Prophylactic Perioperative Terlipressin Therapy for Preventing Acute Kidney Injury in Living Donor Liver Transplant Recipients: A Systematic Review and Meta-Analysis
Journal of clinical and experimental hepatology. 2022;12(2):417-427
BACKGROUND Acute kidney injury (AKI) is common in the perioperative transplant period and is associated with poor outcomes. Few studies reported a reduction in AKI incidence with terlipressin therapy by counteracting the hemodynamic alterations occurring during liver transplantation. However, the effect of terlipressin on posttransplant outcomes has not been systematically reviewed. METHODS A comprehensive search of electronic databases was performed. Studies reporting the use of terlipressin in the perioperative period of living donor liver transplantation were included. We expressed the dichotomous outcomes as risk ratio (RR, 95% confidence interval [CI]) using the random effects model. The primary aim was to assess the posttransplant risk of AKI. The secondary aims were to assess the need for renal replacement therapy (RRT), vasopressors, effect on hemodynamics, blood loss during surgery, hospital and intensive care unit (ICU) stay, and in-hospital mortality. RESULTS A total of nine studies reporting 711 patients (309 patients in the terlipressin group and 402 in the control group) were included for analysis. Terlipressin was administered for a mean duration of 53.44 ± 28.61 h postsurgery. The risk of AKI was lower with terlipressin (0.6 [95% CI, 0.44-0.8]; P = 0.001). However, on sensitivity analysis including only four randomized controlled trials (I(2) = 0; P = 0.54), the risk of AKI was similar in both the groups (0.7 [0.43-1.09]; P = 0.11). The need for RRT was similar in both the groups (0.75 [0.35-1.56]; P = 0.44). Terlipressin therapy reduced the need for another vasopressor (0.34 [0.25-0.47]; P < 0.001) with a concomitant rise in mean arterial pressure and systemic vascular resistance by 3.2 mm Hg (1.64-4.7; P < 0.001) and 77.64 dyne cm(-1).sec(-5) (21.27-134; P = 0.007), respectively. Blood loss, duration of hospital/ICU stay, and mortality were similar in both groups. CONCLUSIONS Perioperative terlipressin therapy has no clinically relevant benefit.
Effect of washed versus unwashed red blood cells on transfusion-related immune responses in preterm newborns
Clinical & translational immunology. 2022;11(3):e1377
OBJECTIVES Transfusion with washed packed red blood cells (PRBCs) may be associated with reduced transfusion-related pro-inflammatory cytokine production. This may be because of alterations in recipient immune responses. METHODS This randomised trial evaluated the effect of transfusion with washed compared with unwashed PRBCs on pro-inflammatory cytokines and endothelial activation in 154 preterm newborns born before 29 weeks' gestation. Changes in plasma cytokines and measures of endothelial activation in recipient blood were analysed after each of the first three transfusions. RESULTS By the third transfusion, infants receiving unwashed blood had an increase in IL-17A (P = 0.04) and TNF (P = 0.007), whereas infants receiving washed blood had reductions in IL-17A (P = 0.013), TNF (P = 0.048), IL-6 (P = 0.001), IL-8 (P = 0.037), IL-12 (P = 0.001) and IFN-γ (P = 0.001). The magnitude of the post-transfusion increase in cytokines did not change between the first and third transfusions in the unwashed group but decreased in the washed group for IL-12 (P = 0.001), IL-17A (P = 0.01) and TNF (P = 0.03), with the difference between the groups reaching significance by the third transfusion (P < 0.001 for each cytokine). CONCLUSION The pro-inflammatory immune response to transfusion in preterm infants can be modified when PRBCs are washed prior to transfusion. Further studies are required to determine whether the use of washed PRBCs for neonatal transfusion translates into reduced morbidity and mortality.
Pre-term newborns (n= 154).
Washed leucodepleted packed red blood cells (PRBCs), (n= 77).
Standard unwashed leucodepleted PRBCs (n= 77).
