ACUTE RESPIRATORY DISTRESS SYNDROMEAND

HOW TO MANAGE

Wahju Aniwidyaningsih-

Division of Interventional Pulmonology & Respiratory Critical CareDepartment of Pulmonology & Respiratory Medicine

Faculty of Medicine University of Indonesia – Persahabatan Hospital

DEFINITION

• N Engl J Med 2000;342:1301–8 – The original description of ARDS included the

presence of bilateral infiltrates on the chest radiograph

– Insult: pulmonary and non-pulmonary

Ware, L. B. et al. N Engl J Med 2000;342:1334-1349

Definitions of the Acute Respiratory Distress Syndrome

The American-European Consensus Conference definition

• Recognizes the severity of clinical lung injury : – Patients with less severe hypoxemia (as defined by a ratio of the partial

pressure of arterial oxygen to the fraction of inspired oxygen of 300 or less) are considered to have acute lung injury

– Patients with more severe hypoxemia (as defined by a ratio of 200 or less) are considered to have the acute respiratory distress syndrome

– facilitate earlier management.

• Simple to apply in the clinical setting.

• Disadvantage not assessing underlying cause and whether other organ systems are affected

Am J Respir Crit Care Med 149:818—824, 1994

Incidence• Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome

(ARDS) are still common problems in many countries with high morbidity and mortality

• In the United States over 100,000 individuals each year develop Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS)

• No Indonesian data need integrated epidemiological study between centres and institutions in Indonesia

• Many studies suggest that ARDS mortality has improved during the past two decades, but remains high, ranging between 25 and 50% in the most current series

Underlying etiologies of pulmonary and extrapulmonaryacute respiratory distress syndrome

Eur Respir J 2003; 22: Suppl. 42, 48s–56s.

Pathophysiology of ARDS• Driven by an aggressive inflammatory reaction

• Triggered by local events such as noxious inhalation or aspiration or by systemic processes such as sepsis and pancreatitis activate ,an infammatory response, many mediators are released into the pulmonary and systemic circulations.

• Result endothelial damage cause pulmonary edema and disturbances of the pulmonary and systemic microcirculations.

• The neutrophil is a major component of this infammatory response,

• Key mediators eg TNFα promote neutrophil adherence to the endothelium and neutrophil activation

• Other cytokines, such as interleukin (IL)-8 : neutrophil chemoattractants and enhance neutrophil activation degranulate neutrophils, release proteases, reactive oxygen species (ROS), leukotrienes.

• The lipid mediators and platelet activating factor (PAF) decrease vascular reactivity and promote further inflammation.

• The coagulation and complement systems also are activated, with enhanced coagulation and decreased fibrinolysis.

• Endothelial damage leaky capillaries, formation of nonhemody-namic pulmonary edema and alterations in the pulmonary microcirculation.

• The end result respiratory failure, decreased systemic oxygenation, and ultimately death.

Pathogenesis of ARDS

N Eng J Med 2000; 342:1334-1349

Clinical presentation

• ARDS developed rapidly, 12-18 hours from insulting injury up to 5 days

• Restlessness, agitation and hypoxemia.

• Pulmonary changes due to inflammation reduced lung compliance small tidal volume, increased respiratory rate and increased work of breathing

• If the patients still able to tolerate respiratory alcalosis

• Worsening can occur in few hours & may need intubation and mechanical ventilation due to respiratory acidosis.

Supporting diagnostic procedure• No laboratory findings are specific for ARDS other than

diagnostic criteria

• Blood gas analysis :– In early phase hypoxemia & respiratory alkalosis due to shunt

or low ventilation-perfusion ratio (V/Q)– In late phase increased deadspace ventilation & work of

breathing, reduced CO2 elimination respiratory acidosis

• Hematological abnormalities– Anemia, leucocytosis/leucopenia, thrombocytopenia due

systemic inflammation and endothelial injury– DIC eg in sepsis, head trauma or severe trauma– Increased von Willebrand's factor (VWF) antigen in serum

• Acute phase reactant : – Increased ceruloplasmin– Reduced albumin

• Proinflammatory cytokines:– Increased tumor necrosis factor α (TNF- α) and IL-1, -6, -8

