The potential utility of urinary biomarkers for risk prediction in combat casualties: a prospective observational cohort study.

INTRODUCTION: Traditional risk scoring prediction models for trauma use either anatomically based estimations of injury or presenting vital signs. Markers of organ dysfunction may provide additional prognostic capability to these models. The objective of this study was to evaluate if urinary biomarkers are associated with poor outcomes, including death and the need for renal replacement therapy. METHODS: We conducted a prospective, observational study in United States Military personnel with traumatic injury admitted to the intensive care unit at a combat support hospital in Afghanistan. RESULTS: Eighty nine patients with urine samples drawn at admission to the intensive care unit were studied. Twelve patients subsequently died or needed renal replacement therapy. Median admission levels of urinary cystatin C (CyC), interleukin 18 (IL-18), L-type fatty acid binding protein (LFABP) and neutrophil gelatinase-associated lipocalin (NGAL) were significantly higher in patients that developed the combined outcome of death or need for renal replacement therapy. Median admission levels of kidney injury molecule-1 were not associated with the combined outcome. The area under the receiver operating characteristic curves for the combined outcome were 0.815, 0.682, 0.842 and 0.820 for CyC, IL-18, LFABP and NGAL, respectively. Multivariable regression adjusted for injury severity score, revealed CyC (OR 1.97, 95 % confidence interval 1.26-3.10, p = 0.003), LFABP (OR 1.92, 95 % confidence interval 1.24-2.99, p = 0.004) and NGAL (OR 1.80, 95 % confidence interval 1.21-2.66, p = 0.004) to be significantly associated with the composite outcome. CONCLUSIONS: Urinary biomarker levels at the time of admission are associated with death or need for renal replacement therapy. Larger multicenter studies will be required to determine how urinary biomarkers can best be used in future prediction models.

Traumatic Hemothorax Blood Contains Elevated Levels of Microparticles that are Prothrombotic but Inhibit Platelet Aggregation.

OBJECTIVES: Autotransfusion of shed blood from traumatic hemothorax is an attractive option for resuscitation of trauma patients in austere environments. However, previous analyses revealed that shed hemothorax (HX) blood is defibrinated, thrombocytopenic, and contains elevated levels of D-dimer. Mixing studies with normal pooled plasma demonstrated hypercoagulability, evoking concern for potentiation of acute traumatic coagulopathy. We hypothesized that induction of coagulopathic changes by shed HX blood may be due to increases in cellular microparticles (MP) and that these may also affect recipient platelet function. METHODS: Shed HX blood was obtained from 17 adult trauma patients under an Institutional Review Board approved prospective observational protocol. Blood samples were collected every hour up to 4 h after thoracostomy tube placement. The corresponding plasma was isolated and frozen for analysis. The effects of shed HX frozen plasma (HFP) and isolated HX microparticles (HMP) on coagulation and platelet function were assessed through mixing studies with platelet-rich plasma at various dilutions followed by analysis with thromboelastometry (ROTEM), platelet aggregometry (Multiplate), enzyme-linked immunosorbent assays, and flow cytometry. Furthermore, HFP was assessed for von Willebrand factor antigen levels and multimer content, and plasma-free hemoglobin. RESULTS: ROTEM analysis demonstrated that diluted HFP and isolated HMP samples decreased clotting time, clotting formation time, and increased α angle, irrespective of sample concentrations, when compared with diluted control plasma. Isolated HMP inhibited platelet aggregation in response to adenosine diphosphate, arachidonic acid, and collagen. HFP contained elevated levels of fibrin-degradation products and tissue factor compared with control fresh frozen plasma samples. MP concentrations in HFP were significantly increased and enriched in events positive for phosphatidylserine, tissue factor, CD235, CD45, CD41a, and CD14. von Willebrand factor (vWF) multimer analysis revealed significant loss of high molecular weight multimers in HFP samples. Plasma-free hemoglobin levels were 8-fold higher in HFP compared with fresh frozen plasma. CONCLUSION: HFP induces plasma hypercoagulability that is likely related to increased tissue factor and phosphatidylserine expression originating from cell-derived MP. In contrast, platelet dysfunction is induced by HMP, potentially aggravated by depletion of high molecular weight multimers of vWF. Thus, autologous transfusion of shed traumatic hemothorax blood may induce a range of undesirable effects in patients with acute traumatic coagulopathy.

Early acute kidney injury in military casualties.

BACKGROUND: While acute kidney injury (AKI) has been well studied in a variety of patient settings, there is a paucity of data in patients injured in the course of the recent wars in Iraq and Afghanistan. We sought to establish the rate of early AKI in this population and to define risk factors for its development. METHODS: We combined the results of two studies performed at combat support hospitals in Afghanistan. Only US service members who required care in the intensive care unit were included for analysis. Data on age, race, sex, Injury Severity Score (ISS), first available lactate, and requirement for massive transfusion were collected. Univariate analyses were performed to identify factors associated with the subsequent development of early AKI. Multivariable Cox regression was used to adjust for potential confounders. RESULTS: The two observational cohorts yielded 134 subjects for analysis. The studies had broadly similar populations but differed in terms of age and need for massive transfusion. The rate of early AKI in the combined cohort was 34.3%, with the majority (80.5%) occurring within the first two hospital days. Patients with AKI had higher unadjusted mortality rates than those without AKI (21.7% vs. 2.3%, p < 0.001). After adjustment, ISS (hazard ratio, 1.02; 95% confidence interval, 1.00-1.03; p = 0.046) and initial lactate (hazard ratio, 1.16; 95% confidence interval, 1.03-1.31; p = 0.015) were independently associated with the development of AKI. CONCLUSION: AKI is common in combat casualties enrolled in two prospective intensive care unit studies, occurring in 34.3%, and is associated with crude mortality. ISS and initial lactate are independently associated with the subsequent development of early AKI. LEVEL OF EVIDENCE: Prognostic and epidemiologic study, level III.

Effects of rib raising on the autonomic nervous system: a pilot study using noninvasive biomarkers.

CONTEXT: Rib raising is an osteopathic manipulative treatment technique used to address restricted excursion of the rib cage and modulate sympathetic nervous system (SNS) activity. However, the physiologic effects of this technique have not been well documented. OBJECTIVE: To investigate the effects of rib raising on the autonomic nervous system and the hypothalamic-pituitary-adrenal axis using noninvasive biomarkers. METHODS: Changes in salivary biomarkers after rib raising were investigated using a pretest-posttest, placebo-controlled design. Healthy adult participants were recruited and randomly assigned to rib raising or placebo (light touch) groups. All participants provided baseline saliva samples and samples immediately and 10 minutes after receiving the rib raising or placebo procedure. Salivary flow rate, alpha-amylase activity, and cortisol levels were measured for each sample. RESULTS: Twenty-three participants were recruited, of whom 14 completed the study (7 in each group). Subjects who received rib raising had a statistically significant decrease in alpha-amylase activity both immediately after (P=.014) and 10 minutes after (P=.008) the procedure. A statistically significant change in alpha-amylase activity was not seen in the placebo group at either time point. Changes in salivary cortisol levels and flow rate were not statistically significant in either group. CONCLUSIONS: The results of the present pilot study suggest that SNS activity may decrease immediately after rib raising, but the hypothalamic-pituitary-adrenal axis and parasympathetic activity are not altered by this technique. Salivary alpha-amylase may be a useful biomarker for investigating manipulative treatments targeting the SNS. Additional studies with a greater number of subjects are needed to expand on these results.