Erik Sowder, PhD, BCIAC Richard Gevirtz, PhD, BCIAC Warren Shapiro, MD, FAAP California School of Professional Psychology at Alliant International University, San Diego, CA in collaboration with Kaiser Permanente/ Southern California Permanente Medical Group HRV Biofeedback for Patients with Recurrent Abdominal Pain

HISTORICAL PERSPECTIVE Man should strive to have his intestines relaxed all the days of his life Moses Maimonedes , AD 1135-1204 A good set of bowels is worth more to a man than any quantity of brains. Josh Billings ( Henry Wheeler Shaw ), AD 1818-1885

Man should strive to have his intestines relaxed all the days of his life

Moses Maimonedes , AD 1135-1204

A good set of bowels is worth more to a man than any quantity of brains.

Josh Billings ( Henry Wheeler Shaw ), AD 1818-1885

Epidemiology 10-30% of children and adolescents have recurrent abdominal pain. 5-15% of middle school and high school students have symptoms consistent with IBS Approx 5% of middle and high school students note dyspeptic symptoms.

10-30% of children and adolescents have recurrent abdominal pain.

5-15% of middle school and high school students have symptoms consistent with IBS

Approx 5% of middle and high school students note dyspeptic symptoms.

EPIDEMIOLOGY More than one third of children complain of pain lasting 2 weeks or longer. 15% of U.S adults report symptoms that are consistent with the diagnosis of the irritable bowel syndrome. IBS is the most common diagnosis made by gastroenterologists in the US and accounts for 12% of visits to primary care providers

More than one third of children complain of pain lasting 2 weeks or longer.

15% of U.S adults report symptoms that are consistent with the diagnosis of the irritable bowel syndrome.

IBS is the most common diagnosis made by gastroenterologists in the US and accounts for 12% of visits to primary care providers

School Age children who had complained of at least 3 episodes of pain severe enough to affect their activities over a period longer than 3 months. JOHN APLEY

School Age children who had complained of at least 3 episodes of pain severe enough to affect their activities over a period longer than 3 months. JOHN APLEY

The Irritable Bowel Syndrome accounts for an estimated $8 billion in direct medical costs and $25 billion in indirect costs annually in the US

The Irritable Bowel Syndrome accounts for an estimated $8 billion in direct medical costs and $25 billion in indirect costs annually in the US

OVER THE PAST 2 DECADES THER HAS BEEN A TENFOLD INCREMENT IN MEDLINE CITATIONS ABOUT IBS.

OVER THE PAST 2 DECADES THER HAS BEEN A TENFOLD INCREMENT IN MEDLINE CITATIONS ABOUT IBS.

International Index of Sophistication The more sophisticated the country,the more little bellyachers will it have. JOHN APLEY

The more sophisticated the country,the more little bellyachers will it have. JOHN APLEY

A deficient freedom of relaxation in some part of the intestinal canal. JOHN HOWSHIP: Surgeon To St George’s infirmary. London 1830

A deficient freedom of relaxation in some part of the intestinal canal. JOHN HOWSHIP: Surgeon To St George’s infirmary. London 1830

Intestinal neuroses diminish in frequency as we descend the social scale. HAWKINS 1906.

Intestinal neuroses diminish in frequency as we descend the social scale. HAWKINS 1906.

SYMPTOMS IN SCHOOL AGE CHILDREN WITH RECURRENT ABDOMINAL PAIN OFTEN MEET THE ROME CRITERIA FOR FUNCTIONAL ABDOMINAL PAIN IN ADULTS.

SYMPTOMS IN SCHOOL AGE CHILDREN WITH RECURRENT ABDOMINAL PAIN OFTEN MEET THE ROME CRITERIA FOR FUNCTIONAL ABDOMINAL PAIN IN ADULTS.

Neurotransmitter Imbalance 5% of serotonin is located in the CNS 95% is in the GI tract. Serotonin release results in intestinal secretions and the peristaltic reflex. Patient with IBS may have increased serotonin levels in plasma and the rectosigmoid colon

5% of serotonin is located in the CNS

95% is in the GI tract.

Serotonin release results in intestinal secretions and the peristaltic reflex.

