ACUTE RESPIRATORY

DISTRESS SYNDROME
(ARDS)

DR. MONDAY ZACCHEAUS

REGISTRAR, RESPIRATORY/INFECTIOUS DISEASE
UNIT, INTERNAL MEDICINE DEPT, UPTH.
OUTLINE
 Introduction
 Epidemiology
 Aetiology/Risk factors
 Pathophysiology
 Clinical Presentation
 Differential diagnosis
 Investigations
 Treatment
 Complications
 Prognosis
 Recommendations
 Conclusion
 References
 INTRODUCTION

 Acute respiratory distress syndrome

(ARDS) is a rapid onset, diffuse,
inflammatory form of lung injury and
life-threatening condition,
characterized by poor oxygenation,
pulmonary infiltrates, leading to
respiratory failure.
CONSENSUS DEFINITION
• It was developed in 1994 by the American-European

Consensus Conference (AECC) on ARDS

• The AECC defined ARDS as an acute condition

characterized by bilateral pulmonary infiltrates and

severe hypoxemia in the absence of evidence for

cardiogenic pulmonary edema.

• The severity of hypoxemia necessary to make the diagnosis

of ARDS was defined by the ratio of the partial pressure of

oxygen in the patient’s arterial blood (PaO2) to the fraction

of oxygen in the inspired air (FiO2).

 BERLIN DEFINITION
• The consensus definition was further refined in

2012 by a panel of experts and is termed the

Berlin definition of ARDS.

• ARDS is defined by timing (within 1 week of

clinical insult or onset of respiratory symptoms);

• radiographic changes (bilateral opacities not

fully explained by effusions, consolidation, or

 BERLIN DEFINITION
• origin of edema (not fully explained by cardiac

failure or fluid overload); and

• severity based on the PaO2/FiO2 ratio on 5 cm

of continuous positive airway pressure (CPAP).

• The 3 categories are mild (PaO2/FiO2 200-

300), moderate (PaO2/FiO2 100-200), and

severe (PaO2/FiO2 ≤100).

 INTRODUCTION
• Once ARDS develops, patients usually
have varying degrees of pulmonary artery
vasoconstriction and may subsequently
develop pulmonary hypertension.
• ARDS carries a high mortality, and few
effective therapeutic modalities exist to
combat this condition.
 EPIDEMIOLOGY
The annual incidence of ARDS prior to the COVID-19
pandemic was estimated to be as high as 60 cases/100,000
population.
• Estimates of the incidence of ARDS in the United States
range from 64.2 to 78.9 cases/100,000 person-years.
• ARDS may occur in people of any age.
• Its incidence increases with advancing age, ranging from
16 cases per 100,000 person-years in those aged 15-19
years to 306 cases per 100,000 person-years in those
between the ages of 75 and 84 years.
 EPIDEMIOLOGY
 For ARDS associated with sepsis and
most other causes, no differences in
the incidence between males and
females appear to exist.
 However, in trauma patients only, the
incidence of the disease may be slightly
higher among females.
AETIOLOGY/RISK
Risk factors for ARDS include
FACTORS
1. Advanced age
2. Female gender
3. Smoking
4. Alcohol use
5. Aortic vascular surgery
6. Cardiovascular surgery
7. Traumatic brain injury
8. Pancreatitis
9. Pulmonary contusion
10. Infectious pneumonia
11. Drugs (radiation, chemotherapeutic agents, amiodarone
AETIOLOGY/RISK FACTORS
Common causes and conditions associated with
development of ALI/ARDS
Indirect causes:
Direct causes: 1. Severe sepsis
Pulmonary infection (pneumonia) 2. Shock
Inhalation injury (smoke, toxins) 3. Transfusion related lung
Trauma (pulmonary contusion) injury
Embolism (amniotic fluid, fat) 4. Nonpulmonary
Aspiration injury (gastric, near trauma(multiple bone
drowning) fractures, flail chest,head
Re-expansion injury trauma, burns)
1. Reperfusion injury (post lung 5. Medications (opiods,
transplant, pulmonary salicylates, amiodarone
embolectomy) tocolytics, chemotherapy)
6. Cardiopulmonary bypass
7. Anaphylaxis
8. Acute pancreatitis
 PATHOPHYSIOLOGY
Injured lung believed go through three

phases:

