ARDS.ppt

2/5/2023 2
ACUTE RESPIRATORY
DISTRESS SYNDROME
Dr Sweta Salgaonkar
Dr Pallavi M, Dr.Prashant P
Dr Siva K, Dr Vijay R

2/5/2023 3
ETIOLOGY
&
PATHOGENESIS
Dr Vijay Rangani

2/5/2023 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

2/5/2023 5
Distinguishing cardiogenic from non-
cardiogenic pulmonary oedema.
CARDIOGENIC
 Heart disease.
 Third heart sound
 Central distribution
of infiltrates
 Widening of
vascular pedicles.
NON- CARDIOGENIC
 Absence of heart
disease
 No third heart sound
 Peripheral distribution
 Normal width of
vascular pedicle

2/5/2023 6
History of ARDS
 Petty Ashbaugh Severe Dyspnea, Tachypnea
et. al ,1971 Cyanosis refractory to O2
Decreased Pulmonary
compliance
Atelectasis, vascular congestion,
hyaline membrane at autopsy.

2/5/2023 7
History contd….
 Murray et al Preexisting Lung injury
1988 Mild to moderate or
severe lung injury
Non pulmonary organ
dysfunction

2/5/2023 8
History contd….
 Bernard et Acute onset
al 1994 Bilateral infiltrates on
chest x-ray
PAWP <18 mm Hg
Absence of clinical evidence
of left atrial hypertension

2/5/2023 9
Synonyms
 Adult hyaline membrane disease
 Congestive atelectasis
 Progressive pulmonary consolidation
 Hemorrhagic atelactasis
 Pump lung
 Shock lung
 Wet lung
 White lung

2/5/2023 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

2/5/2023 11
Inflammatory reaction

2/5/2023 12
components of DAD
 Initiating Agents
 activation of inflammatory cascade
 Lung sequestration of neutrophils
 Release of neutrophilic cytotoxic products
ALVELOAR WALL INJURY

2/5/2023 13
AETIOLOGY
PULMONARY EXTRA-PULMONARY

2/5/2023 14
Etiology (contd….)
Direct lung injury(pulmonary)
 Pneumonia ( most common )
 Aspiration
 Pulmonary contusion
 Fat emboli
 Near drowning
 Inhalation injury
 Oxygen
 Transthoracic radiation
 Reperfusion pulmonary oedema after Lung
Transplantation

2/5/2023 15
Etiology (contd….)
Indirect lung injury
( Extra-pulmonary)
 Sepsis (most common) – bacterial/viral/parasitic
 Sever Trauma with Shock
 Cardio Pulmonary Bypass
 Drug overdose
 Acute Pancreatitis
 Transfusion of blood products
 Hypothermia
 Eclampsia
 Embolism

2/5/2023 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

2/5/2023 17
ARDS
A : ASPIRATION
R : ROAD TRAFFIC ACCIDENTS
D : DIFFUSE ALVEOLAR DISEASE
S : SEPSIS

2/5/2023 18
Pathogenesis of ARDS
Focus of infection
Endotoxin
Complement direct cellular Cellular
Activation injury activation
Clotting cascade cytokine act. And
proteolytic enzymes
MODS (lung, heart,
GI, kidney, brain )

2/5/2023 19
Inflammatory mediators
 Cytokines
 Complement proteins
 Coagulation proteins
 Prostaglandins
 Vaso-active peptides
 Platelet Activating Factor
 Neutrophil products

2/5/2023 20
PATHOPHYSIOLOGY
& DIAGNOSIS
Dr Siva Krishna Kota

2/5/2023 21
Definition
Acute onset life threatening respiratory
failure with characteristic
ALI : PaO2/FiO2 < 300
ARDS : PaO2/FiO2 < 200
Physiological
features
Pathological
features
Radiological
features

2/5/2023 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)

2/5/2023 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

2/5/2023 26
Exudative phase (contd….)
Microatelectasis / alveolar collapse
-- interstitial edema
-- necrosed capillary endothelial
cell
-- alveolar cell + fibrin + plasma
protein together form hyaline
membrane

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Exudative phase (contd….)

2/5/2023 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

2/5/2023 29
Fibro-proliferative phase

2/5/2023 30
(c) Fibrotic phase
Characterized by:
– local fibrosis
– vascular obliteration
Repair process:
– resolution or fibrosis depending on
timing of intervention and management

2/5/2023 31
Clinico-pathological
correlation
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
on ventilator

2/5/2023 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.
respiratory failure unless assisted

2/5/2023 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

2/5/2023 34
ARDS: Radiological feature
Vascular pedicle
< 55mm
No distention of UL
zone vessels
Peripheral shadows
No pleural effusion
No septal lines

2/5/2023 35
Criteria for diagnosis
Clinical setting
Chest Xray findings
Physiological parameters
Pathological features
DIAGNOSIS

2/5/2023 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

2/5/2023 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
-heavy lungs(>1kg), a post mortem
finding
-congestive atelectasis
-hyaline membrane + fibrotic changes

