anesthetic considerations for diastolic dysfunction suneel.p.r associate professor sctimst...
TRANSCRIPT
![Page 1: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/1.jpg)
Anesthetic Considerations for Diastolic Dysfunction
Suneel.P.R
Associate Professor
SCTIMST
Trivandrum
![Page 2: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/2.jpg)
Dysfunction: systolic vs. diastolic
• Systolic function is intuitively meaningful
• Diastology is a relative newcomer
![Page 3: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/3.jpg)
Diastolic damages
• Nearly 50% of all cardiac failures
• Prognosis and mortality same as systolic
• Mortality is four times when compared with normal population
![Page 4: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/4.jpg)
Diastolic heart failure
• The Ejection Fraction will be normal
• Called Heart failure with normal EF (HFnlEF)
• Diastolic dysfunction can occur along with systolic dysfunction
![Page 5: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/5.jpg)
Diastology
When does diastole begin ?
•Anatomical -when aortic valve closes
•Molecular level- dissociation of the actin- myosin cross-bridges
•The heart begins the relaxation process in systole !!
![Page 6: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/6.jpg)
Relaxation-requires energy
BJA 98 (6): 707–21 (2007
![Page 7: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/7.jpg)
Diastolic dysfunction definition
Inability of the ventricles to fill at low pressure
The end-diastolic pressure is 16-26 mm Hg
(normal EDP is < 12 mm Hg)
The atrial pressures that are needed to complete filling are even higher
![Page 8: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/8.jpg)
Pathophysiology- two key terms
Increased filling pressures are due to
1.Abnormality of relaxation
2.Decreased compliance
![Page 9: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/9.jpg)
Physiology: The stages
1.Isovolumic relaxation
2.Rapid filling
3.Diastasis
4.Atrial contraction
![Page 10: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/10.jpg)
Physiology
![Page 11: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/11.jpg)
Isovolumetric relaxation
AoVC
MVO
![Page 12: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/12.jpg)
Isovolumetric contraction
• Occurs between two closed valves
• Active relaxation occurs during this time
• The ventricular pressures continue to fall
• Mitral valve opening creates “suction effect”
![Page 13: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/13.jpg)
Physiology
![Page 14: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/14.jpg)
Rapid filling phase
![Page 15: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/15.jpg)
Diastasis
![Page 16: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/16.jpg)
Atrial “kick”
![Page 17: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/17.jpg)
Active diastolic dysfunction
Abnormality of relaxation
Failure of energy dependent part of diastole
•Myocardial ischemia
•Hypertension
•Aortic stenosis
•Hypertrophic cardiomyopathy
![Page 18: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/18.jpg)
Passive diastolic dysfunction
Increase in chamber stiffness
•Infiltrative disorders ( amyloidosis)
•Myocardial fibrosis
•Progression from impaired relaxation
![Page 19: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/19.jpg)
Physiology
End systole
End Diastole
![Page 20: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/20.jpg)
![Page 21: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/21.jpg)
Physiology
![Page 22: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/22.jpg)
Impaired relaxation
![Page 23: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/23.jpg)
![Page 24: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/24.jpg)
![Page 25: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/25.jpg)
![Page 26: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/26.jpg)
Diagnosis of diastolic dysfunction
• Echocardiography
![Page 27: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/27.jpg)
Transmitral Pulse Wave Doppler
![Page 28: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/28.jpg)
Transmitral Pulse Wave Doppler
E A
![Page 29: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/29.jpg)
Stage I of diastolic dysfunction
1. Impaired relaxation
![Page 30: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/30.jpg)
Stage II diastolic dysfunction• Pseudonormalization
![Page 31: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/31.jpg)
Stage III of diastolic dysfunction
• Restrictive filling
![Page 32: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/32.jpg)
Improvement to a worse grade
• Tachycardia
• Loss of atrial contraction
• Volume excess
![Page 33: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/33.jpg)
Improvement to a milder grade
Reduction in preload• Reverse Trendelenburg
• Diuresis
• Amyl nitrate inhalation
• Valsalva maneuver
Relief of tachycardia
Return from AF to Sinus
![Page 34: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/34.jpg)
Stage IV diastolic dysfunction
• Irreversible restrictive filling pattern
![Page 35: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/35.jpg)
Pulmonary venous Doppler
![Page 36: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/36.jpg)
Pulmonary venous Doppler
![Page 37: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/37.jpg)
Pulomnary venous Doppler
Impaired relaxation
•D wave decreases in size
•S/D ratio >1
Pseudonormal and Restrictive filling
•Increase in D
•S/D < 1
•Increase in A wave duration
![Page 38: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/38.jpg)
Other echocardiographic tools
• Tissue Doppler imaging to assess mitral annular movement
• Color M mode of the Mitral valve to assess the propagation velocity
![Page 39: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/39.jpg)
Diastolic dysfunction vs. failure
• Dysfunction is a physiologic or preclinical state
• Abnormal relaxation and increased chamber stiffness compensated by increased LAP
• The LV preload is maintained
• When these mechanisms are stressed, diastolic heart failure ensues
![Page 40: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/40.jpg)
Braunwald 8th edition
![Page 41: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/41.jpg)
![Page 42: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/42.jpg)
Diastolic heart failure
Definite
•C/F of heart failure
Within72 hours
•Echo evidence of normal LVEF
•Echo evidence of diastolic dysfunction
![Page 43: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/43.jpg)
Most likely diastolic heart failure
• SBP >160 mm Hg
• DBP> 100 mm Hg
• Concentric LVH
• Worsened by– Tachycardia– Volume bolus
• Improved by– Reducing HR– Restoring sinus rhythm
![Page 44: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/44.jpg)
When to suspect diastolic dysfunction
• History of previous diastolic heart failure
• Age > 70 years
• Female sex
• Uncontrolled hypertension
• Myocardial ischemiaDiabetes mellitus
• Comorbidities: Obesity, renal failure
![Page 45: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/45.jpg)
Echo
• Specifically documented
If not then, look for – LVH –absence does not rule out!
