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Methylene Blue: Vasoplegic Syndrome Finally Resolved ?

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Presentation on theme: "Methylene Blue: Vasoplegic Syndrome Finally Resolved ?"— Presentation transcript:

1 Methylene Blue: Vasoplegic Syndrome Finally Resolved ?
Malte Book Department of Anaesthesiology and Pain Medicine

2 Vasoplegic syndrome after cardiac surgery
Incidence 5% to 25% Levin et al. Circulation Oct 27;120(17): Hypotension Cardiac output  or  Systemic vascular resistence  Requirement for fluid and vasopressors 

3 Levin et al. Circulation. 2009;120:1664-1671

4 Methylene Blue, the magic bullet?

5 Mode of action Inhibitor of NO Sythase NO scavenger
Inhibitor of Guanulate Cyclase, cGMP  cGMP mediated vasodilatation  Interleukin-1 dependent Superoxide dependent

6 Side effects Cardiac arrhythmias Coronary vasoconstriction
Angina/precordial pain Cardiac output  Renal/mesenteric blood flow  Methemoglobinemia Hemolysis Monoamine oxidase inhibitor

7 Contraindications Severe renal impairment
Glucose 6 Phosphat Dehydrogenase deficiency Serotoninergic medication

8 Evidence?

9 CVP < 5 mmHg and PCWP < 10 mmHg CI > 2.5 l/min/m2
Hypotension MAP < 50 mmHg CVP < 5 mmHg and PCWP < 10 mmHg CI > 2.5 l/min/m2 SVR < 800 dyn/s/cm-5 Vasopressor requirement Levin et al. Ann Thorac Surg 2004;77:496 –9

10 638 patients, 56 with vasoplegic syndrome
Randomization: 3 hours after arrival in the recovery room  1.5 mg/kg methylene blue Levin et al. Ann Thorac Surg 2004;77:496 –9

11 100 patients at risk for vasoplegia
ACE inhibitors Calcium channel blockers Heparine 1 hour preoperative 2 mg/kg methylene blue

12 SVR during cardiopulmonary bypass
Özal et al. Ann Thorac Surg 2005;79:1615–9

13 Korean J Anesthesiol 2012 August 63(2): 142-148
Preoperative Prophylactic Methylene blue before CPB No differences in: MAP, MPAP, CI, PCWP, SVR Need for vasopressor/inotrope Less erythrocyte/platelet concentrates and FFP transfusion in the MB group Korean J Anesthesiol 2012 August 63(2):

14 Several studies showed potential
benefit in the treatment or prevention of vasoplegic syndrome

15 Indication No standard indication Prevention of vasoplegic syndrome
Reversal of vasoplegic syndrome Inconsistant definition of vasoplegic syndrome

16 Timing + dosing No standard timing of administration Preoperative
Intraoperative During CPB Postoperative No standard dosing 1.5 to 7.0 mg/kg bolus Continious infusion

17 Data quality + safety Few RCTs Mainly case reports/case series
No phase 1 studies IMA contraction in clinically achieved concentrations Ulusoy et al. J Cardiothorac Vasc Anesth Aug;22(4):560-4

18 Recommendation No routine use of Methylene Blue
Application within clinical trials Might be considered as final therapeutic option

19 Alternative Arginin Vasopressin (AVP) Up to 0.1 U/min
Higher number of RCTs investigated the clinical administration Vasoplegia due to relative AVP deficiency Colson et al. Critical Care 2011, 15:R255 Possibly causal therapy

20 ende



23 Anästhesiologisches Management
Monitored Anaesthesia Care (MAC), Lokalanästhesie Sedierung mit Dexmedetomidin 6l O2/Min über Maske Monitoring: EKG, invasiver RR, ZVD, Kapnometrie, SpO2 Invasivitäten: A. rad. li., 3-Lumen ZVK, 6 Fr. Schleuse + Einschwemm-Pacer, ext. Defi-Pads

24 komplikationslos bis zum Freisetzen der Prothese (TF-AVI MCV 26)

25 CPR 09:44 hämodynamische Verschlechterung: Perikarderguß (KM Halo im Fluoro) Volumen + Noradrenalin Boli; Protamin 09:50 RR syst. 55mmHg, Vigilanz ↓ Maskenbeatmung 09:52 CPR + Adrenalin + Intubation subxyphoidale Drainage 5 F  (Re-)Transfusion TEE Einlage (Bilder Xcelera ?) Fortsetzung CPR durch LUCAS, dann offen Windi: Zunächst V a Perf RV durch Pacer vermutet

