Updated definition of ards

• Heba Ismail, M.B.Ch.B

• Assistant Clinical Professor
• Division Of Pulmonary and Critical Care Medicine

Updated definition of ARDS

• Updated definition of ARDS

• Briefly review Pathophysiology and Pathogenesis

• Etiology/Risk factors

• Clinical Presentation

• Diagnosis, Differential Diagnosis

• Management

A 70-year-old man was admitted to the ICU

• A 70-year-old man was admitted to the ICU

• acute hypoxemic respiratory failure

• 48 hours earlier

• He underwent a surgical resection of the left lower lobe for stage IIIB adenocarcinoma of the lung.

• Intra-operative course

• He received a total fluid infusion of 5.5 L (including 3 units of packed red blood cells)
• The cumulative fluid infusion given during the peri-operative period was 8.0 L with a net negative 0.7L

Post Operative course

• Post Operative course
• Extubated and transferred to the ward
• 36 hours later
• dyspnea and hypoxemia were noted
• re-intubated

Past Medical History

• Past Medical History

• Adenocarcinoma of the lung, stage IIIb, diagnosed 3 months before surgery, treated with preoperative neo-adjuvant chemotherapy and radiotherapy
• History of moderate COPD

• Social History

• 80-pack-years of cigarette smoking
• chronic alcohol consumption of approximately 30g of ethanol per day.

Pre-operative evaluation

• Pre-operative evaluation

• Complete blood count and blood chemistry were normal
• Pre-operative evaluation for chronic heart disease was negative
• Forced Expiratory Volume in 1s (FEV1) was 1.79 L; 58% of the predicted value; calculated post-operative FEV1 was 49% of the predicted value

Physical examination 

• Physical examination 

• Vital signs,
• BP 100/70 mmHg, Pulse 120/min, Respirations 33/min, SpO2 of 85% on 100% Non rebreather, Temperature 37.0 C
• Cardiovascular
• S1, S2 normal
• Respiratory
• Decreased breath sounds over the left lower lung field, diffuse end-inspiratory crackles over the remaining lobes.

•  Laboratory Data

• Normal complete blood count and chemistry
• Blood  and bronchoalveolar lavage (BAL) specimens were collected and sent for microbiologic analysis.
• Blood cultures, done

• Arterial blood gases: (on FiO2 0.6), PaO2 70mmHg,, PaCO2 45mmHg, HCO3 24, PaO2/ FiO2 117

What is your next diagnostic study?

• What is your next diagnostic study?

• CT chest/PE Protocol
• Transthoracic Echocardiogram
• Right Cardiac Catheterization
• Repeat Bronchoscopy

Transthoracic echocardiography:

• Transthoracic echocardiography:

• Ejection fraction 60 %, normal left ventricular systolic function. Mild right ventricular dilation

• Right heart catheterization:

• Cardiac Output (CO): 7.74 L/min (normal 5-7 L/min)
Cardiac Index (CI): 4.8 L/min/m2(normal 3-5 L/min/m2)
CVP 8 mmHg
SVRI: 960 dynes/sec/cm5/m2 (normal 1200-1800)
Pulmonary artery systolic pressure (PASP): 59 mmHg 
Pulmonary Wedge Pressure: 11 mmHg

Which of the following statements is true:

• Which of the following statements is true:

• The Development of acute respiratory failure in this patient is due to:

• A. Pulmonary edema due to fluid overload


• B. Cardiogenic pulmonary edema due to left-sided heart failure


• C. Acute respiratory distress syndrome (ARDS) 


• D. Pneumonia


• E. Massive pulmonary embolism

Factors that affect PaO2/FiO2 vs FiO2

• Factors that affect PaO2/FiO2 vs FiO2

• Cardiac output
• A-V O2 Difference
• Distribution of blood flow to different V/Q regions
• Low V/Q
• Shunt
• Oxygen consumption
• Hemoglobin concentration

• New Definition

ESICM convened an international panel of experts, with representation of ATS and SCCM

