Biomedical subjects
Publications and source records attributed to E E Moore.
The nonresectional approach to major liver trauma is clearly preferred. Unfortunately, trachotomy with vessel ligation, selective hepatic arterial ligation, perihepatic pack, and fibrin glue are not viable options with high-energy bilobar liver injuries. We have fashioned a balloon tamponade device that has proved very effective for these transfixing hepatic gunshot wounds.
Tumor necrosis factor (TNF), rapidly becoming recognized as a mediator of inflammation, may be important in the pathogenesis of acute lung injury. Its role in the development of the adult respiratory distress syndrome (ARDS) in humans, however, has been difficult to clarify. To determine if TNF could be important early in the development of acute lung injury from multiple causes, we enrolled 103 patients within 8 h of meeting the criteria for an at-risk illness (sepsis, aspiration of gastric contents, severe pancreatitis, hypertransfusion, abdominal trauma, chest trauma, multiple fractures) and obtained multiple frequent blood samples for TNF measurements. Using five methods of TNF analysis, we were unable to find an association between TNF and the development of ARDS. However, we found significant differences in TNF measurements depending on the methods of analysis used, which could, at least in part, account for the inconsistencies in the published literature regarding the relationship between TNF and disease processes.
Excessive hydrogen peroxide (H2O2) generation appears to contribute to the development of the adult respiratory distress syndrome (ARDS), but H2O2-combatting antioxidant defenses have not been evaluated. We found that serum from septic patients with ARDS scavenged more (p less than 0.05) H2O2 in vitro (82.7 +/- 3.8%) than did serum from septic patients without ARDS (56.9 +/- 3.1%) or control subjects (20.2 +/- 2.4%). Serum from septic patients with ARDS also had more (p less than 0.05) catalase activity (54.9 +/- 10.9 U/ml) than did serum from septic patients without ARDS (28.6 +/- 3.4 U/ml) or control subjects (7.3 +/- 0.8 U/ml). In contrast, serum from septic patients with or without ARDS and control subjects had the same glutathione peroxidase (GPX) activity. Serum H2O2 scavenging activity correlated with serum catalase (r = 0.77) but not GPX (r = 0.33) activity and was inhibitable (greater than 90%) by sodium azide, a catalase inhibitor. Increases in serum catalase activity did not appear to be derived from erythrocytes (RBC) because septic patients with or without ARDS and control subjects had similar RBC hemolysis in response to osmotic stress in vitro and serum haptoglobin concentrations. Serum from septic patients with ARDS also protected endothelial cells against H2O2-mediated damage (34.5 +/- 2.2% 51Cr release) better (p less than 0.05) than serum from septic patients without ARDS (47.3 +/- 7.4%) or control subjects (82.1 +/- 10.2%), but killing of bacteria by neutrophils in vitro was the same in serum from patients and control subjects. Our findings indicate that patients with sepsis and/or ARDS have increased serum catalase activity, which may alter H2O2-dependent processes.
Metabolic support is an integral component in the care of the critically injured patient. When hypermetabolism occurs, there are increases in energy demands along with changes in substrate utilization. This article reviews the prospective randomized clinical trials that were undertaken at Denver General Hospital over the past decade that address both the timing of nutritional support and the route of administration in this critically injured population. Also discussed is a review of a meta-analysis that attests to the feasibility of early postoperative enteral feeding with the possibility of decreased septic morbidity in high-risk surgical patients. With the clinical knowledge gained from these trials, an algorithm for nutritional intervention was developed that represents our current standard of practice.
BACKGROUND: Phospholipase A2 (PLA2) has recently been implicated as a key enzyme of local inflammation after gut ischemia-reperfusion (I/R). The hypothesis of this study is that PLA2 inhibition decouples remote organ injury from gut I/R. METHODS: Sprague-Dawley rats were pretreated with a PLA2 inhibitor, quinacrine (10 mg/kg, intravenously), before the induction of gut ischemia (45 minutes of superior mesenteric artery occlusion) followed by 6 hours of reperfusion. 125I-labeled albumin leak was employed as a marker of pulmonary endothelial permeability and myeloperoxidase as a monitor of neutrophil (PMN) traffic in the gut and lung. To further characterize the impact of PLA2 inhibition, PMNs were harvested at 6 hours of reperfusion and superoxide production was measured in the presence or absence of an activating stimulus, N-formyl-methionyl-leucyl-phenylalanine. RESULTS: Gut I/R increased gut PLA2 activity, elicited gut PMN influx, and produced lung leak; these events were prevented by PLA2 blockade. Gut I/R also markedly enhanced PMN superoxide production with N-formyl-methionyl-leucyl-phenylalanine, and this priming was ablated by PLA2 inhibition. CONCLUSION: These data suggest that PLA2 activation is a proximal step in the pathogenesis of distant organ injury after splanchnic hypoperfusion, a process that appears to involve PMN priming in the gut bed.