26 Erste Stabilisierung, 2. CPR
Noradrenalin/Adrenalin kontinuierlich Aufrechterhaltung mit Fentanyl/Midazolam 10:00 – 10:30 Massivtransfusion + Retransfusion der Drainageverluste bei andauerndem Volumenverlust  keine Stabilisierung Trotz Infusion hypovolämer Kreislaufstillstand mit CPR, 10:20 ROSC mit Katecholaminen und Volumen

27 Limitations? Volume therapy intra- and 6 hour postoperative
Crystalloid (ml) Colloid (ml) RBC FFP Methylene blue Placebo

28 Recommendation Few RCTs Mainly case reports/case series
No phase 1 studies IMA contraction in clinically achieved concentrations

29 Inclusion criteria Hypotension MAP < 50 mmHg
CVP < 5 mmHg and PCWP < 10 mmHg CI > 2.5 l/min/m2 SVR < 800 dyn/s/cm-5 Vasopressor requirement Levin et al. Ann Thorac Surg 2004;77:496 –9

30 Levin et al. Ann Thorac Surg 2004;77:496 –9

31 Limitations? Liberal inclusion criteria
Anaesthetic drugs in the recovery room? Volume therapy? Vasopressin? Levin et al. Ann Thorac Surg 2004;77:496 –9

32 Pericardiotomie, Sternotomie
Indikation subxyphoidale Pericardiotomie Einlage großlumiger Perikarddrainage mit Retransfusion  initiale Stabilisierung Ca 10:50 Sternotomie: Blutung aus LV-Apex (hellrot, spritzend)

33 Verlauf Seldinger-Tausch 3-L-ZVK  9,0 Fr. MAC Katheter
Transfusion mit Rapid Infusion System Übernähung des LV Apex Stabilisierung der Patientin Verlegung ICU

34 Keine Stellungnahme zur Anästhesie  Keine Guidelines
 Warten auf Part II? Catheter Cardiovasc Interv Mar 1. doi: /ccd [Epub ahead of print] Multisociety (AATS, ACCF, SCAI, and STS) expert consensus statement: Operator and institutional requirements for transcatheter valve repair and replacement, part 1: Transcatheter aortic valve replacement. Tommaso CL, Bolman RM 3rd, Feldman T, Bavaria J, Acker MA, Aldea G, Cameron DE, Dean LS, Fullerton D, Hijazi ZM, Horlick E, Miller DC, Moon MR, Ringel R, Ruiz CE, Trento A, Weiner BH, Zahn EM. J Thorac Cardiovasc Surg Jun;143(6):

35 Kontroverse MAC  GA “The current technology and procedure necessitates general anesthesia, endotracheal intubation, and TEE.” Billings et al. Anesth Analg May;108(5): “TAVR is typically performed under general anesthesia with central monitoring, using a pulmonary artery catheter and transesophageal echocardiography“ Holmes et al. J Am Coll Cardiol Mar 27;59(13):


37 Konversion MAC  GA L. Bergmann et al. Anaesthesia, 2011, 66, 977–982
17/100 Konversionsrate zu GA  15/17 nicht in Notfall-Situation  12/17 hatten Gefäßkomplikationen Billings et al. Anesth Analg May;108(5): 7 transapikale + 29 transfemorale Patienten (alle GA) 25/29 chirurgische Leistenrevision Berner Zahlen

38 Inselspital Heart Team: TAVI Anaesthesia and Outcomes
08/2007 to 10/2011 Anaesth technique AVI % (n) LA → GA conversion CPR intra-proced. Mortality intra- proced. Extubat. end of proced. ICU post- All cause mortality 30 d GA TA TS TF 39% (157) -- 3.8 % (6) 0.6 % (1) 76 % (120) 66 % (103) 8.3 % (13) LA-MAC 61% (245) 6.9 % (17) 2.1 % (5) 1.2 % (3) 97 % (240) 8 % (19) 5.3 % p=0.45 p=0.95 p<0.001 p=0.33 Total 100 % (402) 2.7 % (11) 1.0 % (4) 90 % (360) 30 % (122) 6.5 % (26) Prospective Registry Data, Swiss CV Center