• ESICM convened an international panel of experts, with representation of ATS and SCCM

• The objectives were to update the ARDS definition using a systematic analysis of:

• current epidemiologic evidence
• physiological concepts
• results of clinical trials

All modifications were based on the principle that syndrome definitions must fulfill three criteria:

• All modifications were based on the principle that syndrome definitions must fulfill three criteria:

• Feasibility
• Reliability
• Validity

No change in the underlying conceptual understanding of ARDS

• No change in the underlying conceptual understanding of ARDS

• “acute diffuse, inflammatory lung injury, leading to increased pulmonary vascular permeability, increased lung weight, and loss of aerated lung tissue…[with] hypoxemia and bilateral radiographic opacities, associated with increased venous admixture, increased physiological dead space, and decreased lung compliance.”

• Although the authors emphasize the increased power of the new Berlin definition to predict mortality compared to the AECC definition, in truth it’s still poor, with an area under the curve of only 0.577, (95% CI, 0.561-0.593) compared to 0.536, (95% CI, 0.520-0.553;P < 001 ) for the old definition.

Initial "exudative" stage-diffuse alveolar damage within the first week

• Initial "exudative" stage-diffuse alveolar damage within the first week

• “Proliferative" stage-resolution of pulmonary edema, proliferation of type II alveolar cells, squamous metaplasia, interstitial infiltration by myofibroblasts, and early deposition of collagen.

• Some patients progress to a third "fibrotic" stage, characterized by obliteration of normal lung architecture, diffuse fibrosis, and cyst formation

Sepsis

• Sepsis

• Severe trauma

• Surface burns

• Multiple blood transfusions

• Drug overdose

• Following bone marrow transplantation

• Multiple fractures

Type of Non-Cardiogenic Pulmonary Edema

• Type of Non-Cardiogenic Pulmonary Edema

• Mechanism

• Rapid resolution of large levels of negative intra-thoracic pressures by removal of airways obstruction ------leads to alveolar and capillary damage ------ leads to increased vascular permeability

Dyspnea, Tachypnea

• Dyspnea, Tachypnea

• Persistent hypoxemia, despite the administration of high concentrations of inspired oxygen

• Increase in the shunt fraction
• Decrease in pulmonary compliance
• Increase in the dead space ventilation

Identify and treat underlying causes

• Identify and treat underlying causes

• Ventilatory support

• Lung protective ventilatory support strategy
• Application of PEEP

• Restore and maintain hemodynamic function

• Conservative fluid replacement strategy
• Vasopressors and inotropics support

• Prevent complications of critical illness

• Ensure adequate nutrition

• Avoid oversedation

• Using weaning protocol with spontaneous breathing trials

• Continous use of steroids for fibroproliferative phase ?questionable

SAFE trial

• SAFE trial

• Resuscitation with saline is as beneficial as resuscitation with albumin in critically ill patients with shock

• FACTT trial

• Prospective, Randomized, Multi-Center Trial
• Utility and safety of using a pulmonary artery catheter versus central venous catheter to guide the volume replacement
• Liberal versus conservative fluid replacement

Patients were treated with the specific fluid management strategy (to which they were randomized) for 7 days or until unassisted ventilation, whichever occurs first.

• Patients were treated with the specific fluid management strategy (to which they were randomized) for 7 days or until unassisted ventilation, whichever occurs first.

• The study enrolled 1000 patients and showed no benefit with PAC guided fluid therapy over the less invasive CVC guided therapy.

