pRBC Units Research Articles

Ammonia concentration and bacterial evaluation of feline whole blood and packed red blood cell units stored for transfusion

Ammonia concentrations increase in human, canine and equine WB and PRBC units during storage. The aim of this study was to determine the effect of storage on ammonia concentration in feline WB and PRBC units stored in a veterinary blood bank and to evaluate possible correlations with bacterial contamination. Ammonia concentration was evaluated in 15 WB units and 2 PRBC units on day 1 and at the end of storage after 35 and 42 days, respectively. In an additional 5 WB units and 4 PRBC units ammonia concentrations were determined daily until the day the normal reference range was exceeded and then weekly to the end of storage. All units were evaluated for bacterial contamination. Ammonia increased markedly during storage as a linear function over time. On the 35th and 42th day of storage at 4±2°C mean±SD ammonia concentration reached 909±158 µg/dl and 1058±212 µg/dl in WB and PRBC units, respectively. Bacterial culture was negative in all units. High ammonia concentrations in stored WB and PRBC units could result in toxicity, particularly in feline recipients with liver failure, portosystemic shunts or those receiving large transfusion volumes. Clinical in vivo studies evaluating the effects on recipients should be performed.

Transfusion utilization at the end of life.

303 Background: Both the AMA’s Consortium for Performance Improvement and the Joint Commission have identified blood transfusions as one of the top 5 treatments that are over-utilized. We sought to quantify packed red blood cell transfusion (PRBT) utilization among ovarian cancer (OCa) pts in the last 6 months of life and identify risk factors for PRBT. Methods: We performed a retrospective cohort study of deceased OCa pts treated at our institution in their last 6 months of life from 2007-2011. Pts who underwent emergent procedures for bleeding were excluded. Demographic and end of life-interventions were compared between transfusion and non-transfusion groups using chi-squared and univariate analysis. End-of-life interventions included anti-cancer treatment (chemotherapy radiation, or hormonal therapy), invasive procedure or abdominal surgery, as well as aggressive end-of-life care as defined by the NQF. Results: Of the 182 pts who met inclusion criteria, 59.9% received a PRBT in the last 6 months of life. Of those pts, 54.1% received a PRBT in the last 30 days of life. Mean hgb level at which pts were transfused was 8.4 ± 0.9 g/dL. Pts received a combined total of 436 units of PRBC. The majority of pts received 1 transfusion (n=50, range 1-16). Mean number of total units transfused was 4 (range 1-25). The most common indication for PRBT was hgb < 9 g/dL (61.1%), followed by symptomatic anemia (21.9%). There was no difference in PRBT rate between pts who received medical interventions in the last 6 months of life v. those who did not. Specifically, transfusion rate was not correlated with: anti-cancer treatments (93.2% v. 92.7%, OR 0.93; 95% CI (0.29, 2.96)), invasive procedures (82.2% v. 81.7%, OR 0.96; CI (0.45,2.08)), abdominal surgery (11.0% v. 11.0%, OR 1.01; 95% CI(0.39,2.59)), or aggressive end-of-life care (46.6% v. 56.9%, OR 1.51; 95% CI (0.83,2.74)). Conclusions: The majority of our pts received a PRBT in the last 6 months of life. We did not identify significant differences in clinical interventions between pts who received a PRBT and those who did not. Based on our analysis, transfusion practices in terminally ill OCa pts should be reevaluated. Creation of transfusion guidelines for cancer pts could potentially result in better utilization of blood bank resources.

Massive GI Bleeding Due to Jejunal Diverticulosis: A Rare Diagnostic Dilemma Highlighting the Importance of Endoscopic Timing and Multidisciplinary Care

SymbolIntroduction: Jejunal diverticula form as a result of increased intraluminal pressure at the weakest points of the jejunum, usually near the site of entry of blood vessels into the bowel wall, leading to herniation of mucosa/submucosa through the muscle layer. Patients present with melena and obscure GI bleeding. Once the diagnosis is established, the treatment of choice is surgical resection of the jejunal segment and primary anastomosis. A 77-year-old man presented to an outside institution with 3 days of shortness of breath and melena. Hemoglobin was 7.6 g/dL on admission. Transfused 3 units of pRBC and incremented to 9.2 g/dL, but fell to 7.2 g/dL the following day. EGD was normal. Colonoscopy with TI intubation showed pan-colonic diverticulosis without active bleeding. Melena continued and small bowel enteroscopy performed showing diverticula in the duodenum and proximal jejunum without any blood or clots. Melena continued and an abdominal CT angiography was performed. No bleeding seen. Patient transferred to our institution and capsule endoscopy was performed. Findings suggested a jejunal source of bleeding and a double balloon-assisted enteroscopy was performed. Surgical consultation obtained and stated that since multiple diverticula were found in the duodenum/jejunum but no active bleeding was seen, any surgical intervention in this area would be technically difficult and a targeted resection could not be performed; UGI series with small bowel follow-through performed to assess number and extent of diverticula. Multiple diverticula noted in the second/third portions of the duodenum, proximal/mid-jejunal loops and distal ileum. On hospital day 7, the patient began to have maroon-stools. Taken for urgent enteroscopy with a cap-fitted pediatric colonoscope. Cap used to carefully examine small bowel mucosa and interrogate diverticula. Actively bleeding jejunal diverticula located but no targets for endoscopic treatment identified. Area tattooed and patient sent for surgical resection. Patient did well following surgical resection of jejunal segment. No additional episodes of melena/hematochezia occurred. He was discharged from the hospital and no further GI hemorrhage at 6 months of follow-up.In summary, massive gastrointestinal hemorrhage from jejunal diverticulosis is extremely rare and preoperative localization of the bleeding intestinal segment is challenging. This case illustrates the importance of endoscopic timing in reaching the appropriate diagnosis and the multidisciplinary approach used in its successful management. Urgent endoscopy at the time of active bleeding may be the key to establishing the diagnosis and allow for targeted surgical resection and definitive hemostasis.Symbol