Changes in plasma cytokines and measures of endothelial activation in recipient blood were analysed after each of the first three transfusions. By the third transfusion, patients receiving unwashed blood had an increase in IL-17A and TNF, whereas patients receiving washed blood had reductions in IL-17A, TNF, IL-6, IL-8, IL-12 and IFN-γ. The magnitude of the post-transfusion increase in cytokines did not change between the first and third transfusions in the unwashed group but decreased in the washed group for IL-12, IL-17A and TNF, with the difference between the groups reaching significance by the third transfusion for each cytokine.
Coagulation in pediatric extracorporeal membrane oxygenation: A systematic review of studies shows lack of standardized reporting
Research and practice in thrombosis and haemostasis. 2022;6(2):e12687
OBJECTIVES Extracorporeal membrane oxygenation (ECMO) involves complex coagulation management and frequent hemostatic complications. ECMO practice between centers is variable. To compare results between coagulation studies, standardized definitions and clear documentation of ECMO practice is essential. We assessed how study population, outcome definitions, and ECMO-, coagulation-, and transfusion-related parameters were described in pediatric ECMO studies. DATA SOURCES Embase, Medline, Web of Science, Cochrane Library and Google Scholar. STUDY SELECTION English original studies of pediatric ECMO patients describing hemostatic tests or outcome. DATA EXTRACTION Eligibility was assessed following PRISMA guidelines. Study population, outcome and ECMO-, coagulation, and transfusion parameters were summarized. DATA SYNTHESIS A total of 107 of 1312 records were included. Study population parameters most frequently included (gestational) age (79%), gender (60%), and (birth) weight (59%). Outcomes, including definitions of bleeding (29%), thrombosis (15%), and survival (43%), were described using various definitions. Description of pump type, oxygenator and cannulation mode occurred in 49%, 45%, and 36% of studies, respectively. The main coagulation test (53%), its reference ranges (49%), and frequency of testing (24%) were the most prevalent reported coagulation parameters. The transfusion thresholds for platelets, red blood cells, and fibrinogen were described in 27%, 18%, and 18% of studies, respectively. CONCLUSIONS This systematic review demonstrates a widespread lack of detail or standardization of several parameters in coagulation research of pediatric ECMO patients. We suggest several parameters that might be included in future coagulation studies. We encourage the ECMO community to adopt and refine this list of parameters and to use standardized definitions in future research.
Association Between Type of Fluid Received Prior to Enrollment, Type of Admission, and Effect of Balanced Crystalloid in Critically Ill Adults: A Secondary Exploratory Analysis of the Balanced Solutions in Intensive Care (BaSICS) Study
American journal of respiratory and critical care medicine. 2022
RATIONALE The effects of balanced crystalloid vs saline on clinical outcomes for intensive care unit patients may be modified by the type of fluid patients received for initial resuscitation and by the type of admission. OBJECTIVES To assess whether results of a randomized controlled trial could be affected by fluid use before enrollment and admission type. METHODS Secondary post-hoc analysis of the Balanced Solution in Intensive Care (BaSICS) trial, which compared a balanced solution to 0.9% saline in intensive care unit. Patients were categorized according to fluid use in the 24 hours before enrollment in four groups: balanced solutions only; 0.9% saline only; mix both, and no fluid before enrollment, and according to admission type. The association between 90-day mortality and the randomization group was assessed using an hierarchical logistic Bayesian model. MEASUREMENTS AND MAIN RESULTS 10,520 patients were included. There was a low probability that the balanced solution was associated with improved 90-day mortality in the whole trial population (odds ratio, 0.95; 89% credible intervals [CrI], 0.66-1.51; probability of benefit, 0.58); however, probability of benefit was high for patients that received only balanced solutions before enrollment (regardless of admission type, odds ratio, 0.78, 89% CrI, 0.56,1.03; probability of benefit, 0.92), mostly due to a benefit in unplanned admissions due to sepsis (odd ratio, 0.70; 89% CrI, 0.50-0.97; probability of benefit, 0.96) and planned admissions (odds ratio, 0.79; 89% CrI, 0.65-0.97; 0.97 probability of benefit, 0.97). CONCLUSION There is a high probability that balanced solution use in the ICU reduces 90-day mortality in patients that exclusively received balanced fluids before trial enrollment.
