3. Timeline
• In 1967 – Ashbaugh, Bigelow, Petty, Levine - described Acute
Respiratory Distress Syndrome in adults
• In 1971, Petty and Ashbaugh modified its name from ‘acute’ to ‘adult’
Respiratory Distress Syndrome; to differentiate it from its newborn
counterpart
• In 1974, Webb and Tierney confirmed the existence of ventilator
associated lung injury
4. Timeline
• In 1992, American European Consensus Conference (AECC) gave
standardized definition for ARDS
• In 1997, Tremblay et al introduced the concept of biotrauma
• In 1998, Amato et al, conducted RCT - decrease in mortality using
low tidal volume ventilation and high PEEP (open lung strategy)
• In 2000, ARDS network trial demonstrated the benefits of low tidal
volume and PEEP ventilation
5. Definitions of ARDS
Ashbaugh and colleagues, 1967
• Severe dyspnea
• Tachypnea
• Cyanosis refractory to oxygen therapy
• Decreased pulmonary compliance
• Diffuse alveolar infiltrates on chest radiograph.
Loosely defined criteria
Definition of hypoxemia inconsistent
6. Bernard and colleagues, 1992
(American European Consensus conference definition)
A three-criteria system including chest radiograph, oxygenation score,
and exclusion of cardiogenic causes:
• Acute onset, bilateral infiltrates on chest radiography,
• Acute lung injury ~ PaO2/FIO2 ≤ 300
ARDS subset~ PaO2/FIO2 ≤ 200
• Pulmonary-artery wedge pressure of <18 mm Hg or the absence of
clinical evidence of left atrial hypertension
7. Bernard and colleagues, 1992
(American European Consensus conference definition)
Problems
• Acute onset : arbitrary; <1 week
• Bilateral infiltrates: inter observer variation, b/l pneumonia,
atelectasis, cardiogenic pulmonary edema
• PAOP of <18 mm Hg /absence of clinical evidence of left atrial
hypertension : PAOP: poor estimate of PVH, falsely raised with high
airway pressures
• Acute lung injury present if PaO2/FIO2 is 300 : new and arbitrary
value
10. Precipitating Factors
Direct Lung Injury
• Pneumonia
• Aspiration of gastric contents
• Pulmonary contusion
• Near-drowning
• Toxic inhalation injury
Indirect Lung Injury
• Sepsis
• Severe trauma
Multiple bone fractures
Head trauma
Burns
• Multiple transfusions
• Drug overdose
• Pancreatitis
• Post-cardiopulmonary bypass
11. Pathophysiology in ARDS
Based on the histological appearance -
Exudative phase (0-4 days)
• Alveolar and interstitial edema
• Capillary congestion
• Destruction of type I alveolar cells
• Early hyaline membrane formation
Proliferative Phase (3-10 days)
• Increased type II alveolar cells
• Cellular infiltration of alveolar septum
• Organisation of hyaline membranes
Fibrotic Phase (>10 days)
• Fibrosis of hyaline membranes and alveolar septum
• Alveolar duct fibrosis
12. Pathology in ARDS
Mechanisms in early phase -
• Release of inflammatory cytokines – TNF alpha, IL- 1,6,8
• Failure of alveolar edema clearance, epithelial and endothelial damage
• Increased permeability of alveolo – capillary membrane
• Neutrophil migration and oxidative stress
• Procoagulant shift – fibrin deposition
• Surfactant dysfunction
Mechanism in late (repair) phase –
• Fibroproliferation -TGF beta, MMPs, thombospondin, plasmin, ROS
• Remodelling - matrix and cell surface proteoglycans, MMP, imbalance of
coagulation and fibrinolysis.
