CPAP, BiPAP  High Frequency Oscillatory Ventilation � HFOV  Airway Pressure Release Ventilation � APRV  Prone Positioning 12/20/13 62 Prone Positioning  Improves oxygenation  Reduces V/Q mismatch  Reduces ventilator induced lung injury  Improves lung compliance  Improves survival in severe ARDS  Complications: pressure sores, dislodgement of tubes 12/20/13

1. 12/20/13
1

2. 12/20/13
2
ACUTE RESPIRATORY
DISTRESS SYNDROME
Dr RAHUL ARORA

3. 12/20/13
3
ETIOLOGY
&
PATHOGENESIS

4. ARDS- Definition
Acute Respiratory Distress Syndrome
is diffuse pulmonary parenchymal
injury associated with :
Non Cardiogenic Pulmonary Edema
resulting in severe respiratory distress
and hypoxemic respiratory failure
12/20/13
4

5. Distinguishing cardiogenic from noncardiogenic pulmonary oedema.
CARDIOGENIC
NON- CARDIOGENIC
 Heart disease.
 Third heart sound
 Absence of heart
 Central distribution
of infiltrates
 Widening of
vascular pedicles.
12/20/13
disease
 No third heart sound
 Peripheral distribution
 Normal width of
vascular pedicle
5

6. History of ARDS
 Petty Ashbaugh Severe Dyspnea, Tachypnea
et. al ,1971
12/20/13
Cyanosis refractory to O2
Decreased Pulmonary
compliance
Atelectasis, vascular congestion,
hyaline membrane at autopsy.
6

7. History contd….
 Murray et al
1988
Preexisting Lung injury
Mild to moderate or
severe lung injury
Non pulmonary organ
dysfunction
12/20/13
7

8. History contd….
 Bernard et
al 1994
Acute onset
Bilateral infiltrates on
chest x-ray
PAWP <18 Mm Hg
Absence of clinical evidence
of left atrial hypertension
12/20/13
8

9. Synonyms
 Adult hyaline membrane disease
 Congestive atelectasis
 Progressive pulmonary consolidation
 Hemorrhagic atelactasis
 Pump lung
 Shock lung
 Wet lung
 White lung
12/20/13
9

10. DAD(Diffuse Alveolar Damage )
 DAD is a series of consistent although non
specific pathological change in the lung that result
from any injurious factor that damage
ENDOTHELIUM or ALVEOLAR EPITHELIUM
1) BRONCHIOLITIS OBLITERANS ORGANISING
PNEUMONIA
2) ACUTE INTERSTITIAL PNEUMONIA
DAD follows known catastrophic event that
result in ARDS
Sudden idiopathic Respiratory failure without
history of catastrophic event seen in AIP
12/20/13
10

11. Inflammatory reaction
12/20/13
11

12. components of DAD
 Initiating Agents
 activation of inflammatory cascade
 Lung sequestration of neutrophils
 Release of neutrophilic cytotoxic products
ALVELOAR WALL INJURY
12/20/13
12

13. AETIOLOGY
PULMONARY
12/20/13
EXTRA-PULMONARY
13

14. Etiology (contd….)
Direct lung injury(pulmonary)









12/20/13
Pneumonia ( most common )
Aspiration
Pulmonary contusion
Fat emboli
Near drowning
Inhalation injury
Oxygen
Transthoracic radiation
Reperfusion pulmonary oedema after Lung
Transplantation
14

15. Etiology (contd….)
Indirect lung injury
( Extra-pulmonary)
12/20/13









Sepsis (most common) – bacterial/viral/parasitic
Sever Trauma with Shock
Cardio Pulmonary Bypass
Drug overdose
Acute Pancreatitis
Transfusion of blood products
Hypothermia
Eclampsia
Embolism
15

16. TRALI :
Sudden onset of non-cardiogenic
pulmonary edema
 Often with systemic hypovolemia and
hypotension occuring during or within few
hours of transfusion
 Thought to be resulting from interaction of
specific leucocyte antibodies with leucocytes

12/20/13
16

17. ARDS
A : ASPIRATION
R : ROAD TRAFFIC ACCIDENTS
D : DIFFUSE ALVEOLAR DISEASE
S : SEPSIS
12/20/13
17

18. Pathogenesis of ARDS
Focus of infection
Endotoxin
Complement
Activation
direct cellular
injury
Clotting cascade
Cellular
activation
cytokine act. And
proteolytic enzymes
MODS
12/20/13
(lung, heart,
GI, kidney, brain )
18

