Wolfgang Ertel

Incidence and clinical pattern of the abdominal compartment syndrome after "damage-control" laparotomy in 311 patients with severe abdominal and/or pelvic trauma.

Objective To investigate the incidence, main physiologic effects, and therapeutic management of the abdominal compartment syndrome (ACS) after severe abdominal and/or pelvic trauma. Design Retrospective analysis from January 1991 to December 1996; prospective study from January 1997 to August 1998. Setting Level I trauma center, intensive care unit. Patients A total of 311 patients with severe abdominal and/or pelvic trauma and “damage-control” laparotomy on day of admission. Interventions The ACS was defined as the development of significant respiratory compromise, including elevated inspiratory pressure of >35 mbar, a decreased Horowitz quotient (<150 torr [<20 kPa]), renal dysfunction (urine output, <30 mL/hr), hemodynamic instability necessitating catecholamines, and a rigid or tense abdomen. Beginning with January 1997, urinary bladder pressure as an additional variable for the diagnosis of ACS was continuously measured in patients (n = 12) at risk. Bladder pressures of >25 mm Hg indicated ACS. Measurements and Main Results Seventeen patients (5.5%) developed ACS because of persistent intra-abdominal/retroperitoneal bleeding (n = 12; 70.6%) or visceral edema (n = 5; 29.4%). All patients with ACS underwent primary fascial closure. In eight of these patients (47%), abdominal and/or pelvic packing for hemostasis was performed. All patients with ACS required decompressive emergency laparotomies because of physiologic derangements. The time between primary laparotomy and decompressive laparotomy was 12.9 ± 2.0 hrs. Emergency decompression of the abdomen resulted in a significant increase in the cardiac index (+146%), tidal volume (+133%), Horowitz quotient (+156%), and urine output (+1557%), whereas bladder pressure (−63%), heart rate (−19%), central venous pressure (−30%), pulmonary artery occlusion pressure (−43%), peak airway pressure (−31%), partial pressure arterial carbon dioxide (−30%), and lactate (−40%) markedly (p < .05) decreased. In two multiply injured patients with additional head trauma, ACS caused a critical increase of the intracranial pressure, which markedly dropped after the release of abdominal tension. Conclusions Risk factors for the occurrence of ACS are severe abdominal and/or pelvic trauma, which require laparotomy and packing for the control of hemorrhage. The ACS occurs within hours and causes life-threatening physiologic derangements and a critical rise in intracranial pressure in patients with combined abdominal/pelvic and head trauma. Decompressive laparotomy immediately restores impaired organ functions. In patients at risk, the continuous measurement of urinary bladder pressure as a simple, noninvasive, and less expensive diagnostic tool for early detection of elevated intra-abdominal pressure is mandatory.

Control of severe hemorrhage using C-clamp and pelvic packing in multiply injured patients with pelvic ring disruption.

Objectives Evaluation of diagnostic and therapeutic workup in multiply injured patients with pelvic ring disruption and hemorrhagic shock. Design Prospective study. Patients Twenty consecutive multiply injured patients (ISS: 41.2 ± 15.3 points) with pelvic ring disruption and hemorrhagic shock. Intervention A C-clamp was used for primary stabilization of the pelvic ring instability. In patients with persistent or massive hemorrhage, laparotomy and pelvic packing were performed. Consecutive measurements of blood lactate levels during the early period after injury. Main Outcome Measurements Lactate, mortality. Results A C-clamp was applied in all patients within 57.4 ± 30.6 minutes of arrival. Fourteen patients underwent laparotomy with pelvic packing for control of hemorrhage, three patients additional resuscitation thoracotomy (aortic clamping:n = 2). Four patients died of exsanguinating hemorrhage during the first 5.4 ± 3.3 hours from arrival, one patient because of septic multi-organ failure twenty-three days after injury (total mortality: 5/20; 25 percent). Lactate levels at admission were elevated in all patients (5.1 ± 2.6 mmol/l). Increased blood lactate levels (4.8 ± 1.7 mmol/l) (+71 percent;p < 0.05) were observed in survivors undergoing laparotomy compared with survivors without laparotomy (2.8 ± 1.1 mmol/l). In contrast, hemoglobin (7.0 ± 2.6 g/dl versus 7.9 ± 2.2 g/dl) and hematocrit (21.4 ± 6.4 percent versus 23.2 ± 6.8 percent) were similar in both groups. In patients who died during the first hours after admission, lactate levels were elevated (8.6 ± 2.5 mmol/l) compared with survivors (4.2 ± 1.8 mmol/l) and increased further. Conclusions Sequential measurements of blood lactate levels during the early period after injury may provide a more rapid and reliable estimation of true severity of hemorrhage than routinely used parameters. Pelvic packing in addition to pelvic ring fixation with a C-clamp allows for effective control of severe hemorrhage in multiply injured patients with pelvic ring disruption.

