"Best Paper Presentation Award" Presented at 3rd Annual Critical Care Medicine Conference , Sir Gangaram Hospital, New Delhi "A Case of H1N1 ARDS - Journey from NIV to Invasive Ventilation to recruitment to proning to ECMO & Nitric Oxide" For PPT, Check following link http://www.medicalgeek.com/clinical-cases/36303-h1n1-ards-case-presentation.html

1. A Case of Acute Hypoxemic
Respiratory Failure
DR. VITRAG SHAH
FIRST YEAR FNB RESIDENT,
DEPARTMENT OF CCEM,
SGRH, DELHI

2. History
• 32 year old male
• Farmer by occupation
• Resident of Gwalior
• No past comorbidities
• Non-smoker, Non-Alcoholic
• Symptoms :
• Fever with chills
• Cough with scanty expectoration for 5 days
• Breathlessness mMRC II—III for 3 days
• No other significant history

3. History
• Initially admitted at Gwalior on 29/09/15
• Routine blood tests : Normal
• Chest x-ray : B/L lower zone infiltrates (Lt>Rt)
• Managed with IV antibiotics, oxygen & other supportive
treatment
• Then brought to SGRH for further management &
admitted to Respiratory HDU on 02/10/15.
• Initially maintained SpO₂ 90-92% on 100% O₂ mask
• On 03/10/15 in view of worsening breathlessness and
desaturation on 100% mask, patient was shifted to ICU

4. Initial Chest X-Ray & CT Thorax
(Gwalior)

5. Physical Examination on ICU admission
• Patient was conscious, oriented
• Respiratory distress present, using accessory muscles
• Temperature : 37.6°c (Axillary)
• Pulse : 104/min, regular
• RR : 32/min, thoracoabdominal
• BP : 130/70 mmhg
• SpO₂ : 88% on 100% Oxygen Mask
• No pallor, clubbing, cyanosis, edema, lymphadenopathy

6. Systemic Examination on ICU admission
 Respiratory system :
• Inspection – bilateral hemithorax movement equal
• Palpation – bilateral hemithorax expansion equal
• Percussion – no abnormality seen
• Auscultation – Bronchial breath sounds & bilateral fine
inspiratory creps heard over bilateral infraaxillary and
infrascapular region

7. Other System Examination
 Cardiovascular – S1, S2 heard-normal and no murmurs
 Gastroenterology – soft, bowel sounds heard, no free fluid or
organomegaly seen, no guarding/rigidity
 Neurological – Higher function – normal, no focal
neurological deficit

8. ROUTINE BLOOD INVESTIGATIONS
ABGA on ICU admission (on 100% O2
Mask)
pH 7.45 PO₂ 49.8 PCO2 42 HCO3 28.9
Lactate 1.18
BUN / Creatinine 31.85 / 0.95
Na/K 134/3.66
Total/direct bilirubin 0.92/0.37
Prot/Alb 5.79/2.62
SGOT/PT 100/46
PT/aPTT WNL
Procalcitonin 1.5
Hb/TLC/PLT 14.6/10.2/193

9. Rest Investigations
• RBS : 118, ECG : Incomplete RBBB
• H1N1 RT PCR was also sent on the day of admission
and report was awaited.
• Malarial antigen, PS for MP, Scrub typhus IgM,
Leptospirosis IgM, Dengue NS1 antigen & IgM-IgG were
sent
• Blood & urine culture were sent. Cough was non-
productive, so sputum gram stain-culture were not sent.

10. Chest X-Ray on Day-1 ICU Admission

11. What are the differential
diagnosis in this patient?

12. Differential Diagnosis
• Bilateral pneumonia with ARDS (Viral / Bacterial)
• Tropical illness (Dengue/Malaria/Scrub Typhus/Leptospirosis)
• Cardiac abnormalities- valvular dysfunctions, cardiomyopathy
and congestive cardiac failure
• Connective tissue disorders
• Septic source from other organs

13. How will you manage
this patient?

14. Management plan on Day-1 ICU admission
• NIV (CPAP-PSV) ,Plan for SOS ET Intubation, relatives
were counseled for same
• IV Antibiotics (Meropenam & Teicoplanin)
• Cap. Doxycycline (For atypical coverage & scrub typhus)
• Tab.Oseltamivir (For H1N1 Influenza)
• SOS Inj.Paracetamol (Antipyretic) , Other supportive
treatment & IV Fluids