Efficacy and safety of nafamostat mesilate anticoagulation in blood purification treatment of critically ill patients: a systematic review and meta-analysis
Renal failure. 2022;44(1):1263-1279
BACKGROUND Nafamostat mesilate (NM), a broad-spectrum and potent serine protease inhibitor, can be used as an anticoagulant during extracorporeal circulation, as well as a promising drug effective against coronavirus disease 2019 (COVID-19). We conducted a systematic meta-analysis to evaluate the safety and efficacy of NM administration in critically ill patients who underwent blood purification therapy (BPT). METHODS The Cochrane Library, Web of Science and PubMed were comprehensively searched from inception to August 20, 2021, for potential studies. RESULTS Four randomized controlled trials (RCTs) and seven observational studies with 2723 patients met the inclusion criteria. The meta-analysis demonstrated that conventional therapy (CT) significantly increased hospital mortality compared with NM administration (RR = 1.25, p = 0.0007). In subgroup analyses, the in-hospital mortality of the NM group was significantly lower than that of the anticoagulant-free (NA) group (RR = 1.31, p = 0.002). The CT interventions markedly elevated the risk ratio of bleeding complications by 45% (RR = 1.45, p = 0.010) compared with NM interventions. In another subgroup analysis, NM used exhibited a significantly lower risk of bleeding complications than those of the low-molecular-weight heparin (LMWH) used (RR = 4.58, p = 0.020). The filter lifespan was decreased significantly (MD = -10.59, p < 0.0001) in the NA groups compared with the NM groups. Due to the poor quality of the included RCTs, these results should be interpreted with caution. CONCLUSION Given the better survival outcomes, lower risk of bleeding, NM anticoagulation seems to be a safe and efficient approach for BPT patients and could yield a favorable filter lifespan. More multi-center RCTs with large samples are required for further validation of this study.
A Novel Risk Prediction Model for Severe Acute Kidney Injury in Intensive Care Unit Patients Receiving Fluid Resuscitation
Frontiers in cardiovascular medicine. 2022;9:840611
BACKGROUND To develop a risk prediction model for the occurrence of severe acute kidney injury (AKI) in intensive care unit (ICU) patients receiving fluid resuscitation. METHODS We conducted a secondary analysis of the Crystalloid vs. Hydroxyethyl Starch Trial (CHEST) trial, a blinded randomized controlled trial that enrolled ICU patients who received intravenous fluid resuscitation. The primary outcome was the first event in a composite outcome of doubling of serum creatinine and/or treatment with renal replacement treatment (RRT) within 28 days of randomization. The final model developed using multivariable logistic regression with backwards elimination was validated internally and then translated into a predictive equation. RESULTS Six thousand seven hundred twenty-seven ICU participants were studied, among whom 745 developed the study outcome. The final model having six variables, including admission diagnosis of sepsis, illness severity score, mechanical ventilation, tachycardia, baseline estimated glomerular filtration rate and emergency admission. The model had good discrimination (c-statistic = 0.72, 95% confidence interval 0.697-0.736) and calibration (Hosmer-Lemeshow test, χ(2) = 14.4, p = 0.07) for the composite outcome, with a c-statistic after internal bootstrapping validation of 0.72, which revealed a low degree of over-fitting. The positive predictive value and negative predictive value were 58.8 and 89.1%, respectively. The decision curve analysis indicates a net benefit in prediction of severe AKI using the model across a range of threshold probabilities between 5 and 35%. CONCLUSIONS Our model, using readily available clinical variables to identify ICU patients at high risk of severe AKI achieved good predictive performance in a clinically relevant population.
