Beyond Traditional PAP therapy Brian Gaden BSRT, RRT, RPSGT Sleep Consultant Philips Home Healthcare Solutions

Objectives Review of pathology behind the need for ventilation Central Sleep Apnea Overlap Disease Obesity Hypoventilation Neuromuscular Disorder Describe the use of Servo ventilation for patients with Complex and Central Apnea Describe the use of BiPAP S/T with AVAPS for patients with pulmonary disorders Describe the titration methods for patients requiring NIV

Sleep Impact on the Respiratory System Cerebrum Brain Stem Spinal Cord Controller Sleep Impact on the Respiratory System Effector Respiratory Muscles Airway Vessels and Function Gas Exchange Result This introductory slide highlights the major factors that may be impacting the respiratory system. The brainstem and the ability to fire an impulse to stimulate breathing. This maybe a problem with patients who have idiopathic central apnea, patients who are on high levels of pain medications or patients with a history of stroke. The area the brain impacts is the respiratory system including airway diameter as well as muscles that move the system. If the system is diseased (due to airway destruction or restriction, muscle function negatively impacted due to REM sleep paralysis or neurological disorders like ALS) as a result it impacts Gas Exchange. Once gas exchange is impacted, then a feedback loop to the brain thru the chemorecptors or mechanicoreceptors in the body will impact the feedback to the brain. This may also be the problem with patients who have complex apnea. You will cover this further. Mechanicoreceptors Chemorecptors Sensors/Feedback

Sleep Disordered Breathing- Physiology review

Factors that may impact the function of the brain during sleep Cerebrum Brain Stem Spinal Cord Controller Factors that may impact the function of the brain during sleep Change in blood flow Drug administration Change in cortical inputs Disease of the Cerebrum/Brain Stem/Spinal cord Loss of motor neurons due to disease Severing of the motor neurons This graphic outlines the factors that may impact the way the brain functions and fires at night while the patient sleeps: changes in blood flow due to perfusion and postional changes in the patient as they sleep. Drug administration thru pain medications or medications they patient may change, can impact the respiratory drive while the paitent sleeps. Changes or damage to the brain due to disease (ALS, dementia, stoke) or loss of motor neurons going to the peripheral

Impact of the respiratory muscles and airway vessels during sleep Effector Respiratory Muscles Airway Vessels Function Impact of the respiratory muscles and airway vessels during sleep Any change can directly impact the respiratory system Positional changes Damage or loss of the respiratory muscles will Damage to the airway support system Damage to the airway vessels Damage or loss of blood supply This area is focuses on the site which is moving by the brain stem stimuli which is movement of gas into the lungs thru the airway and also movement of the muscles to pull air into the lungs. During sleep muscle fucntion will change as well as positioning of the lungs and blood supply can impact the patient. Patients with ALS have issues with this area due to loss of muscle strength due to interrupted signals from the brain, also COPD and restrictive disorders may also have problems here due changes in the airway support and airway vessels.

Problems with Gas Exchange during sleep Result Problems with Gas Exchange during sleep There can be several reasons for gas exchange to not occur: Poor perfusion of the pulmonary system Positional changes in perfusion Destruction of the alveolar sacs due to underlying disease Lack of ability to move gas into the alveolar sacs Muscle loss Conduction problem with nervous system impulse Eventually changes in the respiratory mechanic’s, respiratory system or brian system will negatively impact gas exchange. The impact on gas exchange is what arouses a patient from sleep as well as stimulates the nervous system to respond to stimuli. The way it does that is thru the feedback system known as the chemoreceptors and mechanico receptors.