15. Course in ICU
• Malarial antigen, PS for MP, Scrub typhus IgM,
Leptospirosis IgM, Dengue NS1 antigen & IgM-IgG were
negative.
• Initial Blood & urine culture were negative.
• H1N1 RT PCR came positive.
• 2D Echo on Day-1 ICU admission – Normal , No PAH
• USG Abdomen – Normal

16. Course in ICU
• ICU Day 1&2 (03/10/15 - 04/10/15) :
• Managed on NIV (CPAP-PSV), was maintaining
SpO2 around 93-94%
• ABGA on ICU Day-2 ICU(04/10/15) :
• pH 7.45 PO₂ 82 PCO₂ 39 HCO3 26.8 Lactate 1.91
• ICU Day 3 (05/10/15) :
• I/V/O decreasing SpO₂ and increasing respiratory
distress, intubated & taken on mechanical ventilator

17. Chest X-Ray after ET Intubation

18. How will you ventilate
this patient?
• What is Lung Protective Ventilation?
• What is open lung ventilation?
• How to Titrate PEEP?
• Fluid management
• Evidence

19. Initial Ventilatory Settings
• Ventilated as per lung protective ventilation strategy
• Height - 175 cm , IBW - 70.5kg
 Mode : CMV
 FiO₂ : 100%  85%
 PEEP : 12
 RR : 24
 TV : 430
• ABGA after 6 hours of mechanical ventilation :
• pH 7.37 PCO₂ 44 PO₂ 75 HCO₃ 25.7 Lactate 1.46

20. How will you manage
further?
• Proning
• Recruitment maneuvers

21. Course in ICU (ICU Day 3 onward)
• Still PO2/FiO2 < 100, so proning done for 26 hours. After
1st cycle of proning, there was significant improvement in
oxygenation.
• ABGA (on CMV, 40% FiO2):
• pH 7.37 PCO2 52 PO2 97.7 HCO3 29.8 Lactate 1.03
• Total 5 cycles of proning ranging from 16-26 hours were
done from 05/10/15 to 10/10/15
• Patient has very high sedation requirement. To prevent
ventilatory dyssynchrony, patient was on atracurium +
Midazolam+Fentanyl infusion with regular sedation &
relaxant free interval in between.

22. Course in ICU (ICU Day 7 onward)
• CXR showed worsening with increasing TLC
• ET c/s – Acinetobacter
• Antibiotics were modified to Cefipime, Tigecycline and
Colistin.
• Serum Galactomannan – negative
• 10/10/15 onwards, patient was not maintaining adequate
saturation above 90% on 100% FiO2 & 12 PEEP & not even
while proning and after recruitment manuvouers.

23. How will you proceed
further?
• How will you manage refractory
hypoxemia?
• Role of Extracorporeal membrane
oxygenation (ECMO)
• VV vs VA ECMO
• Indications & Contraindication
• Evidence

24. Further plan of action
• ABGA on 11/10/15:
• pH 7.36 PO2 55.7 PCO2 70 HCO3 39 Lactate 2.35
• Till now, patient was hemodynamically stable, sensorium
was intact, had no other organ dysfunction & was passing
adequate urine output.
• Consensus was arrived after detailed discussion with
chest physician, among ICU team & with family to put
patient on ECMO. Patient was kept on VV ECMO on
11/10/15 with Right IJ & Right Femoral cannulation.
• Multiple sessions of bronchoscopies were done for lavage
as well as sampling.

25. Chest X-Ray (Before starting ECMO)

26. Date pH PCO2 HCO3 Lactate PO2 FiO2 PEEP
3/10
On 100% O2Mask
7.45 42 28.9 1.18 49.8 100%
4/10
On NIV
7.45 39 26.8 1.91 82 80% 8
5/10
Before Intubation – ON NIV
7.49 33 24.9 1.38 70 100% 8
5/10/15
After Intubation
7.37 44 25.7 1.46 75 85% 12
6/10
After 1st cycle of proning
7.37 52 29.8 1.03 97.7 40% 12
11/10
Before ECMO Initiation
7.36 70 39 2.35 55.7 100% 12

27. PO2 & FiO2 before ECMO Initiation
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
0.00
50.00
100.00
150.00
200.00
250.00
300.00
PO2
FiO2

