Satish S.C. Rao, MD, PhD, FACG

Dyssynergic DefecationDyssynergic Defecation

Satish S.C. Rao, MD, PhD, FACGProfessor of Medicine

Chief, Division of Gastroenterology/HepatologyDirector, Digestive Health Center, MCG

Augusta University, Augusta, GA

ObjectivesObjectives

What is Dyssynergic Defecation?

Pathophysiology of DD?

Advances in diagnosis and treatment

RCTs for Biofeedback Therapy Dyssynergic Defecation

How does Biofeedback work?

Insights from studies of Brain-Gut Interactions

ACG 2016 Annual Postgraduate Course Copyright 2016 American College of Gastroenterology

Page 1 of 21

Satish S.C. Rao, MD, PhD, FACG

Constipation & Most Bothersome symptomConstipation & Most Bothersome symptom

Symptoms US Household

n= 10,018

Self-Reported

(27%),n=312

Rome II (15%)

n=171

Straining during B.M 32.4% 17.5%

Hard /Lumpy Stool 29% 20.4% 11.1%

< 3 B.M /week 9% 13.2% 12.3%

Sensation stool can’t be passed 24% 12.9% 5.8%

Feeling of Incomplete evacuation 30% 12.4% 6.4%

A need to press around anus 12% 5.6% 6.4%

Pare et al, Canada

Pare et al. Am J Gastroenterol 2001Stewart et al. Am J Gastroenterol 1999

Stewart et al

EvacuationDisorders

Primary Constipation

Rao SSC. Gastroenterol Clin North Am. 2003;32:659-683.

Pathophysiology of Constipation

Dyssynergic Defecation

RectoceleProlapse

Perineal descent

ACG 2016 Annual Postgraduate Course Copyright 2016 American College of Gastroenterology

Page 2 of 21

Satish S.C. Rao, MD, PhD, FACG

What’s in a Name?What’s in a Name?

Anismus

Paradoxical puborectalis contraction

Pelvic outlet obstruction

Spastic pelvic floor syndrome

Pelvic floor dyssynergia- Rome II

Obstructive Defecation

Dyssynergic Defecation-Rome III/IV

Case Study 48-year-old secretary

Case Study 48-year-old secretary

Increasing constipation- 5 years Began during college days B.M once or twice a week Hard, pellet-like stool, excessive straining, incomplete

evacuation and occasional bleeding Spends 30 mins on toilet Occasional digital disimpaction Tried OTC laxatives, lubiprostone, PEG-no relief BM only after enema + suppository and laxatives

ACG 2016 Annual Postgraduate Course Copyright 2016 American College of Gastroenterology

Page 3 of 21

Satish S.C. Rao, MD, PhD, FACG

History Contd..History Contd..

Past Hx: Migraines, seasonal allergy, No back or pelvic injury, Gravida 1, para 1

Drugs: HFD=30g/day, Senna=2/day, lubiprostone=24 mcg/bid

O/E: lower abdominal fullness

What would you do next?What would you do next?

Who wants a Rectal exam?

ACG 2016 Annual Postgraduate Course Copyright 2016 American College of Gastroenterology

Page 4 of 21

Satish S.C. Rao, MD, PhD, FACG

0

50

100

150

200

GI Faculty

GI Fellows

Primary Care

Internal Med

Med Students

DREs performed in previous

year(n)

Rectal Examinations Performed in Previous Year by Clinical Status (5% - 95%)*

Figure 2 Boxplot – Rank, Revised

* GI faculty and fellows had 18 outlier values ranging from 205 -1600

Wong et al, AJG,2012

3-step DRE-PROTOCOL3-step DRE-PROTOCOL

1) Inspection

2) Perianal sensation & anocutaneous reflex: normal, impaired, absent

3) Digital maneuvers: mass, tenderness, stool

Squeeze x 2: normal, weak, increased

Bearing down x 2 push effort, sphincter relaxation, perineal descent

Clinically dyssynergia if … any 2; • inability to

•contract abdominal muscles •relax anal sphincter

• paradoxical contraction of anal sphincter • absence of perineal descent

Tantiphlachiva K, Rao S et al, CGH 2010

ACG 2016 Annual Postgraduate Course Copyright 2016 American College of Gastroenterology

Page 5 of 21

Satish S.C. Rao, MD, PhD, FACG

Yield of rectal exam in dyssynergia, n=209Yield of rectal exam in dyssynergia, n=209

� All patients had DRE and anorectal manometry and BET

ParameterSensitivity

(%)Specificity

(%)

