Blunt carotid and vertebral arterial injuries.

Blunt carotid and vertebral arterial injuries are uncommon but have the potential for devastating consequences. The classic presentation is a neurologic deficit unexplained by computed tomographic scan findings. Screening patients based on injury mechanisms and patterns allows the diagnosis and treatment of injuries while they are still asymptomatic, potentially improving neurologic outcomes. The development of a grading scale may help refine treatment guidelines. Accessible grade II, III, and V carotid injuries should be repaired surgically. Anticoagulation should be considered first-line therapy for grade I and IV, and inaccessible grade II and III carotid lesions, and grade I-IV vertebral injuries. Grade V and persistent grade III lesions may be best treated employing endovascular techniques.

Routine intraoperative laparoscopic ultrasonography with selective cholangiography reduces bile duct complications during laparoscopic cholecystectomy.

BACKGROUND: Laparoscopic cholecystectomy (LC) is the preferred treatment for gallstone disease, even in many complicated cases. Perhaps the only downside to LC is a two- to threefold increase in common bile duct (CBD) injuries compared with open cholecystectomy (OC). Intraoperative cholangiography may prevent inj uries, but its routine use remains controversial. Our institution adopted a policy of selective intraoperative cholangiography in 1993. When intraoperative laparoscopic ultrasonography (IOUS) emerged as a viable diagnostic adjunct, it was hypothesized that the routine use of IOUS would facilitate dissection, detect occult choledocholithiasis, and prevent bile duct injuries during LC. STUDY DESIGN: The experience with LC at our university-affiliated teaching hospital was reviewed. Over a 4 1/2-year period (June 1, 1995, to January 31, 2000), two surgeons used IOUS routinely during LC (ultrasonography [US] group, n = 248); three other surgeons did not (non-US group, n = 594). We compared patient data and outcomes between the two groups. Continuous, data are expressed as mean +/- SEM. RESULTS: During the study period, 842 LCs were attempted. Patient age (37+/-1 years) and gender (85% female) did not differ between the groups. In the US group, more patients had acute cholecystitis (p < 0.05). More LCs were performed per year by non-US surgeons than US surgeons (45 versus 37). Despite this, all bile duct complications occurred in non-US cases (2.5% overall): five CBD injuries (0.8%), six bile leaks (1%), and four retained CBD stones (0.7%). In the subgroup of patients with acute cholecystitis, there were fewer conversions to OC in US compared with non-US cases (24% versus 36%, p = 0.09). CONCLUSIONS: IOUS is noninvasive, fast, repeatable, and can corroborate real-time visualization of the operative field. We have found that LC with IOUS is associated with fewer bile duct complications (CBD injuries, bile leaks, and retained CBD stones) than LC without adjunctive imaging. The success rate of LC in cases of acute cholecystitis is slightly higher when IOUS is used as an aid to dissection. In the absence of definitive prospective data, we recommend routine use of IOUS when performing LC, particularly in patients with acute cholecystitis.

Phospholipase A(2)--derived neutral lipids from posthemorrhagic shock mesenteric lymph prime the neutrophil oxidative burst.

BACKGROUND: Our previous work identified posthemorrhagic shock mesenteric lymph (PHSML) lipids as key elements in polymorphonuclear neutrophil (PMN)--provoked acute lung injury. We hypothesize that gut phospholipase A(2) (PLA(2)) is responsible for the generation of proinflammatory lipids in PHSML that primes circulating PMNs for enhanced oxidative burst. METHODS: Mesenteric lymph was collected from rats (n = 5) before (preshock), during the induction of hemorrhagic shock (mean arterial pressure, 40 mm Hg x 30 minutes), and at resuscitation (shed blood + 2x lactated Ringer's solution). PLA(2) inhibition (quinacrine, 10 mg/kg, intravenously) was given before shock was induced. Extracted lipids were separated by normal phase high-pressure liquid chromatography and resuspended in albumin. PMNs were exposed to a 5% vol:vol concentration of eluted lipids and activated with N-formyl-methionyl-leucyl-phenylalanine (1 micromol/L). Superoxide production was assessed by cytochrome C reduction. RESULTS: High-pressure liquid chromatography--extracted neutral lipids of lymph collected before hemorrhagic shock did not prime the PMN oxidase, whereas isolated neutral lipids of postshock lymph primed PMNs 2.6- +/- 0.32-fold above baseline (P <.05). PLA(2) inhibition returned PHSML neutral lipid priming to baseline levels. CONCLUSIONS: PLA(2) inhibition before hemorrhagic shock abrogates the neutrophil priming effects of PHSML through reduction of the accumulation of proinflammatory neutral lipids. Identification of these PLA(2)-dependent lipids provides a mechanistic link that may have therapeutic implications for postshock acute lung injury.