Patient with IBS may have increased serotonin levels in plasma and the rectosigmoid colon

OVER THE PAST 2 DECADES THERE HAS BEEN A SHIFT FROM Disease based Reductionistic Model with a single underlying biological etiology TO Integrated biopsychosocial model of illness: altered motility,enhanced visceral sensitivity,brain gut dysregulation all modified by sociocultural and psychosocial influences .

Disease based Reductionistic Model with a single underlying biological etiology

TO

Integrated biopsychosocial model of illness: altered motility,enhanced visceral sensitivity,brain gut dysregulation all modified by sociocultural and psychosocial influences .

Psychosocial Factors Altered Motility Distension Spasm Visceral Hypersensitivity Pain Bloating Urge to defecate Pathophysiologic Factors in the Development of the Irritable Bowel Syndrome

Epidemiology of Functional Abdominal Pain [Recurrent Abdominal Pain (RAP) and Irritable Bowel Syndrome (IBS)] The most Common GI disorders in Primary Care 11%-20% 0f US population (Drossman,1993, Talley et al., 1992) 25% seek care 12%-19.5% of Primary Care visits (Longstreth & Wolde-Tsadik,1993) $8 Billion annually in direct medical costs ($742 vs $429 Annual costs, Gralnek, 1998) $25 Billion annually in indirect costs

The most Common GI disorders in Primary Care

11%-20% 0f US population (Drossman,1993, Talley et al., 1992)

25% seek care

12%-19.5% of Primary Care visits (Longstreth & Wolde-Tsadik,1993)

$8 Billion annually in direct medical costs ($742 vs $429 Annual costs, Gralnek, 1998)

$25 Billion annually in indirect costs

Impact of RAP Disruption of daily activities/missed school days Over-utilization of healthcare Unnecessary surgeries Learning difficulties Anxiety Leibman, 1978; Hymans, Burke, David, Rzepski, & Andrulonis, 1996; DiPalma & DiPalma, 1997; Jansdottir, 1997

Disruption of daily activities/missed school days

Over-utilization of healthcare

Unnecessary surgeries

Learning difficulties

Anxiety

Leibman, 1978; Hymans, Burke, David, Rzepski, & Andrulonis, 1996; DiPalma & DiPalma, 1997; Jansdottir, 1997

Etiology Research over the past 10 to 15 years suggests that RAP is associated with family illness behavior increased somatic and emotional distress increased anxiety and depression in parents and children the supporting evidence remains inadequate and inconsistent for any particular model ( Fritz et al., 1997 ) Autonomic dysfunction appears to be a promising etiological factor

Research over the past 10 to 15 years suggests that RAP is associated with

family illness behavior

increased somatic and emotional distress

increased anxiety and depression in parents and children

the supporting evidence remains inadequate and inconsistent for any particular model ( Fritz et al., 1997 )

Autonomic dysfunction appears to be a promising etiological factor

Gastrointestinal motility changes such as a decreased vagal activation of gastric motility and regulation of tone and compliance of the gastrointestinal tract may be due to alteration in autonomic output (Mayer, 1999). Dysregulation of the autonomic nervous system may be reflecting changes occurring in sympathetic output to the small and large intestine.

Gastrointestinal motility changes such as a decreased vagal activation of gastric motility and regulation of tone and compliance of the gastrointestinal tract may be due to alteration in autonomic output (Mayer, 1999).

Dysregulation of the autonomic nervous system may be reflecting changes occurring in sympathetic output to the small and large intestine.

IBS Dysregulation of the autonomic nervous system is a component of IBS (Aggarwal et al., 1994; Karling et al., 1998; Smart & Atkinson, 1987; Lee et al., 1998). Aggarwal et al. (1994) studied variability in pulse rate, through use of a continuous electrocardiogram (EKG) strip measuring the R-R interval (RRI) to demonstrate that the parasympathetic system is less efficient at achieving homeostasis in IBS sufferers. These researchers used the RRI to calculate vagal response, a measure of vagal dysfunction.

Dysregulation of the autonomic nervous system is a component of IBS

(Aggarwal et al., 1994; Karling et al., 1998; Smart & Atkinson, 1987; Lee et al., 1998).

Aggarwal et al. (1994) studied variability in pulse rate, through use of a continuous electrocardiogram (EKG) strip measuring the R-R interval (RRI) to demonstrate that the parasympathetic system is less efficient at achieving homeostasis in IBS sufferers.