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A progressive color-coded light activation panel is described that enhances in-hospital activation of the trauma team. This communication system creates a network among the resuscitation suite of the emergency department, the operating room, the anesthesiology department, and the surgery department.
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A multi-center experience with 210 severe liver injuries was reviewed to define postoperative changes in hepatic enzyme levels and body temperature profile. The 129 patients who survived initial operation comprised the data base. Serum glutamic oxaloacetic transaminase (SGOT) and lactate dehydrogenase (LDH) peaked within 24 hours (750 +/- 92 IU/L, 870 +/- 120 IU/L) and decreased rapidly during the first 4 days. Serum bilirubin was maximal at 7 days, while alkaline phosphatase rose slowly throughout 14 days. Hepatic enzyme elevations were more dramatic after blunt trauma, reflecting greater hepatocellular disruption. Maximum daily temperatures exceeding 38.0 degrees C and 39.0 degrees C were recorded for the first 3 postoperative days in 82 (64%) patients and 14 (11%) patients, respectively. No infectious source was evident in 13 (93%) of 14 patients with severe hyperpyrexia, implicating release of inflammatory mediators associated with major hepatic trauma. Convalescence from severe hepatic injury is marked by release of SGOT and LDH, as well as fever, which may be anticipated during the first 4 days postinjury.
We reviewed the recent experience with urgent thoracotomy performed in the operating room (OR) to compare the relative indications and injury pattern after blunt versus penetrating trauma. Among 2,316 patients admitted with acute trauma of the chest, excluding 319 undergoing thoracotomy at the emergency department, 83 required urgent OR thoracotomy; 27 patients (3 percent) sustained blunt trauma, 32 (4 percent) had stab wounds (SW) and 24 (7 percent) had gunshot wounds (GSW). The indications for operation after blunt trauma were shock (48 percent) and angiographically defined great vessel injuries (48 percent). For SW, thoracotomy was done for tamponade (50 percent), excessive chest tube output (28 percent) or shock (15 percent), and for GSW, thoracostomy output (50 percent), shock (25 percent) or tamponade (12.5 percent). Descending thoracic aorta (DTA) or other arch vessel tears were confirmed in 48 percent of patients with blunt trauma requiring thoracotomy; the remaining had pulmonary (31 percent) or cardiac wounds (7 percent). The most frequently encountered injuries in patients with SW were cardiac (46 percent) and pulmonary (37 percent), while the patients with GSW had predominantly pulmonary (72 percent) and cardiac (14 percent) injuries. The surgical management of blunt versus penetrating chest trauma differs with respect to the indications for urgent thoracotomy as well as the underlying injury pattern. The most common indication for urgent thoracotomy after penetrating injuries was excessive chest tube output (37.5 percent). Excluding torn DTA, only 14 of 822 patients (1.7 percent) admitted with blunt chest trauma required urgent thoracotomy and 13 of these patients (93 percent) presented in a state of refractory shock because of active thoracic hemorrhage. Thus, in contrast with penetrating wounds, urgent thoracotomy for blunt trauma is rarely justified on the basis of chest tube output alone.
OBJECTIVE: To determine the relationship between cigarette smoking and primary female infertility. DESIGN: Retrospective, case-control study. SETTING: Population-based and randomly selected from eight geographic areas in the United States. PARTICIPANTS: Women, 20 to 54 years of age, who were randomly selected to serve as the control group of the Cancer and Steroid Hormone Study were used for this study. Within this group, there were 483 women who were classified as having experienced primary infertility and 2,231 women eligible to serve as controls. Primary infertility, defined as 24 consecutive months of unprotected intercourse without conception, was documented from a calendar of each women's reproductive and contraceptive history. RESULTS: Smoking one pack of cigarettes per day (odds ratio = 1.36) and starting to smoke before 18 years of age (odds ratio = 1.30) were significantly associated with increased risk of infertility. Life table and proportional hazards analysis indicated that smoking did not significantly increase the time required to conceive among infertile women. CONCLUSIONS: Number of cigarettes smoked and age when the women began smoking contributed to infertility in this study. It is reasonable, therefore, to recommend that women stop smoking when they are attempting to become pregnant.