Avoidance of abdominal compartment syndrome in damage-control laparotomy after trauma.

HYPOTHESIS: Abdominal compartment syndrome (ACS) is a morbid complication of damage-control laparotomy. Moreover, the technique of abdominal closure influences the frequency of ACS. DESIGN: Retrospective cohort study. SETTING: Urban level I trauma center. PATIENTS: We studied 52 patients with trauma who required damage-control laparotomy during the 5 years ending December 31, 1999, and who survived longer than 48 hours. MAIN OUTCOME MEASURES: Abdominal compartment syndrome, acute respiratory distress syndrome (ARDS), and multiple organ failure (MOF). RESULTS: Mean (+/- SD) age was 33 +/- 2 years; 38 (73%) were male. Mechanism of injury was blunt in 29 patients (56%), and mean (+/- SD) Injury Severity Score was 28 +/- 2. Development of ARDS and/or MOF was seen in 23 patients (44%); ARDS and MOF increased mortality from 12% (3/26) to 42% (11/26). Abdominal compartment syndrome was a common complication (17/52), and was associated with an increase in ARDS and/or MOF (12 patients [71%] vs 11 patients [31%] without ACS; P =.02, chi(2) test) and death (6 [35%] vs 8 patients [23%] without ACS). Primary fascial closure (n = 10) at the initial laparotomy was associated with ACS in 8 (80%) (P =.001, chi(2) test) and ARDS and/or MOF in 9 (90%) (P =.01, chi(2) test); skin closure (n = 25), with ACS in 6 (24%) and ARDS/MOF in 9 (36%); and Bogotá bag closure (n = 17), with ACS in 3 (18%) and ARDS/MOF in 8 (47%). CONCLUSIONS: Damage-control laparotomy is associated with frequent complications. In particular, ACS is a serious complication that increases ARDS and/or MOF and mortality. Avoiding primary fascial closure at the initial laparotomy can minimize the risk for ACS.

Evolution of a multidisciplinary clinical pathway for the management of unstable patients with pelvic fractures.

OBJECTIVE: To determine whether the evolution of the authors' clinical pathway for the treatment of hemodynamically compromised patients with pelvic fractures was associated with improved patient outcome. SUMMARY BACKGROUND DATA: Hemodynamically compromised patients with pelvic fractures present a complex challenge. The multidisciplinary trauma team must control hemorrhage, restore hemodynamics, and rapidly identify and treat associated life-threatening injuries. The authors developed a clinical pathway consisting of five primary elements: immediate trauma attending surgeon's presence in the emergency department, early simultaneous transfusion of blood and coagulation factors, prompt diagnosis and management of associated life-threatening injuries, stabilization of the pelvic girdle, and timely insinuation of pelvic angiography and embolization. The addition of two orthopedic pelvic fracture specialists led to a revision of the pathway, emphasizing immediate emergency department presence of the orthopedic trauma attending to provide joint decision making with the trauma surgeon, closing the pelvic volume in the emergency department, and using alternatives to traditional external fixation devices. METHODS: Using trauma registry and blood bank records, the authors identified pelvic fracture patients receiving blood transfusions in the emergency department. They analyzed patients treated before versus after the May 1998 revision of the clinical pathway. RESULTS: A higher proportion of patients in the late period had blood pressure less than 90 mmHg (52% vs. 35%). In the late period, diagnostic peritoneal lavage was phased out in favor of torso ultrasound as a primary triage tool, and pelvic binding and C-clamp application largely replaced traditional external fixation devices. The overall death rate decreased from 31% in the early period to 15% in the later period, as did the rate of deaths from exsanguination (9% to 1%), multiple organ failure (12% to 1%), and death within 24 hours (16% to 5%). CONCLUSIONS: The evolution of a multidisciplinary clinical pathway, coordinating the resources of a level 1 trauma center and directed by joint decision making between trauma surgeons and orthopedic traumatologists, has resulted in improved patient survival. The primary benefits appear to be in reducing early deaths from exsanguination and late deaths from multiple organ failure.

