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1.
Mar Drugs ; 17(9)2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31533230

RESUMO

Protamine sulfate (PS) is a polycationic protein drug obtained from the sperm of fish, and is used to reverse the anticoagulant effect of unfractionated heparin (UFH). However, the interactions between PS, UFH, and platelets are still not clear. We measured the platelet numbers and collagen-induced aggregation, P-selectin, platelet factor 4, ß-thromboglobulin, prostacyclin metabolite, D-dimers, activated partial thromboplastin time, prothrombin time, anti-factor Xa, fibrinogen, thrombus weight and megakaryocytopoiesis in blood collected from mice and rats in different time points.. All of the groups were treated intravenously with vehicle, UFH, PS, or UFH with PS. We found a short-term antiplatelet activity of PS in mice and rats, and long-term platelet-independent antithrombotic activity in rats with electrically-induced thrombosis. The antiplatelet and antithrombotic potential of PS may contribute to bleeding risk in PS-overdosed patients. The inhibitory effect of PS on the platelets was attenuated by UFH without inducing thrombocytopenia. Treatment with UFH and PS did not affect the formation, number, or activation of platelets, or the thrombosis development in rodents.


Assuntos
Anticoagulantes/efeitos adversos , Antagonistas de Heparina/efeitos adversos , Heparina/efeitos adversos , Protaminas/efeitos adversos , Trombocitopenia/diagnóstico , Animais , Anticoagulantes/administração & dosagem , Plaquetas/efeitos dos fármacos , Modelos Animais de Doenças , Hemorragia/sangue , Hemorragia/induzido quimicamente , Hemorragia/prevenção & controle , Heparina/administração & dosagem , Antagonistas de Heparina/administração & dosagem , Humanos , Masculino , Camundongos , Tempo de Tromboplastina Parcial , Agregação Plaquetária/efeitos dos fármacos , Protaminas/administração & dosagem , Ratos , Trombocitopenia/sangue , Trombocitopenia/induzido quimicamente , Fatores de Tempo
2.
Scand Cardiovasc J ; 53(6): 355-360, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31476919

RESUMO

Objectives: Protamine reduces platelet aggregation after cardiopulmonary bypass (CPB). We studied the inhibitory effect of a reduced protamine dose, the duration of impaired platelet function and the possible correlation to postoperative bleeding. Design: Platelet function was assessed by impedance aggregometry in 30 patients undergoing cardiac surgery with CPB at baseline, before protamine administration, after 70% and 100% of the calculated protamine dose, after 20 minutes and at arrival to the intensive care unit. Adenosine diphosphate (ADP), thrombin receptor activating peptide-6 (TRAP), arachidonic acid (AA) and collagen (COL) were used as activators. Blood loss was measured during operation and three hours after surgery. Results are presented as median (25th-75th percentile). Results: Platelet aggregation decreased markedly after the initial dose of protamine (70%) with all activators; ADP 89 (71-110) to 54 (35-78), TRAP 143 (116-167) to 109 (77-136), both p < .01; AA 25 (16-49) to 17 (12-24) and COL 92 (47-103) to 60 (38-81) U, both p < .05. No further decrease was seen after 100% protamine. The effect was transient and after twenty minutes platelet aggregation had started to recover; ADP 76 (54-106), TRAP 138 (95-158), AA 20 (10-35), COL 70 (51-93) U. Blood loss during operation correlated to aggregometry measured at baseline and after protaminization. Conclusions: Protamine after CPB induces a marked decrease in platelet aggregation already at a protamine-heparin ratio of 0.7:1. The impairment seems to be transient and recovery had started after 20 minutes.


Assuntos
Ponte de Artéria Coronária , Implante de Prótese de Valva Cardíaca , Antagonistas de Heparina/efeitos adversos , Agregação Plaquetária/efeitos dos fármacos , Protaminas/efeitos adversos , Idoso , Perda Sanguínea Cirúrgica/prevenção & controle , Ponte Cardiopulmonar , Ponte de Artéria Coronária/efeitos adversos , Relação Dose-Resposta a Droga , Transfusão de Eritrócitos , Feminino , Implante de Prótese de Valva Cardíaca/efeitos adversos , Antagonistas de Heparina/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Função Plaquetária , Hemorragia Pós-Operatória/etiologia , Hemorragia Pós-Operatória/terapia , Protaminas/administração & dosagem , Fatores de Tempo , Resultado do Tratamento
3.
Biosci Biotechnol Biochem ; 83(6): 1094-1101, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30871430