19. Inflammatory mediators
 Cytokines
 Complement proteins
 Coagulation proteins
 Prostaglandins
 Vaso-active peptides
 Platelet Activating Factor
 Neutrophil products
12/20/13
19

20. 12/20/13
20
PATHOPHYSIOLOGY
& DIAGNOSIS
Dr Siva Krishna Kota

21. Definition
Acute onset life threatening respiratory
failure with characteristic
Physiological
features
Pathological
features
Radiological
features
ALI : PaO2/FiO2 < 300
ARDS : PaO2/FiO2 < 200
12/20/13
21

22. Pathophysiology
Profound inflammatory response secondary to a
pulmonary or extrapulmonary insult.
Diffuse alveolar damage
– acute exudative phase (1-7days)
– proliferative phase
(3-10 days)
– chronic/fibrotic phase (> 1-2 weeks)
12/20/13
22

23. (a) Exudative phase
 Basement membrane disruption
--Type I pneumocytes destroyed
--Type II pneumocytes preserved
 Surfactant deficiency
-- inhibited
by fibrin
--decreased type II cell production
-- impaired surfactant funtion
12/20/13
23

24. Exudative phase
12/20/13
24

25. Exudative phase
12/20/13
25

26. Exudative phase (contd….)
 Microatelectasis / alveolar collapse
-- interstitial edema
-- necrosed capillary endothelial
cell
-- alveolar cell + fibrin + plasma
protein together form hyaline
membrane
12/20/13
26

27. Exudative phase (contd….)
12/20/13
27

28. (b) Fibroproliferative phase
 Type II pneumocyte proliferate
-differentiate into Type I cells
-reline alveolar walls
-Regeneration of capillary endothelial cells
 Fibroblast proliferation
-interstitial/alveolar fibrosis
-Lymphocytic infiltration
-Collagen deposition
12/20/13
28

29. Fibro-proliferative phase
12/20/13
29

30. (c) Fibrotic phase
 Characterized by:
– local fibrosis
– vascular obliteration
 Repair process:
– resolution or fibrosis depending on
timing of intervention and management
12/20/13
30

31. Clinico-pathological
correlation
12/20/13
Stage I : unless direct lung injury is there
clear on auscultation
CXR unremarkable
Stage II : Hemodynamically stable
no respiratory distress
only mild tachypnea ( > 20/min )
ABG may show mild hypoxia
Stage III:worsening hypoxemia
dyspneic and cyanotic pt.
ed work of breathing
ed insp. pressure requirement in a patient
31
on ventilator

32. ARDS : Physiological features
A. Decreased lung compliance and volumes
microatelectasis
altered surfactant production & function
FRC causes distal air trapping
B. Increased work of breathing
in spontaneously breathing pts,
increased ratio of Vd/Vt ratio.
12/20/13
respiratory failure unless assisted
32

33. Physiological features (contd….)
C. Alteration in gas exchange (hypoxia)
- perfusion of underventilated lung
- perfusion of non ventilated lung
- impaired diffusion
- loss of HPV
D. Pulmonary hypertension and RVF
- pulmonary vasoconstriction
- platelet aggregation and micro thrombosis
- direct tissue damage & neurohormonal factors
12/20/13
33

34. ARDS: Radiological feature
Vascular pedicle
< 55mm
No distention of UL
zone vessels
Peripheral shadows
No pleural effusion
No septal lines
12/20/13
34

35. Criteria for diagnosis
Clinical setting
Chest Xray findings
Physiological parameters
Pathological features
DIAGNOSIS
12/20/13
35

36. Criteria for diagnosis
A. Clinical Settings :
(i) pulm/extrapulm catastrophe
(ii)exclusion of chronic pulmonary &
left heart diseases
(iii)clinical respiratory distress
B. CXRay :
diffuse bilateral infiltrates sparing apex,
cp- angle; with a narrow vascular pedicle
12/20/13
36

37. Criteria for diagnosis ( cont..)
C. Physiologic parameters :
(i) ABG :PaO2< 50 with FiO2 of > 0.6
(ii)Compliance < 50 ml/ cm of H2O
(iii) shunt fraction (Qs/Qt>20%)
(iv) dead space ventilation (Vd/Vt)
D. Pathologically
12/20/13
-heavy lungs(>1kg), a post mortem
finding
-congestive atelectasis
-hyaline membrane + fibrotic changes
37

