Peak Bilirubin Research Articles

Potential protective effects of bilirubin following the treatment of neonatal hypoxic-ischemic encephalopathy with hypothermia therapy.

Background: Therapeutic hypothermia (TH) is the standard therapy for hypoxic-ischemic encephalopathy (HIE) and is associated with a wide range of physiological changes. Objective: We re-evaluated the effects of HIE and TH on bilirubin measurements following HIE in a center involved in the China cooling randomized controlled trial (RCT). Methods: Serial serum bilirubin concentrations measured during the first week of life were compared among the HIE + NT (normothermia) group, HIE + TH treatment group and control group (without HIE). Survivors of HIE were followed and assessed at approximately 2 years of age, and the results were correlated with peak bilirubin levels during the first week of life. Results: One hundred and thirty-eight infants were available for analysis. Significantly lower bilirubin levels were recorded in the HIE + NT group than in the controls (P<0.05). Significant differences were not observed among the patients in the HIE + NT group (mild to severe) or between the HIE + TH group and the HIE + NT group at any time point (P>0.05). The peak serum bilirubin concentrations recorded at 96 h of age showed a good correlation with the results of the Bayley Scales of Infant and Toddler Development, third edition (BSID-III) (P=0.02). Conclusion: Bilirubin potentially exerts a neuroprotective effect during the first week of life, and low temperature does not affect the possible antioxidant function of bilirubin during TH following HIE.

Hyperbilirubinaemia after cardiac surgery: the point of no return.

AimsThe occurrence of hyperbilirubinaemia after heart surgery using cardiopulmonary bypass or post‐operative heart failure is fairly common. We investigated the incidence, predictive value, and post‐operative outcome of hyperbilirubinaemia after cardiac surgery in an effort to identify potential risk factors and significance on clinical outcome.Methods and resultsBetween 2006 and 2016, 1272 (10.1%) out of 12 556 patients developed hyperbilirubinaemia, defined as bilirubin concentration >3 mg/dL, during post‐operative course at our institution. All patients who were operated using cardiopulmonary bypass were included. Hepatic dysfunction was diagnosed preoperatively in 200 patients (15.7%), whereas mean model of end‐stage liver disease score was 11.22 ± 4.99. Early mortality was 17.4% with age [hazard ratio (HR) 1.019, 95% confidence interval (CI) 1.008–1.029; P = 0.001], diabetes (HR 1.115, CI 1.020–1.220; P = 0.017), and emergent procedures (HR 1.315, CI 1.012–1.710) as multivariate predictors. Post‐operative predictors were low‐output syndrome (HR 3.193, 95% CI 2.495–4.086; P < 0.001), blood transfusion (HR 1.0, CI 1.0–1.0; P < 0.001), and time to peak bilirubin (HR 1.1, CI 1.0–1.1; P < 0.001). We found an increased correlation with mortality at 3.5 post‐operative day as well as an optimal cut‐off value for bilirubin of 5.35 mg/dL. A maximum bilirubin of 25.5 mg/dL was associated with 99% mortality. Survival analysis showed significantly decreased survival for patients who developed late, rather than early, hyperbilirubinaemia.ConclusionsPost‐operative hyperbilirubinaemia is a prevalent threat after cardiopulmonary bypass, associated with high early mortality. The timing and amount of peak bilirubin concentration are linked to the underlying pathology and are predictors of post‐operative outcome. Patients with late development of steep hyperbilirubinaemia warrant meticulous post‐operative care optimizing cardiac and end organ functions before reaching the point of no return.

3. Live Liver Donors: Is Left Still Right?

Background and Aims: Conventional wisdom dictates that a larger hepatectomy, is more complication prone. Consequently, with the donor safety as paramount, the transplant community has intuitively been proponents of left lobe donation in live donor liver transplantation (LDLT), thereby satisfying the tenet of double equipoise. More recently some data suggest that this may not always be the case, especially in established centres. We aim to compare right and left lobe donor outcomes in LDLT from a centre with cumulative experience. Methods: Review of a prospectively collected database of right and left lobe liver donors operated between Aug 2009 and July 2017 was performed. Their preoperative demographics, operative and postoperative outcomes were compared. Results: Of 904 liver transplantations, 458 were right lobe donors {379 without middle hepatic vein (MHV), 79 with MHV} and 58 left lobe donors. There was a significant difference in GRWR and functional liver remnant between the right and left lobe donors (1.27±0.45 vs 1.03±0.28 p = 0.004, & 63.2±7.9 vs 37.7±16.3 respectively). The end portal pressure (7 vs 8 mmHg p= <0.001), peak bilirubin (1.6±0.8 vs 2.9±1.5 p=<0.001), and Day 5 bilirubin (0.8±0.3 vs 1.4±0.9 p= <0.001) were significantly higher in right lobe donors. There was no difference in blood loss, duration of surgery or peak lactate between the groups. Complications (20.7% vs 26.5% p = 0.43), including serious complications (Clavien-Dindo >III) (6.9% vs 7.7% p = 0.94), duration of ICU and hospital stay were comparable between the groups. Subgroup analysis between left lobe and right lobe with and without MHV donor were also comparable. Conclusions: Though biochemical differences exist between the groups, no difference in outcomes was noted. Despite larger liver mass loss in right lobe donors, a strict protocoled approach to donor selection leads to comparable outcomes between left lobe and right lobe donations. The authors have none to declare.