UNLABELLED: OBJECTIVE--To determine the impact of the pneumatic antishock garment on survival in patients with cardiac wounds. DESIGN--A retrospective review of a 6.5-year experience in a population of patients with gunshot or stab wounds to the heart (N = 70). SETTING--The city and county of Denver, Colo, where all patients were transported by paramedic ambulances to Denver General Hospital, an urban, level 1 trauma center. PATIENTS--All patients were analyzed, including those transported to the emergency department with no vital signs at the trauma scene. Only patients with definite penetrating cardiac injuries were included. METHODS--Paramedic trip sheets and emergency department, operating room, in-hospital, and autopsy records were reviewed. Demographic, clinical outcome, and treatment data were collected. A multiple logistic regression model was developed to determine which characteristics and treatment variables were independently predictive of patient outcome. The ability of each independent variable to predict outcome was determined by calculating adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS--Seventy patients (31 gunshot and 39 stab wounds) had a revised trauma score of 2.8 +/- 4.0 (mean +/- SD; range, 0-12; median, 0). Thirty-two (46%) had cardiac tamponade. Overall, 21 (30%) of the patients survived. In the logistic model, the presence of cardiac tamponade (OR, 9.1; 95% CI, 1.5 to 56.1) and a higher revised trauma score were associated with higher survival. Inflation of the pneumatic antishock garment was associated with sevenfold lower survival (adjusted OR, 0.14; 95% CI, 0.02 to 0.86); the effect was negative across all trauma score groups. CONCLUSION: --Survival in patients with penetrating cardiac wounds is highly associated with anatomic and physiologic factors, while application of the pneumatic antishock garment appears to be detrimental.
Recent animal data suggest that the gut plays a far more important metabolic role than previously thought. During critical illness, disruption in bowel barrier function may result in a chronic hypermetabolic state and contribute to multiorgan failure. Animal studies have demonstrated that enterocytes of the gastrointestinal tract use glutamine as a respiratory fuel and during critical illness the consumption of glutamine by the gut significantly increases. The selective uptake of glutamine by the gut, to date, has not been confirmed in humans. Seven patients who sustained multisystem trauma necessitating laparotomy underwent portal venous catheterization. This was done by carefully reopening the obliterated umbilical vein and facilitating access to the left branch of the portal vein using a standard central venous catheter. Portal venous and systemic blood samples were recorded for 5 days after operation. Amino acid levels in both circulations were recorded at 48 h and 5 days. Using Student's t test for related samples, the differences between individual amino acids in portal and systemic circulations were compared. At 48 h, mean(s.d.) portal venous glutamine was 85(5) per cent of the systemic levels (253(80) compared with 296(90) mumol/ml, P less than 0.002). At 5 days, portal glutamine was 87(3) per cent of the systemic levels (255(69) compared with 292(83) mumol/ml, P less than 0.003). Levels of citrulline, a breakdown product of glutamine metabolism, were elevated in the portal venous circulation at 48 h (20(4) compared with 16(3) mumol/ml, P less than 0.005) and at 5 days (21(5) compared with 14(3) mumol/ml, P less than 0.002). No significant differences between any of the other amino acids analysed were identified. This study confirms, for the first time in humans, that selective uptake of glutamine occurs in the gut. In stressed states, glutamine deficiency is associated with gut mucosal atrophy. This has significant implications as glutamine is not provided in most commercially available parenteral and enteral nutrition formulations.
In a 12-year period, 188 patients with penetrating wounds to the anterior neck were managed selectively. The 69 symptomatic patients were explored promptly. The remaining 119 patients (63%) were observed in the hospital using ancillary diagnostic tests based on injury location and trajectory. In the explored group, significant injuries were found in 60 patients (87%). In the observed group, one patient (0.8%) required delayed exploration for an occult injury. Average hospital stay for patients after neck exploration was 8.4 days, for patients after negative exploration 4.2 days, and for patients after observation 1.7 days. This ongoing experience confirms the efficacy and safety of selective neck exploration in a Level I Trauma Center.
In a 3-year experience treating 12 patients with blunt torn thoracic aorta, the repair technique was "clamp and sew" with an intraluminal graft in the initial six patients and partial left heart bypass using a centrifugal pump in the more recently treated six. Patients in the two groups were similar in regard to age, sex, and injury severity score. In the intraluminal graft group, graft insertion was abandoned for sutured anastomosis in two patients. Two patients sustained spinal cord ischemia, and two developed hypertension due to "pseudo-coarctation" syndrome. Because of these side effects related to the performance of intraluminal graft, partial left heart bypass was adopted as our routine procedure and was successful in all subsequent patients. Based on our experience and on reports in the current literature, we recommend left atrial-femoral bypass with the centrifugal pump for repair of the torn thoracic aorta.