38. ALI (MURRAY) SCORE :
A. Chest Xray findings
(alveolar consolidation)
B. Oxygenation status
(PaO2 / FiO2 )
C. Pulmonary compliance
D. PEEP required
to maintain oxygenation
12/20/13
38

39. ALI score (MURRAY-score)
1.
Chest X film finding
Alveolar consolidation
One quadrant
Two quadrant
Three quadrant
Four quadrant
12/20/13
Score
1
2
3
4
cont…..
2. Oxygenation status
PaO2 / FiO2
> 300 mmHg
225-299 mmHg
175-224 mmHg
100-174 mmHg
< 100 mmHg
Score
0
1
2
3
4
39

40. ALI score (MURRAY-score)
3. Pulmonary compliance
4. PEEP settings
Compliance
(ml/cmH2O)
PEEP
(cmH2O)
cont…..
> 80
60-79
40-59
20-39
< 19
12/20/13
Score
0
1
2
3
4
<5
6-8
9-11
12-14
> 15
Score
0
1
2
3
4
40

41. ALI score (contd….)
Score:
0
0.1-2.5
> 2.5
12/20/13
= none,
= mild - moderate
= severe
41

42. 12/20/13
42
VENTILATORY
MANAGEMENT OF ARDS
Dr Pallavi Marghade

43. Treatment Strategies

Rx underlying cause
 Respiratory therapy for adequate
oxygenation/ventilation
 Adjunctive therapies
12/20/13
43

44. Aims of Respiratory therapy
 to attempt to avoid tracheal intubation
 to reduce maximum pulmonary pressures
generated
 avoid high Fio2 to prevent oxygen toxicity
 maximise alveolar recruitment
 finally at minimal cost to the
cardiovascular system
12/20/13
44

45. Conventional ventilation
 Consists of large tidal volume of 10-
15ml/kg
 Arterial oxygenation supported by
raising Fio2
 Applying PEEP
12/20/13
45

46. Ventilator-Induced Lung
Injury(VALI)
Conventional ventilation
In injured lungs
High peak inflation and plateau pressure
Overdistention of alveoli
Volutrauma, Barotrauma, Induction of cytokines
12/20/13
MODS
46

47. VALI : Volutrauma
Direct physical damage to A-C membrane
stress failure
sudden & rapid increase in permeability
Gattinoni described three areas of lung on CT
Can’t be ventilated
at all
12/20/13
can be expanded in insp.
but collapses during exp.
Normal lung
(baby lung)
overdistention of alveoli
with normal 47
Vt

48. Flow L/min
60
0
60
Paw - Time
20
0
Volume - Time
600
VT ml
Paw cmH2O
VCV
Flow - Time
0
12/20/13
Time
48

49. VALI (contd…..)
Barotrauma Application of excessive pressure to the alveoli
Air passes from damaged A-C membrane into
the interstitium,pleural space,mediastinum
12/20/13
49

50. Flow - Time
Flow L/min
60
PCV
0
60
Paw cmH2O
20
Paw - Time
0
Volume - Time
VT ml
600
0
12/20/13
Time
50

51. VALI (contd….)
Cyclical airway closure –
Repeated opening & closing of airways with each tidal
volume
Atelectrauma
Surfactant loss
high forces needed to open
closed lung unit
Epithelial damage
12/20/13
51

52. How does PEEP work?
20
0
12/20/13
52

53. Mechanism of PEEP
12/20/13
53

54. PEEP Vs Fio2 : A Dilemma
 PEEP reduces intrapulmonary shunt and improves
arterial oxygenation at lower Fio2
 PEEP
cardiac output
pulmonary edema
dead space
resistance to bronchial circulation
lung volume and stretch during
inspiration
12/20/13
54
LUNG INJURY( more in direct lung injury)

55. “Open-Lung ” Approach to PEEP
 “Open-lung” approach
– Not practical
– Does not improve
outcomes
 Optimal PEEP
– ???
– Most cases: PEEP
15 – 20 cmH2O
12/20/13
55

56. Fio2
 No detectable oxygen toxicity Fio2<
50%
 Diseased lungs more prone to injury
due to hyperoxia
 Fio2 < 0.6 considered to be safe
12/20/13
56

57. Optimal PEEP
 Maximize O2 delivery
DO2 = 10 x CO x (1.34 x Hb x SaO2)
 Maximize lung compliance
Crs = Vt/(Pplateau – PEEP)
 Lowest PEEP to oxygenate @ FIO2 < .60
 Empiric approach:
PEEP = 16 cmH2O and Vt = 6 ml/kg
12/20/13
57

