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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 -
Diabetology & Metabolic Syndrome Oct 2022To assess the impact of long-acting insulin analogues, compared to intermediate acting neutral protamine Hagedron (NPH), on maternal, perinatal and neonatal outcomes. (Review)
Review
Maternal and neonatal outcomes with the use of long acting, compared to intermediate acting basal insulin (NPH) for managing diabetes during pregnancy: a systematic review and meta-analysis.
BACKGROUND
To assess the impact of long-acting insulin analogues, compared to intermediate acting neutral protamine Hagedron (NPH), on maternal, perinatal and neonatal outcomes.
METHODS
Studies for inclusion in the review were identified using a structured search strategy in PubMed, Scopus and Cochrane Central Register of Controlled Trials (CENTRAL) database. Studies that were randomized controlled trials or observational in design were considered for inclusion. Eligible studies should have compared the maternal, perinatal and neonatal outcomes between pregnant women with gestational diabetes mellitus (GDM) managed by intermediate acting (NPH) and by long-acting insulin analogues. Statistical analysis was performed using STATA software.
RESULTS
We found 17 studies to be eligible for inclusion. The mean gestational weight gain and risk of maternal hypoglycaemia, hypertensive disorder, caesarean delivery, spontaneous abortion, endometritis and wound infection or dehiscence were similar among pregnant women with GDM managed using long-acting insulin analogues and NPH. Those receiving long-acting insulin analogues had significantly lower HbA1c values in the second (WMD - .09, 95% CI 0.12, - 0.06; N = 4) and third trimester (WMD - 0.08, 95% CI - 0.14, - 0.02; N = 12). The mean gestational age and birth weight and risk of perinatal mortality, prematurity, large for gestational age, small for gestational age, shoulder dystocia and congenital abnormalities was similar among babies in both groups. No statistically significant differences in risk of admission to neonatal intensive care unit, respiratory distress, neonatal hypoglycaemia, 5 min APGAR score of < 7, neonatal hyperbilirubinemia and sepsis was observed. The quality of pooled evidence, as per GRADE criteria, was judged to be "very low" for all the maternal and neonatal outcomes considered.
CONCLUSIONS
Findings suggest no significant differences in the maternal, perinatal and neonatal outcomes between intermediate and long-acting insulin analogues. The results provide support for use of long-acting insulin analogues in women with GDM. However, evidence is still needed from high quality randomized controlled trials to arrive at a recommendation for inclusion in routine clinical care.
PubMed: 36271431
DOI: 10.1186/s13098-022-00925-7 -
Cureus Feb 2024The conventional method of heparin and protamine management during cardiopulmonary bypass (CPB) is based on total body weight which fails to account for the... (Review)
Review
BACKGROUND
The conventional method of heparin and protamine management during cardiopulmonary bypass (CPB) is based on total body weight which fails to account for the heterogeneous response to heparin in each patient. On the other hand, the literature is inconclusive on whether individualized anticoagulation management based on real-time blood heparin concentration improves post-CBP outcomes.
METHODS
We searched databases of Medline, Excerpta Medica dataBASE (EMBASE), PubMed, Cumulative Index to Nursing and Allied Health Literature (CINHL), and Google Scholar, recruiting randomized controlled trials (RCTs) and prospective studies comparing the outcomes of dosing heparin and/or protamine based on measured heparin concentration versus patient's total body weight for CPB. Random effects meta-analyses and meta-regression were conducted to compare the outcome profiles. Primary endpoints include postoperative blood loss and the correlation with heparin and protamine doses, the reversal protamine and loading heparin dose ratio; secondary endpoints included postoperative platelet counts, antithrombin III, fibrinogen levels, activated prothrombin time (aPTT), incidences of heparin rebound, and re-exploration of chest wound for bleeding.
RESULTS
Twenty-six studies, including 22 RCTs and four prospective cohort studies involving 3,810 patients, were included. Compared to body weight-based dosing, patients of individualized, heparin concentration-based group had significantly lower postoperative blood loss (mean difference (MD)=49.51 mL, 95% confidence interval (CI): 5.33-93.71), lower protamine-to-heparin dosing ratio (MD=-0.20, 95% CI: -0.32 ~ -0.12), and higher early postoperative platelet counts (MD=8.83, 95% CI: 2.07-15.59). The total heparin doses and protamine reversal were identified as predictors of postoperative blood loss by meta-regression.