• BAL– High neutrophils (>60%)– High eosinophils (>15%–20%) : possibilities of eosinophilic

pneumonia– High lymphocytes differential diagnosis hypersensitivity

pneumonitis, sarkoidosis, cryptogenic organizing pneumonia (bronchiolitis obliterans organizing pneumonia), other acute form ILD (interstitial lung disease)

– High erythrocytes and hemosiderin laden macrophages : pulmonary haemmorhage

• BAL should be processed for :– Cultures for possible infection– Cytological examination– PCP– Viral inclusion bodies

• Bronchoscopy with PSB, not suggested to do TBLB (escp patients with mechanical ventilation)

Principles of ARDS Management• Standard supportive therapy for ALI/ARDS is

directed toward identification and management of pulmonary and nonpulmonary organ dysfunction

• Most common disease processes associated with ALI include sepsis, pneumonia, aspiration of gastric contents, trauma, multiple transfusions, and ischemia reperfusion

• Treat the underlying etiology

• Careful evaluation– Pulmonary etiology– Nonpulmonary sources of infection or other

insult should be made.

• In many cases, inciting cause of lung injury cannot be directly treated, such as aspiration or multiple transfusions optimizing supportive care of the patient.

Mechanical Ventilation• The mainstay of supportive care in ALI/ARDS is

positive pressure mechanical ventilation.

• Intrapulmonary shunt and ventilation-perfusion imbalances life-threatening hypoxemia.

• High work of breathing from increased alveolar dead space and reduced respiratory system compliance may cause ventilatory failure with hypercapnia and respiratory acidosis.

• By stabilizing respiration, mechanical ventilation allows time for administration of treatment for the underlying cause of ALI/ARDS (eg, infection) and for the evolution of natural healing processes.

• Arterial oxygenation can be supported by raising the fraction of inspired oxygen (FIO2) and applying positive end-expiratory pressure (PEEP).

• Ventilation can be supported with intermittent positive airway pressure

Volutrauma & Atelectrauma

• Volutrauma – Occurs when the lung is overinflated and alveoli are overstretched– Tidal stretch, rate of stretch, and frequency of stretch.

• Atelectrauma– Caused by the repetitive opening and closing of recruitable alveoli. – In the injured lung, positive-pressure ventilation can force open some

airless alveoli, but on expiration these same alveoli again collapse. recruitment-derecruitment of alveoli.

– Shear stresses trauma, resulting in disruption of the surfactant monolayer, especially when the opening/closing cycle is repetitive.

– Loss or disruption of the surfactant monolayer requirement for higher pressures to achieve alveolar opening, and may affect the permeability of the alveolar-capillary barrier to proteins and other solutes.

Airway pressure and lung distension

• Inflation of the lung will cause damage if airway pressures are high enough.

• The important issues for the clinician ?– What levels of airway pressure are dangerous – Can they be avoided in the mechanical

ventilation of patients with stiff lungs, as in ARDS?

Effects of the distribution of ventilation in two-unit lung models with homogeneous mechanical properties, with abnormal compliance distribution,

and with abnormal resistance distribution.

Respir Care Clin 10 (2004) 309–315

Rat lungs ventilated for 1 hour at three pressure settings: 14/0; 45/10, and 45/0 cm H2O.Lungs of the control animals (14/0 cm H2O) seem to be uninjured. The lungs ventilated at 45/

0 cm H2O are markedly congested and hemorrhagic, whereas the lungs ventilated at 45/10 cmH2O seem only slightly edematous.

Am Rev Respir Dis 1974;110:556–65;

Lung protective ventilation• Clinical hallmarks of ALI/ARDS is decreased respiratory system

compliance

• Traditional tidal volumes of 10 to 15 mL/kg are used in patients with ALI/ARDS receiving mechanical ventilation resulting airway pressures are frequently elevated, reflecting overdistention of the less-affected lung regions

• Ventilation with small tidal volumes and limited airway pressures can reduce ventilator-associated lung injury from overdistention may cause complications acute respiratory acidosis

• Prospective studies mortality was reduced substantially from 40% (traditional strategy) to 31% (lower tidal volume strategy) in a larger trial by the National Institutes of Health (NIH) ARDS Network

Support of Arterial Oxygenation (PEEP)

• PEEP reduces intrapulmonary shunt and improves arterial oxygenation adequate arterial oxygenation at a lower FiO2, reduce pulmonary oxygen toxicity.

