Comparison of 3-factor versus 4-factor prothrombin complex concentrate for emergent warfarin reversal: a systematic review and meta-analysis
BMC emergency medicine. 2022;22(1):14
BACKGROUND Patients requiring emergent warfarin reversal (EWR) have been prescribed three-factor prothrombin complex concentrate (PCC3) and four-factor prothrombin complex concentrate (PCC4) to reverse the anticoagulant effects of warfarin. There is no existing systematic review and meta-analysis of studies directly comparing PCC3 and PCC4. METHODS The primary objective of this systematic review and meta-analysis was to determine the effectiveness of achieving study defined target INR goal after PCC3 or PCC4 administration. Secondary objectives were to determine the difference in safety endpoints, thromboembolic events (TE), and survival during the patients' hospital stay. Random-effects meta-analysis models were used to estimate the odds ratios (OR), and heterogeneity associated with the outcomes. The Newcastle-Ottawa Scale was used to assess study quality, and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. RESULTS Ten full-text manuscripts and five abstracts provided data for the primary and secondary outcomes. Patients requiring EWR had more than three times the odds of reversal to goal INR when they were given PCC4 compared to PCC3 (OR = 3.61, 95% CI: 1.97-6.60, p < 0.001). There was no meaningful clinical association or statistically significant result between PCC4 and PCC3 groups in TE (OR = 1.56, 95% CI: 0.83-2.91, p = 0.17), or survival during hospital stay (OR = 1.34, 95% CI: 0.81-2.23, p = 0.25). CONCLUSION PCC4 is more effective than PCC3 in meeting specific predefined INR goals and has similar safety profiles in patients requiring emergent reversal of the anticoagulant effects of warfarin.
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.
Prothrombin complex concentrate in major bleeding associated with DOACs; an updated systematic review and meta-analysis
Journal of thrombosis and thrombolysis. 2021
BACKGROUND Four-factor prothrombin complex concentrate (PCC) is frequently used as a reversal agent for major bleeding in patients on factor Xa inhibitors. Piran et al. reviewed its safety and efficacy for the first time in 2018. However, more studies have been published on the matter since then. The aim of this study is to investigate the efficacy and safety of this use and update this review. METHODS We systematically searched in Medline, Scopus, and the Cochrane Library from 1/1/2018 to 6/19/2020. A random effects model meta-analysis of proportions was used to study the efficacy of PCC on major bleeding control, mortality and thrombosis incidence. RESULTS 33 studies (n = 2568 patients), with the majority of studies being uncontrolled retrospective cohort studies, were included; atrial fibrillation was the main factor Xa inhibitors indication and approximately 62% of patients presented with intracranial hemorrhage. We estimated the pooled proportion outcomes for hemostasis (80%, CI 0.75-0.84), mortality (15%, CI 0.11-0.19) and thromboembolic adverse events (3%, CI 0.02-0.05). High versus low dose PCC did not affect hemostasis or thrombosis. Patients with ICH had higher mortality rates (22%, CI 0.13-0.32). Heterogeneity was significant (Ι(2) > 50% with p < 0.05) for all pooled proportional outcomes. The quality of evidence was low given that included studies were not randomized or controlled. CONCLUSION Our study demonstrates the efficacy and safety of the off label use of 4F PCC in major bleeding associated with factor Xa inhibitors. Our data require further validation with future randomized clinical trials.