The complex pattern of cytokines in sepsis. Association between prostaglandins, cachectin, and interleukins.

Although the cytokines tumor necrosis factor (TNF), interleukin-1 (IL-1), and interleukin-6 (IL-6) are important mediators of hemodynamic, metabolic, and immunologic alterations in the host during sepsis, it is not known whether there is any association between the release of these cytokines and prostanoids during sepsis. Sepsis induced by cecal ligation and puncture in rats led to a persistent elevation (p ≤ 0.05) of plasma TNF until 10 hours, steadily increasing (p ≤ 0.05) IL-1 plasma levels, and enhanced (p ≤ 0.05) IL-6 plasma levels at all time points compared to the sham group. Prostaglandin E2 plasma levels were elevated (p ≤ 0.05) at 5 hours (153 ± 29 pg/mL; control: 47 ±11 pg/mL) and 10 hours (96 ± 16 pg/mL; control: 21 ± 5 pg/ mL). Prostaglandin E2 production by splenic macrophages (sMø) from septic animals was increased (p ≤ 0.05) at 5 hours (9.1 ±2.2 ng/mL) and 10 hours (5.6 ±1.5 ng/mL) compared to controls (3.3 ± 0.3. ng/mL at 5 hours; 1.3 ± 1.3 ng/mL at 10 hours). Incubation of sMø from septic animals with ibuprofen enhanced (p ≤ 0.05) IL-1 and TNF synthesis, while IL-6 production was reduced (p ≤ 0.05). These results indicate that the alterations in prostanoid release and elevated plasma prostanoids may regulate the release and consequently the circulating levels of cytokines during sepsis.

Liver Ischemia And Reperfusion Induces A Systemic Inflammatory Response Through Kupffer Cell Activation

To study the role of Kupffer cells (KC) as a cellular source of proinflammatory cytokines in hepatic ischemia/reperfusion, Sprague-Dawley rats were subjected to 20 min global hepatic ischemia. Sham-operated animals served as controls. Blood levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1 alpha), and interleukin 6 (IL-6) were determined after 10, 30, 60, 120, and 240 min of reperfusion and compared with spontaneous cytokine release by KC isolated after 60 min of reperfusion. Hepatic ischemia/reperfusion resulted in an enhanced (p < .01) spontaneous release of TNF-alpha (+482%), IL-1 alpha (+33%), and IL-6 (+175%) by KC. Kinetic analysis of cytokinemia revealed an early increase (p < .01) of TNF-alpha and IL-1 alpha within minutes upon reperfusion, while an elevation of IL-6 serum levels was observed with a delay of 2 h. Early cytokinemia was associated with dysfunction/injury of the liver, lung, and kidney after 4 and 24 h of reperfusion, respectively. These data indicate that hepatic ischemia/reperfusion results in Kupffer cell activation and increased cytokine levels, which may produce systemic inflammation and may be responsible for tissue injury locally and on remote sites.

Relationship between procalcitonin plasma levels and severity of injury, sepsis, organ failure, and mortality in injured patients.

