1. Papel del diafragma en la VM
Fernando Suarez Sipmann
Sect. Anesthesia and Intensive Care
Dept. Surgical Sciences
Hedenstierna Laboratory
University of Uppsala
Servicio de Medicina Intensiva
Hospital Universitario de La Princesa
Universidad Autonoma de Madrid
Madrid, Spain

2. Conflicts of Interest Maquet Critical Care (Getinge)
HULP
Maquet Critical Care (Getinge)
Scientifiic Advisor
Consultant
Received Research Grants
Timpel-
Co-founder
Scientific Advisor

3. Diaphragm Disuse Atrophy
HULP
∼50% reduction in type I (slow-twitch) and type II (fast-twitch) muscle fiber area in the costal diaphragm within 18 to 69h mechanical ventilation
Degree of atrophy would predict a 55% decrease transdiaphrabmatic pressure (Pdi)
∼50% reduc- tion in type I (slow-twitch) and type II (fast-twitch) muscle ber area in the costal diaphragm within 18 to 69 h mechan- ical ventilation in brain-dead organ donors
Levien et al N Engl J Med 2008;358:

4. Ventilator Induced Diaphragmatic Dysfunction
HULP
Ventilator Induced Diaphragmatic Dysfunction
Diaphragm structural injury and atrophy +
Reduction of diaphragmatic force-generating capacity
Dres M et al ICM (2017) 43:1441–1452
Jaber et al. Critical Care 2011, 15:206

5. Difficult to wean patients in numbers
HULP
Weaning ∼40% of time spent on the ventilator
Prolonged weaning is associated to an
estimated ICU mortality as high as 25%
∼15% of medical ICU patients remain dependent
on ventilator support for longer than 21 days
Annual costs for prolonged weaning estimated to exceed 50 billion dollars in USA by 2020
Long term functional limitations
Prolongued weaning is associated to significant morbidity and mortality adding a significant burden to mondern intensive care

6. Clinical Assessment of Diaphragmatic function
HULP
Clinical Assessment of Diaphragmatic function
Prevalence 30 to 85%
Ultrasound
EAdi
Dres M et al Intensive Care Med (2017) 43:1441–1452

7. Diaphragmatic Ultrasound
HULP
Diaphragmatic thickening at end inspiration (Tei) and end expiration (Tee)
Thickening fraction
Tei – Tee/Tee

8. VIDD strongly affects Outcomes
HULP
N = 191 patients
↑ Tdi >10%
↓ Tdi >10%
25%
34%
41%
Diaphragm atrophy developing during MV was specifically associated with substantial delays in liberation from mechanical ventilation and a significant increase in the risk of serious complications including reintubation, tracheostomy and prolonged ventilation.
HR 0.69, 95% CI
HR 0.81, 95% CI
Goligher EC et al .. Am J Respir Criti Care Med 2018; 197:204–213

9. EAdi: NAVA Neurally Adjusted Ventilatory Assist EAdi Catheter HULP
Sinderby et al. Nature Med 1999;(5):
EAdi Catheter

10. HULP
NAVA – Basic concept 10

11. Eadi: Cycling and Assisting
HULP
Edi (V) 12
TE Neural
TI Neural
Passist= Edi x NAVAlevel = cmH2O x volt
NAVA level: proportionality constant 10
Trigger
Cycle-off 8 6 4 2
Suarez-Sipmann F et Med Intensiva 2008; 32:398–403

12. NAVA in operation
HULP

13. Proportionality Edi - Pdi
HULP D i a p h r g m c t v o n ( . u )
Time (sec) P d H O 2
pressure support = 0 cm H2O
pressure support = 5 cm H2O
pressure support = 10 cm H2O
pressure support = 15 cm H2O
Beck
J, AJRCCM 2001;164:419 -
424
Example of averaged inspirations in one patient mechanically
ventilated on four different pressure support levels (see legend).
Left panel shows diaphragm electrical activity (y axis), and right panel
shows transdiaphragmatic pressure (y axis) plotted versus time (x axis).
Pdi transdiaphragmatic pressure. a.u. arbitrary units.