Plasma from aged stored red blood cells delays neutrophil apoptosis and primes for cytotoxicity: abrogation by poststorage washing but not prestorage leukoreduction.

BACKGROUND: Blood transfusion-particularly that of older stored red blood cells (RBCs)--is an independent risk factor for postinjury multiple organ failure. Immunomodulatory effects of RBC transfusion include neutrophil (PMN) priming for cytotoxicity, an effect exacerbated by longer RBC storage times. We have found that delayed PMN apoptosis in trauma patients is provoked by transfusion, independent of injury severity. We hypothesized that aged stored RBCs delay PMN apoptosis, but that prestorage leukodepletion or poststorage washing could abrogate the effect. METHODS: Healthy volunteers each donated 1 unit of blood. One half was leukodepleted, and RBC units were processed in the usual fashion and stored at 4 degrees C. Aliquots were removed on days 1, 14, 21, and 42 and the plasma fraction isolated. Selected aliquots were washed with normal saline before plasma isolation. PMNs harvested from healthy controls were incubated (5% CO2, 37 degrees C) with unmodified, leukoreduced, or washed RBC plasma (20% plasma/80% RPMI 1640), and apoptosis assessed by morphology after 24 hours. Apoptotic index (apoptotic PMNs/total PMNs) was compared. PMN priming for superoxide release was also assessed after plasma exposure. RESULTS: PMN apoptosis was delayed by RBCs stored for 21 or 42 days. Prestorage leukodepletion did not alter the effect. However, washing 42-day-old RBCs abrogated the effect. PMN priming for superoxide was provoked by stored packed RBCs in an identical pattern to delayed apoptosis. CONCLUSION: Plasma from stored RBCs-even if leukoreduced-delays apoptosis and primes PMNs. The effect becomes evident at 21 days and worsens through product outdate (42 days), but may be prevented by poststorage washing. Inflammatory agents contaminating stored blood likely mediate the effect. Modification of transfusion practices (e.g., giving fresher or washed RBCs or blood substitutes) may attenuate adverse immunomodulatory effects of transfusion in trauma patients.

Resuscitation with a blood substitute abrogates pathologic postinjury neutrophil cytotoxic function.

BACKGROUND: Resuscitation with oxygen-carrying fluids is critically important in the patient with hemorrhagic shock caused by trauma. However, it is clear that a number of biologic mediators present in stored blood (packed red blood cells [PRBCs]) have the potential to exacerbate early postinjury hyperinflammation and multiple organ failure through priming of circulating neutrophils (PMNs). PolyHeme (Northfield Laboratories, Evanston, IL), a hemoglobin-based substitute that is free of priming agents, provides an alternative. We hypothesized that PMN priming would be attenuated in patients resuscitated with PolyHeme in lieu of stored blood. METHODS: Injured patients requiring urgent transfusion were given either PolyHeme (up to 20 units) or PRBCs. Early postinjury PMN priming was measured via beta-2 integrin expression, superoxide production, and elastase release. RESULTS: Treatment groups were comparable with respect to extent of injury and early physiologic compromise. PMNs from patients resuscitated with PRBCs showed priming in the early postinjury period by all three measures. No such priming was evident in patients resuscitated with PolyHeme. CONCLUSION: The use of a blood substitute in the early postinjury period avoids PMN priming and may thereby provide an avenue to decrease the incidence or severity of postinjury multiple organ failure.

