-
The Cochrane Database of Systematic... Nov 2020Evidence that antihyperglycaemic therapy is beneficial for people with type 2 diabetes mellitus is conflicting. While the United Kingdom Prospective Diabetes Study... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Evidence that antihyperglycaemic therapy is beneficial for people with type 2 diabetes mellitus is conflicting. While the United Kingdom Prospective Diabetes Study (UKPDS) found tighter glycaemic control to be positive, other studies, such as the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, found the effects of an intensive therapy to lower blood glucose to near normal levels to be more harmful than beneficial. Study results also showed different effects for different antihyperglycaemic drugs, regardless of the achieved blood glucose levels. In consequence, firm conclusions on the effect of interventions on patient-relevant outcomes cannot be drawn from the effect of these interventions on blood glucose concentration alone. In theory, the use of newer insulin analogues may result in fewer macrovascular and microvascular events.
OBJECTIVES
To compare the effects of long-term treatment with (ultra-)long-acting insulin analogues (insulin glargine U100 and U300, insulin detemir and insulin degludec) with NPH (neutral protamine Hagedorn) insulin (human isophane insulin) in adults with type 2 diabetes mellitus.
SEARCH METHODS
For this Cochrane Review update, we searched CENTRAL, MEDLINE, Embase, ICTRP Search Portal and ClinicalTrials.gov. The date of the last search was 5 November 2019, except Embase which was last searched 26 January 2017. We applied no language restrictions.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing the effects of treatment with (ultra-)long-acting insulin analogues to NPH in adults with type 2 diabetes mellitus.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials, assessed risk of bias, extracted data and evaluated the overall certainty of the evidence using GRADE. Trials were pooled using random-effects meta-analyses.
MAIN RESULTS
We identified 24 RCTs. Of these, 16 trials compared insulin glargine to NPH insulin and eight trials compared insulin detemir to NPH insulin. In these trials, 3419 people with type 2 diabetes mellitus were randomised to insulin glargine and 1321 people to insulin detemir. The duration of the included trials ranged from 24 weeks to five years. For studies, comparing insulin glargine to NPH insulin, target values ranged from 4.0 mmol/L to 7.8 mmol/L (72 mg/dL to 140 mg/dL) for fasting blood glucose (FBG), from 4.4 mmol/L to 6.6 mmol/L (80 mg/dL to 120 mg/dL) for nocturnal blood glucose and less than 10 mmol/L (180 mg/dL) for postprandial blood glucose, when applicable. Blood glucose and glycosylated haemoglobin A1c (HbA1c) target values for studies comparing insulin detemir to NPH insulin ranged from 4.0 mmol/L to 7.0 mmol/L (72 mg/dL to 126 mg/dL) for FBG, less than 6.7 mmol/L (120 mg/dL) to less than 10 mmol/L (180 mg/dL) for postprandial blood glucose, 4.0 mmol/L to 7.0 mmol/L (72 mg/dL to 126 mg/dL) for nocturnal blood glucose and 5.8% to less than 6.4% HbA1c, when applicable. All trials had an unclear or high risk of bias for several risk of bias domains. Overall, insulin glargine and insulin detemir resulted in fewer participants experiencing hypoglycaemia when compared with NPH insulin. Changes in HbA1c were comparable for long-acting insulin analogues and NPH insulin. Insulin glargine compared to NPH insulin had a risk ratio (RR) for severe hypoglycaemia of 0.68 (95% confidence interval (CI) 0.46 to 1.01; P = 0.06; absolute risk reduction (ARR) -1.2%, 95% CI -2.0 to 0; 14 trials, 6164 participants; very low-certainty evidence). The RR for serious hypoglycaemia was 0.75 (95% CI 0.52 to 1.09; P = 0.13; ARR -0.7%, 95% CI -1.3 to 0.2; 10 trials, 4685 participants; low-certainty evidence). Treatment with insulin glargine reduced the incidence of confirmed hypoglycaemia and confirmed nocturnal hypoglycaemia. Treatment with insulin detemir compared to NPH insulin found an RR for severe hypoglycaemia of 0.45 (95% CI 0.17 to 1.20; P = 0.11; ARR -0.9%, 95% CI -1.4 to 0.4; 5 trials, 1804 participants; very low-certainty evidence). The Peto odds ratio for serious hypoglycaemia was 0.16, 95% CI 0.04 to 0.61; P = 0.007; ARR -0.9%, 95% CI -1.1 to -0.4; 5 trials, 1777 participants; low-certainty evidence). Treatment with detemir also reduced the incidence of confirmed hypoglycaemia and confirmed nocturnal hypoglycaemia. Information on patient-relevant outcomes such as death from any cause, diabetes-related complications, health-related quality of life and socioeconomic effects was insufficient or lacking in almost all included trials. For those outcomes for which some data were available, there were no meaningful differences between treatment with glargine or detemir and treatment with NPH. There was no clear difference between insulin-analogues and NPH insulin in terms of weight gain. The incidence of adverse events was comparable for people treated with glargine or detemir, and people treated with NPH. We found no trials comparing ultra-long-acting insulin glargine U300 or insulin degludec with NPH insulin.
