2010Early_on-treatment_prediction

子痫前期预测和预防的研究进展何雪仪;王晨虹【摘要】子痫前期是妊娠期间出现血压升高、蛋白尿等症状的一种疾病，是孕产妇及围生儿患病及死亡的主要原因之一。

因此，子痫前期的预测和预防有重要意义。

如何找到早期预测子痫前期的方法，一直是围生医学研究的重点。

预测子痫前期的方法有多种，包括母亲临床综合评估、子宫动脉多普勒和血清学指标等。

近年来，子痫前期预测的研究已从妊娠中期提前到妊娠早期。

目前子痫前期预防性治疗的方案较有效的是小剂量阿司匹林。

综述子痫前期的预测和预防的现状。

%Pre-eclampsia,considered a leading cause of maternal and perinatal morbidity and mortality,is defined as new-onset hypertension and proteinuria during pregnancy. It is very important to develop effective prediction and prevention of pre-eclampsia. Finding a method to predict pre-eclampsia precisely has been a focus for many years. Varied tests used to predict pre-eclampsia include clinical identification of high risk ,uterine artery Doppler and maternal peripheral blood correlation protein detection. In recent years ,the focus has evolved from screening in the second trimester to screening beginning in the first trimester. The beneficial effect of preventing pre-eclampsia was observed only in low aspirin treatment. The aim of this review is to discuss the progress of the prediction and prevention of the pre-eclampsia.【期刊名称】《国际妇产科学杂志》【年(卷),期】2014(000)002【总页数】4页(P171-174)【关键词】先兆子痫;预测;综合预防;妊娠初期【作者】何雪仪;王晨虹【作者单位】518028 广东省深圳市，南方医科大学附属深圳市妇幼保健院;518028 广东省深圳市，南方医科大学附属深圳市妇幼保健院【正文语种】中文子痫前期是指妊娠20周后发病，以高血压和蛋白尿为主要表现的临床综合征，发病率为2%～3%，可伴有脑、心、肝、肾等重要脏器的功能损害，也是导致母儿围生期死亡的重要原因[1]。

熊去氧胆酸联合维生素D治疗PBC患者疗效和外周血T淋巴细胞亚群的变化刘映川;赵鹏程;游亭;邓红英;薛江凤【摘要】目的研究应用维生素D辅助熊去氧胆酸(UDCA)治疗原发性胆汁性肝硬化(PBC)患者的疗效及其对血清25-羟基维生素D3(25-(OH)2-D3)和外周血T淋巴细胞亚群的影响.方法 2013年4月～2016年4月收治的70例PBC患者,采用随机数字表法分为观察组35例和对照组35例,分别给予UDCA或UDCA联合骨化三醇胶丸治疗.采用全自动电化学发光免疫分析法检测血清25-(OH)2-D3,使用流式细胞仪检测外周血T淋巴细胞亚群.结果在治疗1年末,观察组血清25-(OH)2-D3水平为(24.5±4.2)ng/ml,外周血CD8+细胞百分比为(29.0±5.2)％,显著高于对照组的(20.2±3.6)ng/ml和(26.3±4.8)％(P<0.05),CD4+细胞百分比和CD4+/CD8+比值分别为(31.8±5.9)％和(1.1±0.2),显著低于对照组的[(36.2±6.4)％和(1.4±0.3),P<0.05];应用巴塞罗那标准考核,观察组对UDCA应答率为85.7％,显著高于对照组的62.9％(P<0.05);观察组血清二胺氧化酶(DAO)、D-乳酸、谷草转氨酶(AST)和碱性磷酸酶(ALP)水平分别为(3.5±0.6)U/ml、(8.2±1.5)μg/ml、(62.3±11.2)U/L和(317.5±57.3)U/L,显著低于对照组的[(3.9±0.7)U/ml、(9.4±1.7)μg/ml、(76.9±13.9)U/L和(355.4±64.2)U/L,P<0.05].结论应用维生素D辅助治疗PBC患者可以提高对UDCA的应答率,纠正免疫功能紊乱,保护肠道屏障功能,促进肝功能恢复.【期刊名称】《实用肝脏病杂志》【年(卷),期】2018(021)006【总页数】4页(P907-910)【关键词】原发性胆汁性肝硬化;熊去氧胆酸;维生素D;T淋巴细胞亚群;应答【作者】刘映川;赵鹏程;游亭;邓红英;薛江凤【作者单位】610041 成都市第七人民医院消化科;610041 成都市第七人民医院消化科;610041 成都市第七人民医院消化科;610041 成都市第七人民医院消化科;610041 成都市第七人民医院消化科【正文语种】中文原发性胆汁性肝硬化（PBC）是一种慢性胆汁淤积性疾病，多发于中年女性。

ISSN: 1524-4628Copyright © 2010 American Heart Association. All rights reserved. Print ISSN: 0039-2499. OnlineStroke is published by the American Heart Association. 7272 Greenville Avenue, Dallas, TX 72514DOI: 10.1161/STR.0b013e3181ec611bpublished online Jul 22, 2010; Stroke Cardiovascular Nursingand on behalf of the American Heart Association Stroke Council and Council onMacdonald, Steven R. Messé, Pamela H. Mitchell, Magdy Selim, Rafael J. Tamargo Loch P. Broderick, E. Sander Connolly, Jr, Steven M. Greenberg, James N. Huang, R. Lewis B. Morgenstern, J. Claude Hemphill, III, Craig Anderson, Kyra Becker, JosephAssociation/American Stroke Association Guideline for Healthcare Professionals From the American HeartGuidelines for the Management of Spontaneous Intracerebral Hemorrhage. A located on the World Wide Web at:The online version of this article, along with updated information and services, is/reprints Reprints: Information about reprints can be found online atjournalpermissions@ 410-528-8550. E-mail:Fax:Kluwer Health, 351 West Camden Street, Baltimore, MD 21202-2436. Phone: 410-528-4050. Permissions: Permissions & Rights Desk, Lippincott Williams & Wilkins, a division of Wolters/subscriptions/Subscriptions: Information about subscribing to Stroke is online atGuidelines for the Management of SpontaneousIntracerebral HemorrhageA Guideline for Healthcare Professionals From the American HeartAssociation/American Stroke AssociationThe American Academy of Neurology affirms the value of this guideline as an educationaltool for neurologists.The American Association of Neurological Surgeons and the Congress of Neurological Surgeons have reviewed this document and affirm its educational content.Lewis B.Morgenstern,MD,FAHA,FAAN,Chair;J.Claude Hemphill III,MD,MAS,FAAN,Vice-Chair;Craig Anderson,MBBS,PhD,FRACP;Kyra Becker,MD;Joseph P.Broderick,MD,FAHA;E.Sander Connolly,Jr,MD,FAHA; Steven M.Greenberg,MD,PhD,FAHA,FAAN;James N.Huang,MD;R.Loch Macdonald,MD,PhD;Steven R.Messé,MD,FAHA;Pamela H.Mitchell,RN,PhD,FAHA,FAAN;Magdy Selim,MD,PhD,FAHA;Rafael J.Tamargo,MD;on behalf of the American Heart AssociationStroke Council and Council on Cardiovascular NursingPurpose—The aim of this guideline is to present current and comprehensive recommendations for the diagnosis and treatment of acute spontaneous intracerebral hemorrhage.Methods—A formal literature search of MEDLINE was performed.Data were synthesized with the use of evidence tables.Writing committee members met by teleconference to discuss data-derived recommendations.The American Heart Association Stroke Council’s Levels of Evidence grading algorithm was used to grade each recommendation.Prerelease review of the draft guideline was performed by6expert peer reviewers and by the members of the Stroke Council Scientific Statements Oversight Committee and Stroke Council Leadership Committee.It is intended that this guideline be fully updated in3years’time.Results—Evidence-based guidelines are presented for the care of patients presenting with intracerebral hemorrhage.The focus was subdivided into diagnosis,hemostasis,blood pressure management,inpatient and nursing management, preventing medical comorbidities,surgical treatment,outcome prediction,rehabilitation,prevention of recurrence,and future considerations.Conclusions—Intracerebral hemorrhage is a serious medical condition for which outcome can be impacted by early, aggressive care.The guidelines offer a framework for goal-directed treatment of the patient with intracerebral hemorrhage.