Lorrie A. Langdale

Fluosol-DA as a red-cell substitute in acute anemia.

Abstract We assessed the safety and efficacy of Fluosol-DA as a red-cell substitute in acute anemia. Twenty-three surgical patients with blood loss and religious objections to receiving blood transfusions were evaluated. Fifteen moderately anemic patients with a mean hemoglobin level (±SE) of 7.2±0.5 g per deciliter had no evidence of a physiologic need for increased arterial oxygen content and did not receive Fluosol-DA. Eight severely anemic patients with a mean hemoglobin level of 3.0±0.4 g per deciliter met the criteria of need and received the drug until the physiologic need disappeared or a maximal dose of 40 ml per kilogram of body weight was reached. We observed no adverse reactions to Fluosol-DA. The average peak increment in arterial oxygen content with the drug was only 0.7±0.1 ml per deciliter. There were no appreciable beneficial effects of Fluosol-DA, perhaps because of the small increase in arterial oxygen content, the brief half-life of the drug (24.3±4.3 hours), and the limited total dose...

Safety and efficacy of video-assisted retroperitoneal debridement for infected pancreatic collections: a multicenter, prospective, single-arm phase 2 study.

BACKGROUND The feasibility of video-assisted retroperitoneal debridement (VARD) for infected pancreatic walled-off necrosis is established. We provide prospective data on the safety and efficacy of VARD. DESIGN Multicenter, prospective, single-arm phase 2 study. SETTING Six academic medical centers. PATIENTS We evaluated 40 patients with pancreatic necrosis who had infection determined using Gram stain or culture. INTERVENTIONS Percutaneous drains were placed at enrollment, and computed tomographic scans were repeated at 10 days. Patients who had more than a 75% reduction in collection size were treated with drains. Other patients were treated with VARD. Crossover to open surgery was performed for technical reasons and/or according to surgeon judgment. MAIN OUTCOME MEASURES Efficacy (ie, successful VARD treatment without crossover to open surgery or death) and safety (based on mortality and complication rates). Patients received follow-up care for 6 months. RESULTS We enrolled 40 patients (24 men and 16 women) during a 51-month period. Median age was 53 years (range, 32-82 years). Mean (SD) Acute Physiology and Chronic Health Evaluation II score at enrollment was 8.0 (5.1), and median computed tomography severity index score was 8. Of the 40 patients, 24 (60%) were treated with minimally invasive intervention (drains with or without VARD). Nine patients (23%) did not require surgery (drains only). For 31 surgical patients, VARD was possible in 60% of patients. Most patients (81%) required 1 operation. In-hospital 30-day mortality was 2.5% (intent-to-treat). Bleeding complications occurred in 7.5% of patients; enteric fistulas occurred in 17.5%. CONCLUSIONS This prospective cohort study supports the safety and efficacy of VARD for infected pancreatic walled-off necrosis. Of the patients, 85% were eligible for a minimally invasive approach. We were able to use VARD in 60% of surgical patients. The low mortality and complication rates compare favorably with open debridement. An unexpected finding was that a reduction in collection size of 75% according to the results of computed tomographic scans at 10 to 14 days predicted the success of percutaneous drainage alone.

Near-infrared spectroscopy : Continuous measurement of cytochrome oxidation during hemorrhagic shock

OBJECTIVE Mitochondrial cytochrome a,a3 redox shifts can be determined by near-infrared wavelength reflection. Since near-infrared wavelengths penetrate skin and bone, a potential exists to noninvasively measure mitochondrial oxidation using this phenomenon. The purpose of this study was to compare conventional parameters of resuscitation with regional measurements of spectroscopically derived cytochrome redox state in a hemorrhagic shock model. DESIGN Prospective, controlled laboratory investigation. SETTING Animal research laboratory of a university medical center. SUBJECTS New Zealand white rabbits (n = 23), weighing 2 to 3 kg. INTERVENTIONS After anesthesia and instrumentation, the subjects underwent laparotomy with placement of near-infrared spectroscopy probes on the stomach, liver, kidney, and hamstring muscle. Baseline measurements were obtained, and phlebotomy was used to reduce cardiac output by 60% for 30 mins. Animals were resuscitated with shed autologous blood and crystalloid to reach baseline cardiac output (0.9%), and were monitored for an additional 60 mins. MEASUREMENTS AND MAIN RESULTS Significant correlations between mitochondrial cytochrome a,a3 redox state, cardiac output, and oxygen delivery were observed throughout shock and resuscitation. However, gastric cytochrome oxidation did not recover after shock, despite systemic evidence of adequate resuscitation (p < .05). CONCLUSIONS Resuscitation from severe hemorrhagic shock may not uniformly restore cellular oxygenation, despite normalization of traditional parameters of resuscitation. Direct monitoring of cytochrome oxidation may be useful in identifying regional areas of dysoxia.