Design of a prospective multicenter randomized controlled trial evaluating the effects of gastric lavage on coffee-ground emesis in neonates: study protocol.

ABSTRACTNeonates who swallow a considerable amount of maternal blood may exhibit vomiting and suckling disorder during the first few days of the postnatal period. Some clinicians treat these neonates with gastric lavage (GL) to prevent vomiting and the establishment of enteral feeding empirically, but there was no study assessing the effect of GL for neonates with coffee-ground emesis. We designed a multicenter randomized controlled trial to evaluate the efficacy and safety of GL in neonates with coffee-ground emesis. Vigorous neonates with birth weight ranging from 2500 g to 3999 g and gestational age between 37w0d and 41w6d who presented with coffee-ground emesis on more than twice and diagnosed as false melena, were divided into two groups using computerized randomization. We defined feeding intolerance (FI) as (1) ≥2 vomiting episodes in 4h or ≥3 episodes in 24h and/or (2) feeding failure on at least two occasions because of retching or poor sucking. Primary outcome is percentage of infants who present FI within 24 hours from admission. We also assessed the residual volumes, number of vomiting episodes, percentage of weight reduction at postnatal day 4, rates of body weight gain at 1 month of age, and peak serum total bilirubin value before discharge. To our knowledge, this is the first study to evaluate the safety and efficacy of GL for neonates with coffee-ground emesis. This trial is registered at UMIN Clinical Trials Registry as UMIN000026483.

Delayed clamping vs milking of umbilical cord in preterm infants: a randomized controlled trial

It has been established that delayed umbilical cord clamping in preterm infants results in improvement in neonatal anemia, need for transfusion, incidence of necrotizing enterocolitis, and intraventricular hemorrhage by increasing neonatal circulating blood volume. However, the effects of umbilical cord milking as an alternative to delayed clamping in preterm infants are unclear. The primary objective of this study was to compare the effect of delayed clamping vs milking of the umbilical cord on the initial hematocrit concentration in preterm births (23-34 weeks gestation). In addition, we sought to compare the effects of delayed clamping vs milking on the incidences of intraventricular hemorrhage, necrotizing enterocolitis, and need for transfusion (secondary objectives). The study was an unblinded randomized controlled trial of singleton preterm infants who were born 23 weeks 0 days to 34 weeks 6 days gestation and were assigned to 1 of 2 controlled study groups: delayed cord clamping for 60 seconds or milking of the cord towards the infant 4 times before clamping. Randomization occurred via block randomization with an allocation ratio of 1 to 1. The patients' third stage of delivery was standardized for route of delivery and randomization arm. All comparisons were preformed with an intent-to-treat analysis approach. The study was powered at 80% with a probability value of .05 for the primary outcome measure of a hematocrit difference of 3% between the 2 groups. Of the 204 randomized patients, 104 were assigned to the delayed subgroup, and 100 were assigned to the milking subgroup. There were no significant differences in baseline maternal characteristics noted between groups. Though there was not any statistically significant difference in neonatal outcomes between the cord clamping and milking groups, the occurrences of transfusion (15.5% vs 9.1%; P=.24), necrotizing enterocolitis (5.8% vs 3.0%; P=.49), and intraventricular hemorrhage (15.5% vs 10.1%; P=.35) were all lower in the milking group. The milking group had higher initial hematocrit concentration compared with the delayed clamping group, although this was not significant (51.8 [6.2%] vs 49.9 [7.7%]; P=.07]. Peak bilirubin levels and need for phototherapy were similar between groups. This study demonstrates that milking the umbilical cord may be an acceptable alternative to delayed cord clamping because there were similar effects on neonatal hematocrit concentrations and the need for neonatal transfusions and no increased risk for complications or neonatal morbidity. The present data support the concept that milking of the umbilical cord may offer an efficient and timely method of providing increased blood volume to the infant.