RESUMO

Oxidized low-density lipoprotein (ox-LDL) leads to atherosclerosis via lectin-like oxidized lipoprotein receptor-1 (LOX-1), one of the major receptor for ox-LDL. Inhibition of the binding of ox-LDL to LOX-1 decreases the proinflammatory and atherosclerotic events. The aim of the present study was to investigate whether protamine, a polybasic nuclear protein, interferes the binding of ox-LDL to LOX-1. Using sandwich ELISA with newly generated antibody, we measured the blocking effect of protamine on the binding of ox-LDL to LOX-1. Protamine dose-dependently inhibited the binding of ox-LDL to LOX-1. DiI-labeled ox-LDL uptake assay in two types of cultured human endothelial cells was performed with fluorescence microplate reader. Activation of extracellular-signal-regulated kinase (ERK)1/2 by ox-LDL was analyzed by immunoblotting. We found that protamine suppressed uptake of ox-LDL in endothelial cells and inhibited ERK1/2 activation by ox-LDL. These results suggest that protamine may possess anti-atherogenic potential by inhibiting ox-LDL binding to LOX-1 through electrostatic interactions.


Assuntos
Aterosclerose/prevenção & controle , Lipoproteínas LDL/metabolismo , Protaminas/farmacologia , Receptores Depuradores Classe E/metabolismo , Células Cultivadas , Relação Dose-Resposta a Droga , Células Endoteliais/metabolismo , Endotélio Vascular/citologia , Endotélio Vascular/metabolismo , Fluorescência , Humanos , Lipoproteínas LDL/antagonistas & inibidores , Protaminas/administração & dosagem , Ligação Proteica , Receptores Depuradores Classe E/antagonistas & inibidores
4.
Thorac Cardiovasc Surg ; 67(3): 191-202, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-29290078

RESUMO

INTRODUCTION: The recommended minimum activated clotting time (ACT) level for cardiopulmonary bypass (CPB) of 480 seconds originated from investigations with bubble oxygenators and uncoated extracorporeal circulation (ECC) systems. Modern minimal invasive ECC (MiECC) systems are completely closed circuits containing a membrane oxygenator and a tip-to-tip surface coating. We hypothesized that surface coating and the "closed-loop" design allow the MiECC to safely run with lower ACT levels and that an ACT level of 300 seconds can be safely applied without thromboembolic complications. The aim of this study was to investigate the potential risks during application of reduced heparin levels in patients undergoing coronary surgery. METHODS: In this study, 68 patients undergoing coronary artery bypass grafting with MiECC were randomized to either the study group with an ACT target of 300 seconds or the control group with an ACT of 450 seconds. All other factors of MiECC remained unchanged. RESULTS: The study group received significantly less heparin and protamine (heparin [international units] median [min-max], Red_AC: 32,800 [23,000-51,500] vs. Full_AC: 50,000 [35,000-65,000] p < 0.001; protamine [international units], Red_AC: 18,000 [10,000-35,000] vs. Full_AC: 30,000 [20,000-45,000] p < 0.001). The ACT in the study group was significantly lower at the start of MiECC (mean ± standard deviation: study group 400 ± 112 vs. control group 633 ± 177; p < 0.0001). Before termination of CPB the ACT levels were: study group 344 ± 60 versus control group 506 ± 80. In both groups, the values of the endogenous thrombin potential (ETP) decreased simultaneously. None of the study participants experienced thromboembolic complications. CONCLUSION: Since no evidence of increased thrombin formation (ETP) was found from a laboratory standpoint, we concluded that the use of MiECC with a reduced anticoagulation strategy seems possible. This alternative anticoagulation strategy leads to significant reduction in dosages of both heparin and protamine. We can confidently move forward with investigating this anticoagulation concept. However, to establish clinical safety of ACT below 300 seconds, we need larger clinical studies.