CONCLUSIONS
There was a significant correlation between the doses of heparin and protamine with postoperative blood loss; therefore, précised dosing of both could be critical for reducing bleeding and transfusion requirements. Data from the enrolled studies indicated that compared to conventional weight-based dosing, individualized, blood concentration-based heparin and protamine dosing may have outcome benefits reducing postoperative blood loss. The dosing calculation of heparin based on the assumption of a one-compartment pharmacokinetic/pharmacodynamic (PK/PD) model and linear relationship between the calculated dose and blood heparin concentration may be inaccurate. With the recent advancement of the technologies of machine learning, individualized, precision management of anticoagulation for CPB may be possible in the near future.
PubMed: 38357407
DOI: 10.7759/cureus.54144 -
BMJ Open Feb 2016To compare the efficacy and safety of a concentrated formulation of insulin glargine (Gla-300) with other basal insulin therapies in patients with type 2 diabetes... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To compare the efficacy and safety of a concentrated formulation of insulin glargine (Gla-300) with other basal insulin therapies in patients with type 2 diabetes mellitus (T2DM).
DESIGN
This was a network meta-analysis (NMA) of randomised clinical trials of basal insulin therapy in T2DM identified via a systematic literature review of Cochrane library databases, MEDLINE and MEDLINE In-Process, EMBASE and PsycINFO.
OUTCOME MEASURES
Changes in HbA1c (%) and body weight, and rates of nocturnal and documented symptomatic hypoglycaemia were assessed.
RESULTS
41 studies were included; 25 studies comprised the main analysis population: patients on basal insulin-supported oral therapy (BOT). Change in glycated haemoglobin (HbA1c) was comparable between Gla-300 and detemir (difference: -0.08; 95% credible interval (CrI): -0.40 to 0.24), neutral protamine Hagedorn (NPH; 0.01; -0.28 to 0.32), degludec (-0.12; -0.42 to 0.20) and premixed insulin (0.26; -0.04 to 0.58). Change in body weight was comparable between Gla-300 and detemir (0.69; -0.31 to 1.71), NPH (-0.76; -1.75 to 0.21) and degludec (-0.63; -1.63 to 0.35), but significantly lower compared with premixed insulin (-1.83; -2.85 to -0.75). Gla-300 was associated with a significantly lower nocturnal hypoglycaemia rate versus NPH (risk ratio: 0.18; 95% CrI: 0.05 to 0.55) and premixed insulin (0.36; 0.14 to 0.94); no significant differences were noted in Gla-300 versus detemir (0.52; 0.19 to 1.36) and degludec (0.66; 0.28 to 1.50). Differences in documented symptomatic hypoglycaemia rates of Gla-300 versus detemir (0.63; 0.19 to 2.00), NPH (0.66; 0.27 to 1.49) and degludec (0.55; 0.23 to 1.34) were not significant. Extensive sensitivity analyses supported the robustness of these findings.
CONCLUSIONS
NMA comparisons are useful in the absence of direct randomised controlled data. This NMA suggests that Gla-300 is also associated with a significantly lower risk of nocturnal hypoglycaemia compared with NPH and premixed insulin, with glycaemic control comparable to available basal insulin comparators.
Topics: Body Weight; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine
PubMed: 26880669
DOI: 10.1136/bmjopen-2015-009421 -
Value in Health : the Journal of the... Feb 2018To assess the relative efficacy and safety of basal insulin regimens in adults with type 1 diabetes mellitus (T1DM). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To assess the relative efficacy and safety of basal insulin regimens in adults with type 1 diabetes mellitus (T1DM).
