Early decreased neutrophil responsiveness is related to late onset sepsis in multitrauma patients: An international cohort study.

BACKGROUND: Severe trauma can lead to the development of infectious complications after several days, such as sepsis. Early identification of patients at risk will aid anticipating these complications. The aim of this study was to test the relation between the acute (<24 hours) inflammatory response after injury measured by neutrophil responsiveness and the late (>5 days) development of septic complications and validate this in different trauma populations. METHODS AND FINDINGS: Two prospective, observational, cohort series in the Netherlands and South Africa, consisting of severely injured trauma patients. Neutrophil responsiveness by fMLF-induced active FcγRII was measured in whole blood flowcytometry, as read out for the systemic immune response within hours after trauma. Sepsis was scored daily. Ten of the 36 included Dutch patients developed septic shock. In patients with septic shock, neutrophils showed a lower expression of fMLF-induced active FcγRII immediately after trauma when compared to patients without septic shock (P = 0.001). In South Africa 11 of 73 included patients developed septic shock. Again neutrophils showed lower expression of fMLF induced active FcγRII (P = 0.001). In the combined cohort, all patients who developed septic shock demonstrated a decreased neutrophil responsiveness. CONCLUSIONS: Low responsiveness of neutrophils for the innate stimulus fMLF immediately after trauma preceded the development of septic shock during admission by almost a week and did not depend on a geographical/racial background, hospital protocols and health care facilities. Decreased neutrophil responsiveness appears to be a prerequisite for septic shock after trauma. This might enable anticipation of this severe complication in trauma patients.

Serum lipase should be the laboratory test of choice for suspected acute pancreatitis.

Background. Serum lipase and amylase are biochemical analyses used to establish the diagnosis of acute pancreatitis (AP). Despite lipase having been shown internationally to be a more sensitive and specific test, amylase remains a popular first-line test.Objective. To provide a local basis for the recommendation of the best first-line laboratory test, an assessment of their performance in our local setting was undertaken.Methods. From a prospective dataset on patients with acute abdominal pain and raised serum lipase and/or amylase values, the sensitivity and specificity of serum lipase, amylase and the two in combination was calculated for the diagnosis of AP, as defined by the Atlanta criteria.Results. During the study period, 476 patients presented with acute upper or generalised abdominal pain and raised serum amylase and/or lipase values. The median age of the patients was 43 years (range 14 - 85), and 58% were men and 42% women. Of the patients, 322 (68%) presented with abdominal conditions other than AP, and 154 (32%) had AP. Ethanol abuse and gallstones accounted for 55% and 23% of cases of AP, respectively. Lipase displayed a sensitivity of 91% for AP, against 62% for amylase. Specificity was 92% for lipase and 93% for amylase. Dual testing with lipase and amylase had a sensitivity of 93%.Conclusions. Lipase is a more sensitive test than amylase when utilising cut-off levels to diagnose AP. Lipase should replace amylase as the first-line laboratory investigation for suspected AP.

Penetrating thorax injury leads to mild systemic activation of neutrophils without inflammatory complications.

INTRODUCTION: Trauma is one of the major causes of morbidity and mortality. Thoracic injuries are associated with inflammatory complications such as ARDS. The pathogenesis of this complication after pulmonary injury is incompletely understood, but neutrophils are thought to play a pivotal role. The aim of this project was to gain more insight in the role of thoracic injuries in the pathophysiological processes that link systemic neutrophil activation with inflammatory complications after trauma. METHODS: In this prospective cohort study fifty-five patients with isolated penetrating thoracic injury were included at a level one Trauma Unit. Blood samples were analysed for neutrophil phenotype with the use of flowcytometry within 3 h of trauma and repeated six and 24 h after injury. The presence of inflammatory complications (e.g. ARDS or sepsis/septic shock) was assessed during admission, and this was related to the neutrophil phenotpe. RESULTS: The clinical follow-up of fifty-three patients was uneventful. Only two patients developed an inflammatory complication. Within 3 h after trauma, neutrophils showed a decreased expression of FcγRII (p=0.007) and FcγRIII (p=0.001) compared to healthy individuals. After 6 h, expression of active FcγRII (p=0.017), C5aR (p=0.004) and CAECAM8 (p=0.043) increased, whereas L-selectin (p=0.002) decreased. After 24 h also CXCR-2 (CD182) expression increased compared to healthy individuals (p=0.001). CONCLUSIONS: Penetrating thoracic trauma leads to a distinct primed activation status of circulating neutrophils within hours. In addition to activation of cells, both young and reverse migrated neutrophils are released into the circulation. This degree of systemic inflammation does not exceed a threshold of inflammation that is needed for the development of inflammatory complications like ARDS.

