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.
Prophylactic intravenous calcium therapy for exchange blood transfusion in the newborn
The Cochrane Database of Systematic Reviews. 2017;((10)):CD011048.
BACKGROUND Exchange blood transfusion (EBT) is a form of whole blood transfusion in which the total blood volume is replaced within a few hours. In perinatal and neonatal medicine, EBT is most often used in the management of severe anaemia or severe hyperbilirubinaemia in the first week of life. Hypocalcaemia, one of the common morbidities associated with EBT, is thought to arise from the chelating effects of the citrate commonly used as an anticoagulant in the donor's blood. This disorder manifests with muscular and nervous irritability and cardiac arrhythmias. OBJECTIVES To determine whether the use of prophylactic calcium reduces the risk of hypocalcaemia-related morbidities and death among newborn infants receiving EBT. SEARCH METHODS We used the standard search strategy of the Cochrane Neonatal Review group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 5), MEDLINE via PubMed (1966 to 29 June 2016), Embase (1980 to 29 June 2016), and CINAHL (1982 to 29 June 2016). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA All randomised and quasi-randomised trials of prophylactic intravenous calcium in EBT for newborns. DATA COLLECTION AND ANALYSIS Two review authors independently assessed and extracted data on methods, participants, interventions, and outcomes (mean total and ionised serum calcium before and after EBT and the presence of adverse events such as hypoglycaemia, apnoea, cardiac arrest, and death immediately after EBT). We reported results as means difference (MD) with 95% confidence intervals (CI) for continuous outcomes and risk ratio (RR) and risk differences (RD) and 95% CIs for dichotomous outcomes. We assessed quality using the Cochrane 'Risk of bias' assessment tool and the GRADE system. MAIN RESULTS We found only one quasi-randomised trial with 30 participants that met our inclusion criteria. In the small trial, total and ionised serum calcium levels were measured immediately before and immediately after EBT. All the participants were included in the final analysis and all the important outcomes were reported. Primary outcomesThere was one death in each group (RR 1.00, 95% CI 0.07 to 14.55; RD 0.00, 95% CI -0.18 to 0.18; participants = 30; studies = 1). The study did not report the presence of cardiac arrhythmias within one week of EBT and the number of infants with serum calcium levels (total less than 8 mg/dL (2 mmol/L) or ionised less than 4.4 mg/dL (1.1 mmol/L)).Pair-wise comparison of EBT with intravenous 10% calcium gluconate versus EBT without intravenous calcium (change from baseline) showed mean total serum calcium was raised in the intervention group compared to the control group (MD -0.46, 95% CI -0.81 to -0.11; participants = 30; studies = 1). Very low-quality evidence also indicated an increase in the levels of mean ionised serum calcium in the intervention group compared to the control group (MD -0.22, 95% CI -0.33 to -0.11; participants = 30; studies = 1). Secondary outcomesAdverse reactions to intravenous calcium therapy included cardiac arrest in one neonate in the intervention arm (RR 3.00, 95% CI 0.13 to 68.26; RD 0.07, 95% CI -0.10 to 0.23; participants = 30; studies = 1). There was apnoea and hypoglycaemia (RR 1.00, 95% CI 0.07 to 14.55; RD 0.00, 95% CI -0.18 to 0.18; participants = 30; studies = 1) in the two neonates who died. Data were not available for other major secondary outcomes such as the number of infants with reduced serum magnesium, reduced parathormone, increased calcitonin, presence of seizures, carpopedal spasm, jitteriness and prolonged QTc interval on electrocardiography within one week of EBT. AUTHORS' CONCLUSIONS Very low-quality data from one quasi-randomised controlled trial suggested that the mean serum total and ionised calcium increased in the study group but decreased in the control group immediately after EBT. However, the mean values of total and ionised cal
The effect of plasmapheresis on treating disseminated intravascular coagulation (DIC) caused by a Hemiscorpius lepturus (Gadim) sting
Clinical Toxicology (Philadelphia, Pa.). 2017;:1-6.
