Alterations in glucose-6-phosphatase gene expression in sepsis.

BACKGROUND: The influence of sepsis on the expression and activity of hepatic glucose-6-phosphatase (Glu-6-Pase) was examined during the early hyperglycemic phase and the later hypoglycemic phase. METHODS: Sepsis was induced in anesthetized, fasted rats by cecal ligation and puncture, and liver samples were taken at 0, 0.5, 1, 1.5, and 20 hours after cecal ligation and puncture. RESULTS: The mRNA abundance of hepatic Glu-6-Pase increased fourfold at 0.5 hours over healthy control values, two-fold after 1 hour, and returned to normal after 1.5 hours. This finding was followed by a corresponding increase in Glu-6-Pase activity and was coincident with increased plasma glucose levels and decreased liver glucose-6-phosphate (Glu-6-P) at 0.5 and 1 hours. Plasma insulin and glucagon levels remained unchanged during this period, whereas corticosterone levels increased 2.5-fold over control values. At 20 hours cecal ligation and puncture, plasma glucose levels returned to normal, coincident with a 90% reduction in Glu-6-Pase mRNA abundance. Glu-6-Pase activity and Glu-6-P concentration returned to normal levels, while insulin, glucagon, and corticosterone levels increased significantly, i.e., 40-fold, 6.5-fold, and 6-fold, respectively. CONCLUSION: The initial rise and subsequent decline in blood glucose correlate very well with a corticosterone-dependent induction of hepatic Glu-6-Pase, mRNA, and protein, followed by an insulin-dependent suppression of its expression.

Hyperventilation increases muscle protein synthesis in critically ill trauma patients.

BACKGROUND: Critically ill trauma patients are often in negative nitrogen balance and demonstrate advanced muscle protein wasting, which is in part due to a decrease in muscle protein synthesis. Previous studies have been performed on the relationship between pH and protein metabolism. Some evidence suggests that alkalosis might enhance protein synthesis. The purpose of the present study is to determine whether protein synthesis is increased in trauma patients who have a respiratory alkalosis from hyperventilation. METHODS: Trauma patients in the intensive care unit (n = 8) who were treated with hyperventilation for elevated intracranial pressures were enrolled. Muscle protein synthesis rates were determined in vivo using the flooding method with l-[(2)H(5)]phenylalanine. Measurements were performed twice on each patient within a 36-h period, first during hyperventilation and then after hyperventilation was discontinued. Hemoglobin oxygen saturation was maintained above 95% for all measurements. RESULTS: Protein synthesis in muscle was 1.38 +/- 0.11%/day during hyperventilation (pH 7.50 +/- 0.02, pCO(2) 27.3 +/- 1.0 mm Hg) and 0.93 +/- 0.15%/day after respiratory parameters were normalized (pH 7.39 +/- 0.01, pCO(2) 39.4 +/- 1.5 mm Hg). The synthesis rate was significantly higher (P < 0.01, paired t test), 0.46 +/- 0.13%/day (32.6%), at the time of hyperventilation. CONCLUSION: Muscle protein synthesis is elevated during hyperventilation in critically ill patients with traumatic brain injury. We believe this preliminary study provides data that warrant confirmation in larger clinical studies. It suggests that this ventilatory therapeutic strategy may have a role in mitigating the negative nitrogen balance and muscle protein wasting that can impair the recovery of these patients.

Critical analysis of injuries sustained in the TWA flight 800 midair disaster.