Long-term results of stent graft treatment of subclavian artery injuries: management of choice for stable patients?

BACKGROUND: The management of penetrating subclavian artery injuries poses a formidable surgical challenge. The feasibility of stent graft repair is already established. General use of this modality is not widely accepted due to concerns regarding the long-term outcome in a generally young patient population. We review our stent graft experience to examine long-term outcomes. METHODS: All patients with penetrating subclavian artery injuries were evaluated for stent graft repair. Patients were excluded when hemodynamically unstable or unsuitable on other clinical and angiographic grounds. Patients were followed prospectively for early (<30 days) and late (>30 days) complications. Clinical and telephone evaluation, Doppler pressures, duplex Doppler, and angiography (when indicated), were used to asses patients at follow-up. Outcomes were recorded as technical success of procedure, graft patency, arm claudication, limb loss, the need for open surgical repair, the presence or absence of other complications, and death. RESULTS: Fifty-seven patients underwent stent graft treatment during the 10-year period. Mean age was 34, and 91% were men. There were 53 stab wounds and four gunshot injuries. Pathology included false aneurysms (n = 42), arteriovenous fistula (n = 12), and three arterial occlusions. Early complications: One patient (2%) had a femoral puncture site injury which was managed with open surgical repair. One patient died early due to multiple organ failure related to concomitant injuries. Three patients (5%) presented with graft occlusion and nonlimb threatening ischemia in the first week after treatment. All three patients were managed successfully with a second endovascular intervention. Late complications: Twenty-five (44%) of the 57 patients with subclavian artery injuries were followed-up with a mean duration of 48 months. Two patients died as a result of fatal stab wounds months after their first injuries. Five patients (20%) and three patients (12%) presented with angiographically significant stenosis and occlusions, respectively. The stenotic lesions were successfully managed with endovascular intervention, and the occluded lesions were managed conservatively. No patient experienced life or limb loss or any incapacitating symptoms at the end of the study period. There was no need for conversion to open surgery. CONCLUSIONS: This study has reaffirmed the feasibility and safety of stent graft repair in treating stable patients with selected penetrating subclavian artery injuries. The results of this study also confirmed acceptable long-term follow-up without any limb or life threatening complications. We conclude that endovascular repair should be considered the first choice of treatment in stable patients with subclavian artery injuries.

Benefit/risk profile of high-dose antithrombin in patients with severe sepsis treated with and without concomitant heparin.