These researchers used the RRI to calculate vagal response, a measure of vagal dysfunction.

ANS as a mechanism in RAP/IBS Literature on RAP/IBS Deficit in ANS recovery to stress Enhanced behavioral and subjective response to pain Most currently empirically validated treatments make use of this hypothesis to some extent. Karling et al. (1998) found autonomic dysregulation in IBS sufferers by using a spectral analysis of low and high frequency activity. (Gupta V, Sheffield D, Verne GN., 2002) Evidence for autonomic dysregulation in the irritable bowel syndrome. (Iovino P, Azpiroz F, Domingo E, Malagelada JR., 1995) The sympathetic nervous system modulates perception and reflex responses to gut distention in humans.

Literature on RAP/IBS

Deficit in ANS recovery to stress

Enhanced behavioral and subjective response to pain

Most currently empirically validated treatments make use of this hypothesis to some extent.

Karling et al. (1998) found autonomic dysregulation in IBS sufferers by using a spectral analysis of low and high frequency activity.

(Gupta V, Sheffield D, Verne GN., 2002)

Evidence for autonomic dysregulation in the irritable bowel syndrome.

(Iovino P, Azpiroz F, Domingo E, Malagelada JR., 1995)

The sympathetic nervous system modulates perception and reflex responses to gut distention in humans.

Waring WS, Chui M, Japp A, Nicol EF, Ford MJ. Autonomic cardiovascular responses are impaired in women with irritable bowel syndrome. J Clin Gastroenterol . 2004 Sep;38(8):658-63.

Waring WS, Chui M, Japp A, Nicol EF, Ford MJ.

Autonomic cardiovascular responses are impaired in women with irritable bowel

syndrome. J Clin Gastroenterol . 2004 Sep;38(8):658-63.

How can IBS/RAP be best treated? Previous studies (Gevirtz, 2000; Whitehead, 1992; Bassotti & Whitehead, 1994) have shown biofeedback to be successful in the treatment of IBS.

Previous studies (Gevirtz, 2000; Whitehead, 1992; Bassotti & Whitehead, 1994) have shown biofeedback to be successful in the treatment of IBS.

Figure 1. Visual Analog scale from daily pain diary records, pre & post treatment, by group (Humphreys, Gevirtz, & Jacobs, 1999) Pre = Pre-treatment Post = Post-treatment 4 component = fiber+biofeedback+cognitive restructuring+parental support 3 component = fiber+biofeedback+cognitive restructuring 2 component = fiber+biofeedback

Figure 2. Parent observation rating of pain, pre & post treatment, by group (Humphreys, Gevirtz, & Jacobs, 1999) Pre = Pre-treatment Post = Post-treatment 4 component = fiber + biofeedback + cognitive restructuring + parental support 3 component = fiber + biofeedback + cognitive restructuring 2 component = fiber + biofeedback

Objectives 1) Clinically investigate the efficacy of a treatment protocol for RAP that focuses on autonomic balance. 2) Investigate autonomic function as a mechanism of RAP.

1) Clinically investigate the efficacy of a treatment protocol for RAP that focuses on autonomic balance.

2) Investigate autonomic function as a mechanism of RAP.

RAP Patients and Healthy Control Participants RAP Inclusion Criteria RAP diagnosis Ages 5-17 Female and male Exclusion Criteria Lactose Intolerant Urinary tract infections Recent head trauma Medications that could interfere with treatment Current medical treatment for RAP Recent/ related surgical procedure before/ during biofeedback Remarkable mental status Healthy Control Inclusion Criteria Healthy Ages 5-17 Female and male Exclusion Criteria Medications Remarkable mental status

RAP

Inclusion Criteria

RAP diagnosis

Ages 5-17

Female and male

Exclusion Criteria

Lactose Intolerant

Urinary tract infections

Recent head trauma

Medications that could interfere with treatment

Current medical treatment for RAP

Recent/ related surgical procedure before/ during biofeedback

Remarkable mental status

Healthy Control

Inclusion Criteria

Healthy

Ages 5-17

Female and male

Exclusion Criteria

Medications

Remarkable mental status

Procedures RAP group (n=20) Reviewed patients’ medical records at Kaiser/Children’s Specialists Routine 6 HRV biofeedback sessions conducted on-site 2 sessions ambulatory HRV monitoring Healthy control group (n=10) Recruited participants (verbal / flyers) during well-checks at Kaiser / Children’s Specialists 2 sessions ambulatory HRV monitoring