METHODS
A systematic review and Bayesian network meta-analysis (NMA) of randomized controlled trials comparing two or more basal insulin regimens were conducted. The following basal insulin regimens were included: Neutral Protamine Hagedorn (iNPH) (once [od], twice [bid], and four times daily [qid]), insulin detemir (iDet) (od and bid), insulin glargine 100 IU (iGlarg) (od), and insulin degludec (iDegl) (od). We searched the following databases: MEDLINE via OVID, Embase via OVID, and the Cochrane Library (Wiley). Study quality was appraised using Cochrane risk-of-bias checklist for randomized controlled trials. Two outcomes (change in hemoglobin A [HbA] and rate of severe/major hypoglycemia [SH]) were analyzed. Network inconsistency was assessed using Bucher and chi-square tests.
RESULTS
Thirty studies met the eligibility criteria. Twenty-five were included in the HbA network and 16 in the SH network. All studies were of moderate quality. No network inconsistency was evident in the HbA network. Of the seven regimens of interest, iDet (bid) had the highest probability of being best (mean change in HbA -0.48; 95% credible interval -0.69 to -0.29). In contrast, the SH network demonstrated both considerable uncertainty and significant network inconsistency (χ test, P = 0.003).
CONCLUSIONS
Of the specified frequency regimens, iDet (bid) had the highest probability of being the best basal insulin regimen in terms of reduction in HbA. Ranking of the regimens in terms of the SH rate was highly uncertain and no clear conclusion could be made.
Topics: Adult; Bayes Theorem; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Humans; Hypoglycemia; Insulin; Randomized Controlled Trials as Topic
PubMed: 29477399
DOI: 10.1016/j.jval.2017.04.024 -
Journal of Cardiothoracic and Vascular... Feb 2018The aim was to evaluate the predictive value of thromboelastometry for postoperative blood loss in adult cardiac surgery with cardiopulmonary bypass. (Review)
Review
OBJECTIVE
The aim was to evaluate the predictive value of thromboelastometry for postoperative blood loss in adult cardiac surgery with cardiopulmonary bypass.
DESIGN
Retrospective cohort study and systematic review of the literature.
SETTING
A tertiary university hospital.
PARTICIPANTS
202 patients undergoing elective cardiac surgery.
INTERVENTIONS
Thromboelastometry was performed before cardiopulmonary bypass and 3 minutes after protamine administration.
MEASUREMENTS AND MAIN RESULTS
The cohort study showed that the preoperative and postoperative thromboelastometric positive predicting value was poor (0%-22%); however, the negative predicting value was high (89%-94%). The systematic review of the literature to evaluate the predictive value of thromboelastometry for major postoperative bleeding in cardiac surgery resulted in 1,311 articles, 11 of which were eligible (n = 1,765; PubMed and Embase, until June 2016). Two studies found a good predictive value, whereas the other 9 studies showed a poor predictability for major postoperative bleeding after cardiac surgery. The overall negative predicting value was high.
CONCLUSIONS
Thromboelastometry does not predict which patients are at risk for major postoperative bleeding.
Topics: Adult; Aged; Aged, 80 and over; Cardiac Surgical Procedures; Cohort Studies; Humans; Middle Aged; Postoperative Hemorrhage; Predictive Value of Tests; Retrospective Studies; Thrombelastography
PubMed: 29126688
DOI: 10.1053/j.jvca.2017.08.025 -
International Journal of Cardiology Oct 2023To determine the safety and efficacy of protamine in the reversal of heparin in percutaneous coronary intervention (PCI). (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To determine the safety and efficacy of protamine in the reversal of heparin in percutaneous coronary intervention (PCI).
BACKGROUND
Heparin is routinely used for anticoagulation in PCI. Protamine is not used routinely to reverse heparin's effects in PCI, partly due to the perceived risk of stent thrombosis.
METHODS
Relevant studies published in English were searched for in PubMed, Embase, and Cochrane databases from inception to April 26th, 2023. Our primary outcome of interest was stent thrombosis in patients receiving PCI for all indications. Secondary outcomes included mortality, major bleeding complications, and hospitalization length. Dichotomous outcomes were analyzed using a Mantel-Haenszel random-effects model and expressed as odds ratios (OR) with their 95% confidence intervals (CI), while continuous outcomes were analyzed using an inverse variance random-effects model expressed as mean differences (MD) with their 95% CI.