Management of Massive Parastomal Variceal Bleed by Minimally Invasive Percutaneous N-butyl-2-cyanoacrylate Embolization

Introduction: Parastomal variceal bleed is a serious problem in patients with surgical stomas and portal hypertension. They are difficult to manage due to challenges in hemorrhage control and tendency to rebleed. We present a case of massive parastomal variceal bleed successfully treated using fluoroscopic guidance injection of N-butyl-2-cyanoacrylate (NBCA). Case Report: A 56-year-old man presented to the emergency department with profuse bleeding from colostomy site. The patient had significant history for alcoholic cirrhosis and post-colostomy from Hartmann’s procedure for diverticular bleed 10 years ago. He failed 2 previous attempted closure of colostomy due to bleeding diathesis. He had numerous recurrent parastomal bleed requiring multiple blood transfusions, treated by silver nitrate cauterization and suture ligation. On admission, Hb was 4.6. Parastomal bleeding was severe, requiring 14 units of PRBC despite topical surgical ligation and cauterization. A CT angiogram to assess for parastomal variceal bleed was requested by the liver team, which showed an extensive network of varices adjacent to the left lower quadrant ostomy draining into an enlarged inferior mesenteric vein. Transjugular intrahepatic portosystemic shunt (TIPS) was considered, but the patient was deemed not a candidate due to moderate aortic stenosis, mild pulmonary hypertension, and MELD of 17. Instead, he underwent radiology-guided embolization by using sonographic guidance. Varices were confirmed and venography revealed a network of varices overlying the ostomy. Under fluoroscopy, 2 cc NBCA was injected percutaneously into the varicose veins at 2 locations, respectively. The embolization was successful without complication. Hemoglobin remained stable at 8.6 over the next 3 days. He was discharged and had no parastomal bleeding over the past 4 months. Discussion: Parastomal variceal bleed should be highly suspected in patients with cirrhosis and portal hypertension. TIPS has been recommended for control of stomal variceal bleeding. However, our case demonstrated that percutaneous fluoroscopic embolization with NBCA is a simple, safe, and effective procedure in control of parastomal variceal bleed when TIPS was infeasible.

Striking a balance in massive transfusion for traumatic brain injury: do the crystalloid to blood product ratios matter?

METHODS: A retrospective data review from a prospectively collected MTP and Trauma registry, at a Level I trauma center, was conducted. All TBI patients who received 10 units PRBC in their 1st 24 hours were included. Patients were divided into two groups: survivors[S] and non-survivors[NS]. Demographic information, clinical characteristics and outcome measures were compared and tested for their association with the crystalloid to blood product ratios administered at 4 and 24 hours post-injury.

