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Updates on Acute respiratory distress syndrome
Hamdi Turkey - chest physician
I hope you are still awake at the end of this lecture !
Case presentation
A 35 year old male patient was r u s h e d i n t o t h e E R complaining of SOB for the past 3 days, he has fever, Tachypnea, pulse 110 bpm,BP 80/50 mmHg, pal lor and cyanosed, normal JVP, normal S1 and S2 with no added sounds, on chest auscultation there was bilateral diffuse crackles.
SpO2 on room air was 60, ABG : PaO2= 40, Pco2= 40, pH=7.3
What's the diagnosis?
Learning Objectives
To know the new definition of ARDS
To understand the pathology and pathophysiology of ARDS
To devise a ventilation strategy for these patients.
To introduce the concept of ventilator induced lung injury
To address adjunct and rescue therapy for patients with resistant hypoxemia.
History I n 1 9 6 7 A s h b a u g h a n d colleagues published a case series in the Lancet which described a clinical syndrome, which they (later) termed “Adult R e s p i r a t o r y D i s t r e s s Syndrome” (ARDS). The 12 patients involved complained of acute respirator y distress, cyanosis refractory to oxygen t h e r a p y, d e c r e a s e d l u n g c o m p l i a n c e a n d d i f f u s e pulmonary infiltrates on chest x-ray.
Trauma doctors involved in treating victims of war had long been familiar with this syndrome, which came to be known as “wet lung”, “shock lung” or “Da-nang lung”.
This problem had been identified during World War II but with the advent of advanced trauma (M.A.S.H. units during the Vietnam war) the prevalence of this form of respiratory failure was truly recognized.
Over the past 30 or so years, this syndrome has come to be one of the central problems of intensive care: lung injury arising from a variety of different etiologies, each characterized by bilateral diffuse infiltrates on x-ray, hypoxemia, and non-cardiogenic pulmonary edema.
History
In 1988, an expanded definition was proposed that quant ified the physiologic respiratory impairment through the use of a four-point lung-injury scoring system that was based on:
level of positive end-expiratory pressure ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen static lung compliance degree of infiltration evident on chest radiographs.
History
Before research into the pathogenesis and treatment of this syndrome could proceed, it was necessary to formulate a clear definition of the syndrome. Such a definition was developed in 1994 by the American-European Consensus Conference (AECC) on acute respiratory distress syndrome (ARDS).
The term “acute respiratory distress syndrome” was used instead of “adult respiratory distress syndrome” because the syndrome occurs in both adults and children.
History
The Berlin Definition of ARDS (published in 2012) has replaced the American-European Consensus Conference’s definition of ARDS (published in 1994). However, it should be recognized that most evidence is based upon prior definitions.
History
Other terms Shock lung Pump lung Traumatic wet lung Post traumatic atelectasis Adult hyaline membrane disease Progressive respiratory distress Acute respiratory insufficiency syndrome Haemorrhagic atelectasis Hypoxic hyperventilation
Postperfusion lung Oxygen toxicity lung Wet lung White lung Transplant lung Da Nang lung Diffuse alveolar injury Acute diffuse lung injury Noncardiogenic pulmonary edema. Progressive pulmonary consolidation
AECC Past definition of ARDS
ARDS was defined as:
the acute onset of respiratory failure, bilateral infiltrates on chest radiograph, hypoxemia as defined by a PaO2/FiO2 ratio ≤200 mmHg, and no evidence of left atrial hypertension or a pulmonary capillary pressure <18 mmHg (if measured) to rule out cardiogenic edema. In addition, Acute Lung Injury (ALI), the less severe form of acute respiratory failure, was different from ARDS only for the degree of hypoxemia, in fact it was defined by a 200 < PaO2/FiO2 ≤300 mmHg.
The 1994 AECC definition became globally accepted, but had limitations
The current definition is the ‘Berlin Definition’ published in 2013, which was created by a consensus panel of experts convened in 2011 (an initiative of the European Society of Intensive Care Medicine endorsed by the American Thoracic Society and the Society of Critical Care Medicine)
AECC Past definition of ARDS
ARDS BERLIN DEFINITION
ARDS is an acute diffuse, inflammatory lung injury, leading to increased pulmonary vascular permeability, increased lung weight, and loss of aerated lung tissue…[ w i t h ] h y p o x e m i a a n d b i l a t e r a l radiographic opacities, associated with increased venous admixture, increased physiological dead space and decreased lung compliance.