Andexanet Alfa or Prothrombin Complex Concentrate for Factor Xa Inhibitor Reversal in Acute Major Bleeding: A Systematic Review and Meta-Analysis
Critical care medicine. 2021
OBJECTIVES To combine evidence on andexanet alfa and prothrombin complex concentrates for factor Xa inhibitor-associated bleeding to guide clinicians on reversal strategies. DATA SOURCES Embase, Pubmed, Web of Science, and the Cochrane Library. STUDY SELECTION Observational studies and randomized clinical trials studying hemostatic effectiveness of andexanet alfa or prothrombin complex concentrate for acute reversal of factor Xa inhibitor-associated hemorrhage. DATA EXTRACTION Two independent reviewers extracted the data from the studies. Visualization and comparison of hemostatic effectiveness using Sarode et al or International Society of Thrombosis and Hemostasis Scientific and Standardization Committee criteria at 12 and 24 hours, (venous) thrombotic event rates, and inhospital mortality were performed by constructing Forest plots. Exploratory analysis using a logistic mixed model analysis was performed to identify factors associated with effectiveness and venous thromboembolic event. DATA SYNTHESIS A total of 21 studies were included (andexanet: 438 patients; prothrombin complex concentrate: 1,278 patients). The (weighted) mean effectiveness for andexanet alfa was 82% at 12 hours and 71% at 24 hours. The (weighted) mean effectiveness for prothrombin complex concentrate was 88% at 12 hours and 76% at 24 hours. The mean 30-day symptomatic venous thromboembolic event rates were 5.0% for andexanet alfa and 1.9% for prothrombin complex concentrate. The mean 30-day total thrombotic event rates for andexanet alfa and prothrombin complex concentrate were 10.7% and 3.1%, respectively. Mean inhospital mortality was 23.3% for andexanet versus 15.8% for prothrombin complex concentrate. Exploratory analysis controlling for potential confounders did not demonstrate significant differences between both reversal agents. CONCLUSIONS Currently, available evidence does not unequivocally support the clinical effectiveness of andexanet alfa or prothrombin complex concentrate to reverse factor Xa inhibitor-associated acute major bleeding, nor does it permit conventional meta-analysis of potential superiority. Neither reversal agent was significantly associated with increased effectiveness or a higher rate of venous thromboembolic event. These results underscore the importance of randomized controlled trials comparing the two reversal agents and may provide guidance in designing institutional guidelines.
Albumin therapy for acute ischemic stroke: a meta-analysis
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2021
Human serum albumin has shown remarkable efficacy in rodent models of ischemic stroke, while results from relevant clinical research on albumin therapy remain controversial. We conducted a meta-analysis of published studies to quantitatively analyze the neurofunctional outcomes of patients with ischemic stroke treated with albumin. PubMed, Embase, and Cochrane Library were searched in July 2020. A total of four studies and 1611 patients were included. The aggregated results indicated that there were 635 patients with good neurological outcomes, among which 321 patients were in the albumin group (39.8%) and 314 patients in the control group (39.1%), showing no statistically significant difference between the albumin and control groups (OR = 1.04, 95% CI 0.85-1.27). The results suggest that albumin therapy at the acute stage of ischemic stroke has no beneficial effect on the long-term neurological function of patients with ischemic stroke. Considering pulmonary edema and other complications are more likely to occur in such patients after albumin infusion, the administration of albumin therapy for acute ischemic stroke should be done with utmost caution.
[Evaluation of pharmaceutical prevention and treatment of intensive care unit-acquired weakness: a Meta-analysis]
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2020;32(3):357-361
OBJECTIVE To evaluate the effect of preventing and treatment of pharmaceuticals on intensive care unit-acquired weakness (ICU-AW) by systematic review. METHODS The randomized controlled trials (RCTs) concerning pharmaceutical prevention and treatment about ICU-AW in SinoMed, CNKI, Wanfang data, PubMed, Cochrane Library, Web of Science, EMbase, and other sources were searched from their foundation to May 30th, 2019. The patients in the intervention group were treated with drugs to prevent or treat ICU-AW; and those in control group were treated with other rehabilitation methods. Data searching, extracting and quality evaluation were assessed by two reviewers independently. Stata 12.0 software was then used for Meta-analysis. Only descriptive analysis was conducted when only one study was enrolled. RESULTS A total of 11 RCTs were enrolled with 1 865 patients in the intervention group and 1 894 in the control group. The results of quality evaluation showed that 4 studies were A-level and 7 studies were B-level, indicating that the overall quality of the enrolled literature was high. Meta-analysis showed that intensive insulin therapy could prevent ICU-AW [relative risk (RR) = 0.761, 95% confidence interval (95%CI) was 0.662-0.876, P = 0.000], but reduced phenylalanine loss (nmolx100 mL(-1)xmin(-1): -3+/-3 vs. -11+/-3, P < 0.05) and glutamine intake (nmolx100 mL(-1)xmin(-1): -97+/-22 vs. -51+/-13, P < 0.05). There was no significant difference in the prevention and treatment of ICU-AW between other drugs (including growth hormone, glutamine, dexmedetomidine, neostigmine, oxandrolone, and intravenous immunoglobulin) and control group. CONCLUSIONS Intensive insulin therapy can prevent ICU-AW, but the risk of hypoglycemia will increase. Other drugs including growth hormone, glutamine, dexmedetomidine, neostigmine, oxandrolone, and intravenous immunoglobulin have no obvious advantages in the prevention and treatment of ICU-AW, so no drug has been recommended to prevent and treat ICU-AW.
