Which PAP device to which patient?

Which PAP device to which patient? Claudio Rabec, MD FCCP Service de Pneumologie et Ranimation Respiratoire Centre Hospitalier Universitaire de Dijon

The international classification of sleep disorders ( ASSM, ICSD2, 2005)Medical conditions

Parenchymal Neuromuscular Thoracic cage

Adult

PediatricOverlap: COPD + OSAOHS + OSA

1Normal inspirationSaO2

Flow

Thx

Abd

HypoventilationSaO2

Flow

Thx

Abdor

Rhytmogenesis failure (central apneas)1) Blunted ventilatory driveSaO2

Flow

Thx

Abd

SaO2

Flow

Thx

AbdRhytmogenesis failure (central apneas)2) Ventilatory instability

UA obstruction(obstructive apnea)SaO2

Flow

Thx

Abd1

SBSBSBCPAPSB NIVSB PS

Abnormal respiratory events during sleep Apneas Hypopneas RERA Obstructive, central, mixed

+ Clinical signs

90 % of sleep apnea patients have an obstructive form(0SA)

Normal flowFlow limitationComplete Obstruction

Episodic asphyxia Sleep fragmentation Intermittent hypoxemia Sympathetic hyperesponsiveness Episodes of intrathoracic depression Oxydative stress/endothelial dysfunction Sleepiness Daytime fatigue Vascular complications

OSA-related morbidityCardiovascular morbidityNeurovascular morbidityHypertensionArrhytmiasMotor vehicle and working accidents

Fixed CPAPAuto CPAPCflex /EPR Alter CPAPBilevel devicesSevere OSATherapeutic options

CPAPHow it works?

CPAP: How do it works? CPAP Pneumatic splint Presurize and stabilize UA Additionaly increase FRC

obstructivemixedsome centralTreat apneas and hypopneas Sometimes improves hypercapnia

Potential mechanismsTreat respiratory events reset ventilatory driveIncrease FRCCounterbalance AutoPEEP (mainy in COPD)Normalize UA function

Immediate effectsImproving sleep architectureReducing arousalsReducing flow limitationReducing ou abolishing nocturnal respiratory events

Long term effectsImprovement in daytime alertnessNormalization of sleep qualityReduction of risks of motor vehicles and working accidentsQuality of life improvementReduction in risk of cardiovascular and neurovascular accidentsImproving survival?

Stradling Thorax 2000

Before CPAPPepperell Lancet 2002After CPAP1) Hypertension

2) Secondary stroke preventionMartinez Garcia; Chest 2005

3) Cardiovascular morbidity

4) Sleepiness

5) Traffic accidentsTeran Santos, NEJM 1999

CPAP effective pressureGoalsReducing arousals Normalising sleep architectureNormalizing flow Reducing ou abolishing nocturnal respiratory eventsTools Manual titrationFull or "Split night"Hoffstein formulaAutoCPAP devices

What is an autoCPAP?Auto CPAP machine (APAP) is a device commited to deliver a variable pressureat a customized, regularly adjusted levelbetween a pre established rang Designed to increase pressure in response to predetermined respiratory events

Use sophisticated algorithms to detect pressure requirements

Rationale of AutoCPAPAn individuals pressure profile varies over time

Over the same nightBody positionSleep State (REM vs. NREM)

Over different nightsNasal congestionAlcohol and sedative useSleep deprivation

Fixed pressure does not accommodate for these changes

Overnight

over different nights

APAP: some main questionsWhat is the better signal to detect events?

The method used to evaluate this signal is appropriate?

Is there an interest to reduce pressure level overnight ?

How an APAP works? Two different targets

FlowAirway resistancePneumotachForced oscillation technique

How an APAP works?1) Flow

Estimating airway resistance by FOTPrinciple: to send high frequency - small pressure oscillation to test airway pattencySymetric pattern: Airways closedAsymetric pattern:Airways open

Flow vs combined flow + FOTDuring partial airway collapsusPTG (flow target) is able to responde toSnoringFlow limitation (then to react only to hypopneas with flow limitation)

Flow alone vs combined flow + FOTDuring complete airway collapsusThere is not flow how to classify apneas?Airway resistance Useful for differenciate central from obstructives apneasAPAP devices combining PTG +FOT could apriopratelly respond To snoringTo flow limited hypopneas Only to obstructive apneas

S9 Autoset (Resmed) FOT algorhytmeWaiting timeFOT signal sent (4 Hz, 1 cm H2O)Exploringairway pattency

Closed airwayFlowMask pressureSymetric pattern

Open airwayFlowMask pressureAsymetric pattern(cardiac oscillations)


Is the method used to evaluate this signal appropriate?