The Use of Conservative fluid management strategy was associated with

• The Use of Conservative fluid management strategy was associated with

• Significant improvement in oxygenation index
• Significant improvement in Lung Injury score
• increase in the number of ventilator- free days

Ventilator associated lung injury

• Ventilator associated lung injury

• Volutrauma
• Atelectotrauma
• Biotrauma
• Barotrauma
• Air embolism/translocation

Compared low tidal volumes (6ml/kg of ideal body weight ) against conventional tidal volumes (12ml/kg ideal body weight )

• Compared low tidal volumes (6ml/kg of ideal body weight ) against conventional tidal volumes (12ml/kg ideal body weight )

• Significant decrease in mortality associated with the use of low tidal volumes (39.8% versus 31%, P= 0.007)

Initial tidal volumes of 8 mL/kg predicted body weight in kg, calculated by:

• Initial tidal volumes of 8 mL/kg predicted body weight in kg, calculated by:

•  [2.3 *(height in inches - 60) + 45.5 for women or + 50 for men].

• Respiratory rate up to 35 breaths/min

•  expected minute ventilation requirement (generally, 7-9 L /min)

• Set positive end-expiratory pressure (PEEP) to at least 5 cm H2O (but much higher is probably better)

• FiO2 to maintain an arterial oxygen saturation (SaO2) of 88-95% (paO2 55-80 mm Hg).

• Titrate FiO2 to below 70% when feasible.

• Over a period of less than 4 hours, reduce tidal volumes to 7 mL/kg, and then to 6 mL/kg.

Plateau pressure (measured during an inspiratory hold of 0.5 sec) less than 30 cm H2O,

• Plateau pressure (measured during an inspiratory hold of 0.5 sec) less than 30 cm H2O,

• High plateau pressures vastly elevate the risk for harmful alveolar distension ( volutrauma).

• If plateau pressures remain elevated after following the above protocol, further strategies should be tried:

• Reduce tidal volume, to as low as 4 mL/kg by 1 mL/kg stepwise increments.
• Sedate the patient to minimize ventilator-patient dyssynchrony.
• Consider other mechanisms for the increased plateau pressure

Decrease in TNF-alpha release by alveolar macrophages

• Decrease in TNF-alpha release by alveolar macrophages

• Decrease in PMNL-endothelial cell adhesion

• Decrease in Xanthine oxiedase activity

• Decrease in NOS activity

• Reduction of IL-8

Higher PEEP along with low tidal volume ventilation should be considered for patients receiving mechanical ventilation for ARDS. This suggestion is based on a

• Higher PEEP along with low tidal volume ventilation should be considered for patients receiving mechanical ventilation for ARDS. This suggestion is based on a

• 2010 meta-analysis of 3 randomized trials (n=2,229) testing higher vs. lower PEEP in patients with acute lung injury or ARDS, in which ARDS patients receiving higher PEEP had a strong trend toward improved survival.

However, patients with milder acute lung injury (paO2/FiO2 ratio > 200) receiving higher PEEP had a strong trend toward harm in that same meta-analysis.

• However, patients with milder acute lung injury (paO2/FiO2 ratio > 200) receiving higher PEEP had a strong trend toward harm in that same meta-analysis.

• Higher PEEP can conceivably cause ventilator-induced lung injury by increasing plateau pressures, or cause pneumothorax or decreased cardiac output. These adverse effects were not noted in the largest ARDSNet trial (2004) testing high vs. low PEEP.

Neuromuscular blockers in early acute respiratory distress syndrome. 

• Neuromuscular blockers in early acute respiratory distress syndrome. 

• N Engl J Med, 2010;363:1107-16. 
• This multicenter RCT of 340 patients with severe ARDS found early use of 48 hours of neuromuscular blockade reduced mortality compared to placebo (NNT of 11 to prevent one death at 90 days in all patients, and a NNT of 7 in a prespecified analysis of patients with a PaO2:FiO2 less than 120).

Identify and treat underlying causes

• Identify and treat underlying causes

• Ventilatory support

• Lung protective ventilatory support strategy
• Application of PEEP

• Restore and maintain hemodynamic function

• Conservative fluid replacement strategy
• Vasopressors and inotropics support

• Prevent complications of critical illness

• Ensure adequate nutrition

• Avoid oversedation

• Using weaning protocol with spontaneous breathing trials

• Continous use of steroids for fibroproliferative phase,?questionable

On admission to the ICU, the patient was sedated and placed on volume control  mechanical ventilation with the follow settings: FiO2: 0.6,  VT: 450 ml, RR:18,   PEEP:10 cm H2O, VΕ:8 L/min.

