Lung protective strategies,2019 - Dr Karthik Nagesh

1. Dr.N.Karthik Nagesh
MD,FRCPCH ( U.K.),FNNF
Neonatal Intensive Care Fellowship ( U.K.)
• Chairman-HOD, Neonatology &
NICUs Manipal Hospitals Group.
• Chairman – Manipal Advanced
Children’s Centre (MACC),
Manipal Hospitals,Bangalore
• Professor (Adjunct) – Neonatology
& Pediatrics, Manipal University

2. Karthik Nagesh N, Abdul
Razak,2016;0:F1–F5. doi:10.1136/
Arch. Dis.Child-2016-308169;F1

3. Advances in Neo.Respiratory Care
• 1970s
• Ventilatory Care
• 1980s
• Surfactant Replacement
Therapy
• ECMO
• 1990s
• HFOV,Nitric Oxide Therapy,
• Liquid Ventilation
• 2000s
• NIV, CPAP , INSURE
• 2011-2012
• Early CPAP alone +/- Surfactant
• 2013
• HHHFNC

4. ELBW-Principles of Care in First Week
• Antenatal Steroids/MagSulf
• In-Utero Transfer
• Delayed Cord Clamping
• Delivery Room Management
• Delivery Room CPAP>>NICU
• Surfactant Therapy
• INSURE
• Ventilation-SIPPV,SIMV,PSV, VG
• NIV/CPAP/HHHFNC
• Caffeine
• Hemodynamics
• PDA Monitoring/Management
• Aggressive Early Nutrition
• Fluids/Electrolytes
• Antibiotic Stewardship
• Aseptic Protocols
• Hyperbilirubinemia Management

5. NICU, Manipal hospital, Bangalore

6. Aim…
Treat RESPIRATORY
FAILURE…
RDS (HMD)
RDS (HMD)
• Hypoxemia (Pa O2 <
50)
• Hypercarbia (Pa Co2 >
50)
• Acidosis (Ph < 7.25)
Pressure Limited Time Cycled Ventilators…IMV

7. Problems With Invasive Ventilation
• Consequences of presence of endotracheal tube
– ↑infection/inflammation- VAP
– VILI
– Local trauma to trachea, larynx
• Subglottic stenosis
• Need for postnatal steroids
– Need for emergency reintubation
• Consequences of bypassing the larynx
– Loss of humidification
– Disruption of normal adaptive breathing
NIPPV reduces endotrauma, ADC F&N 2008

8. “Inappropriate Ventilation Of A
Neonate Can Be More Harmful
Than The Disease Itself”
Lancet editorial

9. Mechanisms of Lung Injury
• Structural Immaturity
• Prenatal chorioamnionitis
• Lung remodelling
• Resuscitation
• Oxygen
• Mechanical Ventilation
• Pneumonia

11. Chronic Lung Disease
Etiologic Associations
Predisposed Baby
•Immaturity
•Family History
•RDS
Severe Lung
Disease
•PDA
•Fluid Overload
•PIE
Contributory Factors
•Infection
•Surfactant
Abnormalities
•Disturbance of
Elastase/Protease
High Level of
Respiratory
Support
•Oxygen
Toxicity,
•Baro-
volutrauma

12. Lung Injury- VILI
Bland RD et al.
Am J Physiol Lung cell
Mol physiol’
Control lung After 24hrs of invasive ventilation
BPD

13. How does injury from MV occur?
• Volutrauma
• Too much stretch at maximum lung capacity
• Atelectotrauma
• Opening and closing of areas of lung at low
tidal volumes
• Both generate an inflammatory response

14. Capillary leak
A syndrome of
inflammation
Diffuse
alveolar
epithelial
damage
Breakdown of
endothelial
barrier
Interstitial
edema
Proteinaceous
alveolar
flooding
Type 2 cell
Apoptotic
Type 1 cell
Pathophysiology of Acute Lung Injury in HMD
Acute Lung Injury in
Preterms
Acute Lung Injury

15. Traditional Concepts of Barotrauma Due
to Ventilation

16. P-V curve in RDS
Pressure
Concept of Volutrauma

17. Alveolar Collapse
Pressure

18. Pressure
PEEP Upper limit Pr. or Vol.
Limiting Volutrauma

19. Prevention of Lung Injury
• Don’t ventilate if you can
avoid it!
• CPAP
• INSURE
• Nasal Ventilation
• Caffeine
• Permissive
Hypercapnia

