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From Surviving to Thriving:Phrenic Nerve Graft Surgery and Rehab.
Dr. Matthew Kaufman MD, FACS
The Institute for Advanced Reconstruction
Patricia West-Low, PT, MA, DPT, PCS
Children’s Specialized Hospital
Conflict of Interest
Neither Dr. Matthew Kaufman, nor Patricia West-Low have any conflict of interest in regard to this presentation
Objectives
• 1. Demonstrate awareness of appropriate candidates and the options for surgical re-innervation of the diaphragm muscle.
• 2. Identify and prioritize the multiple body systems requiring assessment and treatment post surgery.
• 3. Discuss appropriate and effective treatment strategies and sequencing.
• 4. Discuss the case of a 14-year-old athlete, surviving treatment for lymphoma, who underwent a sural to phrenic nerve graft and postsurgical rehabilitation, to re-innervate and reeducate her left hemi diaphragm after a tumor and subsequent ablation, crushed the phrenic nerve.
• Background– Introduction to pediatric phrenic nerve graft case
• Roles of the diaphragm– 3 systems– Multi-system function
• Phrenic Nerve Graft Surgery– Technical aspects– Algorithm for patient selection
• Post-operative PT examination– Participation– Function– System strengths/impairments
• Patient case– Surgical stand point– PT treatment
Back Story
• 8 year old female– C/O SOB
• Dx: “asthma exacerbation”
• Tx: Steroids & antibiotics
– Progressive SOB for 10 additional days• Seen in ER
– Oral steroids
– X-ray: Total left lung collapse
– CT Scan: 10 cm tumor on Thymus gland, also crushing L Phrenic N.
• Surgical excision of the tumor, and 2 years of chemo
Back Story
• Chemo drugs: • IV daunorubicin, IV doxorubicin, IV cyclophosphamide, IV
cytarabine and IV vincristine.• High dose methotrexate infusion followed by a leucovorin
"rescue" to save the liver and kidneys.• Intrathecal cytarabine and methotrexate.• SQ injections of cytarabine (at home)• IM Peg-Asparaginase.• oral mercaptopurine for twenty-eight days during one
phase and forty-two during another, and daily during the last eighteen months of treatment.
• oral thioguanine for fourteen days during one phase.• oral methotrexate once weekly during the last eighteen
months of treatment.
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Back Story
• “Ancillary Drugs”– High doses of oral prednisone for 35 continuous
days.
– High doses of oral dexamethasone twenty-eight straight days.
– For the last eighteen months of treatment, high doses of prednisone for five days each month.
– Multiple courses of antibiotics for upper respiratory infections
Pediatric Cancer Survivorship
• Physical Function/Activity Level
– Childhood Cancer Survivors (CCS) scored lower on tests of LE strength, the TUG and the 6MWT (Hoffman et al 2013)
– CCS nearly 2x more likely to report performance limitations (Ness et al 2009)
– CCS 1.4 x more likely to be inactive (Rueeg et al 2013)– Only 42% CCS reach healthy activity levels (Rueegg et al
2013)– High PA in CCS correlated with improved cardiovascular
profile (Slater et al 2014)– Factors predictive of decline in PA include female gender,
BMI >30 kg/m not completing high school and chronic musculoskeletal conditions(Wilson et al 2014)
Pediatric Cancer Survivorship
• Quality of Life Level
– Female survivors reports lower HRQOL in Physical and Emotional QOL subscales than males
– Female survivors ≥ 16 years of age scored lower on school QOL subscales than males
Cardio-toxicity of Chemo Drugs
– Cyclophosphamide as well as cytarabine & asparaginase have been associated with cardio-toxicity (Simbre et al 2005; Pai & Nahata, 2000)
– Cardio-toxicity may occur in 20% of patients treated with Doxorubicin and Daunorubicin (Pai & Nahata2000)
– Effects include asymptomatic ECG abnormalities, blood pressure changes, arrhythmias, myocarditis, pericarditis, Acute MI, Cardiac failure, cardiac shock and long term cardiomyopathy (Simbre et al 2005)
Complications of Left HemidiaphragmInactivity
• Dyspnea– Decreases breathing capacity by >1/3 (Elefteriades et