Dyssynergia from DRE 75% 87%

Balloon expulsion test 49 90%

Tantiphlachiva K, Rao P, Attaluri A, Rao S, CGH 2010

Pathophysiology of DyssynergiaPathophysiology of Dyssynergia

35 patients with chronic constipation,

m/f = 5/30, x age = 44 yrs (21-81 yrs),

25 healthy controls

ASSESSMENTS:• Anorectal manometry• Simulated defecation with 50 cc balloon• Defecography• Colonic transit study

Rao et al,Am J Gastroenterol 1998;93:1042-50

ACG 2016 Annual Postgraduate Course Copyright 2016 American College of Gastroenterology

Page 6 of 21

Satish S.C. Rao, MD, PhD, FACG

A CB

0

65

130

0

65

130

0

65

130

Non-Obstructive

P < 0.0001

Obstructive

P Š 0.001

AnalSphincterPressure(mmHg)

Normals

P < 0.0001

RestingPressure

ResidualPressure

RestingPressure

ResidualPressure

BeforeBiofeedback

RestingPressure

ResidualPressure

ResidualPressure

AfterBiofeedbackRao, et al

Am J Gastroenterology1998; 93: 1042-50

Manometric Changes during Attempted DefecationManometric Changes during Attempted Defecation

Dyssynergic Defecation-Pathophysiology

� Impaired Rectoanal coordination– Paradoxical anal contraction

– Inadequate rectal contraction/pushing force

– Absent/Inadequate anal relaxation

� Impaired Rectoanal sensation ~ 50%

� Learnt = 67%

� Yet to Learn = 33%

Rao et al, Am J Gastroenterol 1997;92:469-75

Rao et al, J Clin Gastro 2004;38;680-5

ACG 2016 Annual Postgraduate Course Copyright 2016 American College of Gastroenterology

Page 7 of 21

Satish S.C. Rao, MD, PhD, FACG

Can symptoms predict dyssynergia?Can symptoms predict dyssynergia?

Symptom prevalenceNormal pattern

(n=30)Dyssynergia

(n=70)

Excessive straining 92% 89%

Abdominal fullness 80% 84%

Incomplete evacuation 72% 95%

Abdominal discomfort 88% 77%

Digital maneuvers to defecate 28% 51%

Rao et al, Neurogastroenterol Motil 2004; 16: 589

100 patients with difficult defecation

Tools for EvaluationTools for Evaluation

� History

� Physical Examination

– Digital Rectal Examination

� Stool Diary-Bristol Stool Scale

� Diagnostic Tests

– Physiological

– Morphological

– StructuralRao SSC. Gastroenterol Clin N Am 36 (2007) 687-711

ACG 2016 Annual Postgraduate Course Copyright 2016 American College of Gastroenterology

Page 8 of 21

Satish S.C. Rao, MD, PhD, FACG

Date Time of Bowel

Movement

Straining

Yes/No

Feeling of incomplete

BM

Yes/No

Stool Consiste-ncy (1-7)

Urge

Yes/No

Digital

Yes/No

Drug Comments

Stool Diary-Constipation; Rao ©Record your stool habit for one week

1

3

4

5

6

1

1

2

7Liqui

Name:Hosp. No:

Evaluation of Colonicand Anorectal FunctionEvaluation of Colonic

and Anorectal Function

Colonic Marker StudyAnorectal manometry

Day 1- Bisects

Day 2- Rings

Day 3-Trisects

Day 6 (120 hrs)

- Plain abdomen x-ray

-

Balloon Expulsion Test

ACG 2016 Annual Postgraduate Course Copyright 2016 American College of Gastroenterology

Page 9 of 21

Satish S.C. Rao, MD, PhD, FACG

Normal Bearing DownNormal Bearing Down

Types of Dyssynergic DefecationTypes of Dyssynergic Defecation

Normal

Rectal

Anal

Rao et al, Neurogastroenterol Motil 2004; 16: 589

ACG 2016 Annual Postgraduate Course Copyright 2016 American College of Gastroenterology

Page 10 of 21

Satish S.C. Rao, MD, PhD, FACG

Dyssynergic patterns:PhenotypesDyssynergic patterns:Phenotypes

P-

Puborectalis

EAS-

External anal sphincter

D -

Difusse

P-

Puborectalis

EAS-

External anal sphincter

D -

Diffuse

I II III IV

S.Rao et al DDW 2016

Dyssynergia Type 1- SubtypesDyssynergia Type 1- Subtypes

Type I-PuborectalisType I-Puborectalis

Type I- EASType I- EAS

Type 1-DiffuseType 1-Diffuse

S.Rao et al DDW 2016

ACG 2016 Annual Postgraduate Course Copyright 2016 American College of Gastroenterology

Page 11 of 21

Satish S.C. Rao, MD, PhD, FACG

48-yr old Secretary

Effect of Body Position on Defecation Patterns

Rest Bearing down

Rectal pressure

Rest Bearing down

Rectal pressure

Anal pressure

Bearing Down Lying Bearing Down on Commode

Courtesy of S.Rao

ACG 2016 Annual Postgraduate Course Copyright 2016 American College of Gastroenterology