Fibrin tissue sealant and minor skin grafts in burn surgery: A systematic review and meta-analysis
Journal of plastic, reconstructive & aesthetic surgery : JPRAS. 2019
BACKGROUND The indications for use of fibrin glue in skin grafting burn patients remains understudied. The purpose of this study is to review the efficacy of fibrin tissue sealant in skin graft adherence, establish guidelines for use of fibrin tissue sealant, and review the cost effectiveness of fibrin glue. METHODS Publications with the following criteria were included: comparative human studies, autologous skin grafts, and autologous or commercial fibrin sealant. Outcomes assessed included evidence of engraftment, wound closure, rates of hematoma/seroma, graft loss and infection. Meta-analysis obtained pooled odds ratios for outcomes of interest. Cost analysis was performed using data available in the literature. RESULTS 7 studies and 751 interventions (fibrin) and controls (staples) were included in the final analysis. 67.6% grafts with fibrin were 100% adherent by one week, vs. 55.5% (OR 1.45, p=0.086). Complete wound closure by one month was 80.2% with fibrin, vs. 73.3% (OR 1.34, p=0.187). Hematoma/seroma occurred 38.2% with fibrin, vs. 64.7% (OR 0.487, p=0.122). Graft loss was higher in the control group, 21% vs. 12.6% (OR 0.891, p=0.604). Average cost of fibrin glue was $50 per ml, and averaged costs of stapler and staple remover was $30 USD ($10-50). CONCLUSION Fibrin glue is as effective as staples for adhering skin grafts, and trends towards lower rates of hematoma/seroma. In topographically complex regions, fibrin glue may be a better choice for adherence of skin grafts.
Evaluation of the Effect of Intravenous Immunoglobulin Dosing on Mortality in Patients with Sepsis: A Network Meta-analysis
Clinical therapeutics. 2019
PURPOSE Intravenous immunoglobulin (IVIG) has been proposed as an adjunctive therapy for sepsis. Related systematic reviews and meta-analyses of IVIG in sepsis indicate that IVIG can reduce the mortality of sepsis in adults. However, the effective dose of IVIG has not been clearly determined to date. We aimed to conduct an updated meta-analysis and use a network meta-analysis to elucidate the efficacy of IVIG dosing regimens in sepsis treatment. METHODS We searched PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), and EMBASE for articles published on or before February 14, 2019. We performed a direct meta-analysis to update a previous meta-analysis of the effects of IVIG therapy on mortality in adult patients with septic shock and a network meta-analysis to evaluate the efficacy of IVIG dosing regimens in sepsis treatment. FINDINGS Compared with the control treatment, the IVIG treatment reduced the all-cause mortality of patients with sepsis (odds ratio = 0.61; 95% CI, 0.41-0.92; P = 0.018), but significant heterogeneity was found across the studies (I(2) = 45.0%; P = 0.04). Regarding the IVIG dosage regimens, the highest total dose range (1.5-2 g/kg) was the optimal dose of administration (surface under the cumulative ranking curve = 84.7%). IMPLICATIONS On the basis of the available data, IVIG treatment is likely to reduce the all-cause mortality of patients with sepsis, and the highest total dose range (1.5-2 g/kg) is likely the optimal dose of administration.