15. Cardiogenic vs Non-cardiogenic edema
1.1. Prior h/o cardiac diseasePrior h/o cardiac disease
22.Third heart sound.Third heart sound
3.3. CardiomegalyCardiomegaly
44. Infiltrates : Central distribution. Infiltrates : Central distribution
55. Widening of vascular pedicle No widening of vascular pedicle. Widening of vascular pedicle No widening of vascular pedicle
( ↑ width of mediastinum)( ↑ width of mediastinum)6.6. PA wedge pressurePA wedge pressure
7.7. Positive fluid balancePositive fluid balance
Cardiogenic
Absence of heart diseaseAbsence of heart disease
No third heart soundNo third heart sound
Normal sized heartNormal sized heart
Peripheral distributionPeripheral distribution
N orN or ↓↓ PA wedge pressurePA wedge pressure
Negative fluid balanceNegative fluid balance
Non-cardiogenic
16. Management
• Treatment of the precipitating cause
• Mechanical ventilation –
Core ventilator management - protective lung ventilation strategy
- role of ‘open lung approach’
Adjuncts to core ventilation -
1. Fluid restriction
2. Permissive hypercapnia
3. Prone positioning
4. Recruitment maneuvers
17. Management contd.
• Non conventional/Salvage interventions
a. High frequency ventilation
b. Airway pressure release ventilation
c. Tracheal gas insufflation
d. Inverse ratio ventilation
e. Inhaled nitric oxide
f. Inhaled prostacyclin
g. Corticosteroids
h. Surfactant administration
i. Liquid ventilation
j. Extracorporeal membrane oxygenation
• Supportive therapy – nutrition, prevention of infection
18. Concept of VALI
Mechanical ventilation - Basic care in critically ill ICU patients
May cause or worsen lung injury – ventilator induced/associated lung
injury
Components –
• Barotrauma
• Volutrauma
• Atelectrauma
• Biotrauma
20. Concept of ‘baby lung’
• Put forward by Gattinoni and colleagues first in 1987
• Lung injury in ARDS - non homogenous, basal
• Edema and consolidation > dependent lung regions - ↑ density of dorsal
regions
• Aerated ventral regions – ‘baby lung’ (300-500gms) – high compliance
• Ventilation of baby lung with normal tidal volumes and pressures – alveolar
over distension – injury to functional lung tissue
21. Management
Lung protective ventilation ARDS network protocol
• Goals
Oxygenation : PaO2 55-80 mmHg, or SpO2 88 – 94% (excluding
pregnancy, intracranial hypertension or stroke where SaO2
goal>94%)
Ventilation :
Tidal volume : 4-6 ml/kg ideal body weight
Plateau pressure : <30cmH2O
Ph: 7.25-7.35
I:E ratio of 1:1 – 1:3
22. Management contd.
Oxygenation
• Initially high Fio2 given (1.0) to correct hypoxia
• Fio2 and PEEP adjusted to the lowest level compatible with the
oxygenation goals
• Fio2 and PEEP adjusted in the following fixed combinations
{fio2/PEEP(mmHg)}
0.3 0.4 0.4 0.5 0.5 0.6 0.7 0.7 0.7 0.8 0.9 0.9 0.9 1.0
5 5 8 8 10 10 10 12 14 14 14 16 18 20-
24
FIO2
PEEP
23. Management contd
Initial ventilator set up and adjustments
STEP 1- Calculation of ideal body weight(IBW):
For males, IBW(kg) = 50+2.3{height(inch)– 60}
Or IBW(kg)=50 + 0.91{height(cm)–152.4}
For females, IBW(kg) = 45.5+2.3{height(inch)– 60}
Or IBW(kg)=45.5 + 0.91{height(cm)–152.4}
24. Management contd
STEP 2 - Volume assist control selected as ventilator mode
Initial tidal volume (TV) set at 8ml/kg IBW
TV reduced by 1ml/kg IBW 2 hourly until TV = 6ml/kg IBW
Initial ventilator rate set to maintain baseline minute ventilation( not
>35/min)
TV and respiratory rate adjusted to achieve the pH and plateau
pressure goals
Inspiratory flow rate set above patients demand (usually >80L/min)
25. Open Lung Approach
• Introduced by Amato et al in 1998 – use of low tidal volume + high
PEEP+ recruitment (Open lung strategy) – reduce mortality in ARDS
• Maintaining inflation & deflation between 2 inflection points during entire
respiratory cycle
• Ventilatory settings - PEEP >Pflex & TV reduced so that Pplat < UIP
• Advantages- avoids repetitive opening and closing of alveoli (VALI)
- minimizes shear injury
27. Management
• Treatment of the precipitating cause
• Mechanical ventilation –
Core ventilator management – protective lung ventilation strategy
role of ‘open lung approach’
Adjuncts to core ventilation –
1. Fluid restriction
2. Permissive hypercapnia
3. Prone positioning
4. Recruitment maneuvers
28. Fluid restriction in ARDS
• Rationale – alveolar flooding depends on :
1. Capillary hydrostatic pressure
2. Oncotic pressure
3. Alveolar–capillary permeability
• Capillary permeability increased in ARDS
• ↓ hydrostatic pressure and ↑ oncotic pressure may help.