THE ABC TRIAL - DOES ALL-BLOOD CARDIOPLEGIA PREVENT BLOOD TRANSFUSION IN CARDIAC SURGERY? A SINGLE CENTER PILOT STUDY

s S227 was classified into a high RDW group and others were classified into a control group. Thrombolysis in Myocardial Infarction (TIMI) risk scores, angiographic characteristics, inhospital percutaneous or surgical revascularization, as well as 30-days major adverse cardiac event (MACE) including death, recurrent myocardial infarction, target vessel revascularization and lethal ventricular arrhythmias were compared between the two groups. RESULTS: Among 340 patients, 31 patients (9.1%) were classified into the high RDW group and 309 patients (90.9%) were classified into the control group. Mean RDW was 18.3 2.6% in the high RDW group and 13.8 0.9% in the control group. Patients with high RDW were more likely to have hypertension (93.5% vs. 73.1%, p1⁄40.01), chronic kidney disease (51.6% vs. 30.4%, p1⁄40.02) and anemia (11.3 1.6 g/dl vs. 13.2 1.7g/dl, p<0.001). Patients with high RDW had higher TIMI risk scores (4.2 1.2 vs. 3.6 1.5, p1⁄40.017) compared to the control group. Patients with high RDW had a higher rate of 30-days MACE (12.9% vs. 2.9%, p1⁄40.001) compared to the control group, and this association remained significant after adjusting for the baseline hemoglobin levels (odds ratio 2.878; 95% confidence interval 1.66 to 24.1; p1⁄40.004). There was no significant difference in peak troponin values, the rates of inhospital revascularization, pre-procedural impaired coronary flow, and the existence of coronary thrombus between the two groups. CONCLUSION: In patients with NSTEMI, high RDW defined as greater than 1SD was significantly associated with a higher TIMI risk score and a higher rate of 30-days MACE. After adjusting for the baseline hemoglobin levels, high RDW remained significantly associated with a higher rate of 30-days MACE. 337 THE ABC TRIAL DOES ALL-BLOOD CARDIOPLEGIA PREVENT BLOOD TRANSFUSION IN CARDIAC SURGERY? A SINGLE CENTER PILOT STUDY C Deshaies, RD Stanzel, KJ Buth, AB Fagan, GM Hirsch, SB O’Blenes Halifax, Nova Scotia BACKGROUND: All-blood cardioplegia (ABC) has emerged as an alternative to standard 4:1 diluted blood cardioplegia (DBC) due to its theoretical advantages of limiting hemodilution, blood transfusion, and myocardial edema. METHODS: We performed a randomized, double blind pilot study to determine feasibility and sample size for a multicenter trial comparing both strategies. Patients were eligible if undergoing CABG, aortic, mitral or combined surgery. Exclusion criteria included pre-op mechanical support, endocarditis, previous cardiac surgery, and recent irreversible anticoagulation. Retrograde autologous priming was used in all cases. Strict transfusion criteria were followed during hospital admission. RESULTS: Of 650 cases performed at our centre between February and September 2013, 246 patients were screened and 36 of them (15%) were eligible, consented, and randomized (ABC n1⁄418; DBC n1⁄418). Comorbidities, procedure types, and cross-clamp time, were similar in each group (table 1). There was no mortality. The total volume of cardioplegia delivered in each group was similar but the amount of crystalloid in the cardioplegia was significantly less in the ABC group (73 vs. 516 mL; p < .0001) (figure 1). Nonetheless, crystalloid in the cardioplegia represented only 1% (ABC) vs. 8% (DBC; p < .0001) of the total intraoperative crystalloid administration, and 0.7% (ABC) vs. 5% (DBC; p < .0001) of the fluid received in the first 24 hours of care. Four ABC and 2 DBC patients were transfused a total of 6.75 and 5 pRBC units. There was 100% adherence to our transfusion protocol. One subject in the ABC group, who was initially transfused during his admission, also received an additional unit in a peripheral center after discharge. The drop in hemoglobin from pre-op to lowest value (g/L: 51 vs. 49; p 1⁄4 0.60), the incidence of low cardiac output (%: 16 vs. 22; p 1⁄4 0.99) and markers of myocardial injury (16-hr Tn-T: 227 vs. 327; p 1⁄4 0.08) were similar in each group. Based on the DBC transfusion rate of 11% and a power of 80%, 898 to 2892 patients per arm would be required to show a relative risk reduction between 20 and 35%. CONCLUSION: The study demonstrated the feasibility of our design. However, over 1000 subjects per group will be required to detect a clinically significant reduction in transfusion. Modification of inclusion criteria, targeting patients at high risk of transfusion, would likely reduce the necessary sample size but would negatively impact recruitment rate and generalizability of the results. S228 Canadian Journal of Cardiology Volume 3

Intraoperative Continuous Veno-Venous Hemofiltration Facilitates Surgery in Liver Transplant Patients With Acute Renal Failure.

We have aggressively utilized continuous veno-venous hemofiltration (CVVH) on high MELD liver transplant patients with acute kidney injury in an effort to decrease transfusion requirements and complications, and improve overall outcomes. Methods: We performed a retrospective review of all adult, single organ, liver transplant recipients requiring pre-operative renal replacement therapy between 2011 and 2013. Intra- and peri-operative records were collected to create a database of these patients. Patients were grouped according to whether or not they underwent CVVH at the time of liver transplant. Results: Twenty-one 21 patients requiring CVVH received a liver transplant alone. Of these 21 patients, 14 received intraoperative CVVH and 7 patients did not. The average MELD score was similar between groups (34 for CVVH vs. 35, p=0.8). Pre-operative sodium and potassium were higher for the group receiving CVVH (p<0.01, p=0.02) but still fell within normal ranges. Pre-operative lactate levels were higher in the group that received intraoperative CVVH (4.7 vs. 2.0 mmol/L (p=0.01)). Intraoperative CVVH did not decrease intraoperative transfusion requirements (16 vs. 20 units PRBC, p=0.6; 17 vs. 19 units FFP, p=0.7; 8 vs. 16 units platelets, p=0.2), post-operative acidosis (7.40 vs. 7.35, p=0.8), or ICU and hospital lengths of stay. Furthermore, post-operative day 1 transfusion requirements were not decreased by intraoperative CVVH, (3 vs. 2 units PRBC, p=0.4; 2 vs. 1 unit FFP, p=0.2; 0.8 vs. 0.4 units platelets, p=0.4). Differences in reoperative rates did not reach statistical significance (29% with CVVH vs. 50%, p=0.6.) All patients were weaned off renal replacement therapy. Rolling one-year patient and graft survival was 100% for intraoperative CVVH versus 71% without, but this was not statistically significant (p=0.2). Conclusions: Patients undergoing intraoperative CVVH achieved statistically equivalent survival and transfusion outcomes despite higher pre-operative sodium, potassium, and lactate values, with trends of higher survival and decreased re-operative rates. The judicious use of intraoperative CVVH therapy may permit patients with increasing severity of illness to achieve outcomes comparable to less ill patients; however, aggressive pre- and post-operative CVVH may diminish the effect of intraoperative CVVH in cases with relatively short operative times.