➢ exudative,

➢ proliferative,

➢ Fibrotic
 PATHOPHYSIOLOGY-
Exudative Phase
• In this phase, alveolar capillary endothelial cells and type I
pneumocytes (alveolar epithelial cells) are injured, with
consequent loss of the normally tight alveolar barrier to fluid and
macromolecules.
• Edema fluid that is rich in protein accumulates in the interstitial
and alveolar spaces.
• Proinflammatory cytokines (e.g., interleukin 1, interleukin 8, and
tumor necrosis factor α [TNF-α]) and lipid mediators (e.g.,
leukotriene B4) are increased in this acute phase, leading to the
recruitment of leukocytes (especially neutrophils) into the
pulmonary interstitium and alveoli.
 PATHOPHYSIOLOGY- Exudative Phase
• In addition, condensed plasma proteins aggregate in
the air spaces with cellular debris and dysfunctional
pulmonary surfactant to form hyaline mem-brane
whorls.
• Pulmonary vascular injury also occurs early in ARDS,
with vascular obliteration by microthrombi and
fibrocellular proliferation.
• Alveolar edema predominantly involves dependent
portions of the lung with diminished aeration.
Collapse of large sections of dependent lung can
contribute to decreased lung compliance.
 PATHOPHYSIOLOGY- Exudative Phase

Consequently, intrapulmonary shunting and hypoxemia

develop and the work of breathing increases, leading
to dyspnea.
• The pathophysiologic alterations in alveolar spaces
are exacerbated by microvascular occlusion that
results in reductions in pulmonary arterial blood
flow to ventilated portions of the lung (and thus in
increased dead space) and in pulmonary
hypertension.
PATHOPHYSIOLOGY- Proliferative Phase

• Histologically, the first signs of resolution are often

evident in this phase, with the initiation of lung repair,
the organization of alveolar exudates, and a shift from
neutrophil to lymphocyte-predominant pulmonary
infiltrates.
• As part of the reparative process, type II pneumocytes
proliferate along alveolar basement membranes.
• These specialized epithelial cells synthesize new
pulmonary surfactant and differentiate into type I
pneumocytes.
 PATHOPHYSIOLOGY- Fibrotic phase
• Histologically, the alveolar edema and inflammatory
exudates of earlier phases convert to extensive alveolar-
duct and interstitial fibrosis.
• Marked disruption of acinar architecture leads to
emphysema-like changes, with large bullae.
• Intimal fibro-proliferation in the pulmonary
microcirculation causes progressive vascular occlusion and
pulmonary hypertension.
• The physiologic consequences include an increased risk of
pneumothorax, reductions in lung compliance, and
increased pulmonary dead space.
CLINICAL PRESENTATION
NATURAL HISTORY AND CLINICAL COURSE
CLINICAL PRESENTATION
HISTORY:
• Dyspnoea
• Fatigue
• History of exposure to underlying cause

PHYSICAL EXAMINATION
• Respiratory distress
• Tachypnea
• Cyanosis- central & Peripheral
• Tachycardia
• Altered mental status
• Bibasal crepitations
• Low oxygen saturation
 DIAGNOSTIC CRITERIA FOR ARDS
SEVERITY: ONSET CHEST ABSENCE OF
OXYGENATION RADIOGRAPH LEFT ATRIAL
HYPERTENSION

Mild: 200 mmHg < Acute: Within 1 Bilateral opacities Hydrostatic edema
Pao2/Fio2 ≤ 300 week of a clinical consistent with is not the primary
mmHg insult or new or pulmonary edema cause of respiratory
worsening not fully explained failure. If no ARDS
Moderate: 100 respiratory by effusions, risk factor is
mmHg < Pao2/Fio2 symptoms lobar/lung collapse, present, then some
≤ 200 mmHg or nodules objective evaluation
is required (e.g.,
Severe: Pao2/Fio2 echocardiography)
≤100 m to rule out
hydrostatic edema.
 DIFFERENTIAL DIAGNOSIS
Cardiogenic pulmonary edema
Exacerbation of interstitial lung disease
Acute interstitial pneumonia
Diffuse alveolar hemorrhage
• Acute eosinophilic lung disease
• Hypersensitivity Pneumonitis
• Organizing pneumonia
• Bilateral pneumonia
• Pulmonary vasculitis
• Cryptogenic organizing pneumonia
• Disseminated malignancy
• Radiation pneumonitis
• Neurogenic pulmonary oedema
INVESTIGATIONS

• Specific: • General:
1. CXR
1. FBC +ESR, CRP
2. Chest CT
2. E/U/Cr, serum mg , ionized
3. ABG
calcium, phosphate
4. Bronchoscopy
3. LFT
5. ECHO
4. Serum Lactate
5. Clotting profile
6. Cardiac troponins, CKMB
7. BNP
CXR:
Anteroposterior
chest x-ray in the
exudative phase of
acute respiratory
distress syndrome
(ARDS) shows
bilateral opacities
consistent with
pulmonary edema
that can be
difficult to
distinguish from
left ventricular
failure.
CHEST CT

A
representative
CT scan of the
chest during the
exudative phase
of ARDS in
which dependent
alveolar edema
and atelectasis
predominate.
NOVEL BIOMARKERS IN ARDS
INVESTIGATIONS- BIOMARKERS IN ARDS
 KEY PRINCIPLES OF MANAGEMENT