58. ARDS Network protocol
FIO2 - 0.3 0.4 0.5 0.6
0.3
0.4 0.5 0.6
0.7 0.8 0.9 1.01.0
0.7
0.8
0.9
PEEP -
10-14
12/20/13
5
5-8
8-10
10
14
14-18
18-22
58

59. Lung-Protective Ventilation
 VT = 6 mL/kg
 Limit plateau pressures < 30 cmH2O
– Volume controlled ventilation
 Limit peak airway pressures < 40 cmH2O
– Pressure controlled ventilation
12/20/13
59

60. Outcome
12/20/13
60

61. Lung-Protective Ventilation
 Complications: (derecruitement)
– Elevated PaCO2
• Limit: pH > 7.20 –7.25
– Worsening hypoxemia
• Correction:
– Recruitement maneuver
– increasing PEEP
12/20/13
61

62. Alternate Modes of
Mechanical Ventilation
 Non invasive ventilation
 Inverse-ratio ventilation
 Airway pressure-release ventilation
 Bilevel airway pressure ventilation
 Proportional-assist ventilation
 High-frequency ventilation
 Tracheal gas insufflation
 ECMO
12/20/13
62

63. Non Invasive
Positive Pressure Ventilation
 Tight fitting face
mask as a interface
between the ventilator
and patient.
 Pressure controlled
ventilation to prevent
leaks
 Pressure support
ventilation
 patient’s effort
12/20/13
63

64. NIPPV (contd….)
ADVANTAGES
 Can maintain verbal communication
 Can eat during therapy
 Decreased incidence of nosocomial
pneumonia
 Shorter requirement of ventilator assistance
and ICU stay
DISADVANTAGES
Not feasible in obtunded and delirious patients
 Additional time commitments from nurses and
respiratory therapist

12/20/13
64

65. Proportional-Assist ventilation
 Elevates airway pressure during inspiration
 Inspiratory airway pressure varies directly
with pt’s effort allowing breath to breath
variation
 Inspiratory assistance can be customised to
the elastance and resistance properties
 Best mode to use with NIPPV
12/20/13
65

66. Inverse Ratio Ventilation
 Atelectatic alveoli are recruited and stabilised by
increasing the duration of inspiration
 I/E should be > 1
12/20/13
During PCV---- inspiratory time
VCV---- using deccelerating flow or
adding inspiratory pause
Disdvantages : Auto PEEP
Uncomfortable requiring
sedation/paralysis
66

67. Normal ventilation
Flow L/min
60
I
E
I
E
0
60
12/20/13
Flow - Time
67

68. Inverse ratio ventilation
I
E
I
E
I
E
Flow L/min
60
0
60
12/20/13
Reduce auto-PEEP by reducing I-time
- Decrease respiratory rate
- Decrease tidal volume
- Increase Inspiratory flow rate
68

69. Airway Pressure
Release Ventilation
 Similar to IRV but Pt. can breath
spontaneously during prolonged period of
increased airway pressure
 Potential lung protective effects of IRV
 Air trapping occurs
12/20/13
69

70. TRACHEAL GAS INSUFFLATION
(TGI)
In ARDS/ALI
1. Increase physiological dead space
2. permissive hypercapnia
DURING CONVENTIONAL VENTILATION :
Bronchi and trachea are filled with alveolar gas
at end exhalation which is forced back into the
alveoli during next inspiration.
12/20/13
70

71. TGI (contd…..)
IN TGI
Stream of fresh air (4 to 8 L/min)
insufflated through a small catheter or
through small channel in wall of ET into
lower trachea flushing Co2 laden gas.
COMPLICATION
1) Dessication of secretions
2) Airway mucosal injury
3) Nidus for accumulation of secretions
4) Auto – PEEP
12/20/13
71

72. HIGH FREQUENCY VENTILATION
Utilizes small volume (<VD) and high RR (100 b/min)
 Avoids over distention (VALI).
 Alveolar recruitment.
 Enhances gas mixing, improves V/Q.
APPLICATION :
1. Neonatal RDS.
2. ARDS.
3. BPF.
12/20/13
COMPLICATION :
1. Necrotizing trachebronchitis.
2. Shear at interface of lung.
3. Air trapping.
Two controlled studies (113 and 309) no benefit.
72