Neutrophil apoptosis is delayed by trauma patients' plasma via a mechanism involving proinflammatory phospholipids and protein kinase C.

BACKGROUND: Delayed apoptosis of primed neutrophils (PMNs) may facilitate PMN-mediated tissue injury leading to multiple organ failure (MOF). We previously reported delayed apoptosis and priming of PMNs in severely injured patients at risk for MOF. Our in vitro and in vivo data have implicated phospholipids in PMN cytotoxicity following trauma and shock. The phospholipid signaling pathway remains to be elucidated, but may involve protein kinase C (PKC). We hypothesized that circulating platelet-activating factor (PAF) and PAF-like proinflammatory phospholipids mediate delayed postinjury PMN apoptosis and that PKC is integral to the signaling pathway. METHODS: Blood was drawn from severely injured patients (n = 6; mean injury severity score = 21 and transfusion = 10 units) at 6 h postinjury. The plasma fraction was isolated and incubated (5% CO(2), 37 degrees C, 24 h) with PMNs harvested from healthy volunteers. Some PMNs were preincubated with a PAF receptor antagonist (WEB 2170, 400 microM) or a PKC inhibitor (Bis I, 1 microM). Apoptotic index (% PMNs undergoing apoptosis) was assessed morphologically. RESULTS: Trauma patients' plasma delayed PMN apoptosis compared with plasma from controls. The PMN apoptotic index was not altered by WEB 2170 or Bis I alone; however, WEB 2170 or Bis I pretreatment abrogated delayed PMN apoptosis in response to trauma patients' plasma. CONCLUSION: Trauma patients' plasma delays apoptosis of PMNs. Our data implicate PAF-like phospholipids in this effect, and PKC appears to be integral in the signaling process. Further elucidation of specific lipids and signaling pathways may reveal clinically accessible therapeutic targets to prevent PMN-mediated hyperinflammation.

The abdominal compartment syndrome is a morbid complication of postinjury damage control surgery.

BACKGROUND: The abdominal compartment syndrome (ACS) is a recognized complication of damage control surgery (DCS). The purposes of this study were to (1) determine the effect of ACS on outcome after DCS, (2) identify patients at high risk for the development of ACS, and (3) determine whether ACS can be prevented by preemptive intravenous bag closure during DCS. METHODS: Patients requiring postinjury DCS at our institution from January 1996 to June 2000 were divided into groups depending on whether or not they developed ACS. ACS was defined as an intra-abdominal pressure (IAP) greater than 20 mm Hg in association with increased airway pressure or impaired renal function. RESULTS: ACS developed in 36% of the 77 patients who underwent DCS with a mean IAP prior to decompression of 26 +/- 1 mm Hg. The ACS versus non-ACS groups were not significantly different in patient demographics, Injury Severity Score, emergency department vital signs, or intensive care unit admission indices (blood pressure, temperature, base deficit, cardiac index, lactate, international normalized ratio, partial thromboplastin time, and 24-hour fluid). The initial peak airway pressure after DCS was higher in those patients who went on to develop ACS. The development of ACS after DCS was associated with increased ICU stays, days of ventilation, complications, multiorgan failure, and mortality. CONCLUSIONS: ACS after postinjury DCS worsens outcome. With the exception of early elevation in peak airway pressure, we could not identify patients at higher risk for ACS; moreover, preemptive abdominal bag closure during initial DCS did not prevent this highly morbid complication.

Secondary abdominal compartment syndrome is a highly lethal event.