20. Initial Stabilization After Delivery
• Resuscitation (NRP)
• O2 – Cautiously
• ?? Room Air !!
• IPPV- high risk of CLD.
• T-Piece Resuscitator
• Gentle ventilation
• Strict Asepsis…

21. CXR

22. Lung Ultrasound in NICU

23. Noninvasive ventilation/respiratory
support
 Providing respiratory support with an
interface which is above the level of glottis
 A bridge between autonomous breathing and
mechanical ventilation
 Modes of respiratory support
 CPAP
 NIPPV

24. COIN* Trial
• 610 infants, 25 to 28 weeks
• Distress at 5 minutes of life
• CPAP or Ventilation
• Surfactant only if intubation and criteria for this
not pre-specified
• In CPAP group
– Only 46% required intubation in first 5 days
– Nearly 50% escaped surfactant
Early Rescue CPAP
*CPAP or Intubation and Ventilation without surfactant (CPAP
or Intubation (COIN Trial)) ,Morley CJ et al,2008
Grade A

25. CPAP is an alternative to intubation and surfactant in
preterm infants (Grade A)
• 1316 infants, 24 to 27 weeks
• CPAP vs. Intubation and
Surfactant at birth
• For CPAP group surfactant
was given
– If intubated at birth
– Failed CPAP i.e. FiO2>50%
Prophylactic CPAP
• In CPAP group
– 33% did not receive
surfactant
– 83% got intubated
– Lesser need for
ventilation in first 7
days
“SUPPORT” trial,NEJM,2010

26. Both SUPPORT and COIN trials support
CPAP alone a safe alternative to
intubation and surfactant
Primary outcome was Death or BPD
•Intubation rates of 83% and 46% Only
• 33% and 50% lesser need of surfactant

27. T piece
Oxygen
Air
Cork
remove
CPAP
pressure
ET tube
Indigenous BUBBLE CPAP
AIR
Prof. Wung
1998

28. FiO2 : Air-oxygen Blending
1 2 3 4 5 6 7
50%
FiO2
40%
FiO2
Oxygen flow L/min
Air
flow
L/min
80%
FiO2
90%
FiO2
FiO2 = 0.2x air flow + O2 flow
air flow + O2 flow

29. • Helps clear lung fluid at birth
• Helps establish and maintain lung aeration
• Improves oxygenation
• Conserves surfactant
• Decreases upper & lower airway resistance
• Improves the compliance of stiff lungs
• Regularises and slows respiratory rate
• Reduces apnoea
• Reduces lung injury and inflammation
• Reduces energy expenditure
• Reduces the need for ventilation
CPAP is a very effective respiratory support for
preterms…Proven!

30. EARLY CPAP IN RDS in babies breathing
spontaneously
• Improves FRC & lung volume
• Prevents progressive atelectasis
• Avoids need for intubation / ventilation
• Minimises volutrauma & lung injury
•Reduces need for tertiary transfer of babies with RDS
•The use of CPAP with early rescue surfactant should be
considered in babies with RDS in order to reduce need
for MV (A)
•Cochrane Systematic Review 2008 , European Guidelines,2007

31. Patient interfaces for CPAP
Hudson’s prongs
Bi-nasopharyngeal
prongs
Short bi-nasal
prongs
Argyle
prongs
Masks
CPAP Delivery
Systems
• Ventilator
CPAP
• Bubble CPAP
• Variable flow
CPAP

32. CPAP versus Intubation
Reduction of mechanical ventilation (MV) and
trends toward reduction in the incidence of
Bronchopulmonary Dysplasia (BPD).
Morley CJ, Davis PG, Doyle LW, Brion LP, Hascoet JM, Carlin JB; COIN Trial. N Engl J
Med. 2008;358(7):700–708
Finer NN, Carlo WA, Walsh MC, et al; SUPPORT Study Group. N Engl J Med.
2010; 362(21): 1970–1979

33. How does NIV work?
CPAP
• ↑FRC
• Stabilization of the
chest wall
• ↓in airway
resistance
• Improvement in lung
volume and
oxygenation
NIPPV
• ↑in MAP allowing
better recruitment
of alveoli
• ↓work of breathing
• ↑in Vt and minute
volume
• Improving the
respiratory drive

34. Synchronized NIPPV
GRASEBYABDOMINAL SENSOR Air way Flow sensor
A A
S S S S

35. NIPPV- as primary mode
Study Inclusion Control group Outcome(s) in NIPPV
Santin et al’04 28-34 wks
gestation
SIMV ↓ Duration of O2
exposure
↓ Length of stay
**Bhandari et al’
07
600-1250 gms SIMV ↓ Death/BPD
Comparison with mechanical ventilation
Comparison with CPAP
Kugelman et al 07 < 34 wks CPAP
↓ need for intubation
(25% vs. 49%)
↓ BPD
(2% vs. 17%)
Grade A
Karthik Nagesh N. Editorial-
Neonatal intensive Care. Journal of Neonatology 2006, Volume : 20, Issue : 3.Online ISSN : 0973-2187.
Print ISSN : 0973-2179.

