Objectives

Gain an appreciation and understanding of incidence and impact of atrial fibrillation in post-esophagectomy patients

Review the evidence supporting selection of a prophylactic medication

Mrs. CW

48 yo female admitted to ICU 24 May ID ht: 165 cm wt: 61 kg BMI: 22.4 CC: post surgical – 3 hole esophagectomy HPI: Nausea and hemoptysis while

vacationing in Costa Rica – Hosp admit upper GI Bleed with massG&E upon return - squamous cell Ca by biopsy

PMH: hypertension, hypothyroid, alcohol abuse

Mrs. CW

Allergies: none Intolerance: none Surgeries: none Social History

Non-smokerAdmits to past alcohol abuse

○ Currently 4-5 per week

Medications PTACondition Medication

Bronchitis ciprofloxacin 250 mg bid x 5 days (28/4)

Hypertension ramipril 5 mg daily

Esophageal Ca pantoprazole 40 mg dailymorphine syrup 20 mg TID

Hypothyroid levothyroxine 100mcg daily

Current MedicationsCondition Medication

Alcohol abuse thiamine 100 mg IV daily x3d (2nd today)folate 5 mg IV dailymultivitamin IV daily

Hypertension ramipril 5 mg daily

Post esophagectomy

pantoprazole 40 mg daily

Constipation Docusate 200 mg BIDBowel protocol

Current MedicationsCondition Medication

Hypothyroid levothyroxine 75 mcg daily

DVT Prophylaxis heparin 5000 U subcut daily

Hypokalemia prevention

potassium chloride 20 MEq/L IV x 3 days (2nd today)

Pain Hydromorphone/bupivacaine epidural PCACelecoxib 200 mg NJ BID x2dAcetaminophen 1000 mg NJ QID

Review of systems

Vitals MAP 87, HR 75 NSR, Resp 20, T 37.5, O2

Sat 96% RA

UnremarkablePsych, EENT, Resp, CVS, GI, GU, MSK,

Skin, Endocrine, Fluids, ID

Labs 24 May

WBC 9.3 Hg 86 (110 preop) MCV 97 Plt 120

Na 140, K 4.6 Cl 108 BUN 5.4 Scr 66, eGFR 83 Alb 28 Ca 2.07 Mg 0.83 PO4 1.21 Bili 11 AST 53 ALT 28 ALP 34 GGT 28

DRPs Patient is at risk DVT secondary to sub-

therapeutic dose of anti-coagulation Patient is at risk of atrial fibrillation

secondary to lack of prophylactic therapy Patient is receiving potassium

supplementation with no clear indication Patient is at risk of hypothyroid due to

reduced dose of levothyroxine in hospital Patient is at risk of alcohol withdrawal

Primary Goals of Therapy Health Care Team

Post operative recovery/rehabilitationReduce morbidity associated with atrial

fibrillationMinimize medication adverse effects

PatientPain managementDischarge home

Guideline - A Fib Associated with General Thoracic SurgeryLobectomy Pneumonectomy Esophagectomy

Should continue β-blockers if taking prior to surgeryreduce dose by half if epidural (IB)

Diltiazem reasonable- not taking β-blockers pre-op (IIaB)

Amiodarone (IIaB) Amiodarone (IIaB)

Initiate β-blockers (IIbB)

Magnesium supplementation as augmentation (IIaB)

Ann Thorac Surg 92(3):1144–52

PICO

Patient: post-esophagectomy

Intervention: anti-arrhythmics

Comparator: placebo

Outcome: prevention of atrial fibrillation

Literature Search

Search termsEsophagectomy, atrial fibrillation

DatabasesMedline, IPA, CDSR, ACP Journal Club

LimitsHumans, English

Results1 review - 3 RCTs

A Fib Post Esophagectomy 13 - 46% occurrence post surgery Most common POD 2-3 Risk factors

Postop hypoxiaMaleAge > 65COPDHeart diseaseGastric conduit dilitation

Etiology

Better understood with pulmonary resectionInflammationIncreased heart pressureIncreased risk with larger resections

Unknown with esophagectomyHigher incidence with larger resections

Impact of AFib

Hemodynamic instability Increased pulmonary complications Increased length of hospitalization by 5

days Increased mortality

Bayliff C, Massel D, Inculet R. Propranolol for the prevention of postoperative arrhythmias in general thoracic surgery. The Annals of thoracic surgery.[Internet]. 1999 [cited 2012 Jun 20];67:182–6.