BACKGROUND: Previous reports of commercial airline disasters have reviewed incidents occurring at takeoff and landing. The purpose of the present study, which represents the first analysis of aviation injuries incurred during a midflight incident, was to examine the injuries sustained by the victims of the TWA Flight 800 disaster and to determine any correlation of injuries with structural damage and seat location. METHODS: Complete autopsy records, toxicology screening, and forensic analysis were reviewed. Injuries were assessed by anatomic region and severity by using the Abbreviated Injury Scale. The National Transportation Safety Board report of the investigation was applied to correlate individual injuries with seat location and structural damage. A comparison was performed against injury data from takeoff and landing incidents. RESULTS: All 230 passengers of TWA Flight 800 were recovered as fatalities. Head, thoracic, and abdominal injuries were multiple and severe, contributing to the mortality of the occupants. Analysis revealed that the severity of injury and anatomic injury pattern did not generally correlate with seating position or structural damage. A comparison of these injuries with those of takeoff and landing crashes showed differences in injury pattern and severity. CONCLUSION: Passengers of Flight 800 sustained instantaneous fatal blunt force injury. Analysis of the data revealed no global correlation between seat position and pattern of injury. In contrast to injuries incurred during crashes at takeoff and landing, these midflight injuries were too extreme to warrant a reappraisal of current passenger protective safety measures or standards.

Carboxyhemoglobin elevation in trauma victims.

BACKGROUND: Products of the hemeoxygenase enzyme include carboxyhemoglobin (COH) and bilirubin, which have protective effects in stressed states. Hemeoxygenase-1 enzyme up-regulates in states of oxidative stress. We hypothesized that COH is elevated in septic trauma patients compared with nonseptic patients. METHODS: A prospective study was carried out at a Level I trauma center involving all patients admitted to the trauma intensive care unit. During a 3.5-month period, 45 patients were enrolled, with 76 samples being drawn on admission and at later time points. The samples were classified as septic (Bone's criteria), stressed (based on expired gas analysis), or nonstressed nonseptic. Correlations with Acute Physiology and Chronic Health Evaluation III score, white blood cell count, temperature, partial pressure of oxygen, and percentage of inspired oxygen were evaluated. RESULTS: COH levels in samples drawn from patients presenting in shock (systolic blood pressure < or =90 mm Hg) were significantly higher than levels in samples from patients not in shock (systolic blood pressure >90 mm Hg) (3.27+/-1.09 vs. 2.75+/-0.64; p = 0.013). Samples from septic patients with infection were associated with significantly higher Injury Severity Scores (34.1+/-11.2 vs. 21.8+/-18.3; p< or =0.05) and a lower percentage of inspired oxygen (41.6+/-10.3 vs. 61.0+/-26.3; p< or =0.05). CONCLUSION: COH was significantly elevated in samples drawn during stress, sepsis, and shock states. There was overlap between sepsis and stress COH sample values, limiting the clinical usefulness of the assays in predicting sepsis. Further studies focusing on hemeoxygenase-1 expression and the role of its by-products in the outcomes of trauma patients are warranted.

A critical analysis of on-scene helicopter transport on survival in a statewide trauma system.

BACKGROUND: Recently, questions have been raised regarding the effectiveness of helicopters in trauma care. We conducted a retrospective study to evaluate the effect of on-scene helicopter transport on survival after trauma in a statewide trauma system. METHODS: Data were obtained from a statewide trauma registry of 162,730 patients treated at 28 accredited trauma centers. Patients transported from the scene by helicopter (15,938) were compared with those transported by ground with advanced life support (ALS) (6,473). Interhospital transfers and transports without ALS were excluded. Statistical analysis was performed using one-way analysis of variance and logistic regression. RESULTS: Patients transported by helicopter were significantly (p < 0.01) younger, were more seriously injured, and had lower blood pressure. They were also more likely to be male and to have systolic blood pressure < 90 mm Hg. Logistic regression analysis revealed that when adjusting for other risk factors, transportation by helicopter did not affect the estimated odds of survival. CONCLUSION: A reappraisal of the cost-effectiveness of helicopter triage and transport criteria, when access to ground ALS squads is available, may be warranted.

Unopposed interleukin-1 is necessary for increased plasma cytokine and eicosanoid levels to develop in severe sepsis.