A randomised, prospective, placebo-controlled phase III multicentre clinical trial (KyberSept) has been performed to test the efficacy of high-dose antithrombin therapy in patients with severe sepsis. Concomitant low-dose heparin has been routinely given in two thirds of patients for deep vein thrombosis prophylaxis. This study analyses heparin - antithrombin interactions in terms of long-term mortality, adverse events, and thromboembolic events. From a total of 2,314 patients with severe sepsis (placebo: n = 1,157; antithrombin: n = 1,157) 1,616 patients (placebo: 811, antithrombin: 805) received heparin concomitantly with study drug (antithrombin 30,000 IU) over four days, whereas 698 patients (346 and 352, respectively) did not. In patients with no concomitant heparin, 28-day mortality was lower with antithrombin than with placebo (37.8% vs. 43.6%; absolute reduction: 5.8%; risk ratio: 0.860 [0.725-1.019]), which increased until day-90 (44.9% vs. 52.5%; absolute reduction: 7.6%; risk ratio: 0.851 [0.735-0.987]). In patients with concomitant heparin, no effect of antithrombin on mortality was seen (28-day mortality: 39.4% vs. 36.6%; absolute increase: 2.8%; risk ratio: 1.08 [0.96-1.22]). Frequency of use of concomitant heparin increased during conduct of the study. Increased bleeding incidences were reported with antithrombin plus concomitant heparin as compared to antithrombin alone. Rates of thromboembolic events were similar when antithrombin was given with or without concomitant heparin. In the treatment of severe sepsis, high-dose antithrombin may sufficiently protect against development of venous thromboembolism when no concomitant heparin is given. Combined administration of the two increases bleeding risk and probably abolishes efficacy of antithrombin.

Telavancin versus standard therapy for treatment of complicated skin and skin structure infections caused by gram-positive bacteria: FAST 2 study.

Telavancin is a bactericidal lipoglycopeptide with a multifunctional mechanism of action. We conducted a randomized, double blind, active-control phase II trial. Patients > or = 18 years of age with complicated skin and skin structure infections caused by suspected or confirmed gram-positive organisms were randomized to receive either telavancin at 10 mg/kg intravenously every 24 h (q24h) or standard therapy (antistaphylococcal penicillin at 2 g q6h or vancomycin at 1 g q12h). A total of 195 patients were randomized and received at least one dose of study medication. Clinical success rates were similar in all analysis populations at test of cure. In microbiologically evaluable patients with Staphylococcus aureus at baseline (n = 91), 96% of the telavancin group and 90% of the standard-therapy group were cured. Among patients with methicillin-resistant S. aureus (MRSA) at baseline (n = 45), clinical cure rates were also 96% for telavancin and 90% for standard therapy. Microbiologic eradication in patients with S. aureus infection was better with telavancin compared to standard therapy (92% versus 78%, P = 0.07) and significantly better in patients with MRSA (92% versus 68%; P = 0.04). Therapy was discontinued for an adverse event (AE) in 6% and 3% of the patients receiving telavancin and standard therapy, respectively. Except for two cases of rash in the telavancin group, these AEs were similar in type and severity in the two groups. The overall incidences and severities of AEs and laboratory abnormalities were similar between the two groups. These data support the ongoing studies assessing the efficacy and safety of telavancin in the treatment of serious gram-positive infections, particularly involving MRSA.

High-dose antithrombin III in the treatment of severe sepsis in patients with a high risk of death: efficacy and safety.

OBJECTIVE: To explore if patients with severe sepsis and with a predicted high risk of death (according to the Simplified Acute Physiology Score II) might have a treatment benefit from high-dose antithrombin III. DESIGN: Subgroup analysis of a randomized, placebo-controlled, double-blind, prospective phase III study. SETTING: Unifactorial and multifactorial reanalysis of prospectively defined populations from the KyberSept trial. PATIENTS: We studied 1,008 patients (43.6% of the overall intention-to-treat population, n = 2,314) with a predicted mortality rate of 30-60% at study entry as defined by the Simplified Acute Physiology Score II. INTERVENTIONS: Patients were randomized in a 1:1 fashion to receive either high-dose antithrombin III (30,000 IU intravenously over the period of 4 days) or placebo. MEASUREMENTS AND MAIN RESULTS: In a Kaplan-Meier analysis of patients with a predicted mortality of 30-60%, the survival time when followed up for 90 days after admission was increased in the high-dose antithrombin III group compared with placebo (p = .04). If heparin was avoided during the 4-day treatment phase with high-dose antithrombin III (n = 140) or placebo (n = 162), the treatment effect appeared to be even more pronounced: 28-day mortality rate, 35.7% vs. 44.4% (risk ratio, 0.804; 95% confidence interval, 0.607-1.064); 56-day mortality rate, 39.9% vs. 52.2% (risk ratio, 0.764; 95% confidence interval, 0.593-0.984); 90-day mortality rate, 42.8% vs. 55.1% (risk ratio, 0.776; 95% confidence interval, 0.614-0.986). Like in the overall population, the percentage with any bleeding was increased in patients receiving high-dose antithrombin III compared with placebo. Survival rates were in favor of high-dose antithrombin III in patients both with and without bleeding complications. CONCLUSIONS: Treatment with high-dose antithrombin III may increase survival time up to 90 days in patients with severe sepsis and high risk of death. This benefit may even be stronger when concomitant heparin is avoided.