AUTHORS' CONCLUSIONS
While the effects on HbA1c were comparable, treatment with insulin glargine and insulin detemir resulted in fewer participants experiencing hypoglycaemia when compared with NPH insulin. Treatment with insulin detemir also reduced the incidence of serious hypoglycaemia. However, serious hypoglycaemic events were rare and the absolute risk reducing effect was low. Approximately one in 100 people treated with insulin detemir instead of NPH insulin benefited. In the studies, low blood glucose and HbA1c targets, corresponding to near normal or even non-diabetic blood glucose levels, were set. Therefore, results from the studies are only applicable to people in whom such low blood glucose concentrations are targeted. However, current guidelines recommend less-intensive blood glucose lowering for most people with type 2 diabetes in daily practice (e.g. people with cardiovascular diseases, a long history of type 2 diabetes, who are susceptible to hypoglycaemia or older people). Additionally, low-certainty evidence and trial designs that did not conform with current clinical practice meant it remains unclear if the same effects will be observed in daily clinical practice. Most trials did not report patient-relevant outcomes.
Topics: Bias; Diabetes Mellitus, Type 2; Hemoglobin A; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Randomized Controlled Trials as Topic
PubMed: 33166419
DOI: 10.1002/14651858.CD005613.pub4 -
Scandinavian Journal of Surgery : SJS :... Jun 2021Acute mesenteric venous thrombosis accounts for up to 20% of all patients with acute mesenteric ischemia in high-income countries. Acute mesenteric venous thrombosis is...
BACKGROUND AND AIMS
Acute mesenteric venous thrombosis accounts for up to 20% of all patients with acute mesenteric ischemia in high-income countries. Acute mesenteric venous thrombosis is nowadays relatively more often diagnosed with intravenous contrast-enhanced computed tomography in the portal phase than at explorative laparotomy No high-quality comparative studies between anticoagulation alone, endovascular therapy, or surgery exists. The aim of the present systematic review was to offer a contemporary overview on management.
MATERIALS AND METHODS
Eleven relevant published original studies with series of at least ten patients were retrieved from a Pub Med search between 2015 and 2020 using the Medical Subject Heading term "mesenteric venous thrombosis."
RESULTS
When MVT is diagnosed early, immediate anticoagulation with either unfractionated heparin or subcutaneous low-molecular-weight heparin should commence. Surgeons need to be aware of the importance to scrutinize the computed tomography images themselves for assessment of secondary intestinal abnormalities to mesenteric venous thrombosis and the risk of bowel resection and worse prognosis. Progression toward peritonitis is an indication for explorative laparotomy and assessment of bowel viability. Frank transmural small bowel necrosis should be resected and bowel anastomosis may be delayed for several days until second look. Meanwhile, intravenous full-dose unfractionated heparin should be given at the end of the first operation. Postoperative major intra-abdominal or gastrointestinal bleeding occurs rarely, but the heparin effect can instantaneously be reversed by . Patients who do not improve during conservative therapy with anticoagulation alone but without developing peritonitis may be subjected to endovascular therapy in expert centers. When the patient's intestinal function has recovered, with or without bowel resection, switch from parenteral unfractionated heparin or low-molecular-weight heparin therapy to oral anticoagulation can be performed. There is a trend that direct oral anticoagulants are increasingly used instead of vitamin K antagonists. Up to now, direct oral anticoagulants have been shown to be equally effective with the same rate of bleeding complications. Patients with no strong permanent trigger factor for mesenteric venous thrombosis such as intra-abdominal cancer should undergo blood screening for inherited and acquired thrombophilia.