Systemic monitoring systems that influence ventilation and oxygenation Mechanicoreceptors Chemorecptors Sensors/ Feedback Systemic monitoring systems that influence ventilation and oxygenation Central Chemoreceptors Found inside of the brain to regulate and stimulate the respiratory system in the brain stem Feedback system is thru acid/ carbon dioxide levels in the brain and body Peripheral Chemorecptors Chemical Receptors found on the aortic arch and carotid artery Send impulses to the brain stem to change the respiratory rate and pattern Respond to both oxygen and carbon dioxide levels There are 2 main systems for responses back to the brain to regulate breathing is thru central and peripheral chemoreceptors. There are also stretch receptors in the lungs that need to be activated as well to maintain stable breathing. IF any of the feedback systems are not triggered the patient will increase their rate. On the other hand, if the feedback system is over stimulated, the patient may stop breathing or may start cycling breathing (hypoventilation to hyperventilation).

What happens in the lungs?

One thing to remember The primary drive to breathe is based upon the CO2 level in the blood. The secondary drive to breathe is based upon the O2 level in the blood. If CO2 levels are too high, the body responds by increasing ventilation to get rid of excess CO2 If CO2 levels are too low, the body responds by decreasing ( or stopping ) ventilation to allow CO2 to build back to normal levels

Effect of Sleep on Normal Respiration 20 – 50% The following areas are normally impacted during the sleep process causing a slight variation of a patients breathing pattern, oxygen levels and carbon dioxide levels. For a normal patient, these drops can easily be compensated for over a night. For the patient with COPD or OSA or both, the effects are more compounded due causing an abnormal response by the body during sleep. For a normal patient, cortical inputs to the Reticular activation center of the brain decreases, chemorecepotor sensitivity decreases by 20 – 50%, respiratory motor neurons transmit less impulses due to less activity by the respiratory muscles and brain activity, RR generally remains the same but tidal volumes will decrease due to either increased airway resistance may increase due to body position or drop in muscle stimulation, this causes ventilation to decrease by 0.5 – 1.5 LP. ABG changes due to Decrease in Min. V 0.5 – 1.5 LPM McNicholas, Chest 2000; 117:488-538

Normal Changes During Sleep Decrease in chemoreceptor sensitivity Both oxygen and CO2 by 20 – 50% Reduction in Alveolar Ventilation due to decrease in Reticular Activation Center activity Body position & increased airway resistance Decrease in tidal and minute volume Sum total of physical change causes the following for a normal patient : Increase PaCO2 - 2 – 8 mmHg Decrease PaO2 - 3 – 10 mmHg Decrease SaO2 - by 2% For a Normal Person during sleep the changes that occur are due to primarily 4 items: Decreased activation of the brain center (Reticular Activation Center), increased airway resistance, decrease in metabolic rate (by 10 – 15%) and decreased chemosenstivity for oxygen and carbon dioxide (by 20 – 50%). As a result of these 4 items, the body has a reduction in alveolar ventilation (by 0.5 – 1.5 LPM) causing a change in the patients areterial blood gases. For a patient with normal lungs and normal sleeping patterns, the effect is a drop in oxygen saturation by ~2%, a drop in oxygenation by 3 – 10 mmHg, and an increase in arterial carbon dioxide levels by 2 -8 mmHg. McNicholas, Chest 2000; 117:488-538

The complicated world of sleep disordered breathing Vast majority of SDB patients typical OSA profile 80 – 90% OSA AHI controlled by CPAP therapy Central Sleep Apnea Idiopathic Central Sleep Apnea Complex Sleep Apnea “CPAP Emergent events” Periodic Breathing (such as CSR) CO2 and Chemoreceptor issue Usually secondary to CHF Pulmonary Disorders: CO2 retention Overlap Syndrome (OSA and COPD) Restrictive Disorders Neuromuscular Disorders Obesity Hypoventilation Syndrome OSA Idiopathic/PB Complex So when talking about patients walking into the sleep laboratory, there are a variety of patients you may need to treat. This includes the majority of them being your standard OSA patient. In addition, patients may have central apnea including Complex Sleep Apnea which is OSA with emergent central apneas with treatment or periodic breathing such as Cheynne-Stokes Respiration. Lastly, there is a growing number of patients coming into the sleep center who have underlying pulmonary disorders in addition to sleep disorders. This includes patients with Overlap syndrome which includes COPD and OSA, Restrictive Thoracic disorders like kyphosis and neuromuscular disorders like ALS. Lets talk about each of them