73. Prone Ventilation
Proposed mechanism – how it improves oxygenation
1) Increase in FRC
2) Improved ventilation of previously dependent regions.
(a) Difference in diaphragmatic
supine: dorsal and ventral portion move
symmetrically
prone :dorsal > ventral
PPL at dorsal
TP pressure
Result
Higher
Lower
Atelactasis
Less
More
opening
PPL
-3.0
12/20/13
Supine
PPL
-1.0
+2.8
prone
+1.0
73

74. Prone ventilation (contd….)
c)
c)
1.
2.
3.
Decrease chest wall compliance in p.p
Redistribution of tidal volume to atelactatic dorsal region.
Weight of heart may affect ventilation.
Improvement in Cardiac output
Better clearance of secretions
Improved lymphatic damage
Effect on gas exchange
Improves oxygenation – allows decrease Fio2; PEEP
- Variable
- not predictable
response rate – 50-70%
12/20/13
74

75. Prone Ventilation (contd…)
12/20/13
75

76. PRONE VENTILATION (contd….)
CONTRAINDICATION
Unresponsive cerebral hypertension
Unstable bone fractures
Left heart failure
Hemodynamic instability
Active intra abdominal pathology
TIMING
ARDS > 24 hrs./ 2nd day
FREQUENCY
Usually one time per day
DURATION 2 to 20 hrs/day.
OUTCOME
Improvement in oxygenation
No improvement in survival
POSITIONING ACHIEVED BY
12/20/13
Circ electric, bed (Late 1970s).
Manual 2 step
76
Light weight portable support frame (Vollman prone positioner)

77. PRONE VENTILATION (contd….)
NO. OF PERSONS 3-5
POSITION OF ABDOMEN
allowed to protrude ; partial/complete restriction
POSITION OF HEAD
Head down/ Head up position.
ADEQUATE SEDATION +/- NMBA
COMPLICATIONS
pressure sore
Accident removal of ET; Catheters
Arrhythmia
Reversible dependent odema (Face, anterior chest wall)
Gattinoni et al, in a MRCT evaluated the effect of 7 hr / day
prone positioning x 10 day
improvement in oxygenation, no survival benefit
12/20/13
77

78. EXTRACORPOREAL
MEMBRANE OXYGENATION
Adaptation of conventional cardiopulmonary bypass technique.
Oxygenate blood and remove CO2 extracorporally.
12/20/13
78

79. ECMO (contd….)
TYPES
1.
High-flow venoarterial bypass system.
2.
Low-flow venovenous bypass system.
Criteria for treatment with extracorporeal gas exchange
Fast entry criteria
PaO2 <50 mmHg for >2 h at FiO2 1.0; PEEP > 5 cmH2O
Slow entry criteria
PaO2 <50 mmHg for >12 h at FiO2 0.6; PEEP > 5 cmH2O
maximal medical therapy >48 h
Qs /Qt > 30%; Cstat <30 ml/cmH2O
12/20/13
Gattinoni showed decreased mortality to 50% by using ECMO as
compared to 90% mortality in historical control group, therefore
79
the results are encouraging

80. ARDS study : KEM Hospital
Statistics:
 study done over 2 years,
 mortality – 46.2%
 commonest etiology – pneumonia &
tropical diseases
 50% of pts with renal and hematologic complication
didn’t survive
 MODS, LIS, APACHE-II were the mortality predictors
12/20/13
80

81. ARDS study : KEM Hospital (contd….)
 60% of pts required mechanical ventilation
 survivors spent less no. of days than the non
survivors on ventilator due to innate complication
of mechanical ventilation
 Use of steroids didn’t reduce mortality
 PFT done in 7 survivors showed abnormality due
to both ARDS & VALI
 long term assessment was not possible because of
non-compliance of patients to follow up.
12/20/13
81

82. 12/20/13
82
ADJUNCTIVE THERAPY
IN ARDS
Dr Prashant Pawar

83. Adjunctive therapies
1.
2.
3.
4.
5.
6.
7.
8.
9.
12/20/13
Treatment of infective complications/inciting cause
Hemodynamic Management – Fluids, Vasopressors.
Nutritional support
Selective Pulmonary vasodilators.
Surfactant replacement therapy.
Anti-inflammatory Strategies.
a)
Corticosteroids.
b)
Cycloxygenase & lipoxygenase inhibitors.
c)
Lisofylline and pentoxifylline.
Antioxidants – NAC : Procysteine
Anticoagulants.
Partial liquid ventilation.
83