The utility of routine preoperative computed tomography scanning in the management of veterans with colon cancer

BACKGROUND The aim of this study is to assess the clinical utility of routine preoperative computed tomography (CT) scanning in patients with cancer of the intraperitoneal colon. METHODS From November 1997 to June 2001, all patients at VA Puget Sound Healthcare System with a diagnosis of colon cancer were referred for a preoperative CT scan. Medical records and operative notes were reviewed to determine the influence of preoperative CT on clinical management. RESULTS Seventy patients received a CT per protocol. Preoperative CT provided information that was used in treatment planning and management in 26 (37%) cases. However, if preoperative scans had not been performed, the clinical management would have been definitively altered in only 13 (19%) patients. CONCLUSIONS Although these data suggest potential benefit for routine preoperative CT scanning, we believe additional study, including cost analysis, should precede the adoption of CT scanning as a routine preoperative study in patients with colon cancer.

Suppressor of cytokine signaling expression with increasing severity of murine hepatic ischemia-reperfusion injury

BACKGROUND/AIMS Preservation of function requires tight regulation of the cellular events initiated when hepatic ischemia is followed by reperfusion (IR). One important mechanism modulating the cytokine-directed response to injury is Suppressors of Cytokine Signaling. SOCS1 and SOCS3 ensure appropriate intensity and duration of cytokine signaling through negative feedback on JAK-STAT signaling. The contribution of SOCS1 and SOCS3-mediated regulation to the evolution of hepatic IR injury is unknown. METHODS C57Blk6 mice were subjected to mild (20 min) or severe (90 min) hepatic ischemia. Liver was analyzed for cytokine and SOCS1/3 induction as well as JAK-STAT activation at intervals after reperfusion. RESULTS Tnf, Il-1beta, and Il-6 expression paralleled increasing injury severity. Despite early phosphorylation of both STAT1 and STAT3 after severe injury, only nuclear translocation of activated STAT3, suggesting that the induction of target genes through JAK-STAT after IR is predominantly via STAT3. Socs3 was expressed across the injury spectrum while Socs1 was induced only in the face of severe IR injury. Severe IR in Il-6 deficient mice confirmed that Il-6, acting via STAT3, serves as a primary inducer of both regulatory mechanisms. CONCLUSIONS Under the influence of IL-6-mediated STAT3 signaling, Socs1 serves as a complimentary regulatory mechanism when Socs3 is insufficient to limit cytokine-mediated inflammation after hepatic IR.

Sustained tolerance to lipopolysaccharide after liver ischemia-reperfusion injury.

Liver ischemia-reperfusion injury (IR) would be expected to alter the capacity of previously ischemic as well as continuously perfused segments that are exposed to circulating inflammatory mediators to respond to a subsequent infectious insult. IR is reported to induce tolerance to subsequent endotoxin stimulation if the lipopolysaccharide (LPS) challenge is delayed until the late, neutrophil-mediated phase of reperfusion. Whether ischemic or perfused liver is differentially affected and whether LPS-tolerance may be overcome by increasing exposure is unknown. We hypothesized that late tolerance after IR reflects a refractory state in which the livers expression of pro-inflammatory mediators in response to secondary LPS is limited. Precision-cut tissue culture methodology was used to investigate the capacity of rabbit liver to respond to a spectrum of LPS stimulation 24 h after partial IR. Slices from normal liver showed a dose-dependent response to LPS for tumor necrosis factor (TNF-&agr;) expression. Slices from both previously ischemic and continuously perfused lobes retained dose responsiveness for TNF-&agr;, although TNF-&agr; was significantly decreased at high LPS concentrations compared with normal liver. Ischemic liver sustained this blunted response despite extended exposure to LPS, whereas perfused slices recovered responsiveness to high dose LPS with prolonged stimulation. IR induced interleukin-8 in both ischemic and perfused liver, but secondary LPS stimulation did not augment interleukin-8 expression. Hepatic IR induces a late tolerance to secondary LPS challenge in locally ischemic tissue that cannot be overcome by increasing LPS exposure. Nonischemic liver exposed to the systemic effects of IR injury, however, retains a capacity to respond to LPS with sufficient stimulation.