Are all APAP equally effective?


Principe : tester les machines sur banc de test boucle ferme

APAP: the same concept but different algorhitmes

Farr, AJRCCM 2002

APAP testing in the clinical setting

Some APAP raise even in normal subjectsMwenge ERJ 2011Good news!

APAP: which applications? (AASM) AutoCPAPs could be used for two main purposes:

Determining effective pressure TitrationTo determine a single fixed pressure suitable for home treatmentOnce therapeutic pressure is determined (90-95th percentile pressure) treatment can commence with a conventional CPAP

Long term home treatmentVariable pressure delivered on overnight and daily basis

Determining effective pressure RationaleManual CPAP titration needsA second PSG to verify effectiveness of choosen pressureAn available trained sleep technologist during the night only possible in specialized sleep labs inappropriate for a high prevalent diseaseMorevoer, no clear standardized procedure to titrate CPAP overnight Less and less applied

Automatic titration using an APAPClinically validated with several devicesNo significant differences between the optimal CPAP level achieved with full PSG or with auto-CPAP.(Teschler H ARJCCM 1996, Lloberes, AJRCCM, 1996)Long-term CPAP efficacy and compliance similar for the two methods (Stradling JR, Thorax 1997; Teschler H, ERJ 1997, Gagnadoux F, Sleep 1999).Allows to perform home titration during several nights (reflects better real life)Cost-benefit approach: allows to optimise OSA management (Teschler H, AJRCCM, 1996)

Teschler H, AJRCCM, 1996

APAP titrationLimits and risksLimitsPatient that dont slept or that awakens frequently during titration nightMajor leaks Presence of non obstructive respiratory sleep disordersRisksCaution if unstable cardiac failure!


Is the method used to evaluate this signal appropriate?

Are all APAP equally effective?


Long term APAP treatment:Theoretical advantagesImproving toleranceImproving complianceReducing mean overnight pressure

ResultsThere were no differences in compliance, clinical symptoms or QOL scores, and similar clinical and PSG improvements were seen in all groups

ConclusionsAutoCPAP is equally as effective as fixed CPAP for long-term home treatment in severe SAHS patients.

, Ayas Sleep 2004 (mta-analysis) Less mean pressure .but same compliance and same AHIand also same ESS

APAP as a long term treatmentLimitsMore expensive and more complex (more complex is not bettermake it easier!)APAP chases after events (higher residual AHI)Pressure variations could awake patientIneffective if leaks or fragmented sleepCaution if cardiac failure

Intelligentuse of APAP for long term treatmentPositional OSA

Large pressure variations overnight or over several nights

High effective pressure

Patient not tolerating CPAP (Hukins C, Sleep 2004, Marrone Sleep Med 2004)

Low CPAP compliance

Some alter CPAP: only gadgets? Expiratory pressure relief Rationale: As CPAP deliver a continous positive pressure during whole breathing cycle, it may be difficult to fully exhale against expiratory pressure

Goal: Reducing pressure at the beginning of exhalation and returning to therapeutic pressure just before inhalation

Different trade marks offer this modification in expiratory pattern: Cflex (Philips Respironics), EPR (Resmed), softPAP (Weinmann), eAdapt (Breas)

This novel setting could be applied during either fixed CPAP or APAP mode

Cflex, EPR, etc

What about published data?Same quality of sleep, same efficacy. No or little difference in compliance. Not significant difference in pattient preference (Mulgrew Sleep Breath 2007, Marshall Sleep Breath 2008, Aloai Chest 2005, Dolan Sleep Breath 2009, Nilius Chest 2006)

Better compliance in low CPAP users (Pepin Chest 2009)

And still more.. A-Flex (Philips Respironics)Rationale: in addition to provide pressure relief at the beginning of exhalation, this tool also softens the pressure transition from inhalation to exhalation Goal: matching pressure delivery to the patients entire breathingNo validation study until now