CONCLUSION
Early diagnosis with emergency computed tomography with intravenous contrast-enhancement and imaging in the portal phase and anticoagulation therapy is necessary to be able to have a succesful non-operative succesful course.
Topics: Anticoagulants; Heparin; Humans; Mesenteric Ischemia; Mesenteric Veins; Venous Thrombosis
PubMed: 33118463
DOI: 10.1177/1457496920969084 -
The Cochrane Database of Systematic... Oct 2020The Cystic Fibrosis Foundation recommends both short-term and long-acting insulin therapy when cystic fibrosis-related diabetes (CFRD) has been diagnosed. Diagnosis is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The Cystic Fibrosis Foundation recommends both short-term and long-acting insulin therapy when cystic fibrosis-related diabetes (CFRD) has been diagnosed. Diagnosis is based on: an elevated fasting blood glucose level greater than 6.94 mmol/L (125 mg/dL); or oral glucose tolerance tests greater than 11.11 mmol/L (200 mg/dL) at two hours; or symptomatic diabetes for random glucose levels greater than 11.11 mmol/L (200 mg/dL); or glycated hemoglobin levels of at least 6.5%. This is an update of a previously published review.
OBJECTIVES
To establish the effectiveness of insulin and oral agents for managing diabetes in people with cystic fibrosis in relation to blood sugar levels, lung function and weight management.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also handsearched abstracts from pulmonary symposia and the North American Cystic Fibrosis Conferences. Date of most recent register search: 10 September 2020. We searched online trials registries; date of most recent searches: 21 March 2020.
SELECTION CRITERIA
Randomized controlled trials comparing all methods of pharmacological diabetes therapy in people with diagnosed CFRD.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data and assessed the risk of bias in the included studies. Authors also used GRADE to assess the quality of the evidence.
MAIN RESULTS
The searches identified 29 trials (45 references). Four included trials provide results: one short-term single-center cross-over trial (seven adults) comparing insulin with oral repaglinide and no medication in adults with CFRD and normal fasting glucose; one long-term multicenter trial (61 adults with CFRD) comparing insulin with oral repaglinide and placebo; one long-term multicenter trial (67 adults) comparing insulin with oral repaglinide; and one 12-week single-center cross-over trial (20 adults) comparing the long-acting insulin glargine to short-term neutral protamine Hagedorn insulin. Two ongoing trials of newly approved incretin mimics have been noted for possible future inclusion. Downgrading of the quality of the evidence was mainly due to risks of bias across all domains, but particularly due to concerns surrounding allocation concealment and selective reporting. There were also some concerns due to imprecision from small sample sizes and low event rates. Finally, there may be some bias due to the amounts of insulin and repaglinide given not being comparable. Data from one trial comparing insulin to placebo (39 participants) did not show any difference between groups for the primary outcomes of blood glucose levels (very low-quality evidence), lung function (low-quality evidence) or nutritional status (low-quality evidence). Similarly, no differences between groups were seen for the secondary outcomes of number of hypoglycemic episodes (low-quality evidence), secondary infection complications or quality of life (QoL). These results were mirrored in the narrative reports for the second trial in this comparison (seven participants). Data from the one-year trial comparing repaglinide to placebo (38 participants), showed no differences between groups for the primary outcomes of blood glucose levels (very low-quality evidence), lung function (low-quality evidence) and nutritional status (low-quality evidence). Also, no differences were seen between groups for the secondary outcomes of number of hypoglycemic episodes (low-quality evidence), secondary infection complications or QoL. These findings were mirrored in the narrative reports for the second trial (n = 7) in this comparison. Three trials compared insulin to repaglinide (119 participants). Data from one trial (n = 67) showed no difference in blood glucose levels at either 12 months (high-quality evidence) or 24 months; narrative reports from one trial (45 participants) reported no difference between groups, but the second trial (7 participants) reported a beneficial effect of insulin over repaglinide. Two trials (112 participants) found no difference between insulin and repaglinide in lung function or nutritional status (moderate-quality evidence). Two trials (56 participants) reported no difference in the number of hypoglycemic episodes (low-quality evidence). One trial (45 participants) reported no difference between groups in secondary infections and cystic fibrosis QoL. The single trial comparing glargine to neutral protamine Hagedorn insulin did not report directly on the review's primary outcomes, but did report no differences between groups in post-prandial glucose values and weight; neither group reported infectious complications. There was no difference in episodes of hypoglycemia (very low-quality evidence) and while there was no difference reported in QoL, all participants opted to continue treatment with glargine after the trial was completed. Mortality was not reported by any trial in any comparison, but death was not given as a reason for withdrawal in any trial.
