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Pre-Operative Bowel Preparation for Elective

Colorectal Surgery

Shermaine Ngo, LMPS Pharmacy Resident Preceptor: Bruce Liao, General Surgery

Nov 10, 2016

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Outline • Learning Objectives • Patient Case • Drug Therapy Problems • Background • PICO • Literature Search • Recommendations • Monitoring Plan

Learning Objectives

• List and describe 2 types of bowel preparations used for elective colorectal surgeries

• List complications associated with elective colorectal surgeries

• Describe the evidence behind oral antimicrobial bowel decontamination and mechanical bowel preparation

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Meet the Patient

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Patient Case: DS ID 55 year old Caucasian male (Ht = 175cm, Wt = 59kg,

BMI = 19.3kg/m2), admitted on Oct 20, 2016 c/c Admitted for laparoscopic sigmoid resection for Oct 26 HPI Since a right hemicolectomy for a colonoscopy-related

cecal perforation in 2012: • fistulas and abscesses in the rectosigmoid region • known complex abscess which communicates with anterior margin of the rectosigmoid region via fistula Since 2014: Chronic diverticulitis • persistent thickening of sigmoid colon • losing weight (?amount)

Allergies NKDA

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Patient Case: DS

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Past Medical History Medications PTA GERD • Pantoprazole 40mg PO daily Anemia of chronic disease (Hb: 70s to low 90s)

• No treatment

Chronic Diverticulitis • No treatment Social Hx: No Caffeine. Occasional Marijuana. Drinks 3-5 beers per day. Smokes 1 pack of cigarettes/day x 25 years Independent with activities of daily living Previous Surgeries: • Right hemicolectomy for colonoscopy-related cecal perforation in 2012

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Review of Systems (Oct 24, 2016) Vitals Temp 36.4oC BP 113/73 HR 86 RR 16 O2Sat 97% RA

CNS Alert and oriented x3 GCS 15 EENT Unremarkable

CVS No CP, No S3 + S4, No edema

RSP No cough/SOB

GI No BRBPR, No melena stools, Reports multiple loose stools daily GU/renal Unremarkable Liver Endo MSK Derm

Unremarkable

Review of Systems

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Relevant Labs – Oct 24, 2016 Serum [Na+] 135 mmol/L

Serum [K+] 3.9 mmol/L

Serum [Cl-] 105 mmol/L

Serum [Mg+] 0.7 mmol/L

sCr 35 umol/L

eGFR 114 mL/min/1.73m2

Albumin 28 g/L

LFTs WNL

CIWA 0

Relevant Labs

Diagnostics

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Diagnostics Colonoscopy (Sept 21/16)

Pelvic air and fluid collection (↓ in size) • Contiguous with the anterior rectum and superior sigmoid colon

CXR (Oct 24/16) Unremarkable

Current Medications Medical Problems Medications (Oct 24, 2016) GERD • Pantoprazole 40mg PO daily Anemia • Iron sucrose 300mg IV daily

• Vitamin B12 1000mcg PO daily Alcohol Withdrawal/ Alcohol Use

• CIWA • Thiamine 100g PO daily • Multi-vitamin 1 tablet PO daily

DVT Prophylaxis • Heparin 5000 U SC BID Bowel Preparation Day prior to operation:

• Peglyte 70g PO x 2 doses • Metronidazole 1g PO at 1300hr, 1500hr, 2000hr • Neomycin 1g PO at 1300hr, 1500hr, 2000hr

Pre-operative • Standard pre-operative PPO orders

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Drug Therapy Problems

• DB is at increased risk of developing antimicrobial resistance and adverse drug reactions (e.g. headache, diarrhea), secondary to receiving pre-operative bowel preparation. He would benefit from reassessment of therapy.

