Acute Respiratory Distress Syndrome

ByDr.Adel Hamada

EDICMD Chest

ARDS definition is based upon 5 key clinical features:

(1) a risk factor for the development of acute respiratory distress

(e.g., sepsis, trauma, pneumonia, aspiration, pancreatitis)

(2) severe hypoxemia despite a relatively high fraction of inspired

oxygen (FIO2).

(3) decreased lung compliance.

(4) bilateral pulmonary infiltrates.

(5) lack of clinical evidence of cardiogenic pulmonary edema.

DEFINITION

Lung Injury Scoring System

American-European Consensus Conference (definition and limitation)

Definitions of Acute Respiratory Distress Syndrome in Several Published Reports

The Berlin Definition of Acute Respiratory Distress Syndrome

INCIDENCE OF ARDS

The most common figure cited for the annual incidence of ARDS based on

an American Lung Program Task Force of the National

Heart and Lung Institute in 1972 was 75 cases per 100,000 population.

In 1988, in England an estimated incidence of 4.5 cases per 100,000

population, was reported.

in 1989, in Spain an estimated incidence of 3.5 cases per 100,000

population per year , was calculated.

Most epidemiologic studies report an ARDS incidence ranging from

4 to 8 cases per 100,000 population per year.

ARDS is caused by an insult to the alveolar-capillary membrane that results in increased permeability and subsequent interstitial and alveolar edema.

ALI includes injury to both the pulmonary capillary endothelium and the alveolar epithelium. In the ARDS lung, an influx of protein-rich edema fluid into the air spaces occurs as a

consequence of increased permeability of the alveolar-capillary barrier.

The pathogenesis of ARDS is a result of two different pathways: a direct (pulmonary) insult to lung cells and an indirect (nonpulmonary)insult occurring as a result of an acute systemic inflammatory response.

PATHOPHYSIOLOGY AND

HISTOPATHOLOGY

The loss of epithelial integrity in ARDS has several consequences:First, under normal conditions, the epithelial barrier is much less permeable than the endothelial barrier; thus epithelial injury can contribute to alveolar flooding. Second, the loss of epithelial integrity and injury to type II cells serve to disrupt normal epithelial fluid transport, impairing the removal of edema fluid from the alveolar space. Third, injury to type II cells reduces the production and turnover of surfactant. Fourth, loss of epithelial barrier can lead to sepsis in patients with bacterial pneumonia. Finally, in severe alveolar epithelium injury, pulmonary fibrosis can develop.

The typical histopathologic features of ARDS are collectively known as diffuse alveolar damage. The early phase of ALI—the exudative phase—is characterized by leakage of

protein-rich edema fluid into the lung and inflammatory cellular alveolar infiltrates. During

this phase, a cytokine storm and an array of inflammatory mediators are released into the

interstitium and alveolar space, perpetuating inflammation and promoting the

development of atelectasis and structural damage to the lung architecture.

An important source of these inflammatory mediators is neutrophils, which play a

key role in the pathogenesis and progression of ALI.

Clinically, this exudative phase is manifested as marked hypoxemia and

reduced lung compliance.

Eventually, these changes evolve to a fibroproliferative phase

in which capillary thrombosis, lung fibrosis, and neovascularization take

place.

Most nonsurvivors of ARDS die during the fibroproliferative

phase , only a small proportion of patients with ARDS die of hypoxemia.

The development of multiple organ dysfunction – the

main cause of death in ARDS -is due to alveolar epithelial-endothelial

barrier disruption and the migration of cytokines produced in the lungs into

the systemic circulation.

ETIOLOGY OF ARDS

Clinical Disorders Associated with Development of (ARDS)

GENETICS OF ARDS

some patients progress despite therapy, whereas others do better than

predicted. It is now well accepted that these responses may be related to

variations in the genome.

The identification of important associations between genotype and clinical

outcomes will have an impact on the development of more efficient genotype-

or phenotype-guided therapies for patients with ALI or ARDS.

Positive genetic association studies with susceptibility to and/or outcome of

ARDS have been done

RESCUE STRATEGIES FOR

REFRACTORY HYPOXEMIA

MANAGEMENT OF ARDS

VENTILATORY MANAGEMENT

SUPPORTIVE TREATMENT

As part of the therapy for the underlying disease, patients with ARDS

invariably require endotracheal intubation and mechanical ventilation to

decrease the work of breathing and to improve oxygen transport. An

improvement in oxygenation can be obtained in many patients with ARDS by

an increase in PEEP.

It is generally accepted that the primary ventilator strategy for patients with

ALI/ARDS should be the one reported in 2000 by the National Institutes of

Health ARDS Network, which to date is the only ventilator-related therapy showing a benefit regarding mortality.

