2. BY
DR.SOLIMAN M .M. ALI
ASSITANT PROFESSOR ANESTHESIA
AL AZHAR UNIVERSITY (Assiut)

3. Introduction:
DURING General Anesthesia Patients are at risk for
several types of lung injury in the perioperative period
including:-
>Atelectasis.
>Pneumonia.
>Pneumothorax,
>ALI, ARDS.
>This review discusses ventilator-induced lung injury.
>Lung protective ventilatory strategies to specific clinical
situations such as CPB and one-lung ventilation along
with newer novel lung protective strategies are discussed.

4. •Key points
on
# Mechaniical ventilation can have adverse effects
on pulmonary function by several mechanisms.
# Patients undergoing one-lung ventilation or
cardiopulmonary bypass are at increased risk of
developing acute lung injury (ALI).
# Protective ventilatory strategies may prevent or
reduce ALI.
# There is a lack of randomized controlled trials to
guide optimal intra-operative ventilation.

5. Ventilator-induced Lung Injury
Lung inflammation “biotrauma”
• Lung overinflation or overstretching produces regional and systemic
inflammatory response that may generate or amplify multiple-system organ
failure.
• Factors converting the shear stress applied to an injured lung into regional
and systemic inflammation are still incompletely elucidated but could
include:
- Repetitive opening and collapse of atelectatic lung units
- Surfactant alterations
- Loss of alveolo-capillary barrier function
- Bacterial translocation
-Overinflation of health lung regions
• The degree of overinflation is dependent on:
- Tidal volume
- Peak airway pressure
- Duration of mechanical ventilation
- Time exposed to an Fio2 > 0.6
Rouby JJ, et al. Anesthesiology. 2004.
Dreyfuss D, et al. Am J Respir Crit Care Med. 2003.

6. Conclusions
Search for ventilatory “lung protective” strategies
Positive pressure ventilation may injure the lung
via several different mechanisms
Alveolar distension Repeated closing and opening Oxygen toxicity
“VOLUTRAUMA” of collapsed alveolar units
“ATELECTRAUMA”
Lung inflammation
“BIOTRAUMA”
VILI
Multiple organ dysfunction syndrome

7. End-Expiration Pathways to VILI
Extreme Stress/Strain Tidal Forces Moderate Stress/Strain
(Transpulmonary and
Microvascular
Pressures)
Rupture Signaling
Mechano signaling via
integrins, cytoskeleton, ion channels
inflammatory cascade
Cellular Infiltration and
Inflammation
Marini / Gattinoni CCM 2004

8. Recognized Mechanisms of Airspace Injury
Airway Trauma
“Stretch”
“Shear”

9. Links Between VILI and MSOF
Biotrauma and Mediator
De-compartmentalization
Slutsky, Chest 116(1):9S-16S

10. Protective Lung Strategy
Low Tidal Volume 4-8 ml/kg
P plat < 30 cmH2O
Best PEEP
Permissive Hypercarbia
Recruitment maneuvers to open lung

11. Atelectasis
Introduction
 General anesthesia is associated with impaired
oxygenation  pulmonary atelectasis was
suspected as the major cause
 Decrease in lung compliance and the partial
pressure of arterial oxygen (PaO2)
 Atelectasis occurs in the most dependent parts of
the lung of 90% of patients who are anesthetized
 gas exchange abnormalities and reduced static
compliance associated with acute lung injury 
perioperative morbidity

12. Pathogenic mechanisms to
development atelectasis

13. Effects of atelectasis
Decreased compliance
Impaired oxygenation
Pulmonary vascular resistance
increase
Lung injury

15. Postoperative period
 Atelectasis can persist for 2 days after major surgery
 The lung dysfunction is often transient; may be
related to reduction in FRC
 Postoperative mechanical respiratory abnormality
after abdominal or thoracic surgery is a restrictive
pattern with severely reduced inspiratory
capacity, vital capacity, and FRC pain control in
preventing postoperative atelectasis
 Atelectasis and pneumonia are often considered
together because the changes associated with
atelectasis may predispose to pneumonia

16. Prevention / reversal of atelectasis
 Healthy lungs
Reversible by passive hyperinflation (i.e., three
successive inflations: a pressure of 20cmH2O for
10s; then a pressure of 30cm H2O for 15s; and third,
a pressure of 40 cm H2O sustained for 15s)
High initial pressures are needed to overcome the
anesthesia-induced collapse and that PEEP of 5cm
H2O or more is required to prevent collapse
No evidence of barotrauma or pulmonary
complications occurred in the high initial airway
pressure

17. Spectrum of Regional Opening Pressures (Supine Position)
Opening
Pressure
Superimposed
Pressure Inflated 0
Small Airway 10-20 cmH2O
Collapse
Alveolar Collapse
(Reabsorption) 20-60 cmH2O
Consolidation 
l= Units at Risk for Tidal
Lung
Opening & Closure
(from Gattinoni)