• DS is at risk of developing delayed wound healing, coronary heart disease and pulmonary diseases, secondary to smoking. He would benefit from smoking cessation

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Background

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Colorectal Surgery • For colorectal surgeries, with no antibiotics:

Abdominal surgical wound infection occurs in approximately 40% of patients

• Complications of infection: – Doubles the risk of death – Increases the likelihood of an ICU admission – Lengthens average hospital stay by 5 days

Cochrane Database of Systematic Reviews 2014, Issue 5. Art. No.: CD001181 13

Pre-operative Bowel Preparation • Mechanical Bowel Preparation (MBP):

– Examples: polyethylene glycol, sodium phosphate, sodium picosulphate, magnesium citrate

– ↓ intraluminal fecal mass – ↓ bacterial load in the bowel

• Advantages: generally safe • Disadvantages:

– may be unpleasant for patients

Can J Surg, Vol. 53, No. 6, December 2010

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Pre-operative Bowel Preparation • Antimicrobial Bowel Decontamination:

– Antibiotics administered pre-operatively • Usual coverage: anaerobic and aerobic bacteria

– ↓ microbial contamination at the surgical site • ↓ the risk of abdominal surgical wound infections

• Disadvantages: – Adverse Drug Reactions – ↑ risk for resistant bacteria – ↑ risk for Clostridium Difficile colitis

ARCH SURG/VOL 140, AUG 2005 Clinics in Colon and Rectal Surgery Vol. 26 No. 3/2013

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Potential Pathogens

Colorectal: • Bacteroides spp. • Clostridium spp. • Enterobacteriaceae

(e.g. E.coli, Klebsiella spp.)

ASHP Antibiotic Streaming 2008

Skin: • Staphylococci

(especially epidermidis) • Diphtheroids

(e.g. Corynebacterium spp.) • Propionobacteria

Goals of Therapy

• ↓ the risk of post-operative surgical infections • Minimize length of hospital stay • Prevent hospital re-admissions for post-

operative complications • Prevent mortality • Minimize adverse drug reactions

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PICO P Adult patient with elective sigmoid colonscopy/resection

I Oral mechanical bowel preparation AND Oral antibiotic bowel decontamination

C Placebo/No Preparation Oral antibiotic bowel decontamination ALONE Oral mechanical bowel preparation ALONE

O Efficacy: • Incidence of surgical-related post-operative infections • Length of hospital stay • Hospital readmissions • Mortality Safety: • Adverse Drug Reactions

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Literature Search Databases PubMed, Medline

Key Search Words “Mechanical Bowel Preparation” AND “Antibiotic Bowel Preparation” OR “Neomycin” OR “Metronidazole” OR “Antibiotic Bowel Decontamination” AND “Colorectal Surgery”

Inclusion Available in English, Humans, Full article available

Results • 3 Systematic Reviews • 6 Retrospective Studies • 4 Prospective Studies • 5 Randomized Controlled Trials • 2 Meta-Analysis

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1. For a 55 year old male requiring sigmoid resection, is mechanical bowel preparation and antibiotic

bowel decontamination better than placebo or either alone?

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Annals of Surgery Volume 261, Number 6, June 2015 21

Morris et al. Design Retrospective analysis of the National Surgical Quality

Improvement Program colectomy cohort (2011-2012) Patients N = 8415 colorectal operations (62.9% were minimally invasive)

Exclusion • Cases missing information on type of pre-op preparation given • Non-elective or emergent surgery

Intervention/ Comparator

• No preoperative preparation • MBP only • Oral antibiotic with or without MBP

Outcome • Postoperative surgical site infections • Length of hospital stay • All cause readmission within 30 days after colectomy Secondary: Postoperative wound disruption; Anastomic leak; Ileus; Acute renal

failure; Sepsis; Bleeding needing > 4units; Death within 30 days

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Patient Population Characteristics None (%)

N = 2150 MBP only (%) N = 3779

OABP + MBP (%) N = 2486

Males 1031 (48%) 1840 (48.7%) 1256 (50.5%)

Smoking 375 (17.4%) 638 (16.9%) 439 (17.7%)

Functional Health -Independent

2095(97.4%) 3708 (98.1%) 2452 (98.6%)

Surgeries

MIS 1191 (55.4%) 2447 (64.8%) 1652 (66.5%)

Ileocolic procedure 557 (25.9%) 650 (17.2%) 389 (15.7%)

LAR/APR/Hartmann 567 (26.4%) 1271 (33.6%) 661 (26.6%)

Partial colectomy 914 (42.5%) 1725 (45.7%) 1368 (55.0%)

Total colectomy 112 (5.2%) 133 (3.5%) 68 (2.7%)

Indications

Diverticulitis 341 (15.9%) 943 (25.0%) 158 (6.4%)

Colon and rectal ca 917 (42.7%) 1725 (45.7%) 997 (40.1%)

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MIS = Minimally Invasive Surgery, LAR = Low Anterior Resection, APR = AbdominoPerioneal Resection

