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.
Adsorption of insulin onto neonatal infusion sets: should intravenous administration of insulin to treat hyperglycemia in preterm babies on the NICU be proceeded by priming of the intravenous system, adding of albumin, or non-priming to get to a stable insulin dose?
Molecular and cellular pediatrics. 2022;9(1):20
Insulin is used to treat neonatal hyperglycaemia when blood glucose concentrations are consistently high, and to treat neonatal diabetes. Within this brief report, a review of the existing literature is conducted to determine if intravenous administration of insulin should be proceeded by priming of the intravenous system, adding of albumin, or non-priming to get a stable insulin dose. Within this literature search, we focused on experimental insulin adsorption data (in vitro studies).
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.
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.
Clinically Significant Gastrointestinal Bleeding Using Proton Pump Inhibitors or Histamine Type-2 Receptor Antagonists in Patients Intubated for over 48 Hours: A Systematic Review and Meta-Analysis
American journal of therapeutics. 2022
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.
Resuscitative Endovascular Balloon Occlusion of Aorta Versus Aortic Cross-Clamping by Thoracotomy for Noncompressible Torso Hemorrhage: A Meta-Analysis
The Journal of surgical research. 2021;270:252-260
BACKGROUND The effect of resuscitative endovascular balloon occlusion of aorta (REBOA) in lowering mortality rate compared to resuscitative thoracotomy (RT) is inconclusive. In this updated systematic review and meta-analysis, we determined the effectiveness of the two techniques in patients with noncompressible torso hemorrhage (NCTH). MATERIALS AND METHODS Online databases (PubMed, Embase, and MEDLINE) were searched until April 23, 2021, for original articles investigating the effect of REBOA on relevant outcomes (e.g., mortality in ED, mortality before discharge, in-hospital mortality, length of hospital stay and length of ICU stay) among NCTH patients in contrast to open aortic occlusion by RT. Data on baseline characteristics and endpoints were extracted. Review Manager version 5.4.1 and OpenMetaAnalyst were used for analyses. Risk ratios (RR) and the weighted mean differences (WMD) with corresponding 95% confidence intervals were calculated. RESULTS Eight studies were included having 3241 patients in total (REBOA 1179 and RT: 2062). The pooled analysis demonstrated that compared to RT, mortality was significantly lower in the REBOA group in all settings: In emergency department (ED) (RR 0.63 [0.45, 0.87], P = 0.006, I(2) = 81%), before discharge (RR= 0.86 [0.75, 0.98], P = 0.03, I(2 =) 93%), and in-hospital mortality (RR 0.80 [0.68, 0.95], P = 0.009, I(2 =) 85%). Similarly, the length of ICU stay was significantly lower in REBOA group (WMD = 0.50 [-0.48, 1.48], P = 0.32, I(2 =)97%). However, no significant differences were observed in the length of hospital stay (WMD = 0.0 [-0.26, 0.26] P = 1). CONCLUSIONS Our pooled analysis shows REBOA to be effective in reducing mortality among NCTH patients. However, due to limited studies, the positive findings should be viewed discreetly and call for further investigation.
Prophylactic Erythropoietin for Neuroprotection in Very Preterm Infants: A Meta-Analysis Update
Frontiers in pediatrics. 2021;9:657228
A meta-analysis update of randomized controlled trials investigating recombinant human erythropoietin suggests improved neurodevelopmental outcome in preterm infants. There was substantial heterogeneity, which could be ascribed to a single trial. Exclusion of this trial featuring a high risk of bias abolished heterogeneity and any effects of recombinant human erythropoietin treatment.
Balanced crystalloids versus saline in critically ill patients: The PRISMA study of a meta-analysis
OBJECTIVE To compare the safety of balanced crystalloids and saline among critically ill patients in intensive care unit (ICU). METHODS The Medline, EMBASE, Web of Science, Cochrane Library databases were systematically searched from the inception dates to May 17, 2020 in order to identify randomized controlled trials which evaluated the safety of balanced crystalloids and saline in critically ill patients. The primary outcome was major adverse kidney events within 30 days (MAKE30). The second outcomes included 30-day mortality, ICU mortality, In-hospital mortality, ICU length of stay, hospital length of stay, creatinine highest before discharge (mg/dl) and needs for renal replacement therapy (RRT). RESULTS A total of nine randomized controlled trials involving 19,578 critical ill patients fulfilled the inclusion criteria. The outcomes of this meta-analysis showed that balanced crystalloids treatment shared the same risk of MAKE30 with saline treatment among critical ill patients [RR = 0.95; 95%CI, 0.88 to 1.01; Z = 1.64 (P = .102)]. The clinical mortality which included 30-day mortality [RR = 0.92; 95%CI, 0.85 to 1.01; Z = 1.78 (P = .075)], ICU mortality [RR = 0.92; 95%CI, 0.83 to 1.02; Z = 1.67 (P = .094)] and In-hospital mortality [RR = 0.93; 95%CI, 0.71 to 1.21; Z = 0.55 (P = .585)] were similar between balanced crystalloids treatment and saline treatment among critical ill patients. Patients who received balanced crystalloids treatment or saline treatment needed the same length of ICU stay [WMD = 0.00; 95%CI, -0.09 to 0.10; Z = 0.09 (P = .932)] and hospital stay [WMD = 0.59; 95%CI, -0.33 to 1.51; Z = 1.26 (P = .209)]. Critical ill patients who received balanced crystalloids treatment or saline treatment had the same level of creatinine highest before discharge [WMD = 0.01; 95%CI, -0.02 to 0.04; Z = 0.76 (P = .446)] and needs for RRT [RR = 1.04; 95%CI, 0.75 to 1.43; Z = 0.21 (P = .830)]. Similar results were obtained in subgroups of trials stratified according to the age of patients (children or adults). CONCLUSIONS When compared with saline, balanced crystalloids could not reduce the risk of MAKE30, 30-day mortality, ICU mortality and in-hospital mortality, could not reduce the length of ICU stay, length of hospital stay, the level of creatinine highest before discharge and the needs for RRT among critical ill children and adults. Therefore, it was still too early for balanced crystalloids to replace normal saline among critical ill patients.
Pulmonary haemorrhage in neonates: Systematic review of management
Acta paediatrica (Oslo, Norway : 1992). 2021
AIM: Pulmonary haemorrhage (PH) is an acute catastrophic event with low incidence yet high mortality among neonates. We aimed to systematically review the management of PH. METHODS A search was carried out of the PubMed, Embase and Cochrane databases according to the PRISMA guidelines. Data was extracted on study design and size, patient demographics, primary and adjunctive treatment methods, and treatment outcomes. RESULTS Sixteen studies with 385 newborn infants were included and were significantly heterogenous regarding treatment methods. Primary treatments included surfactant, High Frequency Oscillatory Ventilation (HFOV), epinephrine, coagulopathy management, intermittent positive pressure ventilation, cocaine, and tolazoline. Adjunctive treatment methods included blood products, HFOV, increased positive end expiratory pressure, vitamin K, surfactant, adrenaline, vasopressors, and inotropes. All five studies using surfactant as primary treatment were effective in improving oxygenation index measures and preventing recurrence of PH, and three studies found no association between surfactant and death or long-term disability. Ventilatory support, epinephrine, management of coagulopathy and tolazoline were all found to be effective primary treatments for PH. CONCLUSION There are several effective methods of managing PH in neonates. Further understanding of the aetiology of PH and ongoing research will allow future prevention and improvements in management of PH.