Fresh frozen plasma transfusion in the neonatal population: A systematic review
Blood reviews. 2022;:100951
Although fresh frozen plasma (FFP) transfusions are common practice in neonatology, robust evidence on their use is lacking. The aim of this study was to systematically review the literature for data on the practice of FFP transfusions in neonates and their association with neonatal morbidity and mortality. The authors identified 40 studies, which met the inclusion criteria for this review. It was demonstrated that the practice of FFP transfusions significantly varies throughout the world. The majority of FFP transfusions are administered "prophylactically", without evidence of active bleeding. Although FFP transfusions may restore coagulation tests results, they do not alter the clinical outcome of the neonates. Reactions following transfusions are probably underestimated in neonates, often undiagnosed and thus, underreported. High quality RCTs aiming to evaluate the effectiveness of FFP in specific clinical conditions are urgently needed, as they could change long-standing FFP transfusion practices, and help reduce neonatal morbidity and mortality.
Effects of Freshly Irradiated vs Irradiated and Stored Red Blood Cell Transfusion on Cerebral Oxygenation in Preterm Infants: A Randomized Clinical Trial
JAMA pediatrics. 2022;:e220152
IMPORTANCE Gamma irradiation of leukoreduced red blood cells (RBCs) prevents transfusion-associated graft-vs-host disease but also exacerbates storage lesion formation in RBCs. It is unknown whether freshly irradiated RBCs are more efficacious than irradiated and stored RBCs in preterm infants with high transfusion requirements. OBJECTIVE To examine whether transfusion of freshly irradiated vs irradiated and stored RBC components improves cerebral oxygen delivery in preterm infants with anemia. DESIGN, SETTING, AND PARTICIPANTS This single-center, double-blinded, proof-of-concept randomized clinical trial was conducted at the neonatal intensive care unit of Wellington Regional Hospital in Wellington, New Zealand, between December 1, 2017, and November 30, 2018. Participants were preterm infants (<34 weeks' gestation at birth) who were at least 14 days of age and had anemia. Participants underwent nonurgent transfusions, and these episodes were randomized to the intervention group (in which the infants received a transfusion of RBCs that were freshly irradiated on the day of transfusion) or control group (in which the infants received a transfusion of RBCs that were irradiated and stored for up to 14 days). Data were analyzed using the evaluable population approach. INTERVENTION Transfusion of freshly irradiated RBCs. MAIN OUTCOMES AND MEASURES The prespecified primary outcome was the change in cerebral regional oxygen saturation (crSO2) from baseline (immediately before) to immediately after the transfusion. The prespecified secondary outcomes were the change in cerebral fractional tissue oxygen extraction (cFTOE) at different time points (immediately after, 24 hours after, and 120 hours or 5 days after transfusion). Outcomes were measured by blinded clinicians using near-infrared spectroscopy. A covariate-adjusted linear mixed model was used to quantify mean treatment effects and account for multiple transfusions in some infants. RESULTS A total of 42 infants (mean [SD] gestational age, 26  weeks and 3 days; 29 [69%] boys) were enrolled in the trial and underwent 64 transfusion episodes, which were randomized to the intervention (n = 31) or control (n = 33) group. Compared with infants in the control group, those in the intervention group showed a covariate-adjusted mean increase in crSO2 (2.0 percentage points; 95% CI, 1.2-2.8 percentage points) and a mean decrease in cFTOE (0.02; 95% CI, 0.01-0.04) immediately after transfusion. These differences were sustained up to 120 hours or 5 days after transfusion. There were negligible mean changes in crSO2 or cFTOE in infants in the control group at any of the follow-up time points. CONCLUSIONS AND RELEVANCE Results of this trial showed that transfusion of freshly irradiated RBCs conferred a small advantage in cerebral oxygenation for at least 5 days after transfusion compared with transfusion of irradiated and stored RBC components. On-demand irradiation of RBC components may be considered to optimize oxygen delivery in the recipient, but this physiological finding requires further research. TRIAL REGISTRATION ANZCTR Identifier: ACTRN12617001581358.
Preterm infants with anaemia (n= 42).
Transfusion of red blood cells (RBCs) freshly irradiated on the day of transfusion (n= 31).
Transfusion of RBCs irradiated and stored for up to 14 days, (n= 33).