Assuntos
Anticoagulantes/administração & dosagem , Coagulação Sanguínea/efeitos dos fármacos , Ponte Cardiopulmonar/métodos , Ponte de Artéria Coronária , Oxigenação por Membrana Extracorpórea/métodos , Heparina/administração & dosagem , Tempo de Coagulação do Sangue Total , Idoso , Anticoagulantes/efeitos adversos , Ponte Cardiopulmonar/efeitos adversos , Ponte de Artéria Coronária/efeitos adversos , Oxigenação por Membrana Extracorpórea/efeitos adversos , Estudos de Viabilidade , Feminino , Alemanha , Heparina/efeitos adversos , Antagonistas de Heparina/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos , Valor Preditivo dos Testes , Protaminas/administração & dosagem , Fatores de Risco , Tromboembolia/sangue , Tromboembolia/etiologia , Tromboembolia/prevenção & controle , Fatores de Tempo , Resultado do Tratamento
5.
J Cardiothorac Vasc Anesth ; 33(4): 985-992, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30206011

RESUMO

OBJECTIVES: The aim of the study was to investigate whether the HeProCalc algorithm affects heparin and protamine dosage, postoperative blood loss, and transfusion rate. DESIGN: Randomized controlled trial. SETTING: University hospital. PARTICIPANTS: The study comprised 210 cardiac surgery patients undergoing cardiac surgery with cardiopulmonary bypass. Twenty patients were excluded because of re-exploration for localized surgical bleeding (n = 9), violation of protocol (n = 2), aprotinin use (n = 3 and nadir body temperature <32°C (n = 6). INTERVENTIONS: Study participants were randomly assigned to either traditional heparin and protamine dosage based on body weight only (control group) or dosage based on the HeProCalc algorithm (intervention group). MEASUREMENTS AND MAIN RESULTS: The initial median heparin dose was 32,500 IU (interquartile range [IQR] 30,000-35,000) in the intervention group compared with 35,000 IU (IQR 30,000-37,500) (p = 0.025) in the control group. The total heparin dose in the intervention group was 40,000 IU (IQR 32,500-47,500) compared with 42,500 IU (IQR 35,000-50,000) in the control group (p = 0.685). The total protamine dose was 210 mg (IQR 190-240) in the intervention group compared with 350 mg (IQR 300-380) (p < 0.001) in the control group. The ratio of total protamine to initial dose of heparin in the intervention group was 0.62 compared with 1.0 (p < 0.001). The amount of chest tube bleeding after 12 postoperative hours was 320 mL (IQR 250-460) in the intervention group compared with 350 mL (IQR 250-450) (p = 0.754) in the control group. Neither the transfusion rate nor postoperative blood loss differed significantly between the 2 groups. CONCLUSION: Use of the HeProCalc algorithm reduced protamine dosage and the protamine/heparin ratio after cardiopulmonary bypass compared with conventional dosage based on weight without significant effect on postoperative blood loss or the transfusion rate.


Assuntos
Algoritmos , Perda Sanguínea Cirúrgica/prevenção & controle , Transfusão de Sangue/tendências , Procedimentos Cirúrgicos Cardíacos/tendências , Antagonistas de Heparina/administração & dosagem , Protaminas/administração & dosagem , Idoso , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Método Simples-Cego
6.
Drug Deliv Transl Res ; 9(1): 227-239, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30519937

RESUMO

Diabetic wounds as chronic wounds represent a severe, persistent complication of diabetes and, in the most extreme cases, can lead to amputation. Two critical and unfavorable factors affecting diabetic wound healing are sustained bacterial-induced chronic inflammation and disrupted vascularization. In this paper, we presented a novel, pH-responsive calcium alginate hydrogel laden with protamine nanoparticles and hyaluronan oligosaccharides, and explored its potential for accelerating diabetic wound healing. A thorough investigation indicated that the drug- and nanoparticle-loaded hydrogel demonstrated strong bactericidal behavior mediated by protamine nanoparticles and reduced bacterial-induced chronic inflammation at the wound site. Furthermore, it accelerated the wound-healing process by promoting angiogenesis in skin wounds with the hyaluronan oligosaccharide-mediated enhanced expression of vascular endothelial growth factor.


Assuntos
Alginatos/química , Diabetes Mellitus Experimental/complicações , Ácido Hialurônico/administração & dosagem , Neovascularização Fisiológica/efeitos dos fármacos , Protaminas/administração & dosagem , Cicatrização/efeitos dos fármacos , Animais , Antibacterianos , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Hidrogéis/química , Concentração de Íons de Hidrogênio , Nanopartículas/química , Protaminas/química , Protaminas/farmacologia , Ratos , Estreptozocina , Fator A de Crescimento do Endotélio Vascular/metabolismo
7.
Semin Thorac Cardiovasc Surg ; 31(3): 394-396, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30578828

RESUMO

Cognitive workload data of members of the cardiac surgery team can be measured intraoperatively and stored for later analysis. We present a case of a near-miss (medication error) that underwent root cause analysis using workload data. Heart rate variability data, representing workload levels, were collected from the attending surgeon, attending anesthesiologist, and lead perfusionist using wireless heart rate monitors. An episode of cognitive overload of the anesthesiologist due to a distractor was associated with the preventable error. Additional studies are needed to better understand the role of psychophysiological data in enhancing surgical patient safety.


