Blood clotting and traumatic injury with shock mediates complement-dependent neutrophil priming for extracellular ROS, ROS-dependent organ injury and coagulopathy.

Polymorphonuclear (PMN) leucocytes participate in acute inflammatory pathologies such as acute respiratory distress syndrome (ARDS) following traumatic injury and shock, which also activates the coagulation system systemically. Trauma can prime the PMN nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex for an enhanced respiratory burst, but the relative role of various priming agents in this process remains incompletely understood. We therefore set out to identify mediators of PMN priming during coagulation and trauma-shock and determine whether PMN reactive oxygen species (ROS) generated in this manner could influence organ injury and coagulation. Initial experiments demonstrated that PMN are primed for predominantly extracellular ROS production by products of coagulation, which was abrogated by CD88/C5a receptor(C5aR) inhibition. The importance of this was highlighted further by demonstrating that known PMN priming agents result in fractionally different amounts of extracellular versus intracellular ROS release depending on the agent used. Plasma from trauma patients in haemodynamic shock (n = 10) also primed PMN for extracellular ROS in a C5a-dependent manner, which correlated with both complement alternative pathway activation and thrombin generation. Furthermore, PMN primed by preincubation with products of blood coagulation directly caused loss of endothelial barrier function in vitro that was abrogated by C5aR blockade or NADPH oxidase inhibition. Finally, we show in a murine model of trauma-shock that p47phox knock-out (KO) mice with PMN incapable of generating ROS were protected from inflammatory end-organ injury and activated protein C-mediated coagulopathy. In summary, we demonstrate that trauma-shock and coagulation primes PMN for predominantly extracellular ROS production in a C5a-dependent manner that contributes to endothelial barrier loss and organ injury, and potentially enhances traumatic coagulopathy.

Measurement of haemolysis markers following transfusion of uncrossmatched, low-titre, group O+ whole blood in civilian trauma patients: initial experience at a level 1 trauma centre.

BACKGROUND/OBJECTIVES: The safety of administering uncrossmatched, group O, cold-stored, whole blood (cWB) during civilian trauma resuscitation was evaluated. METHODS/MATERIALS: Male trauma patients with haemorrhage-induced hypotension who received leuko-reduced uncrossmatched group O+, low titre (<50) anti-A and -B, platelet-replete cWB during initial resuscitation were included. The biochemical markers of haemolysis (lactate dehydrogenase, total bilirubin, haptoglobin, creatinine, serum potassium) were measured on the day of cWB receipt (day 0), and over the next 2 days, reports of transfusion reactions and total blood product administration in first 24 h of admission were recorded. RESULTS: There were 27 non-group O and 17 group O cWB recipients. The median number of cWB units transfused was 1 [interquartile range (IQR): 1-2] in both groups. The median day 0 post-transfusion serum total bilirubin concentration, although still in the normal range, was higher in the non-group O versus group O recipients (1·4 versus 0·5 mg/dL, P < 0·01). There were no significant differences in any of the other biochemical parameters at any other time point. Non-group O recipients received a median of 3 times more red blood cell (RBC) units compared with group O recipients (P = 0·01 RBCs), likely explaining the bilirubin difference on day 0. The median volume of ABO-incompatible plasma transfused to non-group O recipients was 600 mL (IQR: 300-1140 mL). There were no reports of adverse events related to the cWB transfusion in either group. CONCLUSIONS: Administration of ≤2 units of cWB in civilian trauma resuscitation was not associated with clinically significant changes in laboratory haemolysis markers. Efficacy will be determined when larger quantities are transfused.

Increased platelet:RBC ratios are associated with improved survival after massive transfusion.