84. Treatment of infective
complications
Most common complication is nosocomial
infection due to gram negative organisms and it
is the major cause of death
Antibiotics to be chosen as per :
• Initial insult of ARDS
• Sputum culture best taken shortly after
intubation
• Bronchoalveolar lavage
• Blood culture & sensitivity
12/20/13
84

85. HEMODYNAMIC MANAGEMENT
 Controversial
 Restrictive Fluid management
 Benefits shown by studies
∀ ↓pulmonary edema formation
∀ ↑ compliance and lung function
• Negative fluid balance is associated with
improved survival
• Net positive balance <1 litre in first 36 hrs.
associated with improved survival
• decrease length of ventilation, ICU stay and
hospitalization.
12/20/13
.
85

86. Fluid management (contd..)
Detrimental effects
Ineffective Circulatory Volume (Sepsis).
Reduced cardiac output and decreased tissue perfusion.
Goal
1.
2.
3.
4.
12/20/13
5.
Guidelines for management of tissue hypoxia International
consensus conference (AJRCCM- 1996)
Promote oxygen delivery
Adequate volume CVP – 8-12 mmHg
PAOP-14-16 mmHg (Optimal CO; less risk of Edema)
Crystalloids vs Colloids:No clear evidence
Blood Transfusion : Hb < 10 gm/dl
Reduce oxygen demand :
a) Sedation : Analgesia, NMBA
b) Treat Hyperpyrexia
c) Early institution of mech. vent. (shock).
No role of supraphysiological. oxygen delivery.
86

87. Vasopressors
Vasopressors
 Following restoration of intravascular volume to
euvolemic levels
(CVP:4-8cm of H2O, PCWP:6-14 mmHg)
 GOAL to achieve MAP 55 to 65 mmHg
 No clear evidence that any vasopressor or
combination of them is superior.
12/20/13
87

88. Nutritional support
Goals of nutritional support
 nutrients as per pt’s metabolic demand
 Treatment & prevention of macro/micro
nutrients deficiency.
 Enteral mode is to be preferred
( less infection and low cost)
 High fat, low carbohydrate diet es RQ,
CO2 production and duration of ventilation
 Immunomodulatory nutrition like amino acids,
omega-3 fatty acids. ( no survival benefit)
12/20/13
88

89. Selective pulmonary
vasodilators
1.
2.
3.
4.
5.
12/20/13
Inhaled Nitric oxide (iNo)
iv almitrine with/without iNo.
Aerosolized prostacyclins.
Inhibition of cyclic nucleotide phosphodiesterase.
Inhalation of Endothelin receptor antagonists
89

90. Inhaled nitric oxide
Mechanism : Endothelial derived relaxing factor
Smooth muscle vasodilation through
activation of cyclic GMP
Benefits in ARDs
1. Improves Oxygenation
2. Improves V/Q mismatch.
3. Reduction in pulmonary artery pressure
4. Inhibits platelet aggregation and neutrophil
adhesion.
12/20/13
Selectivity of iNO
Rapid inactivation on contact with hemoglobin.
90

91. Inhaled nitric oxide
 DOSAGE:
Effect
Increase PaO2
decrease PAP
Dose
1-2 ppm to <10 ppm
10-40 ppm
 Time of Response :
<10 min to several hours.
Response to iNo is not static phenomenon.
 Mortality Benefits : None
 Possible role in severe refractory hypoxemia a/w PAH
12/20/13
91

92. Inhaled nitric oxide
Side effects :
Usually Minimal
1. Rebound pulmonary hypertension & hypoxemia
2. Methemoglobinemia
3. Toxic NO2 ; Nitrous & Nitric Acid
Prevented by decreasing contact time & conc. of gas.
12/20/13
92

93. Almitrine
 Given iv : in low doses
 Potentates hypoxic pulmonary vasoconstriction
 Decreases shunt and thus improved oxygenation
Has additive effect with :
iNo
iNo + prone position
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93

94. Pulmonary vasodilators(contd…)
Prostacyclins:



iv prostacyclin decreases pulmonary arterial pressure non
selectively, can increase shunt; worsen oxygenation.
Inhaled prostacyclin selectively vasodilates the well
ventilated areas
Selectivity in dose of 17-50 ng/kg/min.
PGI2- Not metabolized in lung so lost at higher doses.
PGE1- 70-80% is metabolized in lung.
PDE –5 Inhibitors: Dipyridamole ; Sildenafil
Endothelin receptor antagonist
Nonselective ET antagonist-bosentan
Selective ETA 2 antagonist –LU-B1352
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94