2/5/2023 38
ALI (MURRAY) SCORE :
A. Chest Xray findings
(alveolar consolidation)
B. Oxygenation status
(PaO2 / FiO2 )
C. Pulmonary compliance
D. PEEP required
to maintain oxygenation

2/5/2023 39
ALI score (MURRAY-score) cont…..
1. Chest X film finding
Alveolar consolidation Score
One quadrant 1
Two quadrant 2
Three quadrant 3
Four quadrant 4
2. Oxygenation status
PaO2 / FiO2 Score
> 300 mmHg 0
225-299 mmHg 1
175-224 mmHg 2
100-174 mmHg 3
< 100 mmHg 4

2/5/2023 40
ALI score (MURRAY-score) cont…..
3. Pulmonary compliance
Compliance Score
(ml/cmH2O)
> 80 0
60-79 1
40-59 2
20-39 3
< 19 4
4. PEEP settings
PEEP Score
(cmH2O)
< 5 0
6-8 1
9-11 2
12-14 3
> 15 4

2/5/2023 41
ALI score (contd….)
Score:
0 = none,
0.1-2.5 = mild - moderate
> 2.5 = severe

2/5/2023 42
VENTILATORY
MANAGEMENT OF ARDS
Dr Pallavi Marghade

2/5/2023 43
Treatment Strategies
 Rx underlying cause
 Respiratory therapy for adequate
oxygenation/ventilation
 Adjunctive therapies

2/5/2023 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

2/5/2023 45
Conventional ventilation
 Consists of large tidal volume of 10-
15ml/kg
 Arterial oxygenation supported by
raising Fio2
 Applying PEEP

2/5/2023 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
MODS

2/5/2023 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 can be expanded in insp. Normal lung
at all but collapses during exp. (baby lung)
overdistention of alveoli
with normal Vt

2/5/2023 48
Flow - Time
Paw - Time
Volume - Time
0
60
60
Flow
L/min
Paw
cmH
2
O
V
T
ml
0
0
20
600
Time
VCV

2/5/2023 49
VALI (contd…..)
Barotrauma -
Application of excessive pressure to the alveoli
Air passes from damaged A-C membrane into
the interstitium,pleural space,mediastinum

2/5/2023 50
Flow - Time
Paw - Time
Volume - Time
0
60
60
Flow
L/min
Paw
cmH
2
O
V
T
ml
0
0
20
600
Time
PCV

2/5/2023 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

2/5/2023 52
How does PEEP work?
0
20

2/5/2023 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
LUNG INJURY( more in direct lung injury)

2/5/2023 55
“Open-Lung ” Approach to PEEP
 “Open-lung” approach
– Not practical
– Does not improve
outcomes
 Optimal PEEP
– ???
– Most cases: PEEP
15 – 20 cmH2O

2/5/2023 56
Fio2
 No detectable oxygen toxicity Fio2<
50%
 Diseased lungs more prone to injury
due to hyperoxia
 Fio2 < 0.6 considered to be safe

2/5/2023 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

2/5/2023 58
ARDS Network protocol
FIO2 - 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0
PEEP - 5 5-8 8-10 10 10-14 14 14-18 18-22
0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0

2/5/2023 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

2/5/2023 61
Lung-Protective Ventilation
Complications: (derecruitement)
– Elevated PaCO2
• Limit: pH > 7.20 –7.25
– Worsening hypoxemia
• Correction:
– Recruitement maneuver
– increasing PEEP

2/5/2023 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

2/5/2023 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
triggers the ventilator

2/5/2023 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

2/5/2023 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

2/5/2023 66
Inverse Ratio Ventilation
 Atelectatic alveoli are recruited and stabilised by
increasing the duration of inspiration
 I/E should be > 1
During PCV---- inspiratory time
VCV---- using deccelerating flow or
adding inspiratory pause
Disdvantages : Auto PEEP
Uncomfortable requiring
sedation/paralysis

2/5/2023 67
Flow - Time
0
60
60
Flow
L/min
I E I E
Normal ventilation

2/5/2023 68
0
60
60
Flow
L/min
I E I E I E
Reduce auto-PEEP by reducing I-time
- Decrease respiratory rate
- Decrease tidal volume
- Increase Inspiratory flow rate
Inverse ratio ventilation

2/5/2023 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

2/5/2023 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.

2/5/2023 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

2/5/2023 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.
COMPLICATION :
1. Necrotizing trachebronchitis.
2. Shear at interface of lung.
3. Air trapping.
Two controlled studies (113 and 309) no benefit.

2/5/2023 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 Higher Less
TP pressure Lower More
Result Atelactasis opening
PPL
-3.0
+2.8
PPL
-1.0
+1.0
Supine prone

2/5/2023 74
Prone ventilation (contd….)
c) Decrease chest wall compliance in p.p
Redistribution of tidal volume to atelactatic dorsal region.
d) Weight of heart may affect ventilation.
3. Improvement in Cardiac output
4. Better clearance of secretions
5. Improved lymphatic damage
Effect on gas exchange
Improves oxygenation – allows decrease Fio2; PEEP
- Variable
- not predictable
response rate – 50-70%

2/5/2023 75
Prone Ventilation (contd…)

2/5/2023 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
Circ electric, bed (Late 1970s).
Manual 2 step
Light weight portable support frame (Vollman prone positioner)

2/5/2023 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

2/5/2023 78
EXTRACORPOREAL
MEMBRANE OXYGENATION
Adaptation of conventional cardiopulmonary bypass technique.
Oxygenate blood and remove CO2 extracorporally.

