Andrea VianelloFisiopatologia e

Terapia Intensiva RespiratoriaOspedale-Università di Padova

Andrea VianelloFisiopatologia e

Terapia Intensiva RespiratoriaOspedale-Università di Padova

La gestione respiratoria del pazientecon Malattia di Pompe e

altre MalattieNeuromuscol

ari

La gestione respiratoria del pazientecon Malattia di Pompe e

altre MalattieNeuromuscol

ari

Diseases than can benefitfrom LTMV

Robert, Critical care 2007

↑↑ ventilator

dependency

Acute exacerbati

on

Life expectancy

Neuromuscular

Thoracic cage

Lung/Airway

Clinical Course according to Underlying Disease Category

The concept of the traffic light

ALSALS

DMDDMD

Type II GlycogenosisType II GlycogenosisLTMVLTMV

Clinical Course according to Baseline Disease

Advanced care initiatives in progressive NMD

1. Prompt response to intercurrent exacerbation;

2. “Hospital at home” as an alternative to hospitalization;

3. Full time NIV use for 24-hrs ventilator dependent patients.

Prompt response to intercurrent exacerbation

Criteria that should define transition from home to acute care

setting

• Acute loss of clinical stability;

• Need for escalating medical/health care that cannot be provided in home environment;

• The patient’s and family’s wishes for full intervention for reversible condition.

Study Design No of patients (age) Interventions Main Results Limit

Vianello 2000

prospective case-control

14 patients (38,8+ 23 yrs) versus 14 historical controls

E= NIPPV + CM C= MV via ETI

Mortality and treatment failure significantly lower in the NPPV group

Severe bulbar involvement

Servera 2005

prospective cohort study

17 patients (48,7+ 20 yrs) NIPPV + MI-E Successful in averting death and ETI in 79.2% of the acute episodes

Severe bulbar involvement

Vianello 2005

prospective case-control

11 patients (34,9+ 17,3 yrs) versus 16 historical controls

E= NIPPV + MI-E+ CPTC= NIPPV+ CPT

Treatment failure was significantly lower in the experimental group

Padman1994

Retrospective study

11 NMD patients(+ 4 cystic fibrosis patients) with acute on chronic respiratory failure (4-21 yrs)

NIPPV Treatment failure = 6,6% Significant RR and PaCO2 improvement Number of intubated patients=1

Niranjan 1998

Retrospective study 10 patients (13-21 yrs) NIPPV + MI-E Avoidance of ETI

Bach 2000

Retrospective study

11 children suffering from SMA type 1 (6–26 months) 28 distinct episodes of ARF

Immediately upon extubation the patients received NIPPV + MI-E

NIPPV was to a large extent successful even in very young children with severe skeletal and bulbar muscle weakness.

Piastra2006

Retrospective study 10 children (3month-12yrs) NIPPV + CPT The treatment was successful in 8 of 10

patients

Efficacy of NIPPV plus assisted coughing on exacerbated NMD patients

E, Experimental ; C, Control; NIPPV, Non invasive positive pressure ventilation CM, Cricothyroid-mini-tracheostomy; MV, mechanical ventilation; ETI, endotracheal intubation; CPT, chest physical treatments ; MI-E, mechanical insufflation– exsufflation; NMD, neuromuscolare disease; RR,

respiratory rate; ARF, acute respiratory failure; SMA, spinal muscular atrophy

NIV in NMD patients in the acute setting

Extreme ventilator dependency

Extreme ventilator dependency

Severe inability to cough Severe inability to cough

Severe risk of inhalation

Severe risk of inhalation

Invasive mechanical ventilation

DMD, 24 yrs, administered HMV.He developed bilateral CAP.Ineffective NIV approach → endotracheal intubation

Weaning process

Admit Discharge

Treatment of ARF

Suspicion

Assessing readiness to

wean

SBT

Extubation

Re-intubation

Tobin MJ. Role and interpretation of weaning predictors. 5° International Consesus Conference in Intensive Care Medicine: Weaning from Mechanical Ventilation. Hosted by ERS, Ats, ESICM, SCCM and SRLF; Budapest April 28-29, 2005

Wean the patient from endotracheal tube and avoid tracheostomy!