VENTILATORY MANAGEMENT

It is recommended that critical care physicians utilize the ventilation protocol outlined by (ARDSNet) investigators. This protocol involves the following principles:

1. High tidal volumes and high plateau pressures are to be avoided.

2. Tidal volume size should be based on predicted body weight,

calculated from gender and height—50 + 0.91 × (height in cm − 152.4) for men and 45.5 +

0.91 × (height in cm − 152.4) for women—rather than on actual body weight.

3. Tidal volumes should be systematically adjusted (from 4 to 8 mL/kg of

predicted body weight) to maintain a plateau pressure of 30 cm H2O or less.

4. The respiratory rate should be titrated as needed (over a range of 10 to 35

breaths/minute) to maintain a pH of 7.3 to 7.45.

5. An appropriate combination of FIO2 and PEEP should be used to achieve

adequate oxygenation (PaO2 of 55 to 85 mm Hg, or SpO2 of 90% or greater).

RESCUE STRATEGIES FOR REFRACTORY HYPOXEMIA

A number of alternative techniques (currently available worldwide or under evaluation) can

be used to improve oxygenation and ventilation in patients with ALI or ARDS who have

refractory hypoxemia.

In most reports refractory hypoxemia. has been defined as having a PaO2 below 60

mm Hg on an FIO2 0.8 to 1.0 and PEEP 10 to 20 cm H2O for more than 12 to 24 hours.

RECRUITMENT MANEUVERS

Recruitment maneuvers are intended to reopen collapsed and consolidated alveoli and to

attenuate the injurious effects of the repetitive opening and closing of the alveolar unit.

defined as applying a pressure higher than that applied during a normal breath either

intermittently (for 2 to 3 minutes) or sustained for a short period of time (up to about 40

seconds).

it is essential to stabilize the patient hemodynamically before a recruitment maneuver

procedure.

when recruiting pressures are maintained at or below 50 cm H2O peak alveolar pressure,

barotrauma has been rarely reported.

Most recent data suggest that a recruitment maneuver performed in the early phase of

ARDS might be more effective than in late-stage ARDS.

EXTRACORPOREAL MEMBRANE OXYGENATION

Extracorporeal membrane oxygenation (ECMO) is a technique that originally was applied in

patients with acute respiratory failure of such severity that it was impossible to provide adequate

oxygenation by conventional mechanical ventilation.

Most long-term adult ECMO procedures are performed using the venovenous approach.

Access for both blood removal and return is by way of the femoral, saphenous, or jugular vein.

The highly specialized equipment and knowledge required to provide ECMO make this

technique available only in specific medical centers.

The CESAR study investigated the use of ECMO in severe respiratory failure:

■Patients were randomized to transfer to a specialist respiratory failure centre

for ECMO

or standard treatment at current hospital.

■ There was a significant decrease in mortality in the intervention group,

although not all

patients transferred received ECMO.

■ It has been suggested, therefore, that transfer to a specialist respiratory

centre may be

the key component of the intervention.

Evidence

HIGH-FREQUENCY OSCILLATORY VENTILATION

HFOV should theoretically be an ideal mode to ventilate patients with severe lung damage,

because it achieves gas exchange by delivering very small tidal volumes that typically are 1 to 3

mL/kg (often less than the anatomic dead space) at frequencies ranging from 3 to 10 Hz around a

relatively constant mean airway pressure.

Recent prospective, observational studies have reported that HFOV is a feasible and efficient

method of ventilation that results in rapid and sustained improvement in oxygenation in patients

with severe ARDS.

All of the randomized controlled trials to date have compared HFOV with a less-than-

optimal approach to conventional ventilation. Several ongoing trials, however, are

comparing HFOV with low-tidal-volume ventilation.

PRONE POSITIONING

Because most lung infiltrates in patients with ARDS are seen in dependent lung regions,

it was postulated that prone positioning of patients redistributes blood flow and ventilation

to the least affected areas of the lung, promotes secretion clearance, and shifts the weight

of the mediastinal contents anteriorly, to assist in the recruitment of atelectatic regions.

Thus, the proposed mechanisms by which prone positioning improves oxygenation

include:

1. an increase in functional residual capacity

2. a change in regional diaphragm motion

3. redistribution of perfusion to better-ventilated lung units, redistribution of ventilation

to better-perfused lung units

4. improved secretion clearance

PRONE POSITIONING

Three recent systematic reviews and metaanalysis in patients with ALI or ARDS have shown

that in general, prone positioning does not reduce mortality or duration of mechanical ventilation

despite improved oxygenation and a decreased risk of pneumonia.