AUTHORS' CONCLUSIONS
This review has not found any conclusive evidence that any agent has a distinct advantage over another in controlling hyperglycemia or the clinical outcomes associated with CFRD. Given the treatment burden already experienced by people with cystic fibrosis, oral therapy may be a viable treatment option. While some cystic fibrosis centers use oral medications to help control diabetes, the Cystic Fibrosis Foundation (USA) clinical practice guidelines support the use of insulin therapy and this remains the most widely-used treatment method. Randomized controlled trials specifically related to controlling diabetes and its impact on the course of pulmonary disease process in cystic fibrosis continue to be a high priority. Specifically, investigators should evaluate adherence to different therapies and also whether there is benefit in using additional hypoglycemic agents as well as the newly approved incretin mimics. Agents that potentiate insulin action, especially agents with additional anti-inflammatory potential should also be further investigated as adjuvant therapy to insulin.
Topics: Administration, Oral; Bias; Blood Glucose; Carbamates; Cystic Fibrosis; Diabetes Mellitus; Fasting; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Piperidines; Randomized Controlled Trials as Topic
PubMed: 33075159
DOI: 10.1002/14651858.CD004730.pub5 -
Scientific Reports Oct 2020Studies have reported the genetic gives rise to male infertility. The aim of the present meta-analysis was to evaluate the association between PRM1 (rs737008 and... (Meta-Analysis)
Meta-Analysis
Studies have reported the genetic gives rise to male infertility. The aim of the present meta-analysis was to evaluate the association between PRM1 (rs737008 and rs2301365) and PRM2 (rs1646022 and rs2070923) polymorphisms and susceptibility to male infertility. The association between PRM1 and PRM2 polymorphisms and the risk of male infertility was evaluated using specific search terms in the Web of Science, Cochrane Library, PubMed, and Scopus databases without language restriction until January 28, 2020. The association was determined by odds ratio (OR) and 95% confidence interval (CI) on five genetic models using Review Manager 5.3 software. The funnel plot analysis and sensitivity analysis were done by the Comprehensive Meta-analysis 2.0 software. Out of 261 records retrieved from the databases, 17 studies were analyzed in the meta-analysis, including the four PRM polymorphisms. The pooled results as OR (P-value) showed 0.96 (0.44), 1.04 (0.70), 0.94 (0.51), 0.94 (0.48), and 1.03 (0.72) for PRM1 rs737008 polymorphism and 1.67 (0.0007), 1.73 (0.06), 1.50 (0.007), 1.56 (0.004), and 1.62 (0.33) for PRM1 rs2301365 polymorphism in allele, homozygous, heterozygous, recessive, and dominant models, respectively. Moreover, the pooled results as OR (P-value) showed 1.19 (0.004), 1.15 (0.26), 1.08 (0.70), 1.05 (0.76), and 0.98 (0.82) for PRM2 rs1646022 and 0.88 (0.04), 0.84 (0.10), 1.05 (0.81), 0.90 (0.24), and 0.80 (0.02) for PRM2 rs2070923 in allele, homozygous, heterozygous, recessive, and dominant models, respectively. The results showed PRM1 rs2301365 and PRM2 rs1646022 polymorphisms were associated with an elevated risk of male infertility and PRM2 rs2070923 polymorphism had a protective role in infertile men.
Topics: Alleles; Genes, Dominant; Genes, Recessive; Genetic Association Studies; Genetic Predisposition to Disease; Heterozygote; Homozygote; Humans; Infertility, Male; Male; Polymorphism, Genetic; Protamines; Regression Analysis; Risk
PubMed: 33057064
DOI: 10.1038/s41598-020-74233-3 -
Journal of Clinical Anesthesia Dec 2020Activated clotting time (ACT) is a non-specific test to evaluate the adequacy of systemic heparinization whose value could be influenced by many factors. Tranexamic acid... (Meta-Analysis)
Meta-Analysis
STUDY OBJECTIVE
Activated clotting time (ACT) is a non-specific test to evaluate the adequacy of systemic heparinization whose value could be influenced by many factors. Tranexamic acid (TXA) is a widely used antifibrinolytic agent worldwide and whether TXA influences ACT value in cardiac surgical patients remains unknown. Current study was performed to address this question.