– LA enlargement
– RV enlargement
– Pulmonary hypertension
![Page 46: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/46.jpg)
Perioperative worsening
Deterioration in diastolic dysfunction
•Myocardial ischemia– Directly affects relaxation– Induces rhythm disturbances
•Hypovolemia
•Tachycardia
•Rhythms other than sinus
![Page 47: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/47.jpg)
Perioperative worsening
• Shivering
• Anemia
• Hypoxia
• Electrolyte imbalances
![Page 48: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/48.jpg)
Perioperative worsening
• Post-op sympathetic stimulation
• Post-op hypertensive crisis
![Page 49: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/49.jpg)
Periop-risks
• Delayed weaning from mechanical ventilation
• Difficulty weaning from CPB
• More use of vasoactive agents
• Prolonged ICU stay & mortality
![Page 50: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/50.jpg)
Conducting the anesthetic
Pre-operative evaluation
Functional status & exercise tolerance
Optimizing the perioperative drugs
![Page 51: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/51.jpg)
Perioperative drugs
• Diuretics
• Beta blockers, calcium channel blockers
• ACEI & ARBs
• Statins
• Antiplatlets
![Page 52: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/52.jpg)
Monitoring - Major surgeries
• Standard monitoring tools
• Invasive arterial pressures
• Monitoring volume status is important
• Central venous pressures or Pulmonary artery catheter or TEE ?
![Page 53: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/53.jpg)
![Page 54: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/54.jpg)
GA or Regional
• No definite recommendation either way
• Epidural vs. spinal ?
Epidural wins
![Page 55: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/55.jpg)
General anesthesia
• IV induction & maintained with volatile agents and opioids
• Greater hemodynamic instability
![Page 56: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/56.jpg)
General anesthesia
Good induction practices
•Consideration for age
•Titrate to effect
•Smooth take over from spontaneous-bag mask
•Hpoxia, hypercarbia worsens PHT
![Page 57: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/57.jpg)
GA-control of BP
• Systolic BP within 20 % of baseline
• Maintain diastolic BP
• Keep pulse pressure < DBP
![Page 58: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/58.jpg)
Control of BP
Rule of the 70s
•Age >70 years
•Pulse rate around 70s
•DBP >70
•Pulse pressure < 70
![Page 59: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/59.jpg)
Drug combination for hemodynamics
• Low dose nitroglycerin and titrated phenylephrine
• Either agent alone can worsen the hemodynamics
![Page 60: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/60.jpg)
Nitroglycerine + Titrated phenylephrine
1. Preserves vascular distensibility
2. Avoids reduction in preload
3. Maintains coronary perfusion pressure
4. Maintains stroke volume with minimal cardiac work
![Page 61: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/61.jpg)
Management of hypertensive crisis
Sound anesthetic practices
Plan for post-op analgesia
Prevention of shivering
Intravenous calcium channel blocker
IV nitroglycerin
![Page 62: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/62.jpg)
Post-op diastolic heart failure
• Reduce preload
• Diuretics
• Use of nitrates
• CPAP
• Use of adrenaline, dobutamine, dopamine
![Page 63: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/63.jpg)
Specific drugs for diastole
Milrinone
•Phosphodiesterase III inhibitor
•Inotropic, vasodilatory with minimal chronotropy
•Increases calcium ion uptake to SR
![Page 64: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/64.jpg)
Milrinone
• Lusitropic effect more evident in heart failure
• Bolus dose of 50µgm/Kg over 60 minutes
• Infusion of 0.5 to 0.75µgm/Kg/min
![Page 65: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/65.jpg)
Specific drugs for diastole
Levosimendan
•Sensitizes the contractile elements to calcium
•Has a vasodilator effect
•Improves both systolic and diastolic function
![Page 66: Anesthetic Considerations for Diastolic Dysfunction Suneel.P.R Associate Professor SCTIMST Trivandrum](https://reader035.vdocuments.site/reader035/viewer/2022062421/56649da85503460f94a94a90/html5/thumbnails/66.jpg)
Thank you