OBJECTIVE: The purpose of the study was to identify the changes in plasma prostaglandin, leukotriene, and cytokine levels during clinical severe sepsis for which interleukin-1 was necessary. SUMMARY BACKGROUND DATA: Circulating prostaglandins, leukotrienes, and cytokines have been implicated as causative agents of systemic inflammation due to sepsis. However, interactions between interleukin-1 and the other cytokine and eicosanoid mediators of severe sepsis are not well-defined. METHODS: As part of two sequential multisite, prospective, randomized, double-blind, placebo-controlled clinical trials, 37 patients with severe sepsis received interleukin-1 receptor antagonist (IL-1ra) 100-mg bolus followed by 2 mg/kg per hour intravenously for 72 hours (n = 20) or placebo (n = 17). Plasma thromboxane B2 (TxB2), prostaglandin 6-keto-F1alpha (PGI), leukotriene B4 (LTB4), leukotriene C4D4E4 (LTC4D4E4), interleukin-1 beta (IL-1), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha) were measured by enzyme-linked immunosorbent assay before study drug infusion (baseline) and at 24, 48, and 72 hours after the beginning of the study drug infusion. RESULTS: Differences between placebo and IL-1ra for plasma LTB4 were not significant, but only IL-1ra LTB4 increased from baseline. Plasma TxB2, PGI, LTC4D4E4, TNF, and IL-6, expressed as % baseline, decreased significantly in patients receiving IL-1ra compared with the placebo group (p < 0.05), whereas plasma IL-1 increased significantly. CONCLUSIONS: Interleukin-1 may be a necessary mediator of increased circulating PGI, TxB2, LTC4D4E4, TNF, and IL-6 levels in patients with severe sepsis. Plasma IL-1 and LTB4 are increased with infusion of IL-1 receptor antagonist. The clinical significance of IL-1 in modifying circulating eicosanoid and cytokine concentrations in clinical sepsis is not clear from the data.

Nutritional implications of significant small bowel resection.

Nutrition support of the patient with short bowel syndrome is determined by the extent and location of bowel resection, the functional status of residual bowel, and presence or absence of the ileocecal valve. The authors discuss the consequences and treatments for bowel resection.

Synthesis, activity and toxicity of novel macrocyclic ligands against HIV-1 in Jurkat and CEM-SS cell lines.

We have developed versatile synthetic routes that afford metal-free macrocycles containing different functionalities in their framework. Novel oxaziridine and amide containing macrocycles were synthesized, and the metal complexes of the latter were also prepared. A series of theophilline and thymidine side-arm containing podands as well as macrocycles were obtained employing the same methodology. The primary anti-viral tests of these synthetic compounds for anti-HIV-1 activity was carried out using the XTT-based cytopathicity assay (CEM-SS cells) with AZT as positive control. It was found that the nature of the macrocyclic headgroups affected the anti-HIV-1 activity. Heteroatom containing macrocyclic headgroups displayed activity in the micromolar range. Metal complexation did not enhance the activity and side-arm substitution resulted in inactive compounds. Cell viability determined in both Jurkat and CEM-SS cells was strongly dependent on the structure of the macrocyclic framework. The oxaziridine moieties in the macrocycle were highly toxic to CEM-SS and less toxic to Jurkat cell lines, while amide containing macrocycles were toxic to neither.

The pivotal role of transesophageal echocardiography in the management of traumatic thoracic aortic rupture with associated intra-abdominal hemorrhage.

Rupture of the thoracic aorta after blunt trauma, particularly when associated with multiple injuries, presents a major problem of resuscitation and management. Transesophageal color Doppler echocardiography (TEE) during laparotomy played a major role in confirming the diagnosis of thoracic aortic rupture in a patient.

Complications of anticoagulation for pulmonary embolism in low risk trauma patients.