Idiopathic Central Sleep Apnea Problem is with the controller mechanism (the brain) Can be secondary to stroke, brain injury Cause not always known Treatment is the same

Idiopathic central sleep apnea – PSG view No output from respiratory center of the brain causing lack of movement of the thorax. No movement of thorax & abdomen causes apnea Idiopathic central sleep apnea is when there is no output from the respiratory center of the brain (the medullary center) which causes lack of movement of the thorax. As a result of no movement of the thorax and abdomen, the patient stops breathing. This is an Alice screen shot of a patient having a central event. Notice there is no movement of air, thorax and abdomen.

Idiopathic central sleep apnea Cause of Idiopathic Central Apnea: The respiratory center of the brain does not fire during sleep causing periodic apnea (see below) Seen during the diagnostic night and titration night Generally seen in non REM sleep clears during REM sleep Generally seen in younger populations May appear as part of a neurological disease process or injury Relationship between chronic opioid therapy and central sleep apnea1 Impacts very small population of people Cause of idiopathic central sleep apnea: The respiratory center of the brain does not fire during sleep causing periodic apneas. This pattern is demonstrated on the PowerPoint. Notice how the patients have periods of breathing followed by times of complete cessation of breathing. Idiopathic central sleep apnea can be seen during the diagnostic night as well as the titration night. Generally seen in non REM sleep. It also has been shown to clear up during REM sleep.. Generally seen in younger populations May appear as part of a neurological disease process or injury. In a recent study, there was a direct relationship found between the central apnea index and daily dosage of methadone and benzodiazepines used for chronic pain management (Webster, et al. 2007) Twenty-four percent of patients in the study were identified as having central sleep apnea. Interestingly, Cheyne-Stokes Respiration was not observed in these patients, suggesting the mechanism for CSA due to opioid therapy is different and may be related to the direct effects of opioids on the respiratory controller. Impacts a very small population of people, estimated to be 1-2% of those in the SDB population Apnea Apnea 1 Webster,et al. American Academy of Pain Medicine 2007

Treatment recommendations for idiopathic central sleep apnea Oxygen therapy Respiratory Stimulant medications NIV BiPAP S/T Must be able to differentiate between Idiopathic CSA and Complex Apnea Treatment of idiopathic central sleep apnea may include some or all of the following: Oxygen therapy ** If the patient has significant desaturation during the night, the patient may qualify for oxygen therapy. The patient must have desaturation below 88% for 5 minutes or longer to qualify for oxygen therapy (CMS guidelines) OR 89% for 5 minutes with history of either Congestive Heart Failure (CHF), Pulmonary Hypertension (Pulm HTN), Cor Pulmonale or Increased Red Blood Cell (RBC) count. The use of oxygen therapy will help to prevent significant desaturation during central events. Oxygen therapy and CPAP therapy CPAP therapy may also be used for patients who are having a combination of central and obstructive events. The CPAP therapy may help with airway stability; the oxygen therapy will help with preventing desaturation during the night. In order to qualify, the patient must have desaturation + AHI >5 with EDS or AHI>15 without EDS (CMS guidelines). Medications have been shown to be an effective method to help control and regulate breathing at night for the patient with central sleep apnea. Two common medications used are: Theophylline 1, 3 and Acetazolamide 2, 3. Additionally, Eckert, et al., reports that “gradual dose reduction of opioid medication may improve high-dose narcotic-induced CSA”3. Remember: <2% of SDB

What is complex apnea? Complex apnea occurs with the application of PAP therapy Central apneas occur Relative CO2 drop from application of PAP therapy REMEMBER: PAP does NOT fix central events!

