for perfusion students

1. Effects of CPB on Lungs
NAHAS N
Clinical perfusionist
NIMS Medicity

2. Introduction

3.  The lungs receive blood from pulmonary arteries and the bronchial arteries, that supply blood to
nourish the lung tissues.
 Most of the blood from the lungs returns to the heart through the pulmonary veins ( left heart
venting necessary).
 The longer the pump run the more likely there will be pulmonary dysfunction.

4. Triggers of lung impairment during CPB
Due to,
the CPB circuit with the patients’ blood being exposed to a wide range of synthetic materials (
results in SIRS and the ischemia –reperfusion injury). This can lead to
Post-op bleeding
Infection
MODs – ALI or ARDS
Alveolar and endothelial damage- resulting in Pulmonary edema, accumulation of alveolar
protein, facilitation of inflammatory cell sequestration and brocho-alveolar lavage fluid (thickened
alveolar-endothelial barrier).
Metabolic acidosis
Neutrofilic infiltration in lung tissues.

5. Respiratory changes after cardiac
surgery
 Deleterious effect on the muscle pump and chest wall, phrenic nerve damage
and/or diaphragm dysfunction ( cold CPG solution)
 Normal respiratory function may interfere both surgery stress and the
presence of chest tube drains.
 Alveolar edema due to LV distension or elevated pressures.
 Capillary permeability ( leading to alveolar flooding) may due to either
transfusion reactions or allergic reactions to drugs.

6. Lung mechanics
 The mechanical properties of respiratory system is
referred as :
Compliance –
Describes the stiffness of the lungs
Change in volume over the changes in pressure
Elastance/ elastic recoil –
The tendency of the lung to return to its resting
state
Resistance –
Airway resistance

7. Effects of CPB on Lung mechanics:
- Thoracotomy decreases the lung compliance.
- Forced expiratory volume (FEV1) is decreased immediately after CABG.
- Changes in flows and volumes both reduces inspiratory strength and reduced on
uncoordinated ribcage expansion.
- Increases in respiratory rate and a decrease in Tidal volume(TV).
- Decrease in respiratory efficiency and increasing the oxygen cost of breathing.

8. Respiratory sequelae of CPB
 Reduced respiratory system compliance
 Increased respiratory system resistance
 Reduced lung volumes and gas flows rates
 Impaired gas exchange
 Atelectasis
 Phrenic nerve damage/ dysfunction
 Reduced pump function (muscle weakness)
 Cardiogenic pulmonary edema
 ‘Pump lung’ or ARDS

9. Phrenic nerve damage:
-Frost-bitten phrenic nerve was originally described in 1963.
-Phrenic nerve damage / dysfunction secondary to trauma or extreme cold may result in
significant post-op loss of lung volume.

10. Surfactant :
Special alveolar epithelial cells secrete surfactant leads to fluid that coat inside
surface of alveoli lead to 2-10 times decrease surface tension in alveoli which prevents
alveolar collapse
Alveoli lead to decrease surfactant result in increase surface tension lead to lung
collapse (The lack of surfactant function therefore leads to atelectasis).
Surfactant changes occur only after significant microvascular damage.

12. Gas exchange:
Alveolar to arterial oxygen gradient increases immediately after cardiac surgery
Decrease in paO2 appears to be due to :
-The mechanical changes
-Atelectasis
-Decrease in lung volume
-Increase in pulmonary ventilation
-Pleural effusion and/or pleural thickening and greater still if an
internal mammary artery graft has been placed.

13. CPB induced Hemodilution and post-op
lung function
Hemodilution during CPB results from,
- Non-Haemic prime for the bypass circuitry
- Crystalloid CPG infusion
- Fluid administration by anesthetists

14.  Starling equation which relates,
capillary permeability
factors to hydrostatic and colloid osmotic pressure
 An increase in capillary hydrostatic pressure or reduction in colloid osmotic pressure should promote
fluid transduction from the capillary.
 Hemodilution alone results in fluid accumulation and reduced plasma oncotic pressure (may responsible
for gas exchange abnormalities after CPB).
 Interstitial and alveolar edema will develop due to trans-capillary fluid transduction (rapid or
excessive).
 The development of lung edema after CPB due to post- op ventricular dysfunction.

15. When a decrease in capillary pressure, the Starling Equation suggests that fluid will move from the interstitial
space into the vascular space. This, finally, is what leads to anemia. The plasma is "diluted" by fluid shifting from
the interstitium.

