Emergency administration of fibrinogen concentrate for haemorrhage: systematic review and meta-analysis
World journal of emergency surgery : WJES. 2023;18(1):27
INTRODUCTION The occurrence of massive haemorrhages in various emergency situations increases the need for blood transfusions and increases the risk of mortality. Fibrinogen concentrate (FC) use may increase plasma fibrinogen levels more rapidly than fresh-frozen product or cryoprecipitate use. Previous several systematic reviews and meta-analyses have not effectively demonstrated FC efficacy in significantly improving the risk of mortality and reducing transfusion requirements. In this study, we investigated the use of FC for haemorrhages in emergency situations. METHODS AND ANALYSIS In this systematic review and meta-analysis, we included controlled trials, but excluded randomized controlled trials (RCTs) in elective surgeries. The study population consisted of patients with haemorrhages in emergency situations, and the intervention was emergency supplementation of FC. The control group was administered with ordinal transfusion or placebo. The primary and secondary outcomes were in-hospital mortality and the amount of transfusion and thrombotic events, respectively. The electronic databases searched included MEDLINE (PubMed), Web of Science, and the Cochrane Central Register of Controlled Trials. RESULTS Nine RCTs in the qualitative synthesis with a total of 701 patients were included. Results showed a slight increase in in-hospital mortality with FC treatment (RR 1.24, 95% CI 0.64-2.39, p = 0.52) with very low certainty of the evidence. There was no reduction in the use of red blood cells (RBC) transfusion in the first 24 h after admission with FC treatment (mean difference [MD] 0.0 Unit in the FC group, 95% CI - 0.99-0.98, p = 0.99) with very low certainty of the evidence. However, the use of fresh-frozen plasma (FFP) transfusion significantly increased in the first 24 h after admission with FC treatment (MD 2.61 Unit higher in the FC group, 95% CI 0.07-5.16, p = 0.04). The occurrence of thrombotic events did not significantly differ with FC treatment. CONCLUSIONS The present study indicates that the use of FC may result in a slight increase in in-hospital mortality. While FC did not appear to reduce the use of RBC transfusion, it likely increased the use of FFP transfusion and may result in a large increase in platelet concentrate transfusion. However, the results should be interpreted cautiously due to the unbalanced severity in the patient population, high heterogeneity, and risk of bias.
Patients admitted to hospital with emergency haemorrhage (9 randomised controlled trials, n= 701).
Emergency supplementation of fibrinogen concentrate (FC).
Standard transfusion treatments or placebo.
Results showed a slight increase in in-hospital mortality with FC treatment (RR 1.24; 95% CI [0.64, 2.39]) with very low certainty of the evidence. There was no reduction in the use of red blood cells transfusion in the first 24 h after admission with FC treatment (mean difference [MD] 0.0 Unit in the FC group, 95% CI [- 0.99, 0.98]) with very low certainty of the evidence. The use of fresh-frozen plasma transfusion significantly increased in the first 24 h after admission with FC treatment (MD 2.61 Unit higher in the FC group, 95% CI [0.07, 5.16]). The occurrence of thrombotic events did not significantly differ with FC treatment.
Intravenous immunoglobulin in the management of neonatal sepsis: A randomised controlled trial
Tropical doctor. 2023;:494755221138689
Sepsis is a leading cause of neonatal mortality and morbidity in low and middle-income countries. We designed a double-blinded randomised controlled trial in a neonatal intensive care unit (NICU) of a tertiary care teaching hospital to determine the role of intravenous immunoglobulin (IVIG) in decreasing hospital stay. Eighty neonates with clinical features of sepsis were enrolled in the study and placebo groups to receive 500 mg/kg of IVIG for three consecutive days or a placebo. The primary outcome measure was duration of hospital stay in days. The babies in both groups were comparable in terms of birth weight, gestation and sex distribution. There was no significant difference in duration of hospital stay (days) in the study and placebo groups. We found that treatment with IVIG did not shorten the duration of hospital stay in our setting.