Perform early clinical determination of respiratory

difficulty
Perform objective assessment with arterial blood gas and
chest radiograph
1. Provide supplemental oxygen, monitor saturation, and
investigate risk factors for ARDS
2. Determine the need for intubation and mechanical
ventilation
3. Use low tidal volume, low plateau pressure, lung-
protective ventilator strategies
4. Optimize fluid status, nutrition, and pulmonary toilet,
and treat complication
 TREATMENT

GENERAL PRINCIPLES
1. The recognition and treatment of underlying medical
and surgical disorders (e.g., pneumonia, sepsis,
aspiration, trauma);
2. The minimization of unnecessary procedures and their
complications;
3. Standardized “bundled care” approaches for ICU
patients, including prophylaxis against venous
thromboembolism, gastrointestinal bleeding, aspiration,
excessive sedation, prolonged mechanical ventilation,
and central venous catheter infections;
4. Prompt recognition of nosocomial infections; and
5. Provision of adequate nutrition via the enteral route
when feasible.
 TREATMENT

A. MECHANICAL VENTILATION:
1. Assit control Ventilation (ACV)
2. Pressure regulated volume control Ventilation (PRVC)
3. Pressure support Ventilation (PSV)
4. Non invasive positive pressure ventilation(NIV)
• CPAP
• BIPAP
5. Other strategies:
• Extracorporeal membrane oxygenation (ECMO)

B. FLUID MANAGEMENT:
Aggressive attempts to reduce left atrial filling pressures with
fluid restriction and diuretics should be an important aspect of
ARDS management, limited only by hypotension and hypoperfusion
of critical organs such as the kidneys.
C. NEUROMUSCULAR BLOCKADE:
• In severe ARDS, sedation alone can be inadequate for
the patient-ventilator synchrony required for lung-
protective ventilation.
• In a multicenter, randomized, placebo-controlled trial
of early neuromuscular blockade (with cisatracurium
besylate) for 48 h, patients with severe ARDS had
increased survival and ventilator-free days without
increasing ICU-acquired paresis.
• This more recent study supports the notion that
selective use of neuro-muscular blockade might be
beneficial in those ARDS patients with ventilatory
 TREATMENT

D. GLUCOCORTICOIDS:
• Glucocorticoid administration – no routine use of systemic
glucocorticoid therapy in ARDS
• Patients in whom systemic glucocorticoids can be given
include the following
• A steroid-responsive background process (eg, acute
eosinophilic pneumonia, organizing pneumonia
• Refractory septic shock
• COVID-19 patients
 TREATMENT

• Patients who are relatively early in the

disease course (within 14 days of onset) who
have persistent or refractory moderate to
severe ARDS (partial arterial pressure of
oxygen/fraction of inspired oxygen
[PaO2/FiO2] ratio <200) despite initial
management with standard therapies,
including low tidal volume ventilation, can be
given glucocorticoid therapy.
TREATMENT

E. ANTIBIOTICS:

• Pneumonia and other site-specific infections

should be adequately treated with antibiotics

based on appropriate culture and sensitivity

F. OTHER THERAPIES:

• Routine stress ulcer and thromboembolic

prophylaxis is recommended
 TREATMENT
OTHER THERAPIES
Inhaled Nitric oxide & Epoprostenol
sodium(Inhaled pulmonary vasodilators) –
not found to be particularly effective
(reserve their use for patients with ARDS
who have severe hypoxemia refractory to
standard therapies
• Molecular mechanisms – cell or therapy
gene in experimental models
ALGORITHM FOR INITIAL MGT OF ARDS
EVIDENCE BASED RECOMMENDATIONS FOR
ARDS THERAPIES
 COMPLICATIONS

Barotrauma from high PEEP

Prolonged mechanical ventilation –thus the need for
tracheostomy
Post-extubation laryngeal edema and subglottic stenosis
Nosocomial infections
Pneumonia
Line sepsis
Urinary tract infection
Deep venous thrombosis
Antibiotic resistance
Muscle weakness
Renal failure
1. Post-traumatic stress disorder
 PROGNOSIS
The prognosis for ARDS was abysmal until very recently.
• Usually, survivors start to recover within two weeks of
the onset of ARDS
• The overall mortality rate in ARDS is now about 32 to
45 percent, compared with 53 to 68 percent in the 1980s
• Age younger than 55yrs, and trauma etiology predict a
more favorable outcome.
• Populations associated with higher mortality rates are
the elderly, immunosuppressed persons, patients with
chronic liver disease
• In cases of ARDS, death is usually caused by progressive
multisystem organ failure rather than respiratory
deterioration
• Underlying cause of ARDS is the most common cause of
death in patient who die early.
CONCLUSION
REFERENCES
Thank You For
Listening!