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

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Presentation on theme: "Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Malte Book Department of Anaesthesiology and Pain Medicine."— Presentation transcript:

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

2 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine Vasoplegic syndrome (VS) after cardiac surgery MAP < 50 mmHg CVP < 5 mmHg, PCWP < 10 mmHg CI > 2.5 l/min/m 2 SVR < 800 dyn/s/cm -5 vasopressor requirement Incidence 5% to 25% Özal et al. Ann Thorac Surg 2005;79:1615 Levin et al. Ann Thorac Surg 2004;77:496 –9 Differential diagnosis: Hypovolemia with good LV function? Hemodilution (crystalloid cardioplegia)? Central-peripheral AP gradient? Inodilator overdose? SIRS? a-v shunting (cirrhosis, dialysis)? 1 to 2 VS per week

3 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine Alternative definition of VS Epi-/norepinephrine >150 ng kg -1 min -1 or Dopamine >10 μg kg -1 min -1 or Vasopressin > 4 U/h Levin et al Circulation. 2009;120: Treatment defines diagnosis

4 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine Levin et al. Circulation. 2009;120: CHF patients? Sepsis? Low volume? More serious surgical procedures? Finally: Serious ill patients are at risk for postoperative inotrope/vasopressor dependency

5 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine Methylene Blue, the new magic bullet?

6 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine

7 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine Mode of action Inhibitor of NO Sythase NO scavenger Inhibitor of Guanulate Cyclase, cGMP cGMP mediated vasodilatation Interleukin-1 dependent Superoxide dependent

8 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine Side effects Cardiac arrhythmias Coronary vasoconstriction Angina/precordial pain Cardiac output Renal/mesenteric blood flow Methemoglobinemia Hemolysis Monoamine oxidase inhibitor Interference with oximetry

9 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine Contraindications Severe renal impairment Glucose 6 Phosphat Dehydrogenase deficiency Serotoninergic medication

10 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine Evidence?

11 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine Levin et al. Ann Thorac Surg 2004;77:496 –9 MAP < 50 mmHg CVP < 5 mmHg and PCWP < 10 mmHg CI > 2.5 l/min/m 2 SVR < 800 dyn/s/cm -5 Vasopressor requirement

12 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine Levin et al. Ann Thorac Surg 2004;77:496 –9 638 patients, 56 with vasoplegic syndrome Randomization:3 hours after arrival in the recovery room 1.5 mg/kg methylene blue

13 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine Levin et al. Ann Thorac Surg 2004;77:496 –9 Limitations? Unblinded procedure Liberal inclusion criteria/VS definition Anaesthetic drugs in the recovery room? Volume therapy? Vasopressin? High overall mortality (4.2%)

14 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine 100 patients at risk for VS o ACE inhibitors o Calcium channel blockers o Heparine 1 hour preoperative 2 mg/kg methylene blue

15 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine SVR during cardiopulmonary bypass Özal et al. Ann Thorac Surg 2005;79:1615–9

16 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine Limitations? Crystalloid (ml) Colloid (ml) RBC FFP Methylene bluePlacebo Unblinded procedure Liberal inclusion criteria/VS definition Volume therapy intra- and 6 hour postoperative 26% in the placebo group Norepi. 0.5 μg kg -1 min -1 Need for RBC/FFP/Norepi. substandard Özal et al. Ann Thorac Surg 2005;79:1615–9

17 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine Cho et al. Korean J Anesthesiol 2012 August 63(2): Prophylactic Methylene blue before CPB (2 mg/kg) No differences in:MAP, MPAP, CI, PCWP, SVR Need for vasopressor/inotrope Fewer PRBC transfused, less FFP exposure with MB

18 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine Two questionable studies postulate potential benefit in treatment/prevention of vasoplegic syndrome (and were constantly cited) One underpowered RCT showed no influence on primary endpoint (vasopressor need)

19 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine Indication pre/post CPB No evidence-based indication Off label o Rescue in vasoplegic syndrome (refractory to norepinephrine/vasopressin) Problem: Inconsistent definition of vasoplegic syndrome

20 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine Timing + dosing No evidence-based timing of administration o Preoperative o Intraoperative o During CPB o Postoperative No evidence-based dosing o 1.5 to 7.0 mg/kg bolus o Continuous infusion

21 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine Data quality + safety Few questionable, underpowered RCTs Conflicting results Mainly case reports/case series None phase 1 study Documented Adverse Effects o IMA contraction in clinically achieved concentrations Ulusoy et al. J Cardiothorac Vasc Anesth Aug;22(4):560-4

22 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine Ultimate MB indication in cardiac surgery?