Efficacy and Safety of Early Administration of 4-Factor Prothrombin Complex Concentrate in Patients With Trauma at Risk of Massive Transfusion: The PROCOAG Randomized Clinical Trial
IMPORTANCE Optimal transfusion strategies in traumatic hemorrhage are unknown. Reports suggest a beneficial effect of 4-factor prothrombin complex concentrate (4F-PCC) on blood product consumption. OBJECTIVE To investigate the efficacy and safety of 4F-PCC administration in patients at risk of massive transfusion. DESIGN, SETTING, AND PARTICIPANTS Double-blind, randomized, placebo-controlled superiority trial in 12 French designated level I trauma centers from December 29, 2017, to August 31, 2021, involving consecutive patients with trauma at risk of massive transfusion. Follow-up was completed on August 31, 2021. INTERVENTIONS Intravenous administration of 1 mL/kg of 4F-PCC (25 IU of factor IX/kg) vs 1 mL/kg of saline solution (placebo). Patients, investigators, and data analysts were blinded to treatment assignment. All patients received early ratio-based transfusion (packed red blood cells:fresh frozen plasma ratio of 1:1 to 2:1) and were treated according to European traumatic hemorrhage guidelines. MAIN OUTCOMES AND MEASURES The primary outcome was 24-hour all blood product consumption (efficacy); arterial or venous thromboembolic events were a secondary outcome (safety). RESULTS Of 4313 patients with the highest trauma level activation, 350 were eligible for emergency inclusion, 327 were randomized, and 324 were analyzed (164 in the 4F-PCC group and 160 in the placebo group). The median (IQR) age of participants was 39 (27-56) years, Injury Severity Score was 36 (26-50 [major trauma]), and admission blood lactate level was 4.6 (2.8-7.4) mmol/L; prehospital arterial systolic blood pressure was less than 90 mm Hg in 179 of 324 patients (59%), 233 patients (73%) were men, and 226 (69%) required expedient hemorrhage control. There was no statistically or clinically significant between-group difference in median (IQR) total 24-hour blood product consumption (12 [5-19] U in the 4F-PCC group vs 11 [6-19] U in the placebo group; absolute difference, 0.2 U [95% CI, -2.99 to 3.33]; P = .72). In the 4F-PCC group, 56 patients (35%) presented with at least 1 thromboembolic event vs 37 patients (24%) in the placebo group (absolute difference, 11% [95% CI, 1%-21%]; relative risk, 1.48 [95% CI, 1.04-2.10]; P = .03). CONCLUSIONS AND RELEVANCE Among patients with trauma at risk of massive transfusion, there was no significant reduction of 24-hour blood product consumption after administration of 4F-PCC, but thromboembolic events were more common. These findings do not support systematic use of 4F-PCC in patients at risk of massive transfusion. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03218722.
Patients with trauma at risk of massive transfusion enrolled in the PROCOAG trial, in 12 level I trauma centers in France (n= 327).
Intravenous administration of 4-factor prothrombin complex concentrate (4F-PCC group, n= 164).
Saline solution (placebo group, n= 160).
The primary outcome was the total number of all blood product units (RBC, FFP, and platelet concentrate) consumed within the first 24 hours after arrival in the trauma bay. The secondary outcomes were arterial or venous thromboembolic events. There was no statistically or clinically significant between-group difference in median (IQR) total 24-hour blood product consumption (12 [5-19] U in the 4F-PCC group vs. 11 [6-19] U in the placebo group; absolute difference, 0.2 U, 95% CI [-2.99, 3.33]). In the 4F-PCC group, 56 patients (35%) presented with at least 1 thromboembolic event vs. 37 patients (24%) in the placebo group (absolute difference, 11%, 95% CI [1%, 21%]; relative risk, 1.48, 95% CI [1.04, 2.10]).