BACKGROUND: Several recent military and civilian trauma studies demonstrate that improved outcomes are associated with early and increased use of plasma-based resuscitation strategies. However, outcomes associated with platelet transfusions are poorly characterized. We hypothesized that increased platelet:red blood cells (RBC) ratios would decrease hemorrhagic death and improve survival after massive transfusion (MT). METHODS: A transfusion database of patients transported from the scene to 22 Level I Trauma Centers over 12 months in 2005 to 2006 was reviewed. MT was defined as receiving ≥ 10 RBC units within 24 hours of admission. To mitigate survival bias, 25 patients who died within 60 minutes of arrival were excluded from analysis. Six random donor platelet units were considered equal to a single apheresis platelet unit. Admission and outcome data associated with the low (>1:20), medium (1:2), and high (1:1) platelet:RBC ratios were examined. These groups were based on the median value of the tertiles for the ratio of platelets:RBC units. RESULTS: Two thousand three hundred twelve patients received at least one unit of blood and 643 received an MT. Admission vital signs, INR, temperature, pH, Glasgow Coma Scale, Injury Severity Score, and age were similar between platelet ratio groups. The average admission platelet counts were lower in the patients who received the high platelet:RBC ratio versus the low ratio (192 vs. 216, p = 0.03). Patients who received MT were severely injured, with a mean (± standard deviation) Injury Severity Score of 33 ± 16 and received 22 ± 15 RBCs and 11 ± 14 platelets within 24 hours of injury. Increased platelet ratios were associated with improved survival at 24 hours and 30 days (p < 0.001 for both). Truncal hemorrhage as a cause of death was decreased (low: 67%, medium: 60%, high: 47%, p = 0.04). Multiple organ failure mortality was increased (low: 7%, medium: 16%, high: 27%, p = 0.003), but overall 30-day survival was improved (low: 52%, medium: 57%, high: 70%) in the high ratio group (medium vs. high: p = 0.008; low vs. high: p = 0.007). CONCLUSION: Similar to recently published military data, transfusion of platelet:RBC ratios of 1:1 was associated with improved early and late survival, decreased hemorrhagic death and a concomitant increase in multiple organ failure-related mortality. Based on this large retrospective study, increased and early use of platelets may be justified, pending the results of prospective randomized transfusion data.

Word recognition performance in various background competitors.

Word recognition performance was measured for 18 normal-hearing subjects using the female talker version of the Northwestern University Auditory Test No. 6 (NU-6) in the presence of three background competitors: (1) a meaningful multitalker competing message consisting of three male and three female talkers (forward multitalker competing message [FCM]), (2) the same multitalker competing message recorded in reverse to eliminate semantic content (backward multitalker competing message [BCM]), and (3) an amplitude-modulated speech-spectrum noise (SSN) having the same long-term average spectrum and amplitude fluctuations as the meaningful multitalker competing message. The meaningful competitor had a significantly more deleterious effect on recognition performance compared to performance for the two nonmeaningful competitors. Furthermore, the nonmeaningful speech competitor produced a significantly greater degradation in performance than that for the SSN.

Masking-level difference for spondaic words in 2000-msec bursts of broadband noise.

One protocol developed for the Tonal and Speech Materials for Auditory Perceptual Assessment audio compact disc was the masking-level difference (MLD) for spondaic words in which the words and broadband noise were mixed and recorded at 16 selected signal-to-noise ratios. Four words were recorded at each level. Because it was impossible to monitor the word presentations at negative signal-to-noise ratios, a different paradigm was devised in which the spondaic words were embedded in 2000-msec bursts of noise. Before the materials were finalized for the compact disc, two experiments studied the perceptual characteristics of the paradigm. Experiment I was performed to determine the characteristics of the MLD for spondaic words in 2000-msec bursts of noise at 70 dB SPL. An unexpected finding was that the mean SoNo thresholds were at signal-to-noise ratios 3-4 dB lower than previously reported spondaic word thresholds in continuous broadband noise. Experiment II examined this discrepancy with the spondaic words embedded in continuous noise and in the 2000-msec noise bursts. The results confirmed the 3-4 dB difference between thresholds for the two masker conditions. Based on the pilot data, the spondaic words embedded in 2000-msec bursts of broadband noise at signal-to-noise ratios of 0 dB to -30 dB were recorded on the compact disc in the S pi No paradigm. In the compact disc trials, which involved 120 subjects with normal hearing, the MLDs for the spondaic words recorded on the compact disc were measured on 60 subjects at each of two noise levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of time compression and time compression plus reverberation on the intelligibility of Northwestern University Auditory Test No. 6.

The Tonal and Speech Materials for Auditory Perceptual Assessment, Disc 1.0 audio compact disc developed in 1992 includes several sets of degraded speech materials, two of which, time compression and reverberation, are described in this paper. The digital techniques used to compress the NU No. 6 materials (female speaker) on an 80386-based computer are described, along with a series of experiments on subjects with normal hearing that document the effects of the time compression on recognition performance. Experiment I examined at 70 dB SPL the effect on word recognition of 45, 55, 65, 70, and 75 percent compressions. Experiment II developed psychometric functions for the 45, 65, and 75 percent time-compression conditions. Experiment III defined the effects that time-compression degradation (45% and 65%) plus reverberation degradation (0.3 sec) had on the recognition performance on the NU No. 6 materials. Based on the experiments, four conditions (45% compression, 65% compression, 45% compression plus 0.3-sec reverberation, and 65% compression plus 0.3-sec reverberation) were selected and recorded on the compact disc. In the compact disc trials, normative data on the four conditions were developed from 120 listeners with normal hearing.