 who did not receive a CT scan within 2 hours of admission; (2) subdural/ epidural hematomas who did not undergo craniotomy within 4 hours; (3) open tibial fractures who did not undergo debridement within 8 hours; (4) abdominal gunshot wounds who did not undergo laparotomy within 4 hours; and (5) all deaths where a quality assurance action was taken. The filters were used for 1 year. Mortality was compared between fallouts and nonfallouts in each category and the frequency of corrective actions for each category were determined. RESULTS: Corrective actions were taken in 97 of the 418 fallouts from 3,787 patients at risk. The majority (77%) of these actions were for patients in the death audit filter group. There were 343 nondeath fallouts, representing 13% of the 2,719 nondeath patients at risk. Of these, 22 corrective actions were taken, representing 6.4% of the fallouts and less than 1% of the patients at risk. CONCLUSION: The non-death process based audit filters that we evaluated in our trauma system documented adherence to care process standards but found few opportunities for quality improvement, suggesting that audit filters should be periodically evaluated and changed when their goals have been accomplished.

Prostaglandin E2 production by endotoxin-stimulated alveolar macrophages is regulated by phospholipase C pathways.

BACKGROUND: Eicosanoids play an important role in many aspects of systemic inflammatory responses and host defense. Although the synthesis of eicosanoids by different enzymes has been elucidated, the regulatory mechanism of eicosanoid production is not clear. We designed this study to investigate the hypothesis that PGE2 production by endotoxin (lipopolysaccharide; LPS)-stimulated macrophages (MO) is dependent on phospholipase C (PLC) signaling pathways. METHODS: Rabbit alveolar macrophages (MO) were obtained by bronchoalveolar lavage. MO were suspended in RPMI-1640 medium at 1 x 10(6)/mL and were exposed to Escherichia coli LPS (10 ng/mL) +/- various agonists and antagonists of PLC and its secondary messengers. After 24 hours of incubation, prostaglandin E2 (PGE2) production was measured by ELISA. RESULTS: LPS-activated MO produced four times as much PGE2 as did control unstimulated MO. The increase in PGE2 production was inhibited by PLC inhibitors (U73122 or D609) and a low-molecular-weight PLA2 inhibitor, manoalide. An increase in intracellular calcium and activation of both the calmodulin and protein kinase C kinase pathways increase PGE2 production. CONCLUSIONS: PGE2 production is intimately dependent on several phospholipases. Production is not only dependent on low-molecular-weight PLA2 cleavage of arachidonic acid from membrane phospholipids, but also by-products of PLC activation. PLC-dependent intracellular Ca-calmodulin signaling and protein kinase C activation provide significant modulation of PGE2 production.

Calcium and calmodulin regulate lipopolysaccharide-induced alveolar macrophage production of tumor necrosis factor and procoagulant activity.

BACKGROUND: Alterations in macrophage (M phi) function are responsible, in part, for adult respiratory distress syndrome and multiple organ failure developing in patients with sepsis. Elucidation and control of these M phi mechanisms during sepsis are crucial to our understanding of this disease and, ultimately, to improving survival of these patients. OBJECTIVE: To investigate the involvement of calcium flux in endotoxin-induced alveolar M phi production of tumor necrosis factor (TNF) and procoagulant (PC) activity. DESIGN: Rabbit alveolar M phi obtained by bronchoalveolar lavage were exposed to endotoxin in the form of lipopolysaccharide (LPS) extracted from Escherichia coli 0111:B4 in the presence of different specific calcium agonists and antagonists. The TNF expression was measured in the supernatant by L929 bioassays. The PC activity was determined in cell lysates by a one-step coagulation assay. RESULTS: Macrophages activated by LPS produce enormous levels of TNF and PC. Either W7 (20 mumol/L), a calmodulin antagonist, or TMB-8 (50 mumol/L), which prevents calcium release from the endoplasmic reticulum, inhibited production of both TNF and PC activity. Verapamil (50 mumol/L) alone or combined with TMB-8 significantly inhibited both TNF and PC production by LPS-stimulated M phi. Elevating intracellular calcium ([Ca2+]i), using the calcium ionophore, A23187, or thapsigargin alone, did not induce M phi production of TNF but significantly augmented LPS-stimulated TNF production. CONCLUSION: Our results indicate that increased intracellular calcium causing signal transduction activation through the calmodulin pathway is a necessary, but insufficient, component of the LPS signaling in M phi.

Case study: when the nurse and physician don't agree.

Nurses and physicians by virtue of their roles as health care professionals must work together to provide care for their patients. Decisions regarding life support and death and dying are made almost daily in most intensive care units. Conflicts frequently arise among health care providers when decisions of this nature are made. Nurses and physicians, despite having similar value systems, operate under a different frame of reference. Understanding the differences and how they play themselves out in the clinical setting can alleviate much of the stress and frustration common when these issues are encountered. This article examines the value systems and perspectives of nurses and physicians using a case study format.

Differential microvascular response to cyclooxygenase blockade in the rat small intestine during acute bacteremia.

To determine whether arachidonic acid metabolites are mediators of regional blood flow changes during sepsis, we examined the effects of cyclooxygenase blockade on intestinal microvascular diameters and blood flow during acute bacteremia, induced in the rat by the intravenous injection of 10(9) live Escherichia coli. Mean arterial pressure, cardiac output, intestinal microvascular diameters, and blood flow were measured in the presence or absence of a topically applied selective cyclooxygenase inhibitor (mefenamate). Bacteremia caused a diffuse constriction of both arterioles and venules and a concomitant 50% decrease in blood flow. Treatment with mefenamate did not affect baseline intestinal microvascular tone or bacteremia-induced arteriolar constriction and hypoperfusion, but did reverse an intense venular constriction. Our results suggest that the small intestinal microcirculation has a differential response to cyclooxygenase products of arachidonic acid metabolism during acute bacteremia. They appear not to be mediators of the intestinal arteriolar constriction and hypoperfusion observed during acute E. coli bacteremia, but profoundly influence the mesenteric venular constriction. These observations support the concept that microvascular control mechanisms are different not only between but within organ specific vascular beds.