Efficacy of IVIG therapy for patients with sepsis: a systematic review and meta-analysis
Journal of translational medicine. 2023;21(1):765
BACKGROUND Sepsis is an overwhelming reaction to infection that comes with high morbidity and mortality. It requires urgent interventions in order to improve outcomes. Intravenous immunoglobulins (IVIG) are considered as potential therapy in sepsis patients. Results of trials on IVIG as adjunctive therapy for sepsis have been conflicting due to the variability in population characteristics, country geography and drug dosage form in different studies. METHODS A systematic article search was performed for eligible studies published up to January, 31, 2023, through the PubMed, Embase, Cochrane Library and Chinese National Knowledge Infrastructure database. The included articles were screened by using rigorous inclusion and exclusion criteria. Subgroup analyses were conducted according to different IVIG types, ages and economic regions. All analyses were conducted using Review Manager 5.4. Quality of studies and risk of bias were evaluated. RESULTS In total, 31 randomized controlled trials were included with a sample size of 6,276 participants. IVIG could reduce the mortality (RR 0.86, 95% CI: 0.77-0.95, p = 0.005), the hospital stay (MD - 4.46, 95% CI: - 6.35 to - 2.57, p = 0.00001), and the APACHE II scores (MD - 1.65, 95% CI: - 2.89 to - 0.63, p = 0.001). Additionally, the results showed that IgM-enriched IVIG was effective in treating sepsis (RR 0.55, 95% CI: 0.40 - 0.76; p = 0.0003), while standard IVIG failed to be effective (RR 0.91, 95% CI: 0.81-1.02, p = 0.10). And the effect of IVIG in reducing neonatal mortality was inconclusive (RR 0.93, 95% CI: 0.81-1.05, p = 0.24), but it played a large role in reducing sepsis mortality in adults (RR 0.70, 95% CI: 0.57-0.86, p = 0.0006). Besides, from the subgroup of different economic regions, it indicated that IVIG was effective for sepsis in high-income (RR 0.89, 95% CI: 0.79-0.99, p = 0.03) and middle-income countries (RR 0.49, 95% CI: 0.28-0.84, p = 0.01), while no benefit was demonstrated in low-income countries (RR 0.56, 95% CI: 0.27-1.14, p = 0.11). CONCLUSIONS There is sufficient evidence to support that IVIG reduces sepsis mortality. IgM-enriched IVIG is effective in both adult and neonatal sepsis, while standard IVIG is only effective in adult sepsis. IVIG for sepsis has shown efficacy in high- and middle-income countries, but is still debatable in low-income countries. More RCTs are needed in the future to confirm the true clinical potential of IVIG for sepsis in low-income countries.
Effects of serum fibrinogen correction on outcome of traumatic cranial surgery: A randomized, single-blind, placebo-controlled clinical trial
Clinical neurology and neurosurgery. 2023;229:107709
BACKGROUND Traumatic brain injury (TBI) is strongly associated with coagulopathy that occurs in 25-35% of patients. This complication is linked to higher mortality and morbidity. Recent lines of evidance have supported administration of fibrinogen concentrate (FC) in patients with severe TBI, while its efficacy remains controversial. In this study we aim to evaluate the effectiveness of serum fibrinogen level correction from 1.5 and 2.0Â g/l to more than 2.0Â g/l in patients with severe TBI undergoing traumatic cranial surgery. METHOD This randomized, single-blind, placebo-controlled clinical trial included trauma patients who had abbreviated injury scale (AIS) more than 3 in head and below 3 in other organs. FC was administered intravenously to patients with severe TBI undergoing TBI to correct the fibrinogen level above 2Â g/l. Patients were randomly assigned to FC and control groups. The amount of intra-operative blood loss, packed cell (PC) transfusion, formation of new intracranial hemorrhage, and hemovac drainage were compared between the two study groups. RESULTS Forty-seven of 65 participants received the study intervention within 40-112Â min of admission. Intra-operative PC transfusion was higher in FC group (80%) compared to control group (55.5%) while the differance was not statistically significant (pÂ >Â 0.05). Intra-operative blood loss was significantly higher in control group than FC group (PÂ =Â 0.036). Chance of re-operation and new intracranial hematoma were not significantly different between two study groups. CONCLUSION Early delivery of FC, decreases intraoperative bleeding. Although based on our findings it has no other effect on other parameters, further multicenter studies are recommended to investigate the role of early FC administration in management of post traumatic coagulopathy.
