2023+SIAARTI专家共识声明：β受体阻滞剂在重症患者中的作用（英文版）.pdf

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1、Guarracinoetal.J Anesth Analg Crit Care https:/doi.org/10.1186/s44158-023-00126-2ORIGINAL ARTICLEOpen Access The Author(s)2023.Open Access This article is licensed under a Creative Commons Attribution 4.0 International License,which permits use,sharing,adaptation,distribution and reproduction in any

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3、cated otherwise in a credit line to the material.If material is not included in the articles Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use,you will need to obtain permission directly from the copyright holder.To view a copy of th

4、is licence,visit http:/creativecommons.org/licenses/by/4.0/.Journal of Anesthesia,Analgesia and Critical CareThe role ofbeta-blocker drugs incritically ill patients:aSIAARTI expert consensus statementFabio Guarracino1,Andrea Cortegiani2,3*,Massimo Antonelli4,Astrid Behr5,Giandomenico Biancoore6,Alfr

5、edo Del Gaudio7,Francesco Forfori8,Nicola Galdieri9,Giacomo Grasselli10,11,Gianluca Paternoster12,Monica Rocco13,Stefano Romagnoli14,15,Salvatore Sardo16,Sascha Treskatsch17,Vincenzo Francesco Tripodi18 and Luigi Tritapepe19 Abstract Background The role of-blockers in the critically ill has been stu

6、died,and data on the protective eects of these drugs on critically ill patients have been repeatedly reported in the literature over the last two decades.However,consensus and guidelines by scientic societies on the use of-blockers in critically ill patients are still lacking.The purpose of this doc

7、ument is to support the clinical decision-making process regarding the use of-blockers in critically ill patients.The recipients of this document are physicians,nurses,healthcare personnel,and other profes-sionals involved in the patients care process.Methods The Italian Society of Anesthesia,Analge

8、sia,Resuscitation and Intensive Care(SIAARTI)selected a panel of experts and asked them to dene key aspects underlying the use of-blockers in critically ill adult patients.The methodology followed by the experts during this process was in line with principles of modied Delphi and RAND-UCLA methods.T

9、he experts developed statements and supportive rationales in the form of informative text.The overall list of statements was subjected to blind votes for consensus.Results The literature search suggests that adrenergic stress and increased heart rate in critically ill patients are associated with or

10、gan dysfunction and increased mortality.Heart rate control thus seems to be critical in the manage-ment of the critically ill patient,requiring careful clinical evaluation aimed at both the dierential diagnosis to treat secondary tachycardia and the treatment of rhythm disturbance.In addition,the us

11、e of-blockers for the treatment of persistent tachycardia may be considered in patients with septic shock once hypovolemia has been ruled out.Intravenous application should be the preferred route of administration.Conclusion-blockers protective eects in critically ill patients have been repeatedly r

12、eported in the literature.Their use in the acute treatment of increased heart rate requires understanding of the pathophysiology and careful dier-ential diagnosis,as all causes of tachycardia should be ruled out and addressed rst.Keywords-blockers,Critically ill patient,ICU,Tachyarrhythmia,Sepsis,Ad

13、ults*Correspondence:Andrea Cortegianiandrea.cortegianiunipa.itFull list of author information is available at the end of the articlePage 2 of 9 Guarracinoetal.J Anesth Analg Crit Care BackgroundCritically ill patients admitted to an intensive care unit(ICU)may be aected by dierent degrees of sympa-t

14、hetic overow 14 secondary to the primary acute disease(i.e.,shock,trauma,infection)and often present with preexisting cardiovascular comorbidities.e role of-blockers in critically ill patients has been studied,and data on the protective eects of these drugs on the critically ill have been repeatedly

15、 reported in the litera-ture over the last two decades.-blockers exert their eects through several sub-types of G-protein-coupled-adrenergic receptors 5 expressed on the surface of cell membranes almost ubiq-uitously in the human body.Generally,-blockers interfere with catecholamines and sympathomim

16、etics by preventing and/or modulating the-adrenergic responses.e clinical eects depend on the subtypes of receptors a-blocker binds to and their locations(Table1).Based on their pharmacodynamics,-blockers are cur-rently indicated for treating systemic arterial hyperten-sion,tachyarrhythmias,and hear

17、t failure 6.In addition,-blockers decrease blood pressure by reducing after-load.is in turn together decreases myocardial oxygen consumption and improves myocardial perfusion as well as stroke volume(SV).ey also show eective control of sympathetic activation,and their proven ecacy for treating rhyth

