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Objective To determine which organs produce the increased levels of nitric oxide (NO) seen after hemorrhage and resuscitation. Animals and Interventions Adult male rats underwent laparotomy (ie, trauma induced) and were bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of the maximum bleedout volume was returned in the form of Ringer lactate. The rats were then resuscitated with Ringer lactate, 4 times the maximum bleedout volume for 1 hour. Sham-operated animals underwent only the surgical procedure. Main Outcome Measures Plasma levels of nitrate/nitrite (NO 3 − /NO 2 − , stable products of NO) were measured by colorimetric assay at the maximum bleedout volume; at the end of hemorrhage; at the end of resuscitation; and 1.5, 4, 8, and 24 hours after resuscitation. In additional rats, the heart, liver, small intestine, kidneys, and spleen were harvested 4 hours after resuscitation for the measurement of NO 3 − /NO 2 − levels. Moreover, tissue perfusion was determined in the above-mentioned organs by radioactive microspheres 4 hours after resuscitation in other groups of animals. Results Plasma levels of NO 3 − /NO 2 − were similar to those of sham-operated animals during hemorrhage and at the end of resuscitation. One and a half hours after the end of resuscitation, however, NO production increased significantly. The peak levels of plasma NO 3 − /NO 2 − occurred at 4 hours, and the levels remained elevated even 24 hours after resuscitation. Tissue NO 3 − /NO 2 − levels were significantly increased in the liver, small intestine, and spleen 4 hours after resuscitation. In contrast, the levels of NO 3 − /NO 2 − were similar to those of sham-operated animals in the heart and kidneys at all times. Blood flow in the heart was maintained after hemorrhage, whereas hepatic, intestinal, splenic, and renal perfusion decreased significantly. Conclusions The gut and liver seem to be the sites responsible for the increased NO production seen after trauma and hemorrhage. The overproduction of NO is most likely caused by up-regulation of inducible NO synthase. Thus, attempts to reduce NO production using specific inhibitors for inducible NO synthase might be helpful for improving hepatic and intestinal functions after trauma and hemorrhagic shock.

Objectives To examine the outcomes of patients managed with the palliative triangle method and to evaluate factors associated with effective patient selection. Design Patients receiving a procedure to palliate symptoms of advanced cancer were identified prospectively from all surgical palliative care consultations and observed for at least 90 days or until death. Setting: Academic surgical oncology service. Patients A total of 227 patients symptomatic from advanced incurable cancer. Intervention The palliative triangle technique was used to select patients for palliative operations. Main Outcome Measures Symptom resolution, overall survival, and complications. Results We evaluated 227 patients from July 1, 2004, through June 30, 2009. Reasons cited for not selecting 121 patients (53.3%) for a palliative procedure were low symptom severity (23.9%), decision for nonoperative palliation (19.0%), patient preference (19.8%), concerns about complications (15.7%), and other (21.6%). A palliative operation was performed in 106 patients (46.7%) for complaints of gastrointestinal obstruction (35.8%), local control of tumor-related symptoms (25.5%), jaundice (10.4%), and other (28.3%). Of these 106 patients, 5 required procedures for recurrent symptoms and 6 for additional symptoms; of the 121 patients originally not selected, 12 required procedures for progressive symptoms, for a total of 129 procedures. Patient-reported symptom resolution or improvement was noted in 117 of 129 procedures (90.7%). Palliative procedures were associated with 30-day postoperative morbidity (20.1%) and mortality (3.9%). Median survival was 212 days. Conclusion Palliative operations performed in these carefully selected patients were associated with significantly better symptom resolution and fewer postoperative complications compared with previously published results.

Although adrenal insufficiency may not occur with moderate hypotension, it does occur with severe hemorrhage. Since hepatocellular function is depressed following severe hemorrhage, it remains unknown whether the liver plays any role in regulating adrenal function after trauma and hemorrhagic shock.Hepatic 11beta-hydroxysteroid dehydrogenase (11beta-HSD), a microsomal enzyme responsible for the degradation of bioactive corticosterone, plays a major role in the development of adrenal insufficiency following trauma and severe hemorrhage.Male rats underwent laparotomy to induce trauma before hemorrhage. They were then bled to and maintained at a blood pressure of 40 mm Hg until 40% of the maximal bleed-out volume was returned in the form of Ringer lactate. The rats were then resuscitated with 4 times the volume of maximal bleed-out with Ringer lactate during a 60-minute period. Plasma levels of corticosterone and corticotropin were measured at various intervals. In additional groups, corticotropin-induced corticosterone release, adrenal contents of corticosterone and cyclic adenosine monophosphate (cAMP), hepatic 11beta-HSD activity, and plasma levels of corticosterone-binding globulin were determined at 1.5 hours after resuscitation. Moreover, a model of moderate hypotension (blood pressure, 80 mm Hg) was used to determine whether adrenal function is depressed under such conditions.At the time of maximal bleed-out, plasma corticosterone and corticotropin levels increased by 245% (P.001) and 293% (P.001), respectively. Despite corticotropin levels being similar to those of the animals undergoing sham operation after resuscitation, corticosterone levels in hemorrhaged animals remained elevated up to 4 hours after resuscitation (by 158%-207%; P.001). In addition, corticotropin-induced corticosterone release decreased by 78% at 1.5 hours after resuscitation (P = .009). In contrast, moderate hypotension did not reduce corticotropin-induced corticosterone release. Adrenal corticosterone content and cAMP levels (i.e., the second messenger of corticotropin action) decreased by 55% (P.001) and 25% (P = .03), respectively. Hepatic 11beta-HSD activity decreased significantly at 1.5 hours after resuscitation (P.001).Sustained increase in plasma corticosterone levels following hemorrhage and resuscitation may be, in part, due to the decreased hepatic 11beta-HSD activity. The high level of corticosterone negatively regulates corticotropin release, further reducing adrenal responsiveness to corticotropin stimulation. Thus, the liver appears to play an important role in regulating adrenal function following trauma and severe hemorrhage.