Review article: Shock Index for prediction of critical bleeding post‐trauma: A systematic review

Early diagnosis of haemorrhagic shock (HS) might be difficult because of compensatory mechanisms. Clinical scoring systems aimed at predicting transfusion needs might assist in early identification of patients with HS. The Shock Index (SI) - defined as heart rate divided by systolic BP - has been proposed as a simple tool to identify patients with HS. This systematic review discusses the SI's utility post-trauma in predicting critical bleeding (CB). We searched the databases MEDLINE, Embase, CINAHL, Cochrane Library, Scopus and PubMed from their commencement to 1 September 2013. Studies that described an association with SI and CB, defined as at least 4 units of packed red blood cells (pRBC) or whole blood within 24 h, were included. Of the 351 located articles identified by the initial search strategy, five met inclusion criteria. One study pertained to the pre-hospital setting, one to the military, two to the in-hospital setting, and one included analysis of both pre-hospital and in-hospital values. The majority of papers assessed predictive properties of the SI in ≥10 units pRBC in the first 24 h. The most frequently suggested optimal SI cut-off was ≥0.9. An association between higher SI and bleeding was demonstrated in all studies. The SI is a readily available tool and may be useful in predicting CB on arrival to hospital. The evaluation of improved utility of the SI by performing and recording at earlier time-points, including the pre-hospital phase, is indicated.

Feeding practices and other risk factors for developing transfusion-associated necrotizing enterocolitis

AimsThe objective of this study is to determine the incidence of and risk factors for necrotizing enterocolitis (NEC) and transfusion-associated NEC (TANEC) in very-low-birth-weight (VLBW) infants pre/post implementation of a peri-transfusion feeding protocol. Study designA retrospective cohort study was conducted including all inborn VLBW infants admitted to the Duke intensive care nursery from 2002 to 2010. We defined NEC using Bell's modified criteria IIA and higher and TANEC as NEC occurring within 48h of a packed red blood cell (pRBC) transfusion. We compared demographic and laboratory data for TANEC vs. other NEC infants and the incidence of TANEC pre/post implementation of our peri-transfusion feeding protocol. We also assessed the relationship between pre-transfusion hematocrit and pRBC unit age with TANEC. ResultsA total of 148/1380 (10.7%) infants developed NEC. Incidence of NEC decreased after initiating our peri-transfusion feeding protocol: 126/939 (12%) to 22/293 (7%), P=0.01. The proportion of TANEC did not change: 51/126 (41%) vs. 9/22 (41%), P>0.99. TANEC infants were smaller, more likely to develop surgical NEC, and had lower mean pre-transfusion hematocrits prior to their TANEC transfusions compared with all other transfusions before their NEC episode: 28% vs. 33%, P<0.001. Risk of TANEC was inversely related to pre-transfusion hematocrit: odds ratio 0.87 (0.79–0.95). ConclusionsPre-transfusion hematocrit is inversely related to risk of TANEC, which suggests that temporally maintaining a higher baseline hemoglobin in infants most at risk of NEC may be protective. The lack of difference in TANEC pre-/post-implementation of our peri-transfusion feeding protocol, despite an overall temporal decrease in NEC, suggests that other unmeasured interventions may account for the observed decreased incidence of NEC.

Serial assessment of biochemical changes in irradiated red blood cells

Transfusion associated graft vs host disease (TA-GVHD) is delayed effect of blood component therapy with a very high mortality rate. The use of irradiated blood components is the only proven method to prevent TA-GVHD in susceptible patients. Our study was designed to analyze the quality of irradiated PRBCs in terms of their biochemical parameters during a storage period up to 28 days post irradiation. A total of 80 PRBC units were analyzed, 40 units each stored in CPDA-1 and additive solution-SAGM. The units were evaluated serially for the following biochemical parameters, plasma/ supernatant potassium, sodium, pH, glucose, lactate, plasma/supernatant hemoglobin and red cell ATP. We further evaluated the differences in these parameters between units irradiated on day 1 and day 7 of storage and stored these units up to 28 days and 35 days respectively. Ten units in each group were used as control. The assessment was done at weekly intervals from the day of irradiation. Within each group of red cells, there was a rise in mean concentration of plasma potassium (K(+)) from day 1 to last day of storage. There was a highly significant difference (P<0.01) between irradiated and control units after first week of storage in both types of PRBCs. Irradiated CPDA-1 PRBC had significantly higher (K(+)) than irradiated SAGM PRBC. Intergroup comparison revealed significantly higher (P<0.05) mean hemoglobin in irradiated CPDA-1 PRBC as compared to SAGM PRBC. The mean pH was significantly higher (P<0.05) in irradiated CPDA-1 PRBC as compared to irradiated SAGM PRBC only on day 7 of storage. ATP levels significantly decreased in irradiated units as compared to control units. SAGM PRBCs had significantly higher (P<0.05) mean ATP concentration than CPDA-1PRBCs. Our study demonstrates that SAGM-PRBCs show better stability after irradiation compared to CPDA-1 PRBCs. The limits of safety for CPDA-1 PRBCs appear to be two weeks after irradiation. SAGM-PRBCs on the other hand show acceptable limits of safety up to three weeks of irradiation. The shelf life of irradiated PRBCs may vary depending upon the storage solution and day of irradiation.