Effect of Hydroxyethyl starch (HES) versus 5% albumin solution on intra-abdominal pressure in severe burn patients: A prospective randomized clinical trial
Burns : journal of the International Society for Burn Injuries. 2023
INTRODUCTION Massive burn patients are at risk of developing intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) as a complication of resuscitation. OBJECTIVE This study aimed to evaluate the effect of Hydroxyethyl starch (HES) versus 5% albumin solution on intra-abdominal pressure (IAP) in massive burn patients. METHODS This was a prospective randomized clinical trial carried on at Ain Shams University (ASU) burn unit for 2 years. Where adult patients with burns more than 20% of TBSA were equally randomized into HES group or albumin group. RESULTS Fifty-two patients were equally randomized into 2 groups. We found no difference in age, sex, weight, type of burn, and TBSA between the two groups. The mean total resuscitation fluid volume in the first 48 h was 213 ml/kg and 206.2 ml/kg for the HES group and the albumin group respectively (p = 0.674). IAP statistically was non-significantly higher in the HES group. We found no statistical difference between the two groups as regards the renal function tests. CONCLUSION Both HES and 5% albumin solution are effective and safe colloids for burn resuscitation. As regards the IAP, it seems that both 5% albumin and HES have comparable effect regarding IAH in severely burn patients. Both HES and 5% albumin were partially equal in terms of renal involvement and vital data stability.
Clinical efficacy of IgM-enriched immunoglobulin as adjunctive therapy in neonatal and pediatric sepsis: a systematic review and meta-analysis
Frontiers in pediatrics. 2023;11:1239014
BACKGROUND Sepsis is a major cause of mortality and morbidity globally, with around one-quarter of all sepsis-related deaths occurring in children under the age of 5. We conducted a meta-analysis and systematic review of the literature to evaluate the clinical effectiveness of an IgM-enriched immunoglobulin preparation in pediatrics patients and neonates with sepsis. METHODS Systematic searches of PubMed, the Cochrane Library and Embase databases were performed in November 2022, with no date limitations, to identify studies in which IgM-enriched immunoglobulin was used as adjunctive therapy in neonatal and pediatric patients with sepsis. RESULTS In total, 15 studies fulfilled the eligibility criteria, 13 neonatal studies and 2 pediatric studies. Pooled estimates from all studies indicated that mortality rates were significantly lower in patients who received treatment with the IgM-enriched immunoglobulin compared with controls (OR 0.41; 95% CI 0.32-0.55). Further analyses in neonatal studies, alone, showed a significant benefit with longer treatment durations (>3 days) vs. the recommended treatment duration (3 days) (OR 0.32; 95% CI 0.22-0.47) vs. (OR 0.61; 95% CI 0.41-0.92). Treatment with IgM-enriched immunoglobulin was associated with a lower mortality risk compared with controls in prospective studies vs. retrospective analyses (OR 0.37; 95% CI 0.27-0.51) vs. (OR 0.73; 95% CI 0.41-1.30). CONCLUSIONS This systematic review suggests that adjunctive treatment with IgM-enriched immunoglobulin may reduce the risk of mortality in neonatal and pediatric populations. However, large randomized controlled trials are required to further substantiate and evaluate these findings.