Objective: To compare procalcitonin (PCT) plasma levels of injured patients with the incidence and severity of systemic inflammatory response syndrome (SIRS), infection, and multiple organ dysfunction syndrome (MODS) and to assess the predictive value of PCT for these posttraumatic complications. Design: Retrospective study comparing patients with mechanical trauma in terms of severity of injury, development of infectious complications, and organ dysfunctions. Setting: Level I trauma center with emergency room, intensive care unit, and research laboratory. Patients: Four hundred five injured patients with an Injury Severity Score of ≥9 points were enrolled in this study from January 1994 to February 1996. Interventions: Blood samples were collected on the day of admission and on days 1, 3, 5, 7, 10, 14, and 21 thereafter. Measurements and Main Results: We determined PCT serum levels using a specific immunoluminometric assay. We retrospectively evaluated the occurrence of SIRS, sepsis, and MODS using patients’ charts. Mechanical trauma led to increased PCT plasma levels dependent on the severity of injury, with peak values on days 1 and 3 (p < .05) and a continuous decrease within 21 days after trauma. Patients who developed SIRS demonstrated a significant (p < .05) increase of peak PCT plasma levels compared with patients without SIRS. The highest PCT plasma concentrations early after injury were observed in patients with sepsis (6.9 ± 2.5 ng/mL; day 1) or severe MODS (5.7 ± 2.2 ng/mL; day 1) with a sustained increase (p < .05) for 14 days compared with patients with an uneventful posttraumatic course (1.1 ± 0.2 ng/mL). Moreover, these increased PCT plasma levels during the first 3 days after trauma predicted (p < .0001; logistic regression analysis) severe SIRS, sepsis, and MODS. Conclusions: These data indicate that PCT represents a sensitive and predictive indicator of sepsis and severe MODS in injured patients. Routine analysis of PCT levels seems to aid early recognition of these posttraumatic complications. Thus, PCT may represent a useful marker to monitor the inflammatory status of injured patients at risk.

Incidence of septic complications and multiple organ failure in severely injured patients is sex specific.

BACKGROUND Sexual hormones are potent regulators of various immune functions. Although androgens are immunosuppressive, estrogens protect against septic challenges in animal models. This study correlates sexual dimorphism with the incidence of posttraumatic complications in severely injured patients. METHODS From January of 1991 to February of 1996, 1,276 consecutive injured patients (Injury Severity Score [ISS] > or = 9 points) were studied. Males (n = 911) did not differ from females (n = 365) with regard to severity of injury (ISS) and injury pattern. RESULTS The incidence of posttraumatic sepsis (30.7%) and multiple organ dysfunction syndrome (29.6%) was significantly increased in severely injured males with ISS > or = 25 points in comparison to the equivalent group of females (sepsis, 17.0%; multiple organ dysfunction syndrome, 16.0%). No difference was found in patients with ISS < 25 points. Moreover, plasma levels of procalcitonin and interleukin-6 were elevated (p < 0.05) in severely injured males compared with females. CONCLUSION Sex influences posttraumatic morbidity in severely injured patients and supports the concept that females are immunologically better positioned toward a septic challenge.

Relationship of interleukin-10 plasma levels to severity of injury and clinical outcome in injured patients.

Interleukin-10 (IL-10) markedly inhibits lymphocyte and phagocytic functions, which are essential for an adequate immune response to invading microbes. Although various animal and clinical studies revealed an increased release of IL-10 during sepsis, alterations of circulating IL-10 after injury and potential relationships to severity of injury and clinical outcome are unknown. Injured patients (n = 417) showed elevated (p < 0.001) IL-10 levels throughout the observation period of 21 days compared with healthy volunteers (n = 137). Patients with severe injury (Injury Severity Score > or = 25 points) demonstrated significantly increased IL-10 levels compared with patients with minor trauma (Injury Severity Score < 25 points). Patients who died from injury or developed posttraumatic complications (sepsis, multiple organ dysfunction syndrome) revealed elevated IL-10 levels in comparison with injured patients with uneventful posttraumatic course. Thus, trauma causes an enhanced release of IL-10 dependent on the severity of injury. Because increased IL-10 levels are significantly related to posttraumatic complications, IL-10 may be involved in their pathogenesis.

The gut : A cytokine-generating organ in systemic inflammation?