Medical treatment for botulism
The Cochrane database of systematic reviews. 2019;4:Cd008123
BACKGROUND Botulism is an acute paralytic illness caused by a neurotoxin produced by Clostridium botulinum. Supportive care, including intensive care, is key, but the role of other medical treatments is unclear. This is an update of a review first published in 2011. OBJECTIVES To assess the effects of medical treatments on mortality, duration of hospitalization, mechanical ventilation, tube or parenteral feeding, and risk of adverse events in botulism. SEARCH METHODS We searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, and Embase on 23 January 2018. We reviewed bibliographies and contacted authors and experts. We searched two clinical trials registers, WHO ICTRP and clinicaltrials.gov, on 21 February 2019. SELECTION CRITERIA Randomized controlled trials (RCTs) and quasi-RCTs examining the medical treatment of any of the four major types of botulism (infant intestinal botulism, food-borne botulism, wound botulism, and adult intestinal toxemia). Potential medical treatments included equine serum trivalent botulism antitoxin, human-derived botulinum immune globulin intravenous (BIG-IV), plasma exchange, 3,4-diaminopyridine, and guanidine. DATA COLLECTION AND ANALYSIS We followed standard Cochrane methodology.Our primary outcome was in-hospital death from any cause occurring within four weeks from randomization or the beginning of treatment. Secondary outcomes were death from any cause occurring within 12 weeks, duration of hospitalization, duration of mechanical ventilation, duration of tube or parenteral feeding, and proportion of participants with adverse events or complications of treatment. MAIN RESULTS A single RCT met the inclusion criteria. Our 2018 search update identified no additional trials. The included trial evaluated BIG-IV for the treatment of infant botulism and included 59 treatment participants and 63 control participants. The control group received a control immune globulin that did not have an effect on botulinum toxin. Participants were followed during the length of their hospitalization to measure the outcomes of interest. There was some violation of intention-to-treat principles, and possibly some between-treatment group imbalances among participants admitted to the intensive care unit and mechanically ventilated, but otherwise the risk of bias was low. There were no deaths in either group, making any treatment effect on mortality inestimable. There was a benefit in the treatment group on mean duration of hospitalization (BIG-IV: 2.60 weeks, 95% confidence interval (CI) 1.95 to 3.25; control: 5.70 weeks, 95% CI 4.40 to 7.00; mean difference (MD) -3.10 weeks, 95% CI -4.52 to -1.68; moderate-certainty evidence); mechanical ventilation (BIG-IV: 1.80 weeks, 95% CI 1.20 to 2.40; control: 4.40 weeks, 95% CI 3.00 to 5.80; MD -2.60 weeks, 95% CI -4.06 to -1.14; low-certainty evidence); and tube or parenteral feeding (BIG-IV: 3.60 weeks, 95% CI 1.70 to 5.50; control: 10.00 weeks, 95% CI 6.85 to 13.15; MD -6.40 weeks, 95% CI -10.00 to -2.80; moderate-certainty evidence), but not on proportion of participants with adverse events or complications (BIG-IV: 63.08%; control: 68.75%; risk ratio 0.92, 95% CI 0.72 to 1.18; absolute risk reduction 0.06, 95% CI 0.22 to -0.11; moderate-certainty evidence). AUTHORS' CONCLUSIONS We found low- and moderate-certainty evidence supporting the use of BIG-IV in infant intestinal botulism. A single RCT demonstrated that BIG-IV probably decreases the duration of hospitalization; may decrease the duration of mechanical ventilation; and probably decreases the duration of tube or parenteral feeding. Adverse events were probably no more frequent with immune globulin than with placebo. Our search did not reveal any evidence examining the use of other medical treatments including serum trivalent botulism antitoxin.
Pediatric Toxic Shock Syndrome After a 7% Burn: A Case Study and Systematic Literature Review
Annals of plastic surgery. 2019
INTRODUCTION Toxic shock syndrome (TSS) is a life-threatening condition, which occurs in children after sustaining a burn. Often diagnosed retrospectively, many patients may not receive optimal treatment.The primary objective of this study was to evaluate a severe and complex case of TSS at our unit and subsequently conduct a Preferred Reporting for Systematic Reviews and Meta-Analyses-compliant systematic literature review, to identify cases of postthermal injury TSS and evaluate their presentation and management. CASE REPORT A 9-year-old boy with Down syndrome presented with a 7% total body surface area scald to his back and posterior head. Four days after discharge, he developed a fever. The following day, he deteriorated, becoming stridulous and unresponsive. A working diagnosis of TSS was made. The patient's intensive care stay was arduous with multiple complications, including 2 cardiac arrests. METHODS A Preferred Reporting for Systematic Reviews and Meta-Analyses-compliant systematic literature review was conducted. MEDLINE, PubMed, and Web of Science were searched using key terms "burns, thermal injury, scalds, paediatric, child, infant, neonate, toxic shock syndrome" to identify cases. Two authors independently checked each study against inclusion criteria. RESULTS The systematic literature search yielded 9 articles, identifying 40 cases. Ages ranged between 9 months and 8 years. The mean number of days' postburn patients presented with symptoms of TSS was 2.5 days (1-7 days). The most common presenting symptoms were fever (75%), rash (70%), and diarrhea, and/or vomiting (52.5%). Intravenous immunoglobulins were administered in 11 (27.5%) cases. DISCUSSION We have highlighted a case where a possible delayed diagnosis along with the immunodeficiency seen in Down syndrome may have impacted the severity of TSS. The literature review highlighted that a significant proportion of patients do not meet diagnostic criteria. CONCLUSIONS It is fundamental that appropriate diagnostic and management guidelines are developed. Furthermore, this case highlights the importance of educating patient's carers and health professionals of key symptoms to be wary of postburn.