14. NAVA Close loop control
HULP
NAVA Close loop control
EAdi
Up-regulation
Down-regulation
Delivered Vt < Demand
Delivered Vt > Demand
Muscular
Unloading
Over-Under
Assistance
Not to forget:
Patient has freedom (and control..)
Status of Respiratory Control System
Respiratory drive
Neuromuscular Coupling

15. EAdi derived measurement of Diaphragmatic efficiency
HULP
Neuroventilatory efficiency(NVE)
NVE = Vt/EAdi
Neuromechanical efficiency (NME)
NME = (Paw – PEEP)/EAdi
Muscular fatigue and/or excessive respiratory load
Diaphragmatic dysfunction Critical illness
VIDD
Standardization tests NVE o NME
Cpacidad del diafragma para generar presion NME
Capacidad del diafragma para generar volumen (NVE)

16. Neuro-Ventilatory Efficiency
HULP
SBT = CPAP 5 cmH2O
Cut-Off 80
AUC P = 0.012
Sens
Spec
Cut-Off 24
AUC 0.84; P < 0.001
Sens. 0.69
Spec
Weaning success
Weaning Failure
Liu et al. Critical Care 2012, 16:R143
52 mixed ICU patients during a PSV 5/10 and a SBT.
The NVE index (Vt/EAdi), reflects determinants of the volume generated (that is, the respiratory drive, dia- phragm function, and respiratory load). In agreement with the notion that weaning failure is caused by respiratory demand exceeding the capacity of the respiratory muscles [12-16], NVE was the variable that demonstrated the largest difference between groups (50% lower NVE in the extubation-failure group) and best predictability for extubation outcome with the lar- gest AUC (0.84)
Figure 2 The development of (top to bottom) diaphragm electrical activity (EAdi), neuromechanical efficiency (NVE), and neuroventilatory efficiency (NME) during pressure support of 10 above 5 cm H2O of PEEP (PSV10) and throughout the spontaneous breathing trial (SBT) on CPAP of 5 cm H2O. On the X-axis: T1, T5, T10, T15, T30, and Tend indicate minutes 1, 5, 10, 15, and 30, as well as the last data obtained during the SBT. In the successfully extubated group, n = 35 at all time points. In the group for whom extubation failed, n = 17 at PSV10, T1, and T5; n=16 at T10 and T15; n=14 at T30 (three for whom SBT failed at 30 minutes and 11 who were initially extubated but were later reintubated or provided with noninvasive ventilation or died). Data were obtained for the remaining three patients meeting SBT exclusion criteria at T30. At Tend, n = 17 in the group for whom extubation failed. *Difference (P < 0.05) between failure and successfully extubated groups at the same time point. †Differences (P < 0.05) between PSV10 and other time points in the group for whom extubation failed. ‡Differences (P < 0.05) between PSV10 and other time points in the group that was successfully extubated.
Figure 4 Upper left panel shows the ROC curve (receiver operating characteristic) for neuroventilatory efficiency (NVE) to predict
extubation success after 5 minutes of the spontaneous breathing trial (T5). Area under the curve (AUC) was 0.84 (P < 0.001). Upper right
panel shows the ROC curve for diaphragm electrical activity (EAdi) to predict extubation failure at T5. AUC was 0.73 (P < 0.009). Lower left panel
shows ROC curve for neuromuscular efficiency (NME) to predict extubation success at T5. AUC = 0.70 (P < 0.02).The lower right panel shows the
ROC curve for the ratio of breathing frequency and tidal volume (f/Vt) to predict extubation failure at T5. AUC was 0.72 (P = 0.012).
Liu et al. Critical Care 2012, 16:R143

17. NAVA: Potenciales Ventajas
HULP
NAVA: Potenciales Ventajas
Mejora la sincronía ins y espiratoria
Mantiene la actividad diafragmática durante el TI
Puede mejorar la descarga muscular diafragmatica
Asistencia proporcional intra e inter ciclo
Variabilidad respiratoria (frecuencia y VT)
EAdi nuevas opciones de monitorización

18. Tx Strategies for Diaphragmatic weakness in MV
HULP
Tx Strategies for Diaphragmatic weakness in MV
Preventive Strategies
Level of Evidence
Clinical Recommendations
Prevention of Disuse Atrophy
Maintaining Insp efforts
High. Exp+Clin data
Spont. breathing when possible
Phrenic Nerve Pacing
Low. Only Exp. Data
Not in routine Clinical Practice
Inspiratory Muscle Training
Progressive Threshold Loading
Moderate. Clinical Data
Implemented in long term MV pts
Pharmacologic Approach
Antioxidants (N-Acetylcysteine)
Low. Only Exp. Data
Not recomended
Dres M et al Intensive Care Med (2017) 43:1441–1452