(Stroke.2010;41:00-00.)Key Words:AHA Scientific StatementsⅢintracerebral hemorrhageⅢtreatmentⅢdiagnosisⅢintracranial pressureⅢhydrocephalusⅢsurgeryThe American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal,professional,or business interest of a member of the writing panel.Specifically,all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest. This statement was approved by the American Heart Association Science Advisory and Coordinating Committee on May19,2010.A copy of the statement is available at /presenter.jhtml?identifierϭ3003999by selecting either the“topic list”link or the“chronological list”link(No.KB-0044).To purchase additional reprints,call843-216-2533or e-mail kelle.ramsay@.The American Heart Association requests that this document be cited as follows:Morgenstern LB,Hemphill JC3rd,Anderson C,Becker K,Broderick JP,Connolly ES Jr,Greenberg SM,Huang JN,Macdonald RL,MesséSR,Mitchell PH,Selim M,Tamargo RJ;on behalf of the American Heart Association Stroke Council and Council on Cardiovascular Nursing.Guidelines for the management of spontaneous intracerebral hemorrhage:a guideline for healthcare professionals from the American Heart Association/American Stroke Association.Stroke.2010;41:●●●–●●●.Expert peer review of AHA Scientific Statements is conducted at the AHA National Center.For more on AHA statements and guidelines development, visit /presenter.jhtml?identifierϭ3023366.Permissions:Multiple copies,modification,alteration,enhancement,and/or distribution of this document are not permitted without the express permission of the American Heart Association.Instructions for obtaining permission are located at /presenter.jhtml? identifierϭ4431.A link to the“Permission Request Form”appears on the right side of the page.©2010American Heart Association,Inc.Stroke is available at DOI:10.1161/STR.0b013e3181ec611bS pontaneous,nontraumatic intracerebral hemorrhage(ICH) is a significant cause of morbidity and mortality throughout the world.Although much has been made of the lack of a specific targeted therapy,much less is written about the success and goals of aggressive medical and surgical care for this disease.Recent population-based studies suggest that most patients present with small ICHs that are readily survivable with good medical care.1This suggests that excellent medical care likely has a potent,direct impact on ICH morbidity and mortality now,even before a specific therapy is found.Indeed,as discussed later,the overall aggressiveness of ICH care is directly related to mortality from this disease.2One of the purposes of this guideline,therefore,is to remind clinicians of the impor-tance of their care in determining ICH outcome and to provide an evidence-based framework for that care.In order to make this review brief and readily useful to practicing clinicians,the reader is referred elsewhere for the details of ICH epidemiology.1,3,4Similarly,there are many ongoing clinical studies throughout the world related to this disease.The reader is encouraged to consider referring patients to these important efforts,which can be found at /trials/.We will not discuss on-going studies because we cannot cover them all;the focus of this statement is on currently available therapies.Finally,a recent guideline on pediatric stroke was published5that obviates the need to repeat the issues of pediatric ICH here. The last ICH Guidelines were published in2007,6and this current article serves to update those guidelines.As such, differences from former recommendations are specified in the current work.The writing group met by phone to determine subcategories to evaluate.These included emergency diagnosis and assessment of ICH and its causes;hemostasis,blood pressure(BP);intracranial pressure(ICP)/fever/glucose/ seizures/hydrocephalus;iron;ICP monitors/tissue oxygenation; clot removal;intraventricular hemorrhage(IVH);withdrawal of technological support;prevention of recurrent ICH;nursing care;rehab/recovery;future considerations.Each subcategory was led by an author with1or2additional authors making contributions.Full MEDLINE searches were done of all English-language articles regarding relevant human disease treatment.Drafts of summaries and recommendations were circulated to the whole writing group for feedback.A conference call was held to discuss controversial issues.Sections were revised and merged by the Chair.The resulting draft was sent to the whole writing group for ments were incor-porated by the Vice Chair and Chair,and the entire committee was asked to approve the final draft.Changes to the document were made by the Chair and Vice Chair in response to peer review,and the document was again sent to the entire writing group for suggested changes and approval.Recommendations follow the American Heart Association Stroke Council’s methods of classifying the level of certainty of the treatment effect and the class of evidence(Tables1and2).All Class I recommendations are listed in Table3.Emergency Diagnosis and Assessment of ICHand Its CausesICH is a medical emergency.Rapid diagnosis and attentive management of patients with ICH is crucial because early deterioration is common in the first few hours after ICH onset.More than20%of patients will experience a decrease in the Glasgow Coma Scale(GCS)score ofՆ2points between the prehospital emergency medical services assess-ment and the initial evaluation in the emergency department (ED).7Among those patients with prehospital neurological decline,the GCS score decreases by an average of6points and the mortality rate isϾ75%.Further,within the first hour of presentation to a hospital,15%of patients demonstrate a decrease in the GCS score ofՆ2points.8The risk for early neurological deterioration and the high rate of poor long-term outcomes underscores the need for aggressive early management.Prehospital ManagementThe primary objective in the prehospital setting is to provide ventilatory and cardiovascular support and to transport the patient to the closest facility prepared to care for patients with acute stroke (see ED Management section that follows).Secondary priorities for emergency medical services providers include obtaining a focused history regarding the timing of symptom onset(or the time the patient was last normal)and information about medical history, medication,and drug use.Finally,emergency medical services providers should provide advance notice to the ED of the impending arrival of a potential stroke patient so that critical pathways can be initiated and consulting services can be alerted.Advance notice by emergency medical services has been demonstrated to significantly shorten time to computed tomography(CT)scanning in the ED.9 ED ManagementIt is of the utmost importance that every ED be prepared to treat patients with ICH or have a plan for rapid transfer to a tertiary care center.The crucial resources necessary to man-age patients with ICH include neurology,neuroradiology, neurosurgery,and critical care facilities including adequately trained nurses and physicians.In the ED,appropriate consul-tative services should be contacted as quickly as possible and the clinical evaluation should be performed efficiently,with physicians and nurses working in parallel.Table4describes the integral components of the history,physical examination, and diagnostic studies that should be obtained in the ED. For patients with ICH,emergency management may in-clude neurosurgical interventions for hematoma evacuation, external ventricular drainage or invasive monitoring and treatment of ICP,BP management,intubation,and reversal