95. Surfactant replacement
therapy




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Deficiency and functional abnormality of surfactant
1. Decreases production
2. Abnormal composition
3. Inhibitors of surfactant function
4. Conversion of large to small surfactant aggregates
5. Alteration/Destruction caused by substances in alveolar space
(plasma, fibrinogen, fibrin, alb; Hb)
Impaired surfactant function:
1) Atelactasis / collapse
2) Increase edema formation
Benefits : Improved lungs function., compliance,
oxygenation.
Mortality benefits: none
95

96. Surfactant Delivery Techniques
Instillation
• Rapid
Lavage
• May remove toxic
volume
•Homogenous
distribution
substances.
•Can deliver large
volume.
•Homogenous
distribution.
• Techn. Not
• Vol. recover can
•Can deliver large
standardized
• Short term
impairment in
ventilation
be poor
• Short term
impairment in
ventilation.
Aerosolization
Continuous smaller
volume.
Non uniform
distribution.
Slow, no optimal
device, Filters may
plug.

97. Anti inflammatory therapy
Glucocorticoids:
 No evidence of benefit in early sepsis/ARDS
 Methyl prednisolone in late stages associated
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with improved LIS score & decreased mortality
 Steroids
-Inhibit transcriptional activation of various
cytokines
-Inhibit synthesis of phospholipase A2
-Reduced production of prostanoids, PAF
-Decreases Fibrinogenesis
 Increased Risk of Nosocomial Infection 97

98. Anti infl. Therapy(contd….)
Lisophylline & Pentoxifyline

Phosphodiesterase inhibitor
-Inhibit neutrophil chemotaxis & activation

Lisophylline inhibits release of FreeFattyAcids from cell
membrane under oxidative stress

NIH ARDS trial shows no benefits.
Ketoconazole

Potent inhibitor of thromboxane and LT synthesis

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Reported to prevent ALI/ARDS in high risk surgical
patients

NIH ARDS trial shows no benefits.
98

99. Cycloxygenase inhibitors




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TxA2 and Prostaglandin produced from AA by
Cyclooxygenase pathway.
Cause
1. Neutrophil chemotaxis and adhesion
2. Broncho-constriction
3.↑ vascular permeability
4. platelet aggregation
Animal studies shown that Cycloxygenase inhibitors
attenuate lung injury ;and improve pulmonary
hypertension and hypoxemia
Clinical trials of ibuprofen : No proven benefits
99

100. Antioxidants therapy
 Reactive oxygen metabolites derived from neutrophils,




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macrophages and endothelial cells
OXIDANTS INCLUDE
Super oxide ion (02-), hydrogen peroxide (H2O2)
hypochlorous acid (Hocl), hydroxyl radical (OH..)
Interact with proteins, lipid and DNA
ENDOGENOUS ANTIOXIDANTS
Superoxide dismutase, Glutathione, Catalase
Vit E & Vit C ; Sulfhydryls
Antioxidant therapy
replenishing glutathione-cysteine derivatives :
N-Acetyl Cysteine & procysteine
Beneficial effects not proven
100

101. ANTICOAGULANT THERAPY
IN ARDS
In ARDS – Fibrin deposition intra-alveolar and interstitial.
Local procoagulant activity and reduced fibrinolysis.
↑ Procoagulant
↓ Fibrinolysis
↑ TF (VIIa)
Fibrinolytic inhibitors
↑ PAI–1 ; PAI-2, α2
antiplasmin
↓ urokinase and tPA
↑ Fibrin causes__
Inhibit surfactant → atelactasis
with Fibrinonectin → Matrix on which fibroblast aggregation
and fibroblast proliferation
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Potent chemotactic (Neutrophil recruitment)
101

102. Activated Protein- C




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Protein-c :Naturally occuring anticoagulant
1.Inactivates Va & VIIa – limit thrombin generation.
2.Inhibit PAI-1 activity - ↑ fibrinolysis.
3.Anti-inflam. - ↓ cytokines, inhibit apoptosis.
APC administ. Improved survival.
absolute risk reduction in mortality
Faster resolution of respiratory dysfuntion.
Adverse effects
Risk of bleeding
Efficacy proved in severe sepsis
102

103. ARDS and β-agonists
ENHANCED RESOLUTION
ALVEOLAR EDEMA
Alveolar clearance of edema depends on
active sodium transport across the alveolar
epithelium
β2 adrenergic stimulation :
1.
2.
3.
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Salmeterol
Dopamine
Dobutamine
103