23 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine Recommendation No use of Methylene Blue Application exclusively within clinical trials Consider as last resort option only

24 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine Alternative Arginin Vasopressin (AVP) o Up to 0.1 U/min o Higher number of RCTs investigated the clinical administration o Vasoplegia due to relative AVP deficiency Colson et al. Critical Care 2011, 15:R255 o Possibly causal therapy

25 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine

26 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine

27 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine Anästhesiologisches Management Monitored Anaesthesia Care (MAC), Lokalanästhesie Sedierung mit Dexmedetomidin 6l O 2 /Min über Maske Monitoring: EKG, invasiver RR, ZVD, Kapnometrie, SpO 2 Invasivitäten: A. rad. li., 3-Lumen ZVK, 6 Fr. Schleuse + Einschwemm-Pacer, ext. Defi-Pads

28 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine komplikationslos bis zum Freisetzen der Prothese (TF-AVI MCV 26)

29 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine 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 CPR

30 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine 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 Erste Stabilisierung, 2. CPR

31 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine Limitations? Özal et al. Ann Thorac Surg 2005;79:1615–9 Unblinded procedure Liberal inclusion criteria/VS definition Intraoperative Anaesthetic drugs? Volume therapy? Vasopressin? High overall mortality (4.2%)

32 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine Recommendation Few RCTs Mainly case reports/case series No phase 1 studies IMA contraction in clinically achieved concentrations

33 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine Levin et al. Ann Thorac Surg 2004;77:496 –9 Inclusion criteria Hypotension MAP < 50 mmHg CVP < 5 mmHg and PCWP < 10 mmHg CI > 2.5 l/min/m 2 SVR < 800 dyn/s/cm -5 Vasopressor requirement

34 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine Levin et al. Ann Thorac Surg 2004;77:496 –9

35 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine Indikation subxyphoidale Pericardiotomie Einlage großlumiger Perikarddrainage mit Retransfusion initiale Stabilisierung Ca 10:50 Sternotomie: Blutung aus LV-Apex (hellrot, spritzend) Pericardiotomie, Sternotomie

36 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine Seldinger-Tausch 3-L-ZVK 9,0 Fr. MAC Katheter Transfusion mit Rapid Infusion System Übernähung des LV Apex Stabilisierung der Patientin Verlegung ICU Verlauf

37 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine J Thorac Cardiovasc Surg Jun;143(6): Keine Stellungnahme zur Anästhesie Keine Guidelines Warten auf Part II?

38 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine 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): Kontroverse MAC GA

39 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine

40 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine 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): transapikale + 29 transfemorale Patienten (alle GA) 25/29 chirurgische Leistenrevision Berner Zahlen

41 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine Prospective Registry Data, Swiss CV Center Anaesth technique AVI% (n) LA GA conversion CPR intra- proced. Mortality intra- proced. Extubat. end of proced. ICU post- proced. All cause mortality 30 d GATA TS TF 39% (157) % (6) 0.6 % (1) 76 % (120) 66 % (103) 8.3 % (13) LA-MACTF61% (245) 6.9 % (17) 2.1 % (5) 1.2 % (3) 97 % (240) 8 % (19) 5.3 % (13) p=0.45p=0.95p<0.001 p=0.33 Total100 % (402) % (11) 1.0 % (4) 90 % (360) 30 % (122) 6.5 % (26) 08/2007 to 10/2011

42 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine Berner Lernkurve 555 interventionelle Aortenklappenprozeduren 425/111/11 transfemoral/transapikal/subclavia 85/340 GA/MAC Konversion MAC zu GA 22 von 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

43 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine Individuell angepasstes Vorgehen (da < 5% Anästhesiolg motivierter Konversion LA-GA) Schwieriger Atemweg TEE Compliance Dekompensierte Patienten unkomplizierte Patienten GA MAC

44 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine 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)

45 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine Postmedikation

46 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine Danke Reto Basciani Christoph Huber Stefan Windecker Peter Wenaweser Gabor Erdös Balthasar Eberle

47 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine

48 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine

49 Malte Book - Methylene Blue: Vasoplegic Syndrome Finally Resolved ? Inselspital, Bern University Hospital, Department of Anaesthesiology and Pain Medicine 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


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