PCF : 80 L/minMEP: 20 cmH2O

MIP: -18 cmH2O

Clinical assessmentClinical assessment Adequate cough

Absence of excessive tracheobronchial Absence of excessive tracheobronchial secretionsecretion

Resolution of disease acute phaseResolution of disease acute phase

Objective measurementsObjective measurements Clinical stabilityClinical stability- Stable CV status (FC≤140, sBP 90-160 mmHg)- Stable CV status (FC≤140, sBP 90-160 mmHg)

- Stable metabolic staus- Stable metabolic staus

Adeguate oxygenationAdeguate oxygenation

- SatO- SatO22>90% on FiO>90% on FiO22≤40% or PatO≤40% or PatO22/ FiO/ FiO22≥150 mmHg≥150 mmHg

- PEEP ≤ 8 cmH- PEEP ≤ 8 cmH22OO

Adequate pulmonary function

- - ffRR≤ 35 breaths/min≤ 35 breaths/min

- MIP ≤-20-25 cmH- MIP ≤-20-25 cmH22O, VO, VTT >5 mL/kg, VC >10 mL/kg >5 mL/kg, VC >10 mL/kg

- No significant respiratory acidosis- No significant respiratory acidosis

Adeguate mentation Adeguate mentation - No sedation or stable neurologic patient- No sedation or stable neurologic patient

Assessing readiness to wean

Boles, Eur Respir J 2007

• First attempt extubation success rate was 95%;• Six of 7 patients who initially failed extubation succeeded on subsequent attempts;• Only one patient underwent tracheostomy.

Protocol:1. NIV delivered immediately after extubation;2. Man and/or mech assisted coughing to clear secretions.

1. Preventive use of NIV plus assisted coughing is effective to avert the need for reintubation.

2. Subjects with substantial swallowing dysfunction may still encounter particular difficulties

Disadvantages of hospitalization

for NMD patients1. Lack specific facilities for patients with

physical disabilities and for their carers / family to stay;

2. Need of adequate family support to allow daily attendance;

3. Not appropriate for patients likely to experience problems with acclimatisation;

4. Risk of nosocomial infections.

Greater satisfaction with home care

May a “Hospital at Home” model be as effective as hospitalization for the management of exacerbation in NMD patients?

“Hospital at home”: definition

A service that provides active treatment by health care professionals, in the patient’s home, of a condition that otherwise would require hospitalization.

Aim of the study

To evaluate the efficacy and safety of a hospital-at-home model for the

management of Respiratory Tract Infections in NMD patients.

Patients• Study group: 26 NMD subjects suffering from severe respiratory tract

infection treated with a hospital-at-home program;

• Control group: 27 subjects who were hospitalized

Inclusion criteria:

• Respiratory tract infection: – one or more of the following symptoms or signs: fever, throat irritation or sore

throat, hoarseness, and cough

– diagnosis of pneumonia: concomitant presence of infiltrates on chest x-ray

• Urgent need for hospitalization:– difficulty in breathing

– need for continuous noninvasive ventilatory support

– oxyhemoglobin desaturation with need for assisted cough

Exclusion criteria:– requirement for critical care with 24-hour surveillance

– living outside the geographic area covered by our district nurse service

– no non-professional caregivers or caregiver networks at home

Anthropometric, Clinical, Pulmonary Function, and Blood Gas Data at Study Entry

InterventionsNon-Invasive Ventilation

– Portable ventilator

– Continuous use, except for 30–60 min periods of “rest”

– Oronasal mask

Manually and/or Mechanically Assisted Cough– whenever SpO2, decreased, the ventilator peak inspiratory pressure increased, or the

subject had an increase in dyspnea or sense of retained secretions.