Cut umbilical cord milking: an ineffective method of placental transfusion in preterm infants?

Objective: To determine if umbilical cord milking performed on a cut umbilical cord segment increased the hemoglobin/hematocrit, with a reduction in the incidence of intraventricular hemorrhage, need for blood transfusions, and pressor requirement in infants with <35-weeks gestation.Study design: This was a single center, observational study in the NICU. One-hundred-six neonates received cut umbilical cord milking and two hundred ninety seven served as historical controls.Result: There were no statistically significant differences between the two groups in hemoglobin/hematocrit, peak bilirubin values, the incidence of intraventricular hemorrhage, need for blood transfusions, and the use of pressors.Conclusion: This is the first study using the cut umbilical cord milking technique that includes neonates with <35-weeks gestation. The procedure is safe but did not result in an increase in hemoglobin/hematocrit, nor did it reduce the incidence of intraventricular hemorrhage, need for blood transfusions, and pressor use.

Expanded Makuuchi's criteria using estimated indocyanine green clearance rate of future liver remnant as a safety limit for maximum extent of liver resection

BackgroundRecent advances in liver surgery have dramatically improved the safety of hepatectomy for hepatocellular carcinoma (HCC). The aim of this study was to compare outcomes for patients fulfilling an extended criteria vs. those fulfilling the conventional criteria based on the bilirubin and indocyanine green (ICG) clearance (Makuuchi's criteria). MethodsThe short term outcomes of patients undergoing hepatectomy for HCC and who fulfilled the expanded criteria (ICG clearance of future remnant liver [ICG-Krem] ≥ 0.05 estimated using 3-D volumetry) were retrospectively reviewed and were compared between those fulfilling the conventional criteria. Postoperative hepatic insufficiency (PHI) was defined as peak total bilirubin >7 mg/dL. ResultsA total of 323 patients undergoing resection of whom 269 (83%) met conventional criteria (In-M) and 54 (17%) extended criteria (Ex-M). The overall morbidity rates were not significantly different. The incidence of PHI was 0.37% in In-M and 3.7% in Ex-M (P = 0.074), with no liver-related deaths. When the ICG-Krem ≥ 0.05 criterion was included, major hepatectomy was performed in 24 patients (41%) in Ex-M with no significant increase in major morbidity (13%), PHI(3.3%), or liver-related death (0%) compared with minor hepatectomy (n = 30) in Ex-M(10%, 4% and 0%, respectively). ConclusionsObjective criteria using ICG clearance rate and 3-D volumetry may offer opportunities for safe surgical resection in selected patients exceeding the conventional criteria.

Daily Dosing of Busulfan in Allogeneic Hematopoietic Cell Transplantation Reduces Costs with Equivalent or Superior Outcomes

Introduction Higher costs of healthcare in the United States have not consistently been associated with improved health outcomes or quality of care, necessitating interventions to improve value-based care. We identified busulfan dosing frequency during preparation for allogeneic hematopoietic cell transplantation (HCT) as a potential target for optimization. To improve patient convenience and decrease the cost of the busulfan preparative regimen, our institution changed busulfan dose frequency from every 6 hours (q6h) to once-daily dosing (q24h). We examined differences in costs and patient outcomes between these two protocols. Methods In June 2017, our institution transitioned from q6h to q24h busulfan dosing. We compared patients who received inpatient busulfan and cyclophosphamide (BU/CY) preparative regimens for allogeneic HCT from one year prior to one year after implementation of the dosing change. The primary outcomes were difference in cost, day +90 mortality, and day +90 relapse. Secondary outcomes included hospital length of stay and peak serum total bilirubin level. Two-sided T-test and Chi-squared analyses were conducted to compare these outcomes between the two treatment groups. Results There were a total of 104 patients (age 49 ± 11 years, 55% male) who received the preparatory BU/CY regimen before allogeneic HCT from June 1, 2016 to June 1, 2018 (Table 1). Of these, 43% (N=45) received q24h busulfan. There were fewer men in the q24h busulfan cohort (42%) compared to the q6h busulfan cohort (64%, p=0.024), but there were no other significant differences between the treatment groups (Table 1). There was an average cost savings of $12,554.34 per patient who received q24h busulfan compared to q6h busulfan. There was a significantly lower day +90 mortality in the q24h busulfan cohort compared to the q6h busulfan cohort (0% vs 10%, p=0.028, Table 2). There were no differences in relapse at day +90 or hospital length of stay. Conclusions Busulfan dosing during preparation for allogeneic HCT represents a target for improving value-based care in the inpatient setting. At our institution, patients who received a q24h busulfan dosing regimen had similar or superior outcomes with those receiving q6h dosing, with a reduction in annual hospital drug charges of approximately $500,000. This retrospective study serves as a proof of concept for the adoption of q24h busulfan dosing as a standard of care to improve value-based care in allogeneic HCT.