RAP group (n=20)

Reviewed patients’ medical records at Kaiser/Children’s Specialists

Routine 6 HRV biofeedback sessions conducted on-site

2 sessions ambulatory HRV monitoring

Healthy control group (n=10)

Recruited participants (verbal / flyers) during well-checks at Kaiser / Children’s Specialists

2 sessions ambulatory HRV monitoring

Pre/Post Assessment: VivoMetrics, Inc. LifeShirt,tm The first non-invasive, ambulatory monitoring system that continuously collects, records and analyzes a broad range of cardiopulmonary parameters. Made it possible to monitor children in their natural environments over a full day.

The first non-invasive, ambulatory monitoring system that continuously collects, records and analyzes a broad range of cardiopulmonary parameters.

Made it possible to monitor children in their natural environments over a full day.

Procedures Healthy Control Group Attend Kaiser or Children’s Specialists for 2 30-minute sessions (8 weeks apart) to connect LifeShirt Non-invasively monitored during 4 to 8 hours of daily activities both occasions. Total participating time, including explanation of the study and forms, ambulatory monitoring sessions, and answering any questions, was approximately 9-17 hours.

Healthy Control Group

Attend Kaiser or Children’s Specialists for 2 30-minute sessions (8 weeks apart) to connect LifeShirt

Non-invasively monitored during 4 to 8 hours of daily activities both occasions.

Total participating time, including explanation of the study and forms, ambulatory monitoring sessions, and answering any questions, was approximately 9-17 hours.

Procedures HRV Biofeedback for RAP group Patients diagnosed with RAP by a pediatric gastroenterologist and referred for Heart Rate Variability (HRV) Biofeedback. Patients seen by 1 of 3 pre-doctoral interns at Kaiser Permanente Pediatric Gastroenterology Department or Children’s Specialists of San Diego for an average of 6 sessions. All sessions were conducted in a treatment room or medical office at Kaiser Permanente or Children’s Specialists of San Diego.

Procedures

HRV Biofeedback for RAP group

Patients diagnosed with RAP by a pediatric gastroenterologist and referred for Heart Rate Variability (HRV) Biofeedback.

Patients seen by 1 of 3 pre-doctoral interns at Kaiser Permanente Pediatric Gastroenterology Department or Children’s Specialists of San Diego for an average of 6 sessions.

All sessions were conducted in a treatment room or medical office at Kaiser Permanente or Children’s Specialists of San Diego.

Psychophysiological aspects of Treatment Sympathetic disruption of the gut Parasympathetic influences Using aspects of heart rate variability to create autonomic homeostasis (Lehrer, Vaschillo, et al, 2001)

Sympathetic disruption of the gut

Parasympathetic influences

Using aspects of heart rate variability to create autonomic homeostasis (Lehrer, Vaschillo, et al, 2001)

Valley Pacer set at 7.0 bpm Respiration Heart Rate Peak= 79 Valley= 63

Typical Home Biofeedback Practice Regimen Daily Homework Assignments (Reviewed in weekly sessions) Takes 20 minutes/day Patients keep daily pain/stress diaries and practice logs Patients use self-monitoring practice tools

Daily Homework Assignments (Reviewed in weekly sessions)

Takes 20 minutes/day

Patients keep daily pain/stress diaries and practice logs

Patients use self-monitoring practice tools

Measures Pain severity: visual analogue scale completed by the participants. Symptom frequency: number of episodes per week. Autonomic regulation: Low frequency to high frequency ratio (sympatho-vagal balance) Percent low frequency during resonant frequency breathing Exploratory Measures NN50 High frequency activity Very low frequency activity LF/HF ratio

Pain severity:

visual analogue scale completed by the participants.

Symptom frequency:

number of episodes per week.

