Clinical Outcomes, Blood Utilization, and Ethical Considerations for Pediatric Patients in a Bloodless Medicine and Surgery Program.

BACKGROUND: Pediatric patients requesting bloodless care represent a challenging clinical situation, as parents cannot legally refuse lifesaving or optimal interventions for their children. Here, we report clinical outcomes for the largest series of pediatric inpatients requesting bloodless care and also discuss the ethical considerations. METHODS: We performed a single-institution retrospective cohort study assessing 196 pediatric inpatients (<18 years of age) who requested bloodless care between June 2012 and June 2016. Patient characteristics, transfusion rates, and clinical outcomes were compared between pediatric patients receiving bloodless care and those receiving standard care (including transfusions if considered necessary by the clinical team) (n = 37,271). Families were informed that all available measures would be undertaken to avoid blood transfusions, although we were legally obligated to transfuse blood if the child's life was threatened. The primary outcome was composite morbidity or mortality. Secondary outcomes included percentage of patients transfused, individual morbid events, length of stay, total hospital charges, and total costs. Subgroup analyses were performed after stratification into medical and surgical patients. RESULTS: Of the 196 pediatric patients that requested bloodless care, 6.1% (n = 12) received an allogeneic blood component, compared to 9.1% (n = 3392) for standard care patients ( P = .14). The most common indications for transfusion were perioperative bleeding and anemia of prematurity. None of the transfusions were administered under a court order. Overall, pediatric patients receiving bloodless care exhibited lower rates of composite morbidity compared to patients receiving standard care (2.6% vs 6.2%; P = .035). There were no deaths in the bloodless cohort. Individual morbid events, length of stay, and total hospital charges/costs were not significantly different between the 2 groups. After multivariable analysis, bloodless care was not associated with a significant difference in composite morbidity or mortality (odds ratio [OR], 0.37; 95% confidence interval [CI], 0.12-1.11; P = .077). CONCLUSIONS: Pediatric patients receiving bloodless care exhibited similar clinical outcomes compared to patients receiving standard care, although larger studies with adequate power are needed to confirm this finding. There were no mortalities among the pediatric bloodless cohort. Although a subset of our pediatric bloodless patients received an allogeneic transfusion, no patients required a court order. When delivered in a collaborative and patient-centered manner, blood transfusions can be safely limited among pediatric patients.

Methods of Bloodless Care, Clinical Outcomes, and Costs for Adult Patients Who Decline Allogeneic Transfusions.

BACKGROUND: Providing bloodless medical care for patients who wish to avoid allogeneic transfusion can be challenging; however, previous studies have demonstrated favorable outcomes when appropriate methods are used. Here, we report one of the largest series of patients receiving bloodless care, along with the methods used to provide such care, and the resulting outcomes. METHODS: In a retrospective cohort study, 1111 adult inpatients (age ≥18 years) at a single institution who declined allogeneic transfusion for religious or personal reasons between June 2012 and June 2016 were included, and the patient blood management methods are described. Patient characteristics, laboratory data, and transfusion rates, as well as clinical outcomes (morbidity, mortality, and length of stay) were compared to all other patients in the hospital who received standard care, including transfusions if needed (n = 137,009). Medical and surgical patients were analyzed as subgroups. The primary outcome was composite morbidity (any morbid event: infectious, thrombotic, ischemic, renal, or respiratory). Secondary outcomes included individual morbid events, in-hospital mortality, length of stay, total hospital charges, and costs. RESULTS: The bloodless cohort had more females and a lower case mix index, but more preadmission comorbidities. Mean nadir hemoglobin during hospitalization was lower in the bloodless (9.7 ± 2.6 g/dL) compared to the standard care (10.1 ± 2.4 g/dL) group (P < .0001). Composite morbidity occurred in 14.4% vs 16.0% (P = .16) of the bloodless and standard care patients, respectively. Length of stay and in-hospital mortality were similar between the bloodless and standard care patients. After Bonferroni adjustment for multiple comparisons, hospital-acquired infection occurred less frequently in the bloodless compared to the standard care cohort (4.3% vs 8.3%) (P < .0001) in the medical patient subgroup, but not in the surgical subgroup. After propensity score adjustment in a multivariable model and adjustment for multiple comparisons, bloodless care was associated with less risk of hospital-acquired infection (OR, 0.56; 95% CI, 0.35-0.83; P = .0074) in the medical subgroup, but not in the surgical subgroup. Median total hospital charges (by 8.5%; P = .0017) and costs (by 8.7%; P = .0001) were lower in the bloodless compared to the standard care cohort, when all patients were included. CONCLUSIONS: Overall, adult patients receiving bloodless care had similar clinical outcomes compared to patients receiving standard care. Medical (but not surgical) bloodless patients may be at less risk for hospital-acquired infection compared to those receiving standard care. Bloodless care is cost-effective and should be considered as high-value practice.