36. SURFACTANTs still needed...Inspite of
…ANS/DR-CPAP/INSURE/NIV/HHHFNC
• Surfactant replacement therapy has proven
effective in reducing mortality and pulmonary
morbidity, including pneumothorax
Seger N, Soll R. Animal derived surfactant extract for treatment of respiratory
distress syndrome. Cochrane Database Syst Rev. 2009;(2):CD007836

37. Surfactants
Synthetic
• Protein Free…Exosurf
• Protein
Containing…Surfaxin-
Lucinactant
Natural (Animal derived)
Bovine
• Minced Lung Extract…Survanta
(Beractant), Alveofact (Bovactant)
• Lung Lavage Extract…bLES*
Infasurf(Calfactant)
Porcine
Minced Lung Extract…Curosurf
(Poractant alfa)
Goat…NA (Trial is currently on in India)
*Neosurf

38. European Consensus Guidelines on the Management of
RDS – 2016 Update
Recommendations
• Babies with RDS should be given a natural
surfactant preparation(A)
• A policy of early rescue surfactant should be
standard(A)
• Poractant alfa in an initial dose of 200mg/kg is
better than 100mg/kg of poractant alfa or
beractant for rescue therapy(A)

39. IN-SU-RE
(1) Loading dose of caffeine citrate (20 mg/kg)
(2) Morphine (0.2 mg/kg) for analgesia
(3) Thiopental (2–5 mg/kg) for sedation
(4) Oral intubation
(5) Surfactant through the endotracheal tube
(6) Naloxone administration (0.1 mg/kg) just before
extubation
(7) MV until respiratory stability
(8) Extubation to CPAP
Bohlin K, Henckel E, Blennow M. International perspectives: Surfactant Without
Assisted Ventilation: the Scandinavian perspective. Neoreviews. 2008;9(12):e555–e561

40. IN-SU-RE
• Reduction in the need for further intubation
and MV has been reported….Advantage
• Need for premedication, secondary effects
such as hypotension, and the difficulty in
extubation for a substantial number of
infants….Disadvantage
Escobedo MB, Gunkel JH, Kennedy KA, et al; Texas Neonatal Research Group. Early surfactant for neonates with
mild to moderate respiratory distress syndrome: a multicenter, randomized trial. J Pediatr. 2004;144(6):804–808
Reininger A, Khalak R, Kendig JW, et al. Surfactant administration by transient intubation in infants 29 to 35 weeks’
gestation with respiratory distress syndrome decreases the likelihood of later mechanical ventilation: a randomized
controlled trial. J Perinatol. 2005;25(11):703–708

41. IN-SU-RE technique
Stevens et al. Cochrane 2007
Reduction in mechanical ventilation,
BPD, mortality
Always combine with early CPAP
Grade A
Grade A

42. Minimally Invasive Surfactant Therapy
• These techniques have included administration of
exogenous surfactant by
• Brief tracheal catheterization,
• Aerosolization, and laryngeal mask.
• Of these, the methods involving brief tracheal
catheterization have been most extensively studied,
with surfactant administered by using both a
flexible feeding tube and a semi-rigid vascular
catheter

43. STEPS IN MIST
Neonate with RDS on CPAP with FiO2 > 30-40%
Pre-medicate with Caffeine,
Optional: Atropine, Sucrose analgesia (Avoid narcotic analgesia)
Maintain nasal CPAP throughout with FiO2 adjusted as per pre-ductal
SpO2
Gastric feeding tube is inserted into the trachea with or without using
Magill forceps under direct laryngoscope vision
Surfactant ( 100- 200 mg/kg) is administered over 30-60 minutes with the
infant breathing spontaneously.