28. PO2/FiO2 ratio before ECMO Initiation
0.00
50.00
100.00
150.00
200.00
250.00
300.00
PO2/FiO2
PO2/FiO2

29. • How to Initiate ECMO?
• Monitoring during ECMO

30. ECMO Initiation
• FiO2 : 100%
• Flow : 4.5 lit/min
• Sweep Gas : 3.5 lit/min
• Delta Pressure : 35
• Ventilator settings during ECMO :
• Mode : PCV
• FiO2 : 30%
• Rate : 12
• Pi : 26
• PEEP : 12

31. ECMO Monitoring Protocol
• 1. Ventilatory settings : Low FiO2 (25-30%), Rate
(12/min) Pi (24-26) ; PEEP (10-12) to keep alveoli
open
• 2. Blood gas targets : PO2 > 50, sPO2 >88% PCO2
40-45, pH 7.35-7.45
• 3. Investigations : CBC, ABGA, Electrolytes 8 hourly
for 2 days and then twice daily, ACT 4 hourly, PT,aPTT
once a day, Fibrinogen once and then every 3-4 day
• 4.Fluid management : To maintain flow and prepump
• 5. Adequate urine output and monitor color of urine

32. ECMO Monitoring Protocol
• 6.Transfusion Targets: Hb >9 , Platelet : >30,000 if not
bleeding and >75,000 if bleeding
• 7. Sedation as per requirement
• 8. Heparin infusion 20unit/kg/hr to target ACT around 180
• 9. No lipid based drugs (Propofol, liposomal amphotericin)
• 10. Adequate enteral nutrition
• 11. Genral nursing care while maintaing flow and
saturation

33. Date ECMO Settings Ventilator Setings Generated
Volume-
Avg
(Compliance)
ABGA
Flow Sweep
Gas
∆P FiO2
FiO2 RR PEEP Pi PO2 PCO2
11/10 4.5 3.5 35 100 30 12 12 26 250 86 51
12/10 4 3.5 35 100 30 12 12 26 250 75 48
13/10 4 5 28 100 30 12 12 26 200 78 45
14/10 3.5 5 28 100 30 12 12 26 250 78 40
15/10 3.5 4.5 26 100 30 12 12 26 270 76 38
16/10 3.5 4.5 26 100 30 12 11 26 220 72 36
17/10 3 4 26 100 30 12 10 26 250 84 39
18/10 3 4 24 100 30 12 10 26 220 88 38
19/10 3 3.5 24 60 30 12 10 26 250 84 42
20/10 3.4 3.5 28 100 30 12 10 26 250 82 44
21/10 3.4 3.5 26 60 30 12 10 26 280 81 35
22/10 3.2 2 28 21 40 24 8 26 300 90 42
23/10 3.6 1.5 28 40 45 26 7 26 320 88 44
24/10 3 0 28 0 45 26 6 28 350 82 48
25/10 3 0 28 0 45 28 6 28 380 79 47

34. Chest X-Ray – 5 days after ECMO

35. ECMO & Ventilator FiO2 trend during
ECMO
0
20
40
60
80
100
120
11-Oct
12-Oct
13-Oct
14-Oct
15-Oct
16-Oct
17-Oct
18-Oct
19-Oct
20-Oct
21-Oct
22-Oct
23-Oct
24-Oct
25-Oct
ECMO FiO2
Ventilator FiO 2

36. Flow & Sweep Gas trend during ECMO
0
1
2
3
4
5
6
7
11-Oct
12-Oct
13-Oct
14-Oct
15-Oct
16-Oct
17-Oct
18-Oct
19-Oct
20-Oct
21-Oct
22-Oct
23-Oct
24-Oct
25-Oct
Flow
Sweep Gas

37. Lung Compliance trend during ECMO
0
100
200
300
400
500
600
11-Oct
12-Oct
13-Oct
14-Oct
15-Oct
16-Oct
17-Oct
18-Oct
19-Oct
20-Oct
21-Oct
22-Oct
23-Oct
24-Oct
25-Oct
Generated Volume
Generated Volume

38. ECMO Weaning : How & When ?

39. ECMO weaning
• There was no significant radiological improvement, but
Lung compliance was improved after 10 days.
• From 21/10/15, ECMO weaning was started.
• On 25/10/15, finally ECHO was discontinued.

