External validation of a smartphone app model to predict the need for massive transfusion using five different definitions.

BACKGROUND: Previously, a model to predict massive transfusion protocol (MTP) (activation) was derived using a single-institution data set. The PRospective, Observational, Multicenter, Major Trauma Transfusion database was used to externally validate this model's ability to predict both MTP activation and massive transfusion (MT) administration using multiple MT definitions. METHODS: The app model was used to calculate the predicted probability of MTP activation or MT delivery. The five definitions of MT used were: (1) 10 units packed red blood cells (PRBCs) in 24 hours, (2) Resuscitation Intensity score ≥ 4, (3) critical administration threshold, (4) 4 units PRBCs in 4 hours; and (5) 6 units PRBCs in 6 hours. Receiver operating curves were plotted to compare the predicted probability of MT with observed outcomes. RESULTS: Of 1,245 patients in the data set, 297 (24%) met definition 1, 570 (47%) met definition 2, 364 (33%) met definition 3, 599 met definition 4 (49.1%), and 395 met definition 5 (32.4%). Regardless of the outcome (MTP activation or MT administration), the predictive ability of the app model was consistent: when predicting activation of the MTP, the area under the curve for the model was 0.694 and when predicting MT administration, the area under the curve ranged from 0.695 to 0.711. CONCLUSION: Regardless of the definition of MT used, the app model demonstrates moderate ability to predict the need for MT in an external, homogenous population. Importantly, the app allows the model to be iteratively recalibrated ("machine learning") and thus could improve its predictive capability as additional data are accrued. LEVEL OF EVIDENCE: Diagnostic test study/Prognostic study, level III.

The effects of a data driven maximum surgical blood ordering schedule on preoperative blood ordering practices.

OBJECTIVES: The maximum surgical blood ordering schedule (MSBOS) provides guidelines for pre-operative pre-transfusion testing for elective surgical procedures. This study compared blood ordering and utilization during the period when the MSBOS was created by achieving consensus between the blood bank and the various surgical specialties, and after the introduction of an MSBOS created by using department-specific red blood cell (RBC) transfusion data (data driven MSBOS, dMSBOS). METHODS: The dMSBOS was created by analyzing 12 months of RBC transfusion data for each procedure across a regional health system. Pre-transfusion testing and the RBC crossmatch:transfusion (C:T) ratios at 8 of the hospitals were compared between the 12 month period before the dMSBOS was introduced, and the 15 months after its introduction. RESULTS: There were significant reductions in the median monthly number of type and screens not associated with RBC crossmatches (10 714-10 061; p < 0.0001) and the median number of type and screens associated with RBC crossmatches (10 127-9 349; p = 0.0014) on surgical patients after dMSBOS implementation. There were significant decreases in the median number of monthly RBC units crossmatched (2 981-2 444; p < 0.0001) and transfused (890-791; p < 0.0001) to surgical patients after implementing the dMSBOS. The overall system-wide C:T ratio trended down after dMSBOS implementation (from 3.34 to 3.17, p = 0.067). DISCUSSION: Crossmatching fewer RBC units facilitates more efficient management of the blood bank's inventory. CONCLUSION: The dMSBOS was effective in reducing the extent of unnecessary pre-transfusion testing before surgery and reduced the number of RBCs that were crossmatched for specific patients.

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.

Excessive quantities of red blood cells are issued to the operating room.

OBJECTIVES: To determine what percentage of red blood cell (RBC) units that were issued to the operating room (OR) were returned unused, and to determine how often all of the RBCs that were issued for a patient were returned unused using the institution's maximum surgical blood ordering schedule (MSBOS) as a guide. BACKGROUND: The MSBOS provides guidelines for blood ordering, but is merely a suggestion for the ordering clinicians. This study examined how closely ordering practices followed the MSBOS, and how often ordered RBCs were actually transfused. METHODS: For a 4-week period, RBC issue and utilization data were collected on elective surgery patients who were eligible for electronic cross-match at a tertiary care hospital. These data were compared to the MSBOS. RESULTS: There were 1350 surgical procedures performed. Of these cases, 439 patients had a type and screen (T&S) performed, and 215/439 (49%) patients had at least 1 RBC issued during their case. To these 215 patients, 742 RBC units were issued and 537/742 (72%) of these units were returned to the blood bank unused. In 152/215 (71%) cases with issued RBCs, all of the RBCs were returned to the blood bank unused. Amongst the surgical categories in this study, the percentage of cases where none of the issued RBCs were transfused ranged from 38 to 93%. CONCLUSIONS: Significant numbers of RBC units are issued but not transfused during surgery. Involving the surgical team in the blood issuing process and using a data-driven MSBOS may reduce the number of unused units.

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.

Inducible nitric oxide synthase in the liver: regulation and function.

The inducible nitric oxide synthase (iNOS) gene is expressed by hepatocytes in a number of physiologic and pathophysiologic conditions affecting the liver including septic and hemorrhagic shock. The molecular regulation of iNOS expression is complex and occurs at multiple levels in the gene expression pathway. The cytokines TNF-alpha, IL-1beta, and INF-gamma synergistically activate iNOS expression in the liver, and the human iNOS gene was first cloned from cytokine-stimulated hepatocytes. iNOS expression requires the transcription factor NF-kappaB and is down-regulated by steroids, TGF-beta, the heat shock response, p53, and nitric oxide (NO) itself. In vivo, hepatic iNOS induction is differentially regulated from the typical acute-phase reactants and is not expressed as a mandatory component of the acute phase response. Thus, numerous mechanisms have evolved to regulate iNOS expression during hepatocellular injury. Studies of the effects of NO in the liver demonstrate that induced NO synthesis plays an important role in hepatocyte function and protects the liver during sepsis and ischemia reperfusion. Its cytoprotective role is best exemplified in a rodent model of endotoxemia. Here the addition of the nonspecific NOS inhibitors significantly increased hepatic damage. NO exerts a protective effect through its ability to prevent intravascular thrombosis by inhibiting platelet adhesion and neutralizing toxic oxygen radicals. NO also exerts a protective effects both in vivo and in vitro by blocking TNF-alpha-induced apoptosis and hepatotoxicity, in part by a thiol-dependent inhibition of caspase-3-like protease activity. These studies demonstrate the cytoprotective effects of NO in the liver and suggest hepatic iNOS expression functions as an adaptive response to minimize inflammatory injury. In addition, NO has anti-tumor effects as well as known mutagenic effects, is involved in the systemic vasodilatation of cirrhosis, and has potent antimicrobial properties.