Otmar Trentz

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.

Ultrasound in blunt abdominal and thoracic trauma.

Between July 1989 and June 1991, 312 patients with blunt thoracic or abdominal injuries were examined prospectively. Sonographic examination was performed by surgeons in the emergency room using a mobile ultrasound unit. In 113 (36.2%) cases pathologic findings were demonstrated sonographically. These included 47 cases of hemothorax, 11 pericardial effusions, 52 cases of intra-abdominal fluid, 24 lesions of intra-abdominal organs, and 10 cases of retroperitoneal hematoma. Physical examination findings were positive in 96 (30.8%), negative in 63 (20.2%), and equivocal in 153 (49.0%). Two hundred thirty-nine patients had between one and eight injuries in addition to the blunt abdominal or thoracic trauma. These patients had an average Injury Severity Score (ISS) of 19.9 (range, 1 to 75). The 73 patients with isolated blunt trauma of the thorax or abdomen had an ISS of 4.9 (range, 0-25). None of the 66 patients (21.2%) with positive clinical findings and negative sonographic examination results had to be operated on later in the course of treatment, while 5 (36%) of 14 patients (4.5%) with negative physical examination findings and positive sonographic findings had to undergo surgery. The sensitivity for the demonstration of intra-abdominal fluid and organ lesions was 98.1% and 41.4%, respectively. The overall sensitivity and specificity of the ultrasonic examination were 90.0% and 99.5%, respectively.

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.

IL-10 levels in cerebrospinal fluid and serum of patients with severe traumatic brain injury: relationship to IL-6, TNF-α, TGF-β1 and blood–brain barrier function

Controlling the extent of inflammatory responses following brain injury may be beneficial since posttraumatic intracranial inflammation has been associated with adverse outcome. In order to elucidate the potential role of anti-inflammatory mediators, the production of interleukin-10 (IL-10) was monitored in paired cerebrospinal fluid (CSF) and serum of 28 patients with severe traumatic brain injury (TBI) and compared to control samples. The pattern of IL-10 was analyzed with respect to the patterns of IL-6, tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta1 (TGF-beta1) in both fluids during a time period of up to 22 days. In parallel, the function/dysfunction of the blood-brain barrier (BBB) was monitored using the CSF-/serum-albumin quotient (Q(A)) and compared to intrathecal cytokine levels. Mean IL-10 concentration in CSF was elevated in 26 out of 28 TBI patients (range: 1.3-41.7 pg/ml) compared to controls (cut-off: 1.06 pg/ml), whereas only seven patients had elevated mean IL-10 concentration in serum (range: 5.4-23 pg/ml; cut-off: 5.14 pg/ml). The time course of IL-10 was similar in both fluids, showing a peak during the first days and a second, lower rise in the second week. Intrathecal IL-10 synthesis is hypothesized since CSF-IL-10 levels exceeded serum-IL-10 levels in most of the patients, IL-10-index (CSF/serum-IL-10/QA) was elevated in 23 individuals, and elevation of CSF-IL-10 showed to be independent from severe BBB dysfunction. Neither CSF nor serum IL-10 values correlated with the dysfunction of the BBB. IL-10, IL-6 and TGF-beta1 showed similar patterns in CSF over time, whereas rises of TNF-alpha corresponded to declines of IL-10 levels. Our results suggest that IL-10 is predominantly induced intrathecally after severe TBI where it may downregulate inflammatory events following traumatic brain damage.

Intrathecal and serum interleukin-6 and the acute-phase response in patients with severe traumatic brain injuries.

Patients with severe traumatic brain injury (TBI) show a profound acute-phase response. Because interleukin-6 (IL-6) is an important mediator of these pathophysiological changes, IL-6 levels were monitored in the cerebrospinal fluid (CSF) and serum of 20 patients with severe isolated TBI. All patients received indwelling ventricular catheters for intracranial pressure monitoring and for release of CSF when intracranial pressure exceeded 15 mmHg. CSF and blood samples were drawn daily for up to 14 days. The CSF/serum albumin ratio (QA) served as a parameter of blood brain barrier dysfunction. Differential blood counts as well as the acute-phase proteins C-reactive protein, alpha 1-antitrypsin, and fibrinogen were recorded. IL-6 was detected in all CSF samples and reached values of up to 31,000 pg/mL, while serum levels remained significantly lower (alpha < or = .01) and never exceeded 1,100 pg/mL the entire study period. A correlation between CSF and serum IL-6 was found initially after the trauma and corresponded to a severe dysfunction of the blood brain barrier (r = .637, p = .001). Maximum IL-6 concentrations in serum correlated with peak levels of acute-phase proteins (C-reactive protein, alpha 1-antitrypsin, and fibrinogen). With regard to blood cell count, an initial leukocytosis combined with a borderline lymphocytopenia was observed. Thrombocytes decreased to a subnormal level during the first few days, but reached supranormal numbers by the end of the study period. Our results show that the increase of IL-6 levels in CSF and serum is followed by a profound acute-phase response in patients with TBI. Because cytokine concentrations are significantly lower in serum compared with CSF, we hypothesize that IL-6 produced in the central nervous system may play a role in initiating the acute-phase response.

