Gianna Scannell

Trauma causes early release of soluble receptors for tumor necrosis factor

The importance of tumor necrosis factor (TNF) in the pathophysiology of trauma and hemorrhagic shock is not known. In addition, TNF bioactivity may be modulated by soluble forms of the 55-kd and 75-kd membrane receptors (TNFR). This study was undertaken to determine circulating levels of TNF and TNFR after trauma. Nine severely injured male patients were studied. The mean age was 30 +/- 10 years (range, 15-45). The mean Injury Severity Score (ISS) was 31.3 +/- 17.6 (range, 10-59), and the mean Revised Trauma Score (RTS), 5.7 +/- 2.2 (range, 0.7-7.8). Serum was obtained immediately upon arrival at our trauma center, within 1 hour of injury. The TNF and TNFR levels in the serum were measured using ELISA techniques. After trauma, 55-kd and 75-kd TNFR levels were significantly elevated above those of controls (6.99 +/- 4.57 ng/mL and 5.42 +/- 1.88 ng/mL, respectively, p < 0.01); TNF levels were not increased. Patient serum containing TNFR inhibited in vitro TNF cytotoxicity and correlated with 55-kd TNFR levels (p < 0.05). We conclude that TNF is a strong releasing factor for TNFR; the presence of TNFR may be indirect evidence that TNF is present after trauma, despite low measured levels. Both TNF and TNFR may be more important in trauma and hemorrhagic shock than previously thought.

Decreasing unplanned extubations in the surgical intensive care unit.

BACKGROUND Unplanned extubations are common, but can be life-threatening. METHODS We conducted a prospective evaluation of all intubated patients in our surgical intensive care unit to examine the effects of three parameters on the likelihood of accidental extubation. The parameters were the method of endotracheal tube fixation, the use of sedation/paralysis, and the use of hand restraints. During the baseline period, tubes were secured with cloth or velcro ties, sedation was used conservatively, and hand restraints were used routinely. A change in one study parameter was made prior to each period. Thus, in period II, tubes were secured using waterproof tape; in period III, tubes were secured with waterproof tape and sedation/paralysis was used liberally; and in period IV, tubes were secured with waterproof tape and limited use was made of hand restraints. RESULTS Accidental extubations were significantly less frequent when tubes were secured with waterproof tape (P < 0.0001). No difference was seen when sedation was instituted liberally. Restricted use of hand restraints was associated with significantly increased accidental extubations (P < 0.001). CONCLUSIONS Our data support the use of water resistant tape to secure endotracheal tubes and the routine use of hand restraints.

Soluble cytokine receptors and receptor antagonists are sequentially released after trauma.

Cytokine receptors and receptor antagonists (RAs) have been identified in trauma patients. We hypothesized that after traumatic injury, a sequential release of soluble cytokine receptors and RAs may exist that mirrors the release of the primary cytokines themselves. Twenty-two patients were included in the study: 14 males and 8 females. The mean age was 30.1 +/- 12.5 (range, 19 to 71), and the mean Injury Severity Score was 28.7 +/- 12.6 (range, 4 to 57). There were 15 survivors and 7 nonsurvivors. Samples were collected on arrival to the emergency department and at serial intervals for up to 7 days. Monoclonal antibody enzyme-linked immunosorbent assay kits to tumor necrosis factor (TNF), soluble TNF-receptor (sTNF-R) 55 kd and 75 kd, interleukin (IL)-1 and IL-1 RA, and IL-2 and IL-2r were used. Sera from 22 healthy individuals were used as normal controls. No TNF, IL-1, or IL-2 could be detected in any patient sera after injury. Control levels for the soluble cytokine receptors and RAs were as follows: sTNF-R 55 kd, 607 +/- 89 pg/mL; sTNF-R 75 kd, 2,141 +/- 169 pg/mL; IL-1 RA, 291 +/- 35 pg/mL; and IL-2r, 426 +/- 53 U/mL. In trauma patients, both 55 kd and 75 kd sTNF-R were significantly elevated on arrival to the emergency department, with values of 2,441 +/- 506 pg/mL (p < 0.001) and 4,736 +/- 537 pg/mL (p < 0.001), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

A method to determine the adequacy of resuscitation using tissue oxygen monitoring.