of coagulopathy.Although many centers have critical pathways developed for the treatment of acute ischemic stroke,few have protocols for the management of ICH.18Such pathways may allow for more efficient,standardized,and integrated management of critically ill patients with ICH. NeuroimagingThe abrupt onset of focal neurological symptoms is presumed to be vascular in origin until proven otherwise.However,it is impossible to know whether symptoms are due to ischemia or hemorrhage based on clinical characteristics alone.Vomiting, systolic BPϾ220mm Hg,severe headache,coma or decreased level of consciousness,and progression over minutes or hours all suggest ICH,although none of these findings are specific;2Stroke September2010neuroimaging is thus mandatory.19CT and magnetic resonance imaging(MRI)are both reasonable for initial evaluation.CT is very sensitive for identifying acute hemorrhage and is consid-ered the gold standard;gradient echo and T2*susceptibility-weighted MRI are as sensitive as CT for detection of acute blood and are more sensitive for identification of prior hemorrhage.20,21 Time,cost,proximity to the ED,patient tolerance,clinical status, and MRI availability may,however,preclude emergent MRI in a sizeable proportion of cases.22The high rate of early neurological deterioration after ICH is in part related to active bleeding that may proceed for hours after symptom onset.The earlier time from symptom onset to first neuroimage,the more likely subsequent neuroimages will demonstrate hematoma expansion.15,23,24Among patients undergoing head CT within3hours of ICH onset,28%to 38%have hematoma expansion of greater than one third on follow-up CT.8,25Hematoma expansion is predictive of clinical deterioration and increased morbidity and mortali-ty.8,10,15,25As such,identifying patients at risk for hematoma expansion is an active area of research.CT angiography and contrast-enhanced CT may identify patients at high risk of ICH expansion based on the presence of contrast extravasa-tion within the hematoma.26–30MRI/angiogram/venogram and CT angiogram/venogram are reasonably sensitive at identifying secondary causes of hemorrhage,including arte-riovenous malformations,tumors,moyamoya,and cerebral vein thrombosis.31–33A catheter angiogram may be consid-ered if clinical suspicion is high or noninvasive studies are suggestive of an underlying vascular cause.Clinical suspicion of a secondary cause of ICH may include a prodrome of headache,neurological,or constitutional symptoms.Radio-logical suspicions of secondary causes of ICH should beTable1.Applying Classification of Recommendations and Level ofEvidence*Data available from clinical trials or registries about the usefulness/efficacy in different subpopulations,such as sex,age,history of diabetes,history of prior myocardial infarction,history of heart failure,and prior aspirin use.A recommendation with Level of Evidence B or C does not imply that the recommendation is weak. Many important clinical questions addressed in the guidelines do not lend themselves to clinical trials.Even though randomized trials are not available,there may be a very clear clinical consensus that a particular test or therapy is useful or effective.†In2003,the ACCF/AHA Task Force on Practice Guidelines developed a list of suggested phrases to use when writing recommendations.All guideline recommendations have been written in full sentences that express a complete thought,such that a recommendation,even if separated and presented apart from the rest of the document(including headings above sets of recommendations),would still convey the full intent of the recommendation.It is hoped that this will increase readers’comprehension of the guidelines and will allow queries at the individual recommendation level.Morgenstern et al Intracerebral Hemorrhage Guideline3invoked by the presence of subarachnoid hemorrhage,un-usual(noncircular)hematoma shape,the presence of edema out of proportion to the early time an ICH is first imaged,an unusual location for hemorrhage,and the presence of other abnormal structures in the brain like a mass.An MR or CT venogram should be performed if hemorrhage location,rela-tive edema volume,or abnormal signal in the cerebral sinuses on routine neuroimaging suggest cerebral vein thrombosis. In summary,ICH is a medical emergency,characterized by high morbidity and mortality,which should be promptly diagnosed and aggressively managed.Hematoma expansion and early deteriora-tion are common within the first few hours after onset. Recommendations1.Rapid neuroimaging with CT or MRI is recommendedto distinguish ischemic stroke from ICH(Class I;Level of Evidence:A).(Unchanged from the previous guideline) 2.CT angiography and contrast-enhanced CT may beconsidered to help identify patients at risk for hema-toma expansion(Class IIb;Level of Evidence:B),and CT angiography,CT venography,contrast-enhanced CT,contrast-enhanced MRI,magnetic resonance an-giography,and magnetic resonance venography can beuseful to evaluate for underlying structural lesions, including vascular malformations and tumors when there is clinical or radiological suspicion(Class IIa;Level of Evidence:B).(New recommendation)Medical Treatment for ICH Hemostasis/Antiplatelets/Deep VeinThrombosis ProphylaxisUnderlying hemostatic abnormalities can contribute to ICH. Patients at risk include those on oral anticoagulants(OACs), those with acquired or congenital coagulation factor deficien-cies,and those with qualitative or quantitative platelet abnormal-ities.Patients undergoing treatment with OACs constitute12% to14%of patients with ICH,34,35and with increased use of warfarin,the proportion appears to be increasing.36Recognition of an underlying coagulopathy thus provides an opportunity to target correction in the treatment strategy.For patients with a coagulation factor deficiency and thrombocytopenia,replace-ment of the appropriate factor or platelets is indicated.For patients being treated with OACs who have life-threatening bleeding,such as intracranial hemorrhage,the general recommen-dation is to correct the international normalized ratio(INR)as rapidly as possible.37,38Infusions of vitamin K and fresh-frozen plasma(FFP)have historically been recommended,but more recently,prothrombin complex concentrates(PCCs)and recom-binant factor VIIa(rFVIIa)have emerged as potential therapies. Vitamin K remains an adjunct to more rapidly acting initial therapy for life-threatening OAC-associated hemorrhage be-cause even when given intravenously,it requires hours to correct the INR.39–41The efficacy of FFP is limited by risk of allergic and infectious transfusion reactions,processing time,and the volume required for correction.Likelihood of INR