Results None (%) N = 2150

MBP only (%) N = 3779

OABP + MBP (%) N = 2486

P-value

Superficial SSI 185 (8.6%) 263 (7.0%) 89 (3.6%) < 0.001

Deep Wound SSI 27 (1.3%) 50 (1.3%) 18 (0.7%) 0.07

Organ Space SSI 123 (5.7%) 156 (4.1%) 64 (2.6%) <0.001

Sepsis 88 (4.1%) 104 (2.8%) 59 (2.4%) 0.002

Anastomic Leak 99 (4.6%) 131 (3.5%) 58 (2.3%) <0.001

Post-operative ileus 313 (14.6%) 456 (12.1%) 234 (9.4%) <0.001

Bleeding > 4 units 205 (9.5%) 272 (7.2%) 144 (5.8%) <0.001

Median LOS 5 days (4-8) 5 days (4-7) 4 days (3-6) <0.001

Readmissions 253 (11.8%) 352 (9.3%) 200 (8.1%) <0.001

Death within 30d 26 (1.2%) 21 (0.6%) 9 (0.4%) 0.001

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Results

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Adjusted odds ratio for SSI by bowel preparation type stratified

Propensity Matched Analysis: Odds Ratio (95% CI) Mechanical only 0.87 (0.73 – 1.05) OABP + Mechanical 0.46 (0.36 – 0.58)

Summary • Oral Antibiotic Bowel Preparation + MBP

– ✓Post-operative complications (SSI, anastomic leaks, ileus)

– ✓Length of Hospital Stay – ✓Readmission rates – ✓Death within 30 days

• Evidence for efficacy is greater for OABP

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Strengths and Limitations

Strengths Limitations Methodology: • Relatively large sample size • Propensity Score Matching • Sub-group analysis

Clinically: • Relevant Efficacy Outcomes

Methodology: • Retrospective analysis • Did not separate OABP alone Clinically: • Safety outcomes? • Is the combination of OABP and MBP more effective than OABP alone? • What antibiotics are most effective?

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Mechanical Bowel Preparation • Review by Kumar et al (2013):

– No differences in anastomic leak or wound infections – ?Trend to ↑ infectious complications – ? Reports of earlier return to bowel function and shorter

hospital stays without MBP • RCT by Constant et al (2007):

– ↓ intra-abdominal abscess by absolute difference of 2.4% (95% CI: 0.5-4.4%, P=0.02)

– No difference in anastomic leaks, wound infections, mortality or hospital stay

• Cochrane Review by Guenaga et al (2011): – Omitting MBP not associated with ↑ complications

Clinics in Colon and Rectal Surgery Vol. 26 No. 3/2013 Lancet 2007;370(9605):2112–2117

Cochrane Database Syst Rev. 2011:CD001544. 28

Mechanical Bowel Preparation

• Prospective Cohort by Collin et al. (2014): – Significantly better cancer-related survival rates

• Retrospective Study by Cannon et al. (2012): – Oral antibiotics + MBP: 57% ↓ in SSI – Oral antibiotics alone: 67% ↓ in SSI

• RCT by Brahmania et al. (2014): – 2L of PEGLyte was similar in bowel cleaning

efficacy to 4L, but was more tolerable

Ann Surg. 2015 Sep;262(3):416-25 Gastrointest Endosc. 2014 Mar;79(3):408-416.e4

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Enhanced Recovery After Surgery Society (ERAS) Guidelines 2013

• Most RCTs included open colectomy – ?Extrapolation to laparoscopic surgeries

World J Surg (2013) 37:259–284 30

“

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2. For a 55 year old male requiring sigmoid resection, what

antimicrobial prophylaxis options are the most effective and safe?

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Cochrane Database of Systematic Reviews 2014, Issue 5. Art. No.: CD001181. 32

Nelson et al.

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Design Systematic Review Number 260 trials and 43,451 participants

• 68 different antibiotics Objectives Establish the effectiveness of antimicrobial prophylaxis for the

prevention of surgical wound infections in patients undergoing colorectal surgery

Selection Criteria

RCTs of prophylactic antibiotic use in elective and emergency colorectal surgery, with surgical wound infection as an outcome (from 1954 for MEDLINE and 1974 for EMBASE up to Jan 7, 2013)

Results – Efficacy

Comparisons Risk Ratio (95% CI)

Antibiotics vs. no antibiotics 0.34 (0.28-0.41), P < 0.00001 Short-term vs. Long-term 1.10 (0.93-1.30) Single vs. Multiple Doses 1.30 (0.81-2.10)

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“ Actual choice of antibiotic is probably not as important as the timing of administration, timing of cessation and route of administration.”