Methods

D Double blind RCT in adults

P N=99 Major thoracic surgery – esophagectomy, lobectomy, pneumonectomy, - no previous A Fib

I Propranolol 10 mp PO Q6H starting preop to POD 5

C Placebo

O 1. Arrhythmias (AFib, A Flutter, SVT, VTach, VFib by Holter

2. Adverse events – hypotension, CHF, bronchospasm

3. Duration of hospital stay

T Surgery until discharge

Results Less treated arrhythmias with propranolol 6%

vs 20%ARR = 14% (CI 0.6%-27.2%) p=0.071 NS

Any arrhythmia higher in propranolol72% vs 62%

Adverse effectsHypotension 49% vs 26% p=0.003Bradycardia 25% vs 4% p=0.018NS difference - bronchospam, pulmonary edema, MI3 deaths – 2 in active one in placebo

Esophagectomy Subgroup

N=31 Chi2=1.94 p=0.1621 NS Included AFib, VTach, SVT

Arrhythmia No arrhythmia

Propranolol 0 17

Placebo 3 11

Limitations

small numbers - underpowered Population of interest subgroup Mixture of arrhythmias prevalent Vague definition of treated arrhythmia

Ritchie AJ, Tolan M, Whiteside M, McGuigan J a., Gibbons JRP. Prophylactic digitalization fails to control dysrhythmia in thoracic esophageal operations. The Annals of Thoracic Surgery [Internet]. 1993 Jan [cited 2012 Jun 19];55(1):86–8.

Methods

D Open RCT in adults

P N=80 elective thoracic esophageal operations, benign and malignant, no previous AFib

I Digoxin 0.5 mg BID - 1800 and 2200 1 day preop, then 0.25 mg daily starting with premeds to POD 9 guided by levels target 1-2 mcg/L

C No digoxin

O Arrhythmias by ECG

T Surgery until discharge

Results

More arrythmia in malignant p=0.002 Less arrythmia in placebo p=0.29 NS 76% of arrhythmias within 6 hr post-op

Limitations

Unblinded, small numbers No power calculation No detail of digoxin TTR Subgroups analysis not pre-defined Lacked description of procedure Lacked details of arrythmia observed

Tisdale JE, Wroblewski H a, Wall DS, Rieger KM, Hammoud ZT, Young JV, et al. A randomized, controlled study of amiodarone for prevention of atrial fibrillation after transthoracic esophagectomy. The Journal of thoracic and cardiovascular surgery [Internet]. 2010 Jul [cited 2012 Jun 19];140(1):45–51.

MethodsD Open RCT in adults

P N=80 trans-thoracic esophagectomy (open and min invasive)no previous A Fib or A Flutter, majority for esophageal Ca

I Amiodarone infusion 43.75 mg/h at anesthesia to POD 4 (96 hrs)

C No amiodarone

O 1. Atrial fibrillation by continuous ECG2. Duration of hospital stay3. Duration of ICU stay4. Adverse events – hypotension, bradycardia, respiratory

complications5. Cost of hospitalization

T Surgery until discharge

Results Less AFib with amiodarone15% vs 40%

ARR = 25% (CI 18.8%-43.8%) p=0.02 NNT 4

NS difference in length of stayHospital 11 vs 12 days p=0.31ICU 68 vs 77 hours p=0.097

Adverse effectsNS difference – hypotension, bradycardia,

QTc>500 ms, ARDS, pneumonia, atelectasis2 deaths – placebo – MI, toxic megacolon

NS difference in cost of hospitalization

Limitations

small numbers – unblinded Single centre Decision to treat subject to bias

Reflects clinically important AF

Underpowered for secondary outcomes

Recommendation

Instituting routine prophylaxis is not recommendedamiodarone

○ Reduces AFib, but lacks measurable impact in morbidity/mortality and length of stay

○ Only trend to shorten stay in ICUDigoxin – no benefit

β-blockers – support continuation if taking prior to surgery

Questions

References1. Fernando HC, Jaklitsch MT, Walsh GL, Tisdale JE, Bridges CD, Mitchell JD, et

al. The Society of Thoracic Surgeons practice guideline on the prophylaxis and management of atrial fibrillation associated with general thoracic surgery: executive summary. The Annals of thoracic surgery [Internet]. 2011 Sep [cited 2012 Jun 19];92(3):1144–52.

2. Tisdale JE, Wroblewski H a, Kesler K a. Prophylaxis of atrial fibrillation after noncardiac thoracic surgery. Seminars in thoracic and cardiovascular surgery [Internet]. 2010 Jan [cited 2012 Jun 19];22(4):310–20.

3. Bayliff C, Massel D, Inculet R. Propranolol for the prevention of postoperative arrhythmias in general thoracic surgery. The Annals of thoracic surgery [Internet]. 1999 [cited 2012 Jun 20];67:182–6.

4. Ritchie AJ, Tolan M, Whiteside M, McGuigan J a., Gibbons JRP. Prophylactic digitalization fails to control dysrhythmia in thoracic esophageal operations. The Annals of Thoracic Surgery [Internet]. 1993 Jan [cited 2012 Jun 19];55(1):86–8.

5. Tisdale JE, Wroblewski H a, Wall DS, Rieger KM, Hammoud ZT, Young JV, et al. A randomized, controlled study of amiodarone for prevention of atrial fibrillation after transthoracic esophagectomy. The Journal of thoracic and cardiovascular surgery [Internet]. 2010 Jul [cited 2012 Jun 19];140(1):45–51.

3 hole esophagectomy