The aim of this study was to test the hypothesis that the gut is capable of becoming a cytokine-generating organ following either a lethal or nonlethal inflammatory insult. Adult male rats were given an intraperitoneal challenge with saline, or with a nonlethal (.1 mg/g) or LD50 (.5 mg/g) dose of zymosan. Mesenteric lymph nodes, efferent mesenteric lymph, liver, spleen, and blood (portal and systemic) were obtained at 2, 4, 6, 8, or 10 h post challenge. Organs, lymph, and blood were tested for bacterial translocation (BT); blood and lymph were assayed for tumor necrosis factor (TNF) and IL-6. After .1 mg/g zymosan, BT was limited to the mesenteric lymph node complex only; .5 mg/g zymosan promoted BT to blood, mesenteric lymph, and organs (p < .05 vs. control or .1 mg/g zymosan). The magnitude of portal bacteremia was greater than systemic bacteremia (p < .003). Serum TNF peaked at 2 h (p < .05 vs. control), and serum IL-6 peaked at 4–6 h (p < .05 vs. control) post zymosan challenge. Portal and systemic bioactivity was similar for either cytokine, and serum bioactivity did not correlate with zymosan dose. TNF bioactivity was increased in the mesenteric lymph at 2 h post challenge with .5 mg/g zymosan only (p < .05 vs. control or .1 mg/g zymosan). IL-6 bioactivity was increased in the mesenteric lymph at 4 through 10 h post zymosan challenge (p < .05 vs. control), but was similar with either dosage of zymosan. In conclusion, the gut may be capable of producing cytokines in response to an inflammatory stimulus, even in the absence of portal or systemic spread of bacteria. The magnitude of the cytokine response does not correlate with the magnitude of bacterial translocation.

Hemorrhage induces an increase in serum TNF which is not associated with elevated levels of endotoxin

Although tumor necrosis factor (TNF) and interleukin 6 (IL 6) are purported to be important mediators of inflammatory responses following trauma, it is not known if the serum levels of these cytokines are altered by simple hemorrhage. The objective of this study therefore was to determine whether or not: 1) there is any elevation of TNF or IL 6, and 2) if endotoxin, an important upregulator of these cytokines, is also increased following hemorrhage. To study this, C3H/HeN mice were bled to, and maintained at a mean blood pressure of 35 mmHg for 60 min, and then resuscitated with their own shed blood and adequate fluid. Mice were sacrificed at 30 min into hemorrhage and at 2, 4 or 24 hr post-hemorrhage to obtain serum samples. IL 6 and TNF levels were measured using cytokine dependent cellular assays. Using a quantitative Limulus amebocyte lysate assay, endotoxin levels were determined. TNF levels were significantly elevated at 30 min into hemorrhage, remaining so at 2 hr after resuscitation, but absent by 4 hr. Although there was a trend toward elevated IL 6 levels at 2 hr following hemorrhage, which was sustained up to 24 hr, the values were not significantly different from sham controls. When compared to controls, no marked increase in endotoxin was seen at any time point during or following hemorrhage. These results indicate that hemorrhage, in the absence of significant tissue trauma, causes enhanced TNF release which is not the result of increased endotoxin.

Trauma-induced suppression of antigen presentation and expression of major histocompatibility class II antigen complex in leukocytes.

The immune response to trauma, shock, and/or sepsis appears to exhibit a bimodal response, in which there is an early exaggerated inflammatory response, giving way over time to a state of hyporesponsiveness or immune dysfunction. This state of immune dysfunction is frequently associated with increased infectious complications and/or mortality, seen following shock or trauma. In this article, we present an overview of some of those changes that have been seen with respect to the process of major histocompatibility class II (MHC class II) antigen presentation by macrophage, a key component of the overall host immune response to foreign bacterial and/or fungal pathogens encountered following shock/trauma (with a particular emphasis on hemorrhagic shock as a component of traumatic shock). With respect to the overall process of antigen presentation, defects (dysfunction) are evident not only in models of shock and sepsis, but also in traumatized patients. Studies of the capacity of a monocytes/macrophages ability to present antigen indicate that defects can be detected, not only in those steps involved in antigenic processing, but also in MHC class II molecule expression and accessory molecule function (or its inhibition) following shock. Those changes in the macrophages capacity to process antigen seen during the first 24 h after hemorrhagic shock appear to be associated with the cells metabolic response to regional hypoxia and/or the shift to proinflammatory mediator release (tumor necrosis factor, interleukin [IL]-1, IL-6, etc.). This initial acute response to shock appears to act as the nidus for chronic anti-inflammatory mediator release (prostaglandin E2, transforming growth factor-beta, IL-10, IL-4, nitric oxide, etc.), which may mediate the sustained depression of the antigen-presenting cells function.