ACUTE RESPIRATORY DISTRESS SYNDROME

 ARDS Definition

•         Severe, acute lung injury involving diffuse alveolar damage, increased microvascular permeability and non-cardiogenic pulmonary edema

•         Acute refractory hypoxemia

•         Annual incidence 75/100,000 in the US

•         High mortality- 40%-60%

First described in 1967

ARDS Criteria

•         Acute onset of respiratory failure

•         Bilateral infiltrate on CXR (some cases do present unilaterally or with pleural effusion

•         PCWP <18 or absence of left atrial htn,

•         PaO2/FiO2 < 200

ARDS mechanism of lung injury

•         Activation of inflammatory mediators and cellular components resulting in damage to capillary endothelial and alveolar epithelial cells

•         Increased permeability of alveolar capillary membrane

•         Influx of protein rich edema fluid and inflammatory cells into air spaces

•         Dysfunction of surfactant

ARDS causes

•         Direct Lung Injury:                                     

      a) aspiration of gastric contents or other causes of chemical pneumonitis

       b) pulmonary contusion, penetrating lung injury

       c) fat emboli

       d) near drowning

       e) inhalation injury

       f) reperfusion pulm edema after lung transplant

 

•         Indirect lung injury

            a) sepsis

            b) severe trauma w/ shock hypoperfusion

            c) drug over dose

            d) cardiopulmonary bypass

            e) acute pancreatitis

            f) transfusion of multp blood products

St        Ages of ARDS

•         1. Exudative (acute) phase - 0- 4 days

•         2. Proliferative phase - 4- 8 days

•         3. Fibrotic phase - >8 days

•         4. Recovery

             

Predictors of outcome

•         Factors whose presence can be used to predict the risk of death at the time of diagnosis of acute lung injury and the acute respiratory distress syndrome include

            a) chronic liver disease

            b) non-pulmonary organ dysfunction,

            c) sepsis, 

            d)advanced age.

ARDS network study

•         patients with ALI/ARDS at 10 centers, 861 patients

•         Patients randomized to tidal volumes of 12 mL /kg or 6 ml/kg (volume control, assist control, plat Press = 30 cm H2O)

•          22% reduction in mortality in patients receiving smaller tidal volume

•          Number-needed to treat: 12 patients

ARDS Network Study

                                   6ml/kg             12m/kg

PaCO2                        43 ± 12             36 ±9

Respiratory rate           30 ± 7              17 ± 7

PaO2/F /FIO2             160 ± 68           177 ± 81

Plateau pressure          26 ± 7               34 ± 9

PEEP                          9.2 ± 3.6           8.6 ± 4.2

 

ARDS net protocol

•         Calculated predicted body weight(pbw)

       male: 50+2.3[height(inches)-60]

       female: 45.5+2.3[height(inches)-60]

Mode: Volume assist-control

Change rate to adjust minute ventilation(not>35/min)

PH goal 7.30-7.45

Plateau press<30cmh20

PaO2 goal: 55-80mmhg or SpO2 88-95%

FiO2/PEEP combination to achieve oxygenation goal.

 

ARDS net How to select PEEP

•         PEEP/FiO2 relationship to maintain adequate PaO2/SpO2

•         PaO2 goal: 55-80mmHg or SpO2 88-95% use FiO2/PEEP combination to achieve oxygenation goal

ARDS Ventilator setting

•         Greatest Lung strain PC IRV(I:E 2:1), least w/ PC (I:E 1:2) and intermediate w/ VC (I:E 1:2)

•         No difference in gas exchanged, hemodynamics, and plateau pressure

•         No difference in outcome w/ ARDS pts randomized to pressure control vs volume cycled  PC(n=37), VC(n=42).