Subsequent publications suggested reduced mortality in the most moderate-severe cases of

respiratory failure; similar results were reported in a large multi-centre randomized trial, which

employed tight exclusion criteria.

A. Utilized for those with moderate-severe respiratory failure (P:F ratio of <20 kPa).

B. Employed early in the illness (<36 hours).

C. Delivered for between 14 and 20 hours per day.

Proning recommendation

Contra-indications to proning

● Spinal instability

● Pregnancy

● Pelvic fracture

● Severe haemodynamic instability

● Raised intracranial pressure

● Raised intra-abdominal pressure

INHALED VASODILATORS

Nitric oxide (NO) is important for the regulation of pulmonary vascular smooth muscle tone.

NO appears to be pivotal in acute and chronic hypoxic pulmonary vasoconstriction.

Pulmonary hypertension is a typical feature of ARDS and is a bad prognostic factor in

respiratory failure.

Inhaled NO selectively dilates pulmonary vasculature without systemic effects.

A systematic review and metaanalysis of 12 randomized controlled trials including a total of

1237 patients with severe ALI or ARDS found that overall, NO is associated with limited

improvement in oxygenation at 24 hours of therapy, has no effect on duration of

ventilation, does not confer mortality benefits, and may cause harm.

SUPPORTIVE TREATMENT

SEDATION

Sedation protocols using standardized sedation scales

and sedation goals have been proved to reduce the duration

of mechanical ventilation.

Preference should be given to the daily interruption of sedation and the use of

intermittent boluses, rather than continuous infusions, when tolerated.

MUSCLE PARALYSISCurrent guidelines indicate that neuromuscular blocking agents are appropriate for facilitating mechanical ventilation when sedation alone is inadequate, most notably in patients with severe gas exchange impairment.

MUSCLE PARALYSIS

FLUID MANAGEMENT IN ACUTE RESPIRATORY DISTRESS SYNDROME

The ARDSNet published in 2006 the results of a large randomized trial comparing two fluid

management strategies in 1000 patients with ALI or ARDS. Subjects were randomized to

management with either a conservative or a liberal approach. In other words, the conservative

fluid management group had a net fluid balance of about zero over the first 7 days of the

protocol, whereas the liberal fluid management group had an average daily fluid gain of

approximately 1 L.

All patients received respiratory support using a low-tidal-volume, plateau pressure– limited

ventilation strategy.

Although no significant difference was noted in the primary outcome of 60-day mortality,

the conservative approach improved lung function and shortened the duration of mechanical

ventilation and ICU stay without increasing the rate of nonpulmonary organ failure.

These data provide reassurance and support for the use of a conservative fluid management

strategy in patients with ARDS.

CORTICOSTEROIDS

Several clinical trials have evaluated the utility of corticosteroids in preventing ARDS and in treating

either early-stage (inflammatory) or late-stage (fibrotic) ARDS. None of them have demonstrated a

mortality benefit.

The ARDSNet performed the largest randomized, blinded trial of methylprednisolone versus placebo in

patients with ARDS of at least 7 days’ duration. No survival benefit was noted in the steroid group ;

however, methylprednisolone increased the number of ventilator-free days, shock-free days, and ICU-

free days during the first month. Also, it was associated with a significant increase in 60-day and 180-day

mortality rates among patients enrolled after 13 days from onset of ARDS.

This study argues against the use of corticosteroids to treat patients with ARDS. However, a

metaanalysis of selected trials showed that prolonged administration of systemic steroids is associated

with favorable outcomes and a survival benefit when given before day 14 after onset of ARDS.

Nevertheless, the questionable benefit of steroids in patients with ARDS should not preclude the use of

a low-dose regimen in acutely ill patients with sepsis, including those with ARDS.

PROGNOSIS AND LONG-TERM SURVIVAL Prognosis with ARDS depends primarily on the underlying cause of lung injury.

In an analysis of the ARDSNet database, survival to home discharge was lowest in patients

with sepsis, intermediate in patients with pneumonia, and highest in patients with trauma and

ARDS.

In 2001, a 1-year follow-up study of patients with ARDS in the United States found that a

significant percentage of deaths occurred between day 28 and 4 months, which raised the

potential for longer monitoring in the evaluation of new interventions or therapies.

On the basis of cumulative evidence, a patient surviving hospitalization for ARDS can be

expected to return to a similar lifestyle over the course of a year, with some lingering physical and

psychological challenges. Therefore, in the absence of significant comorbid conditions, the

long-term outcome data are sufficient to warrant aggressive treatment for ARDS.

Thanks