The goal of developing the Berlin definition was to try and improve feasibility, reliability, face and predictive validity
ARDS BERLIN DEFINITION
Timing of acute onsetThe timing of acute onset of respiratory failure to make diagnosis of ARDS is clearly defined in Berlin definition.
It defines the exposure to a known risk factor or worsening of the respiratory symptoms within one week.
It is important to identify risk factors that explain the context of acute respiratory failure arised from
Oxygenation In the Berlin definition, there is no use of the term Acute Lung Injury (ALI).
The committee felt that this term was used inappropriately in many contexts and hence was not helpful.
In the Berlin definition, ARDS was classified as mild, moderate and severe according to the value of PaO2/FiO2 ratio. Importantly, the PaO2/FiO2 ratio value is considered only with a CPAP or PEEP value of at least 5 cmH2O.
The chest radiograph is characterized by bilateral opacities involving at least 3 quadrants that are not fully explained by pleural effusions, atelectasis and nodules.
In the absence of known risk factors, a cardiogenic origin of edema is to be excluded by objective evaluation of cardiac function with echocardiography.
Consequently, the wedge pressure measurement was abandoned because ARDS may coexist with hydrostatic edema caused by fluid overload or cardiac failure.
Chest X-ray
Key componentsacute, meaning onset over 1 week or less
bilateral opacities consistent with pulmonary edema must be present but may be detected on CT or chest radiograph
PF ratio <300mmHg with a minimum of 5 cmH20 PEEP (or CPAP)
must not be fully explained by cardiac failure or fluid overload,” in the physician’s best estimation using available information — an “objective assessment“ (e.g. echocardiogram) should be performed in most cases if there is no clear cause such as trauma or sepsis.
Severity
*on PEEP 5+; **observed in cohort
ARDS is categorized as being mild, moderate, or severe:
ARDS Severity PaO2/FiO2* Mortality**
Mild 200 – 300 27%
Moderate 100 – 200 32%
Severe < 100 45%
Changes from the 1994 AECC definition
the term acute lung injury was abandoned
measurement of the PaO2/FIO2 ratio was changed to require a specific minimum amount of PEEP
3 categories of ARDS were proposed (mild, moderate, and severe) based on the PaO2/FIO2 ratio
Radiographic criteria were changed to improve interrater reliability
PCWP criterion was removed and additional clarity was added to improve the ability to exclude cardiac causes of bilateral infiltrates
1994 AECC DEFINITION
Now obsolete
Shortcoming of the AECC definition
acute is ill defined
PF ratio can be manipulated by adjusting PEEP
CXR interpretation is unreliable
PACs are rarely used
PCWP may oscillate above and below the cut-off and may be elevated for reasons other than heart failure
ALI was used inconsistently, just PF ratio 200 to 300, or all patients <300 including ARDS?
Incidence and outcome
■20-75 per 100,000 ■30% mortality ■Recovery may take 6-12 months ■Residual: Restriction Obstruction Gas- Exchange Abnormalities Reduced Quality of Life
Directpneumonia aspiration of gastric contents lung contusion fat embolism Amniotic fluid embolism near drowning inhalational injury reperfusion injury
non-pulmonary sepsis multiple trauma massive transfusion pancreatitits Salicylate or narcotic overdose cardiopulmonary bypass
Indirect
Risk factors
Cardiogenic Vs non cardiogenic pulmonary edema
Cardiogenic Non-Cardiogenic
Patchy infiltrates in bases Effusions Kerley B lines Cardiomegaly Pulmonary vascular redistribution Excess fluid in alveoli
Homogenous fluffy shadows No effusion No Kerley B lines No cardiomegaly No pulmonary vascular redistribution Protein, inflammatory cells, fluid
Cardiogenic Non-Cardiogenic
Cardiogenic Non-Cardiogenic
Pathophysiology Classical phases
Injury
Exudative – alveolar capillary membrane disruption with inflammatory cell infiltrate and high protein exudate to form hyaline membranes
Proliferative – proliferation of abnormal Type II alveoli cells and inflammatory cells
Fibrotic – infiltration with fibroblasts which replace alveoli and alveolar ducts with fibrosis
Resolution – slow and incomplete repair and restoration of architecture
Pathophysiology 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
Findings on Light Microscopy and Electron Microscopy during the Acute Phase (Panels A and D) and the Fibrosing-Alveolitis Phase (Panels B, C, and E) of Acute Respiratory Distress Syndrome.
Pathophysiology 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.