Complex Apneas on CPAP 7 cm H2O Cycle time for events is ~30 seconds This slide demonstrates a second patient event with complex breathing. On a CPAP of 7 cmH20 they transition from OSA to CSA with cycling events that are occurring at 30 second intervals. Pittman Slides

Complex Sleep Apnea - Characteristics Characteristics of Complex Sleep Apnea Typically emerges during titration not during diagnostic PSG Emerges with the implementation of CPAP to alleviate OSA events1 Occur at ~ 30 second intervals vs. 60-90 second interval with CSR Complex Sleep Apnea is a mixture of OSA which converts over to central apnea upon CPAP application and opening of the airway 1 Minimal data available Estimated prevalence 1/7 or ~15% of the SDB population 1 Morganthaler, et. al. Sleep 2006; 29 (9):1203-1209 The definition of Complex Sleep Apnea is Central Apneas that emerge during the application of CPAP therapy. This typically emerges during the titration night and not during the diagnostic night. As a result, complex sleep apnea is a mixture of both OSA and CSA with CPAP therapy. Some general characteristic of Complex Apnea is that they can occur at 30 second intervals which is different from other types of periodic breathing that may occur at night. Dr. Morganthalier from the Mayo Clinic identified the prevalence to be 1 in 7 patients or 15% of the sleep disordered breathing population.

Possible Cause of Complex Sleep Apnea? Theory of Complex Apnea is due to a combination of airway resistance and respiratory drive 12 Theory: once airway open with low levels of CPAP, OSA is eliminated with CPAP. The airway now allows for normal RR causing instability of CO2 receptors. With a “normal” breathing pattern, the patients brain function reads the change in CO2 and causes hypoventilation to occur. (slight change of 2 can cause instability) Hyperventilation then leads to development of central apneas causing complex breathing events Chemoreceptor issues unmasked when OSA is eliminated Due to the limited amount of research done on this type of breathing pattern, there is limited information on the reasons why this may occur in the sleep population. Several leading researchers (Dr. Sanders who is a consultant with Respironics, Dr. Magdy Younes (u-ness) along with Dr. Morgathaler have several possible reasons why this may occur: Complex ~35 sec 1 Interview with Dr. Younes & Dr. Sanders 2 Moganthaler, et.al. Sleep 2006

Treatment Strategies for Complex Sleep Apnea CPAP + Time on Therapy to reset chemoreceptors for patient Must qualify with AHI > 5 with EDS OR AHI >15 To move to AutoServo Ventilation must meet RAD criteria No improvement, try alternatives below Medications + CPAP Auto Servo Ventilation RAD policy for Complex Sleep Apnea Acetylzolamide is the medication of treatment for stability of RR

Key Strategy When performing a titration where complex apnea presents, patience is the key Usually a difficult and tedious titration In most cases, the CPAP emergent apnea will resolve with time to adjust to PAP pressure. Servo may be required if CSA persists

Periodic Breathing (such as CSR) What is the population mix? What do they look like on PSG? What is the treatment strategy for PB?

This is a sample of a patient with CSR This is a sample of a patient with CSR. They have periods of hyperventilation followed by hypoventilation. They continue to cycle with a waxing and wanning pattern thru out the night.

Periodic Breathing (such as Cheyne Stokes) Prevalence normally about 5% of patients Increase in prevalence with special populations Heart Failure (~40%-50%) Neurologic disorders (stroke) Altitude Renal Failure, Dialysis patients Characteristics Emerges in non REM sleep May resolve in REM sleep May be seen prior to study and during diagnostic study

Periodic Breathing Characteristics: waxing and waning breathing pattern Length is based on disease process causing the breathing pattern Longer events for patients in heart failure 1 (picture A) 50-70 second events of CSR then followed by normal respiration (waxing and waning of Respiration) in patients with Heart failure 1 Shorter events in those with preserved heart function 1 (picture B) 20 – 40 seconds on length with those with preserved heart function 1 Some of the characteristics of patients with periodic breathing like cheyne stokes breathing include waxing and waning breathing patterns. The event characteristic may change based on the underlying disease process. This includes patients with heart failure and cheyne stokes may have longer cycle events vs. patients with periodic breathing who have issues due to altitude, neurological disorders or renal failure ~60 sec A B 1 Thomas, et. al. Curr. Opin Pulm Med. 2005