Trauma patients are at significant risk for deep venous thrombosis (DVT) and pulmonary embolism (PE). Anticoagulation is standard therapy for DVT/PE, but may cause severe complications. We reviewed the course of 70 trauma ICU patients treated over a 28-month period. Thirty-six patients (51.4 percent) were treated by continuous IV heparin and/or oral warfarin. Of these, 13 patients (36 percent) developed complications requiring termination of anticoagulation. These included recurrent PE (four), subdural hematomas (three), hemothorax (two), heparin-induced thrombocytopenia (one), hemorrhagic pericardial effusion (one), retroperitoneal hematoma (one), and sudden unexplained drop in hemoglobin and shock (one). All patients with subdural hematomas had no prior evidence of head injury on brain computed tomography. All patients with recurrent PE received adequate anticoagulation therapy. Age > 55 was associated with increased risk of complications (8 of 13; p = .02:chi 2). Thirty-four other patients (48.6 percent) received inferior vena caval filters with no related complications or deaths. Anticoagulation for DVT/PE should be used selectively in trauma patients and avoided in elderly patients. Such patients should undergo early caval filter placement.

Bacterial translocation occurs in humans after traumatic injury: evidence using immunofluorescence.

UNLABELLED: We evaluated the occurrence of bacterial translocation (BT) in humans after traumatic injury. Twenty trauma patients (18 with blunt trauma) requiring celiotomy and without hollow viscus injury were studied. After surgical hemostasis and repair, portal venous blood (PVB) was sampled for culture. Additionally, a mesenteric lymph node (MLN) was harvested for culture and indirect immunofluorescence analysis using, first, mouse monoclonal antibody to E. coli beta-galactosidase, then goat anti-mouse immunoglobulin G (IgG). Injury Severity Score (ISS), Trauma Score (TS), and period of hemorrhagic shock (HS; systolic BP < 90 mm Hg with blood loss > 500 mL) were recorded before specimens were obtained. RESULTS: Fifteen patients initially had HS (mean period of 60 minutes). Mean TS and ISS were 10 and 29, respectively. Seven patients did not have HS (mean TS and ISS, 10 and 13). Three patients received antibiotics preoperatively. Portal venous blood culture produced positive results in only three patients (two with HS) and culture of the MLN specimen was positive in one. However E. coli beta-galactosidase was detected within the cytoplasm of macrophages in all MLNs. One patient developed multiple organ failure. CONCLUSION: Bacterial translocation occurs in humans following traumatic injury and may be independent of HS. Culture techniques may not detect BT since organisms may have been phagocytized by macrophages. The clinical significance of BT in trauma patients remains unclear.

Continuous pulse oximetry and the diagnosis of pulmonary embolism in critically ill trauma patients.

The diagnosis of pulmonary embolism (PE) may be difficult to establish in trauma patients, particularly those who are unresponsive or mechanically ventilated. Based on a prior retrospective study, we hypothesized that patients monitored by continuous pulse oximetry who experienced a 10% or greater sudden sustained drop in arterial oxygen saturation (SaO2) without a change in static lung compliance (Cst) were most likely to have had a PE. We followed SaO2 in 972 patients admitted to our trauma ICU during the 18-month period ending in December 1990. Forty-eight patients (5%) with SaO2 changes, but no Cst changes, were evaluated for suspected PE using pulmonary arteriography (PA). Of these, 21 (44%) had a positive PA study. All patients with a positive PA had either clear chest roentgenograms or no change in underlying pulmonary pathologic processes. Of the remainder, 26 had evidence of a new pathologic entity on chest roentgenograms and only one patient had a SaO2 decrease, no change in Cst, and a negative PA. All mechanically ventilated trauma patients should have SaO2 monitored continuously. Patients with a > 10% drop in Sao2 with no change in Cst and no new roentgenographic chest findings should undergo PA. Based on our experience, this approach would yield a sensitivity, specificity, and predictive value of 100%, 99.9%, and 95%, respectively, for the diagnosis of clinically significant PE.

Injuries of the abdominal aorta from blunt trauma.