– first 3 days: administered by a respiratory therapist who visited the subjects each morning; subsequently: administered by trained nonprofessional caregivers

Continuous SpO2 Monitoring

Standard pharmacologic treatment

Pulmonology Visit at Home– first 3 days: each morning

– subsequently: at the discretion of the district nurses or patient’s GP

District Nurse Visit at Home– assessment of the subject’s adherence and response to treatment

– requirement for a pulmonology visit

– each morning and afternoon until recovery from exacerbation.

Telephone access to the pulmonologists of our division

ResultsIn the hospital-at-home group, 18 (69.2%) responded well, with an uncomplicated course, and 8 required hospitalization.

Outcomes and Direct Costs of Healthcare of Subjects Treated With the Hospital-at-Home Model Versus Hospitalized Subjects

Anthropometric, Clinical, Pulmonary Function, and Blood Gas Data at Study Entry of Subjects Successfully Treated With the Hospitalat- Home Model Versus

Those Who Required Hospital Admission

By multivariate analysis, hospital-at-home failure wasindependently correlated with type of NMD,

with an odds ratio of failure of 17.3for subjects with ALS. None of the other covariateshad any significant effect on hospital-at-home failure.

Hospital at home for exacerbated NMD patients Conclusions

2. Careful home monitoring is mandatory

4. Hospital at home can be problematic or even ineffective in ALS subjects

5. Non-professional caregivers play a critical role in the transition of the care from hospital to home

6. The cost of hospital-at-home can be impressively lower than hospital care

1. Management at home is a viable option

3. Patients at risk of failing at home should be timely identified

From Nocturnal to Full Time NIV use

1988 2004

When is full time MV required?

1. Worsening of the symptoms and

dyspnoea during the day;

2. Excessive increases in PaCO2 ;

3. VC ≤ 300-400mL .

Toussaint, Chronic Respiratory Disease 2007

Extension is empirically driven

Extension is empirically driven

Ventilator-dependent patient: the one who requires ventilation for ≥ 18 hours/day

Potential Disadvantages of Long-Term Tracheostomy

Expense of procedure Higher risk of respiratory infection Formation of granulation tissue Airway stenosis / malacia Tracheoinnominate-artery fistula Tracheoesophageal fistula Impairs speech and swallowing Skilled assistance for suctioning Increased carer burden Social issues around stoma and tracheostomy tube

To be successful with continuous NIV, the ventilator user

must realise three goals:

• Optimise and maintain respiratory system compliance by frequent full insufflation

• Able to use a variety of interfaces which are alternated night and day

• Able to practice techniques to enhance peak cough flows.

Requirements for Home Full-time Ventilation

• Carefully selected and motivated individuals;

• Intact upper airway function;

• Access to centres with expertise in nocturnal and diurnal ventilation;

• Access to adequate levels of carers who are skilled in NIV and assisted coughing techniques.

Toussaint, Chronic Respiratory Disease 2007

P Soudon, Chron Respir Dis 2008

Outcome of patients oncontinuous NIV

Morbidity in 42 patients receiving ventilation either via tracheostomy (TR) or noninvasive interface (NI).

Outcome of patients oncontinuous NIV

P Soudon, Chron Respir Dis 2008

                                                                           

                                                                                                                                                                                                      

A Fatal Complication of Noninvasive Ventilation

The patient was a previously healthy 53-year-old man with amyotrophic lateral sclerosis who was started on nocturnal noninvasive positive-pressure ventilation (inspiratory pressure, 10 cm of water; expiratory pressure, 2 cm of water). He tolerated this well and decided that he did not want invasive mechanical ventilation in the future. The patient's disease progressed, but he continued to work full-time and used noninvasive positive-pressure ventilation all night and most of the day. He obtained a second ventilator, which he kept at work.