Experimental closed head injury: analysis of neurological outcome, blood-brain barrier dysfunction, intracranial neutrophil infiltration, and neuronal cell death in mice deficient in genes for pro-inflammatory cytokines.

Cytokines are important mediators of intracranial inflammation following traumatic brain injury (TBI). In the present study, the neurological impairment and mortality, blood-brain barrier (BBB) function, intracranial polymorphonuclear leukocyte (PMN) accumulation, and posttraumatic neuronal cell death were monitored in mice lacking the genes for tumor necrosis factor (TNF)/lymphotoxin-α (LT-α) (TNF/LT-α−/−) and interleukin-6 (IL-6) and in wild-type (WT) littermates subjected to experimental closed head injury (total n = 107). The posttraumatic mortality was significantly increased in TNF/LT-α−/− mice (40%; P < 0.02) compared with WT animals (10%). The IL-6−/− mice also showed a higher mortality (17%) than their WT littermates (5.6%), but the difference was not statistically significant (P > 0.05). The neurological severity score was similar among all groups from 1 to 72 hours after trauma, whereas at 7 days, the TNF/LT-α−/− mice showed a tendency toward better neurological recovery than their WT littermates. Interestingly, neither the degree of BBB dysfunction nor the number of infiltrating PMNs in the injured hemisphere was different between WT and cytokine-deficient mice. Furthermore, the analysis of brain sections by in situ DNA nick end labeling (TUNEL histochemistry) at 24 hours and 7 days after head injury revealed a similar extent of posttraumatic intracranial cell death in all animals. These results show that the pathophysiological sequelae of TBI are not significantly altered in mice lacking the genes for the proinflammatory cytokines TNF, LT-α, and IL-6. Nevertheless, the increased posttraumatic mortality in TNF/LT-α-deficient mice suggests a protective effect of these cytokines by mechanisms that have not been elucidated yet.

Interleukin-8 released into the cerebrospinal fluid after brain injury is associated with blood-brain barrier dysfunction and nerve growth factor production.

Interleukin (IL) 8 was measured in CSF of 14 patients with severe traumatic brain injury. IL-8 levels were significantly higher in CSF (up to 8,000 pg/ml) than serum (up to 2,400 pg/ml) (p < 0.05), suggesting intrathecal production. Maximal IL-8 values in CSF correlated with a severe dysfunction of the blood–brain barrier. Nerve growth factor (NGF) was detected in CSF of 7 of 14 patients (range of maximal NGF: 62–12,130 pg/ml). IL-8 concentrations were significantly higher in these patients than in those without NGF (p < 0.01). CSF containing high IL-8 (3,800–7,900 pg/ml) induced greater NGF production in cultured astrocytes (202–434 pg/ml) than samples with low IL-8 (600–1,000 pg/ml), which showed a smaller NGF increase (0–165 pg/ml). Anti-IL-8 antibodies strongly reduced (52–100%) the release of NGF in the group of high IL-8, whereas in the group with low IL-8, this effect was lower (0–52%). The inability of anti-IL-8 antibodies to inhibit the synthesis of NGF completely may depend on cytokines like tumor necrosis factor α and IL-6 found in these CSF samples, which may act in association with IL-8. Thus, IL-8 may represent a pivotal cytokine in the pathology of brain injury.

Interleukin-6 released in human cerebrospinal fluid following traumatic brain injury may trigger nerve growth factor production in astrocytes

Cytokines are involved in nerve regeneration by modulating the synthesis of neurotrophic factors. The role played by interleukin-6 (IL-6) in promoting nerve growth factor (NGF) after brain injury was investigated by monitoring the release of IL-6 and NGF in ventricular cerebrospinal fluid (CSF) of 22 patients with severe traumatic brain injuries. IL-6 was found in the CSF of all individuals and remained elevated for the whole study period. NGF appeared in the CSF if IL-6 levels reached high concentrations and was often detected simultaneously with or following an IL-6 peak. The amounts of NGF correlated with the severity of the injury, as indicated by the clinical outcome of the patients. The functional relationship of IL-6 and NGF was investigated utilizing cultured mouse astrocytes. The CSF of 8 patients containing IL-6 induced NGF production in astrocytes, whereas control CSF without IL-6 had no effect. The induction of NGF was inhibited up to 100% by adding anti-IL-6 antibodies. These results were corroborated when astrocytes were exposed to recombinant IL-6 at different concentrations resulting in NGF production. Thus, the production of IL-6 within the injured brain may likely contribute to the release of neurotrophic factors by astrocytes.

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.