Bilevel that works both in fixed and APAP mode In fixed mode, the physician determines EPAP and IPAP In APAP mode, level of pressure support and EPAP can vary If a snore or apnea is detected, the system raise EPAPIf a hypopnea is detected, the system raise IPAP (Sanders, Chest 1990)No backup respiratory rate. Only S mode

Caution: No comitted to ventilate hypercapnic patientAnd still more..: The bilevel auto sleep Bipap auto with Bi flex (Philips Respironics)

Some concept as Bipap Auto But in this device only EPAP can vary.The physicians set a fixed IPAP and a window of minimal and maximal EPAP (as an APAP)This device reacts varying EPAP level overnight by combining flow pattern and FOT technology to detects eventsAs Bipap auto, this device dont allow to set RR backup and is not comitted to treat hypercapnic respiratory failureAnd still more..: The bilevel auto sleep S9 Auto25 (Resmed)

Alter CPAPs: cautious optimismEven if using very sophisticated algorhytms, these devices did not show comparative advantages over CPAPSome points about the behavior of these devices in the clinical setting need to be clarified (i.e response during leaks and central events, induction of asynchronies, consequences on sleep qualityThey need independient bench and clinical validation

Bilevel devices to treat sleep apnea

Is there a place?

The patient decides

When he begin to breath

How much he breaths Respiratory rateInspiration durationTidal volume

How he breathsInspiratory flow

Spontaneous breathing

Muscle pumpPressure needed to deliver a Vt

VentilatorPressure needed to deliver a Vt

Muscle pumpVentilatorPressure needed to deliver a VtInteraction

Service de Pneumologie et Ranimation RespiratoireGrowing inspiratory effortControlled cyclearousalmicro veilDeb

PrP sustThoAbd

Oesoph

SaO2

fuiteC4A1C3A2C3O1EOG1EOG2EMGPatient ventilator asynchrony

Service de Pneumologie et Ranimation Respiratoire

Treatment of OSAIn summaryUntil now fixed CPAP is the reference to treat OSA

Concerning APAP Good alternative to manual titrationCould be useful as long term treatment in some conditionsHigh effective pressurePositional OSAOvernight and night to night variationCPAP intolerance?



Adult


Central sleep apnea Characterized by complete or partial reductions in central neural outflow during sleep that lead to complete or partial cessation of airflow

Infrequent 50% of the events are central ones

Central sleep apnea2 differents entities

Hypercapnic CSABlunted ventilatory drive: Idiopathic central apnea

Normo-hypocapnic CSAVentilatory drive unstabilityPeriodic breathing

Hypocapnic CSA (periodic breathing) CausesHearth failureHigh AltitudePulmonary hypertension (Shultz ERJ 2002)Renal failure (Markou Lung 2006)Stroke and other neurological conditions

OSACentral Sleep apnea(Periodic Breathing)(33 50%) Combined OSA +CSAPrevalence of SDB in severe hearth failure 50% (90% pure or predominant CSA)Prvalence dinsuffisance cardiaque: 1% des adultes (2.5 millions en UE + USA)

Cheyne StokesNo Cheyne StokesNeed to treat sleep apnea in heart failure!

How to treat periodic breathing?Stabilizing heart failureNocturnal oxygen therapyCPAPAssisted servo ventilationNon invasive ventilation (Bilevel or volumetric)Others (drugs, CO2, resynchronisation, transplantation)

Possibility of undesirable hemodynamic effectsIf LVEF very lowIf pressure very high CPAP: How it works in periodic breathing?