Treatment Recommendations for PB If patient has PB due to disease process, medical management of disease will help with management of PB Medical Management of Heart Failure is KEY in treatment of CSR 1 If the patient has predominately CSR, (CSR >50%), CSA > 5, AHI CPAP Therapy1 Auto Servo Ventilation3 Bi-Level Therapy with back up rate 2 If the patient has predominately OSA (<50% CSR), CPAP should be prescribed If a patient has periodic breathing due to a specific disease process, medical management of that disease process is key in helping to stabilize or regulate the patients respiratory pattern. This is especially true for patients with heart failure. However, if the patient has an AHI > 5 with EDS or AHI >15 without EDS, they can be treated with therapy to help with this sleep disorder. As the titration occurs, if the patient has predominately CSR or Central Apneas, which are greater than 50% of the hourly events and the AHI hits the required number there are options of CPAP therapy, Auto Servo Ventilation or Bilevel therapy with a back up rate to help control not only the OSA events but also regulate the patients respiratory pattern during the central events. If the patient has predominately OSA, they should have CPAP or BiPAP S therapy prescribed to help with management of their obstructive events. 1 Javaheri, et. al. Curr Treatment Option in CV Med: 2005:7:295-306 2 Kasi, et. al. Circ. J.; 200569:913-921 3 Teschler et al, AJRCCM, 164:614-419, 2001

Complicated Patients Patients have complicated and variable breathing Auto PAP treats OSA Auto Backup rate treats CSA Variable IPAP (PS) treats periodic breathing

ASV Initial Settings EPAP min - ?? EPAP max -20cwp PS min – 0 PS max- 10 Backup rate- Auto Max pressure - 25 Be patient Document Must control leak How much leak is too much?

Central Sleep Apnea Summary Idiopathic CSA: BiLevel PAP with Backup rate Complex Apnea: PAP with patience. Servo if needed Periodic Breathing: Servo Ventilation. BiPAP Auto SV Advanced

Absolute Hypoventilation Overlap disease Obesity Hypoventilation Syndrome Neuromuscular Disease CO2 retention

Strategy: Improve ventilation Provide consistent Tidal Volume (Vt) Volume targeted pressure ventilation (AVAPS) Consistent CO2 elimination

Improving Quality of Life

COPD Overlap Syndrome A combination of OSAHS and COPD Patients with overlap disease usually have a more significant oxygen desaturation More likely to develop pulmonary hypertension CO2 retention due to hypoventilation Decrease in O2 levels are very evident on PSG

The COPD patient

Obesity Hypoventilation Syndrome Also known as “Pickwickian Syndrome” Increase in CO2 during sleep (>10mmHg) BMI usually greater than 30kg/m2. No other reason for hypoventilation such as neuromuscluar disease, restrictive thoracic disease, obstructive lung disease or interstitial lung disease Retains CO2

Obesity Hypoventilation Patient

Neuromuscular disease Progressive muscle weakness that increases over time Patient cannot ventilate adequately Example: ALS NIV required to help patient ventilate Retains CO2

Neuromuscular Disease

Pathology Overlaps coming from the Sleep Lab Obesity Hypo-Ventilation Neuro- Muscular Disorders OSA COPD – Overlap Central/ Periodic SDB The majority of patients entering the sleep lab for treatment and titration will have straight OSA. With the data from Dr. Morganthaler, 10 – 20% of patients entering with a possible diagnosis of OSA will end up with complex sleep disorders. That includes periodic breathing, and CPAP induced central apneas. With the release of Neuromusuclar guidelines, patients with several forms of neuromuscular diseases will have issues with their sleep patterns as their disease progresses. As a result, they may enter the sleep lab for treatment of these sleep disorders. In addition, patients with COPD may also be sent to a sleep lab for treatment of a sleep condition. Restrictive Thoracic Disorder Complex SDB

How do we help patients to breathe when they cannot?