Assuntos
Anestesistas/psicologia , Cognição , Ponte de Artéria Coronária/efeitos adversos , Erros de Medicação/prevenção & controle , Near Miss , Equipe de Assistência ao Paciente , Carga de Trabalho , Administração Intravenosa , Competência Clínica , Frequência Cardíaca , Antagonistas de Heparina/administração & dosagem , Antagonistas de Heparina/efeitos adversos , Humanos , Protaminas/administração & dosagem , Protaminas/efeitos adversos , Medição de Risco , Fatores de Risco , Análise de Causa Fundamental
8.
Arch. argent. pediatr ; 116(6): 762-764, dic. 2018. tab
Artigo em Espanhol | LILACS, BINACIS | ID: biblio-973693

RESUMO

La enoxaparina es una heparina de bajo peso molecular utilizada en el período neonatal. Requiere menor monitoreo que la heparina estándar o no fraccionada, si bien es escaso el conocimiento actual acerca de su dosis y de los niveles terapéuticos en los neonatos. Además, existe una información muy limitada respecto del manejo de su sobredosificación en este grupo de edad. Se presenta el primer caso publicado en castellano de un neonato que recibió una dosis de enoxaparina diez veces superior a la terapéutica de forma accidental y en el que se administró una dosis aislada de protamina para revertir su efecto.


Enoxaparin is a low molecular weight heparin used in the neonatal period. It requires less monitoring than standard or unfractionated heparin, although current knowledge about its dose and therapeutic levels in neonates is scarce. In addition, there is very limited information about the management of overdose in this age group. We present the first case published in Spanish of a neonate who accidentally received a dose of enoxaparin ten times higher than the therapeutic one and an isolated dose of protamine to reverse its effect.


Assuntos
Humanos , Masculino , Recém-Nascido , Protaminas/administração & dosagem , Enoxaparina/envenenamento , Antagonistas de Heparina/administração & dosagem , Anticoagulantes/envenenamento , Overdose de Drogas , Erros de Medicação
9.
Arch Argent Pediatr ; 116(6): e762-e764, 2018 12 01.
Artigo em Espanhol | MEDLINE | ID: mdl-30457732

RESUMO

Enoxaparin is a low molecular weight heparin used in the neonatal period. It requires less monitoring than standard or unfractionated heparin, although current knowledge about its dose and therapeutic levels in neonates is scarce. In addition, there is very limited information about the management of overdose in this age group. We present the first case published in Spanish of a neonate who accidentally received a dose of enoxaparin ten times higher than the therapeutic one and an isolated dose of protamine to reverse its effect.


Assuntos
Anticoagulantes/envenenamento , Enoxaparina/envenenamento , Antagonistas de Heparina/administração & dosagem , Protaminas/administração & dosagem , Overdose de Drogas , Humanos , Recém-Nascido , Masculino , Erros de Medicação
10.
Int J Pharm ; 552(1-2): 27-38, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30236648

RESUMO

This work investigates the impact of nanoparticle (NP) composition and effectiveness of cryo-/lyo-protectants in a freeze drying process, which was employed to convert liquid dispersions of polyelectrolyte complex (PEC) NPs into completely redispersible powders. PEC NPs, with and without peptide, were produced by complex coacervation. The cryo-/lyo-protectants investigated were mannitol, trehalose (TRE) and poly(ethylene glycol) (PEG). The solid state of lyophilised powders was studied by thermal analysis and X-ray diffraction. Cytotoxicity studies were done by MTS assay and flow cytometry. The presence of a cryoprotectant was essential to achieve a successful powder reconstitution. The concentration of TRE was optimised for each type of PEC NPs. Protamine- and hyaluronate-based NPs reconstituted better than chitosan- and chondroitin sulphate-based NPs, respectively. PEG polymers were found to be more effective cryoprotectants than TRE and best results were achieved using co-freeze drying of NPs with TRE and PEG. These ternary NPs/TRE/PEG samples were crystalline, with expected better storage stability. PEG polymers were well tolerated by Caco-2 cells, with the exception of linear PEG 10 kDa. This work shows that, as regards the formulation design and maximising NP loading in the dried product, optimisation of the cryoprotectant type and content is needed as it is highly dependent not only on the type of polyelectrolyte pair in the PEC, but also the polyions ratio.