Alternative modes to treat periodic breathingRationaleTo provide a more pathophysiollogic treatmentTo better control CSRTo target central eventsNot to overventilate crescendo phases

AlternativesIntermittent positive pressure ventilationAdaptative servo ventilation (ASV)

IPPV: anecdotal - Volumetric mode (Willson Thorax 1998) 11 pts.AHI reductionNo QOL improvingPoor tolerance

- Barometric mode (Bilevel) Willson (ERJ 2001) 9 ptsAHI reductionImprovement of sleep quality

Kohnlein (ERJ 2002) 16 ptsAHI reductionImprovement of sleep quality

Potential worsening of central apneas or glottic closure induced by NIV (Johnson Chest 2005)

Adaptative servo ventilationHow it works?Basically provides a servo-controlled variable pressure support level to ensure a baseline degree of ventilatory support superimposed to a degree of EPAP levelSubjects ventilation is servo-controlled to moving around a target ventilation based on estimation of average tidal volume or average peak flowAuto or setted backup respiratory rateSome devices allow also to vary EPAP pressure in response to upper airway pattency variation (APAP algorhitm)

Adaptative servo ventilation

Three different devices, three different algorhytms: Autoset CS (Resmed): Fixed EPAP, variable IPAP Servo-controlled to equal a moving target ventilation of 90% of the long-term average ventilation (time constant 3 minutes)BiPAP AutoSV 2 (Philips Respironics), Variable IPAP and EPAPPeak flow is monitored over a moving 4 minute window. At every point, algorithm calculates an average peak flowSomnovent CR (Weinmann). Variable three level pressures EEPAP, EPAP, IPAPSupposed not react to mean spontaneous ventilation, but to adjust tidal volume on a breath by breath basis

ASV: How it works?Regulating pressure support levelPressureFlow

SaO295%85%EMGEOGEEGThoraxAbdomenFlow60 secApnesDsaturationeveilsNo treated

Falling asleep..

SaO295%85%EMGEOGEEGThoraxAbdomenFlowStabilized breathing during sleep60 sec150Press

Have in mind to find the good EPAP level! CSA is rarely pure and frequently combined with OSA Polygraphy under ASV is needed to establish the EPAP level needed to stabilize UA and prevent obstructive apneasThxAbdFlowPressSaO2IPAP raisesObstructive eventASV with fixed EPAP

Sometimes theory dont match real lifeThen, the solution is to choice a device able to automatically vary EPAP level? (APAP algorhytm)

Obstructive eventThe device raises IPAP instead of EPAP.ThxAbdFlowPressSaO2ASV with variable EPAP

Same patient, same ventilatory mode, same event, some differenceThxAbdFlowPressThxAbdFlowPress

Teschler, AJRCCM. 2001

Javaheri, Sleep 2011

Hypercapnic CSA Causes

EtiologiesCongenitalCentral congenital hypoventilation(Ondine course)AcquiredCNS damage

TreatmentIntermittent positive pressure ventilation



Adult


Intermittent positive pressure ventilationBarometricVolumetric(Switch to CPAP)+/- nocturnal oxygenSleep related hypoventilation (with or without sleep apnea)-Therapeutic options-

What is a bilevelPS + EPAP = IPAP (+ backup respiratory rate)

EPAP + Pressure support +/- RR backup EPAP + PS = IPAP

Hypothesis:EPAP to treat obstructive apneasPS to treat residual hypoventilation Bilevel positive pressure ventilationHow it works?

First: To find the good EPAP levelKeep the airway open!ThxAbdFlowPress

Second: Find the appropriate ventilatory levelKeep the airway open!ThxAbdFlowPressSaO2

Bi level Positive Airway PressureSometimes, just an overnight SaO2 is sufficient!

PS to treat residualhypoventilation(Continous desaturation)

EPAP to treat obstructive apneas

(Desaturation dips)

NIV in the sleep labTwo main scenariosHypercapnic OSA (Obesity hypoventilation syndrome)

COPD + OSA (overlap syndrome)

Obesity hypoventilation syndrome Defined as obesity (BMI >30 kg per m2) +Hypercapnia (Pa,CO2 >45 mmHg)

Hypercapnia in obesity recognizes 2 main mechanisms

Hypercapnia related to obesity itself Mechanical disadvantageBlunted ventilatory drive

OSA related hypercapnia Could be reversed by treating OSA

To determine which mechanism predominates we need to effectively treat OSA and to evaluate afterthen CO2 kinetics Need long term NIV

39/41 managed by NIV / 2 needed intubation

Arterial blood gases

A lentre

J7

PO2 mm Hg

48 8

61 7

PCO2 mm Hg

7112

496

Treatment at hospital discharge

BIPAP

CPAP

02

SAS

1

5

SAS+HLO

16 (4+O2)

1

1

OVERLAP

8 (2 + O2)