The prespecified primary outcome was the change in cerebral regional oxygen saturation (crSO2) from baseline (immediately before) to immediately after the transfusion. The prespecified secondary outcomes were the change in cerebral fractional tissue oxygen extraction (cFTOE) at different time points. Compared to infants in the control group, those in the intervention group showed a covariate-adjusted mean increase in crSO2 (2.0 percentage points) and a mean decrease in cFTOE (0.02) immediately after transfusion. These differences were sustained up to 120 hours or 5 days after transfusion. There were negligible mean changes in crSO2 or cFTOE in infants in the control group at any of the follow-up time points.
Iron supplementation and the risk of bronchopulmonary dysplasia in extremely low gestational age newborns
Pediatric research. 2022
BACKGROUND The aim of this study was to determine the relationship between iron exposure and the development of bronchopulmonary dysplasia (BPD). METHODS A secondary analysis of the PENUT Trial dataset was conducted. The primary outcome was BPD at 36 weeks gestational age and primary exposures of interest were cumulative iron exposures in the first 28 days and through 36 weeks' gestation. Descriptive statistics were calculated for study cohort characteristics with analysis adjusted for the factors used to stratify randomization. RESULTS Of the 941 patients, 821 (87.2%) survived to BPD evaluation at 36 weeks, with 332 (40.4%) diagnosed with BPD. The median cohort gestational age was 26 weeks and birth weight 810 g. In the first 28 days, 76% of infants received enteral iron and 55% parenteral iron. The median supplemental cumulative enteral and parenteral iron intakes at 28 days were 58.5 and 3.1 mg/kg, respectively, and through 36 weeks' 235.8 and 3.56 mg/kg, respectively. We found lower volume of red blood cell transfusions in the first 28 days after birth and higher enteral iron exposure in the first 28 days after birth to be associated with lower rates of BPD. CONCLUSIONS We find no support for an increased risk of BPD with iron supplementation. TRIAL REGISTRATION NUMBER NCT01378273. https://clinicaltrials.gov/ct2/show/NCT01378273 IMPACT Prior studies and biologic plausibility raise the possibility that iron administration could contribute to the pathophysiology of oxidant-induced lung injury and thus bronchopulmonary dysplasia in preterm infants. For 24-27-week premature infants, this study finds no association between total cumulative enteral iron supplementation at either 28-day or 36-week postmenstrual age and the risk for developing bronchopulmonary dysplasia.
Randomized controlled trial comparing pit crew resuscitation model against standard advanced life support training
Journal of the American College of Emergency Physicians open. 2022;3(3):e12721
OBJECTIVES Pit crew models are designed to improve teamwork in critical medical situations, like advanced life support (ALS). We investigated if a pit crew model training improves performance assessment and ALS skills retention when compared to standard ALS education. METHODS This was a prospective, blinded, randomized, and controlled, parallel-group trial. We recruited students to 4-person resuscitation teams. We video recorded simulated ALS-situations after the ALS education and after 6-month follow-up. We analyzed technical skills (TS) and non-technical skills (NTS) demonstrated in them with an instrument measuring TS and NTS, and used a linear mixed model to model the difference between the groups in the TS and NTS. Another linear model was used to explore the difference between the groups in hands-on ratio and hands-free time. The difference in the total assessment score was analyzed with the Mann-Whitney U-test. The primary outcome was the difference in the total assessment score between the groups at follow-up. ALS skills were considered to be a secondary outcome. RESULTS Twenty-six teams underwent randomization. Twenty-two teams received the allocated education. Fifteen teams were evaluated at 6-month follow-up: 7 in the intervention group and 8 in the control group. At 6-month follow-up, the median (Q(1)-Q(3)) total assessment score for the control group was 6.5 (6-8) and 7 (6.25-8) for the intervention group but the difference was not significant (U = 133, P = 0.373). The intervention group performed better in terms of chest compression quality (interaction term, β3 = 0.23; 95% confidence interval, 0.01-0.50; P = 0.043) at follow-up. CONCLUSION We found no difference in overall performance between the study arms. However, trends indicate that the pit crew model may help to retain ALS skills in different areas like chest compression quality.