29. Fluid therapy in ARDS
Recommended :
• Central venous pressure guided therapy – 10-14 mmHg
( ARDS Network Trial 2003)
• Restricted fluid intake
• Increased urine output – Diuretics or RRT
Not recommended :
• Vasodilators
• Albumin
30. Management
• Treatment of the precipitating cause
• Mechanical ventilation –
Core ventilator management - protective lung ventilation strategy
- role of ‘open lung approach’
Adjuncts to core ventilation –
1. Fluid restriction
2. Permissive hypercapnia
3. Prone positioning
4. Recruitment maneuvers
31. Permissive Hypercapnia
• Hickling and colleagues 1990
• “Degree of hypercapnia permitted in patients subjected to lower tidal
volumes”
• Upper limit – not defined; >100 mmHg avoided
Advantages
• Increased surfactant secretion (animal models) – improved V/Q match,
oxygenation (improved compliance)
• Increased cardiac output and oxygen delivery (sympathoadrenal effects
predominate over cardiodepressant effects)
• Increased cerebral blood flow and tissue oxygenation
32. Permissive Hypercapnia
Concerns
• Increase in pulmonary vascular resistance
• Impaired diaphragmatic function (impairs afferent transmission)
• Decrease in cardiac contractility
• Raised intracranial tension
Individualize and treat
33. Management
• Treatment of the precipitating cause
• Mechanical ventilation –
Core ventilator management - protective lung ventilation strategy
- role of ‘open lung approach’
Adjuncts to core ventilation –
1. Fluid restriction
2. Permissive hypercapnia
3. Prone positioning
4. Recruitment maneuvers
34. Prone Position Ventilation
First suggested by Piehl and Brown in 1976
Offers improved oxygenation by:
• Increased FRC
• Change in regional diaphragm motion
• Distribution of perfusion
• Better clearance of secretions
35. Prone Position Ventilation
• Sud and colleagues conducted – meta-analysis of 13 RCTs (1559
patients) on supine and prone position ventilation in ARDS/ALI
patients
Median MV of 12 hours ( 4-24hrs) for 4 days( 1-10 days)
Conclusion -cannot be recommended for routine Mx
-no evidence of improved survival
• Gattinoni et al suggested no overall reduction in mortality except in
very sick patients ( SAPS II Score >50)
• No decrease in ventilator associated pneumonia
36. Problems of prone position
• Facial edema
• Airway obstruction
• Difficulties with enteral feeding
• Transitory decrease in oxygen saturation
• Hypotension & Arrhythmias
• Vascular and nerve compression
• Loss of venous accesses and probes
• Loss of chest drain and catheters
• Accidental extubation
• Apical atelectasis d/t incorrect positioning of the tracheal tube
• Increased need for sedation
37. Management
• Treatment of the precipitating cause
• Mechanical ventilation –
Core ventilator management - protective lung ventilation strategy
- role of ‘open lung approach’
Adjuncts to core ventilation –
1. Fluid restriction
2. Permissive hypercapnia
3. Prone positioning
4. Recruitment maneuvers
38. Recruitment maneuvers
• High pressure inflation maneuver aimed at temporarily raising the
transpulmonary pressure above levels typically obtained with
mechanical ventilation
• Types – Elevated sustained pressures : 40 cm H2O for 40 seconds
Sigh breaths : ↑ tidal volume / PEEP for one or several breaths
Extended sigh breath : VCV with PEEP well above LIP for a longer
time
• More effective in early ALI and those with more homogenous
disease; atelectasis > consolidation.