Blood Transfusion is Associated with Increased Perioperative Morbidity and Adverse Oncologic Outcomes in Bladder Cancer Patients Receiving Neoadjuvant Chemotherapy and Radical Cystectomy.

PURPOSE: Perioperative blood transfusion (PBT) has been inconsistently associated with adverse outcomes. Bladder cancer patients are unique as they frequently undergo neoadjuvant chemotherapy (NAC) with resulting immunosuppression, which may be exacerbated by transfusion-related immunomodulation. We examined the effect of leukoreduced PBT on oncologic outcomes and perioperative morbidity in radical cystectomy (RC) patients who received NAC, quantifying exposure with a novel dose-index variable. METHODS: The Johns Hopkins Radical Cystectomy database was queried for patients who had undergone NAC followed by RC from 2010 to 2013. Overall, 119 patients had available PBT and survival data. A multivariable Cox model evaluated risk factors, including pathologic stage, Charlson Comorbidity Index, age, race, year of surgery, surgical margin status, PBT, and preoperative hemoglobin for bladder cancer-specific survival (CSS) and overall survival (OS). Logistic regression models determined factors that were independently associated with perioperative morbidity. RESULTS: Median follow-up was 7.8 months (range 0.2-41.8), and during follow-up there were 25 deaths and 21 cancer deaths. PBT significantly predicted OS (hazard ratio [HR] 1.26, 95 % confidence interval [CI] 1.07-1.49; p = 0.005), CSS (HR 1.32, 95 % CI 1.11-1.57; p = 0.002), and morbidity (odds ratio [OR] 1.67, 95 % CI 1.26-2.21; p = 0.004) in univariate analyses. In multivariable models, PBT was significantly associated with morbidity (OR 1.77, 95 % CI 1.30-2.39; p = 0.0002), but not OS or CSS. Intraoperative transfusion was associated with decreased OS and CSS, and increased morbidity, whereas postoperative transfusion was only associated with increased morbidity. CONCLUSIONS: Intraoperative blood transfusion was associated with increased perioperative morbidity and worsened OS and CSS in patients undergoing RC who had NAC. Although PBT may be life-saving in certain patients, a restrictive transfusion strategy may improve outcomes.

Red blood cells stored 35 days or more are associated with adverse outcomes in high-risk patients.

BACKGROUND: Clinical trials have shown that longer red blood cell (RBC) storage duration does not worsen outcomes; however, these studies included few RBCs near the end of the 42-day storage limit. We tested the hypothesis that these "oldest" RBCs are associated with adverse outcomes. STUDY DESIGN AND METHODS: In a retrospective study, 28,247 transfused patients given 129,483 RBC units were assessed. Morbidity, mortality, and length of stay (LOS) were compared in patients transfused exclusively with RBCs stored not more than 21 days versus patients transfused exclusively with RBCs stored 28 days or more and patients transfused exclusively with RBCs stored 35 days or more. RESULTS: After risk adjustment, ≥35-day RBCs were associated with increased morbidity (adjusted odds ratio [adjOR], 1.19; 95% confidence interval [CI], 1.07-1.32; p = 0.002), but ≥28-day RBCs were not (adjOR, 1.06; 95% CI, 0.97-1.15; p = 0.2). Neither ≥35-day nor ≥28-day RBCs were associated with increased mortality. In critically ill patients, ≥35-day RBCs were associated with increased morbidity (adjOR, 1.25; 95% CI, 1.08-1.44; p = 0.002) and mortality (adjOR, 1.38; 95% CI, 1.08-1.74; p = 0.009), but ≥28-day RBCs were associated with neither. In older patients, ≥35-day RBCs were associated with increased morbidity (adjOR, 1.22; 95% CI, 1.04-1.42; p = 0.01), but not mortality (adjOR, 1.28; 95% CI, 0.96-1.71; p = 0.1), and ≥28-day RBCs were associated with neither. LOS was increased for both ≥28- and ≥35-day RBCs for all patients and the critically ill and older subgroups. CONCLUSIONS: RBCs transfused in the last 7 days of their 42-day storage limit may be associated with adverse clinical outcomes in high-risk patients.