18、m alterations 7 represents a strong patho-physiological rationale to consider such treatment in the management of critically ill patients suering from acute tachyarrhythmias.However,consensus and guidelines by scientic soci-eties on the use of-blockers in critical illness are still lacking,and guide

19、lines on management of septic patients have never recommended their use in this setting.To ll this gap,a group of expert intensivists selected by the Italian Society of Anesthesia,Analgesia,and Intensive Care(SIAARTI)wrote this good clinical practice docu-ment on the use of beta-blockers in critical

20、ly ill patients.Methodologye expert panel members were selected by the two pro-ject coordinators(F.G.,L.T.)based on evidence,clini-cal,and scientic experience on the subject on behalf of SIAARTI.After an initial meeting to dene the meth-odology,the dierent topics were assigned to one or more panel m

21、embers,based on their respective skills,as follows:Evaluate the available evidence.Produce statements and supporting rationales in the form of an explanatory text.e overall list of statements was submitted to a vote,according to the method,to express the degree of consensus.e methodological path of

22、the document was outlined by a methodologist(A.C.)and was based on the auditing principles of scientic literature and the modied Del-phi method 8.More in detail,the literature review was conducted by two subject matter experts with no dened time limit,on PubMed,using MeSH words 1(E-Table1 Additional

23、 File 1).e panel of experts dened four clinical questions(CQ)that were presented and voted during an online scoping workshop.Following up the denition of the questions,the two subject matter experts dened a dedi-cated literature search strategy.e two experts then selected the relevant literature fro

24、m the list generated by the search and correlated each chosen paper to one or more of the four clinical questions.e list of chosen papers was then submitted to the panel for review(Addi-tional File 2).e types of papers included in the search were as fol-lows:randomized controlled trials,systematic r

25、eviews,meta-analysis,guidelines,non-randomized controlled trials,narrative reviews,position papers,and experi-mental studies.Papers with a language dierent from English were excluded,as were conference proceedings,Table 1 Pharmacokinetics and pharmacodynamic properties of intravenous-blockersLegend:

26、Max Maximum,min Minutes,HR Heart rate,MAP Mean arterial pressureDrug Onset(min)Max.elimination half-life(min)Receptors Cardio-selectivity(12)Metabolization HR MAPMetoprolol 13 420 1 3 Cytochrome P2D6(Leber)Labetalol 25 120480 121 No By the liver resulting in an inac-tive glucuronide conjugate Propan

27、olol 5 360600 12 No Cytochrome P2D6 Esmolol 2 9 1 30 ERY esterases Landiolol 1 4 1 250 Pseudocholinesterases/Page 3 of 9 Guarracinoetal.J Anesth Analg Crit Care case reports,and case series.e search was conducted,and the nal reports were generated following the prin-ciples of PRISMA 2020 9(Fig.1 in

28、the Additional File 1).e panelists,using the report from the subject mat-ter experts and their competencies,drafted a list of state-ments and rationales that they then put for vote on a secret ballot.e entire panel(with the exclusion of the search specialist and methodologist)took part in the blind

29、vote.e methodology dictated a maximum of two possible rounds of voting online.e opinion was expressed using an ordinal Likert scale,according to the RAND-UCLA method(minimum score,1=completely disagree;maximum score,9=com-pletely agree).is scale was divided into 3 sections:13 implied refusal/disagre

30、ement(“inappropriate”),46 implied(“uncertainty”),and 79 implied agreement/sup-port(“appropriateness”)10.A consensus was reached when as follows:1)At least 75%of the respondents(excluding the meth-odologist and the search specialist)assigned a score between 13,46,or 79,which meant refusal,uncertainty

31、,and agreement of the statement,respec-tively.2)e median score was within the same range.e type of consensus was determined by the positioning of the median.It was not necessary to run the second Delphi round,as all statements reached consensus at the rst round.e results of the votes were reported i

32、n a tabulated form.e full version of the Italian document issued by the Italian Society of Anesthe-sia,Analgesia,Resuscitation,and Intensive Care(SIAARTI)was published in April 2023 and is freely available on the societys website in Italian(https:/w w w.siaar ti.it/ne ws/15276 82).Question I.What is

33、therationale forcorrecting tachycardia inthecritically ill patients?In critically ill patients,the acute state of illness often increases myocardial and tissue oxygen consumption(VO2)in general and causes profound adrenergic acti-vation.Adrenergic hypertonicity is one of the protag-onists of the com

34、plex neuroendocrine response that the patient exhibits when oxygen delivery(DO2)and hi s VO2 lose the optimal ratio 11,12.e continua-tion of this rapid compensation mechanism,even if the causes that may have triggered it are treated(e.g.,ane-mia,hypovolemia,pain,and hyperthermia),can favor hypoperfu