Surgical Wound Infections:

Antibiotic Prophylaxis • Aerobic + Anaerobic:

– Compared to either alone, significantly ↓ the incidence of surgical wound infections

– Compared to anaerobic coverage only: RR: 0.44, 95% CI: 0.29-0.68, P-value = 0.0002

– Compared to aerobic coverage only: RR: 0.47, 95% CI: 0.31-0.71, P-value = 0.0004

• Oral administration vs. IV administration: – No significant advantage for ↓ surgical wound infections

RR: 2.31, 95% CI: 0.60-8.83, P = 0.22 – Combination more effective than either alone

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BC ERAS Guidelines

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Antimicrobial Coverage • Neomycin: aminoglycoside

– 97% of dose remains in GI tract – Dose: 1 gram TID POD -1 – Coverage: Aerobic gram-negative bacilli

• Metronidazole: – Dose: 1 gram TID POD-1 – Coverage: Anaerobic bacteria

Sanford’s Guide to Antimicrobial Therapy

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Potential Pathogens

Colorectal: • Bacteroides spp. • Clostridium spp. • Enterobacteriaceae

(e.g. E.coli, Klebsiella spp.)

ASHP Antibiotic Streaming 2008

Skin: • Staphylococci

(especially epidermidis) • Diphtheroids

(e.g. Corynebacterium spp.) • Propionobacteria

Metronidazole

Neomycin

Neomycin and Metronidazole

• Debo Adeyemi et al, 1986: – Mechanical + Neo + Metro ↓ post-op infections

from 40-46% to 6% (p < 0.05)

• Lutfiyya et al, 2012: – Colorectal surgery care bundle including

Mechanical + Neo + Metro: ↓ infections from 21.16% to 6.67% (p < 0.0001), ↓ superficial SSI from 15.12% to 3.59% (p < 0.0001)

Eur Surg Res. 1986;18(5):331-6. Perm J 2012 Summer;16(3):10-16

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Safety

• Wren et al, 2005: – Pre-operative oral antibiotics ↑ post-operative

C. difficile infection from 2.6% to 7.4% (P = 0.03)

• Cleary et al, 1998: – Pre-colorectal surgery:

Neomycin + Metronidazole vs. Neomycin + Erythromycin • RR of C. Diff colonization: 4.76 times greater with N/E

(95% CI, 0.581 – 39, p = 0.202)

Arch Surg. 2005;140:752-756

Dis Colon Rectum. 1998 Apr;41(4):464-7. 40

BC ERAS Guidelines

Preferred Mechanical Bowel Preparation: – PegLyte® (polyethylene glycol (PEG) 3350 and

electrolytes for oral solution without bisacodyl)

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Recommendations

Suggest: • No change for POD -1:

Neomycin 1g PO + Metronidazole 1g PO TID – Avoid alcohol for 48 to 72 hours after last dose

Mechanical Bowel Preparation • Encourage smoking cessation to reduce delay

in wound healing

Silverstein P. Am J Med. 1992 42

Monitoring Plan – Efficacy Efficacy Parameter Who Expected ∆? Frequency

Subjective Confusion, Disorientation Around surgical site: • Erythema • Swelling • Pain • Pus

Physician Pharmacist Nurse

Absence Daily

Objective WBCs+ Neutrophils Temperature Respiratory Rate Systolic Blood Pressure

Stable Afebrile RR < 22 bpm Stable (SBP >100mmHg)

Daily

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Monitoring Plan – Safety

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Monitoring Parameters Who Expected ∆? Frequency? CNS Headache, Dizziness, Fever

(T>38.3oC) Pharmacist Physician Nurse

Presence Daily (POD 4-5)

HEENT Metallic taste, Dry mouth, Changes in hearing

Presence

GI Nausea, Vomiting, Diarrhea, Lower abdominal pain, Cramping Clostridium difficile infection (>3 loose stools in 24 hours)

Presence

Renal eGFR, sCr Renal dysfunction

Heme WBC, Neutrophils Increase

Follow up

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Thank you! Questions?

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