BACKGROUND: Recent reports have described resuscitation-induced, "secondary" abdominal compartment syndrome (ACS) in trauma patients without intra-abdominal injuries. We have diagnosed secondary ACS in a variety of nontrauma as well as trauma patients. The purpose of this review is to characterize patients who develop secondary ACS. METHODS: Our prospective ACS database was reviewed for cases of secondary ACS. Physiologic parameters and outcomes were recorded. Data are expressed as mean +/- SEM. RESULTS: Fourteen patients (13 male, aged 45 +/- 5 years) developed ACS 11.6 +/- 2.2 hours following resuscitation from shock. Eleven (79%) had required vasopressors; the worst base deficit was 14.1 +/- 1.9. Resuscitation included 16.7 +/- 3.0 L crystalloid and 13.3 +/- 2.9 red blood cell units. Decompressive laparotomy improved intra-abdominal, systolic, and peak airway pressures, as well as urine output; however, mortality was 38% among trauma and 100% among nontrauma patients. CONCLUSIONS: Secondary ACS may be encountered by general surgeons in a variety of clinical scenarios; resuscitation from severe shock appears to be the critical factor. Early identification and abdominal decompression are essential. Unfortunately, in our experience, this is a highly lethal event.

Single-layer continuous versus two-layer interrupted intestinal anastomosis: a prospective randomized trial.

OBJECTIVE: To determine the suitability of a single-layer continuous technique for intestinal anastomosis in a surgical training program. SUMMARY BACKGROUND DATA: Several recent reports have advocated the use of a continuous single-layer technique for intestinal anastomosis. Purported advantages include shorter time for construction, lower cost, and perhaps a lower rate of anastomotic leakage. The authors hypothesized that the single-layer continuous anastomosis could be safely introduced into a surgical training program and that it could be performed in less time and at a lower cost than the two-layer interrupted anastomosis. METHODS: The study was conducted during a 3-year period ending September 1999. All adult patients requiring intestinal anastomosis were considered eligible. Patients who required anastomosis to the stomach, duodenum, and rectum were excluded. Patients were also excluded if the surgeon did not believe either technique could be used. Patients were randomly assigned to one- or two-layer techniques. Single-layer anastomoses were performed with a continuous 3-0 polypropylene suture. Two-layer anastomoses were constructed using interrupted 3-0 silk Lembert sutures for the outer layer and a continuous 3-0 polyglycolic acid suture for the inner layer. The time for anastomosis began with the placement of the first stitch and ended when the last stitch was cut. Anastomotic leak was defined as radiographic demonstration of a fistula or nonabsorbable material draining from a wound after oral administration, or visible disruption of the suture line during reexploration. RESULTS: Sixty-five single-layer and 67 two-layer anastomoses were performed. The groups were evenly matched according to age, sex, diagnosis, and location of the anastomosis. Two leaks (3.1%) occurred in the single-layer group and one (1.5%) in the two-layer group. Two abscesses (3.0%) occurred in each group. A mean of 20.8 minutes was required to construct a single-layer anastomosis versus 30.7 minutes for the two-layer technique. Mean length of stay was 7.9 days for single-layer patients and 9.9 days for two-layer patients; this difference did not quite reach statistical significance. Cost of materials was $4.61 for the single-layer technique and $35.38 for the two-layer method. CONCLUSIONS: A single-layer continuous anastomosis can be constructed in significantly less time and with a similar rate of complications compared with the two-layer technique. It also costs less than any other method and can be incorporated into a surgical training program without a significant increase in complications.

NISS predicts postinjury multiple organ failure better than the ISS.

BACKGROUND: The Injury Severity Score (ISS) has been observed consistently to be a robust predictor of postinjury multiple organ failure (MOF). However, the ISS fails to account for multiple injuries to the same body region. Recently, the "new" ISS (NISS) has been proposed to address this shortcoming. Preliminary studies suggest the NISS is superior to the ISS in predicting trauma mortality. Our purpose was to determine whether the NISS is a better predictor of postinjury MOF than the ISS. METHODS: A total of 558 patients admitted to our Level I trauma center with ISS > 15, age > 15 years, and survival > 48 hours were prospectively identified; 101 (18%) developed postinjury MOF. Data characterizing postinjury MOF were collected, and the NISS was calculated retrospectively. The ISS and NISS were compared as univariate predictors of MOF. Multivariate analysis was used to determine whether substitution of NISS for ISS resulted in a superior predictive model. RESULTS: In 295 patients (53%), the NISS was greater than the ISS. This subgroup of patients experienced a greater frequency of MOF (26.7% vs. 8.3%, p < 0.0001), a higher mortality (12.8% vs. 4.9%, p < 0.001), and a higher early transfusion requirement (6.7 U vs. 3.6 U, p < 0.0001) compared with the group in which NISS equaled ISS. Moreover, the NISS yielded better separation between patients with and without MOF reflected by the greater difference in median NISS scores compared with ISS scores. The multivariate predictive model, including NISS, showed a better goodness of fit compared with the same model that included ISS. CONCLUSIONS: The NISS is superior to the ISS in the prediction of postinjury MOF. This measure of tissue injury severity should replace the ISS in trauma research.