correction at 24hours was linked to time to FFP administration in1study, although17%of patients still did not have an INRՅ1.4at this time,suggesting that FFP administered in this manner may be insufficient for rapid correction of coagulopathy.42PCCs are plasma-derived factor concentrates primarily used to treat factor IX deficiency.Because PCCs also contain factors II,VII,and X in addition to IX,they are increasingly recommended for warfarin reversal.PCCs have the advan-tages of rapid reconstitution and administration,having high concentrations of coagulation factors in small volumes,and processing to inactivate infectious agents.Though different PCC preparations differ in relative amounts of factors(with VII the most likely to be low),several studies have shown that PCCs can rapidly normalize INR(within minutes)in patients taking OACs(reviewed in43–45).Nonrandomized retrospective reviews and a small case-control study have shown more rapid correction of INR with vitamin K and PCC than vitamin K and FFP,but have not revealed a difference in clinical outcome.46–48One randomized trial compared the use of a PCC(Konyne)to supplement FFP versus FFP alone in patients with OAC-related ICH,finding that those who received PCC had significantly shorter time to INR correction and received less volume of FFP.Although there was no difference in outcome,those who received FFP also had more adverse events,primarily attributable to fluid overload.49 Although PCCs may theoretically increase the risk of throm-botic complications,this risk appears relatively low.43De-Table2.Definition of Classes and Levels of Evidence Used in American Heart Association Stroke Council Recommendations Class I Conditions for which there is evidence forand/or general agreement that theprocedure or treatment is useful andeffectiveClass II Conditions for which there is conflictingevidence and/or a divergence ofopinion about the usefulness/efficacyof a procedure or treatmentClass IIa The weight of evidence or opinion is infavor of the procedure or treatment Class IIb Usefulness/efficacy is less wellestablished by evidence or opinion Class III Conditions for which there is evidenceand/or general agreement that theprocedure or treatment is notuseful/effective and in some casesmay be harmfulTherapeutic recommendationsLevel of Evidence A Data derived from multiple randomizedclinical trials or meta-analysesLevel of Evidence B Data derived from a single randomizedtrial or nonrandomized studiesLevel of Evidence C Consensus opinion of experts,casestudies,or standard of care Diagnostic recommendationsLevel of Evidence A Data derived from multiple prospectivecohort studies using a referencestandard applied by a maskedevaluatorLevel of Evidence B Data derived from a single grade A study,or one or more case-control studies,orstudies using a reference standardapplied by an unmasked evaluator Level of Evidence C Consensus opinion of experts4Stroke September2010spite the lack of large,well-controlled,randomized trials, PCCs are being increasingly recommended as an option in guidelines promulgated for warfarin reversal in the setting of OAC-associated life-threatening or intracranial hemor-rhages.37,38,50–52Table5provides a list of several products for factor replacement in warfarin reversal that are commer-cially available in the United States at the present time. rFVIIa,licensed to treat hemophilia patients with high titer inhibitors or congenital factor VII deficiency,has garnered attention as a potential treatment for spontaneous and OAC-associated ICH.Although rFVIIa can rapidly normalize INR in the setting of OAC-associated ICH,53–57it does not replenish all of the vitamin K–dependent factors and there-fore may not restore thrombin generation as well as PCCs.58 In light of the limited data,a recent American Society of Hematology evidence-based review recommended against routine use of rFVIIa for warfarin reversal.59rFVIIa has also been tested in patients with non-OAC ICH.A phase2randomized trial showed that treatment with rFVIIa within4hours after ICH onset limited hematoma growth and improved clinical outcomes relative to placebo, though with increased frequency of thromboembolic events (7%versus2%).60A subsequent phase3study comparing placebo with20␮g/kg and80␮g/kg of rFVIIa failed to show differences in clinical outcome,despite confirming the ability of both doses to diminish hematoma enlargement.61Although overall serious thromboembolic adverse events were similar, the higher rFVIIa(80␮g/kg)group had significantly more arterial events than the placebo group.The authors noted imbalances in the treatment groups,particularly the greater number of patients with IVH in the higher-dose rFVIIa group.60It remains to be determined whether rFVIIa will benefit a particular subset of patients with ICH,but currently its benefits in ICH patients,whether or not they are under-going treatment with OACs,remain unproven.Studies of the effect of prior antiplatelet agent use or platelet dysfunction on ICH hematoma growth and outcome have found conflicting results.Reported antiplatelet agent use was not associated with hematoma expansion or clinical outcome in the placebo group of an ICH neuroprotective study.62However,others have suggested that platelet dys-function as measured by platelet function assays may be associated with hematoma expansion and clinical out-come.63,64The utility and safety of platelet transfusion orTable3.Class I RecommendationsRecommendations Class/Level of EvidenceEmergency diagnosis and assessment of ICH and its causes Rapid neuroimaging with CT or MRI is recommended to distinguishischemic stroke from ICH.(Unchanged from the previousguideline)Class I,Level AMedical treatment for ICH Patients with a severe coagulation factor deficiency or severethrombocytopenia should receive appropriate factor replacementtherapy or platelets,respectively.(New recommendation)Class I,Level CHemostasis/antiplatelets/DVT prophylaxis Patients with ICH whose INR is elevated due to OAC should havetheir warfarin withheld,receive therapy to replace vitaminK–dependent factors and correct the INR,and receiveintravenous vitamin K.(Revised from the previous guideline)Class I,Level CPatients with ICH should have intermittent pneumatic compressionfor prevention of venous thromboembolism in addition to elasticstockings.(Unchanged from the previous guideline)Class I,Level BInpatient management and prevention ofsecondary brain injuryGeneral monitoring Initial monitoring and management of ICH patients should takeplace in an intensive care unit,preferably one with physicianand nursing neuroscience intensive care expertise.