RESULTS
11 studies were included in our analysis. Protamine use was not associated with stent thrombosis: OR 0.58, 95% CI: 0.33, 1.01 (p = 0.05) nor with mortality (p = 0.89). Protamine administration was associated with a decreased incidence of major bleeding complications: OR 0.48; 95% CI: 0.25, 0.95 (p = 0.03) and decreased length of hospitalization (p < 0.0001).
CONCLUSIONS
In patients pre-treated with dual antiplatelet therapy (DAPT), protamine may be a safe and efficacious option to facilitate earlier sheath removal, reduce major bleeding complications, and reduce length of hospitalization without increased risk of stent thrombosis.
Topics: Humans; Heparin; Percutaneous Coronary Intervention; Protamines; Hemorrhage; Thrombosis; Platelet Aggregation Inhibitors; Treatment Outcome
PubMed: 37429445
DOI: 10.1016/j.ijcard.2023.131168 -
BMJ Open Dec 2014To evaluate the effectiveness and safety of dipeptidyl peptidase-4 (DPP-4) inhibitors versus intermediate-acting insulin for adults with type 2 diabetes mellitus (T2DM)... (Comparative Study)
Comparative Study Meta-Analysis Review
Safety and effectiveness of dipeptidyl peptidase-4 inhibitors versus intermediate-acting insulin or placebo for patients with type 2 diabetes failing two oral antihyperglycaemic agents: a systematic review and network meta-analysis.
OBJECTIVE
To evaluate the effectiveness and safety of dipeptidyl peptidase-4 (DPP-4) inhibitors versus intermediate-acting insulin for adults with type 2 diabetes mellitus (T2DM) and poor glycaemic control despite treatment with two oral agents.
SETTING
Studies were multicentre and multinational.
PARTICIPANTS
Ten studies including 2967 patients with T2DM.
INTERVENTIONS
Studies that examined DPP-4 inhibitors compared with each other, intermediate-acting insulin, no treatment or placebo in patients with T2DM.
PRIMARY AND SECONDARY OUTCOME MEASURES
Primary outcome was glycosylated haemoglobin (HbA1c). Secondary outcomes were healthcare utilisation, body weight, fractures, quality of life, microvascular complications, macrovascular complications, all-cause mortality, harms, cost and cost-effectiveness.
RESULTS
10 randomised clinical trials with 2967 patients were included after screening 5831 titles and abstracts, and 180 full-text articles. DPP-4 inhibitors significantly reduced HbA1c versus placebo in network meta-analysis (NMA; mean difference (MD) -0.62%, 95% CI -0.93% to -0.33%) and meta-analysis (MD -0.61%, 95% CI -0.81% to -0.41%), respectively. Significant differences in HbA1c were not observed for neutral protamine Hagedorn (NPH) insulin versus placebo and DPP-4 inhibitors versus NPH insulin in NMA. In meta-analysis, no significant differences were observed between DPP-4 inhibitors and placebo for severe hypoglycaemia, weight gain, cardiovascular disease, overall harms, treatment-related harms and mortality, although patients receiving DPP-4 inhibitors experienced less infections (relative risk 0.72, 95% CI 0.57 to 0.91).
CONCLUSIONS
DPP-4 inhibitors were superior to placebo in reducing HbA1c levels in adults with T2DM taking at least two oral agents. Compared with placebo, no safety signals were detected with DPP-4 inhibitors and there was a reduced risk of infection. There was no significant difference in HbA1c observed between NPH and placebo or NPH and DPP-4 inhibitors.
TRIAL REGISTRATION NUMBER
PROSPERO # CRD42013003624.
Topics: Diabetes Mellitus, Type 2; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Incretins; Insulin; Insulin, Isophane; Treatment Outcome
PubMed: 25537781
DOI: 10.1136/bmjopen-2014-005752 -
American Journal of Health-system... Apr 2015The comparative efficacy, safety, and cost-effectiveness of rapid and long-acting insulin analogs compared with regular or neutral protamine Hagedorn nonanalog insulins... (Comparative Study)
Comparative Study Meta-Analysis Review
PURPOSE
The comparative efficacy, safety, and cost-effectiveness of rapid and long-acting insulin analogs compared with regular or neutral protamine Hagedorn nonanalog insulins or with oral antidiabetic agents in hospitalized adults were evaluated.