Trends in Transfusion Among Children With Sickle Cell Disease

Source: Raphael JL, Oyeku SO, Kowalkowski MA, et al. Trends in blood transfusion among hospitalized children with sickle cell disease. Pediatr Blood Cancer. 2013; 60(11): 1753– 1758; doi: 10.1002/pbc.24630Investigators from multiple institutions examined trends in use of blood transfusion for hospitalized children with sickle cell disease (SCD) in the United States between 1997 and 2009. The investigators reviewed the Kid’s Inpatient Database (KID), a database sponsored by the Agency of Healthcare Research and Quality and designed to report hospital use and outcomes in children every 3 years. Children ≤18 years of age with a primary or secondary discharge ICD-9 diagnosis associated with SCD were included. The primary outcome was the proportion of hospitalizations for children with SCD requiring transfusions. Child demographics, clinical diagnoses associated with SCD (such as vaso-occlusive crises [VOC] and acute chest syndrome [ACS]/pneumonia), transfusion type (packed red blood cell [pRBC] and exchange), and hospital characteristics were also collected. Multivariate logistic regression was used to identify both specific trends in use of transfusions over time and diagnoses that led to transfusion after accounting for potential demographic, diagnostic, and hospital-level confounders.Over the course of the study period investigators found that the percentage of children hospitalized with SCD who received blood transfusions increased significantly, from 14.2% in 1997 to 28.8% in 2009, and did so incrementally over the study period (16.8% in 2000, 20.4% in 2003, and 24.7% in 2006). The percentage of hospitalizations in which pRBC transfusions were given significantly increased from 13.9% in 1997 to 27.8% in 2009, while exchange transfusions significantly decreased from 2.1% to 1.7%. VOC as a principal diagnosis accounted for 56% of SCD-related hospitalizations when transfusions were administered; ACS/pneumonia accounted for 5.5%. In multivariate analyses, there were significantly higher odds of blood transfusion among all SCD-related hospitalizations for each successive 3-year study interval (adjusted odds ratio [aOR] = 1.23; 95% CI, 1.15–1.32). There were also significantly higher odds of blood transfusion for each successive 3-year study interval among hospitalizations where VOC (aOR = 1.35; 95% CI, 1.27–1.43) and ACS/pneumonia (aOR = 1.24; 95% CI, 1.13–1.35) were the principal diagnoses.The investigators conclude that blood transfusion for hospitalized children with SCD is increasing over time.Dr Onyekwere has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.Blood transfusions remain an essential therapeutic option for patients with SCD. However, children with SCD are at risk of developing transfusional iron overload, alloimmunization to transfused blood products, and transfusion-induced bone marrow transplant rejection1 from multiple blood transfusions (over 10 units of pRBC). Iron is accumulated in the liver, endocrine organs, and heart resulting in multi-organ dysfunction. Multiple transfusions and significant RBC antigen mismatch predisposes the individual to alloimmunization, which leads to life-threatening events.2 Indiscriminate blood transfusion practices cause more harm than good.The results of the current study complement those of earlier work in which investigators have documented that the rate of transfusion in children with SCD in both outpatient and inpatient settings has increased over the years, especially in general hospitals and in outpatient settings.3,4 To prevent associated morbidity and mortality, blood banks should develop a standardized high-quality and effective transfusion therapeutic regimen. In addition, physicians should work to develop transfusion and management guidelines for individuals with sickle cell disease for community and ambulatory care.

Magnetic Nanosensor for Detection and Profiling of Erythrocyte-Derived Microvesicles

During the course of their lifespan, erythrocytes actively shed phospholipid-bound microvesicles (MVs). In stored blood, the number of these erythrocyte-derived MVs has been observed to increase over time, suggesting their potential value as a quality metric for blood products. The lack of sensitive, standardized MV assays, however, poses a significant barrier to implementing MV analyses into clinical settings. Here, we report on a new nanotechnology platform capable of rapid and sensitive MV detection in packed red blood cell (pRBC) units. A filter-assisted microfluidic device was designed to enrich MVs directly from pRBC units, and label them with target-specific magnetic nanoparticles. Subsequent detection using a miniaturized nuclear magnetic resonance system enabled accurate MV quantification as well as the detection of key molecular markers (CD44, CD47, CD55). When the developed platform was applied, MVs in stored blood units could also be monitored longitudinally. Our results showed that MV counts increase over time and, thus, could serve as an effective metric of blood aging. Furthermore, our studies found that MVs have the capacity to generate oxidative stress and consume nitric oxide. By advancing our understanding of MV biology, we expect that the developed platform will lead to improved blood product quality and transfusion safety.

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Introduction: There is a growing debate surrounding the optimal ratio of FFP:RBC in massive transfusion protocols [MTP] for patients with massive traumatic hemorrhage. The discussion has evolved to include the time at which the appropriate ratio is achieved and its effect on mortality, both within and beyond 4 hours. This report aimed to describe the effect of attaining a high FFP:RBC ratio [FFP:RBC ≥ 1–1.5] [HMTP] within 4 hours on a trauma population receiving MTP. Methods: Data were obtained from the trauma registry of the Hamad Trauma Center in Doha, Qatar. All adult [≥ 18 years] patients with traumatic injury who received a massive blood transfusion [≥10 U of PRBC over the initial 24 hours post injury] from 1st January 2010 to 31st December 2012 were included. A low ratio MTP [LMTP] was FFP:RBC ≤ 1–1.5 at 4 hours post-injury. One MTP shipment was defined as infusion of ≥ 6 units of PRBC. Patients were followed up to 30 days, hospital discharge or death. Outcomes measured were mortality, post-shipment International Normalized Ratio [INR], multi-organ failure [MOF] and infectious complications. Data was analyzed using a Chi-square and Student’s T-test, p< 0.05 was considered significant. Results: There were 4864 trauma admissions during the study period, 77 [1.6%] patients met inclusion criteria. Admission hemoglobin level, arterial pH, INR, Injury Severity Score [ISS] and Revised Trauma Score [RTS] were similar between both groups. HMTP was associated with lower crude [41.9% v. 78.3%, p=0.001] and 24-hour mortality [3.2% v. 6.5%, p=0.468] when compared to LMTP. A similar association was noted for MOF [48.4% v 87.0%, p=0.001]. HMTP patients had significantly better mean INR values after the 2nd MTP shipment [1.1 v 1.5, p=0.032]. No significant differences were noted for the incidence of infectious complications between the 2 groups. Conclusions: These results suggest that the survival advantage of HMTP for trauma patients is realized early, within 4 hours post-injury. Our findings demonstrate that aggressive attainment of HMTP within 4 hours post injury can substantially improve coagulopathy, reduce mortality, and multi-organ failure rates.