Permissive Hypercapnia

•         Low Vt (6ml/kg) to prevent over-distention

•          increase respiratory rate to avoid very high level of hypercapnia

•         PaCO2 allowed to rise

•         Usually well tolerated

•         May be beneficial

•         Potential Problems: tissue acidosis, autonomic dysregulation, CNS effect, and circulatory effects

ARDS Treatment

•         Ventilator-induced lung injury: it was previously thought that oxygen toxicity was one of the most important factors in the progression of ARDS and resultant mortality. Recently, it was found that high volume(volutrauma) and high press(barotrauma) are equally if not more detrimental to these pts

•         Treatment strategy is one of low volume and high frequency ventilation (ARDS Net protocol)

•         Search for and treat the underlying cause

•         Treat abdominal infx promptly w/ abx and surgery

•         Ensure adequate nutrition and place on GI/DVT prophylaxis

•         Prevent and treat nosocomial infx

•         Consider short course of high dose steroids in pts w/ severe dz that is not resolving.

ARDS net and Long-term outcome

120pts randomized to low Vt or high Vt      

         a) 25%mortality w/ low tidal volume

         b) 45% mortality w/ high tidal volume

      20% had restrictive defect and 20% had obstructive defect 1 yr after recovery

      About 80% had DLCO reduction 1 yr after recovery

      Standardized tested showed health-related quality of life lower than normal

     No difference in long-term outcomes between tidal volume group

Unstable Angina Management

 

NSTEMI & Unstable Angina Management

 

—  NSTEMI or EKG changes suggest ischemia with high risk:

¡ Aspirin

¡ Beta blocker

¡ Nitrates

¡ Heparin (UFH or LMWH)

¡ ACE-I/ARB

¡ Statin

¡ Consider GP IIb/IIIa inhibitor and clopidogrel

—  EKG normal or non-specific changes with intermediate or low risk:

¡ Rule out ACS with 3 sets of troponin, EKG

¡ Consider pre-discharge stress test

 

Early Treatment

q MONA

•         Morphine- for analgesia

•         Oxygen- sPO₂ >94%

•         Sublingual nitroglycerin

•         Aspirin, 160 to 325 mg

•         Clopidogrel

•         Adjunct therapy

 

Acute MI:  Outcome

•         Outcome after acute myocardial infarction is a function of vessel patency rate and time from occlusion to reperfusion

•         Benefits of Rapid Reperfusion

–        Decreased mortality

–        Decreased morbidity

–        Increased myocardial salvage

–        Increased left ventricular function

 

•         Preferred therapy if performed in a timely fashion by skilled individuals in high-volume centers

•         Reperfusion strategy in patients with risk of bleeding contraindications to thrombolytic therapy

Acute MI:  Thrombolysis

•         Benefit greatest if therapy initiated early

•         Highly significant reduction in mortality

•         Benefits patients irrespective of age, gender, and comorbid conditions

•         Slightly increased risk of intracerebral hemorrhage

•         Candidates

Ø Time to therapy 12 hours or less

Ø Acute ST-segment elevation

Ø Symptoms consistent with acute MI and presence of Left Bundle Branch Block

Ø Patients without ST-segment elevation should not receive thrombolytic therapy

Thrombolytic Therapy

 

Contraindications

•         Active bleeding

•         Recent major trauma/surgery in 3 weeks

•         Recent GI bleed in 1 month

•         Ischemic stroke within 6 months

•         Haemorrhagic stroke at any time

•         Markedly elevated blood pressure

•         Significant bleeding diathesis

•         Pregnancy or post partum

 

Thrombolytic Agents

•         Nonspecific agents deplete coagulation factors

            A.  Streptokinase

            B.  Anistreplase

            C.  Urokinase

•         Specific agents do not deplete coagulation factors

            A.  Alteplase (tPA)

            B.  Reteplase

 

Thrombolytic Agents:
Comparative Pharmacologic Features

     Feature                     SK         APSAC       UK       SCUPA      rtPA

Half-Life (min)                 18             90           20             7              5

Fibrin-Selective                +               +           ++         ++++          +++

Duration of

  Infusion                    60 min        2-5 m      5-15 m    Hours      Hours

Antigenicity                    Yes           Yes          No          No?        No?