Oxidative stress and rheologic properties of stored red blood cells before and after transfusion to surgical patients.

BACKGROUND: The loss of structural and functional integrity of red blood cells (RBCs) during storage, collectively referred to as "storage lesion," has been implicated in reduced oxygen delivery after transfusion. RBCs are highly susceptible to oxidative damage from generation of reactive oxygen species by autoxidation of hemoglobin. Therefore, we examined whether increased oxidative stress (OS) in stored RBCs is associated with impaired cell membrane deformability before or after transfusion. STUDY DESIGN AND METHODS: Thirty-four patients undergoing multilevel spine fusion surgery were enrolled. OS in RBCs was assessed by the presence of fluorescent heme degradation products and methemoglobin, which were measured with fluorimetric and spectrophotometric methods, respectively. Deformability and aggregation were determined by ektacytometry in stored RBCs, autologous salvaged RBCs, and posttransfusion blood samples. RESULTS: OS in stored RBCs was significantly increased with longer storage (R = 0.54, p = 0.032) and significantly higher than that in fresh RBCs (9.1 ± 1.3 fluorescent arbitrary units vs. 7.7 ± 0.9 fluorescent arbitrary units, p < 0.001). Deformability decreased (R = -0.60, p = 0.009) with increasing storage duration. OS was elevated (p < 0.05) and deformability was decreased (p < 0.05) in postoperative blood from patients who had undergone moderate (≥4 RBC units) but not minimal or no transfusion. Neither the decrease in deformability of RBCs nor the aggregation changes were correlated with OS. CONCLUSIONS: Although stored RBCs show signs of increased OS and loss of cell membrane deformability, these changes were not directly correlated and were only evident after moderate but not lower dose transfusion in postoperative surgical patients. These findings suggest that factors other than OS may contribute to impaired rheology with stored RBCs in the clinical setting.

Morbidity and Mortality after High-dose Transfusion.

BACKGROUND: It is well recognized that increased transfusion volumes are associated with increased morbidity and mortality, but dose-response relations between high- and very-high-dose transfusion and clinical outcomes have not been described previously. In this study, the authors assessed (1) the dose-response relation over a wide range of transfusion volumes for morbidity and mortality and (2) other clinical predictors of adverse outcomes. METHODS: The authors retrospectively analyzed electronic medical records for 272,592 medical and surgical patients (excluding those with hematologic malignancies), 3,523 of whom received transfusion (10 or greater erythrocyte units throughout the hospital stay), to create dose-response curves for transfusion volumes and in-hospital morbidity and mortality. Prehospital comorbidities were assessed in a risk-adjusted manner to identify the correlation with clinical outcomes. RESULTS: For patients receiving high- or very-high-dose transfusion, infections and thrombotic events were four to five times more prevalent than renal, respiratory, and ischemic events. Mortality increased linearly over the entire dose range, with a 10% increase for each 10 units of erythrocytes transfused and 50% mortality after 50 erythrocyte units. Independent predictors of mortality were transfusion dose (odds ratio [OR], 1.037; 95% CI, 1.029 to 1.044), the Charlson comorbidity index (OR, 1.209; 95% CI, 1.141 to 1.276), and a history of congestive heart failure (OR, 1.482; 95% CI, 1.062 to 2.063). CONCLUSIONS: Patients receiving high- or very-high-dose transfusion are at especially high risk for hospital-acquired infections and thrombotic events. Mortality increased linearly over the entire dose range and exceeded 50% after 50 erythrocyte units.

The Impact of Surgery and Stored Red Blood Cell Transfusions on Nitric Oxide Homeostasis.