Transfusion Practices and Infections At Four Level III Neonatal Intensive Care Units

IntroductionTransfusions of packed red blood cell (pRBC) units to infants in Neonatal Intensive Care Units (NICUs) may predispose neonates to healthcare-associated infections (HAIs). We compared neonatal pRBC transfusion practices at four NICUs (Morgan Stanley Children's Hospital of NewYork-Presbyterian, Columbia University Medical Center, Komansky Children's Hospital of Weill Cornell Medical Center, Christiana Care Health System, and Children's Hospital of Philadelphia). In addition, because prolonged refrigerator storage of pRBC may further predispose to HAIs, we tested the hypothesis that an increased mean RBC storage age was associated with a greater risk of infections. DesignThe interdisciplinary NICU Antimicrobial Prescribing (iNAP) study was conducted in four Level III NICUs from May 2009 to April 2012 to assess HAIs and improve antimicrobial prescribing in NICUs. Eligible infants were admitted <7 days of age and hospitalized ≥4 days. Demographic (e.g., sex, birth weight [BW]) and clinical data (e.g., HAIs and surgical procedures) were collected. HAI included culture negative sepsis defined by treating clinicians, necrotizing enterocolitis, or bacteremia treated for ≥ 4 days. pRBC transfusions were collected from blood bank records at each site. Descriptive statistics were performed using GraphPad Prism 6. ResultsAll sites used irradiated, leukoreduced, CMV negative pRBCs and practiced donor limitation. Blood bank preparation procedures were similar at all sites except that one site stored 3% of units in CPDA-1 in addition to units stored in Additive Solutions (AS), and another site irradiated the parent unit instead of the aliquot; the other sites irradiated the aliquot prior to release. During the study period, 6411 pRBC transfusions were administered to 1381 (21.5%) of 6184 enrolled infants. The transfusion rate was 12.6%, 37.3%, 16.7%, and 25.1% at sites 1-4, respectively. The rate of transfusion by normal BW (≥2500g), low BW (1500-2499g), very LBW (<1500g), and extremely LBW (<1000g) was 0.8, 0.4, 2.8, and 5.5 per patient, respectively. Transfused infants received an average of 4.7 transfusions (range 1-63; average of 3.5, 4.5, 4.5, and 6.0 transfusions at each respective site) with a mean donor exposure of 2.1 (range 1-23). Overall, 50% of pRBC transfusions occurred in the first 17 days of life and 34% occurred during the first week of life. Surgical and post-surgical transfusions accounted for 1389 (21.7%) of 6411 transfusions in 486 (35%) of 1381 transfused infants. Infants undergoing congenital diaphragmatic hernia repair required the most transfusions; 34 infants received 537 ECMO-related transfusions. The average storage age of the pRBC transfused was 16.1 days, but differed by site (12.5, 14.6, 16.7, 19.9 days for each site, respectively, p< 0.001 by Kruskal-Wallis test with Dunns Multiple Comparison Test) and by aliquot (1st-5th aliquot average age 12, 16, 19, 21, and 23 days, respectively). The average age of units transfused in infants without HAIs (n=5693) was 15.2 days; while the average age of units transfused in infants with HAIs (n=491) that developed after transfusion was 15.4 (p=0.04). An ecological study comparing all sites did not find a significant association between the average storage age of units transfused per site (excluding units transfused after onset of infection) and the proportion of neonates with HAIs at the site (R2=0.29; p=0.46; see Figure). [Display omitted] ConclusionsTo our knowledge, this is the largest cohort study of neonatal transfusion practices in Level III NICUs. Transfusion practices were similar at each site. The average storage age of transfused pRBC units varied among the four sites; however, the mean RBC storage age of RBCs transfused to patients with or without HAIs was not markedly different and hospitals with a longer mean storage age did not have a higher proportion of neonates with HAIs. Further analysis is needed to explore the relationship between pRBC storage and HAIs, while controlling for differences in patient characteristics. Disclosures:No relevant conflicts of interest to declare.

Bacteremia and Ventilator-Associated Pneumonia: A Marker for Contemporaneous Extra-Pulmonic Infection

