A A place for Beta Blocker Agents in Perioperative : When and How

Ike Sri Redjeki Department of Anesthesiology and ICU Medical Faculty/ Padjadjaran University

Bandung

Introduction to β-blockers Are a class of drugs used for –  Management of cardiac arrhythmia –  Cardioprotection after myocardial infarction –  Once first-line treatment for hypertension (their role was

downgraded in June 2006 in the United Kingdom to fourth-line) –  Propanolol was the first clinically useful beta adrenergic receptor

antagonist –  Direct sympatho adrenal inhibition à reduction of heart rate à

play a major role in the therapeutic efficacy of beta-blockade in congestive heart failure

–  In chronic heart failure à the myocardium undergoes a phenotype change à alterations of the activity of enzymes regulating calcium homoeostasis

Site of action of beta blocker

Indications

•  Reduction of risk of cardiovascular mortality in the early phase following an acute MI in hemodynamically stable patients

•  Treatment of mild to moderate hypertension (in which a cardioselective beta-blocker is preferred)

•  Angina pectoris when oral therapy is not feasible •  Management of hypertensive urgencies •  Peri -operative, cardioselective beta blockade,

when indicated •  Possible therapy in acute aortic dissection

Indication of Beta Blocker Therapy

•  Hypertension •  Arrhythmias •  Angina/Coronary artery disease •  Acute coronary syndromes •  Congestive Heart Failure •  Postmyocardial infarction •  Perioperative

Role of Peri-operative Beta-Blockers •  Beta -blockers are used to correct the imbalance between

myocardial oxygen demand and supply in times of stress •  Reduce HR: increase diastolic time and increase coronary artery

perfusion •  Reduce myocardial oxygen consumption by suppressing

lipolysis, causing myocardium to metabolize more glucose compared to free fatty acid

•  May increase stability of coronary atherosclerotic plaques •  May increase the threshold for ventricular fibrillation in presence

of ischemia

Important question; the use of beta blocker in perioperative period

•  Which patients should be targeted ? •  What is the optimal time to begin these agents, and when

should they be stopped ? •  Which type of beta blocker should be used ? •  How can a practical and effective strategy be

implemented at hospitals on the basis of this evidence ?

Which patients should be targeted ?

Minor criteria •  Age > 65 years •  Current smoking •  Hypercholesterolemia •  Hypertension

Major criteria •  History of MI, angina, or any

revascularization, Q waves on ECG, current or past use of nitroglycerine

•  History of transient ischemic attack or cerebrovascular accident

•  Diabetes •  Vascular surgery planned for

arteries of chest, abdomen, or pelvis

•  Creatinin > 2mg/dl

Patients at risk who should not received Beta Blockers

2 type of patients : •  Focus primarily on the patients ability to handle fluids

load and cardiac output : congestive heart failure caused by depressed ejection fraction and systolic dysfunction à beta blocker therapy improves long term survival in these group à but it should not be started in the perioperative period as part of routine practice

•  Focus on improving myocardial perfusion à patients with physiologically significant aortic valvular disease beta blocker should not be given

What is the optimal time to begin these agents, and when should they be stopped ?

•  Pre – induction period à still an unanswered question •  It seems sensible to try to developed an approach in which beta

blocker started as far in advance as possible à giving the opportunity to titrate the drug to an effective heart rate before surgery

•  But last minute identification and administration on the day of surgery are likely to be effective

•  Longer treatment with beta blocker appears to extend the protective benefit of adrenergic blockade

•  For patients who do not require lifelong beta blocker therapy à th/ up to 30 days à provides maximal protective benefit

Which type of beta blocker should be used ?  

•  Metoprolol is probably the most common agent available à the parenteral form can lead directly to oral administration à for NPO ( R/ Farpressor )

•  Short acting beta blocker à esmolol à for unstable patients

•  Atenolol

Prehospitalization / immediately following admission •  Giving metoprolol 25 – 100 mg/ PO bid •  Begin as outpatient surgery up to 30 days prior

to surgery •  Titrate new or pre-existing beta blocker to heart

rate of < 65/minute

Preoperative Period ( in pre-anesthesia holding area )

•  All Patients : Give metoprolol 5 mg iv every 10 minute to reach target heart rate before induction anesthesia if needed

In hospital period and transition to oral medication à Patients not taking oral medication who are hemodynamically stable •  Metoprolol 5 mg iv every 15 minute up to 15 mg titrate

to heart rate of 65/mnt repeat every 6 hour à monitoring continuous ECG

•  Alternatives à clonidin ICU patients à HD unstable caused by blood loss or prolonged surgery •  Esmolol 500micr/kg iv over 1 minute then infuse 50 –

200 micr/kg/min to target heart rate •  May also use metoprolol per floor protocol

One of the most crucial practices in the use of

perioperative beta blocker Is

They be titrated in such a way that a target heart rate

is achieved

Important data àβ-blockers for ICU and perioperative

•  Metoprolol iv àwhen it was infused over 10 minute à in normal volunteers à maximum beta blockade was achieved at approximately 20 minute