104. Partial Liquid Ventilation
In ARDS there is increased surface tension which can be
eliminated by filling the lungs with liquid (PFC).
Perflurocarbon:
Colourless, clear, odourless, inert, high vapour
pressure
Insoluble in water or lipids
Most common used – perflubron ( Perfluoro octy
bromide)
Characteristics of PLV
1.Improved Compliance/ Gas exchange
2. Anti-inflam. properties
3.Decreased risk of nosocomial pneumonia.
4.Reduces pulmonary vascular resistance.
5.Little effect on hemodynamics
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104

105. Partial Liquid Ventilation (contd.. ..)
Mechanism of action




A.
B.
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Reduces surface tension
Alveolar recruitment – liquid PEEP. Selective distribution
to dependent regions.
surfactant phospholipid synthesis and secretion.
Anti Inflammatory properties
Indirect : mitigation of VALI
Direct
a) endotoxin stimulated release of TNF; IL-1;
IL8.
b) decreases production of reactive oxygen species.
c) Inhibit neutrophil activation and chemostaxis.
d) Lavage of cellular debris.
105

106. Partial Liquid Ventilation (contd..)
Total Liquid
Ventilation
Partial Liquid
Ventilation
1. Ventilator
Liquid
Conventional
2. Tidal volume delivered of
Oxygenated PFC
Gas
3. Lungs are filled
Completely by
PFC
Filled till FRC by
PFC
4. Feasibility
Experimental
Yes
5. Disadvantage
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Loss of gas by evap.,
cost.
106

107. Partial Liquid Ventilation (contd..)
Recommended dose of PFC
20ml/kg
-Beyond this dose – decrease
cardiac output
-More clinical trials are required to
demonstrate efficacy.
 Additive effect of PLV has been
shown in combination with:
-NO
-Surfactant
-HFOV
-prone ventilation
 Trials of PLV in ARDS confirmed
safety but not efficacy.
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107

108. Mystery Unsolved
12/20/13
THRIVE FOR THE BEST
108

109. 12/20/13
109
What have we learnt?
ALI- Syndrome of
pulmonary inflammation,
 vasoconstriction,
greater permeability of both alveolar
capillary endothelium & epithelium,
non-cardiogenic pulmonary oedema

 arterial hypoxemia resistant to O2
therapy,
 appearance of diffuse infiltrates on
X-ray chest

110. ARDS
 Not a single disease but rather a
pathophysiologic syndrome
 Catastrophic acute respiratory failure of
diverse etiology & high mortality
 No single test or marker to accurately
diagnose or predict the outcome of ARDS
 Represents the pulmonary expression of
systemic inflammatory process
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110

111. ARDS
 Associated with triggering events.
 Lungs bear the brunt of the injury as it
receives entire C O with exposure to
circulating agents and
exposure to environmental insults during
ventilation
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111

112. ARDS
Dysregulated inflammatory-reparative processes  lung
injury & repair
 Important to understand the initiators & mediators of
immunochemical response of ARDS & its effects  O2
debt & tissue hypoxia , improper tissue O2 utilization
 O2 debt from ↓ ed tissue perfusion organ failure ;
monitoring O2 debt & optimizing peripheral tissue
oxygenation imp; transcutaneous surface electrode for
high risk surgical patients
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112

113. ARDS- notions about fluid
therapy
 Hypovolemia – major pathophysiologic factor of
ARDS
 Pulmonary edema – an effect, not the cause of
ARDS
 Fluid restriction may ↓ CO & tissue perfusion &
worsen non pulmonary organ function
 ARDS – an end organ failure of an antecedent
hypovolemic-hypoxemic event except for ARDS
caused by direct lung injury
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113

114. ARDS: Lung Protection
Evidence supports a volume and pressure
limited approach
 In majority of patients with ARDS lung
recruitment and overinflation occur
simultaneously in different lung regions as seen
on CT imaging
• High PAP opens collapsed ARDS lung and
partially opens oedematous ARDS lung.
• High PEEP and Low Vt decrease lung
cytokines and survival.

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114

115. ARDS: Lung Protection


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Use of high PEEP and
Recruitment maneuvers
may not help when low
potential for recruitment.
(consolidation)
Improving oxygenation by
itself does not equate with
improved outcome
115

116. The Future
 Quantify the degree of primary v secondary
ARDS, to optimise ventilation strategy.
 Monitor Real Time changes in ventilation
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116

117. The
End
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117

118. 12/20/13
118