Noah Lechtzin, M.D., M.H.S. Charles M. Weiner, M.D. Lora Clawson, M.S.N., C.R.N.P.

Johns Hopkins University School of Medicine NEJM 344:533 2001 Number 7Baltimore, MD 21287

More than a year after noninvasive ventilation was initiated, the patient's ventilating unit failed. The machine's error code indicated that there had been a power-supply failure. Respiratory distress quickly developed, and the patient was taken to a local hospital but died of respiratory failure before ventilation could be reinstituted.

NEJM 344:533 2001 Number 7

Full-time NIV user: minimizing the risk

• 2 ventilators if use of NIV in day > 4hrs. Service & Maintenance

• Cough machine: indications reduced cough (PF <160), poor clearance of secretions despite assisted cough techniques, physio on NIV, ambu bag

• Continued caregiver training and support [ventilator function, back-up battery systems, back-up ventilator function,action skills for emergencies].

• Problem solving approach• Clear advance directives

Long-Term Non-Invasive Ventilation

Enzyme Replacement Therapy

Treatment of severe ventilatory impairment in late-onset GSDII

patient

Enzyme Replacement Therapy

Ethiologic therapy for GSDII

Bi-weekly intravenous infusion of recombinant GAA enzyme

ERT aims to supplement endogenous GAA through delivery of purified,exogenous GAA

Pre-clinical experiments: i.v. rhGAA therapy → correction of the biochemical phenotype in cardiac, skeletal and smooth muscle in the Gaa−/−mouse model

Sporadic case reports, short case series, and observational studies have demonstrated that ERT has the potential to stabilize or even improve pulmonary function. (Ravaglia 2008, Van Capelle 2008, Strothotte 2010, Bembi 2010, Orlikowski 2011)

Variation in respiratory parameters during ERT

Long-term ERT can be effective in stabilizing respiratory function in

late-onset GSDI

90 patients; 8 yrs of age or older,

ambulatory, free of invasive ventilation

randomly assigned to receive biweekly; IV alglucosidase alfa (20 mg per kilogram) or placebo for 78 weeks;

the two primary end points were distance walked during a 6-minute walk test and percentage of predicted FVC.

Treatment with alglucosidase alfa is associated with stabilization of pulmonary

function over an 18-month period.

The study excluded patients with severe pulmonary impairment:

Predicted FVC < 30% Continuous NIV Mechanical Ventilation via tracheostomy

Aims of the study:

To investigate the long-term efficacy of ERT in patients with late-onset GSDII complicated by severe pulmonary impairment high dependency on MV

Coprimary efficacy end-points

the number of hospitalizations due to pulmonary exacerbations

daily hours of use of HMV

Type of study: controlled; historically matched control patients

Patient populations: 8 consecutive patients with late-onset GSDII and high ventilator dependency

All patients were treated with ERT in addition to conventional HMV

Mean duration of follow-up: 35.8 ± 29.2 vs. 52.6 ± 8.55 months; p = 0.04

The reduction in hours of daily use of HMV from baseline to end of follow-up in Group A was significantly greater compared with that in Group B Patients receiving ERT had a significantly lower number of hospitalizations than the control group ([0.42 (95 % CI 0.2–0.76) vs. 0.96 (95 % CI 0.62–1.42); IRR = 0.43 (95 % CI 0.18–0.93); p = 0.03]. There were no serious adverse events or infusion-associated reactions.

Adapting to the Worsening of the NMD Patient: Take home

messages• Clinicians should remain vigilant Clinicians should remain vigilant

to any potential change in to any potential change in patients’ clinical status;patients’ clinical status;

• In individuals with GSDII, ERT can “turn back the clock”.

• All settings, interfaces, and All settings, interfaces, and strategies should be employed strategies should be employed to achieve goals of good health to achieve goals of good health and optimized quality of life;and optimized quality of life;