40. Management contd.
• Non conventional/Salvage interventions
a. High frequency ventilation
b. Airway pressure release ventilation
c. Tracheal gas insufflation
d. Inverse ratio ventilation
e. Inhaled nitric oxide
f. Inhaled prostacyclin
g. Corticosteroids
h. Surfactant administration
i. Liquid ventilation
j. Extracorporeal membrane oxygenation
• Supportive therapy – nutrition, prevention of infection
41. High Frequency Ventilation
• Mechanical ventilatory support using higher than normal breathing
frequencies
• Smaller tidal pressure swings (within inflection points) along with apt mpaw
• Smaller tidal volumes and higher mean pressure utilized for lung protection
• Special ventilators required
• Types - High Frequency Jet Ventilation (HFJV)
High Frequency Oscillatory Ventilation (HFOV)
42. HFV
HFJV
• A nozzle/injector creates high velocity ‘jet’ of gas directed into the
lung
• Injectors – 1-3mm diameter
• Expiration is passive
• Frequencies available – upto 600 breaths/min
• Available for neonatal and paediatric use only
HFOV
• Characterized by rapid oscillations of a diaphragm (at 3 to 10 hertz i.e
180 to 160 breaths/min) driven by a piston pump
• Frequencies available – 300-3000 breaths/min
• Expiration is also active – risk of air trapping minimal
43. HFV contd
Advantages
• Better oxygenation and ventilation
• Aids lung recruitment (high mpaw)
• Reduces oxygen toxicity (high mpaw)
• Minimizes VILI
Disadvantages
• Delivered tidal volumes difficult to monitor
• Deep sedation and/or paralysis required
• Inadequate humidification
• Direct physical airway damage
44. Airway Pressure Release Ventilation
• Alternative mode of ventilation that applies a form of CPAP that is
released periodically, augmenting CO2 release.
• Pressure limited, time cycled mode
• Permits spontaneous ventilation throughout the respiratory cycle
• Based on the ‘open lung’ concept – maximize and maintain
recruitment throughout the respiratory cycle
45. APRV contd
• Uses 2 airway pressures – P high and P low; 2 set time periods – T high
and T low, usually T high>T low
• P high is set above the closing pressure of recruitable alveoli (lower
inflection point)
• Set T high maintains the P high for several seconds
• T low helps remove CO2
46. APRV contd
Potential benefits :
• ↑ V/Q match
• ↓ diaphragmatic atrophy during critical illness
• ↑ cardiac output and oxygen delivery
• ↑ splanchnic perfusion
• ↑ renal and hepatic function
• Fewer days on mechanical ventilation
• Fewer days in ICU
47. Tracheal Gas Insufflation
• Normal ventilatory cycle - bronchi and trachea filled with alveolar gas
at end expiration
• In the next inspiration, CO2 laden gas forced back into alveoli.