19. Tx Strategies for Diaphragmatic weakness in MV
HULP
Tx Strategies for Diaphragmatic weakness in MV
Rescue Strategies
Level of Evidence
Clinical Recommendations
Phrenic Nerve Pacing
Restoring Diaphragm. function
Low. Only Exp. Data
Not in routine Clinical Practice
Pharmacologic Approach
Annabolics
Low. Only Exp. Data
Not in routine Clinical Practice
Optimization of muscle Contractility
Teophyline
Moderate. Clin+Exp Data
Not in routine Clinical Practice
Levosimendan
Moderate. Clin+Exp Data
Not in routine Clinical Practice
Dres M et al Intensive Care Med (2017) 43:1441–1452

20. Tx Strategies for Diaphragmatic weakness in MV
HULP
Tx Strategies for Diaphragmatic weakness in MV
Rescue Strategies
Level of Evidence
Clinical Recommendations
Phrenic Nerve Pacing
Restoring Diaphragm. function
Low. Only Exp. Data
Not in routine Clinical Practice
Pharmacologic Approach
Annabolics
Low. Only Exp. Data
Not in routine Clinical Practice
Optimization of muscle Contractility
Teophyline
Moderate. Clin+Exp Data
Not in routine Clinical Practice
Levosimendan
Moderate. Clin+Exp Data
Not in routine Clinical Practice
Dres M et al Intensive Care Med (2017) 43:1441–1452

21. Tx Strategies for Diaphragmatic weakness in MV
HULP
Tx Strategies for Diaphragmatic weakness in MV
Preventive Strategies
Level of Evidence
Clinical Recommendations
Prevention of Disuse Atrophy
Maintaining Insp efforts
High. Exp+Clin data
Spont. breathing when possible
Phrenic Nerve Pacing
Low. Only Exp. Data
Not in routine Clinical Practice
Inspiratory Muscle Training
Progressive Threshold Loading
Moderate. Clinical Data
Implemented in long term MV pts
Pharmacologic Approach
Antioxidants (N-Acetylcysteine)
Low. Only Exp. Data
Not recomended
Dres M et al Intensive Care Med (2017) 43:1441–1452

22. Avoid “deconditioning”
HULP
Maintain Inspiratory Effort and diaphrgamatic activity

23. Diaphragmatic efficiency after prolongued MV
HULP
Diaphragmatic efficiency after prolongued MV
NVE
38 patients ventilated > 72h
20 NAVA vs 18 PSV
NAVA improved Diaphragmatic efficiency
NME
Di mussi et al. Critical Care (2016) 20:1

24. Diaphragmatic efficiency after prolongued MV
HULP
Diaphragmatic efficiency after prolongued MV
NAVA better matching between neural and mechanical times , less asynchronies, less over-assistance
EAdi useful tool to monitor diaphragmatic function in critically ill patients
Di mussi et al. Critical Care (2016) 20:1

25. Inspiratory Muscle Training
HULP

26. In summary Managing Diaphragmatic Weakness MONITORING Muscular
HULP
In summary
Managing Diaphragmatic Weakness
Muscular
Capacity
Workload
Optimize muscular loading/unloading
Timely and functionally appropriate use of assited modes of
Avoid Asynchronies
Effort adapted Vent. Modes
Progressive Workload Training
Muscle weakness /wasting
Atrophy
Inactivity
Myopathy
MONITORING

27. Hedenstierna Laboratory
Muchas Gracias
Hedenstierna Laboratory
Ferrnando Suarez-Sipmann
Dept. Surgical Sciences
Hedenstierna Laboratory
Uppsala University
Servicio de Medicina Intensiva
Hospital Universitario de La Princesa
Universidad Autonoma de Madrid
Madrid, Spain

28. HULP

29. HULP

30. HULP

31. HULP

32. HULP

33. HULP

34. Control HULP PSV 12 CMV 12 PSV 18 CMV 18
representative fluorescent staining of MHC I (DAPI filter/blue), MHC IIa (FITC filter/ green), and dystrophin (rhodamine filter/red) proteins in diaphragm samples from CON, 12PSV, 12CMV, 18PSV, and 18CMV
PSV 18
CMV 18