Average Volume Assured Pressure Support (AVAPS) Acts primarily as a bilevel pressure support ventilator that is able to provide a constant tidal volume Automatically adjusts the pressure support level to maintain a consistent tidal volume IPAP will automatically increase or decrease to maintain set tidal volume Volume targeted Pressure Ventilation Progressive Ventilatory Insufficiency Neuromuscular Disease Amyotrophic Lateral Sclerosis COPD Positional Compromised Ventilation Obesity Hypoventilation Syndrome AVAPS is found in our BiPAP S/T platform and is a device with the ability the enable to feature that will alllow the machine to maintain a constant tidal volume if desired. The BIPAP with AVAPS acts primarily as a bi-level pressure support ventilator fluctuating between IPAP and EPAP levels. However the machine is able to adjust itself if a constant tidal volume is requested. The machine will raise it self between an IPAP min and IPAP max setting to maintain a requested tidal volume This device allows for constant ventilation for patients who may need ventilatory support with advancement of their pulmonary or neuromuscular disorder. This includes patients with COPD, restrictive disorders and obesity hypoventilation.

How AVAPS works This provides a graphical representation on how AVAPS works. By setting an IPAP min and IPAP max and tidal volume the machine will fluctuate over time to maintain the desired tidal volume set by the practitioner.

The AVAPS Initial Settings Parameters Range EPAP Start low. Adjust for Apnea IPAP min 4 above EPAP IPAP max 10 above IPAP min Tidal Volume 8ml/kg IBW. Use chart AVAPS is not a mode, but a support function that is activated within the existing S, S/T, PA and timed modes of ventilation. The Low Vte alarm indicates that the target Vte cannot be reached at the maximum IPAP. If the target tidal volume cannot be reached at the maximum pressure for a period of 1 minute, the low tidal volume alarm becomes active. Once active the alarm is reset when the target is reached for 30 seconds. It is a high priority alarm.

Titration Method for Patient on BiPAP AVAPS Continually assess ventilation through the following areas: Respiratory Rate Tidal volume (ratio between EPAP and IPAPmax but must have a large enough delta between IPAPmin and IPAPmax to maintain) CO2 levels* Continually assess oxygenation through SaO2 EPAP settings Try to maintain baseline CO2 levels throughout the night if possible When performing a BiPAP AVAPS titration, there are specific parameters you would want to monitor and adjust based on what parameter you would like to adjust. If the patient is having increases or decreases in their PaCO2, adjustment and monitoring of their respiratory rate and tidal volume (which can be impacted by the difference between EPAP, IPAPmin and IPAPmax) will help to assess ventilation along with patency of the upper airway. Make sure to maintain a large enough delta between the IPAPmin, EPAP and IPAPmax settings to allow the machine to fluctuate and provide a consistent tidal volume over time. To assess oxygenation, monitor the upper airway patency along with lung volumes. Both of these can be addressed by monitoring the SaO2 or SpO2 settings along with EPAP levels or oxygen administration through the system. * If applicable

Be Patient! Break old habits!

AVAPS Strategy Be patient! Titrate EPAP to overcome obstructive apnea Set Tidal Volume properly Monitor patient and document Control leak

Two Different patient groups Absolute Hypoventilation patients AVAPS Overlap disease Neuromuscular disease OHS Central Sleep Apnea Periodic Breathing Idiopathic CSA Complex CSA Servo

Take Away Points AVAPS- you must titrate EPAP Monitor ventilation IPAP min 4 above EPAP Must control leak! Servo- EPAP is auto titration Be patient! PS min is 0 Must control leak!

You might be feeling like this..

Resources Brian, Jerry, Tom, Jeff Andrew and Ben Matt, Brian, Dax Mark, Tom, Darryl The TEXAS team!

Thank you