(Unchangedfrom the previous guideline)Class I,Level B Management of glucose Glucose should be monitored and normoglycemia is recommended Class I,Level CSeizures and antiepileptic drugs Patients with clinical seizures should be treated with antiepilepticdrugs.(Revised from previous guideline)Patients with a change in mental status who are found to haveelectrographic seizures on EEG should be treated withantiepileptic drugs Class I,Level A Class I,Level CProcedures/surgery—clot removal Patients with cerebellar hemorrhage who are deterioratingneurologically or who have brainstem compression and/orhydrocephalus from ventricular obstruction should undergosurgical removal of the hemorrhage as soon as possible.(Revised from the previous guideline)Class I,Level BPrevention of recurrent ICH After the acute ICH,absent medical contraindications,BP shouldbe well controlled,particularly for patients with ICH locationtypical of hypertensive vasculopathy.(New recommendation)Class I,Level ACT indicates computed tomography;MRI,magnetic resonance imaging;DVT,deep vein thrombosis;INR,international normalized ratio;OAC,oral anticoagulants; and EEG,electroencephalogram.Morgenstern et al Intracerebral Hemorrhage Guideline5other agents in patients with a normal platelet count,but use of antiplatelet agents or platelet dysfunction,is not known.Patients with ICH have a high risk of thromboembolic disease.65Women and African Americans appear to be at greater risk.65–67Intermittent pneumatic compression combined with elastic stockings has been shown by a randomized trial to be superior to elastic stockings alone in reducing occurrence of asymptomatic deep vein thrombosis after ICH (4.7%versus 15.9%).68Graduated compression stockings alone are ineffec-tive in preventing deep vein thrombosis.69Less clear,however,is the role of adding anticoagulation to pneumatic compression.Two small randomized studies found no difference in deep vein throm-bosis incidence,and no increase in bleeding,in patients given low-dose subcutaneous heparin initiated at day 4or at day 10after ICH.70,71An uncontrolled study of treatment initiated on day 2found a reduction in thromboembolic disease without increased rebleeding.70Recommendations1.Patients with a severe coagulation factor deficiency or severe thrombocytopenia should receive appropriate fac-tor replacement therapy or platelets,respectively (Class I;Level of Evidence:C).(New recommendation)2.Patients with ICH whose INR is elevated due to OACs should have their warfarin withheld,receive therapy to replace vitamin K–dependent factors and correct the INR,and receive intravenous vitamin K (Class I;Level of Evidence:C).PCCs have not shown improved outcome compared with FFP but may have fewer complications compared with FFP and are reasonable to consider as an alternative to FFP (Class IIa;Level of Evidence:B).rFVIIa does not replace all clotting factors,and although the INR may be lowered,clotting may not be restored in vivo;therefore,rFVIIa is not routinely recommended as a sole agent for OAC re-versal in ICH (Class III;Level of Evidence:C).(Revised from the previous guideline).3.Although rFVIIa can limit the extent of hematoma expansion in noncoagulopathic ICH patients,thereTable 4.Integral Components of the History,PhysicalExamination,and Work-Up of the Patient With ICH in the EDCommentsHistoryTime of symptom onset (or time the patient was last normal)Initial symptoms and progression of symptoms Vascular risk factors Hypertension,diabetes,hypercholesterolemia,and smoking MedicationsAnticoagulants,antiplatelet agents,decongestants,antihypertensivemedications,stimulants (including diet pills),sympathomimeticsRecent trauma or surgeryCarotid endarterectomy or carotid stenting in particular,as ICH may be related to hyperperfusion after such procedures DementiaAssociated with amyloid angiopathy Alcohol or illicit drug useCocaine and other sympathomimetic drugs are associated with ICH,stimulants Seizures Liver diseaseMay be associated with coagulopathy Cancer and hematologic disorders May be associated with coagulopathyPhysical examination Vital signsFever is associated with early neurologic deterioration 10Higher initial blood pressure is associated with early neurologic deterioration and increased mortality 11A general physicalexamination focusing on the head,heart,lungs,abdomen,and extremities A thorough but time-urgent neurologic examinationA structured examination such as the National Institutes of Health Stroke Scale can be completed in minutes and provides a quantification that allows easy communication of the severity of the event to other caregivers.GCS score is similarly well known and easily computed,and the initial GCS score is a strong predictor of long-term outcome.12,13These can be supplemented as needed Serum and urine tests Complete blood count,electrolytes,blood urea nitrogen and creatinine,and glucoseHigher creatinine is associated with hematoma expansion.Higher serum glucose is associated with hematoma expansion and worse outcome(although there are no data to suggest that normalization improves outcome)11,14Prothrombin time or INR and an activated partial thromboplastin timeWarfarin-related hemorrhages are associated with an increased hematoma volume,greater risk ofexpansion,and increased morbidity and mortality 15–17(Continued )Table 4.ContinuedCommentsToxicology screen in young or middle-aged patients to detect cocaine and other sympathomimetic drugs of abuseCocaine and other sympathomimetic drugs are associated with ICHUrinalysis and urine culture and a pregnancy test in a woman of childbearing age Other routine tests ECGTo assess for active coronary ischemia or prior cardiac injury that may indicate poor cardiac function and to obtain a baseline in the event ofcardiopulmonary issues during hospitalization Chest radiograph NeuroimagingAs described in the textGCS indicates Glasgow Coma Scale;ECG,electrocardiogram.6Stroke September 2010。