Prevalence and Impact of Reformed and De Novo Anti-HLA Donor-Specific Antibodies in Liver Transplantation

IntroductionThe prevalence and impact of pre-existing and de novo anti-HLA donor-specific antibodies (DSAs) after orthotopic liver transplantation (OLT) is still controversial. We investigated the prevalence of DSAs and their implication in the development of allograft dysfunction after OLT. Patients and MethodsA total of 65 liver transplant patients were tested for anti-HLA antibodies, with single antigen bead technology, before, 1, 3, 6, and 12 months after transplantation, and thereafter annually, along with other risk factors. Sixteen out of 65 patients (24.6%) had circulating pre-existing anti-HLA antibodies, and 4 of them (25%) had DSAs. All patients positive for anti-HLA antibodies (100%) presented allograft dysfunction. Fourteen out of 65 patients (21.5%) had circulating de novo DSAs, and 12 out of 14 (85.7%) presented allograft dysfunction. The investigated risk factors for allograft dysfunction were: recipient and donor age, time on the waiting list, cold ischemia time, cytomegalovirus infection, immunosuppression regimen, de novo DSAs, Model for End-Stage Liver Disease, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase (GGT), direct bilirubin and total bilirubin peak post-transplant, and alkaline phosphatase. The multivariate analysis showed that de novo DSAs and time on the waiting list were independent risk factors for allograft dysfunction. ConclusionOur results show that de novo DSAs are an independent risk factor for allograft dysfunction, along with time on the waiting list.

Living donor liver transplantation in South Africa: the donor experience

Living donor liver transplantation (LDLT) plays a crucial role in liver transplant programmes, particularly in regions with a scarcity of deceased donor organs and especially for paediatric recipients. LDLT is a complex and demanding procedure which places a healthy living donor in harm's way. Donor safety is therefore the overriding concern. This study aimed to report our standardised approach to the evaluation, technical aspects and outcomes of LDLT donor hepatectomy at Wits Donald Gordon Medical Centre. The study population consisted of all patients undergoing LDLT donor hepatectomy since the inception of the programme in March 2013 until 2018. Sixty five living donor hepatectomies were performed. Primary outcome measures included donor demographics, operative time, peak bilirubin, aspartate and alanine transaminase levels postoperatively, length of hospital stay and postoperative complications using the Clavien-Dindo classification. The majority of the donors were female, most were parents with mothers being the donor almost 85% of the time. The median operative time was 374 minutes with a downward trend over time as experience was gained. The median length of hospital stay was 7 days. There was no mortality and the complication rate was 30% with the majority being minor (Grade 1). Living donor liver transplant from adult-to-child has been successfully initiated in South Africa. Living donor hepatectomy can be safely performed with acceptable outcomes for the donor. Wait-list mortality however remains unacceptably high. Expansion of LDLT as well as real change in deceased donor policy is required to address this issue.

Interstage assessment of remnant liver function in ALPPS using hepatobiliary scintigraphy: introduction of the HIBA index

Background: ALPPS remains controversial given the high rate of liver-related mortality after stage-2. Hepatobiliary scintigraphy (HBS) combined with single photon emission computed tomography (SPECT) could accurately estimates future liver remnant (FLR) function. Our aim was to evaluate interstage liver function in ALPPS using HBS and whether this may help to predict posthepatectomy liver failure (PHLF). Methods: Between 2011 and 2016, 20/39 patients (51.3%) underwent SPECT-HBS before ALPPS stage-2 for primary (n=3) or secondary liver tumors (n=17). PHLF was defined by the International Study Group of Liver Surgery (ISGLS) criteria, 50-50 criteria or peak bilirubin >7 mg/dl. Grade A PHLF was excluded, as it requires no change in clinical management. Different HBS parameters were evaluated. Results: Interstagely, 3 HBS parameters differed significantly between patients with (n=4) and without PHLF (n=16) after stage-2. Among these, the HIBA-index best predicted PHLF, with a cutoff value of 15%. The risk of PHLF in patients with HIBA-index<15% was 80%, whereas no patient withHIBA-index ≥15% developed PHLF Conclusion: Interstage HBS could help to predict clinically significant PHLF after ALPPS stage-2. An HIBA-index cutoff of 15% seemed to give the best diagnostic performance. While further studies are needed to confirm our findings, the routine application of this non-invasive low-cost exam could facilitate decision-making in institutions performing ALPPS