INTRODUCTION The highest mortality from scorpion stings in Iran is due to the stings of a particular type of scorpion known as Hemiscorpius lepturus (H. lepturus, Gadim in local language). The present study aimed at investigating the use of plasmapheresis to treat severe cases of H. lepturus stings. METHOD This pilot study was a randomized clinical trial conducted from June 2015 to June 2016 in Razi hospital of Ahvaz, Iran. Twenty-nine patients who had been stung by H. lepturus and admitted to ICU because of disseminated intravascular coagulation (DIC) were randomly assigned into control (15 patients, supportive treatments) and plasmapheresis (14 patients, supportive treatments + plasmapheresis) groups, and the patient outcomes were compared between the two groups. FINDINGS Eighteen patients were female (62%), and the mean of patient age was 24 +/- 7. Most of the sting cases had occurred in the torso (15 patients, 52%). Only 10 patients (34%) arrived in the hospital within 12 h of being stung. There was no significant difference between the two groups in terms of the demographic and sting features. In the plasmapheresis group, hemoglobin level was significantly lower, while the PT and INR were measurably higher. In total, the plasmapheresis group experienced 29 sessions of treatment (an average of two sessions for each patient). Overall, 19 patients (66%) expired, whereas 10 patients (34%) experienced recovery with or without complications. The rate of recovery was significantly higher in the plasmapheresis group compared with controls, with eight patients (57%) in the plasmapheresis group surviving compared with two (14%) in the control group (p=.045). The duration of hospitalization was higher in the plasmaphersis group (p < .001). A comparison of the dead and recovered patients' features indicated that the dead patients arrived in the hospital significantly later than the recovered ones, and they also had lower platelet counts. CONCLUSIONS The findings of this small-scale pilot study show that using plasmapheresis in treating DIC in patients stung by H. lepturus can prevent death and encourage recovery. However, prior to using plasmapheresis as a routine treatment for severe cases of people stung by this scorpion or other similar ones, further controlled studies with a larger sample size are needed.
The efficacy and safety of plasma exchange in patients with sepsis and septic shock: a systematic review and meta-analysis
Critical Care (London, England). 2014;18((6):):699.
INTRODUCTION Sepsis and septic shock are leading causes of intensive care unit (ICU) mortality. They are characterized by excessive inflammation, upregulation of procoagulant proteins and depletion of natural anticoagulants. Plasma exchange has the potential to improve survival in sepsis by removing inflammatory cytokines and restoring deficient plasma proteins. The objective of this study is to evaluate the efficacy and safety of plasma exchange in patients with sepsis. METHODS We searched MEDLINE, EMBASE, CENTRAL, Scopus, reference lists of relevant articles, and grey literature for relevant citations. We included randomized controlled trials comparing plasma exchange or plasma filtration with usual care in critically ill patients with sepsis or septic shock. Two reviewers independently identified trials, extracted trial-level data and performed risk of bias assessments using the Cochrane Risk of Bias tool. The primary outcome was all-cause mortality reported at longest follow-up. Meta-analysis was performed using a random-effects model. RESULTS Of 1,957 records identified, we included four unique trials enrolling a total of 194 patients (one enrolling adults only, two enrolling children only, one enrolling adults and children). The mean age of adult patients ranged from 38 to 53 years (n=128) and the mean age of children ranged from 0.9 to 18 years (n=66). All trials were at unclear to high risk of bias. The use of plasma exchange was not associated with a significant reduction in all-cause mortality (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.45 to 1.52, I(2) 60%). In adults, plasma exchange was associated with reduced mortality (RR 0.63, 95% CI 0.42 to 0.96; I(2) 0%), but was not in children (RR 0.96, 95% CI 0.28 to 3.38; I(2) 60%). None of the trials reported ICU or hospital lengths of stay. Only one trial reported adverse events associated with plasma exchange including six episodes of hypotension and one allergic reaction to fresh frozen plasma. CONCLUSIONS Insufficient evidence exists to recommend plasma exchange as an adjunctive therapy for patients with sepsis or septic shock. Rigorous randomized controlled trials evaluating clinically relevant patient-centered outcomes are required to evaluate the impact of plasma exchange in this condition.
Intensive plasma exchange increases a disintegrin and metalloprotease with thrombospondin motifs-13 activity and reverses organ dysfunction in children with thrombocytopenia-associated multiple organ failure
Critical Care Medicine. 2008;36((10):):2878-87.