2/5/2023 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
Gattinoni showed decreased mortality to 50% by using ECMO as
compared to 90% mortality in historical control group, therefore
the results are encouraging

2/5/2023 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

2/5/2023 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.

2/5/2023 82
ADJUNCTIVE THERAPY
IN ARDS
Dr Prashant Pawar

2/5/2023 83
Adjunctive therapies
1. Treatment of infective complications/inciting cause
2. Hemodynamic Management – Fluids, Vasopressors.
3. Nutritional support
4. Selective Pulmonary vasodilators.
5. Surfactant replacement therapy.
6. Anti-inflammatory Strategies.
a) Corticosteroids.
b) Cycloxygenase & lipoxygenase inhibitors.
c) Lisofylline and pentoxifylline.
7. Antioxidants – NAC : Procysteine
8. Anticoagulants.
9. Partial liquid ventilation.

2/5/2023 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

2/5/2023 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.
.

2/5/2023 86
Fluid management (contd..)
Detrimental effects
Ineffective Circulatory Volume (Sepsis).
Reduced cardiac output and decreased tissue perfusion.
Goal
Guidelines for management of tissue hypoxia International
consensus conference (AJRCCM- 1996)
1. Promote oxygen delivery
Adequate volume CVP – 8-12 mmHg
PAOP-14-16 mmHg (Optimal CO; less risk of Edema)
2. Crystalloids vs Colloids:No clear evidence
3. Blood Transfusion : Hb < 10 gm/dl
4. Reduce oxygen demand :
a) Sedation : Analgesia, NMBA
b) Treat Hyperpyrexia
c) Early institution of mech. vent. (shock).
5. No role of supraphysiological. oxygen delivery.

2/5/2023 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.

2/5/2023 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)

2/5/2023 89
Selective pulmonary
vasodilators
1. Inhaled Nitric oxide (iNo)
2. iv almitrine with/without iNo.
3. Aerosolized prostacyclins.
4. Inhibition of cyclic nucleotide phosphodiesterase.
5. Inhalation of Endothelin receptor antagonists

2/5/2023 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.
Selectivity of iNO
Rapid inactivation on contact with hemoglobin.

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 DOSAGE:
Effect Dose
Increase PaO2 1-2 ppm to <10 ppm
decrease PAP 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

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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.

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

2/5/2023 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

2/5/2023 95
Surfactant replacement
therapy
 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

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

2/5/2023 97
Anti inflammatory therapy
Glucocorticoids:
 No evidence of benefit in early sepsis/ARDS
 Methyl prednisolone in late stages associated
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

2/5/2023 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
 Reported to prevent ALI/ARDS in high risk surgical
patients
 NIH ARDS trial shows no benefits.

2/5/2023 99
Cycloxygenase inhibitors
 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

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Antioxidants therapy
 Reactive oxygen metabolites derived from neutrophils,
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

2/5/2023 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, 2
antiplasmin
 urokinase and tPA
 Fibrin causes__
Inhibit surfactant  atelactasis
with Fibrinonectin  Matrix on which fibroblast aggregation
and fibroblast proliferation
Potent chemotactic (Neutrophil recruitment)
Lung vasculature  PAH

2/5/2023 102
Activated Protein- C
 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

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ARDS and b-agonists
ENHANCED RESOLUTION
ALVEOLAR EDEMA
Alveolar clearance of edema depends on
active sodium transport across the alveolar
epithelium
b2 adrenergic stimulation :
1. Salmeterol
2. Dopamine
3. Dobutamine

2/5/2023 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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Partial Liquid Ventilation (contd....)
Mechanism of action
 Reduces surface tension
 Alveolar recruitment – liquid PEEP. Selective distribution to
dependent regions.
 surfactant phospholipid synthesis and secretion.
 Anti Inflammatory properties
A. Indirect : mitigation of VALI
B. Direct
a) endotoxin stimulated release of TNF; IL-1; IL-8.
b) decreases production of reactive oxygen species.
c) Inhibit neutrophil activation and chemostaxis.
d) Lavage of cellular debris.

2/5/2023 106
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 Loss of gas by evap.,
cost.
Partial Liquid Ventilation (contd..)

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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.

2/5/2023 108
Mystery Unsolved
THRIVE FOR THE BEST

2/5/2023 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

2/5/2023 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

2/5/2023 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

2/5/2023 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

2/5/2023 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

2/5/2023 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.

2/5/2023 115
ARDS: Lung Protection
 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

2/5/2023 116
The Future
Quantify the degree of primary v secondary
ARDS, to optimise ventilation strategy.
Monitor Real Time changes in ventilation

ARDS.ppt

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