Background: Nonoperative management of blunt hepatic injury in hemodynamically stable trauma patients is now common. Recently, it has been proposed that the finding of hepatic periportal tracking (PPT) of blood on the initial computed tomographic (CT) scan is a sensitive marker of significant hepatic and subhepatic injury that might militate against nonoperative management. While CT scan is useful in diagnosing the injury, the utility of follow-up CT scans has not been elucidated. Design: Retrospective chart review. Setting: Regional trauma center. Patients: The records of 58 hemodynamically stable patients with blunt hepatic trauma were reviewed and the following data recorded: age, outcome, Injury Severity Score (ISS), operative intervention, and complications. Computed tomographic scans were taken on admission and reviewed for the presence of PPT. The timing and radiographic appearance of follow-up CT scans was also recorded. Results: Seventeen patients (29%) had radiographic evidence of PPT while 41 patients (71%) did not. Age, ISS, injury grade, overall success rate of nonoperative management, and incidence of complications were not statistically significant between the two groups. In no instance did a routine follow-up CT scan affect subsequent management of the patient. Conclusions: The finding of PPT on the admission CT scan is not clinically significant and does not preclude nonoperative management of patients with blunt hepatic injury. Furthermore, routine follow-up CT scans are not indicated, as treatment is not influenced by their results. Rather, follow-up CT scans should be obtained as dictated by the patient's clinical course. Extrapolation of these findings to all patients with blunt hepatic trauma in the United States would result in considerable savings of health care dollars, without negatively affecting patient care. (Arch Surg. 1996;131:255-260)

Objective: To evaluate the pulmonary effect of treatment withN-nitro-L-arginine methyl ester (NAME) with and without inhaled nitric oxide (NO) in a swine model of endotoxemia. Design: Randomized controlled trial. Setting: Laboratory. Interventions: Following a 20-minute intravenous infusion ofEscherichia colilipopolysaccharide (LPS) (200 μg/kg), animals were resuscitated with saline solution (1 mL/kg per minute) and observed for 3 hours while mechanically ventilated (fraction of inspired oxygen [Fio2], 0.6; tidal volume, 12 mL/kg; positive end-expiratory pressure, 5 cm H2O). Group 1 (LPS, n=6) received no additional treatment; group 2 (NAME, n=5) received NAME (3 mg/kg per hour) for the last 2 hours; group 3 (NO, n=6) received NAME (3 mg/kg per hour) and inhaled NO (40 ppm) for the last 2 hours; and group 4 (control, n=5) received only saline solution without LPS. Main Outcome Measures: Cardiopulmonary variables and blood gases were measured serially. The multiple inert gas elimination technique was performed at 3 hours. The wet-to-dry lung weight ratio was measured following necropsy. Results: Administration of LPS resulted in pulmonary arterial hypertension, pulmonary edema, and hypoxemia with increased ventilation perfusion ratio mismatching. None of these changes were attenuated by NAME treatment alone but all were significantly improved by the simultaneous administration of inhaled NO. Conclusions: Systemic NO synthase inhibition failed to restore hypoxic pulmonary vasoconstriction following LPS administration. The deleterious effects of endotoxemia on pulmonary function can be improved by inhaled NO but not by systemic inhibition of NO synthase. (Arch Surg. 1994;129:1233-1239)

Injury elicits a response from all cells of the immune system in which cytokines and other metabolic products of activated leukocytes can act either beneficially to provide for enhanced host resistance or deleteriously to depress the function of remote organs and cause what has been termed systemic inflammation . These at times antithecal responses of leukocytes that appear to integrate postinjury changes in the neuroendocrine, immune, and coagulation systems have been implicated as principal causative factors in multiple systems organ failure. Numerous investigators have evaluated a variety of therapeutic agents to prevent and control infection by restoring leukocyte function, while others have evaluated antagonists and monoclonal antibodies as a means of controlling the exaggerated and persistent actions of leukocytes and cytokines caused by systemic inflammation. The redundancies of the cell populations and the cytokines and other metabolites produced by the cells predictably limit the effectiveness of any single agent and make clinical evaluation of such agents difficult. (Arch Surg. 1993;128:1260-1267)