Risk factors of liver dysfunction for donor after extended right lobe graft donation

Introduction: Extended right lobe graft are often used in living donor liver transplantation(LDLT), in the donors with sufficient future liver remnant (FLR) volume. The aim of this study is to review retrospectively and to find risk factors of liver dysfunction for donor after extended right lobe graft donation. Method: From November 2005 to May 2018, a total of 52 living liver donors who underwent extended right lobectomy were included in this study.The subjects were divided into 2 groups.The hazard group was defined as the donors showing at least one of the following criteria:(1)postoperative serum peak bilirubin > 3.0mg/dL; (2) postoperative peak INR > 2.0, (3) posthepatectomy liver failure(PHLF) grade B or C of International Study Group of Liver Surgery(ISGLS), (4) ascites > 500cc on or after pod 5. Other donors with no criteria mentioned above were included in the safety group. Result: In hazard group, they had smaller volume of left lateral section(LLS) compared to safety group and the ratio of left liver volume(LLV) and left lateral section volume(LLSV) to total liver volume (TLV) in hazard group were smaller than in safety group. The mean and median values of the ratio of LLV to TLV(LLV/TLV); 38%, and the ratio of LLSV to TLV(LLSV/TLV); 20%, were used as the cut-off value. In hazard group, there were more patients whose LLV/TLV was less than 38% and whose LLSV/TLV was less than 20%. Using each cut-off values regarded as risk factors, three groups were categorized. This indicates that donors with smaller LLV/TLV or/and LLSV/TLV are more prone to liver dysfunction. Conclusion: The extent of donor hepatectomy must be contemplated based on a careful preoperative evaluation, including the volumetry. In this study, the LLV/TLV less than 38% and/or LLSV/TLV less than 20% were the major risk factors for postoperative liver dysfunction.

Randomised Controlled Trial of Pringle Maneouvre versus Portal Vein Clamping in Patients undergoing Liver Resection for Colorectal Liver Metastasis – A Pilot Study

Introduction: Pringle manoeuvre (PM) is commonly used to prevent blood loss during liver resection. It has been suggested that isolated control of the hepatic portal vein and not clamping the hepatic artery, could potentially reduce the ischaemic reperfusion injury (IRI). We carried out a pilot randomised controlled trial (RCT) to compare the outcomes of portal vein clamping (PVC) versus PM. Method: Eighty patients were recruited in this prospective, parallel group, single blind, pilot study. The first 20 patients were part of a learning curve for PVC. The subsequent 60 patients were randomised 1:1 to PVC or PM procedure. The outcomes from main trial [PVC 30 vs. PM 30 patients] are reported. Result: There was no difference between the two groups in terms of mean age, male gender, mean BMI and major resections. There was no difference in total mean operative time (128.4 vs. 132.8 mins; P=0.711) or the total clamping time (36.3 vs. 34.9 mins; P=0.742) between PVC and PM groups. The total transection time and the estimated blood loss were higher in the PVC group, but this was not statistically significant (53.6 vs. 49.6 mins; P=0.619 and 436.7 vs. 311.6 mls; P=0.060). There were no intra-operative blood transfusions. There was no difference in post-operative peak bilirubin and peak ALT (28.8 vs. 26.7 mmol/L; P=0.706 and 327.0 vs. 336.3 U/L; P=0.919). The Clavien-Dindo complications were grade 2 (5 vs. 8), grade 3a (1 vs. 1) and grade 3b (0 vs. 1) in the PVC versus PM groups respectively. There were no 30-day mortality in both groups. Conclusion: The operating times between the two groups were similar though there was a trend towards more blood loss in the PVC group. There was no difference in IRI in this small pilot RCT. A UK wide consensus is being sought to proceed to a larger multi-centre trial.