Pathophysiology
Complex interplay
pulmonary oedema from damage to the alveolocapillary barrier
inflammatory infiltrates
surfactant dysfunction
It is essential to understand that although ALI is a diffuse process, it is also a heterogeneous process, and not all lung units are affected equally: normal and diseased tissue may exist side-by-side.
Effectshypoxaemia (V/Q mismatch, impaired hypoxic pulmonar y vasoconstriction)
increase in dependent densities (surfactant dysfunction, alveolar instabilities)
decreased compliance (surfactant dysfunction, decreased lung volume, fibrosis)
collapse/consolidation (increased compression of dependent lung)
increased minute ventilation (increased in alveolar dead space)
increased work of breathing (increased elastance, increased minute volume requirement)
pulmonary hypertension (vasoconstriction, microvascular thrombi, fibrosis, PEEP)
Host factors increasing the risk of ARDS
Clinical variables found to be associated with an increased risk of ARDS
Diabetes mellitus decreases the risk of ALI.
chronic alcohol abuse hypoproteinemia advanced age, increased severity,and extent of injury or illness as measured by injury severity score (ISS) or APACHEscore hyper-transfusion of blood products cigarette smoking.
Causative factors in ARDS
Primary injury Host response
Consequences of therapy
Clinical features
Symptoms Acute respiratory distress syndrome (ARDS) is characterized by the development of acute dyspnea and hypoxemia within hours to days of an inciting event, such as trauma, sepsis, drug overdose, massive transfusion, acute pancreatitis, or aspiration. In many cases, the inciting event is obvious, but, in others (eg, drug overdose), it may be harder to identify.
Patients developing ARDS are critically ill, often with multisystem organ failure, and they may not be capable of providing historical information. Typically, the illness develops within 12-48 hours after the inciting event, although, in rare instances, it may take up to a few days.
With the onset of lung injury, patients initially note dyspnea with exertion. This rapidly progresses to severe dyspnea at rest, tachypnea, anxiety, agitation, and the need for increasingly high concentrations of inspired oxygen.
Physical findings Physical findings often are nonspecific and include tachypnea, tachycardia, and the need for a high fraction of inspired oxygen (FIO2) to maintain oxygen saturation. The patient may be febrile or hypothermic. Because ARDS often occurs in the context of sepsis, associated hypotension and peripheral vasoconstriction with cold extremities may be present. Cyanosis of the lips and nail beds may occur.
Examination of the lungs may reveal bilateral rales. Rales may not be present despite widespread involvement. Because the patient is often intubated and mechanically ventilated, decreased breath sounds over 1 lung may indicate a pneumothorax or endotracheal tube down the right main bronchus.
Manifestations of the underlying cause (eg, acute abdominal findings in the case of ARDS caused by pancreatitis) are present.
Symptoms and signs
that suggest a cause of
ARDS
Laboratory investigations Routine blood counts
RFT
LFT
Blood culture
BNP
ABG
BAL
ECHO
Chest CT scan
PCWP
Classic Chest X Ray of a patient with ARDS, although the lung injury appears diffuse, when you look at the CT scan of the same patient on the right you can see that the lower lobes are densely consolidated and the upper lobes relatively spared. Nevertheless, this patient was severely hypoxic, and responded well to prone positioning.
Management
Therapy- goals
Treatment of the underlying cause
Cardio-pulmonary support
Specific therapy targeted at lung therapy
Supportive therapy
Diagnosis and appropriate treatment of the underlying cause to minimise physiological impact of cause (drain collection, antibiotics, resuscitate, splint fractures)
Nutritional support
Standard ICU prophylaxis
Stress ulcer prophylaxis
Prevention of nosocomial infections
CVP monitoring with CV line with appropriate fluid therapy
General measures
Goal of management of a patient with ARDS
Treatable inciting
causes of ARDS
Lung protective strategy in ARDS A myth or a fact!