Blunt injuries of the abdominal aorta are rarely reported in the literature. If left undiagnosed, these injuries may have catastrophic consequences. Four patients with blunt abdominal aortic lesions, identified in the authors' trauma registry, are presented in this report, along with a discussion of the pertinent literature to illustrate clinical management techniques. The mechanisms of injury include motor vehicular crashes (most frequent) with or without seatbelt use, abdominal blows, falls, and abdominal crush injuries. The spectrum of aortic lesions ranges from simple contusion or intramural hematoma to intimal disruption, false aneurysm, or frank rupture. Aortography should be performed in all stable patients with suspected aortic injury. All central-medial retroperitoneal hematomas discovered at laparotomy for blunt trauma should be explored after proximal and distal control of the aorta is obtained. Strict adherence to these principles, maintenance of standard vascular technique, and aggressive, expeditious resuscitative evaluation may improve survival.

Retroperitoneal hematoma after blunt trauma.

We reviewed retrospectively 233 consecutive patients with retroperitoneal hematoma (RPH) resulting from blunt trauma. This study group represented 2.9 per cent of all admissions for blunt trauma and 13 per cent of all admissions for blunt abdominal trauma. Motor vehicle accidents predominated as the cause of injury. Fifty-five per cent of the patients had fractures of the pelvis. Laparotomy was the primary method used in diagnosing RPH (73 per cent). The RPH was located in zone I in 14 per cent of patients, zone II in 37 per cent, zone III in 46 per cent and zone IV in 3 per cent. The RPH was explored in 35 per cent of all patients. Major vessels were the most common organ system injured (21 per cent) in patients with zone I RPH. The kidney was the most commonly injured organ (27 per cent) in patients with zone II RPH. Injury of either the pancreas or duodenum in 14 per cent of patients with right-sided zone II RPH indicates the need for careful evaluation of those organs at operation. Patients with zone III RPH associated with fractures of the pelvis should be explored only rarely--when main iliac vascular injury is suspected (4.6 per cent in this series). Otherwise, a systematic approach using external fixator devices and angiographic embolization should be used. The over-all morbidity and mortality rates of 59 and 39 per cent, respectively, emphasize the need for aggressive resuscitation, rapid control of hemorrhage and a multidisciplinary approach to the management of these patients.

Emergency central venous catheterization during resuscitation of trauma patients.

Central venous catheterization during resuscitation of trauma patients remains controversial. Such catheterizations performed at the UMDNJ-Robert Wood Johnson Medical School at Camden Cooper Hospital/University Medical Center (Camden, NJ) trauma center for the period January 1, 1988 to December 31, 1989 were retrospectively reviewed. Patients with underlying hemothorax, pneumothorax, or resuscitative thoracotomy were excluded. There were 269 catheters inserted using the Seldinger technique. Catheters were placed via the internal jugular or subclavian veins by attending traumatologists or emergency medicine and surgical house staff under direct attending supervision. Of 238 patients ages 6 to 90 years, 156 were men. Mean Trauma Score and Injury Severity Score were 9 and 30, respectively. Patients were divided into two groups: patients undergoing cardiopulmonary resuscitation or in shock (systolic bp less than 90) during resuscitation (Group 1: n - 161); and patients not in shock (Group 2: n - 77). Thirty patients (Group 1a) expired in the resuscitation area. The remainder (Group 1b) with 150 catheterizations had 12 complications (8%): pneumothorax (8), hemothorax (1), and malposition (3). Group 2, with 80 catheterizations, had 6 complications (7.5%): pneumothorax (4), hematoma (1), and malposition (1). The complication rate for patients surviving the resuscitation (230 catheterizations) was 7.8 per cent. There were no catheter-related deaths. In conclusion, emergency central venous catheterization during resuscitation of trauma patients carries a relatively low risk of serious complications when performed by experienced physicians.

Multichamber gunshot wounds of the heart. The utility of transesophageal echocardiography.

A patient had a gunshot wound to the heart involving three cardiac chambers. Conventional echocardiography failed to identify the intracardiac injuries. The utility of transesophageal echocardiography in a patient with cardiac trauma is described.