The devastating potential of blunt vertebral arterial injuries.

OBJECTIVE: To formulate management guidelines for blunt vertebral arterial injury (BVI). SUMMARY BACKGROUND DATA: Compared with carotid arterial injuries, BVIs have been considered innocuous. Although screening for BVI has been advocated, particularly in patients with cervical spine injuries, the appropriate therapy of lesions is controversial. METHODS: In 1996 an aggressive arteriographic screening protocol for blunt cerebrovascular injuries was initiated. A prospective database of all screened patients has been maintained. Analysis of injury mechanisms and patterns, BVI grades, treatment, and outcomes was performed. RESULTS: Thirty-eight patients (0.53% of blunt trauma admissions) were diagnosed with 47 BVIs during a 3.5-year period. Motor vehicle crash was the most common mechanism, and associated injuries were common. Cervical spine injuries were present in 71% of patients, but there was no predilection for cervical vertebral level or fracture pattern. The incidence of posterior circulation stroke was 24%, and the BVI-attributable death rate was 8%. Stroke incidence and neurologic outcome were independent of BVI injury grade. In patients treated with systemic heparin, fewer overall had a poor neurologic outcome, and fewer had a poor outcome after stroke. Trends associated with heparin therapy included fewer injuries progressing to a higher injury grade, fewer patients in whom stroke developed, and fewer patients deteriorating neurologically from diagnosis to discharge. CONCLUSIONS: Blunt vertebral arterial injuries are more common than previously reported. Screening patients based on injury mechanisms and patterns will diagnose asymptomatic injuries, allowing the institution of therapy before stroke. Systemic anticoagulation appears to be effective therapy: it is associated with improved neurologic outcome in patients with and without stroke, and it appears to prevent progression to a higher injury grade, stroke, and deterioration in neurologic status.

Treatment of posttraumatic internal carotid arterial pseudoaneurysms with endovascular stents.

BACKGROUND: The sequelae of blunt injury to the carotid arteries are unusual, but pseudoaneurysms causing subsequent strokes are devastating. The utility of treatment of these pseudoaneurysms was examined. METHODS: All patients at a Level I trauma center with previously documented traumatic risk factors were assessed for blunt injury to the carotid arteries and, when a pseudoaneurysm was present, a self-expanding metallic stent was placed across the lesion and the patient placed on anticoagulation. Follow-up arteriograms were obtained in 2 months and every 6 months thereafter. RESULTS: Fourteen patients (7 men, 7 women) with an average age of 27 years, an Injury Severity Score of 38, had formed pseudoaneurysms in 16 extracranial internal carotid arteries. These were stented with metallic endoprostheses. No strokes occurred after the placement of the stents. Mean follow-up period has been 2.5 years. CONCLUSIONS: Use of metallic endoprostheses is an effective method to treat this potentially devastating injury. However, longer follow-up and more patients studied are needed to further examine this promising treatment.

Complications of prone ventilation in patients with multisystem trauma with fulminant acute respiratory distress syndrome.