Autonomic regulation:

Low frequency to high frequency ratio (sympatho-vagal balance)

Percent low frequency during resonant frequency breathing

Exploratory Measures

NN50

High frequency activity

Very low frequency activity

LF/HF ratio

Data Preparation IBIs visually screened for ectopic beats and interpolated values inserted Respiration rate, tidal volume and movement partialled out using regression analyses Remaining IBIs submitted to Biosignal software analyses Additionally, nominated 5 minute segments with even respiration, tidal volume, and no movement and measured peak valley differences

IBIs visually screened for ectopic beats and interpolated values inserted

Respiration rate, tidal volume and movement partialled out using regression analyses

Remaining IBIs submitted to Biosignal software analyses

Additionally, nominated 5 minute segments with even respiration, tidal volume, and no movement and measured peak valley differences

0

RAP

RAP

0

0

0

Summary Many previous studies have established autonomic dysregulation (including low vagal tone) as a component of IBS. (Gupta et al. 2002, Aggarwal et al., 1994; Karling, 1998; Smart & Atkinson, 1987; Lee 1998) As an example, Waring et al., (2004) examined adult IBS patients in comparison to healthy controls and found a significantly lower vagal tone in the IBS patients, as indicated by their significantly higher LF: HF and lower HF level. The results in the present study appear to support those found by Waring et al., (2004), in a pediatric RAP patient population. The present study also shows LF: HF to be significantly higher at time one in RAP patients than in healthy controls, which supports the hypothesis that the RAP group would have lower vagal tone at time one. These findings provide evidence for autonomic dysregulation as being a potential causal factor for RAP.

Many previous studies have established autonomic dysregulation (including low vagal tone) as a component of IBS.

(Gupta et al. 2002, Aggarwal et al., 1994; Karling, 1998; Smart & Atkinson, 1987; Lee 1998)

As an example, Waring et al., (2004) examined adult IBS patients in comparison to healthy controls and found a significantly lower vagal tone in the IBS patients, as indicated by their significantly higher LF: HF and lower HF level.

The results in the present study appear to support those found by Waring et al., (2004), in a pediatric RAP patient population.

The present study also shows LF: HF to be significantly higher at time one in RAP patients than in healthy controls, which supports the hypothesis that the RAP group would have lower vagal tone at time one.

These findings provide evidence for autonomic dysregulation as being a potential causal factor for RAP.

Previous studies (Gevirtz, 2000; Whitehead, 1992; Bassotti & Whitehead, 1994) have shown biofeedback to be successful in the treatment of IBS. Similarly, the present study’s hypothesis was supported in that HRV biofeedback appeared to be a very effective way to reduce pain. In the present study, 75% of children with RAP significant reduction in pain intensity and frequency 20% of children with RAP total elimination of pain

Previous studies (Gevirtz, 2000; Whitehead, 1992; Bassotti & Whitehead, 1994) have shown biofeedback to be successful in the treatment of IBS.

Similarly, the present study’s hypothesis was supported in that HRV biofeedback appeared to be a very effective way to reduce pain.

In the present study,

75% of children with RAP

significant reduction in pain intensity and frequency

20% of children with RAP

total elimination of pain

Treatment Efficacy The average RAP child prior to HRV biofeedback fairly severe pain 4 to 5 times/ week (e.g., severity rating of 7 on a scale of 1 to 10, with 10=most severe) The composite average child after HRV biofeedback mild level of pain severity 1 to 2 times/ week (e.g., severity rating of 2)

The average RAP child prior to HRV biofeedback

fairly severe pain 4 to 5 times/ week

(e.g., severity rating of 7 on a scale of 1 to 10, with 10=most severe)

The composite average child after HRV biofeedback

mild level of pain severity 1 to 2 times/ week

(e.g., severity rating of 2)

A positive correlation was found between decreased self-reported pain scores and decreased LF:HF in children with RAP.

A positive correlation was found between decreased self-reported pain scores and decreased LF:HF in children with RAP.

Summary 1) Mechanism ANS dysregulation may be a mechanism in etiology & maintenance of RAP. RAP group had more autonomic dysregulation at baseline versus non-RAP 2) Outcome ANS may be a mediator for improvement in RAP HRV biofeedback treatment improved RAP symptoms in correlation with improved ANS function

1) Mechanism

ANS dysregulation may be a mechanism in etiology & maintenance of RAP.

RAP group had more autonomic dysregulation at baseline versus non-RAP

2) Outcome

ANS may be a mediator for improvement in RAP

HRV biofeedback treatment improved RAP symptoms in correlation with improved ANS function