39 Berner Lernkurve 555 interventionelle Aortenklappenprozeduren
425/111/11 transfemoral/transapikal/subclavia 85/340 GA/MAC Konversion MAC zu GA 22 von 340 7 von 22 bei CPR 2 von 22 bei TEE Notwendigkeit 9 von 22 bei Unruhe 2 von 22 bei resp. Problemen 2 von 22 bei sonst. Problemen (= 13/340 = 3.8% „anästhesiolog“. Konversion) = GALA

40 Individuell angepasstes Vorgehen
(da < 5% Anästhesiolg motivierter Konversion LA-GA) Schwieriger Atemweg TEE Compliance  Dekompensierte Patienten „unkomplizierte Patienten“ GA MAC

41 Handlungsfähigkeit im Notfall
vollausgestatteter Anästhesiearbeitsplatz plus tee Monitoring/Invasivitäten GA = MAC  außer Tubus und ggf. TEE getestete Blutprodukte in TAVI Labor Standardkonfiguration der Geräteanordnung konstante Teams (Kardiologie, Anästhesie, Assistenz)

42 Postmedikation

43 Danke Reto Basciani Christoph Huber Stefan Windecker Peter Wenaweser
Gabor Erdös Balthasar Eberle

44 The Heart Team: European Recommendation

45 The Heart Team: North American Recommendation
Holmes DR Jr., Mack MJ, Kaul S, Agnihotri A, Alexander KP, Bailey SR, Calhoon JH, Carabello BA, Desai MY, Edwards FH, Francis GS, Gardner TJ, Kappetein AP, Linderbaum JA, Mukherjee C, Mukherjee D, Otto CM, Ruiz CE, Sacco RL, Smith D, Thomas JD ACCF/AATS/SCAI/STS expert consensus document on transcatheter aortic valve replacement. J Am Coll Cardiol 2012;59:1200 –54.

46 Multidisciplinary Heart Team
Joint planning (HT program, procedures, training, staff, schedule) Core HT: diagnostics, treatment plan, patient process Anaesthesiology: HT partner in large invasive/hybrid procedures pre-anaesthesia patient evaluation procedural anesthesia management trouble shooting Team stability, consistent communication Growing expertise and motivation … in all HT partners Am Heart J Jun;151(6): The SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery (SYNTAX) study: design, rationale, and run-in phase. Ong AT, Serruys PW, Mohr FW, Morice MC, Kappetein AP, Holmes DR Jr, Mack MJ, van den Brand M, Morel MA, van Es GA, Kleijne J, Koglin J, Russell ME. Source Thoraxcentre, Erasmus Medical Centre, Rotterdam, The Netherlands. Abstract BACKGROUND: Changes in the treatment of coronary artery disease both surgically and percutaneously have rendered the major randomized trials historical. Furthermore, the restrictive criteria of previous trials excluded most patients treated in daily practice. Although coronary surgery is still considered the current, evidence-based, gold-standard treatment of left main (LM) and 3-vessel coronary disease, the added benefit of drug-eluting stents has further expanded the use of percutaneous coronary intervention (PCI) beyond less complex populations in daily practice. STUDY DESIGN: The 1500-patient, prospective, multicenter, multinational (European and North American), randomized SYNTAX study with nested registries will enroll "all-comers." Consecutive patients with de novo 3-vessel disease (3VD) and/or LM disease will be screened for eligibility by the Heart Team (composed of an interventionalist, a cardiac surgeon, and the study coordinator) at each site and then allocated to either (1) the randomized cohort, if comparable revascularization can be achieved by either PCI or coronary artery bypass surgery (CABG), or (2) to one of the nested registries for CABG-ineligible patients (PCI registry) or for PCI-ineligible patients (CABG registry). Randomized patients will be stratified based on LM disease and diabetes by site. The primary end point for the randomized comparison is noninferiority of major adverse cardiac and cerebral events between the 2 groups at 1 year. To adequately project the expected enrollment rate per site, a run-in phase was mandated for each site interested in participating in the trial. Both cardiothoracic and interventional cardiology departments within the same institution were asked to complete a questionnaire regarding their frequency of treatment of LM and 3VD over a retrospective 3-month period. IMPLICATIONS: By replacing most traditional inclusion and exclusion criteria with the real-world decision between the cardiothoracic surgeon and the interventionalist, this study will define the roles of CABG and PCI using drug-eluting stents in the contemporary management of LM and 3VD. Results of the run-in phase were used by the steering committee to determine eligibility and to project enrollment for each site.

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