44. MIST using Angiocatheter

45. Less Invasive Surfactant Administration…The
Future
• Surfactant administration by minimally
invasive methods that allow for spontaneous
breathing might be safer and more effective
than administration with endotracheal
intubation and mechanical ventilation in
preterms ‘at risk’ or with RDS
American Academy of Pediatrics ,July 2014, VOLUME 15 / ISSUE

46. IMV – ‘Unsynchronised’
Ventilator Breaths
Baby’s Breaths
Synchronisation by Sedatives,Muscle relaxants.
Synchrony becomes a random event !!!
Ventilator Breaths

47. ‘Trigger’ signal sensors ( PTV)
• Abdominal
movements
• Thoracic
impedance
• Airway flow - Heated
wire anemometer
• Airway pressure
• GOOD Baby Brain
• GOOD Sensors
• GOOD Airway

48. S+IMV
• Inspiration of baby
synchronized to
ventilator breath
• Patient continues to
breath between
ventilator breaths
• Ventilator rate can be
fixed
Ventilator Breaths
Baby’s
Breaths
Baby’s Breaths

49. Assist/ Control Mode**
• All Baby breaths are
synchronized
• All spontaneous
efforts are detected
and assisted (Assist)
• Back up rate ensures
ventilation in apnoeic
baby (Control)
** Also called SIPPV
Baby’s Breaths
Ventilator Breaths
BUT expiration Asynchrony

50. Assist/ Control with
InspirationTermination
Baby’s Breaths
Ventilator Breaths
Hence,Efforts to Terminate Inspiratory
flow

51. Pressure Support Ventilation (PSV)
• Mimics spontaneous breath
• Vent. breath triggered by airway flow due to
patient’s effort
• Vent. breath terminated by reducn. in flow
• Hence patient has control on Ti and rate
• Only “pressure support” is provided

52. *Volume Guarantee ( VG )
• Set Tidal Volume ,
PEEP
–4-5 ml / kg
• PIP variable
and
depends on
lung compliance
• How does the
Ventilator measure
the volume ?
• By flow
• In expiration
*Volume Controlled Ventilation

53. Volume Targetted Ventilation
Uses Lesser PIP once
Lungs Improve
• Relatively constant Tidal
Volumes
• Prevention of
Overdistension and
Volume Trauma- Sudden
changes in Compliance
• Automatic-Weaning
• Compensation for
Variable Respiratory
Drive
Grade A ( Cochrane,2011)

54. VENTILATION STATERGY
• Ventilation strategy- As lung compliance changes rapidly during RDS and
its treatment, volume targeted ventilation appears to be
appropriate.
• Cochrane review reported 21% reduction in death/BPD for VTV
compared to pressure limited MV.*
• Cochrane review on elective use of HFOV soon after intubation
showed significant reduction in death/BPD at 36-37 weeks PMA
or discharge and in BPD alone.*
EARLY BPD
* Klingenberg C, Wheeler KI, McCallion N, et al. Volume-targeted versus pressure limited
ventilation in neonates. Cochrane Database Syst Rev 2017;10:CD003666.
*Cools F, Offringa M, Askie LM. Elective high frequency oscillatory ventilation versus
conventional ventilation for acute pulmonary dysfunction in preterm infants. Cochrane
Database Syst Rev 2015:CD000104

55. Synchronized Noninvasive Positive Pressure
Ventilation
• Neurally Adjusted Ventilatory Assist (NAVA), a
technique that utilizes the electrical activity of the
diaphragm to trigger mechanical breaths
• Has been shown to improve patient-ventilator
interaction and synchrony even in the presence of
large air leaks

57. Which babies might benefit from HFOV?
• Elective HFOV
• Selective HFOV
• Rescue HFOV
If Conventional Ventilation Fails/Ineffective…Severe Air Leaks,PIE

58. Prevention of Lung Injury
• Don’t ventilate if you
can avoid it!
• Early CPAP
• IN-SU-RE
• Nasal Ventilation
• Caffeine
• Permissive
Hypercapnia

59. Journal of Neonatology,2015,July-Aug,In
Print
Guest Editorial
…“This last decade has shown enough
evidence that non invasive modalities like
nasal CPAP and NIV work even better in the
extremely preterm , with hardly any need for
intubation and ventilation except to
administer surfactant by the INSURE
protocol. Most of our care, as we now tend to
look after smaller and more preterm babies,
is focused on being ‘gentler’ in our
ventilation strategies to prevent lung injury
and chronic lung disease.”…
N. Karthik Nagesh,2015
KMC