When we are concerned about the adequacy of peripheral oxygen delivery, our monitoring efforts focus on cardiac output as the component easiest to manipulate. Thermodilution is the current method of determining cardiac output because of logistic convenience, but by no means should it be considered the gold standard. Thoracic electrical bioimpedance is an appealing alternative because of its simplicity, noninvasiveness, and ability to track physiologic trends, but there have been a number of warnings against relying on it exclusively, at least until it is further developed. Doppler ultrasound appears to be a valid method in skilled hands, but its accuracy in quantitating cardiac output, especially in the critically ill, remains questionable. Mixed venous oximetry and transcutaneous oxygen monitoring are promising but are still being evaluated.
STUDY OBJECTIVE: To determine the role of lavage amylase (LAM) and lavage alkaline phosphatase (LAP) in the identification of intraperitoneal hollow visceral injuries. DESIGN: Retrospective. SETTING: Level I trauma center, city/county institution. TYPE OF PARTICIPANTS: Patients with hollow visceral organ injury following major blunt or penetrating trauma whose diagnostic peritoneal lavage was negative by lavage red blood cell and lavage white blood cell were negative. MEASUREMENTS AND MAIN RESULTS: Fifty-one patients with injury isolated to one or more hollow visceral structures underwent diagnostic peritoneal lavage; 28 were positive based on aspirate, lavage red blood cell count (greater than 100,000/mm3), or lavage white blood cell count (greater than 500/mm3). Of the remaining 23 patients, each of 11 with isolated small bowel injury had LAM greater than or equal to 20 IU/L and six of these had LAP levels greater than or equal to 3 IU/L. All six patients with colon injury and two of the patients with gallbladder injury had LAM less than 20 IU/L and LAP less than 3 IU/L. CONCLUSIONS: In patients with hollow visceral injury and otherwise normal diagnostic peritoneal lavage, elevation in LAM is highly specific for isolated small bowel injury. Lavage enzyme determinations appear unhelpful in the detection of colonic injury. We recommend routine enzyme determinations of lavage effluent as a marker for isolated small bowel injury.
Metabolic support is an integral component of surgical critical care. Although prompt restoration of oxygen availability is clearly essential, the timing, composition, and route of nutritional support may also be decisive factors. The ensuing discussion will focus on: (a) timing of substrate delivery and (b) route of administration based on our clinical investigation over the past decade. The acutely injured patient was selected as a model of ICU hypermetabolism because of relative homogeneity with respect to age, comorbid factors, and stress level. Our first study hypothesis was that early nutritional support would improve outcome in the severely injured, but previously well-nourished patient. During an 18-month period, all patients undergoing laparotomy with a abdominal trauma index (ATI) greater than 15 were randomized to a control or total enteral nutrition (TEN) group. The control patients were given total parenteral nutrition (TPN) after POD 5, whereas the TEN cohort had a needle catheter jejunostomy (NCJ) inserted at laparotomy and received an elemental diet within 12 hours. The control (n = 31) and TEN (n = 32) groups were otherwise comparable with respect to risk stratification. The TEN patients, of course, shared improved nitrogen balance (p less than 0.001), but also had significantly (p less than 0.025) less septic morbidity. Nine (29%) of the controls developed major infections, contrasted to three (9%) of the TEN patients. Acknowledging the benefit of early nutrition, the next issue we addressed was the optimal route of substrate delivery; i.e., TEN vs TPN. The hypothesis was that TEN, compared to TPN, would reduce the injury stress response as reflected by the prioritization of hepatic protein synthesis. TEN given via NCJ and a nutritionally matched TPN solution were administered during the same postoperative period. Indeed, the TEN patients (n = 23) had significantly (p less than 0.05) higher constitutive proteins and lower acute-phase proteins, whereas the TPN patients manifested the opposite protein profile as measured by crossed immunoelectrophoresis. In view of these findings, we continued the study to ascertain clinical impact. Ultimately, 75 patients were randomized, providing groups with equivalent risk factors. Eleven (37%) of the TPN patients developed septic complications compared to five (17%) of the TEN group, and the incidence of major infection was six (20%) following TPN vs one (3%) with TEN. Thus, immediate TEN provided an additional clinical benefit compared to early TPN in these high-risk surgical patients.