Clinical features and prognosis of DIHBS (diffuse intrahepatic biliary stricture) after adult ABO-incompatible living donor liver transplantation

Introduction: Despite the advancement in desensitization protocol, diffuse intrahepatic biliary stricture (DIHBS), an attenuated form of antibody mediated rejection (AMR), remains an unresolved problem. As a high-volume LT center, we retrospectively review clinical outcome and prognosis of recipients who developed DIHBS after ABOi LDLT. Method: From November 2008 to December 2017, total of 497 cases of ABO incompatible LDLT were performed at Asan Medical Center. Among them, twenty-four patients (4.83%) developed DIHBS. Retrospective review of medical records of these patients was carried out. Result: Median time of diagnosis for DIHBS after ABOi LDLT was 2.8 months. In patients with DIHBS, the 3-year patient survival rate was 69.9%. Causes of patient death in nine patients were recurrent HCC in four patients, biliary sepsis in two patients, graft failure (not associated with AMR) in one patient, post-operative bleeding after re-LT in one patient, and pneumonia in one patient. Nine patients (37.5%) received re-transplantation. Graft survival rates at 3-year was 40.6%. Both patient survival and graft survival rates were significantly lower than ABOi LDLT recipients without DIHBS (both p< 0.001). Between ABOi LDLT patients with or without DIHBS, there were no significant differences in pre-operative isoagglutinin (IA) titer, post-operative peak bilirubin, AST, ALT, IA titer, and pre- and post-operative frequency of total plasma exchange (TPE). Among the other fifteen patients who are alive, five patients got re-LT, three patients presented mild graft dysfunction with well-functioning PTBD, three patients showed resolution of DIHBS and removed biliary drainage, and four patients demonstrate normal graft function with well-maintained biliary drainage. Conclusion: In this study, DIHBS developed usually before 3 months after ABOi LDLT. DIHBS significantly affects short and long-term outcome in ABOi LDLT. In patients who demonstrated DIHBS, over half of the patient progress to graft failure and need re-LT.

Correlation of Direct Antiglobulin Test Strength in Umbilical Cord Blood and Hyperbilirubinemia in ABO Incompatible Neonates with Two Methods

Introduction: The direct antiglobulin test (DAT) detects the presence of IgG and/or C3 on the red blood cell (RBC) membrane and is used to diagnose autoimmune hemolytic anemias as well as hemolytic disease of the fetus and newborn (HDFN). A positive DAT in a neonate occurs when maternal IgG crosses the placenta and binds to fetal RBCs, which may lead to hemolysis and clinical manifestations of HDFN such as hyperbilirubinemia. Historically, DATs in umbilical cord blood samples were performed manually. We have recently switched to using the Ortho Vision Analyzer (gel technology) for this purpose in our institution, and noticed a trend toward stronger positive reactions. The purpose of this study was to compare the DAT results obtained with the conventional tube method and the gel method, and their association with hyperbilirubinemia and/or the need for phototherapy in the neonates tested.Methods: We retrospectively reviewed all cord DAT results of infants born between January 2016 and June 2018. We included all tests of neonates of blood group A or B born to blood group O mothers who had a positive DAT and performed a retrospective chart review to collect the following data: DAT strength, gestational age, birth weight, hematocrit, blood type, initial and peak serum total bilirubin levels, use of phototherapy, antibody screening results, and transfusion history. Neonates whose mothers had a positive antibody screen were excluded from the analysis.Results: During the study-period, 100 ABO-incompatible neonates with a positive DAT were tested by the tube and gel methods (50 with each methodology) and met our inclusion criteria. Their demographic information and laboratory results, including the strength of the positive DAT are in Table 1. There was a clear trend toward stronger DAT results since the gel methodology was introduced; the most common result in the Ortho Vision Analyzer was 1+ positive (52%), and 40% of neonates had a 2+ positive result. The latter was only seen in 2% with the tube method. Furthermore, although there were no significant differences in any demographic or laboratory parameters between the two groups of neonates, an increased percentage of those tested with the new methodology (23/50 or 46%) received phototherapy compared with 14/50 (28%) of those tested manually (Figure 1).Conclusions: We found that the Ortho Vision Analyzer produced stronger DAT results compared to the tube method without evidence of increased hemolysis. It is essential that Transfusion Medicine physicians communicate the change in methodology to neonatologists to make them aware of the reason for the stronger DAT results in order to avoid unnecessary phototherapy. DisclosuresNo relevant conflicts of interest to declare.