Mechanical ventilation
Therapy- mechanical ventilation
The Problem: Ventilator- Induced Lung Injury ■High volumes and pressures: Stress
( barotrauma) ■Overdistension & Alveolar Cracking
( volumtrauma) ■Cyclic Opening and closing of atelectatic
alveoli ( atelectrauma)
Cause increased permeability and alveolar damage
The Problem: Oxygen Toxicity ■Free Radicals ■Oxygen Washout and De-Recruitment
High FiO2 can lead to further alveolar damage
Therapy- mechanical ventilation
■ Intubation almost always necessary ■ In past, goal was to normalize pH,
PaCO2, PaO2 ■High volumes and pressures were used ■Worse outcomes
Therapy- mechanical ventilation
Lung protective strategy Amato et al. 1998, Effects of a protective-
ventilation strategy on mortality in the acute respiratory distress syndrome. N. Engl. J. Med. 338:347-54
■53 pts with early ARDS ■Compared “conventional” ventilation of 12ml/kg
to “protective” 6ml/kg ■Low PEEP. PaCO2 35-38 ■ Improved survival at 28 days ■Higher percentage of ventilator weaning ■Less barotrauma
The Acute Respiratory Distress Network. 2000. 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. 342:1301-8
■Larger Trial. 861 patients ■Compared 12 ml/kg vs. 6ml/kg ventilation. ■ Plateau pressures 50 cm H2O vs. 30 cm H2O. ■Trial ended early: ■39.8% mortality vs. 31% mortality
THIS HAS CHANGED CLINICAL PRACTICE
Lung protective strategy
Mechanical ventilationARDS Network protective lung ventilation strategy (from the ARMA study)
controlled ventilation
TV 6mL/kg
avoid overstretch (volutrauma) and inadequate recruitment (atelectrauma)
PEEP 5-15
Plateau pressure <30 cmH20 (higher than this contributes to VILI from overstretching and hyperinflation of the functional ‘baby lung’)
mode of ventilation: generally no difference
PCV tends to be used c/o plateau pressure approximates peak pressure, with VC plateau pressure needs to be measured
no role for inverse ratio ventilation (I:E ratio > 1) -> increased mean airway pressure + haemodynamic instability + regional hyperinflation
oxygenation target: SpO2 88-95%, PaO2 > 55-80 mmHg
carbon dioxide target: ARDSnet aimed for a normal CO2 -> but lung is exposed to repeated tidal stretch, ideally hypercapnia should be minimised but there isn’t compelling data to suggest it is harmful unless there is an obvious reason (raised ICP, pregnancy).
Ventilator strategy in ARDS
Ventilator settings for lung protection
Complications related to MV
Other techniques to improve oxygenation
prone posture: improves oxygenation and mortality in severe ARDS
recruitment manoeuvres (e.g. PEEP 30-40cmH2O held for 30 seconds or staircase recruitment manouvre) -> can improve oxygenation but controversial, not everyone responds
inhaled iNO: optimisation of V/Q mismatch, 1-60ppm, on 40-70% will respond, monitor for metHb
inhaled prostacycline (PGI2): optimisation of V/Q mis-match, 1-50ng/kg/min, as effective as iNO
Pharmacological therapysurfactant replacement therapy: theoretically good, improves oxygenation but no improvement in mortality, problems with distribution to alveoli
Diuretics : liberal vs conservative strategy
glucocorticoids: improvement in ventilator free days and shock, no improvement in mortality and increase in weakness
ketoconazole: antifungal that inhibits thromboxane synthase and 5-lipooxygenase -> early data but not confirmed.
others: cytokine antagonism, NSAIDS, scavengers of O2 radicals, lisofylline -> no success
Seek and treat underlying causes and complications
A randomized, clinical trial determined that simvastatin, a hydroxymethylglutaryl-coenzyme A reductase inhibitor, improved oxygenation and respiratory mechanics in patients with ALI. Further studies are needed, but treatment with simvastatin appears safe and may be associated with improved organ dysfunction in patients with ALI.
Statins
Pharmacological therapy
Activated protein C Drotrecogin alfa was withdrawn from the worldwide market October 25, 2011. In the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS)-SHOCK clinical trial, drotrecogin alfa failed to demonstrate a statistically significant reduction in 28-day all-cause mortality in patients with severe sepsis and septic shock. Trial results observed a 28-day all-cause mortality rate of 26.4% in patients treated with activated drotrecogin alfa compared with 24.2% in the placebo group of the study.
In these critically ill patients, pay careful attention to early recognition of potential complications in the intensive care unit (ICU), including pneumothorax, IV line infections, skin breakdown, inadequate nutrition, arterial occlusion at the site of intra-arterial monitoring devices, DVT and pulmonary embolism (PE), retroperitoneal hemorrhage, gastrointestinal (GI) hemorrhage, erroneous placement of lines and tubes, and the development of muscle weakness.
Prognosis
pulmonary function returns to normal at 6-12 months in survivors
occasionally patient have severe restrictive lung disease
although this is the case, many patient have a severe reduction and pulmonary QOL -> depression, anxiety and PTSD are common
patient often have cognitive impairment -> these correlate with the period and severity of hypoxia
Thank you