Assuntos
Quitosana/química , Sulfatos de Condroitina/química , Crioprotetores/química , Ácido Hialurônico/química , Nanopartículas/química , Protaminas/química , Células CACO-2 , Sobrevivência Celular/efeitos dos fármacos , Quitosana/administração & dosagem , Sulfatos de Condroitina/administração & dosagem , Crioprotetores/administração & dosagem , Liofilização , Humanos , Ácido Hialurônico/administração & dosagem , Nanopartículas/administração & dosagem , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/química , Protaminas/administração & dosagem , Trealose/administração & dosagem , Trealose/química
11.
PLoS One ; 13(8): e0201647, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30075017

RESUMO

Low plasma fibrinogen level is common after cardiopulmonary bypass (CPB). Current substitution practice with fibrinogen concentrate generally follows a single measurement and cut-off values from the literature, whereas early postoperative endogenous fibrinogen kinetics is incompletely described and widely disregarded. The aim of this study was to determine the short-term recovery pattern of plasma fibrinogen after CPB weaning. Our hypothesis was that in the absence of surgical bleeding, CPB-induced hypofibrinogenemia would resolve spontaneously and predictably within a few hours. In a prospective, observational study of 26 patients undergoing conventional CPB (cCPB) or minimally invasive extracorporeal circulation (MiECC), Clauss fibrinogen level (C-FIB) was determined at 10 closely spaced time points after protamine administration. Primary endpoint was the time to recovery of post-CPB fibrinogen levels to ≥1.5 g/L. C-FIB reached its nadir after protamine administration corresponding to 62 ± 5% (mean ± SD) of the baseline level after cCPB and 68 ± 7% after MiECC (p = 0.027 vs. cCPB). C-FIB recovered spontaneously at a nearly constant rate of approximately 0.08 g/L per hour. In all patients, C-FIB was ≥1.5 g/L at 4 hours and ≥2.0 g/L at 13 hours after CPB weaning. Following cardiac surgery with CPB and in the absence of surgical bleeding, spontaneous recovery of normal endogenous fibrinogen levels can be expected at a rate of 0.08 g/L per hour. Administration of fibrinogen concentrate triggered solely by a single-point measurement of low plasma fibrinogen some time after CPB is not justified.


Assuntos
Afibrinogenemia/tratamento farmacológico , Ponte Cardiopulmonar/efeitos adversos , Circulação Extracorpórea/efeitos adversos , Fibrinogênio/análise , Protaminas/administração & dosagem , Afibrinogenemia/sangue , Afibrinogenemia/etiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Prospectivos , Protaminas/uso terapêutico , Remissão Espontânea , Resultado do Tratamento
12.
J Thromb Haemost ; 16(10): 1973-1983, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30016577

RESUMO

Essentials Heparin-protamine balance (HPB) modulates bleeding after neonatal cardiopulmonary bypass (CPB). HPB was examined in 44 neonates undergoing CPB. Post-operative bleeding occurred in 36% and heparin rebound in 73%. Thrombin-initiated fibrin clot kinetic assay and partial thromboplastin time best assessed HPB. SUMMARY: Background Neonates undergoing cardiopulmonary bypass (CPB) are at risk of excessive bleeding. Blood is anticoagulated with heparin during CPB. Heparin activity is reversed with protamine at the end of CPB. Paradoxically, protamine also inhibits blood coagulation when it is dosed in excess of heparin. Objectives To evaluate heparin-protamine balance in neonates undergoing CPB by using research and clinical assays, and to determine its association with postoperative bleeding. Patients/Methods Neonates undergoing CPB in the first 30 days of life were studied. Blood samples were obtained during and after surgery. Heparin-protamine balance was assessed with calibrated automated thrombography, thrombin-initiated fibrin clot kinetic assay (TFCK), activated partial thromboplastin time (APTT), anti-FXa activity, and thromboelastometry. Excessive postoperative bleeding was determined by measurement of chest tube output or the development of cardiac tamponade. Results and Conclusions Of 44 neonates enrolled, 16 (36%) had excessive postoperative bleeding. The TFCK value was increased. By heparin in neonatal blood samples, but was only minimally altered by excess protamine. Therefore, it reliably measured heparin in samples containing a wide range of heparin and protamine concentrations. The APTT most closely correlated with TFCK results, whereas anti-FXa and thromboelastometry assays were less correlative. The TFCK and APTT assay also consistently detected postoperative heparin rebound, providing an important continued role for these long-established coagulation tests in the management of postoperative bleeding in neonates requiring cardiac surgical repair. None of the coagulation tests predicted the neonates who experienced postoperative bleeding, reflecting the multifactorial causes of bleeding in this population.