• TGI - stream of fresh gas (at 4-8L/min) insufflated through a small
catheter/channels in the wall of endotracheal tube into the lower
trachea
• CO2 laden gas flushed out of the trachea before next inspiration
48. Tracheal Gas Insufflation contd.
Disadvantages
• Dessication of secretions
• Inadequate humidification
• Airway mucosal injury
• Accumulation of secretions in the TGI catheter
• Creation of auto PEEP from expiratory flow and resistance of the
ventilator-exhalation tubes and valve
49. Inverse Ratio Ventilation
• Alternative mode of ventilation
• Entails use of prolonged inspiratory times (I:E>1) using volume or
pressure cycled mode of mechanical ventilation
• Proposed mechanism of action – alveolar recruitment at lower airway
pressures, optimal distribution of ventilation
• Concerns – generation of auto PEEP
reduced cardiac output ( ↑ MAP)
50. Inhaled Nitric Oxide
NO – endogenous vasodilator, from endothelium
Vasodilatation of alveolar circulation reduces shunt and pulmonary
hypertension
Problems:
• toxic nitrogen compounds
• methemoglobinemia
• pulmonary edema, acute RHF (interrupted flow)
• rebound pulmonary hypertension
• expensive
Routine use not recommended
51. Inhaled Prostacyclin
• Cause vasodilation, inhibit platelet aggregation, reduction of
neutrophil adhesion and activation, ↓ pulmonary hypertension,
improved oxygenation
• Minimal systemic effects, harmless metabolites, no requirements for
monitoring
• Both positive and negative results obtained in various trials
• Presently not recommended
52. Corticosteroids
• Established ARDS – characterized by alveolar fibrosis
• Anti-inflammatory and antifibrotic properties of steroids – probable
role in ARDS
• No role in preventing but may help in treating ARDS
53. Surfactant Therapy
• Reduces alveolar surface tension
• Prevents alveolar collapse
• Anti inflammatory properties
• Anti microbial properties
• Exogenous surfactant – successful in neonatal respiratory distress
syndrome (reduced surfactant production)
• ARDS in adults – increased surfactant removal, altered composition,
reduced efficacy, reduced production
• Surfactant therapy not recommended in adults
54. Liquid Ventilation
• Involves filling the lung with liquid
• Removes the air liquid interface and supports alveoli, prevents
collapse
• Perfluorocarbons – have low surface tension, dissolve oxygen and
carbon dioxide readily, non toxic, minimally absorbed, eliminated by
evaporation though lungs
• Lowered surface tension may improve alveolar recruitment, arterial
oxygenation, increased lung compliance
• Can recruit dependent alveoli (advantage over PEEP)
55. Liquid Ventilation contd.
Types :
• Total – filling the entire lung with liquid, ventilated with a special
ventilator
- Expensive
• Partial - filling the lung to FRC with liquid, ventilated with
conventional ventilator
- Appropriate dose of PFC still to be determined
- ↑ chances of pneumothoraces, hypoxic episodes, hypotensive
episodes
• PFC radiodense – impossible to detect infection or follow the
progress of healing in a chest radiograph
• Liquid ventilation is not FDA approved
56. Extracorporeal Membrane Oxygenation
• Invasive, complex form of cardiopulmonary bypass
• Provides temporary gas exchange and blood circulation outside the
body
• Severe but potentially reversible respiratory failure
• Such periods of “lung rest” allow the lungs to recover
• Used when conventional strategies fail
• No good evidence available over conventional management
57. ECMO contd.
Types
• Veno - arterial – a catheter placed in both vein and artery. Provides
support both for heart and lungs
• Veno - venous – single double lumen catheter placed in the vein.