Incidence of

  Reperfusion (%)         60-70         60-70      60-70       60-70       60-70

Frequency of

  Reocclusion (%)           15              10            10           NA           20

Fibrinogenolysis          ++++          ++++        +++          ++            ++

Platelet Activation         +++            +++           0             ?           ++++

Acute MI
Adjunct Drug Therapy

 

Aspirin

•         Inhibition of Thromboxane A2 formation

•         Blockage of platelet aggregation and thrombus propagation

•         Prevention of coronary re-occlusion after successful thrombolysis

•         Potential Benefits

Ø Mortality decreased 23%

Ø Non-fatal MI decreased 44%

Ø Non-fatal stroke decreased 46%

Ø 42% reduction in mortality when added to Streptokinase

 

Heparin

•         Post thrombolytic therapy, heparin administration based more on current practice than on evidence

•         Intravenously in patients receiving alteplase/retaplase

•         Subcutaneously in all patients not treated with thrombolytic therapy

•         Should be used in large AWMI or in patients with LV mural thrombus to reduce risk of stroke

•         Potential Benefits

Ø Prevention of venous thrombosis

Ø Decrease left ventricular mural thrombus

Ø Decrease arterial embolization

Ø Decrease re-infarction or extension of infarct

 

Beta Blockers

•         Patients without contraindications should receive intravenous beta blockers when acute infarction is suspected, followed by oral agents when they are hemodynamically stable

•         All patients within 12 hours of myocardial infarction

•         Continuing or recurrent ischemic pain

•         Tachyarrhythmias

•         Potential Benefits

Ø 13% reduction in mortality in the pre-thrombolytic trials

Ø Reduce chest pain

Ø Reduce myocardial-wall stress

Ø Reduce infarct size

 

Contraindications

•         Bradycardia

•         Second- or third-degree AV block

•         Hypotension

•         Clinical evidence of congestive heart failure

•         Cardiogenic shock

•         Active bronchospasm

 

Nitrates

•         Intravenously for first 24 to 48 hours

            A.  Acute MI and CHF

            B.  Large anterior infarction

            C.  Persistent ischemia

            D.  Hypertension

•         Beyond 48 hours in patients with recurrent angina or persistent pulmonary congestion

•         Potential Benefits

Ø Primary action is vasodilation

Ø May increase myocardial perfusion

Ø May increase peri-infarct ischemia

Ø Systemic arterial vasodilation decreases blood pressure and decreases myocardial oxygen demand

Ø Increased venous capacitance decreases preload

 

ACE Inhibitors

 

•         Potential Benefits

Ø Mortality benefit when administered within 24 hours of MI

Ø Systemic and coronary vasodilation may:

Ø             A.  Reduce peri-infarct ischemia

Ø             B.  Limit infarct expansion

Ø             C.  Prevent early remodeling

Ø May have some antithrombotic properties 

 

Calcium Channel Blockers

 

•         Reduce angina

•         Reduce blood pressure

•         Reduce coronary spasm

•         No reduction in mortality

•         Short-acting nifedipine may increase mortality (TRENT, SPRINT II)

Ø Not recommended as standard first-line therapy

Ø May be used for significant hypertension or refractory ischemia

 

Rhythm Disturbances
Atrial Fibrillation

 

•         Electrical cardioversion for unstable patients (ischemic chest pain, hypotension, congestive heart failure)

•         Slow the ventricular response:

            A.  IV Digitalis

            B.  IV Beta Blockers

            C.  IV Diltiazem or Verapamil

Post discharge Care

A – Antiplatelets & Antianginals

B – Beta blocker, Blood pressure control

C – Cholesterol lowering, Cigarettes cessation

D – Diabetes control, Diet

E – Education & Exercise

 

Thrombolytic drugs

•         Depletion of fibrinogen, reduction in factor II, V, and VIII levels, impairment of platelet aggregation, and the appearance of fibrin split products.

•         If surgery is required for persistent ischemia after failed thrombolytic therapy, it should be delayed by at least 12–24 hours.

•         If it is required emergently, plasma and cryoprecipitate will probably be necessary to correct the anticipated coagulopathy.