Impact of Donor Pre-Procurement Cardiac Arrest (PPCA) on Clinical Outcomes in Liver Transplantation

BackgroundTransplantation of liver grafts from deceased donors who experienced cardiac arrest prior to liver procurement is now common. This single-center study analyzed the impact of pre-donation arrest time on clinical outcomes in liver transplantation.Material/MethodsRecords of all orthotopic liver transplants performed at a single center over a 15-year period were reviewed. Donor records were reviewed and total arrest time was calculated as cumulative minutes. Post-transplant liver graft function was assessed using laboratory values. Graft survival was assessed with Cox regression analysis.ResultsRecords for 1830 deceased donor transplants were reviewed, and 521 donors experienced pre-procurement cardiac arrest (28%). Median arrest time was 21 min (mean 25 min, range 1–120 min). After transplant, the peak alanine aminotransferase and bilirubin levels for liver grafts from donors with arrest were lower compared to those for donors without arrest (p<0.001). Early allograft dysfunction occurred in 25% (arrest) and 28% (no arrest) of patients (p=0.22). There were no differences in risk of early graft loss (3% vs. 3%, p=0.84), length of hospital stay (10 vs. 10 days, p=0.76), and 1-year graft survival (89% vs. 89%, p=0.94). Cox regression analysis comparing 4 groups (no arrest, <20 min, 20–40 min, and >40 min arrest) demonstrated no statistically significant difference in survival at 10 years. Subgroup analysis of 93 donation after cardiac death grafts showed no significant difference for these same outcomes.ConclusionsThese results support the use of select deceased liver donors who experience pre-donation cardiac arrest. Pre-donation arrest may be associated with less early allograft dysfunction, but had no impact on long-term clinical outcomes. The results for donation after cardiac death donors were similar.

Case 3: Premature Infant with Anemia and High-Output Cardiac Failure

A female singleton is delivered at 30 6/7 weeks’ gestational age via cesarean for preterm labor and breech presentation. The mother is a 37-year-old grand multipara in her 10th pregnancy. The pregnancy is notable for severe fetal anemia, high-output cardiac failure with normal cardiac anatomy, polyhydramnios, and a placental chorioangioma diagnosed at 26 weeks of gestation. Evaluation for congenital infections is negative. At 25 and 28 weeks’ gestation, the fetus had received in utero red blood cell transfusions for severe fetal anemia. At birth, the infant has respiratory depression requiring intubation and ventilation. Apgar scores are 7, 6, and 8 at 1, 5, and 10 minutes, respectively, and her birthweight is 1,416 g. The neonate is noted to have a protuberant abdomen with significant hepatosplenomegaly, diffuse subcutaneous edema, petechiae, and ecchymoses. The infant requires significant ventilator support for the first few weeks after birth. Chest radiography shows no evidence of pleural or pericardial effusion. Echocardiography shows normal cardiac segmental anatomy with significant biventricular hypertrophy, though blood pressure is maintained. Significant anemia, thrombocytopenia, and coagulopathy are noted over the first days after birth, for which the newborn requires multiple blood products. Profound jaundice necessitates multiple double-volume exchange transfusions. Thrombocytopenia and coagulopathy gradually improve over the first week after birth. However, the infant develops significant cholestasis, reaching a peak direct bilirubin of 12.5 mg/dL (213.8 μmol/L) at 2 weeks of age. The unique constellation of findings in this case, anemia, thrombocytopenia, high-output failure, and cholestasis, presented a broad differential diagnosis. The differential included congenital heart disease and vascular malformations, infectious etiologies, metabolic and genetic disorders, and various renal, hepatic, gastrointestinal, and hematologic pathologies. Sepsis evaluation was performed on admission and …

Delayed Cord Clamping Increased the Need for Phototherapy Treatment in Infants With AB0 Alloimmunization Born by Cesarean Section: A Retrospective Study.

Objective: To compare the effect of Delayed Cord Clamping (DCC) to Immediate Cord Clamping (ICC) on phototherapy treatment in a cohort of cesarean-delivered newborns with AB0-alloimmunization.Study Design: In a retrospective cohort study neonates with Gestational Age (GA) ≥ 35 weeks and diagnosed with AB0-alloimmunization before implementation of DCC (ICC group) were compared with neonates born after implementation (DCC group). The primary outcome was the need for phototherapy. Secondary outcomes included hospital stay, readmission rate, need for extra intravenous fluids, maximum bilirubin concentration, and hours of life at bilirubin peak. We used regression models to adjust for weight loss, type of feeding, birth weight, and gestational age.Results: In total 336 neonates were included, of which 192 neonates in the ICC group and 144 in the DCC group. There were no differences in basic characteristics between the two groups except for birth weight (ICC 3193 ± 468 g vs. DCC 3053 ± 446 g, p = 0.01) and GA (ICC 38.2 ± 1 weeks of GA, vs. DCC 37.9 ± 1 weeks of GA; p = 0.01). When adjusted for confounding factors, after implementation of DCC, significantly more infants with AB0 alloimmunization needed phototherapy (22.4% vs. 36.8%, RR 1.61 CI: 1.15–2.28; p = 0.006; Number Needed to Harm 7), needed to stay longer in hospital (20.3% vs. 30.5%, RR 1.53 CI: 1.05–2.23; p = 0.03). The maximum bilirubin was higher (11.4 ± 4.0 mg/dl vs. 12.9 ± 3.5 mg/dl, p < 0.001) and occurred later [74 (67–92) hours vs. 84 (70–103) hours; p = 0.04]. There was no difference in the need for intravenous fluids (1.6% vs. 4.9%; not significant) and readmissions (1.6% vs. 3.5%; not significant).Conclusion: Infants with AB0 alloimmunization needed more often phototherapy and were admitted longer after implementation of DCC policy. Further studies are needed to see whether the benefit of DCC outweighs the increased morbidity, admission days, and related hospital costs.