al 2008)• Reflux
– Decreased competence of the LES-Left crus can result in GERD (Eherer et al 2012)
– Reduced diaphragm function is a predictor of GERD (Pandolfino et al 2007)
– Micro-inhalation of reflux secretions is associated with pneumonia (Gaillet et al (2015)
Complications of Left HemidiaphragmInactivity
• Scoliosis
– Chest wall deformity and scoliosis are common among children with repaired diaphragmatic defects (Peetsold et al 2009)
– Muscle asymmetry is part of the pathogenesis of late onset idiopathic scoliosis (Grivas et al. 2002)
– Increase risk of scoliosis after chest wall resection (Glotzbecker et al (2013)
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Complications of Left HemidiaphragmInactivity
• Decreased balance and postural control
– The diaphragm has a feed forward role in postural stability (Gandevia et al (2002)
– Phrenic motor neurons contribute to both respiration and postural during challenges to posture (Hodges and Gandevia 2000)
Evidence Based Medicine
Best Available Evidence
Clinician Expertise
Patient Family Values
EBM
Roles of the Diaphragm
• Ventilation
• GI function (Pandolfino (2007); Feinsilver, 1944)
• Musculoskeletal structure/function (Grivas et al. 2002; Russell at al 2014)
• Venous return (Willeput 1984)
• Postural control (Hodges & Gandevia, 2000; Smith 2006; Hudson 2010;Hamaoui, 2010; Jansenns, 2013)
Summative Roles of the Diaphragm
The diaphragm is a respiratory muscle
The diaphragm assists the LES in inhibiting reflux
The diaphragm assists in elimination
The diaphragm impacts musculoskeletal alignment
The diaphragm assists in venous return
The diaphragm is a postural muscle
The diaphragm is a pressure regulator!!
Surgical Management of the Paralyzed Diaphragm: A Peripheral Nerve Approach
Matthew R. Kaufman, M.D., F.A.C.S.
The Institute for Advanced Reconstruction at The Plastic Surgery CenterShrewsbury, NJ
Co-Director, Center for Treatment of Paralysis & Reconstructive Nerve SurgeryJersey Shore University Medical Center
Neptune, NJ
Voluntary Clinical Assistant Professor of SurgeryDavid Geffen UCLA Medical Center
Los Angeles, CA
Clinical Assistant Professor of SurgeryDrexel University College of Medicine
Philadelphia, PA
Center for Treatment of Paralysis & Reconstructive Nerve Surgery
Jersey Shore University Medical Center, Neptune, NJwww.compellinghope.com
Regional, national, & international referral center Conditions treated
Peripheral nerve disorders (i.e. trauma, neuropathy) Sequelae of stroke & spinal cord injury
Diaphragmatic paralysis experience (Since 2007) More than 200 patients treated Well over 400 patients evaluated 4-5 new inquiries per week
Official Synapse Pacemaker Treatment Center (2014)
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Peripheral Nerve Disorders
Occipital Neuralgia/Migraine
Facial Paralysis
Cranial Nerve Injury
Brachial Plexus Injury
Diaphragm Paralysis
Upper/Lower Extremity Paralysis
Hand Injury
Perineodynia (Pudendal Neuralgia)
Lower Extremity Neuropathy
Footdrop
CNS Disorders
• Spinal Cord Injury
– Ventilator Dependency
– Pressure Sores
– Upper Extremity
• Stroke
– Dysphagia
– Hemiparesis
– Facial paralysis
• ALS
• Central Sleep Apnea
• CNS tumor
Diaphragm Anatomy
• Diaphragm
– Primary respiratory muscle
– Separates abdominal & thoracic cavities
– Contracts and flattens with inspiration
The Muscles of Respiration
Principal Respiratory MusclesIncrease thoracic dimensions
Diaphragm External intercostal Internal intercostal
Accessory Respiratory MusclesActivate during exercise, stress response, diaphragm paralysis
Sternocleidomastoid Scalenes Other: trapezius, serratus, latissimus, pectoralis
Diaphragm Innervation
• Phrenic Nerve
– Originates from C3-C5
– Motor innervation to diaphragm
– Sensory fibers
• Pleura
• Pericardium
• Abdominal components
Ventilator DependencyImpact On the Diaphragm
Compared 14 brain dead donors on PPV to 8 controls
18 hours of PPV causes marked atrophy
57% decrease Type 1 slow twitch
Active muscles atrophy faster