Assuntos
Anticoagulantes/administração & dosagem , Coagulação Sanguínea/efeitos dos fármacos , Ponte Cardiopulmonar/efeitos adversos , Antagonistas de Heparina/administração & dosagem , Heparina/administração & dosagem , Hemorragia Pós-Operatória/etiologia , Protaminas/administração & dosagem , Anticoagulantes/efeitos adversos , Anticoagulantes/sangue , Testes de Coagulação Sanguínea , Monitoramento de Medicamentos/métodos , Feminino , Heparina/efeitos adversos , Heparina/sangue , Antagonistas de Heparina/efeitos adversos , Antagonistas de Heparina/sangue , Humanos , Recém-Nascido , Masculino , Hemorragia Pós-Operatória/sangue , Hemorragia Pós-Operatória/diagnóstico , Valor Preditivo dos Testes , Estudos Prospectivos , Protaminas/efeitos adversos , Protaminas/sangue , Fatores de Risco , Resultado do Tratamento
13.
Medicine (Baltimore) ; 97(28): e10908, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29995750

RESUMO

Since there were a few articles to report the treatment of severe pulmonary vasoconstriction induced by protamine in cardiac surgery, we described the use of epoprostenol to reverse this condition.A total of 5 cases of severe pulmonary vasoconstriction induced by protamine in cardiac surgery were reviewed. The demographic, clinical data and treatment process were obtained. All the patients were followed up.Severe pulmonary vasoconstriction was occurred 4 to 10 minutes after protamine infusion. The primary sign was sudden hypotension, the pulmonary artery pressure was increased gradually, the arterial oxygen partial pressure was decreased in all the patients. Epoprostenol was infused via pulmonary artery catheter at dosage of 20 to 40 ng/kg·min in all the patients, 2 patients were underwent re-cardiac pulmonary bypass assistance. The hemodynamic instability status lasted 40 to 65 minutes respectively. All the patients were recovered uneventfully.All physicians should alert to the incidence of severe pulmonary vasoconstriction induced by protamine in cardiac surgery. Use epoprostenol through pulmonary artery catheter could treat pulmonary artery vasoconstriction effectively and safely.


Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Epoprostenol/administração & dosagem , Hemodinâmica/efeitos dos fármacos , Hipertensão Pulmonar , Complicações Intraoperatórias , Protaminas/efeitos adversos , Adulto , Idoso , Anti-Hipertensivos/administração & dosagem , China , Monitoramento de Medicamentos/métodos , Feminino , Antagonistas de Heparina/administração & dosagem , Antagonistas de Heparina/efeitos adversos , Humanos , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/tratamento farmacológico , Complicações Intraoperatórias/induzido quimicamente , Complicações Intraoperatórias/diagnóstico , Complicações Intraoperatórias/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória/métodos , Protaminas/administração & dosagem , Estudos Retrospectivos , Resultado do Tratamento , Vasoconstrição/efeitos dos fármacos
14.
Perfusion ; 33(6): 445-452, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29544405