Circulation JournalOfficial Journal of the Japanese Circulation Society http://www.j-circ.or.jpReleased online December 8, 2012Mailing address: Scientific Committee of the Japanese Circulation Society, 8th Floor CUBE OIKE Bldg., 599 Bano-cho, Karasuma Aneyakoji, Nakagyo-ku, Kyoto 604-8172, Japan. E-mail: meeting@j-circ.or.jpThis English language document is a revised digest version of Guidelines for Clinical Cardiac Electrophysiologic Studies reported at the Japanese Circulation Society Joint Working Groups performed in 2010 (website: http://www.j-circ.or.jp/guideline/pdf/JCS2011_ogawas_d.pdf).Joint Working Groups: The Japanese Circulation Society, The Japanese Society of Pediatric Cardiology and Cardiac Surgery, The Japanese College of Cardiology, The Japanese Society of Electrocardiology, The Japanese Heart Rhythm Society ISSN-1346-9843 doi: 10.1253/circj.CJ-66-0055All rights are reserved to the Japanese Circulation Society. For permissions, please e-mail: cj@j-circ.or.jpTable of ContentsIntroduction of the Revised Guidelines ···············498I E quipment, Technology and KnowledgeRequired in Electrophysiologic Studies ···········498 1. Equipment, Technology and Knowledge Required in Electrophysiologic Studies ....................................498 2. Radiation Exposures ................................................498II Sinus Node Function .............................................499III Atrioventricular Block (500)IV B undle Branch Block and IntraventricularConduction Disturbance ·····································501V Preexcitation Syndrome ······································502VI S upraventricular Tachycardia Other Than Atrioventricular ReciprocatingTachycardia ····························································502VII Atrial Flutter ··························································503VIII Atrial Fibrillation ·················································503IX Premature Ventricular Contraction ·················504 1. Methods of Electrophysiologic Studies ·····················504 2. Clinical Significance ··················································505X Nonsustained Ventricular Tachycardia ···········505XI Sustained Ventricular Tachycardia ·················505 1. Definition and the Mechanism ··································505XII Brugada Syndrome ·············································506 1. Indications for Electrophysiologic Studies in Patients With Brugada Syndrome ····························507XIII Idiopathic Ventricular Fibrillation ··················507 1. Idiopathic Ventricular Fibrillation Triggered by Right Ventricular Outflow Tract Premature Ventricular Contraction/Ventricular Tachycardia ······507 2. Early Repolarization Syndrome ································507 3. Short-Coupled Variant of Torsade de Pointes ·········508 4. Short QT Syndrome··················································508 5. Idiopathic Ventricular Fibrillation With No History of ECG Abnormalities ...............................................508XIV Long QT Syndrome . (509)XV V entricular Fibrillation Associated WithStructural Heart Diseases ·································509 1. Introduction ·······························································509 2. Indications for Electrophysiologic Studies ················509 3. Methods of Electrophysiologic Studies ·····················510 4. Clinical Significance ··················································510 5. Criteria for Implementation of Electrophysiologic Studies ······································································510 6. Indications for Treatment Using Electrophysiologic Studies········································510XVI Syncope of Unknown Etiology ·······················510 1. Indications for Electrophysiologic Studies ················510 2. Methods of Electrophysiologic Studies ·····················510 3. Criteria for Electrophysiologic Diagnosis of Syncope (510)XVII P atients After CardiopulmonaryResuscitation ·····················································511XVIII E valuation of Antiarrhythmic DrugEfficacy ·······························································511XIX Surgical Treatment of Arrhythmias ··············512XX Arrhythmias in Children ····································512XXI Cardiac Resynchronization Therapy ············512 1. Introduction ·······························································512 2. Indications for Electrophysiologic Studies ················512 3. Methods of Electrophysiologic Studies ·····················513 4. Clinical Significance ··················································513 5. Criteria for Indication of Cardiac Resynchronization Therapy Based on Electrophysiologic Studies Findings ·······················································513 6. Indications for Cardiac Resynchronization Therapy.....................................................................513XXII Cardiac Pacemaker Implantation .................513XXIII Catheter Ablation .............................................514References .. (514)(Circ J 2013; 77: 497 – 518)JCS GUIDELINES498JCS Joint Working GroupTreatment strategies for severe arrhythmias have evolved sig-nificantly based on the recent development of non-pharmaco-logical procedures such as catheter ablation, implantable car-dioverter defibrillator (ICD), and cardiac resynchronization therapy (CRT). Because of the invasiveness of these proce-dures, their indications should be carefully determined after thorough consideration of their short and long-term effects. Since the results of large-scale clinical studies in Europe and the United States have suggested that ICD/CRT be used for more patients for the primary prevention of sudden death in Japan, appropriate risk stratification is required to determine indications of these procedures.The history of clinical electrophysiologic studies (EPS) began when Scherlag et al. established His bundle electrogram in 1969. Use of His bundle electrogram dominated in the evalu-ation of sinus node function and atrioventricular (AV) conduc-tion during that era. In addition to the His bundle electrogram, the premature stimulation technique significantly contributed to the understanding of the pathogenesis of arrhythmias, and was established as an important method to evaluate the effi-cacy of antiarrhythmic drugs. This method was also used to identify arrythmic foci, which stimulated the development of ablation therapy.Under these circumstances, “the Guidelines for Clinical Car-diac Electrophysiologic Studies” was published in 2006 (2004–2005 Joint Working Groups Report, Chair: Iwao Yamaguchi) to provide guidance to physicians in Japan regarding the use of cardiac EPS in the diagnosis, selection of treatment strate-gies, and prediction of prognosis in patients with arrhythmias.1 The present edition of the guidelines was prepared as a partial revision that is undertaken once every five years. For the pres-ent edition, a new Joint Working Groups was organized and has worked for one year with the following considerations in mind: 1) Contents of this guideline should be consistent with those of “the Guidelines for Non-Pharmacotherapy of Cardiac Arrhythmias” and “the Guidelines for Indications and Proce-dures of Catheter Ablation” which were under preparation by the Japanese Circulation Society, and overlap with these guide-line documents should be avoided; 2) the authors who wrote chapters for the previous edition revised, and, if not possible, specialists with expertise in the relevant therapeutic areas revised each chapter; 3) substantial modifications were made for the