3 (1+O2)

BPCO

3 (3+O2)

HLO

1

Veale, Breathe 2008

Is there a place for volume assured pressure support? (AVAPS, IVAPS, etc) Not as a first intention treatmentMay induce ventilatory instability May promote indesirable events under NIV (asynchrony, glottic apneas)May worsen quality of sleepNo proved benefit

May be useful in some selected cases (i.e residual REM hypoventilation)Jounieaux J Appl Physiol 1995 Janssens Respir Med 2009Murphy Thorax 2012

COPDOSA10-14%2-4%

Overlap syndromeTreatment Need to treat Obstructive apneas COPD related nocturnal desaturations Diurnal hypoxemia (and hypercapnia if is the case)

Therapeutical alternatives CPAP CPAP + oxygen NIV +/- oxygen

Overlap syndromeFirst line treatment: CPAP +/-O2

CPAP is useful!Marin, ARJCCM 2010

Overlap Syndrome NIVIndications for usageSymptoms (such as fatigue, dyspnea, morning headache, etc) andPhysiologic criteria (one of the following)Paco2 > 55 mm HgPaco2 of 50 to 54 mm Hg and nocturnal desaturation Paco2 of 50 to 54 mm Hg and hospitalization related to recurrent episodes of hypercapnic respiratory failureOverlap syndrome

PAP in sleep related disordersMore complex is not betterPrivilegiate CPAP if possible. Make it easier!EffectiveSimpleAvailable CheaperAvoid asynchronisms

In central sleep apnea ASV may be a good alternative

NIV by a bilevel device may be useful in hypercapnic patientsBut try to switch to a CPAP if possible

Saolun!

*********Flow Limitation is shown graphically as Flattening which is an arbitrary scaleWhen the patients airway is narrowed, the Flattening will drop and when the airway is open, it will rise As there is no airflow during apnea flattening can not be calculated, until the resumption of breathDuring periods of apnea and loud snore, it is not meaningful and should be ignored

*********************when optically active sample absorbs left and right hand circular polarized light in a slightly different way, the resulting electromagnetic radiation, coming out from sample compartment is elliptically polarized (different amplitude)Afin dvaluer si ces diffrences taient galement prsentes entre des appareils ayant des algorithmes de rponse diffrents mais dont lanalyse de signal repose sur la mesure du dbit inspiratoire instantan, nous avons compar les valeurs de pression recommandes par trois appareils de PPC automatique utiliss en chass-crois par 16 sujets apniques non pralablement traits . Les rsultats ont t analyss pour des titrations dune nuit et dune semaine ralises domicile. Si les valeurs moyennes des pressions recommandes taient comparables, la variabilit des rsultats ne permettait pas de reproduire individuellement le mme niveau de pression efficace entre les diffrents appareils. Cette variabilit tait galement observe entre les valeurs obtenues aprs une et sept nuits denregistrement.

Ce mode de titration ne peut donc tre considr comme donnant des rsultats quivalents selon le type dappareil utilis.********************Approximately 1% of the adult population have heart failure, and an astonishing 50% of heart failure patients have sleep disordered breathing (Javaheriet al. Circulation 1998;97:2154-9)

Of the 50% with sleep disordered breathing, the majority have Cheyne-Stokes breathing, or a regular waxing and waning of respiration with a cycle time of about 40-60 seconds, associated with oxygen desaturation and arousal.

Javaheri and others have shown that Cheyne-Stokes breathing during sleep is associated with very severe sleep disruption, and Bradley, Naughton and others have shown a (presumbably causal) association with sympathetic activation.

Optimised drug therapy, nasal CPAP, and oxygen therapy all produce some worthwhile improvement.

*Conversely, patients without CSA/CSR had about a four-fold lower mortality rate than patients with CSA/CSR, despite similar ejection fractions.

We now know from the early results of the CANPAP study that partially treating the CSA/CSR with nasal CPAP produces a marked improvement in mortality, suggesting (but not proving) that the CSA/CSR may be causal.***Nasal CPAP, at a pressure of about 10 cmH2O, also acutely produces a 50% reduction in the AHI.

It also produces a partial normalization of the arousal index comparable to that of 2 L/min nasal oxygen, but little acute change in sleep stage depth.