18.  oncotic pressure -
 The osmotic pressure created by colloids (mainly plasma proteins) which are normally retained within
the vascular system;
 oncotic pressure nearly offsets the hydrostatic pressure which acts to drive fluid out of vessels into the
extravascular space;
 the result is that small amounts of fluid cross the vascular barrier, which are then transported back to
the blood via the lymphatics;
 a decrease in oncotic pressure can be a cause of non-inflammatory edema.
 edema -
 Any excessive accumulation of serous fluid or interstitial fluid (lymph) in tissue spaces or a body cavity;
significant edema will produce obvious swelling of the involved tissues;

19. Post perfusion lung syndrome
 Postperfusion lung syndrome is similar to adult respiratory distress syndrome
in clinical features, diagnostic approaches and management strategies. the
etiologies and predisposing risk factors may differ between each other.
 The ARDS that develops early after cardiopulmonary bypass (CPB) is known as
post-perfusion or post-pump syndrome, which remains a significant clinical
problem on those patients receiving heart operations under CPB.
 Postperfusion lung syndrome is rare but refractory.

20.  Both ALI and ARDS were characterized by an acute onset, bilateral pulmonary infiltrations on
chest X-ray and pulmonary wedge pressure <18 mmHg.
 The only differential criterion for both disorders was arterial oxygen tension (PaO2)/fractional
inspired oxygen (FiO2) <300 mmHg in ALI, but PaO2/FiO2 <200 mmHg in ARDS.
 ARDS was classified into 3 levels based on degree of hypoxemia:
 mild (200 mmHg < PaO2/FiO2 <300 mmHg)
 moderate (100 mmHg <PaO2/FiO2 <200 mmHg)
 severe (PaO2/FiO2 <100 mmHg)

21.  CPB may be of considerable pulmonary pathophysiological consequences in terms of
 the alveolar-arterial oxygenation gradient [P(A-a)O2],
 intrapulmonary shunt,
 degree of pulmonary edema,
 pulmonary compliance
 pulmonary vascular resistance,
 may eventually lead to pulmonary dysfunction.
The respiratory dysfunction can be a result of pulmonary
ischemia-reperfusion injury, interstitial edema and
impaired microcirculation induced by CPB with activated
cytokines, enhanced reactive oxygen species and reduced
endogenous nitric oxide production

22. MAJORDIFFERENTIATIONSBETWEENACUTERESPIRATORY
DISTRESSSYNDROMEANDPOSTPERFUSIONLUNGSYNDROME

23. Pathophysiology
 Respiratory indicators
PaO2/FiO2 - termed as oxygenation index, shows a good correlation with intrapulmonary shunting,
and can better reflect anoxia even in the condition of oxygen therapy
PaO2 - is easily influenced by mechanical ventilation. As PaO2 decreases in all types of respiratory
failure, it cannot reflect the actual respiratory function and may therefore be less reliable, but
leading to a delayed diagnosis if taken for an early diagnosis of ARDS
Arterial/alveolar oxygen tension ratio [P(A/a)O2] - is an indicator of gas exchange (oxygen intake)
impairment. Increase of P(A-a)O2 mean deficiency of gas exchange and is likely to be more sensitive
than the decrease of PaO2
Respiratory index (RI) is the ratio of P(A-a)O2 to PaO2. The normal range of RI is 0.1-0.3, ARDS
patients with sustained RI elevation may eventually develop multiple organ failure

24. Lung compliance
Type II cells main function is to produce surfactant.
Surfactant plays an essential role in preventing the alveoli from collapsing.
type II cell impairment may inevitably result in pulmonary compliance reduction.
a marked reduction in lung compliance, the work of breathing and the physiologic dead space
increase.
Mechanical ventilation may reverse hypoxemia of ALI and prevent from developing into ARDS.
With increasing PEEP, PaO2/FiO2 increases and static lung compliance stabilizes.

25. Extravascular lung water
It is composed of intracellular, intra-alveolar and alveolar interstitial fluid.
Increase of extravascular lung water is a prominent feature of ARDS and the actual reason for
refractory hypoxemia.
Clinically, extravascular lung water index (EVLWI) is an indicator for the description of extravascular
lung water. The normal range of EVLWI is 3.0-7.0 mL/kg. An EVLWI >7.0 mL/kg suggests the
presence of pulmonary edema.
ARDS closely correlated with increase of EVLWI and pulmonary vascular permeability index.