• Adverse effects of PEEP include decreased cardiac output, increased pulmonary edema formation,increased resistance of the bronchial circulation, increased lung volume and stretch during inspiration further lung injury or barotrauma.

• In animals, high levels of inspired oxygen cause physiologic and pathologic changes that are similar to other forms of ALI.

• In humans, no detectable oxygen toxicity occurred in normal subjects when the FIO2 was < 50%, but impaired gas exchange was apparent after breathing 100% oxygen at sea level for approximately 40 h.

• Diseased lungs may be more susceptible to injury from moderate hyperoxia.

• Relationship of FIO2 to oxygen-induced lung injury has not been

clearly defined in ALI/ARDS patients, an FIO2 < 0.6 is usually considered to be safe.

Support of Arterial Oxygenation (FiO2)

When should we wean?• The timing and method of discontinuation from

mechanical ventilation remains an important clinical problem.

• Mechanical ventilation can result in life-threatening complications and therefore should be discontinued as soon as possible.

• However, premature attempts at weaning from respiratory support can result in failure and reinstitution of mechanical ventilation, which carries an enhanced risk of morbidity and mortality.

Non-invasive ventilation• Complications of endotracheal intubation :

– upper-airway injuries, tracheomalacia, tracheal stenosis, sinusitis, and ventilator-associated pneumonia.

• Noninvasive positive-pressure ventilation (NIPPV) alternative modality to avoid these complications.

• Advantages of allowing some verbal communication by patients, and some patients can eat during short respites from the face mask.

• Studies in ALI/ARDS patients fewer cases of nosocomial pneumonia and shorter requirements for ventilator assistance in patients who received NIPPV as compared to those who received ventilation via endotracheal tubes.

• Not feasible in delirious or obtunded patients.

High-Frequency Ventilation• Utilizes very small tidal volumes with very

high respiratory rates

• Achieves the two main lung-protective objectives (avoiding both overdistention and ventilation with atelectasis at end-expiration) while maintaining normal PaCO2 as well as arterial oxygenation

High-Frequency Ventilation• Am J Respir Crit Care Med 2002;166,801-808

– Multicenter Oscillatory Ventilation for ARDS Trial– 148 ARDS patients were randomized to either conventional

ventilation with a VT of 5 to 10 mL/kg and PEEP 10 cm H2O or to high-frequency oscillatory ventilation (HFOV).

– The patients in the HFOV group • Ventilation at 5 breaths/s at a mean airway pressure of 5 cm H2O

higher than that observed during conventional ventilation. • The pressure amplitude of ventilation was initially set to achieve

vibration of the chest wall and was adjusted along with frequency to achieve PaCO2 from 40 to 70 mm Hg.

– After 30 days, mortality in the conventional group was 52%, whereas in the HFOV group it was 37% (p = 0.102).

• HFOV is a safe and effective mode of ventilation in ARDS patients.

Management of infection• Patients with ALI/ARDS frequently die from uncontrolled

infection.

• Infection may have been the initial cause of ALI/ARDS

• High risk of developing nosocomial infections, such as pneumonia and catheter-related sepsis.

• Uncontrolled infection associated with the development of multiple organ dysfunction, a major objective of standard supportive care in patients with ALI/ARDS is to identify, treat, and prevent infections.

Vasodilators• Most ALI/ARDS patients have mild-to-moderate pulmonary arterial

hypertension.

• A progressive rise in pulmonary vascular resistance patients die from ALI.

• Etiology of pulmonary arterial hypertension is multifactorial, and may include hypoxic vasoconstriction, destruction and/or obstruction of the pulmonary vascular bed, and high levels of PEEP.

• Inhaled NO encouraging result

• Inhaled NO at a concentration of 18 ppm reduced mean pulmonary artery pressure from a mean of 37 to 30 mm Hg associated with a decrease in intrapulmonary shunt from 36 to 31% and an increase in PaO2/FIO2

Antiinflamatory drugs• ARDS systemic inflammation

• Antiinflammatory drugs controversies exist– Glucocorticoid controversies, which phase, early or

late– Ketokonazole : leucotriene and thromboxane A2

inhibitor– Lisofylline and Pentoxifylline : inhibitor

phosphodiesterase inhibit chemoattractant of neutrophil and TNFα

– Futher research

Antioxidant• Reactive oxygen species play a major role in mediating

injury to the endothelial barrier of the lung in the presence of endotoxin, bacterial sepsis, or hyperoxic lung injury.