Liposome-encapsulated hemoglobin inhibits tumor necrosis factor release from rabbit alveolar macrophages by a posttranscriptional mechanism

Macrophages contribute to the systemic inflammatory response that characterizes the sepsis syndrome through the production of inflammatory cytokines such as tumor necrosis factor (TNF). Liposome‐ encapsulated hemoglobin (LEH), a potential red cell substitute, is cleared by fixed tissue macrophages. In these studies, in vitro incubation of alveolar macrophages with stored LEH was shown to inhibit the expression of TNF induced by endotoxin (lipopolysaccharide, LPS) stimulation. This effect was dependent on LEH dose but independent of the period of exposure to the LEH. Despite inhibition of TNF expression, Northern blot analysis of total cellular RNA from LPS‐stimulated macrophages revealed accumulations of TNF‐specific transcripts in cells treated with or without LEH. Thus the mechanism of LEH inhibition of TNF expression appears to involve a posttranscriptional event. Although these results suggest a potential advantage of resuscitation with LEH when sepsis complicates hemorrhagic shock, immunomodulation in vivo remains to be defined.

Tuberculosis and the surgeon

With the resurgence of active tuberculosis in the United States, surgeons may be called upon to participate in the management of primary tuberculosis as well as major complications of the disease. To define the role of surgery in the diagnosis and treatment of tuberculosis in the 1990s, a 5-year retrospective review of 121 tuberculosis patients requiring invasive procedures in the course of their work-up was performed. Mycobacterium tuberculosis was cultured in 68% of patients, and atypical mycobacteria in 19%. Tissue was required to achieve the definitive diagnosis in 36%. Of the 93 patients with pulmonary evidence of tuberculosis, 54% presented with a pulmonary complication, 19 of whom required operative intervention. Extrapulmonary tuberculosis affected 45% of patients, including nine with miliary tuberculosis. Patients testing seropositive for human immunodeficiency virus accounted for 11% of the patients seen, emphasizing that the re-emergence of tuberculosis is not confined to the immunosuppressed.

Expanding surgical clerkships to remote community sites: the success of the Washington, Wyoming, Alaska, Montana, and Idaho experience

BACKGROUND The purpose of this analysis was to determine if the surgical clerkship model and site affect educational outcomes and student postclerkship perceptions. METHODS Data from University of Washington students participating in surgical clerkships at traditional/academic or community/apprentice sites across Washington, Wyoming, Alaska, Montana, and Idaho (WWAMI) between 2005 and 2007 were gathered retrospectively. Comparisons of final examination scores as well as postclerkship student evaluations of the educational experience were made between traditional and community training sites. RESULTS The mean final examination scores at WWAMI sites were significantly higher than those at traditional academic sites. Furthermore, WWAMI sites were rated higher with respect to time spent by faculty in direct observation, quality of the clerkship as a whole, and overall contribution to medical education. CONCLUSIONS Community surgical clerkship sites remote from an academic institution can provide an excellent learning experience for students.

Assessment of a 35% fluorocarbon emulsion

We have previously reported on the efficacy of a 20% fluorocarbon emulsion (Fluosol-DA, 20%) as an acellular O2 carrier at an FIO2 = 1.0. We are concerned, however, about the potential O2 toxicity that may result from extended exposure to FIO2 = 1.0. The O2 content of the fluorocarbon phase is linearly related to both the FIO2 and the fluorocarbon concentration (Fct). It should therefore be possible to maintain the same O2 content by raising the Fct using a higher fluorocarbon concentration and lowering the FIO2. The purpose of this report is to assess the ability of a 35% fluorocarbon emulsion (Fluosol-DA, 35%) at an FIO2 = 0.6 to support hemodynamics and O2 transport. Five adult baboons were paralyzed, anesthetized, intubated, and mechanically ventilated at FIO2 = 0.6. An isovolemic total exchange transfusion (E.T.) with Fluosol-DA, 35% was performed. Measurements were made at Hcts of 20, 10, 5, and less than 2%. All animals survived the exchange. Total arterial O2 content fell from 17.4 +/- 0.7 to 3.3 +/- 0.2 vol% (p less than 0.01), and O2 delivery decreased from 21.8 +/- 2.2 to 5.1 +/- 0.7 cc/min-kg (p less than 0.01) during the exchange. There was no significant change in MAP, H.R., C.O., or VO2 during the exchange transfusion. Fluosol-DA, 35% maintains normal hemodynamics and O2 transport despite a marked fall in arterial O2 content and total O2 delivery. Fluosol-DA, 35% is thus an effective O2 carrier at the safe FIO2 of 0.6.