26. Intrapulmonary shunting
A pulmonary shunt is a condition of ventilation-perfusion mismatch
with normal blood perfusion but insufficient ventilation of the lungs.
The intrapulmonary shunt is optimal in assessing the severity of
hypoxemia.
Intrapulmonary shunting has a close relation negative to PaO2/FiO2,
but positive to P(A-a)O2, and is also affected by pulmonary artery
wedge pressure and cardiac index

27. Acid-base imbalances
In the early stage of ARDS, respiratory alkalosis is the most common type of acid-base imbalance
followed by metabolic acidosis and combined respiratory alkalosis and metabolic alkalosis.
 while using diuretics and glucocorticoids (for metabolic alkalosis), or in the presence of severe hypoxia,
renal dysfunction, or shock (for metabolic acidosis) and electrolyte imbalance (hypokalemia, normal or
high blood chloride, and normal or reduced blood sodium)
In its late stage, patients may develop respiratory acidosis, respiratory acidosis associated with
metabolic acidosis and even triple acid-base imbalance.
 occur in the condition of reduced ventilation and carbon dioxide retention, often associated with
normal or high blood potassium and normal or reduced blood chloride and sodium

28. Mechanism of post-perfusion lung
syndrome
- Remains uncertain
- May probably be due to the inflammatory cascade induced by contact
between blood and CPB circuit
 subsequent activations of leukocytes, platelets,
coagulation and fibrinolysis system and kallikrein-
bradykinin and complement system
- After crossclamp removal, joint actions of protease release by leukocytes
in the pulmonary vascular beds, production of oxygen free radicals and intestinal
endotoxin translocation lead to increased pulmonary microvascular permeability,
microthrombus formation in the pulmonary vessels and the quality and quantity
changes of pulmonary surfactant predispose to the development of postperfusion
lung syndrome

29. RISK FACTORS
 Insufficient perfusion of visceral organs caused by low output syndrome and
prolonged hypotension might be responsible.
 Preoperative cardiac function impairment,
 bloodstream infection,
 prolonged crossclamp and operation durations,
 hypotension episodes
 hypogammaglobulinemia

30. PREVENTION
 Choices of CPB circuit
 Apparatus
 Innovative CPB techniques
 Modified surgical maneuvers
 Medicinal agents - corticosteroids and aprotinin
 Hyperonocotic CPB-prime with hydroxyethyl starch

31. MANAGEMENT
 Ventilatory treatment
 Pharmaceutical treatment

32. Ventilatory treatment
Mechanical ventilation - high-frequency oscillatory ventilation
Patients with ALI/ARDS, mechanical ventilation with a lower tidal volume (6 mL/kg) than is
traditionally used.
Adequate PEEP levels avoid alveolar collapse and maintain sufficient pulmonary volume at the end
of expiration.
Excessive PEEP increases the risk of pneumothorax and airway impairment, causing adverse
hemodynamic effects by increasing intra-thoracic pressure and reducing venous return
inadequately low PEEP level provokes cyclic alveolar collapse and re-opening, resulting in
atelectrauma.

33.  Pharmaceutical treatment
Surfactant therapy
Vasodilators - Nitric oxide is a powerful endogenous vasodilator
Prostaglandins
Glucocorticoids
Anti-inflammatory agents
Extracorporeal membrane oxygenation (ECMO)

34. Extracorporeal membrane oxygenation (ECMO)
ECMO is a therapeutic option for patients with severe ARDS. The indications for ECMO use in ARDS
patients are failed conventional therapy for 24-96 hours and the conformity of two of the three
required slow-entry criteria for ECMO including PaO2/FiO2 <150 mmHg at PEEP >5 cmH2O, semistatic
compliance <30 mL/cmH2O and right-left shunt >30%. Only in the patients with life-threatening
hypoxemia (PaO2<50 mmHg at FiO2 1.0 and PEEP>5 cmH2O for>2 hours (fast-entry criteria) is
immediate ECMO commenced[81]. Mols et al.[82] reported one-quarter of their 245 ARDS patients
received ECMO treatment. The survival rate was 55% in ECMO patients and 61% in non-ECMO
patients. However, the role of ECMO in the treatment of ARDS is controversial[83]. In neonates
treated with ECMO, a survival rate of 80% was achieved. In adult patients with ARDS, two
randomized controlled trials revealed the survival rates were 10% and 33%, respectively, in the
ECMO groups[84]. Meta-analysis of 9 studies on a total of 1,058 patients with 386 of them treated
with ECMO revealed ECMO increased the mortality of ARDS patients. Therefore, it seems that ECMO
is not beneficial in adult patients with ARDS as in neonates