INTRODUCTION: Prone ventilation improves oxygenation in selected patients with acute respiratory distress syndrome (ARDS). However, prone positioning of critically ill patients with multiple invasive lines and tubes is potentially dangerous. Trauma patients, in particular, may require special consideration because of skeletal fixation devices or prior operative procedures. Our objective was to critically evaluate our experience with prone positioning in patients with severe postinjury ARDS. METHODS: Injured patients admitted to our Level I trauma center who developed ARDS were prospectively identified. Serial lung injury severity and pulmonary mechanical data, as well as complications of prone ventilation were recorded. RESULTS: During the 12-month period ending August of 1998, nine patients with postinjury ARDS were treated with prone ventilation because of hypoxemia refractory to other ventilatory strategies. All patients suffered blunt trauma. Their mean age was 29 +/- 4.5 years; seven patients were men. The average Injury Severity Score was 26 +/- 5; and, at the time of prone positioning, the mean Lung Injury Score was 3.5. The mean PaO2/FIO2 ratio increased from 75 +/- 7 to 147 +/- 27 with prone ventilation (p < 0.05, paired t test); and in six patients, the FIO2 could be decreased. Four major complications occurred (44%). One patient experienced a midline abdominal wound dehiscence. Severe facial or upper chest wall pressure necrosis developed in two patients, despite extensive padding and careful attention to skin care. The fourth patient sustained a cardiac arrest immediately after prone positioning. CONCLUSION: Prone ventilation in postinjury patients with ARDS may improve oxygenation but has the potential for significant complications. Careful consideration is required before prone positioning in this subset of patients.

Maximal human neutrophil priming for superoxide production and elastase release requires p38 mitogen-activated protein kinase activation.

HYPOTHESIS: Neutrophil priming has been implicated in the development of multiple organ failure, although the precise intracellular mechanisms that regulate neutrophil priming remain unclear. Our previous work characterized platelet-activating factor (PAF) priming of human neutrophils for concordant superoxide anion (O2-) generation and elastase degranulation. The p38 mitogen-activated protein kinase (MAPK) is activated by PAF stimulation. We hypothesized that PAF-induced human neutrophil priming for O2- and elastase release is mediated via the p38 MAPK pathway. DESIGN: Isolated neutrophils from 6 human donors were preincubated with the specific p38 MAPK inhibitor SB 203580 (1 micromol/L) or buffer (control) for 30 minutes. Cells were then primed with PAF (200 nmol/L), followed by receptor-dependent (N-formyl-methionyl-leucyl-phenylalanine, 1 micromol/L) or receptor-independent phorbol myristate acetate (PMA, 100 ng/mL) activation. SETTING: Urban trauma research laboratory. PATIENTS: Healthy volunteer donors of neutrophils. MAIN OUTCOME MEASURES: Maximal rate of O2- generation was measured by superoxide dismutase-inhibitable reduction of cytochrome c and elastase release by the cleavage of N-methoxysuccinyl-Ala-Ala-Pro-Val-p-nitroanilide. RESULTS: SB 203580 significantly attenuated the generation of O2- and release of elastase from neutrophils activated with N-formyl-methionyl-leucyl-phenylalanine but not with PMA. Independent of the activator receptor status, SB 203580 almost completely blocked the exaggerated neutrophil cytotoxic response due to PAF priming. CONCLUSIONS: The p38 MAPK pathway is required for maximal PAF-induced neutrophil priming for O2- production and elastase degranulation. Therefore, the MAPK signaling cascade may offer a potential therapeutic strategy to preempt global neutrophil hyperactivity rather than attempt to nullify the end products independently.

Optimal management of complicated empyema.

BACKGROUND: Despite continued improvement in medical therapy, empyema remains a challenging problem for the surgeon. Multiple treatment options are available; however, the optimal therapeutic management has not been elucidated. METHODS: A retrospective review was performed of all adult patients admitted to Denver Health Medical Center between January 1, 1993, and December 31, 1998, with the diagnosis of empyema. Data tabulated included patient demographics, presentation, chest computed tomography (CT) findings, treatment, and outcome. RESULTS: Empyema was diagnosed in 58 patients, 45 cases of which were multiloculated at the time of presentation. Empyema was secondary to pneumonia is 41 patients and posttraumatic in 15. In addition to antibiotic therapy, initial treatment included chest tube drainage alone (n = 6), chest tube drainage with primary operation (n = 19), and chest tube drainage with intrapleural fibrinolytic therapy (n = 33). In 15 patients (45%), fibrinolytic therapy failed. Initial chest CT revealed a pleural peel in 5 patients treated with fibrinolytics and all failed. Multiloculation, however, was not a factor in failure of fibrinolysis. Moreover, chest CT missed the presence of a pleural peel in 17 of 31 patients documented to have a significant peel at the time of thoracotomy. CONCLUSION: Multiple therapeutic options are available for the management of empyema. Multiloculation is not a contraindication to an initial trial of chest tube drainage or fibrinolytic therapy. In contrast, CT evidence of a pleural peel uniformly predicted failure of nonoperative treatment.