BACKGROUND Thrombocytopenia-associated multiple organ failure (TAMOF) is a poorly understood syndrome in critically ill children. A disintegrin and metalloprotease with thrombospondin motifs (ADAMTS-13), formerly known as von Willebrand factor (VWF) cleaving protease, is decreased in adults with VWF-mediated thrombotic microangiopathy, and intensive plasma exchange (PEx) both replenishes ADAMTS-13 and improves outcome in these patients. OBJECTIVES To determine whether: 1) critically ill children with TAMOF syndrome have decreased ADAMTS-13 activity, 2) ADAMTS-13 activity correlates with platelet counts and VWF antigen, 3) the autopsies from patients who died with reduced ADAMTS-13 activity have VWF-rich microthrombi, and 4) intensive PEx will restore ADAMTS-13 activity and facilitate organ failure resolution. DESIGN First study: observational. Second study: randomized control trial. SETTING Single center university pediatric intensive care unit. PATIENTS First study: thirty-seven consecutive children (17 males and 20 females; ages ranging from 9 days to 23 years) identified with > or = 2 organs dysfunction were enrolled. Seventy-six percent of these children had thrombocytopenia (platelet counts < 100,000/mm3). Five additional critically ill children without MOF were also enrolled. In the second study, children with severe TAMOF (platelet counts < 100,000/mm3 and > 3 organ failure) were randomized to PEx or standard therapy. Primary physicians and parents agreed to enrollment in 10 of the 20 eligible patients with ages ranging from 1 year to 18 years. Five patients received PEx and 5 patients received standard therapy. RESULTS First study: children with TAMOF (n = 28) had decreased ADAMTS-13 activity, but similar plasminogen activator inhibitor-1 activity and prothrombin time compared to children with MOF without thrombocytopenia (n = 9, p < 0. 05). All non-survivors (n = 7) had TAMOF, reduced ADAMTS-13 activity, and VWF-rich microvascular thromboses at autopsy. In the second study, PEx (n = 5, median 12 days, 4-28 days) restored ADAMTS-13 activity and organ function, compared to standard therapy (n = 5, p < 0. 05). CONCLUSIONS Children with TAMOF syndrome can have VWF-mediated thrombotic microangiopathy. Similar to adult experience, PEx can replenish ADAMTS-13 activity and reverse organ failure.
Effects of replacement fluids used for therapeutic plasma exchange on plasma viscosity and plasma oncotic pressure
Transfusion and Apheresis Science. 2004;31((2):):89-93.
INTRODUCTION Apheresis is a procedure in which one of the components of blood is removed. The aim of therapeutic plasma exchange (TPE) is to remove a large fraction of the patient's plasma from the body, and to exchange this with replacement solutions using automatic devices. With this procedure circulating pathogens and toxins are reduced. Before each TPE results of a baseline basal complete blood count, serum protein electrophoresis, coagulation tests and serum electrolytes must be known. The efficacy of this therapy is assessed only by these values. The proteins responsible for disease may be monoclonal proteins, cryoglobulins, lipoproteins, auto or allo antibodies or toxins. In this study, we aimed to compare the effects of several replacement fluids on plasma viscosity and oncotic pressure. At the same time, we evaluated the correlation between plasma viscosity and oncotic pressure. MATERIAL AND METHODS 111 TPE were performed on 42 patients. Before TPE, the patients whose veins were not suitable were catheterised either by using a subclavian or jugular 11F dialysis catheter. At each session, approximately 1-1. 5L of plasma was exchanged. The procedure was performed with albumin in patients whose albumin was under 3gr/dl. Over this value, the exchange fluids were randomised. RESULTS When the overall results were analysed, there was no statistically significant difference between groups 1 (HES+albumin) and group 3 (albumin). The statistical difference between group 2 and 3 was significant, but no difference was observed between group 1 and 2. According to the decreasing plasma viscosity, there was a significant difference between group 2 and group 3, but there was no difference between group 1 and group 2. CONCLUSIONS The replacement solutions used for plasmapheresis are similar when compared for hemorheologic effects, but we have chosen fresh frozen plasma because of fewer side effects.
The role of exchange transfusions in the management of low-birth-weight infants with and without severe respiratory distress syndrome. II. Further observations and studies of mechanisms of action
Journal of Pediatrics. 1976;89((2):):279-85.
Exchange transfusion, as a form of therapy, was contrasted with the use of fresh frozen plasma or conventional supportive care alone in the management of 19 infants with birth weights of less than 1,000 gm, without severe respiratory distress, and in the management of 82 infants, birth weights less than 2,000 gm, with severe respiratory distress whose disease manifested itself within the first 24 hours of life. Survival for more than five days was similar, regardless of therapy, in infants weighing less than 1,000 gm without severe RDS. In contrast, the use of exchange transfusion significantly decreased the case fatality rate of infants with severe RDS. In the groups receiving exchange transfusion, the mortality rate was 41%, whereas the groups receiving either plasma or supportive care alone the mortality was 80%. Study of coagulation factors and red cell concentrations of fetal hemoglobin and of 2,3-DPG failed to demonstrate any relationship between either improvement in coagulation or oxygen unloading and the improved survival of infants receiving exchange transfusion. Following exchange transfusion there was a significant decrease in the ratio of FIO2 to PaO2, suggesting that pulmonary perfusion and/or ventilation was improved by the procedure.