DESIGN
Systematic review and meta-analysis. PUBMED, Cochrane Library, EMBASE, OVID and Chinese BioMedical Literature & Retrieval System were searched using search terms "tranexamic acid", "activated clotting time", "cardiac surgery", "randomized controlled trial" till May 7th, 2020, to identify all relevant randomized controlled trials (RCTs).
SETTING
Operating room.
PATIENTS
Cardiac surgical patients.
INTERVENTIONS
TXA or placebo.
MEASUREMENTS
Primary outcomes of interest included peri-operative ACT values. Secondary outcomes of interest include heparin dosage, protamine dosage, postoperative bleeding and blood transfusion.
MAIN RESULTS
Search yielded 13 studies including 1168 patients, and 619 patients were allocated into Group TXA and 549 into Group Control (placebo). Meta-analysis suggested that, ACT values after heparinization [(WMD = -1.45; 95%CI: -12.52 to 15.43; P = 0.84)] and after protamine [(WMD = -1.18; 95%CI: -2.81 to 0.46; P = 0.16)] were comparable between Group TXA and Group Control, and that TXA did not influence heparin dose in adult patients [(WMD = 0.38; 95%CI: 0.30 to 0.46; P<0.00001) with no heterogeneity (I = 4%, P = 0.35)] and protamine dose for heparin reversal [(WMD = 5.23; 95%CI: -0.33 to 10.80; P = 0.07) with no heterogeneity (I = 0, P = 0.58)]. Meta-analysis also demonstrated that, TXA administration significantly reduced post-operative bleeding volume [(WMD = -126.33; 95%CI: -177.46 to -75.19; P < 0.0001), post-operative red blood cell (RBC) transfusion volume [(WMD = -71.86; 95% CI: -88.22 to -55.50; P < 0.00001), fresh frozen plasma (FFP) transfusion volume [(WMD = -13.83; 95% CI: -23.67 to -4.00; P = 0.006) and platelet concentrate (PC) transfusion volume [(WMD = -0.20; 95% CI: -0.29 to -0.10; P < 0.0001).
CONCLUSION
This meta-analysis suggested that, TXA administration did not influence ACT value, heparin and protamine doses, but significantly reduced post-operative blood loss and transfusion requirement in cardiac surgical patients.
Topics: Antifibrinolytic Agents; Blood Loss, Surgical; Cardiac Surgical Procedures; Humans; Postoperative Hemorrhage; Tranexamic Acid
PubMed: 32889412
DOI: 10.1016/j.jclinane.2020.110020 -
World Neurosurgery May 2020Cerebral venous thrombosis (CVT) is a rare type of stroke whose pathophysiology differs from arterial stroke. CVT is treated with systemic anticoagulant therapy even in...
OBJECTIVE
Cerebral venous thrombosis (CVT) is a rare type of stroke whose pathophysiology differs from arterial stroke. CVT is treated with systemic anticoagulant therapy even in the setting of intracerebral hemorrhage. Patients who do not respond adequately may require decompressive surgery. The study objective was to examine the timing of anticoagulation in patients with CVT who require decompressive surgery through systematic literature review and consecutive case series.
METHODS
A review of the literature was performed through PubMed using key word search to identify case series and cohort studies examining timing of anticoagulation following decompressive surgery. Our case series included 4 patients who had decompressive surgery for hemorrhagic CVT between 1 January, 2015 and 31 December, 2016 at our comprehensive stroke center.
RESULTS
The literature review summarizes 243 patients from 15 studies whose timing of anticoagulation varied. The review suggests anticoagulation can be safely resumed at 48 hours postoperatively based on larger series and as early as 12 hours in smaller series, especially when delivered as a half or prophylactic dose. In our case series, timing of anticoagulation varied slightly but was started or resumed within 38-44 hours postoperatively in 3 patients and was started at the time of decompressive surgery without interruption in 1 patient. No patient had worsening hemorrhage or new hemorrhage while 2 patients rethrombosed.
CONCLUSIONS
Despite the lack of high-quality studies, this systematic review of patients with CVT requiring decompressive surgery indicates that anticoagulation can be safely initiated or resumed around 24-48 hours postoperatively; our series supports the existing literature.