Different Concentrations of Albumin Versus Crystalloid in Patients with Sepsis and Septic Shock: A Meta-Analysis of Randomized Clinical Trials
Journal of intensive care medicine. 2023;:8850666231170778
OBJECTIVE The best type of resuscitation fluids for sepsis and septic shock patients remains unclear. The aim of this study was to evaluate the efficacy of different concentrations of albumin on reducing the mortality rate of theses patients by meta-analysis. MATERIALS AND METHODS PubMed, EMBASE, and Web of Science databases were used for screening the relevant studies. Randomized controlled trials (RCTs) were eligible if they compared the effects of albumin with crystalloid on mortality in patients with sepsis and septic shock. Data were examined and extracted by two reviewers independently. Any disagreements were resolved by consensus with or without the help from a third reviewer. Data including mortality, sample size of the patients, and resuscitation endpoints were extracted. Meta-analysis was carried based on the corresponding odds ratios with 95% confidence intervals. RESULTS Eight studies with a total of 5124 septic patients and 3482 septic shock patients were included in this study. Compared with crystalloid, the use of albumin may represent a trend toward reduced the 90-day mortality of septic patients (OR 0.91 [0.80, 1.02]; P = .11) and significantly improved the outcome of septic shock patients (OR 0.85 [0.74, 0.99]; P = .04). Further analysis showed a potentially beneficial role of both 4% to 5% and 20% albumin on reducing the mortality of septic patients. The use of 20% albumin significantly decreased the 90-day mortality of septic shock patients (OR 0.81 [0.67, 0.98]; P = .03), which was better than 4% to 5% albumin and crystalloid. CONCLUSIONS Albumin treatment, particularly 20% albumin, significantly reduced the 90-day mortality in septic shock patients. Both 4% to 5% and 20% of albumin may work better than crystalloid in improving the survival rate of patients with sepsis, but more relative RCTs are required for validation.
Interventions for reducing late-onset sepsis in neonates: an umbrella review
Journal of perinatal medicine. 2022
OBJECTIVES Neonatal sepsis is one of the leading causes of neonatal deaths in neonatal intensive care units. Hence, it is essential to review the evidence from systematic reviews on interventions for reducing late-onset sepsis (LOS) in neonates. METHODS PubMed and the Cochrane Central were searched from inception through August 2020 without any language restriction. Cochrane reviews of randomized clinical trials (RCTs) assessing any intervention in the neonatal period and including one or more RCTs reporting LOS. Two authors independently performed screening, data extraction, assessed the quality of evidence using Cochrane Grading of Recommendations Assessment, Development and Evaluation, and assessed the quality of reviews using a measurement tool to assess of multiple systematic reviews 2 tool. RESULTS A total of 101 high-quality Cochrane reviews involving 612 RCTs and 193,713 neonates, evaluating 141 interventions were included. High-quality evidence showed a reduction in any or culture-proven LOS using antibiotic lock therapy for neonates with central venous catheters (CVC). Moderate-quality evidence showed a decrease in any LOS with antibiotic prophylaxis or vancomycin prophylaxis for neonates with CVC, chlorhexidine for skin or cord care, and kangaroo care for low birth weight babies. Similarly, moderate-quality evidence showed reduced culture-proven LOS with intravenous immunoglobulin prophylaxis for preterm infants and probiotic supplementation for very low birth weight (VLBW) infants. Lastly, moderate-quality evidence showed a reduction in fungal LOS with the use of systemic antifungal prophylaxis in VLBW infants. CONCLUSIONS The overview summarizes the evidence from the Cochrane reviews assessing interventions for reducing LOS in neonates, and can be utilized by clinicians, researchers, policymakers, and consumers for decision-making and translating evidence into clinical practice.
International guidelines regarding the role of IVIG in the management of Rh- and ABO-mediated haemolytic disease of the newborn
British journal of haematology. 2022
Haemolytic disease of the newborn (HDN) can be associated with significant morbidity. Prompt treatment with intensive phototherapy (PT) and exchange transfusions (ETs) can dramatically improve outcomes. ET is invasive and associated with risks. Intravenous immunoglobulin (IVIG) may be an alternative therapy to prevent use of ET. An international panel of experts was convened to develop evidence-based recommendations regarding the effectiveness and safety of IVIG to reduce the need for ETs, improve neurocognitive outcomes, reduce bilirubin level, reduce the frequency of red blood cell (RBC) transfusions and severity of anaemia, and/or reduce duration of hospitalization for neonates with Rh or ABO-mediated HDN. We used a systematic approach to search and review the literature and then develop recommendations from published data. These recommendations conclude that IVIG should not be routinely used to treat Rh or ABO antibody-mediated HDN. In situations where hyperbilirubinaemia is severe (and ET is imminent), or when ET is not readily available, the role of IVIG is unclear. High-quality studies are urgently needed to assess the optimal use of IVIG in patients with HDN.