Like oxygen, nasal CPAP produces an improvement in exercise capacity.

It also produces good improvements in cardiac and stress hormones, ejection fraction, quality of life, and survival.

*****This 60 second slide shows (in cartoon or schematic form - Ill show you real data shortly) the pressure response of AutoSet CS to a central apnea.

In the left hand panel, the subject has been breathing normally and steadily for some time. The device settles down to providing only a bare minimum degree of ventilatory support, here set to a pressure swing of 4 cmH2O. This is sufficient to do about half of all respiratory work, with the goal of increasing respiratory comfort, but the patient must supply the other half, with the goal of keeping PCO2 above the apneic threshold.

In the middle panel, the subject has voluntarily ceased all respiratory effort. The machine continues to cycle, thereby maintaining some respiratory airflow.Over a few breaths, the machine increases the degree of support until ventilation has reached a floating target of 90% of the recent average.

In the right hand panel, the subject resumes spontaneous effort, and the machine responds by reducing support to the minimum again.*Here is a typical 5 minute PSG record from a patient with severe CSA/CSR.

The airflow signal shows five clear apneas.The absence of ribcage/abdomen signal during the apneas show that they are central.The apneas cause clearcut repetitive desaturation.The sleep staging channels show an arousal at the height of each period of overventilation, and a full awakening at each end of the record.The multiple arousals show that these patients are extremely sleep disrupted. *Here we see the device working during the 10 minutes around sleep onset. The patient is in very light NREM sleep. Note the reducing submental EMG.

The patient goes to sleep with their PCO2 well below their apneic threshold, and, as we saw in the previous slide, would have pure repetitive apneas with severe sleep fragmentation if untreated.

Here, on treatment, as the patient starts to enter an apnea, the device supplies rapidly increasing support, converting the apnea to a hypopnea, minimizing the degree of desaturation, and stabilizing sleep. There is only one arousal at the start of this 10 minute epoch.

It is not possible to completely prevent hypopneas during this first 20-40 minutes, because the awake hypocapnia causes vocal cord closure. The PCO2 gradually normalizes over about the first 20-40 minutes of sleep, and the hypopneas become gradually less severe.

It is crucial that the patient not be disturbed during this period. The slamming dooors and banging bedpans of a general ward, or the lights and alarms of an ICU, can extend this period indefinitely.*Here we see the same patient after about 20 minutes. Breathing is now almost completely stable, and sleep is consolidated.

Here, there is a single decrease in ribcage and abdomen movement, and the device responds by immediately increasing support, preventing a hypopnea. There is no desaturation and no arousal.

Note that once the patient is breathing stably, the device provides only the most modest degree of support - finally settling to about 3 cmH2O peak to peak, and using a very smooth and intentionally inefficent waveform.

For this reason, the device cannot overventilate the patient.

Indeed, blood gases normalize on therapy, with the PCO2 actually increasing, due to the patient spending more time at the asleep set-point, less time at the awake set-point, and with fewer arousals. In addition, reduction in lung water probably helps reduce ventilatory drive and thereby normalize PCO2.

*Here we see the results of an acute study by Teschler and colleagues in 14 subjects, treated for 1 night each on oxygen, CPAP, bilevel, and AutoSet CS in random order.Data are presented as box plots, showing median, interquartile range, range excluding outliers, and outliers. Statistical comparisons between treatments use repeated measures ANOVA following rank transform. Untreated, the mean central apnea index was 36/hr. Nasal oxygen (2 L/min) produced about a 50% improvement, confirming the work of Andreas, Franklin, Staniforth, Javaheri and others.Nasal CPAP (approx. 10 cmH2O) also produced a robust 50% improvement, showing that at least some of the longterm improvement shown by Naughton, Bradley and colleagues can be obtained acutely, and contradicting the work of Buckle, Davis and colleagues who found no benefit.Bilevel produced a far better, but variable, improvement, confirming the work of Willson and Sullivan. AutoSet CS produced by far the largest and most consistent improvement, reducing CAI to on average 15% of control, and highly statistically significantly better than all other forms of acute therapy. The remaining 15% were sleep onset closed airway apneas, which were not responsive to ventilatory support.*****

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Which PAP device to which patient?