Ventilator-associated pneumonia (VAP) is a well-known complication of mechanical ventilation in severely injured patients. A subset of patients with VAP develop an associated bacteremia (B-VAP), but the risk factors, microbiology, morbidity, and mortality in this group are not well described. The goal of this study was to examine the incidence, predictors, and outcome of B-VAP in adult trauma patients. We conducted a retrospective review of trauma patients who developed VAP or B-VAP from January 2007 to December 2009 at a single, university-affiliated medical center. Ventilator-associated pneumonia was defined as a clinician-documented instance of VAP together with confirmed positive respiratory cultures (bronchoalveolar lavage [BAL] fluid specimen with ≥10(4) colony forming units (CFU)/mL or tracheal aspirate with moderate-to-many organisms and polymorphonuclear neutrophils [PMN]). Bacteremia associated with VAP (B-VAP) was defined as the blood culture of an organism that matched the pulmonary pathogen in a case of VAP. We reviewed the demographic data, injury severity, transfusion data, and microbiology of patients who developed VAP and B-VAP. Outcome data included the number of days of care in the intensive care unit (ICU) and hospital length of stay, number of days of mechanical ventilation, and survival. A Student t-test, χ(2) test, or logistic regression was used as appropriate for data analysis. During the 36-mo period of the study, 4,018 adult patients were admitted to the hospital. Ventilator-associated pneumonia was diagnosed in 206 (5%) of these patients, and 26 of these latter patients (13%) had an associated bacteremia. The mean time from admission to the development of VAP was 5 d (95% CI 4.6-5.8). Patients who had B-VAP received significantly more units of red blood cell concentrates (PRBC) than those who did not have B-VAP (23 units vs. 9 units of PRBC, respectively, p<0.05). Patients with B-VAP also had higher rates of simultaneous non-pulmonary infections than those with VAP alone (69% vs. 38%, respectively), a greater number of days of mechanical ventilator support (24 d vs. 14 d, respectively, p<0.05), a greater number of days in the ICU (26 d vs. 17 d, respectively, p<0.05), and a greater hospital length of stay (50 d vs. 30 d, respectively, p<0.05). Patients with B-VAP showed a trend toward lower survival than those without B-VAP, but B-VAP was not an independent predictor of mortality. Trauma patients with B-VAP have a similar mortality but greater morbidity than those with VAP alone. The number of PRBC received is the most significant risk factor for developing B-VAP. More than two-thirds of patients with B-VAP have contemporaneous extra-pulmonic infections. Trauma patients with B-VAP may benefit from increased surveillance for additional concomitant infections and from more aggressive empiric antimicrobial coverage.

Cholecystoduodenal Fistula: A Rare Cause of Massive Upper GI Bleeding

Introduction: Rare complications of gallbladder disease include fistula formation, which can lead to further complications including pneumobilia, recurrent cholangitis, Mirizzi's, Bouveret's and gallstone ileus. Due to their rarity and the variability in which it manifests, a high degree of suspicion must be present at the start to reduce morbidity and mortality. We present a case of a cholecystoduodneal fistula that presented with massive upper GI bleeding. Case Report: A 75-year-old female patient with a history of myelodysplastic syndrome, coronary artery disease, GERD, urinary incontinence, and hypertension presented to the ED with weakness and vomiting for 1 day, with fevers and altered mental status. In the ED, the patient's vitals were temperature of 104 F, BP 94/52, and HR 102. Initial labs were significant for a white blood cell count of 24,700 and a Hb of 7.1 g/dL. In the ED, the patient experienced an episode of 200 mL of hematemesis and bright red blood per rectum. The patient was hypotensive to 80/40 with positive orthostatics. Intravenous fluids and 5 units of pRBC were given and her blood pressure improved to 115/59. An urgent EGD was performed and showed old blood in the fundus with no source for the bleeding. On day two, the patient had a recurrent episode of massive hematemesis. A repeat EGD showed bubbles emanating from the papilla, with normal gastric mucosa. A CT and MRCP were ordered showing pneumobilia with air extending to the duodenal bulb and the presence of multiple gallstones. The findings were compatible with persistent cholecystoduodenal fistula and a decompressed gallbladder. Blood cultures confirmed gram negative sepsis. The patient was treated with IV vancomycin and zosyn, improved clinically and discharged in stable condition with no more recurrent bleeding episodes. Despite recommendations, surgery was not performed. One year later, the patient returned to the ED with a several day history of weakness, decreased appetite, and weight loss. The patient's labs were significant for a white blood cell count of 15,630, an AST of 225 IU/L, ALT of 207 IU/L, and alkaline phosphatase of 697 IU/L. CT scan and MRI of abdomen and pelvis revealed an approximately 4.7-cm mass with biliary obstruction at the level of the porta hepatis, with obliteration of the previous choledocystoduodenal fistula. Biopsies confirmed gallbladder carcinoma, and a subsequent ERCP was performed with successful palliative biliary stenting. Discussion: In cases of unexplained massive upper GI Bleeding, careful inspection of the papilla may help rule out hemobilia. In this case, the diagnosis of hemobilia helped lead to the immediate treatment and management of a complicated cholecystoduodenal fistula. Disclosure - Dr. David Lee: CSL Behring: consultant: speaker bureau for a symposium.

Algorithm for Total Face and Multiorgan Procurement From a Brain-Dead Donor

Procurement of a facial vascularized composite allograft (VCA) should allow concurrent procurement of all solid organs and ensure their integrity. Because full facial procurement is time–intensive, “simultaneous–start” procurement could entail VCA ischemia over 12 h. We procured a total face osteomyocutaneous VCA from a brain–dead donor. Bedside tracheostomy and facial mask impression were performed preoperative day 1. Solid organ recovery included heart, lungs, liver, kidneys, and pancreas. Facial dissection time was 12 h over 15 h to diminish ischemia while awaiting recipient preparation. Solid organ recovery began at 13.5 h, during midfacial osteotomies, and concluded immediately after facial explantation. Facial thoracic and abdominal teams worked concurrently. Estimated blood loss was 1300 mL, requiring five units of pRBC and two units FFP. Urine output, MAP, pH and PaO2 remained normal. All organs had good postoperative function. We propose an algorithm that allows “face first, concurrent completion” recovery of a complex facial VCA by planning multiple pathways to expedient recovery of vital organs in the event of clinical instability. Beginning the recipient operation earlier may reduce waiting time due to extensive recipient scarring causing difficult dissection.