Topics: Adult; Anticoagulants; Cerebral Angiography; Cerebral Hemorrhage; Decompressive Craniectomy; Endovascular Procedures; Female; Heparin; Heparin Antagonists; Humans; Male; Middle Aged; Postoperative Hemorrhage; Postoperative Period; Protamines; Sinus Thrombosis, Intracranial; Thrombectomy; Thrombolytic Therapy; Time Factors
PubMed: 32105874
DOI: 10.1016/j.wneu.2020.02.084 -
The International Journal of Artificial... Sep 2020Extracorporeal membrane oxygenation is essential for the treatment of refractory cardiopulmonary failure. Its use may be complicated by worse haemorrhagic complications...
Extracorporeal membrane oxygenation is essential for the treatment of refractory cardiopulmonary failure. Its use may be complicated by worse haemorrhagic complications exacerbated by extracorporeal membrane oxygenation-related therapeutic anticoagulation. Progressive technological advancements have made extracorporeal membrane oxygenation components less thrombogenic, potentially allowing its application with temporary avoidance of systemic anticoagulants. A systematic review of all the available experiences, reporting the use of extracorporeal membrane oxygenation without systemic anticoagulation in the published literature was performed. Only patient series were included, irrespective of the clinical indication. The survival, extracorporeal membrane oxygenation system-related dysfunction and complications rates, as well as in-hospital outcome, were analysed. Six studies were selected for the analysis. Veno-arterial extracorporeal membrane oxygenation was used in 84% of patients, while veno-venous extracorporeal membrane oxygenation was applied in the remaining cases. Anticoagulation was avoided because of the high risk of bleeding after cardiac surgery (64%), active major bleeding (23%) or presence of severe traumatic injury (9%). Duration of support ranged from 0.3 to 1128 h. Heparin was antagonized by protamine in all the post-cardiotomy cases. Successfully extracorporeal membrane oxygenation weaning was achieved in 74% of the treated cases, with a hospital discharge of 58% of patients. Rates of extracorporeal membrane oxygenation malfunctioning due to clot formation and blood transfusion requirement varied remarkably in the published series. Extracorporeal membrane oxygenation without systemic anticoagulation appears feasible in selected circumstances. Further investigations are warranted to elucidate actual aspects regarding extracorporeal membrane oxygenation system performance, related adverse events and benefits associated with this management.
Topics: Adult; Aged; Anticoagulants; Extracorporeal Membrane Oxygenation; Female; Heart Failure; Humans; Male; Middle Aged
PubMed: 32037946
DOI: 10.1177/0391398820904372 -
Medicine Dec 2019Hemocoagulase is isolated and purified from snake venoms. Hemocoagulase agents have been widely used in the prevention and treatment of surgical bleeding. A systematic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hemocoagulase is isolated and purified from snake venoms. Hemocoagulase agents have been widely used in the prevention and treatment of surgical bleeding. A systematic review was performed to evaluate the effects of hemocoagulase on postoperative bleeding and transfusion in patients who underwent cardiac surgery.
METHODS
Electronic databases were searched to identify all clinical trials comparing hemocoagulase with placebo/blank on postoperative bleeding and transfusion in patients undergoing cardiac surgery. Two authors independently extracted perioperative data and outcome data. For continuous variables, treatment effects were calculated as weighted mean difference and 95% confidential interval (CI). For dichotomous data, treatment effects were calculated as odds ratio and 95% CI. Each outcome was tested for heterogeneity, and randomized-effects or fixed-effects model was used in the presence or absence of significant heterogeneity. Sensitivity analyses were done by examining the influence of statistical model and individual trial on estimated treatment effects. Publication bias was explored through visual inspection of funnel plots of the outcomes. Statistical significance was defined as P < .05.
RESULTS
Our search yielded 12 studies including 900 patients, and 510 patients were allocated into hemocoagulase group and 390 into control group. Meta-analysis suggested that, hemocoagulase-treated patients had less bleeding volume, reduced red blood cells and fresh frozen plasma transfusion, and higher hemoglobin level than those of controlled patients postoperatively. Meta-analysis also showed that, hemocoagulase did not influence intraoperative heparin or protamine dosages and postoperative platelet counts. Meta-analysis demonstrated that, hemocoagulase-treated patients had significantly shorter postoperative prothrombin time, activated partial thromboplastin time, and thrombin time, higher fibrinogen level and similar D-dimer level when compared to control patients.