chapters regarding therapeutic areas where new understand-ings of a disease have changed its diagnosis and treatment during the past five years. For example, regarding “Ventricu-lar Fibrillation” a new section “Idiopathic Ventricular Fibril-lation” was added to separate it from “Ventricular Fibrillation Associated with Structural Heart Diseases” because new con-cepts such as early repolarization syndrome and short QT syn-drome have been incorporated in the field. On the other hand, for Brugada syndrome and some other conditions, the indica-tions for EPS remained almost unchanged although new authors were involved since no consensus was achieved regarding the significance of clinical EPS in determining treatment strate-gies despite large amounts of new data were added. The sec-tion for the identification of ablation sites for the treatment of chronic atrial fibrillation (AF) was modified by the author who wrote the section in the previous version to reflect the change in indications for EPS to identify ablation sites in the treatment of chronic AF for which catheter ablation has become increas-ingly common.Indications for EPS (indications by class) are listed in the same format as before in this revision. However, for the points where the members of Joint Working Groups could not reach agreement due to the lack of sufficient evidence, the present view was included upon the discussion among the members for which further revision may be necessary.It is difficult to decide which should be included in a guide-line document to be revised every five years regarding those therapeutic areas that are rapidly evolving. The present guide-lines are the accumulation of wisdom of the members of the Joint Working Groups, who are top experts actively engaged in the area of arrhythmias and cardiac electrophysiology. Readers should use this guideline accordingly.1. Equipment, Technology and KnowledgeRequired in Electrophysiologic Studies2Although many types of electrode catheters are available for cardiac EPS, all electrode catheters share the same basic func-tion of recording intracardiac electrical potentials and stimu-lating heart muscles. Physicians should select appropriate elec-trode catheters according to the purpose of the test. The test requires an X-ray machine, a recorder to record surface elec-trocardiography (ECG) and intracardiac electrical potentials, and a stimulator to determine refractory periods and induce tachycardia (Table 1).3 A defibrillator and emergency resus-citation equipment should be prepared for use. EPS are per-formed by a team of physicians, nurses, radiology technicians and/or clinical engineers.Physicians who perform EPS should have expertise in insert-ing and manipulating electrode catheters and have extensive knowledge of clinical electrophysiology (especially on cardiac conduction and refractory period) (Table 2). The stimulator is used to induce arrhythmias, and the results are used to diag-nose arrhythmias and develop treatment strategies for each case. EPS must be performed carefully by preparing for rare but serious complications.2. Radiation ExposuresEPS may cause radiation exposure not only to the patient but also to the staff members in the laboratory. The amount of radiation exposure increases with the time spent during the test. Usually, the total exposure time rarely exceeds 10 minutes, and the amount of radiation exposure during EPS is smaller than that during coronary angiography.4 Since a posterior-anterior projection is commonly used in EPS, erythema and necrosis of the skin of the back may develop.5 The threshold level of radiation dose that causes radiation-induced skin injuries is 2 Gy, and the absorbed dose in the skin reaches to 2 Gy when the patient received X-rays from a conventional X-ray machine for a total of about 60 minutes.6 An EPS requires at most 10499JCS Guidelines for Clinical EPS minutes of radiation exposure, and the radiation exposure to the skin will not cross the threshold.Staff members are also exposed to X-rays in the laboratory due to X-ray scattering in every direction. Therefore, staff mem-bers should wear protective clothing which also covers their back. The operator who handles electrode catheters should wear a neck guard and goggles as well, and should be careful not to expose his/her hands and arms directly to X-rays. Radiationexposure to the patient and staff members should be mini-mized using appropriate X-ray techniques (e.g., narrowing the radiation field, reducing X-ray exposure time, avoiding mag-nified imaging, and holding the image intensifier close to the patient), appropriate equipment setting (e.g., using pulse radi-ation, a low image acquisition rate, and non-radiological devices), and appropriate protection measures.7(Indications by class are listed in Table 3.)Sinus node function is influenced by three factors, i.e., sinus node automaticity, sinoatrial conductivity, and the activity of the autonomic nerves affecting sinus node. The electrical impulse generated in the sinus node travels through the sino-atrial junction to the atria.Sick sinus syndrome (sinus node dysfunction) is character-ized by bradycardia due to abnormal sinus node automaticity or conductivity that causes central nervous system symptoms such as syncope and blackouts.Increased sinus rate caused by enhanced sinus node auto-maticity may be observed in patients with sympathicotonia, fever, hyperthyroidism and inappropriate sinus tachycardia (IST) or other conditions.Sick sinus syndrome is a clinical term used to describe signsand symptoms of sinus node dysfunction. In order to diagnose the condition, the relationship between sinus bradycardia and the symptoms must be confirmed. Patients in whom the rela-tionship between bradycardia and symptoms can be confirmed by long-term Holter ECG monitoring or other tests are not indi-cated for EPS. For patients who are suspected to have sinus node dysfunction but in whom the relationship between ECG findings and symptoms is not clear, noninvasive, long-term monitoring such as frequent use of Holter ECG monitoring, wireless ECG monitoring, and ambulatory ECG is performed to obtain ECG findings during the onset of symptoms. Elec-trophysiologic evaluation of sinus node function to determine sinus node recovery time (SNRT), sinoatrial conduction time, and intrinsic heart rate is beneficial when no definitive find-ings have been obtained with noninvasive assessment. DuringEPS, cardiac electrophysiologic studies.Adapted from Fujiki A. Electrophysiologic Studies: techniques and devices. In: Inoue H, Okumura K, editors. Clinical Cardiac Electrophysiologic Studies. p24. Igaku-Shion Ltd., Tokyo, 2002.3EPS, cardiac electrophysiologic studies.500JCS Joint Working GroupEPS patients should also be assessed for the presence/absence of supraventricular tachyarrhythmia, AV conduction distur-bance, and retrograde ventriculoatrial conduction to obtain information useful for the determination of treatment strate-gies, drug regimens and pacing modes. EPS are generally not necessary for patients in whom the relationship between bra-dycardia and symptoms has been confirmed with noninvasive methods such as ECG and Holter ECG monitoring and whoare not complicated with AV conduction disturbance or tachy-cardia, or have only asymptomatic sinus bradycardia.A new minimally-invasive ECG monitoring method using an implantable loop recorder implanted under the skin in the left anterior chest has been introduced to obtain detailed ECG data during syncope in patients with syncope of unknown eti-ology.