Provides support only for lungs
• ECMO allows ventilator pressures and volumes to be decreased to
prevent further VILI
• Reduction in intra - thoracic pressure allows fluid removal from lungs
with less risk of cardiovascular instability
59. Management contd.
• Salvage interventions
a. High frequency oscillatory ventilation
b. Airway pressure release ventilation
c. Tracheal gas insufflation
d. Inverse ratio ventilation
e. Inhaled nitric oxide
f. Inhaled prostacyclin
g. Corticosteroids
h. Surfactant administration
i. Liquid ventilation
j. Extracorporeal membrane oxygenation
• Supportive therapy – nutrition, prevention of infection
60. Nutrition
• Enteral over parenteral
• High fat – low carbohydrate diet advocated - ↓ CO2
• Immuno modulatory nutrients
-amino acids - arginine and glutamine
-ribonucleotides
-omega-3 fatty acids
• Diet rich in fish oil, γ-linolenic acid, and antioxidants
• Standard nutritional formulations recommended
61. Antibiotics
• Infection - present initially : nonpulmonary sepsis
• Develop later - nosocomial infections : pneumonia and catheter-
related sepsis.
• Aim : identify, treat, and prevent infections.
• Most pneumonia > 7 days
• Prompt initiation of appropriate empiric therapy.
• Hand washing by medical personnel
• New areas :
- continuous suctioning of subglottic secretions to prevent their
aspiration
-development of new endotracheal tubes - resist formation of
bacterial biofilm that can be embolized distally with suctioning.
62. Management
• Treatment of the precipitating cause
• Mechanical ventilation –
Core ventilator management - protective lung ventilation strategy
- role of ‘open lung approach’
Adjuncts to core ventilation -
1. Fluid restriction
2. Permissive hypercapnia
3. Prone positioning
4. Recruitment maneuvers
63. Management contd.
• Non conventional/Salvage interventions
a. High frequency ventilation
b. Airway pressure release ventilation
c. Tracheal gas insufflation
d. Inverse ratio ventilation
e. Inhaled nitric oxide
f. Inhaled prostacyclin
g. Corticosteroids
h. Surfactant administration
i. Liquid ventilation
j. Extracorporeal membrane oxygenation
• Supportive therapy – nutrition, prevention of infection
65. Long term sequelae of ARDS
• Pulmonary function – mild impairment, improves over 1 year
• Neurocognitive dysfunction
• Post traumatic stress disorder
• Physical debilitation
66. Infantile Respiratory Distress Syndrome
• Hyaline membrane disease
• Deficiency of surfactant : insufficient production in immature lungs,
immature babies
• Genetic mutation in one of the surfactant proteins, SP-B – rare, full
term babies
• Prevention : avoidance of premature birth, corticosteroids
• Treatment : surfactant replacement
67. References
• Harrison’s Principle of Internal Medicine, 16th
ed.
• Christie JD, Lanken PN. Acute lung injury and the acute respiratory distress
syndrome. Critical Care – Hall
• Foner BJ, Norwood SH, Taylor RW. Acute respiratory distress syndrome.
Critical Care, 3rd
ed. Civetta
• Wiener-Kronish JP, et al. The adult respiratory distress syndrome : definition
and prognosis, pathogenesis and treatment. BJA 1990; 65: 107-129.
• Clinical Anaesthesia. Barash, 6th
ed.
• Egans Respiratory Care, 7th
e
68. References
• Acute respiratory distress syndrome network. Ventilation with lower tidal volumes
as compared with traditional tidal volumes for acute lung injury and the acute
respiratory distress syndrome. N Engl J Med. 2000;242:1301-1308
• Brower RG, Morris A, MacIntyre N, et al. Effects of recruitment maneuvers in
patients with acute lung injury and acute respiratiry distress syndrome ventilated
with high positive end expiratory pressure. Crit Care Med.2003;31:2592-2597
• Hickling KG, Henderson SJ, Jackson R. Low mortality associated with low volume
pressure limited ventilationwith permissive hypercapnia in severe adult respiratory
distress syndrome. Intensive care med. 1990;16:372-377
• Hickling KG, Walsh J,Henderson S, Jackson R. Low mortality rate in acute
respiratiry distress syndrome using low volume pressure limited ventilation with
permissive hypercapnia: a prospective study. Crit Care Med.1994;22:1568-1578