CONCLUSION
This meta-analysis has found some evidence showing that hemocoagulase reduces postoperative bleeding, and blood transfusion requirement in patients undergoing cardiac surgery. However, these findings should be interpreted rigorously. Further well-conducted trials are required to assess the blood-saving effects and mechanisms of Hemocoagulase.
Topics: Batroxobin; Blood Transfusion; Cardiac Surgical Procedures; Hemostatics; Humans; Postoperative Hemorrhage
PubMed: 31876750
DOI: 10.1097/MD.0000000000018534 -
European Journal of Vascular and... Jan 2020Heparin has a non-predictable effect in the individual patient. The activated clotting time (ACT) is used to measure the level of anticoagulation after administration of...
OBJECTIVES
Heparin has a non-predictable effect in the individual patient. The activated clotting time (ACT) is used to measure the level of anticoagulation after administration of heparin. To date, appropriate heparin dose protocols and corresponding therapeutic ACT values have not been established in non-cardiac arterial procedures (NCAP). The aim of this review was to study the use of ACT monitoring during NCAP, and whether an optimal ACT could be determined based on the fewest arterial thrombo-embolic complications (ATEC) and bleeding complications.
METHODS
This systematic review was performed in accordance with the PRISMA Guidelines. A systematic search was conducted in MEDLINE, EMBASE, and the Cochrane database. Any associations were evaluated between peri-procedural ACT levels and ATEC and bleeding complications detected during the same admission as the primary procedure or during 30 day follow up. Also, heparin dose protocols, peri-procedural target ACTs, different ACT devices, protamine use and pre-, peri-, and post-procedural anticoagulation therapy were evaluated.
RESULTS
In total, 21 studies with 3982 patients were included, on both open and endovascular NCAP. Four studies were primarily designed to correlate peak peri-procedural ACT with clinical outcomes; however, the definitions of the results and the clinical outcomes were too heterogeneous for analysis. There was major variability in all studied aspects of ACT measurement, heparin and protamine use, and in the type of procedures in the included studies. Overall methodological quality of the included studies was poor. No randomised controlled trials were found. Studies were at a high risk of bias.
CONCLUSIONS
This systematic review demonstrates a lack of data and no consensus in the literature concerning the optimal ACT, and the possible association with haemorrhagic complications and ATEC during NCAP.
Topics: Anticoagulants; Arteries; Blood Coagulation; Blood Loss, Surgical; Consensus; Dose-Response Relationship, Drug; Drug Monitoring; Endovascular Procedures; Heparin; Humans; Monitoring, Intraoperative; Thromboembolism
PubMed: 31699657
DOI: 10.1016/j.ejvs.2019.08.007 -
Cellular and Molecular Biology... Jul 2019Heparin and protamine are two indispensable agents of cardiopulmonary bypass surgery with effects on the cardiovascular and hematological system. Heparin is used as an...
Heparin and protamine are two indispensable agents of cardiopulmonary bypass surgery with effects on the cardiovascular and hematological system. Heparin is used as an anticoagulant in open heart surgery; whereas protamine is used to neutralize heparin effects when surgery is terminated. Protamine is given in order to neutralize heparin effects after cardiopulmonary bypass surgery and it causes hypotension in patients. However, the mechanism of this side effect is not clearly known. Current mechanism is that hypotension occurs after the administration of protamine due to the conformational change in the calcium channels or anaphylactoid thromboxane release or serum ionized calcium levels. The present study was to explain how protamine causes hypotension in evidence-based medicine indexed in PubMed and Web of Science. In addition to above mechanisms, possibly the infused protamine binds heparin and causes the coagulation cascade to activate heparin-AT complex on thrombin beside activating FXIa, FXa and FIXa and causing the re-use of Ca2+. The re-use of Ca2+ at the coagulation cascade initiates an anion gap and it is assumed that hypotension develops because of the Ca2+ deficiency. Ca2+ ions are trapped in the thrombus by the resumption of thrombus formation. Ca2+ ions trapped in the thrombus cannot be used, so that Ca2+ ion deficit will develop in circulation and hypotension occurs due to the insufficiency of Ca2+ ions. The administration of Ca2+ ions together with the protamine might help to eliminate the side effect of the protamine (hypotension) while neutralizing heparin after open heart surgery in light of the information provided in the literature.
Topics: Blood Pressure; Calcium; Cardiopulmonary Bypass; Homeostasis; Humans; Hypotension; Protamines; Thrombosis
PubMed: 31472056
DOI: No ID Found