Comparison of University of Wisconsin (UW) and Histidine-Tryptophan-Ketoglutarate (HTK) Solutions in Pediatric Liver Transplantation

Introduction University of Wisconsin (UW) and Histidine-tryptophan-ketoglutarate (HTK) solutions are the two primary organ preservation solutions used in the United States. Multiple studies have been published comparing the two solutions in adult liver transplantation, most showing similar long-term results. This study analyzes the two solutions in pediatric liver transplantation at a single center. Methods All pediatric liver transplants performed at our center from 2001-2017 were reviewed. Recipients were grouped based on the type of preservation solution used. Outcome measures included early graft function, as well as graft and patient survival. Early graft function was assessed by comparing 1-, 7-, 14-, and 30-day aspartate and alanine aminotransferases, and total bilirubin levels. Survival outcomes were compared between the two groups at 7-, 90- and 365-days post-transplant. Primary use of HTK began at our center as of May 2003. Operative technique, immunosuppressive protocols, and donor acceptance criteria remained uniform among participating surgeons throughout the study period. Results There were 104 pediatric liver transplants with complete data during the study period, 75 preserved with HTK (68%) and 29 with UW (26%). The two groups had similar recipient and donor demographics. The locally procured organs were more likely to be preserved with HTK as that was the preferred solutions of the local center. Cold and warm ischemia times were similar between the groups. Peak alanine-aminotransferase (ALT) post-transplant was higher in the UW group at both peak and post-transplant day 3. The peak total bilirubin levels were similar. Graft survival was statistically similar in the UW and HTK groups at 7-, 90- and 365-days post-transplant.Conclusions Use of HTK has been recommended in pediatric liver transplantation because of its low viscosity which may improve blood clearance from the small pediatric vessels. This study provides evidence that use of HTK in pediatric liver transplantation is safe, and use of this solution results in outcomes which are similar to those seen for UW.

Interstage Assessment of Remnant Liver Function in ALPPS Using Hepatobiliary Scintigraphy: Prediction of Posthepatectomy Liver Failure and Introduction of the HIBA Index.

The aim of this study was to evaluate interstage liver function in associating liver partition and portal vein occlusion for staged hepatectomy (ALPPS) using hepatobiliary scintigraphy (HBS) and whether this may help to predict posthepatectomy liver failure (PHLF). ALPPS remains controversial given the high rate of liver-related mortality after stage 2. HBS combined with single photon emission computed tomography (SPECT) accurately estimates future liver remnant function and may be useful to predict PHLF. Between 2011 and 2016, 20 of 39 patients (51.3%) underwent SPECT-HBS before ALPPS stage 2 for primary (n = 3) or secondary liver tumors (n = 17) at the Hospital Italiano de Buenos Aires (HIBA). PHLF was defined by the International Study Group of Liver Surgery criteria, 50-50 criteria, or peak bilirubin >7 mg/dL. Grade A PHLF was excluded, as it requires no change in clinical management. Receiver-operating characteristic curves were used to determine cutoff for HBS parameters. Interstagely, 3 HBS parameters differed significantly between patients with (n = 4) and without PHLF (n = 16) after stage 2. Among these, the HIBA-index best predicted PHLF, with a cutoff value of 15%. The risk of PHLF in patients with cutoff <15% was 80%, whereas no patient with cutoff ≥15% developed PHLF. Interstage HBS could help to predict clinically significant PHLF after ALPPS stage 2. An HIBA-index cutoff of 15% seemed to give the best diagnostic performance. Although further studies are needed to confirm our findings, the routine application of this noninvasive low-cost examination could facilitate decision-making in institutions performing ALPPS.