BACKGROUND: Cell-free hemoglobin (Hb) forms in stored red blood cells (RBCs) as a result of hemolysis. Studies suggest that this cell-free Hb may decrease nitric oxide (NO) bioavailability, potentially leading to endothelial dysfunction, vascular injury, and multiorgan dysfunction after transfusion. We tested the hypothesis that moderate doses of stored RBC transfusions increase cell-free Hb and decrease NO availability in postoperative surgical patients. METHODS: Twenty-six patients undergoing multilevel spine fusion surgery were studied. We compared those who received no stored RBCs (n = 9) with those who received moderate amounts (6.1 ± 3.0 units) of stored RBCs over 3 perioperative days (n = 17). Percent hemolysis (cell-free Hb), RBC-NO (heme-NO), and plasma nitrite and nitrate were measured in samples from the stored RBC bags and from patients' blood, before and after surgery. RESULTS: Posttransfusion hemolysis was increased approximately 3.5-fold over preoperative levels (P = 0.0002) in blood samples collected immediately after surgery but not on postoperative days 1 to 3. Decreases in both heme-NO (by approximately 50%) and plasma nitrite (by approximately 40%) occurred postoperatively, both in nontransfused patients (P = 0.036 and P = 0.026, respectively) and transfused patients (P = 0.0068 and P = 0.003, respectively) and returned to preoperative baseline levels by postoperative day 2 or 3. Postoperative plasma nitrite and nitrate were decreased significantly in both groups, and this change was slower to return to baseline in the transfused patients, suggesting that blood loss and hemodilution from crystalloid administration contribute to this finding. CONCLUSIONS: The decrease in NO metabolites occurred irrespective of stored RBC transfusions, suggesting this decrease may be related to blood loss during surgery and hemodilution rather than to scavenging of NO or inhibition of NO synthesis by stored RBC transfusions.

2,3-Diphosphoglycerate Concentrations in Autologous Salvaged Versus Stored Red Blood Cells and in Surgical Patients After Transfusion.

BACKGROUND: Stored red blood cells (RBCs) are deficient in 2,3-diphosphoglycerate (2,3-DPG), but it is unclear how autologous salvaged blood (ASB) compares with stored blood and how rapidly 2,3-DPG levels return to normal after transfusion. Therefore, we compared levels of 2,3-DPG in stored versus ASB RBCs and in patients' blood after transfusion. METHODS: Twenty-four patients undergoing multilevel spine fusion surgery were enrolled. We measured 2,3-DPG and the oxyhemoglobin dissociation curve (P50) in samples taken from the ASB and stored blood bags before transfusion and in blood samples drawn from patients before and after transfusion. RESULTS: The mean storage duration for stored RBCs was 24 ± 8 days. Compared with fresh RBCs, stored RBCs had decreased 2,3-DPG levels (by approximately 90%; P < 0.0001) and a decreased P50 (by approximately 30%; P < 0.0001). However, ASB RBCs did not exhibit these changes. The mean 2,3-DPG concentration decreased by approximately 20% (P < 0.05) in postoperative blood sampled from patients who received 1 to 3 stored RBC units and by approximately 30% (P < 0.01) in those who received ≥4 stored RBC units. 2,3-DPG was unchanged in patients who received no stored blood or ASB alone. After surgery, 2,3-DPG levels recovered gradually over 3 postoperative days in patients who received stored RBCs. CONCLUSIONS: Stored RBCs, but not ASB RBCs, have decreased levels of 2,3-DPG and a left-shift in the oxyhemoglobin dissociation curve. Postoperatively, 2,3-DPG levels remain below preoperative baseline levels for up to 3 postoperative days in patients who receive stored RBCs but are unchanged in those who receive only ASB RBCs.

Efficacy of education followed by computerized provider order entry with clinician decision support to reduce red blood cell utilization.