The change in tissue PO2 in response to an increased inspired O2 challenge may be related to the state of cellular oxygenation, and hence the adequacy of resuscitation. To test this hypothesis, we measured tissue PO2 during inspired O2 challenges in 29 injured patients during acute resuscitation or intensive care unit monitoring. The O2 challenge test had 100% sensitivity and specificity in detecting flow-dependent O2 consumption in invasively monitored patients in the intensive care unit. During acute resuscitation, 60% of patients had negative initial O2 challenge test results, indicating that flow-dependent O2 consumption might have been present. Of nine such patients, five had subsequent positive O2 challenge test results after fluid resuscitation, indicating successful resuscitation. Four patients (27% of acute resuscitations), however, had repeatedly negative findings, possibly indicating persistent inadequate cellular oxygenation despite fluid resuscitation. Other commonly measured variables did not differentiate these patients. Monitoring of tissue PO2 during an inspired O2 challenge may be a useful test for determining the adequacy of resuscitation from hypovolemic shock.

Tumor necrosis factor and monocytes are released during hemorrhagic shock

Tumor necrosis factor (TNF) is a key mediator involved in many physiologic processes including immunity, inflammation, and metabolism. A relationship between TNF and hemorrhagic shock has not been clearly demonstrated. To help understand the role of TNF in hemorrhagic shock we developed a hemorrhagic shock model to measure TNF and monocyte levels during hemorrhage and resuscitation. Male Sprague-Dawley rats were anesthetized and subjected to a 50% blood loss (30 ml/kg) over 2 min and left in shock for 58 min. The animals were then resuscitated with two times blood loss (60 ml/kg) using lactated Ringers over 1 h. This model results in 75% mortality within 3 days (LD 75). Blood samples (2 ml) were obtained at intervals during shock and resuscitation, and assayed for TNF concentrations and white blood cell counts. Despite a marked fall in total leukocytes (24,600 pre-hemorrhage to 11,300 post-hemorrhage, P < 0.005), monocytes increased in percentage and in total count. Blood levels of TNF were initially undetectable but rose within 10 min after hemorrhage, peaked at 30 min after hemorrhage, and then became undetectable during resuscitation. In this model, macrophages and TNF are released into the circulation after hemorrhagic shock. TNF may play a role as a mediator in the pathophysiology of hemorrhagic shock.

Effects of trauma on leukocyte intercellular adhesion molecule-1, CD11b, and CD18 expressions

BACKGROUND During traumatic injury, a multitude of events, including ischemia, may cause leukocyte adhesion and margination. In this study, alterations of surface receptors involved in leukocyte adhesion were studied in traumatized patients. In an attempt to discern the role of hypoxia, additional experiments were conducted in which normal human leukocytes were subjected to hypoxic stress in vitro. METHODS Venous blood was obtained from 10 trauma patients within 2 hours of blunt injury (mean Injury Severity Score of 17 +/- 8) and from 8 normal volunteers (controls). Leukocytes were isolated from patients and controls. To assess the effect of hypoxia, normal leukocytes were placed in hermetically sealed environments containing 100% nitrogen. All leukocytes were labeled with phycoerythrin- or fluorescein-bound monoclonal antibodies to intercellular adhesion molecule-1 (ICAM-1), or to integrins CD18 and CD11b. Receptor concentration was measured by flow cytometry. Results were expressed as percentage of receptor-positive cells (%) and mean fluorescence channel units, which directly correlate with monoclonal antibody cell surface density. Significance of differences was tested by analysis of variance/Kruskal-Wallis test. RESULTS Compared with the normal controls, circulating leukocytes obtained from traumatized patients showed decreased expression of ICAM-1, CD11b, and CD18 2 hours after injury. In contrast, normal leukocytes exposed to hypoxic stress in vitro exhibited a marked increase in CD11b and CD18 expression and no change in ICAM-1 expression. CONCLUSIONS Leukocytes obtained from traumatized patients showed a significant decrease in cell surface expression of adhesion receptors. This phenomenon is unlikely to be a direct consequence of hypoxia alone, because exposure to isolated hypoxia in vitro actually increased expression of CD11b and CD18.