METHODS
A literature search was conducted to identify studies that compared the effects of rapid-acting, long-acting, or mixed insulin analogs with short- or intermediate-acting insulin or any other oral antidiabetic medication.
RESULTS
Twenty-three primary studies were included in the review. Rapid-acting analogs and basal-bolus analog regimens were found to reduce the duration of hospital stay by approximately one day compared with regular insulin and basal-bolus nonanalog regimens. One large cohort study found an adjusted 48% relative risk reduction in mortality with rapid-acting analogs versus regular insulin in a heterogeneous hospitalized hyperglycemic population. A randomized controlled trial found a significant reduction in postoperative complications with basal-bolus analogs compared with basal-bolus nonanalog insulin. When compared with regular sliding-scale insulin (SSI), fixed-dose insulin glargine with or without insulin glulisine was found to reduce the blood glucose concentration in patients with type 2 diabetes and reduce postoperative complications in surgical patients with diabetes. The quality of evidence was primarily very low or low for most outcomes.
CONCLUSION
A systematic literature review revealed a very low or low quality of evidence, suggesting that, compared with nonanalog regimens, rapid-acting insulin analogs reduce the duration of hospital stay and mortality rates and that basal- bolus analog regimens may reduce the duration of hospital stay and postoperative complications. There is also a low quality of evidence to suggest that a fixed-dose analog regimen of insulin glargine with or without insulin glulisine is more effective than regular SSI for reducing blood glucose concentrations and postoperative complications.
Topics: Cost-Benefit Analysis; Hospitalization; Humans; Insulin
PubMed: 25788506
DOI: 10.2146/ajhp140161 -
Canadian Journal of Anaesthesia =... May 2015Heparin anticoagulation followed by protamine reversal is commonly used in cardiopulmonary bypass (CPB) cardiac procedures, but this strategy has some limitations. The... (Review)
Review
PURPOSE
Heparin anticoagulation followed by protamine reversal is commonly used in cardiopulmonary bypass (CPB) cardiac procedures, but this strategy has some limitations. The primary objective of this study was to determine the reliable alternatives for anticoagulation during CPB for cardiac surgery. For each drug proposed, the secondary objectives were to outline the main advantages and disadvantages, to propose a therapeutic protocol, and to provide a cost-benefit analysis.
SOURCE
A systematic review of the literature was performed between September 2012 and December 2013. It was based on the protocol established by the "Cochrane collaboration Handbook". Twenty articles were analyzed. The Thériaque database from the University Hospital of Grenoble made the economic analysis possible.
PRINCIPAL FINDINGS
Seven alternative anticoagulation strategies were considered: danaparoid sodium, lepirudin, argatroban, bivalirudin, ancrod, idraparinux, and EP217609. Danaparoid sodium has issues with individual variability. Several studies (EVOLUTION-ON, CHOOSE-ON) proposed a reliable therapeutic protocol for bivalirudin. Ancrod resulted in an increase in the transfusion of blood products. Direct thrombin inhibitors offer a promising alternative. EP217609 is a synthetic anticoagulant currently undergoing Phase IIa clinical trials. It is an indirect inhibitor of factor Xa, a direct inhibitor of free and bound thrombin, and can be neutralized by avidin.
CONCLUSIONS
The ideal anticoagulation strategy for cardiac surgery with CPB does not exist. Heparin and protamine remain the gold standard for anticoagulation therapy. To date, bivalirudin is the most promising molecule despite its high cost and lack of a readily available antagonist.
Topics: Anticoagulants; Cardiopulmonary Bypass; Cost-Benefit Analysis; Drug Costs; Heparin; Hirudins; Humans; Peptide Fragments; Protamines; Recombinant Proteins
PubMed: 25697279
DOI: 10.1007/s12630-015-0339-6