•  Doses 5 – 15 mg à reduced HR ( after stimulation ) 10% - 15%

•  Half – life of drug à 2.8 hour •  Drug disappeared approximately after 5 – 8 hour ( à 5 –

15 mg administration)

Potential Hazard of iv B-Blocker

•  Cardiac failure •  Severe sinus bradycardia: antidote à atropine •  Partial heart block à antidote à atropine; if

unresponsive à isoproterenol or temporary pacing •  Bronchospasm antidote à salbutamol •  Profound beta-blockade à antidote when other

measures have failed à glucagon

Side Effect Management

•  Beta – blocker / Metoprolol à only used in stable HD patients ( not shock state à MAP and peripheral perfusion)

•  AV – Block à if occur after drug administration à Give SA 0.25 – 0.5 mg iv

•  Hypotension : if systolic BP < 90 mmHg à give fluids and positive inotropic, if associated with bradycardia à SA

•  Pheochromocytoma: B-Blocker should be used in combination with alpha – blocker à to avoid paradoxical increase in BP due to the attenuation of B-mediated vasodilatation in skeletal muscle

•  In à DM à may mask tachycardia in hypoglycemia

Perioperative Beta Blocker

•  The stress induced by surgery can cause an asymptomatic coronary plaque unstable and rupture à resulting complete occlusion of a portion of the coronary artery

•  The perioperative risk associated with unstable plaque can be reduced pharmacologically with : aspirin, statin and chronic beta – blocker therapy

•  POISE trial à ( 2008 ) –  9298 patients , RCT, > 45 years old patients, non cardiac surgery,

at high risk of atherosclerotic disease –  Intervention : metoprolol 2 – 4 hour start preoperatively and

continued for 30 days

Risk Stratification

         Revised Cardiac Index ( RCI )

Risk Factors High risk surgery (intraperitoneal, intrathoracic, aortic) Ischemic heart disease (prior MI, angina, nitrate use) History of CHF History of cerebrovascular disease Insulin therapy for diabetes Preoperative serum Cr >2.0 mg/dl

Points 1 1 1 1 1 1

(Lee  et  al,  Circula.on  1999;  100:  1043)  

Risk Stratification

 Revised Cardiac Index              *Cardiac Complication: MI, CHF, VF, complete heart block                   (Lee et al, Circulation 1999; 100: 1043)

Class # Factors Cardiac Complication Rate*

I 0 0.5%

II 1 1.3%

III 2 3.6%

IV 3-6 9.1%

Risk Stratification

 Clinical Markers                         (ACC/AHA Guidelines JACC, 2002)

Major Intermediate Minor "   ACS "   Decompensated CHF "  Significant arrhythmia "  Severe valvular disease

"   Mild angina "   Prior MI "   Compensated CHF "   Diabetes Mellitus

"   Advanced age "   Abnormal ECG "   Rhythm other than sinus "   Low functional capacity "   Prior CVA "   Uncontrolled HTN

Risk Stratification

 Functional Capacity            

                           (ACC/AHA  Guidelines  JACC,  2002)  

1-4 METs 4-10 METs >10 METs

"   ADL’s "   climb flight of stairs "  Heavy house work "  Exercise, golf,dance

"   sports

Risk Stratification

 Surgery Specific Risk                  

                                                 

   (ACC/AHA  Guidelines  JACC,  2002)  

High > 5% Risk of MI/Death

Intermediate < 5% Risk of MI/Death

Low < 1% Risk of MI/

Death "   Emergent surgery "   Aortic or other major vascular surgery "   Peripheral vascular "  Prolonged surgery

"   Carotid endarterectomy "   Head and Neck "   Intraperitoneal "   Intrathoracic "   Orthopedic "   Prostate

"   Endoscopic "   Superficial "   Cataract "   Breast

•  Conclusion : – Perioperative B blocker therapy is associated

with a reduced risk of in hospital mortality à among the High Risk patients – But not in low risk patients – Patient safety may be enhanced by increasing

the use of B blockers in high risk patients

NEJM 2005 ; 349-61

Normalization of cellular

metabolsm

Decrease cardiac

dysfunction Cytokine

effect

Improved glucose metabolism

Preeclampsia with immediate post operative hypertension

•  Post operative post SC patients à HR increase to 170x/ mnt and BP increase to 190/99 mmHg

•  ECG à ST depression in Lead I, II, III •  SpO2 99% with nasal catheter 2l/mnt •  Conscious cm, with no other symptoms •  NRS à 1, no pain only not comfortable

Preeclampsia with immediate post operative hypertension  

•  Metoprolol iv ( R/ Farpressor) strart with 2,5 mg à 15 minute, in 10 minute BP decrease to 170/87 mmHg à HR 160 x/ mnt

•  Another 2,5 mg iv was given in 5 minute à HR decrease to 100/ mnt and BP 160/80 mmHg

•  Patients was observed for 2 hours HR 105/mnt with BP 163/78 mmHg

•  Another 2,5 mg metoprolol iv was given and patients HR 76 – 84 / mnt with PB around 130 – 140 systolic / 75 – 80 mmhg diastolic

Conclusions

If you want to use beta blocker à use them sensibly, carefully, and act directly à for

complication