BACKGROUND: Two necessary components of a patient blood management program are education regarding evidence-based transfusion guidelines and computerized provider order entry (CPOE) with clinician decision support (CDS). This study examines changes in red blood cell (RBC) utilization associated with each of these two interventions. STUDY DESIGN AND METHODS: We reviewed 5 years of blood utilization data (2009-2013) for 70,118 surgical patients from 10 different specialty services at a tertiary care academic medical center. Three distinct periods were compared: 1) before blood management, 2) education alone, and 3) education plus CPOE. Changes in RBC unit utilization were assessed over the three periods stratified by surgical service. Cost savings were estimated based on RBC acquisition costs. RESULTS: For all surgical services combined, RBC utilization decreased by 16.4% with education alone (p = 0.001) and then changed very little (2.5% increase) after subsequent addition of CPOE (p = 0.64). When we compared the period of education plus CPOE to the pre-blood management period, the overall decrease was 14.3% (p = 0.008; 2102 fewer RBC units/year, or a cost avoidance of $462,440/year). Services with the highest massive transfusion rates (≥10 RBC units) exhibited the least reduction in RBC utilization. CONCLUSIONS: Adding CPOE with CDS after a successful education effort to promote evidence-based transfusion practice did not further reduce RBC utilization. These findings suggest that education is an important and effective component of a patient blood management program and that CPOE algorithms may serve to maintain compliance with evidence-based transfusion guidelines.

Compliance with Surgical Care Improvement Project for Body Temperature Management (SCIP Inf-10) Is Associated with Improved Clinical Outcomes.

BACKGROUND: In an effort to measure and improve the quality of perioperative care, the Surgical Care Improvement Project (SCIP) was introduced in 2003. The SCIP guidelines are evidence-based process measures designed to reduce preventable morbidity, but it remains to be determined whether SCIP-measure compliance is associated with improved outcomes. METHODS: The authors retrospectively analyzed the electronic medical record data from 45,304 inpatients at a single institution to assess whether compliance with SCIP Inf-10 (body temperature management) was associated with a reduced incidence of morbidity and mortality. The primary outcomes were hospital-acquired infection and ischemic cardiovascular events. Secondary outcomes were mortality and hospital length of stay. RESULTS: Body temperature on admission to the postoperative care unit was higher in the SCIP-compliant group (36.6° ± 0.5°C; n = 44,064) compared with the SCIP-noncompliant group (35.5° ± 0.5°C; n = 1,240) (P < 0.0001). SCIP compliance was associated with improved outcomes in both nonadjusted and risk-adjusted analyses. SCIP compliance was associated with a reduced incidence of hospital-acquired infection (3,312 [7.5%] vs.160 [12.9%] events; risk-adjusted odds ratio [OR], 0.68; 95% CI, 0.54 to 0.85), ischemic cardiovascular events (602 [1.4%] vs. 38 [3.1%] events; risk-adjusted OR, 0.60; 95% CI, 0.41 to 0.92), and mortality (617 [1.4%] vs. 60 [4.8%] events; risk-adjusted OR, 0.41; 95% CI, 0.29 to 0.58). Median (interquartile range) hospital length of stay was also decreased: 4 (2 to 8) versus 5 (2 to 14) days; P < 0.0001. CONCLUSION: Compliance with SCIP Inf-10 body temperature management guidelines during surgery is associated with improved clinical outcomes and can be used as a quality measure.

Early ambulation after colorectal oncologic resection with perineal reconstruction is safe and effective.

BACKGROUND: Post-operative bedrest is common following perineal reconstruction despite little supporting data. We sought to determine the safety of early ambulation following colorectal oncologic resection and flap-based perineal reconstruction. METHODS: A retrospective cohort study was conducted with two cohorts: standard bedrest (BC) and early ambulation (EAC). Ambulation capacity was objectively assessed. Regression analysis was performed to determine the effects of ambulation timing on 60-day reoperations or readmissions and other surgical outcomes. RESULTS: There were 57 participants. Those in the EAC were significantly more ambulatory on post-operative days one through three (p < 0.0001). There was no significant difference in 60-day reoperations (25% BC versus 9% EAC, p = 0.14) or readmissions (33% BC versus 15% EAC, p = 0.12). Early ambulation significantly reduced minor complication rates (38% BC versus 9% EAC, p = 0.02). CONCLUSIONS: Early ambulation following perineal reconstruction is safe and may potentially decrease wound complications. SUMMARY AND KEYWORDS: Institution of early ambulation protocols is rapidly becoming the standard of care for many oncological surgery patients. In cases requiring perineal reconstruction with vascularized flaps, however, there is no data to uproot the historical practice of mandatory bedrest. Our study demonstrates that the benefits of early ambulation are attainable in these patients without compromising reconstructive outcomes.