(Indications by class are listed in Table 4.)AV block is defined as a delay or interruption in the transmis-sion of an impulse from the atria to the ventricles through the AV node, His bundle and His-Purkinje system. The severity of AV block is determined not only by ECG pattern but also by the sites of block. The severity is high especially among patients where the conduction is blocked within or below the Hisbundle since these blocks may induce more severe conduction block or represent unstable lower pacemakers that generate escape rhythms. It is therefore important to locate the sites of block in predicting prognosis and determining treatment strat-egies. Since there is a limit to locate the sites of block by using the standard 12-lead ECG, Holter ECG monitoring or exerciseECG, EPS is necessary for patients with AV block.AV, atrioventricular; ECG, electrocardiography; EPS, cardiac electrophysiologic studies.501 JCS Guidelines for Clinical EPS(Indications by class are listed in Table 5.)The intraventricular conduction system consists of the His bundle, right bundle branch, left bundle branch and Purkinje fibers. Although the geometry of the left bundle branch can vary greatly among individuals, it generally subdivides into the anterior and posterior fascicles in the interpretation of ECG. Table 6 lists the criteria for ECG-based diagnosis of intraven-tricular conduction disturbance.8 A blockage in either the right or left bundle of the conducting pathway is called bundle branch block. A blockage in either the left anterior or posterior fas-cicle is called fascicular block. Bifascicular (bilateral bundle branch) block shows up on the ECG as a combination of char-acteristic wave patterns of right bundle branch block in con-junction with either left anterior or posterior fascicular block.A conduction disturbance in all three fascicles is called trifas-cicular block, and shows up on the ECG as a mixture of wave-forms of bifascicular block and either first or second degree AV block. EPS using intracardiac electrogram recording andAV, atrioventricular; ECG, electrocardiography; EPS, cardiac electrophysiologic studies. ECG, electrocardiography.502JCS Joint Working Groupcardiac electrical stimulation are useful to predict the risk of AV block among patients with bundle branch block and/or intraventricular conduction disturbance.9 The presence of con-duction disturbance may be determined when at least one of the following criteria are met:1. A n HV interval of 55 msec or more for cases of bifascicular or trifascicular block.2. T he presence of HV block induced by continuous atrial stim-ulation at 150 bpm or less.103. A n effective refractory period of the His-Purkinje system of 450 msec or more.4. A t least a two-fold prolongation of the HV interval from baseline or a prolongation of the HV interval by 100 msec or more (the HV interval may prolong by 20% or less under normal condition), or induction of second or third degree block within or below the His bundle following a procain-amide loading (300 to 1,000 mg intravenous injection [I.V.]); or induction of second or third degree block by continuous ventricular stimulation at baseline or following administra-tion of procainamide or lidocaine (1 to 2 mg/kg I.V.).5. I nduction of ventricular tachycardia (VT) or ventricular fibrillation (VF) by programmed ventricular stimulation.(Indications by class are listed in Table 7.)American College of Cardiology/American Heart Association (ACC/AHA) Guidelines for Clinical Intracardiac Electrophys-iological and Catheter Ablation Procedures were published in 1995, and have been widely used as a guide for clinical EPS in patients with Wolff-Parkinson-White (WPW) syndrome.11 However, indications for EPS in this patient population may be changed when the safety of EPS is improved, the diagnos-tic criteria to specify high-risk patients are established, and the positive predictive value for sudden death is increased.12 Although the prevalence of sudden death is low among patients with WPW syndrome,13–15 it has been reported that 10% of young patients who resuscitated from cardiac arrest have WPWsyndrome.16 A broad consensus has been reached on the use-fulness of EPS in patients with WPW syndrome who have experienced cardiac arrest, syncopal attacks of unknown etiol-ogy, and/or tachycardia attacks.EPS may be indicated for symptomatic patients with Lown-Ganong-Levine (LGL) syndrome, a condition characterized by tachycardia, but are generally not indicated for asymptom-atic patients with LGL syndrome who only show a short PR interval without tachycardia.17Indications for EPS in patients with atypical WPW syndrome where the involvement of the Mahaim fiber is suspected should be in accordance with those in overt WPW syndrome.(Indications by class are listed in Table 8.)Paroxysmal supraventricular tachycardia not involving AV accessory pathways include tachycardias originated from atrial muscle (including the sinoatrial node) other than atrial flutter/AF, and tachycardias originated from the AV junction.18 Since the safety and efficacy of radiofrequency catheter ablation in the treatment of AV nodal reentrant tachycardia (AVNRT), the most common form of this type of tachycardias, have been established, patients with this type of tachycardia are generally indicated for EPS to make a definitive diagnosis prior to cath-eter ablation. EPS is especially useful for patients with uncom-mon-type AVNRT in assessing the mechanism and making differential diagnosis. Even patients in whom ablation is not planned often undergo EPS to determine the optimal drug regi-men and evaluate the efficacy of the treatment regimen. EPS is indicated for patients with atrial tachycardia (AT) when they are symptomatic and should be assessed in detail to clarify the mechanism and origin of tachycardia to select appropriate drugs.EPS, electrophysiologic studies; WPW, Wolff-Parkinson-White.。