Inactivity leads to oxidative stress & proteolysis
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Diaphragmatic ParalysisEtiology
Peripheral
Iatrogenic Surgery
Anesthetic Blocks
Chiropractic
Trauma Blunt
Penetrating
Neuropathy / Neuromuscular
Viral / Idiopathic
Central
Spinal Cord Injury
Cervical Radiculopathy
Central Hypoventilation Syndrome
Tumors
Neurodegenerative conditions
Diaphragmatic Paralysis
Treatment Options Pulmonary rehabilitation
Diaphragm retraining therapy
CPAP/BiPAP
Mechanical ventilation
Plication of the diaphragm
Diaphragm Pacemaker
Phrenic Nerve Surgery
Diaphragm Muscle Replacement Surgery
Diaphragm Pacemakers• Indications
– Ventilator dependency• Cervical tetraplegia
• ALS
• Stroke
• Cord compression
• CNS tumor
• Central sleep apnea
– Off label use• Unilateral diaphragm paralysis
• Intractable hiccups
• Diaphragm flutter/myoclonus
Diaphragm PacemakerHistory
High freq phrenic stim Glenn 1976
Low freq phrenic stim Glenn 1984, Elefteriades 2002
Increased survival Carter 1993
Pacemaker + Nerve transfer Krieger 2000
Long term successful pacing Elefteriades 2002
Diaphragm stim Onders 2004, DiMarco 2005
Prospective comparison Hirschfeld 2008
Diaphragm PacemakerDemonstrable Benefits
Quality of life
Morbidity & mortality
Healthcare costs
Romero-Ganuza et al. Med Intensiva 2011
Diaphragm PacemakerWhen to Refer?
• As early as possible when non-invasive methods have failed or stalled (< 1 year)
• Especially when:– C1-3 or multilevel cervical tetraplegia
– EMG demonstrates uni- or bi-lateral phrenic neuropathy
• Even consider in certain less severe cases to “bridge to independent respiration”– Onders et al. J Trauma Acute Care Surg 2014
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Diaphragm PacemakerWhich Device?
Synapse Laparoscopic or VATS
Wires emerging (FDA application for implantable)
Direct muscle stimulation
Requires IRB for humanitarian use
Good Customer service
Not MRI compatible
Outdated technology
Demonstrable efficacy
Avery Cervical approach or VATS
All implantable
Transmission through applied antennae
Fully FDA approved
Mediocre Customer service (Improving)
Not MRI compatible
Outdated technology
Demonstrable efficacy
Diaphragm Pacemakers
• Up to 20% of attempted pacemaker implantation cases are aborted due to failure to stimulate
– Q: Why?
– A: Loss of phrenic nerve integrity
• Wallerian degeneration along the phrenic nerve(s)
• Progressive diaphragm muscle atrophy
Diaphragmatic Re-Innervation in Ventilator Dependent Patients with Cervical Spinal Cord Injury and Concomitant Phrenic Nerve Lesions
using Simultaneous Nerve Transfers and Implantable NeurostimulatorsKaufman et al. J Reconstr Microsurg, June 2015
Purpose A surgical treatment to reverse ventilator dependency
in pacemaker failures or absent phrenic nerve integrity
Demographics (N=14) Mean age=33 yrs. (range 10-66 yrs.) Injury level
C1 (2), C2 (2), C3 (1), C4 (2), Multilevel (7) ASIA A(13), ASIA B(1)
57% failed prior pacemaker attempt Time from injury to surgery: 34 months (range 6-90
months)
Diaphragmatic Re-Innervation…using Simultaneous Nerve Transfers and Implantable Neurostimulators
Kaufman et al. J Reconstr Microsurg, June 2015
Methods Inclusion Criteria
Cervical Tetraplegia
Ventilator Dependency (>6 mos.)
EMG/Nerve Conduction Studies Absent phrenic nerve conduction
No voluntary motor units detected in diaphragm
Available donor nerve(s) (i.e. spinal accessory, thoracodorsal, intercostal)
No active respiratory infection
Good cognitive function
Adequate family support & nursing care
Diaphragmatic Reinnervation…using Simultaneous Nerve Transfers and Implantable Neurostimulators
Kaufman et al. J Reconstr Microsurg, June 2015
Methods Parameters for assessment Age, Sex
Level of injury, ASIA classification
Time from injury to treatment (mos.)
Time from treatment to re-innervation (mos.) Trans-telephonic monitoring (TTM)* biphasic activity
Average time pacing (hrs.)
*Auerbach A, Dobelle W. Transtelephonic monitoring of patients with implanted neurostimulators. The Lancet.1987;329(8526):224-5.