40. Course after ECMO removal
• Central line & Foley’s catheter were changed on
26/10/15
• Percutaneous tracheostomy was done on 26/10/15
• After tracheostomy, sedation requirement was
significantly decreased. Patient was neurologically
sound.
• Patient was maintaing sPO2 >90% for 3 days after
ECMO removal with FiO2 50-60% and PEEP 8, initially
on PCV and then on CMV.

41. Date pH PCO2 HCO3 Lactate PO2 FiO2 PEEP
11/10
Before ECMO Initiation
7.36 70 39 2.35 55.7 100% 12
11/10
After ECMO Initiation
7.42 35 23 1.01 81 100% 12
25/10
Before ECMO removal
7.38 47 27 1.12 79 45% 6
26/10
1 day after ECMO Removal
7.33 57 29 1.23 86 60% 8
27/10
2 day after ECMO Removal
7.37 56 32 1.01 99 45% 8
28/10
3 day after ECMO Removal
7.43 48 31 1.12 130 45% 8
30/10
5 day after ECMO Removal
7.25 90 39 2.42 48.1 100% 8
31/10
6 day after ECMO Removal
7.27 96 44 2.74 37.4 100% 8

42. PO2 & FiO2 trend after ECMO Removal
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
0
50
100
150
200
250
300
25-Oct 26-Oct 27-Oct 28-Oct 29-Oct 30-Oct 31-Oct
PO2
FiO2

43. Course after ECMO removal
• 2D ECHO (26/10/15) : WNL except PASP 74mmhg.
• iNO at 10-15 ppm was started on 26/10/15.
• Repeat 2D ECHO on 28/10/15 : PASP 45mmhg
• On 29/10/15, patient had increasing FiO2 requirement,
continuous fever, went into shock, vasopressors were
started & antibiotics were modified.

44. What is the Role on
inhaled NO?

45. Further Course in ICU
• Patient’s condition deteriorated inspite of all above
measures, patient developed refractory hypoxia & shock
on 30/10/15 and expired on 31/10/15.

46. Course in Hospital - Summary
2/10
• Admitted in Respi. HDU, ABG s/o Acute Hypoxemic Respiratory Failure, initially maintained sPO2
>90% on 100% O2 Mask
3/10
• Respiratory distress increased, not maintaing sPO2 >90% on 100% Mask
• Shifted to ICU, Managed with NIV (CPAP-PSV)
5/10
• Intubated in view of increasing distress & desaturation
• Taken on mechanical ventilator
5/10
•After 6 hours of mechcanial ventilation, PO2/FiO2 <100% despite recruitment manuvouer, so proning done for 26 hours
•PO2/FiO2 improved to >200 after 1st cycle of proning
5/10-
10/10
•Total 5 cycles of proning done ranging from 16-26 hours from 5/10 to 10/10
• PO2/FiO2 dropped <100 after 4 cycle of proning, Plan to start ECMO discussed with Family after 5th cycle of proning
11/10-
19/10
•ECMO initiated with minimum ventilatory support and 12 PEEP to keep alveoli open, Multiple sessions of broncoscopies done
•Lung complainance improved and ECMO weaning tried from 19/10
19/10-
25/10
• Lung Complaince gradually improved from 21/10 and ECMO weaning progressed
• Finally ECMO removed on 25/10
26/10-
28/10
•Central line & foley’s cather changed & tracheostomy done on 26/10; iNO started on 26/10 at 10-15 ppm i/v/o PASP 74mmhg
•Patient maintained sPO2 till 28/10, PASP went down upto 45
29/10-
31/10
• From 29/10, patient has gone into secondory sepsis with shock, & refractory hypoxia
• Inspite of all above efforts, patient expired on 31/10/15 due to refractory shock and hypoxia.

48. Important trials related to ARDS
• ARMA trial
• FACCT Trial
• Meta-analysis on N-M Blockers (Cisatracurium)
• Meta-analysis on role of steroid
• EXPRESS, LOVS, ALVEOLI trial & Metaanalysis
• OSCAR & OSCILLATE trial
• PROSEVA trial & previous meta-analysis on proning
• Meta-analysis on recruitment maneuvers

49. Questions…….?

50. Thank you
•THANK YOU