Page 12 of 21

Satish S.C. Rao, MD, PhD, FACG

Diagnostic Criteria-Dyssynergic DefecationDiagnostic Criteria-Dyssynergic Defecation

1. The patient must satisfy diagnostic criteria for functional constipation-Rome III

2. During repeated attempts to defecate must demonstrate Dyssynergic pattern of defecationManometryEMG

3. Patient must demonstrate one other abnormal test:a. Abnormal balloon expulsion Test (> 1 minute)b. Prolonged Colonic Transit Time (radioopaque

markers or SmartPill or Scintigraphy)c. Abnormal Defecogarphy (>50% barium retention)

Bharucha et al, Gastroenterology 2006; 130: 1514Rao SSC. Gastroenterol Clin N Am 36 (2007) 687-711

How to Treat Dyssynergic Defecation ?

How to Treat Dyssynergic Defecation ?

General Measures Diet, exercise, fluids & habit training Laxatives/Prokinetics

Specific Treatment Botox injection Biofeedback therapy Cognitive Behavioral Therapy Surgery

Myectomy- 30% improvement Colostomy

Rao SSC. Gastroenterol Clin N Am (2008)

ACG 2016 Annual Postgraduate Course Copyright 2016 American College of Gastroenterology

Page 13 of 21

Satish S.C. Rao, MD, PhD, FACG

Botox-DyssynergiaBotox-Dyssynergia

Ron et al 2001 Dis Col

Joo et al 1996

Dis Col Rec

Hallan et al Lancet 1988

n(f) 25(15) 4 7

Diagnosis ARM + B.Defecation

EMG +Defecography

EMG

Botulinum Toxin A 20 u 6-15u 3 ng

F.up 1,4,12,24 wks 10 mo 4 wks

Success 30% 50% 57%

Complications (pain, incont.) 12.5% 5.6% 29%

3 Uncontrolled trials

Biofeedback TherapyBiofeedback Therapy

A technique of conditioning and/or retraining the mind and body to normalize bowel movement.

�

How many of you perform Biofeedback ?

ACG 2016 Annual Postgraduate Course Copyright 2016 American College of Gastroenterology

Page 14 of 21

Satish S.C. Rao, MD, PhD, FACG

Biofeedback-DyssynergiaBiofeedback-Dyssynergia

» Goals of Therapy :• A) Teach Diaphragmatic

breathing exercise

• B) Teach anal sphincter &

pelvic floor relaxation

• C) Improve Rectal Sensation

• D) Eliminate Sensory Delay

• E) Improve Recto-anal Coordination

Visual/Audio/Verbal Feedback

Doctor/Therapist

Visual, Audio & Verbal Feedback

ACG 2016 Annual Postgraduate Course Copyright 2016 American College of Gastroenterology

Page 15 of 21

Satish S.C. Rao, MD, PhD, FACG

RCT of Biofeedback Therapy Effects on CSBM & Dyssynergia- ITT Analysis

RCT of Biofeedback Therapy Effects on CSBM & Dyssynergia- ITT Analysis

0

1

2

3

4

Biofeedback Sham Feedback Standard

CS

BM

s p

er W

eek

(M

ean

+ S

.E.M

.)

Baseline

Post-Therapy

¤ § §§

§§ p = 0.0062 vs Standard

¤ p < 0.02 vs Baseline

§ p < 0.05 vs Sham¤ § §§

Rao et al Clin Gastro Hepatol 2007

0%

20%

40%

60%

80%

100%

Biofeedback Sham Feedback Standard

% o

f P

atie

nts

wit

h D

yssy

ner

gia

afte

r T

reat

men

t

¤:p < 0.0001 vs Sham,Standard,& Baseline

¤

0

1

2

3

4

5

6

7

Biofeedback Standard

Mea

n C

SB

Ms

/ W

eek

±S

.E.

BaselineOne Year¤ §

§ p<0.0001 vs Standard

¤ p<0.0001 vs Baseline

Rao et al Am J Gastro 2010

Long Term Outcome of Biofeedback- CSBM/weekLong Term Outcome of Biofeedback- CSBM/week

ACG 2016 Annual Postgraduate Course Copyright 2016 American College of Gastroenterology

Page 16 of 21

Satish S.C. Rao, MD, PhD, FACG

Home vs Office Biofeedback-Responder Analysis

Home vs Office Biofeedback-Responder Analysis

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

HOME OFFICE

RESPONDER= > 1 CSBM/wk + > 20 mm Change in VAS

HOME

OFFICE

TOST= p =0.006

Rao et al DDW 2011

Biofeedback Therapy-RCTsBiofeedback Therapy-RCTs Biofeedback Vs PEG 14.6 g for Dyssynergia

