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Transcript of ARDS
04/11/23 1
04/11/23 2
ACUTE RESPIRATORYDISTRESS SYNDROME
Dr RAHUL ARORA
04/11/23 3
ETIOLOGY &
PATHOGENESIS
04/11/23 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
04/11/23 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
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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.
04/11/23 7
History contd….
Murray et al Preexisting Lung injury
1988 Mild to moderate or
severe lung injury
Non pulmonary organ
dysfunction
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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
04/11/23 9
Synonyms
Adult hyaline membrane disease Congestive atelectasis Progressive pulmonary consolidation Hemorrhagic atelactasis Pump lung Shock lung Wet lung White lung
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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
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Inflammatory reaction
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components of DAD
Initiating Agents activation of inflammatory cascade Lung sequestration of neutrophils Release of neutrophilic cytotoxic products
ALVELOAR WALL INJURY
04/11/23 13
AETIOLOGY
PULMONARY EXTRA-PULMONARY
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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
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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
04/11/23 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
04/11/23 17
ARDS
A : ASPIRATION
R : ROAD TRAFFIC ACCIDENTS
D : DIFFUSE ALVEOLAR DISEASE
S : SEPSIS
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Pathogenesis of ARDS
Focus of infection Endotoxin
Complement direct cellular CellularActivation injury activation
Clotting cascade cytokine act. And proteolytic enzymes
MODS (lung, heart,GI, kidney, brain )
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Inflammatory mediators
Cytokines Complement proteins Coagulation proteins Prostaglandins Vaso-active peptides Platelet Activating Factor Neutrophil products
04/11/23 20
PATHOPHYSIOLOGY & DIAGNOSIS
Dr Siva Krishna Kota
04/11/23 21
Definition
Acute onset life threatening respiratory
failure with characteristic
ALI : PaO2/FiO2 < 300
ARDS : PaO2/FiO2 < 200
Physiological features
Pathological features
Radiologicalfeatures
04/11/23 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)
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(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
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Exudative phase
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Exudative phase
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Exudative phase (contd….)
Microatelectasis / alveolar collapse
-- interstitial edema
-- necrosed capillary endothelial
cell
-- alveolar cell + fibrin + plasma
protein together form hyaline
membrane
04/11/23 27
Exudative phase (contd….)
04/11/23 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
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Fibro-proliferative phase
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(c) Fibrotic phase
Characterized by:– local fibrosis– vascular obliteration
Repair process:– resolution or fibrosis depending on timing of intervention and management
04/11/23 31
Clinico-pathological correlation
Stage I : unless direct lung injury is there clear on auscultation CXR unremarkableStage II : Hemodynamically stable no respiratory distress only mild tachypnea ( > 20/min ) ABG may show mild hypoxiaStage III:worsening hypoxemia dyspneic and cyanotic pt. ed work of breathing ed insp. pressure requirement in a patient on ventilator
04/11/23 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
04/11/23 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
04/11/23 34
ARDS: Radiological feature
Vascular pedicle
< 55mm
No distention of UL zone vessels
Peripheral shadows
No pleural effusion
No septal lines
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Criteria for diagnosis
Clinical setting
Chest Xray findings
Physiological parameters
Pathological features
DIAGNOSIS
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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
04/11/23 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
04/11/23 38
ALI (MURRAY) SCORE :
A. Chest Xray findings
(alveolar consolidation)
B. Oxygenation status
(PaO2 / FiO2 )
C. Pulmonary compliance
D. PEEP required
to maintain oxygenation
04/11/23 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
04/11/23 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
04/11/23 41
ALI score (contd….)
Score:
0 = none,
0.1-2.5 = mild - moderate
> 2.5 = severe
04/11/23 42
VENTILATORY MANAGEMENT OF ARDS
Dr Pallavi Marghade
04/11/23 43
Treatment Strategies
Rx underlying cause
Respiratory therapy for adequate oxygenation/ventilation
Adjunctive therapies
04/11/23 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
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Conventional ventilation
Consists of large tidal volume of 10-15ml/kg
Arterial oxygenation supported by raising Fio2
Applying PEEP
04/11/23 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
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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
04/11/23 48
Flow - Time
Paw - Time
Volume - Time
0
60
60
Flo
w L
/min
Paw
cm
H2O
VT
ml
0
0
20
600
Time
VCV
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VALI (contd…..)
Barotrauma - Application of excessive pressure to the alveoli
Air passes from damaged A-C membrane into the interstitium,pleural space,mediastinum
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Flow - Time
Paw - Time
Volume - Time
0
60
60
Flo
w L
/min
Paw
cm
H2O
VT
ml
0
0
20
600
Time
PCV
04/11/23 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
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How does PEEP work?
0
20
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Mechanism of PEEP
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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)
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“Open-Lung ” Approach to PEEP
“Open-lung” approach– Not practical
– Does not improve outcomes
Optimal PEEP– ???