RESUMO

INTRODUCTION: Accurate dosing of protamine reversal following on-pump cardiac surgical procedures is challenging, with both excessive and inadequate administration recognised to increase bleeding risk. We aimed to examine the relationship between three ratios for heparin reversal and markers of haemostasis. METHODS: A retrospective analysis of a prospectively collected database was undertaken at a single tertiary cardiac unit, reviewing all cases of on-pump coronary artery bypass grafts and single valve replacements from 01/01/2011 to 31/12/2015. The ratio between total intra-operative heparin and protamine was stratified to three groups (low: ≤0.6 mg per 100 IU of heparin, moderate: 0.6-1.0 and high: >1.0) and related to the primary outcome of red blood cell (RBC) transfusion, with secondary outcomes being the number of units transfused, the haemoglobin differential and mediastinal drain output at 4 hours. RESULTS: Of the 803 patients identified, 338 received a blood transfusion, with 1035 units being used. Eighteen percent of individuals (145) received a low ratio, 50% (404) received a moderate ratio and 32% (254) a high ratio. Using the moderate group as a reference, the low dose group was 56.5% less likely to have received a RBC transfusion (OR 0.435; 95% CI 0.270:0.703 p=0.001) while the high dose group carried a 241% increased association with transfusion (OR 3.412; 95% CI 2.399:4.853 p<0.001). For those transfused, a lower protamine:heparin ratio was associated with a lower number of units transfused, lesser haemoglobin differential and less mediastinal drain output. CONCLUSION: Higher doses of intra-operative protamine relative to heparin are associated with greater risk of transfusion and post-operative bleeding.


Assuntos
Anticoagulantes/uso terapêutico , Ponte Cardiopulmonar/métodos , Ponte de Artéria Coronária/métodos , Antagonistas de Heparina/uso terapêutico , Heparina/uso terapêutico , Hemorragia Pós-Operatória/terapia , Protaminas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Transfusão de Sangue , Ponte Cardiopulmonar/efeitos adversos , Ponte de Artéria Coronária/efeitos adversos , Feminino , Heparina/administração & dosagem , Antagonistas de Heparina/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Hemorragia Pós-Operatória/etiologia , Protaminas/administração & dosagem , Estudos Retrospectivos , Adulto Jovem
15.
J Thorac Cardiovasc Surg ; 155(2): 643-649, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29033041

RESUMO

OBJECTIVES: Pulmonary endarterectomy (PEA) is the only curative treatment option for patients with chronic thromboembolic pulmonary hypertension. Massive endobronchial bleeding that precludes weaning from cardiopulmonary bypass is an often-fatal complication of PEA. The aim of this study was to determine whether short-term extracorporeal membrane oxygenation (ECMO) is a safe and feasible procedure in patients with severe endobronchial bleeding. METHODS: From January 2014 to December 2016, 396 patients (mean age 60 ± 18 years, 54.5% male) underwent PEA in our department. Patients with severe endobronchial hemorrhage at the time of weaning from cardiopulmonary bypass (CPB) were switched to a heparin-coated venoarterial ECMO circuit. After full-dose protamine administration to restore normal coagulation, weaning from ECMO was attempted in the operating room. RESULTS: In-hospital mortality was 2.3% (9/396 patients). Eight patients (2.0%) developed severe endobronchial bleeding classified as diffuse (n = 6) or localized (n = 2) by bronchoscopy. After reinstitution of CPB and subsequent switch to ECMO, the mean duration of ECMO support was 49 ± 13 minutes, and all 8 patients were weaned successfully from ECMO in the operating theater without further signs of endobronchial bleeding. One patient needed venovenous ECMO support for poor oxygenation 6 hours after surgery. Seven patients were discharged after a prolonged postoperative stay of 17.6 ± 4.1 days. One patient died. This new concept significantly reduced mortality compared with previous (2009-2013) ECMO support (P = .0406). CONCLUSIONS: For patients with massive endobronchial bleeding after PEA, the intraoperative switch from CPB to venoarterial ECMO support with full-dose protamine administration is a new and potentially life-saving treatment concept.


Assuntos
Ponte Cardiopulmonar/efeitos adversos , Endarterectomia/efeitos adversos , Oxigenação por Membrana Extracorpórea , Hemorragia Pós-Operatória/terapia , Artéria Pulmonar/cirurgia , Adulto , Idoso , Anticoagulantes/administração & dosagem , Ponte Cardiopulmonar/mortalidade , Materiais Revestidos Biocompatíveis , Endarterectomia/mortalidade , Desenho de Equipamento , Oxigenação por Membrana Extracorpórea/efeitos adversos , Oxigenação por Membrana Extracorpórea/instrumentação , Oxigenação por Membrana Extracorpórea/mortalidade , Estudos de Viabilidade , Feminino , Heparina/administração & dosagem , Antagonistas de Heparina/administração & dosagem , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Hemorragia Pós-Operatória/diagnóstico , Hemorragia Pós-Operatória/etiologia , Hemorragia Pós-Operatória/mortalidade , Protaminas/administração & dosagem , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
17.
Heart Rhythm ; 15(11): 1642-1647, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30661768