• On admission to the ICU, the patient was sedated and placed on volume control  mechanical ventilation with the follow settings: FiO2: 0.6,  VT: 450 ml, RR:18,   PEEP:10 cm H2O, VΕ:8 L/min.

• Additional supportive therapy included initial, empiric, broad-spectrum antibiotics and restrictive fluid management.

• On Day 3, due to further impairment of oxygenation (SaO2 <80%) that did not improve with increases in both PEEP and FiO2, the patient was placed on high frequency oscillatory ventilation.

• Although he had an initial improvement in oxygenation, his overall condition continued to decline and he died on Day 5 due to multiple organ failure.

Inhaled NO

• Inhaled NO

• Steroids

• Prone Position

• High Frequency Oscillatory Ventilation

• ECMO

It is a bronchial and vascular smooth muscle dilator

• It is a bronchial and vascular smooth muscle dilator

• Decreases the Platelets Adherence and Aggregation

• Improves Ventilation –Perfusion ratio

• Reduction in Pulmonary Artery Pressure and pulmonary Vascular Resistance

Two Prospective, Randomized, Placebo Controlled Clinical Trials failed to demonstrate an improvement in the survival.

• Two Prospective, Randomized, Placebo Controlled Clinical Trials failed to demonstrate an improvement in the survival.

• However, there was improvement in the oxygenation…

A protocol for steroids in late ARDS, based on the Meduri paper*

• A protocol for steroids in late ARDS, based on the Meduri paper*

• The patient must have no demonstrable infection

• broncho-alveolar lavage may be necessary to confirm this. This includes undrained abscesses, disseminated fungal infection and septic shock

• Steroids should not be started less than 7 days, or more than 28 days, from admission

• The patient should not have a history of gastric ulceration of active gastrointestinal bleeding

• Patients with burns requiring skin grafting, pregnant patients, AIDS, and those in whom life support is expected to be withdrawn, are unsuitable

The patient should have evidence of ARDS and require an FiO2 >/= 50%

• The patient should have evidence of ARDS and require an FiO2 >/= 50%

• The steroid regimen:


• Loading dose 2mg/kg

• Then 2mg/kg/day from day 1 to 14

• Then 1mg/kg/day from day 15 to 21

• Then 0.5mg/kg/day from day 22 to 28

• Then 0.25mg/kg/day on days 29 and 30

• Finally 0.125mg/kg on days 31 and 32.



Relieves the cardiac and abdominal compression exerted on the lower lobes

• Relieves the cardiac and abdominal compression exerted on the lower lobes

• Makes regional Ventilation/Perfusion ratios and chest elastance more uniform

• Facilitates drainage of secretions

• Potentiates the beneficial effect of recruitment maneuvers

Placing patients who require mechanical ventilation in the prone rather than the supine position improves oxygenation.

• Placing patients who require mechanical ventilation in the prone rather than the supine position improves oxygenation.

• In this trial, the investigators found a benefit with respect to all-cause mortality with this change in body position in patients with severe ARDS.

In patients with severe ARDS, early application of prolonged prone-positioning sessions significantly decreased 28-day and 90-day mortality.

• In patients with severe ARDS, early application of prolonged prone-positioning sessions significantly decreased 28-day and 90-day mortality.

Respiratory rate

• Respiratory rate

• Max RR at 35 breaths/min
• Efficiency of ventilation decreases with increasing RR
• Decreased time for alveolar emptying

• TV

• Goal of 10 ml/kg
• Risk of volutrauma

• Other means to decrease PaCO2

• Reduce muscular activity/seizures
• Minimizing exogenous carb load
• Controlling hypermetabolic states

• Permissive hypercapnea

• Preferable to dangerously high RR and TV, as long as pH > 7.15