Regional flow during experimental hemorrhage and crystalloid resuscitation: persistence of low flow to the splanchnic organs

UNLABELLED BACKGROUND AND METHODS. Rapid changes in cardiac output (CO) and organ perfusion occur with hemorrhagic shock and fluid resuscitation. To assess regional alterations of flow, 40 Sprague-Dawley male rats were subjected to hemorrhagic shock and crystalloid resuscitation under halothane anesthesia. Polyethylene microspheres were injected before and after hemorrhage and after resuscitation. At sacrifice, brain, lungs, heart, liver, intestine, spleen and kidneys were harvested, weighed and radioactivity counted. Changes in mean arterial pressure, oxygen consumption, organ flow and CO were also measured. RESULTS Cardiac output decreased during hemorrhage (P less than 0.01), it increased with resuscitation but did not return to baseline even with infusion of fluid volumes of three times the blood loss. Flow decreased during hemorrhage in all organs, but the difference was not statistically significant in the liver (P greater than 0.05), since a larger percentage of CO was maintained as hepatic perfusion. During resuscitation, flow to brain and kidneys increased over the percentage values expected by increased CO (P less than 0.01), but flow to the liver did not increase significantly. Flow to small bowel remained depressed (P less than 0.005). CONCLUSIONS Following hemorrhage there is hypoperfusion of all splanchnic organs; however, flow to the liver decreases least. Crystalloid resuscitation in our model failed to return CO to baseline. Blood supply to intestine remained depressed in disproportion to CO both after hemorrhage and resuscitation and hepatic blood flow remained decreased after resuscitation.

A technique for repair of traumatic parasternal lung herniation: case report.

A case of traumatic lung herniation through an area of costalsternal separation in a 36-year-old male is presented. Persistent pain and the threat of strangulated lung tissue prompted repair that was accomplished with an expanded polytetrafluoroethylene Gortex tissue patch.

Continuous arteriovenous hemodiafiltration in postoperative and traumatic renal failure.

Management of acute renal failure (ARF) in surgical patients has relied on supportive measures including hemodialysis and peritoneal dialysis. An alternative technique currently available is continuous arteriovenous hemodiafiltration (CAVH-D). Records of 44 surgical patients with ARF who were treated with CAVH-D in our surgical intensive care unit from 1989 to 1992 were reviewed. Thirty-five patients underwent emergency operations, and 4 patients underwent elective operations. Thirty-three patients were hemodynamically unstable immediately prior to the institution of CAVH-D, making hemodialysis a contraindication. A total of 565 CAVH-D days with an average of 13 days per patient were evaluated. Seventeen patients survived, with recovery of renal function in 13 patients. Vascular access was obtained via 227 percutaneous femoral catheters and 4 Scribner shunts. Seven vascular complications occurred, including arteriovenous fistula, pseudoaneurysm, limb ischemia, femoral artery hemorrhage, and femoral vein thrombosis. Based on these data, we conclude that CAVH-D is a safe and effective alternative in surgical patients with ARF.

Pentoxifylline alone versus pentoxifylline combined with superoxide dismutase prolongs survival in a rat hemorrhagic shock model

Pentoxifylline (PTX) and superoxide dismutase (SOD) have each proven effective in improving survival when administered during resuscitation in animal models of hemorrhagic shock. This study was conducted to determine if PTX and SOD combined would have synergistic effectiveness in the treatment of hemorrhagic shock. Sprague-Dawley rats (n = 40) were phlebotomized at 25 ml/kg for 2 min, then subjected to a 45-min ischemic period, and resuscitated with lactated Ringers solution (LR) (50 ml/kg) over 1 h. This model resulted in 70% mortality over 72 h when resuscitation was with LR alone. Animals were randomized into groups to receive one of the following agents during resuscitation: PTX in LR, SOD in LR, a combination of PTX and SOD in LR, or LR alone. PTX or SOD alone were effective in prolonging survival. However, the combination of PTX and SOD did not prolong survival above LR control.