Diaphragmatic Reinnervation…using Simultaneous Nerve Transfers and Implantable Neurostimulators
Kaufman et al. J Reconstr Microsurg, June 2015
• Outcomes
– 13/14 (93%) successful diaphragm re-innervation
– Time from surgery to re-innervation: 7 mos. (range= 3-18 mos.)
– 8/13 (62%) achieved sustainable pacing (>1 hr. day)
• Mean= 10 hrs. (range >1-24 hrs.)
– Two patients recovered spontaneous respiratory activity (no pacemaker, no vent)
– Treatment resulted in a 20% (p<0.05) reduction in vent. dependency
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Diaphragmatic Reinnervation…using Simultaneous Nerve Transfers and Implantable Neurostimulators
Kaufman et al. J Reconstr Microsurg, June 2015
• Outcomes
– No intra-operative complications
– One patient developed bilateral effusions post-op requiring drainage
– Mean f/u=16 mos. (Range= 6-40 mos.)
Two month follow-up
66 y.o. male, C4,
ASIA A
Nine month follow-up
Diaphragmatic Reinnervation…using Simultaneous Nerve Transfers and Implantable Neurostimulators
Kaufman et al. J Reconstr Microsurg, June 2015
• Benefits of ventilator weaning are dramatic
• Current practice standards seem to under-utilize surgical options for weaning failures, or delay initiation
• Estimated 20-25% of potential pacemaker candidates will never be treated or will undergo failed procedures likely due to “double lesions”
• Consideration of a treatment algorithm that includes the option of phrenic nerve surgery when necessary
• Timing appears to be very critical for pacing success with nerve surgery
– 12 months or less is optimal
Diaphragmatic Reinnervation…using Simultaneous Nerve Transfers and Implantable Neurostimulators
Kaufman et al. J Reconstr Microsurg, June 2015
Limitations
Rapid and progressive diaphragm muscle atrophy = limited clinical success (incomplete weaning)
Electrical recovery without clinical recovery
Evaluation Of Current And Future Surgical Treatment Options For Diaphragmatic Paralysis And Ventilator Dependency In High
Cervical TetraplegiaKaufman et al. (ISCoS/ASIA 2015)
• How do we define progressive diaphragm atrophy?
– Electrodiagnostics: Absent voluntary motor units
– Ultrasound measurements: <2-3mm maximal thickness
Ventilator Weaning in SCIDealing with Progressive Diaphragm Atrophy
Current & Future Directions
• Prevention
– Early electrical stimulation to prevent or delay irreversible muscle atrophy
• Treatment
– Diaphragm muscle replacement surgery when irreversible degeneration
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Ventilator Weaning in SCICurrent & Future Directions
• Peripheral Nerve Stimulation• Preventing irreversible
muscle atrophy– J Neurophysiol, 2015
Ventilator Weaning in SCICurrent & Future Directions
Diaphragm Muscle Replacement Surgery
Transferring innervated, vascularized muscle (rectus abdominis/latissimus dorsi) into the atrophic diaphragm
Implanting a pacemaker into the transferred nerve-muscle unit
Diaphragm Replacement Surgery for SCI
.
First Diaphragm Replacement using Innervated Rectus with Pacemaker for SCI
5/8/2015
22 year-old female, C2-5, ASIA A (May 2014, MVAComplete ventilator dependency
Failed attempt at Synapse pacemaker
ICF Model Starting From the “End Game”
Participation Function Impairment
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“Physical therapy is a health profession whose primary purpose is the promotion of optimal health and function. This purpose is accomplished through the application of evidence-based principles to the processes of examination, evaluation, diagnosis, prognosis, and intervention to prevent or remediate impairments in body structures and function, activity limitations, participation restrictions or environmental barriers as related to movement and health.”APTA House of Delegates, 2012
Post-op Examination
• Integument
– Mobility of all scars in all directions
• How does CT mobility affect symmetry?
• Is scar tissue limiting chest wall expansion?