RESUMO

BACKGROUND: There are no randomized controlled studies of the efficacy and safety of protamine to reverse anticoagulant effects of heparin after catheter ablation (CA) of atrial fibrillation (AF). OBJECTIVE: The purpose of this study was to determine the efficacy and safety of protamine to expedite vascular hemostasis and ambulation after CA of AF. METHODS: CA to eliminate AF (n = 139) or left atrial flutter (n = 11) was performed in 150 patients using radiofrequency catheter ablation (n = 112) or cryoballoon ablation (n = 38). CA was performed under uninterrupted anticoagulation with warfarin in 28 patients or after skipping a single dose of a novel oral anticoagulant in 122 patients who were randomized to receive protamine (n = 77) or to the control group (n = 73). Baseline and procedural characteristics were similar between the 2 groups. Hemostasis was achieved manually once the activated clotting time returned to preprocedural values. RESULTS: The maximum activated clotting time during CA was 359 ± 31 and 359 ± 29 seconds in the protamine and control groups, respectively (P = .91). The time to hemostasis was 123 ± 95 minutes in the protamine group and 260 ± 70 minutes in the control group (P < .001). The time to ambulation was 316 ± 80 and 480 ± 92 minutes in the protamine and control groups, respectively (P < .001). There were no differences in the rates of major or minor vascular access complications or thromboembolic events (P > .05). CONCLUSION: Protamine expedites vascular hemostasis and time to ambulation by ∼3 hours after CA of AF without an increase in the risk of vascular or thromboembolic complications.


Assuntos
Fibrilação Atrial/cirurgia , Coagulação Sanguínea/efeitos dos fármacos , Ablação por Cateter/métodos , Hemorragia/prevenção & controle , Protaminas/administração & dosagem , Idoso , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Fibrilação Atrial/sangue , Fibrilação Atrial/complicações , Esquema de Medicação , Feminino , Hemorragia/sangue , Hemorragia/induzido quimicamente , Antagonistas de Heparina/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Tromboembolia/sangue , Tromboembolia/etiologia , Tromboembolia/prevenção & controle , Resultado do Tratamento , Varfarina/efeitos adversos , Varfarina/uso terapêutico
20.
Pharmacotherapy ; 37(10): e103-e106, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28741720

RESUMO

Few patients presenting with acute ischemic stroke (AIS) are eligible for alteplase, especially those receiving ongoing anticoagulation. We describe the first reported case of a patient receiving full-dose intravenous (IV) alteplase for AIS after heparin reversal with protamine. A 73-year-old man presented with AIS. He was treated with IV heparin, tirofiban, loading-dose prasugrel, and aspirin before percutaneous coronary intervention (PCI) for placement of a right coronary artery stent. One hour following PCI, he abruptly developed left hemiparesis and dysphagia. The National Institutes of Health Stroke Scale was 12, and activated partial thromboplastin time (aPTT) was longer than 150 seconds. Head computed tomography (CT) showed no acute pathology, and CT angiogram showed no large-vessel occlusion amenable to mechanical thrombectomy. Repeat aPTT, obtained 45 minutes later, was 110 seconds, at which time protamine 40 mg IV was administered. At 144 minutes from last known well time, full-dose IV alteplase (0.9 mg/kg) was administered. Follow-up head imaging at 25 hours showed right pontine and cerebellar AIS with no evidence of hemorrhage. The patient was discharged to inpatient rehabilitation 2 days later. Modified Rankin Scale at 3 months was 3, improved from 5 at discharge. Given the lack of adverse events associated with IV alteplase in our patient, we advocate cautious evaluation for potential reversal of acutely administered anticoagulation to facilitate alteplase administration in severely disabled patients who are not eligible for mechanical intervention and would have been excluded from definitive AIS treatment.


Assuntos
Anticoagulantes/uso terapêutico , Antagonistas de Heparina/uso terapêutico , Heparina/uso terapêutico , Protaminas/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Ativador de Plasminogênio Tecidual/uso terapêutico , Idoso , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Isquemia Encefálica/complicações , Isquemia Encefálica/tratamento farmacológico , Heparina/administração & dosagem , Heparina/efeitos adversos , Antagonistas de Heparina/administração & dosagem , Humanos , Masculino , Tempo de Tromboplastina Parcial , Protaminas/administração & dosagem , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/etiologia , Ativador de Plasminogênio Tecidual/administração & dosagem , Resultado do Tratamento
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