– Most cases: PEEP
15 – 20 cmH2O
04/11/23 56
Fio2
No detectable oxygen toxicity Fio2< 50%
Diseased lungs more prone to injury due to hyperoxia
Fio2 < 0.6 considered to be safe
04/11/23 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
04/11/23 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
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Lung-Protective Ventilation
VT = 6 mL/kg
Limit plateau pressures < 30 cmH2O
– Volume controlled ventilation
Limit peak airway pressures < 40 cmH2O
– Pressure controlled ventilation
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Outcome
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Lung-Protective Ventilation
Complications: (derecruitement)
– Elevated PaCO2
• Limit: pH > 7.20 –7.25
– Worsening hypoxemia• Correction:
– Recruitement maneuver – increasing PEEP
04/11/23 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
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Non InvasivePositive 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
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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
04/11/23 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
04/11/23 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 pauseDisdvantages : Auto PEEP Uncomfortable requiring sedation/paralysis
04/11/23 67
Flow - Time
0
60
60
Flo
w L
/min
I E I E
Normal ventilation
04/11/23 68
0
60
60
Flo
w 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
04/11/23 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
04/11/23 70
TRACHEAL GAS INSUFFLATION (TGI)
In ARDS/ALI1. Increase physiological dead space2. 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.
04/11/23 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.
COMPLICATION1) Dessication of secretions 2) Airway mucosal injury 3) Nidus for accumulation of secretions4) Auto – PEEP
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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.
04/11/23 73
Prone Ventilation
Proposed mechanism – how it improves oxygenation 1) Increase in FRC2) Improved ventilation of previously dependent regions.
(a) Difference in diaphragmatic supine: dorsal and ventral portion move
symmetrically prone :dorsal > ventral
PPL at dorsal Higher LessTP pressure Lower MoreResult Atelactasis opening
PPL
-3.0
+2.8
PPL
-1.0
+1.0Supine prone
04/11/23 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%
04/11/23 75
Prone Ventilation (contd…)
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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 dayDURATION 2 to 20 hrs/day. OUTCOME Improvement in oxygenation No improvement in survival
POSITIONING ACHIEVED BY Circ electric, bed (Late 1970s).Manual 2 stepLight weight portable support frame (Vollman prone positioner)
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PRONE VENTILATION (contd….)NO. OF PERSONS 3-5POSITION OF ABDOMEN
allowed to protrude ; partial/complete restrictionPOSITION OF HEAD
Head down/ Head up position. ADEQUATE SEDATION +/- NMBACOMPLICATIONS
- 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
04/11/23 78
EXTRACORPOREAL MEMBRANE OXYGENATION
Adaptation of conventional cardiopulmonary bypass technique.
Oxygenate blood and remove CO2 extracorporally.
04/11/23 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
04/11/23 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
04/11/23 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 mortalityPFT 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.
04/11/23 82
ADJUNCTIVE THERAPYIN ARDS
Dr Prashant Pawar
04/11/23 83
Adjunctive therapies
1. Treatment of infective complications/inciting cause2. Hemodynamic Management – Fluids, Vasopressors.3. Nutritional support4. Selective Pulmonary vasodilators.5. Surfactant replacement therapy. 6. Anti-inflammatory Strategies. a) Corticosteroids. b) Cycloxygenase & lipoxygenase inhibitors. c) Lisofylline and pentoxifylline.7. Antioxidants – NAC : Procysteine8. Anticoagulants.9. Partial liquid ventilation.
04/11/23 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
04/11/23 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.
.
04/11/23 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 mmHgPAOP-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, NMBAb) Treat Hyperpyrexia c) Early institution of mech. vent. (shock).
5. No role of supraphysiological. oxygen delivery.
04/11/23 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.
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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)
04/11/23 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
04/11/23 90
Inhaled nitric oxide
Mechanism : Endothelial derived relaxing factor Smooth muscle vasodilation through
activation of cyclic GMPBenefits in ARDs1. Improves Oxygenation 2. Improves V/Q mismatch.3. Reduction in pulmonary artery pressure4. Inhibits platelet aggregation and neutrophil adhesion.
Selectivity of iNORapid inactivation on contact with hemoglobin.
04/11/23 91
Inhaled nitric oxide
DOSAGE:Effect Dose
Increase PaO2 1-2 ppm to <10 ppmdecrease 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
04/11/23 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.
04/11/23 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
04/11/23 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
04/11/23 95
Surfactant replacement therapy
Deficiency and functional abnormality of surfactant 1. Decreases production 2. Abnormal composition 3. Inhibitors of surfactant function4. 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.
04/11/23 97
Anti inflammatory therapy
Glucocorticoids:No evidence of benefit in early sepsis/ARDSMethyl prednisolone in late stages associated
with improved LIS score & decreased mortalitySteroids
-Inhibit transcriptional activation of various cytokines -Inhibit synthesis of phospholipase A2 -Reduced production of prostanoids, PAF -Decreases Fibrinogenesis Increased Risk of Nosocomial Infection
04/11/23 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.
04/11/23 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
04/11/23 100
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
04/11/23 101
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
04/11/23 102
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
04/11/23 103
ARDS and -agonists
ENHANCED RESOLUTION ALVEOLAR EDEMA Alveolar clearance of edema depends on active sodium transport across the alveolar epithelium
2 adrenergic stimulation :
1. Salmeterol 2. Dopamine3. Dobutamine
04/11/23 104
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
04/11/23 105
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 VALIB. 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.
04/11/23 106
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..)
04/11/23 107
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.
04/11/23 108
Mystery Unsolved
THRIVE FOR THE BEST
04/11/23 109
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
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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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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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ARDSDysregulated 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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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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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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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
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The Future
Quantify the degree of primary v secondary ARDS, to optimise ventilation strategy.
Monitor Real Time changes in ventilation
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The End
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