– Pain can have an impact on internal scar tethering ~(Esposito et al 2013)
– Scars can tether in remote areas ~ (Massery and Vicari 2015)
Post-Op Examination
• Musculoskeletal– Rib mobility
• Ribs 8-10 may be limited due to diaphragm pull• Ribs 4-7 may be limited due to intercostal coupling
– Spinal symmetry• Asymmetrical diaphragm pull
– Upper quarter screen• Effect of pre-surgical breathing pattern• Effects of rib mobility limitations
– Lower quarter screen • Effects of graft site sensory impairments (strength, power,
agility)
Post-op Examination
• Neuromotor– Diaphragm activation
• Look and feel• Supported and unsupported positions• Diaphragm excursion
– Diaphragm intercostal coupling• Watch for intercostal retraction • Lateral chest wall excursion
– Diaphragm/Intercostal muscular endurance• How long can they continue to use the involved side
diaphragm before it fatigues?
Post-Op Examination
• Cardio-pulmonary
– Pre-surgical hx
– Meds
– Breathing pattern, sequence and rate• At rest • With aerobic challenge
– O2 sats. during Cardio-pulm. challenges
– Get as close as possible to the activity they hope to return to
Post-op Examination
• GI System
– Reflux• Frequency
– Constipation• Frequency and ease of BM
– GI Meds?• Anti reflux• Laxatives
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Post-op Examination
• Postural stability
– Can the patient use their diaphragm to breathe while performing activities that challenge their postural stability?
– Timed Unilateral Stance, Pediatric Berg, TUG, Timed floor to stand, Timed shuttle run
Post-op Examination
• Sensory
– Proprioceptive awareness in the graft side Lower Chain
– Reactive postural control
– Unilateral stance eyes open versus eyes closed
• Diagnosis
– Medical Dx:• S/P phrenic Nerve graft
• S/P Lymphoma tx
– PT DX: • Impaired muscle performance Impaired ventilation
impaired aerobic capacity, impaired joint mobility,
• Muscle weakness
• Impaired sensory integrity
Treatment
• Prioritize and treat impairments as they relate to function
• Treat multiple impairments simultaneously
• Track the results of your treatments objectively
MS NM CP INT IO SP
Body Systems
Primary Pathology
Progression of impairments
Current Problems
Prioritize the Impairments
Tests And Measures
Interventions
Body Systems MS NM CP INT IO SP
PrimaryPathology
PhrenicNerve Paralysis
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Body Systems MS NM CP INT IO SP
Progression of impairments
3 1 2 5 4 6
Body Systems
MS NM CP INT IO SP
Current Problems
Shortening left side
Left Ribmobility
Right lateral trunk flexion
Left rotation
Decreased diaphragm Strength
Altered scapulo-humeral mechanics
Altered motor plan for diaphragm useAltered coupling of diaphragm and intercostals
Paralyzed left vocal fold
Altered balance and postural control
Impaired aerobic capacity
Impaired endurance
SOB with moderate exertion
O2 Sats in response to moderate cardio-pulmchallenges
Speed of HR recovery after cardio-pulmchallenge
Moderately decreased mobility of chest tube scarsSignificant adherence of tissues in the left lower leg
Reflux
Constipation
Persistent nausea
Alteredprop left ankle/LE
Altered Kinesth.Awareness
Left hemi-body
Body Systems
MS NM CP INT IO SP
Prioritize the Impairments
1 2 4 3 5 6
Body Systems
MS NM CP INT IO SP
Tests And Measures
Dynamometry
Lateral trunk flexion ROM
Shoulder ROM
DE, CWE, PBERG, TUG, TIMED SHUTTLE RUN
O2 sats.RR Rate/recovery
PFT
RefluxfrequencyBM frequencyMedication use
US EO/EC
MS NM CP INT GI SP
Interventions Rib 4-10 mobilizations
Yoga postures
Closed chain trunk, LE and UE strengthening
ConcentricCW and abdominal strength for airway clearance
PNF Controlledstretch to left diaphragm and left lateral CW –progressing from supported to unsupported
Inhibition of the right diaphragm
Yoga-postures and breathing practices
IMT on unstable surfaces while moving
Sport Specific NM retraining of inspiratory mmPNF to retrain scap-humeral rhythm
IMT-Breatherand Power breathe
O2 sat monitor during progressive challenges on Elliptical trainer, TM, simulated swimming
Ventilatorystrategies for swimming, throwing
CT mobilizationlateral and deep front line
IMT
Timing of meals with travel/sleep and PT
Proprioceptive re-training
Balance trainingTake Home Messages
• The diaphragm impacts multiple systems and functions-treat them all
• Watch and prevent for secondary impairments
• EBM has 3 parts, don’t ignore patient/family values
• Keep learning. Let your curiosity keep pulling you forward. BE A TRAILBLAZER!
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