Neurologic outcome after penetrating extracranial arterial trauma.

PURPOSE: We undertook this study to determine factors that adversely affect outcome in patients with penetrating injury to the extracranial cerebral vasculature. Patients and methods Medical records were reviewed for all patients who had undergone surgical intervention to treat penetrating injury to the extracranial cerebral arteries between January 1989 and December 1999. Forensic autopsy findings were also reviewed for all patients who died as a result of their injury. RESULTS: One hundred fifty-one patients with injury to the brachiocephalic artery (n = 21), common carotid artery (n = 98), or internal carotid artery (n = 32) were identified. Overall mortality was 21.2%, and stroke rate in surviving patients was 15.1%. Twenty-five of 32 deaths (78.1%) were stroke-related. Brachiocephalic artery injury was associated with the highest mortality (38.1%), and survivor stroke rate was highest in patients with internal carotid injuries (22.7%). Hemodynamic instability at presentation led to both higher mortality (30.7%) and stroke rate (19.2%). Preoperative angiography did not influence mortality or stroke rate in hemodynamically stable patients. Procedural mortality associated with arterial ligation was 45% (9 of 20 patients), and no surviving patient experienced a change in pre-ligation neurologic state. Nine patients remained neurologically intact after ligation, and 2 patients with preoperative localized neurologic deficit were unchanged postoperatively. In 131 patients, mortality after arterial repair was 17.6%, and in 5 surviving patients (5.4%) an ischemic neurologic deficit developed. Twelve of 15 surviving patients (80%) with preoperative neurologic deficit who underwent arterial repair had improved neurologic status. Cerebral infarcts were confirmed at autopsy in 23 patients; 18 infarcts were ischemic (10, repair; 8, ligation), and 5 infarcts were hemorrhagic (all, repair). No factor was identified that was predictive of ischemic versus hemorrhagic infarction in patients undergoing repair. CONCLUSIONS: The presence of hypovolemic shock, internal carotid artery injury, complete vessel transection, and arterial ligation are associated with unfavorable outcome. Penetrating injury to the brachiocephalic, common carotid, or internal carotid artery should be repaired rather than ligated when technically possible. Subsequent ischemic or hemorrhagic cerebral infarction is unpredictable, but overall outcome is superior to that with ligation of the injured artery.

Duodenal injuries: surgical management adapted to circumstances.

OBJECTIVES: To evaluate the results of an evolving policy of primary repair of duodenal injuries, when considered feasible and safe, complemented by pyloric exclusion if any doubt as to the integrity of the repair existed. PATIENTS AND METHODS: A prospective analysis of all patients with surgically identified duodenal injuries treated at a single institution over a 3-year period. RESULTS: In 30 patients studied, there were four deaths (13%) and an overall complication rate of 47%. There were 68 associated intra-abdominal injuries in 29 patients. Primary duodenorraphy was employed in 18 patients (60%), pyloric exclusion in 11 (37%) and pancreatoduodenectomy in one patient (3%). No failures of duodenal repair were recorded. CONCLUSION: Adverse results in patients with duodenal trauma are largely a reflection of frequent associated injuries and their consequences. Selective, liberal employment of pyloric exclusion, based on individualized intra-operative assessment, can minimize duodenum-related morbidity.