35、sion secondary to vasoconstriction and an inevitable increase in myocardial VO2 linked to tachy-cardia or heart failure 3,4.is scenario is commonly accompanied by an increase in heart rate,which can take the form of sinus tachy-cardia or lead to tachyarrhythmias possibly associated with hemodynamic

36、instability(hypotension and/or hypoperfusion).is excessive adrenergic stress and increased heart rate have been associated with organ dysfunction and increased mortality 1315.In this pathophysiological scenario,in light of litera-ture data,heart rate control assumes an important role in the manageme

37、nt of the critically ill patient,requiring careful clinical evaluation aimed at both the dierential diagnosis of secondary tachycardia and the treatment of the rhythm alteration.Physiologically,the main compensation mechanisms involve the release of endogenous catecholamines with sympathetic hyperst

38、imulation.e use of exogenous cat-echolamines may also be necessary for the treatment of hemodynamic instability.However,in both cases,exces-sive adrenergic stimulation is related to organ damage with worsening of the outcome and increased mortality.e diagnostic framework of tachycardia requires the

39、analysis of the electrocardiographic tracing and the appropriate integration of this within an echocar-diographic examination 16.It is dened as a heart rate(HR)greater than 100bpm 12,17.It can originate as follows:At sinus node and is dened as sinus tachycardia;At the ventricular level and is dened

40、as ventricular tachycardia,usually of short duration and accompa-nied by important hemodynamic alterations;From supraventricular origin and is generally rep-resented by an altered electrical activity in the atrial chambers and is due either to the re-entry mecha-nism or to an increase in automaticit

41、yIn the latter case,it can manifest itself as follows:Atrial utter with regular sawtooth waves at a rate of 180250/min;Tachyarrhythmia absoluta with atrial brillation waves replacing P waves followed by abnormal QRS complexes;Ventricular tachycardia with irregular RR intervals and QRS complexes with

42、 abnormal duration and morphology and not associated with a previous P wave.Echocardiography performed in order to diagnose the origin of tachycardia and to guide the appropriateness of beta-blockers administration should focus on both sys-tolic and diastolic function,as well as on volume status.Pag

43、e 4 of 9 Guarracinoetal.J Anesth Analg Crit Care e calculation of the ventriculo-arterial coupling,a more complex evaluation,can be added to this echocar-diographic evaluation to understand the eciency of the cardiovascular system 18 and to reassess the patients physiology after treatment.Question I

44、I.What istherationale forusing a-blocker tocorrect tachycardia incritical patients?In thecritically ill patient,tachycardia control should be achieved withtheuse of-blocking drugsA recent meta-analysis of 11 studies,including 2103 criti-cally ill patients,showed a signicant reduction in mor-tality(r

45、isk ratio 0.65,95%CI 0.530.79;P 0.0001)in patients treated with-blockers compared to controls 12.However,it is important to note that this systematic review and meta-analysis included a diverse set of stud-ies,with the majority of them focusing on patients with myocardial ischemia or those undergoin

46、g cardiac sur-gery.As a result,it becomes challenging to make deni-tive conclusions regarding the observed dierences in mortality.Another recent retrospective study of 204,981 patients undergoing major abdominal surgery,conducted with propensity score analysis,found no dierences in the incidence of

47、postoperative stroke among patients receiv-ing-blocker in chronic therapy(odds ratio,0.86;95%CI,0.65 to 1.15;P=0.901)and patients in whom the drug was started within 60days before surgery(odds ratio,0.90;95%CI,0.31 to 2.04;P=0.757)19.Additionally,patients on chronic-blocker therapy had a lower risk

48、of major cardiac events(odds ratio,0.81;95%CI,0.72 to 0.91;P=0.007)19.-blockers in the acute setting are only protective if there is“tachycardia.”ey do not encounter a“self-eect”independent of the patients situation 20.To attribute condence of recommendation to the use of these drugs in critically i

49、ll patients,further randomized controlled trials(RCTs)are needed to answer questions regarding patient selection,the choice of drug,timings,and optimal hemodynamics targets.In patients withseptic shock,theuse of-blockers fortreating persistent tachycardia may be considerede distinction between secon

50、dary(induced by a low SV)and non-secondary(generated by an excessive sym-pathetic response or arrhythmic disorder)tachycardia is therefore the main element to identify patients who may benet from-blocker therapy.In the rst phase of septic shock,uncontrolled inammation causes vasodilation and an incr