Blunt carotid arterial injuries: implications of a new grading scale.

BACKGROUND: Blunt carotid arterial injuries (BCI) have the potential for devastating outcomes. A paucity of literature and the absence of a formal BCI grading scale have been major impediments to the formulation of sound practice guidelines. We reviewed our experience with 109 BCI and developed a grading scale with prognostic and therapeutic implications. METHODS: Patients admitted to a Level I trauma center were evaluated with cerebral arteriography if they exhibited signs or symptoms of BCI or met criteria for screening. Patients with BCI were treated with heparin unless they had contraindications, and follow-up arteriography was performed at 7 to 10 days. Endovascular stents were deployed selectively. A prospective database was used to track the patients. RESULTS: A total of 76 patients were diagnosed with 109 BCI. Two-thirds of mild intimal injuries (grade I) healed, regardless of therapy. Dissections or hematomas with luminal stenosis (grade II) progressed, despite heparin therapy in 70% of cases. Only 8% of pseudoaneurysms (grade III) healed with heparin, but 89% resolved after endovascular stent placement. Occlusions (grade IV) did not recanalize in the early postinjury period. Grade V injuries (transections) were lethal and refractory to intervention. Stroke risk increased with injury grade. Severe head injuries (Glasgow Coma Scale score < or =6) were found in 46% of patients and confounded evaluation of neurologic outcomes. CONCLUSION: This BCI grading scale has prognostic and therapeutic implications. Nonoperative treatment options for grade I BCI should be evaluated in prospective, randomized trials. Accessible grade II, III, IV, and V lesions should be surgically repaired. Inaccessible grade II, III, and IV injuries should be treated with systemic anticoagulation. Endovascular techniques may be the only recourse in high grade V injuries and warrant controlled evaluation in the treatment of grade III BCI.

Male gender is a risk factor for major infections after surgery.

BACKGROUND: Accumulating clinical and epidemiological evidence suggests significant gender differences in the incidence of and outcome following major infection. In a rodent model of hemorrhagic shock, investigators have shown that males manifest depressed cell-mediated immunity that is reversed by castration or pharmacologic testosterone receptor blockade. Female rats, in contrast, show enhanced immune function that is reduced to male levels by testosterone administration. This sexual dimorphism is believed responsible for the improved outcome in female mice following septic challenge. HYPOTHESIS: Male gender is a risk factor for major infections following severe injury. DESIGN: Five-year prospective cohort study ending October 1998. SETTING: Urban level I regional trauma center. PATIENTS AND METHODS: A total of 545 trauma patients older than 15 years with an Injury Severity Score greater than 15 and survival more than 48 hours were prospectively identified and studied. Collected data included age, injury mechanism, and Injury Severity Score. Major infections, defined as pneumonia, abdominal and pelvic abscess, wound infection requiring operative debridement, and meningitis, were tabulated. The occurrence of major infections in males and females was compared using multiple logistic regression analysis. MAIN OUTCOME MEASURE: Postinjury major infectious complications. RESULTS: Of the 545 patients, 135 (24.8%) were female and 410 (75.2%) were male. Major infections occurred in 219 (40.2%) patients. Logistic regression confirmed that male gender is an independent risk factor for major infections (P=.04) after controlling for age and Injury Severity Score. Males had a 58% greater risk of developing a major infection (odds ratio, 1.58; 95% confidence interval, 1.01-2.48). CONCLUSIONS: Male gender is associated with a dramatically increased risk of major infections following trauma. This effect is most significant following injuries of moderate severity (Injury Severity Score 16-25) and persists in all age groups.