Chiarioni et al, Gastroenterology 2006; 130: 657-64

Biofeedback vs Diazepam for Dyssynergia Heymen et al, Dis Col Rectum 2007

Biofeedback vs Sham Therapy vs Standard Therapy Rao et al CGH 2007

Biofeedback vs Standard Therapy-One Year outcome Rao et al Am J Gastroenterol 2010

Home vs Office Biofeedback Therapy- Efficacy & Cost Effectiveness Rao et al, DDW 2011 & Go et al, DDW 2011

Evidence Level: Type 1; Recommendation Grade : ARao et al: American & European NGM Societies, Neurogastro Mot 2015

ACG 2016 Annual Postgraduate Course Copyright 2016 American College of Gastroenterology

Page 17 of 21

Satish S.C. Rao, MD, PhD, FACG

Biofeedback Bowel RetrainingBiofeedback Bowel Retraining

Advantages:

Safe Effective Painless And Well Tolerated Inexpensive

�

Stimulation Parameters• Sample frequency 2000 Hz• Epoch duration 300 ms• Amplifier gain 100,000 Hz• Artifact rejection = On• Band pass filter 1-500 Hz• Stimulus frequency 0.2 Hz• Number of stimuli : 200 (50 x 4)

Electrical Stimulation

Aff

eren

t Pa

thw

ay

CEPs recording

Recto-Cortical and Ano-Cortical Evoked Potentials (Afferent Brain-gut interaction)

1

2

3

4 Computer system analysis

ACG 2016 Annual Postgraduate Course Copyright 2016 American College of Gastroenterology

Page 18 of 21

Satish S.C. Rao, MD, PhD, FACG

Recto-Cortical Evoked Potentials (CEP)-Grand average of 200 electrical stimulations

Recto-Cortical Evoked Potentials (CEP)-Grand average of 200 electrical stimulations

50 (ms)

P1

N1

P2

N2

Normal

50 (ms)

P1

N1

P2

N2

Onset to P1: 48.1 milisecondsAmplitude: 4. 96 µV

Onset to P1: 66.62 milisecondsAmplitude: 1.04 µV

7

6

5

4

3

2

1

0

7

6

5

4

3

2

1

0

50 (ms)

P1

N1

P2

N2

Onset to P1: 44 milisecondsAmplitude: 2.79 µV

7

6

5

4

3

2

1

0

Dyssynergic-After BF

µv

Dyssynergic-Before BF

Rao et al DDW 2011

Efferent Brain-Gut axis Assessment

MEPs recording

Eff

eren

t p

ath

way

2

4 Computer system analysis

1

3

TMS stimulation

Stimulation Parameters• Stimulation intensity 85-100%• Good response = MEP amplitude >10 V • 3-6 consecutive trials

Coss Adame E, Rao S et al NGM 2012

ACG 2016 Annual Postgraduate Course Copyright 2016 American College of Gastroenterology

Page 19 of 21

Satish S.C. Rao, MD, PhD, FACG

Results

Trans-cranial magnetic stimulation

Left Right

Anal(ms)

Rectal(ms)

Anal(ms)

Rectal (ms)

Before Treatment 26±1 24±0.7 24±0.7 24±0.6

After Treatment 22±0.5* 21±0.4* 21±0.4* 21±0.5*

Healthy Controls 22±1† 21±1† 22±1† 20±1†

* p<0.05, Before vs After Treatment ; Pair t test, values expressed mean ± SEM† p<0.05, Before Treatment vs Healthy Controls

Coss Adame E, Rao S et al NGM 2012

CONCLUSIONSCONCLUSIONS

• Biofeedback therapy modulates the neurobiologic brain-gut axis and thereby improves bowel function in patients with DD

• Our study provides a mechanistic basis for biofeedback therapy in DD

Coss Adame E, Rao S et al NGM 2012

ACG 2016 Annual Postgraduate Course Copyright 2016 American College of Gastroenterology

Page 20 of 21

Satish S.C. Rao, MD, PhD, FACG

Take Home PointsTake Home Points

� Dyssynergic Defecation causes Constipation in ~40%� HRAM increases sensitivity but body position is critical � Biofeedback is mainstay treatment & not Experimental� RCTs have established short term and long term

efficacy of biofeedback in dyssynergic defecation– -Grade A Evidence- Rao et al Neurogastro Motil 2015

� Gut-Brain-gut axis is deranged in Dyssynergic patients & Biofeedback Therapy restores altered function

� Home Biofeedback is efficacious and cost-effective

ACG 2016 Annual Postgraduate Course Copyright 2016 American College of Gastroenterology

Page 21 of 21