• Antioxidant therapy has been useful in the prevention and the treatment of ALI in some animal models

• N-acetylcysteine and procysteine, oxygen free-radical scavengers and precursors for glutathione, were efficacious in some experimental studies

• Large scale study failed to show improvement

Beta adrenergic agonist• B-adrenergic stimulation is known to

reduce infammation

• Adrenergic agents can inhibit the increased lung vascular permeability seen in ARDS and favor resorption of edema.

• Increased sodium-chloride transport transepithelial

Hemodynamic Management• Optimal fluid management in patients with ALI/ARDS is a

controversial issue.

• Data from animal experimentation suggest that fluid restriction may reduce pulmonary edema in patients with increased pulmonary vascular permeability, as in ALI/ARDS.

• Other experimental data suggest that ALI/ARDS patients may benefit from a hemodynamic management strategy that increases oxygen delivery, which may require increased vascular volume.

• Tissue hypoxia: how to detect, how to correct, how to prevent; consensus conference (Am J Respir Crit Care Med 1996; 154:1573–1578)– The consensus committee concluded that "... timely

resuscitation and achievement of normal hemodynamics is essential."

• Vasopressors ?– Needed to support systemic BP or to increase cardiac

output in patients with shock. – No clear evidence that any vasopressor or

combination of vasopressors is superior.

Surfactant therapy• Surfactant normally produced by type II pneumocytes,

decreases surface tension at the air-fluid interface of small airways and alveoli.

• Without surfactant, alveoli may collapse and resist opening, even with high airway pressures.

• In respiratory distress syndrome of premature infants, surfactant production by the immature lung is deficient and surfactant replacement therapy is beneficial.

• In adult ?

Nutrition

• The goals of nutritional support include the provision of adequate nutrients for the patient’s level of metabolism, and the prevention and treatment of deficiencies of macronutrients and micronutrients while attempting to minimize complications related to the mode of nutritional support.

• The route of administration of nutrition in ALI/ARDS will be influenced by the individual patient’s condition and ability to tolerate enteral feeding.

• Parenteral nutrition has been used frequently in ALI/ARDS patients, but experimental and clinical trials suggest that enteral nutrition may be superior.

• Enteral nutrition less complications

• Which composition ? further research

Prone Positioning• Prone positioning leads to substantial improvements in arterial oxygenation

in approximately 65% of ARDS patients

• Improved ventilation to previously dependent (dorsal) regions in the prone position.

• In the supine position, pleural pressures were higher near the more dependent dorsal regions due to hydrostatic gradients reduced transmural pressures of dependent bronchioles and alveoli, contributing to the tendency for atelectasis in these lung zones.

• In the prone position, pleural pressures appeared more uniform, allowing some dorsal regions to open and participate in ventilation and gas exchange could prevent VILI , more uniform distribution of tidal volume and by recruiting dorsal lung regions, preventing repeated opening and closing of small airways or excessive stress at margins between aerated and atelectatic dorsal lung units.

• How many hours a day?

Conclusion• Management of ARDS still have great controversies

• Mechanical ventilation still play great role in ARDS management

• Lung protective ventilation strategy

• Treat underlying etiologies

• Other alternatives of modalities

• Further researches

NIH ARDS Network Lower Tidal Volume Ventilation for ALI/ARDS Protocol Summary

• SpO2 = oxyhemoglobin saturation by pulse oximetry.

•   Further increases in PEEP to 34 cm H2O allowed but not required.

Variables Protocol

Ventilator mode Volume assist-control

Tidal volume   6 mL/kg predicted body weight  

Plateau pressure   30 cm H2O

Ventilation set rate/pH goal 6–35/min, adjusted to achieve arterial pH   7.30 if possible

Inspiratory flow, I:E Adjust flow to achieve I:E of 1:1–1:3

Oxygenation goal 55   PaO2   mm Hg or 88   SpO2   95%

FIO2/PEEP (mm Hg) combinations

 

0.3/5, 0.4/5, 0.4/8, 0.5/8, 0.5/10, 0.6/10, 0.7/10, 0.7/12, 0.7/14, 0.8/14, 0.9/14, 0.9/16, 0.9/18, 1.0/18, 1.0/22, 1.0/24

WeaningAttempts to wean by pressure support required when F IO2/PEEP   .40/8

Lung Injury Score