A Rare Case of Massive GI Bleeding due to Jejunal Diverticulosis: A Diagnostic Dilemma and the Importance of Endoscopic Timing and a Multidisciplinary Treatment Approach

Purpose: A 77-year-old man with no significant past medical history presented to an outside institution with worsening shortness of breath and melena. Hemoglobin 7.6 g/dL on admit. Transfused 3 units pRBC. Incremented to 9.2 g/dL but then fell to 7.2 g/dL the following day. EGD was normal. Colonoscopy with TI intubation showed pan-colonic diverticulosis without active bleeding. He continued to pass melena and require pRBC transfusions. Second EGD and small bowel (SB) enteroscopy performed showing diverticulum in proximal and mid-jejunum without bleeding. Abdominal CT angiography showed no active hemorrhage. He was transferred to our institution. Capsule endoscopy showed large jejunal diverticula with old blood. Balloon-assisted enteroscopy showed multiple large-sized diverticula in distal duodenum, proximal/mid-jejunum. Diverticula contained old blood/clots, but no actively bleeding lesion or recent stigmata seen. Surgical consultation obtained andopined since diverticula involved proximal duodenum and no active bleeding seen, any surgical intervention involving resection of this area would be technically difficult. Mesenteric angiogram showed no active bleeding. Patient required daily pRBC transfusion (total of 12 units since admission). Then began to pass maroon colored stools. Urgent SB enteroscopy with cap-fitted pediatric colonoscope performed. Fresh blood found in proximal jejunum. Large diverticulum with fresh clot/oozing blood identified (Fig 1) but no definitive target seen for endoscopic therapy. Tattoo marking applied. Patient taken for urgent surgery. Laparotomy showed jejunal tattoo with multiple surrounding large diverticuli. 40 cm segment containing tattooed jejunum resected (Fig 1) and fresh blood found inside. Pathology confirmed tattooed region of the diverticuli to be source of bleeding. No further episodes of rebleeding post-surgery or at 60 days. This case illustrates the importance of endoscopic timing in reaching the appropriate diagnosis and the multidisciplinary approach used in successful management. Evaluation of the SB during an episode of active bleeding, particularly in cases when EGD/Colonoscopy are non-diagnostic, can be the key to finding the correct diagnosis. In cases where the etiology of intestinal bleeding is unclear or other diagnostic testing is inconclusive, more urgent endoscopy at the time of active bleeding may have a role in establishing the diagnosis and providing treatment.Figure 1

Laboratory analysis of canine packed red blood cells—effects of collection and processing on haemolysis, haemoglobin concentration, haematocrit and blood culture

The aim of this study was to evaluate the relationship between blood collection and processing techniques and the quality of canine packed red blood cell (pRBC) units. This prospective study analysed 235 canine blood donations, followed by processing and evaluation of pRBC units. The need for sedation, number of venepunctures, whole blood volume, time to processing and time to analysis were registered, and five different centrifugation protocols were performed. The final pRBC volume, haematocrit, total haemoglobin concentration, haemolysis and bacterial contamination of pRBC units were evaluated. Obtained results were within the reference range of human blood banks' guidelines. One unit presented a positive bacteriologic analysis. No significant differences in haemolysis were detected when factors related to sedation, blood collection, time to processing or centrifugation protocols were studied. Significantly higher haematocrit values were detected in units centrifuged in a faster and longer programme (3,500×g, 15 min). There was a direct increase of haemolysis with longer time spent between centrifugation and analysis. This study demonstrates that haemolysis is significantly higher when analyses post centrifugations take 48–72 h to be performed than in short periods.

Initial assessment on the impact of crystalloids versus colloids during damage control resuscitation

BackgroundHigh ratios of fresh frozen plasma:packed red blood cells in damage control resuscitation (DCR) are associated with increased survival. The impact of volume and type of resuscitative fluid used during high ratio transfusion has not been analyzed. We hypothesize a difference in outcomes based on the type and quantity of resuscitative fluid used in patients that received high ratio DCR. MethodsA matched case control study of patients who received transfusions of ≥ four units of PRBC during damage control surgery over 4 1/2 y, was conducted at a Level I Trauma Center. All patients received a high ratio DCR, >1:2 of fresh frozen plasma:packed red blood cells. Demographics and outcomes of the type and quantity of resuscitative fluids used in combination with high ratio DCR were compared and analyzed. A Kaplan-Meier survival analysis was computed among four groups: colloid (median quantity = 1.0 L), <3 L crystalloid, 3–6 L crystalloid, and >6 L crystalloid. ResultsThere were 56 patients included in the analysis (28 in the crystalloid group and 28 in the colloid group). Demographics were statistically similar. Intraoperative median units of PRBC: crystalloid versus colloid groups was 13 (IQR 8-21) versus 16 (IQR 12–19), P = 0.135; median units of FFP: 12 (IQR 7–18) versus 12 (IQR 10–18), P = 0.440. OR for 10-d mortality in the crystalloid group was 8.41 [95% CI 1.65–42.76 (P = 0.01)]. Kaplan-Meier survival analysis demonstrated lowest mortality in the colloid group and higher mortality with increasing amounts of crystalloid (P = 0.029). ConclusionsDuring high ratio DCR, resuscitation with higher volumes of crystalloids was associated with an overall decreased survival, whereas low volumes of colloid use were associated with increased survival. In order to improve outcomes without diluting the survival benefit of hemostatic resuscitation, guidelines should focus on effective low volume resuscitation when high ratio DCR is used. A multi-institutional analysis is needed in order to validate these results.