18. Recruitment Maneuvers (RMs)
Proposed for improving arterial oxygenation and enhancing alveolar
recruitment
All consisting of short-lasting increases in intrathoracic pressures
• Vital capacity maneuver (inflation of the lungs up to 40 cm H2O,
maintained for 15 - 26 seconds) (Rothen HU. BJA. 1999; BJA 1993.)
• Intermittent sighs (Pelosi P. Am J Respir Crit Care Med. 2003.)
• Extended sighs (Lim CM. Crit Care Med. 2001.)
• Intermittent increase of PEEP (Foti G. Intensive Care Med. 2000.)
• Continuous positive airway pressure (CPAP) (Lapinsky SE. Intensive
Care Med. 1999. Amato MB. N Engl J Med. 1998.)
• Increasing the ventilatory pressures to a plateau pressure of 50 cm
H2O for 1-2 minutes (Marini JJ. Crit Care Med. 2004. Maggiore SM.
Am J Respir Crit Care Med. 2003.)
Lapinsky SE and Mehta S, Critical Care 2005

19. Treating atelectasis in the postoperative
period
 Encourage or force patients to inspire
deeply
 Method: intermittent positive-pressure
breathing, deep-breathing exercises, and
chest physiotherapy
 A simple posture change from supine to
seated

20. Aspiration
 Defined as the inhalation of material into the
airway below the level of the true vocal cords
 Two primary mechanisms of injury may ensue:
 Aspiration pneumonitis– non-infectious acute
inflammatory reaction characterized by infiltration on
radiography
 Aspiration pneumonia– parenchymal inflammatory
reaction to an infectious agent characterized by an
infiltrate on chest radiograph
McClave SA, DeMeo MT, DeLegge MH et al. North American summit on aspiration in the critical illpatient: consensus statement. Journal
of Parenteral and Enteral Nutrition; 6: S80–85
Marom EM, McAdams HP, Erasmus JJ. The many faces of pulmonary aspiration. AJR Am Roentgenol. Jan 1999;172(1):121-8

21. Aspiration Pneumonitis
 Severity of lung injury is primarily based on three
factors; the pH, volume, and particulate nature of
aspirated contents. A pH of <2.5, volume of
>0.3ml/kg (20-25ml in average adult) and the
presence of particulate matter result in more
significant lung injury.
James CF, Modell JH, Gibbs CP, Kuck EJ, Ruiz BC. Pulmonary aspiration -- effects of volume and pH in the rat. Anesth Analg 1984;63:665-668
Kennedy TP, Johnson KJ, Kunkel RG, Ward PA, Knight PR, Finch JS. Acute acid aspiration lung injury in the rat: biphasic pathogenesis. Anesth
Analg 1989;69:87-92
Knight PR, Rutter T, Tait AR, Coleman E, Johnson K. Pathogenesis of gastric particulate lung injury: a comparison and
interaction with acidic pneumonitis. Anesth Analg 1993;77:754-760

22. Aspiration Pneumonitis
 The chemical pneumonitis and lung injury was first
described by Mendelson in 1946.
 Characterized by a biphasic injury pattern based on animal
models
 Initial phase: peaks within 1 hour; increase in capillary permeability
secondary to direct chemical burn.
 Second phase: peaks at 4 hours; acute inflammatory response with
infiltration of inflammatory mediators into lung interstitium and
alveoli.
Kennedy TP, Johnson KJ, Kunkel RG, Ward PA, Knight PR, Finch JS. Acute acid aspiration lung injury in the rat: biphasic pathogenesis.
Anesth Analg 1989;69:87-92

23. Prevention/Treatment
Cricoid Pressure
 Described by Sellick in 1961 as a means to prevent
regurgitation and aspiration on induction of anesthesia by
applying backward pressure of the cricoid cartilage against
the bodies of the cervical vertebrae.
 Positioning: slight head down tilt, head and neck in full
extension (as in position for tonsillectomy), which
increases convexity of cervical spine and stretches
esophagus.
Sellick BA. Cricoid pressure to control regurgitation of
stomach contents during induction of anaesthesia.
Lancet 1961; 2: 404–406.

24. Prevention/Treatment

25. Prevention/Treatment
 Antacids, prokinetic agents
H2-blockers have been
shown to decrease gastric
volume and or pH, but no
studies have been shown to
improve outcome.
 The ASA does not
recommend the routine
administration of these
drugs.
Engelhardt T &Webster NR. Pulmonary aspiration of gastric contents. British
Journal of Anaesthesia 1999; 83: 453–460
Practice guidelines for preoperative fasting and the use of pharmacologic
agents to reduce the risk of pulmonary aspiration: application to healthy
patients undergoing elective procedures: a report by the American
Society of Anesthesiologist Task Force on Preoperative Fasting.
Anesthesiology. 1999 Mar;90(3):896-905

26. Ventilatory-based Strategies in
the Management of ARDS/ALI

27. Recommendations in Practice
Limited VT 6 mL/kg PBW to avoid alveolar distension
End-inspiratory plateau pressure < 30 - 32 cm H2O
Adequate end-expiratory lung volumes utilizing PEEP and higher mean airway
pressures to minimize atelectrauma and improve oxygenation
Consider recruitment maneuvers
Avoid oxygen toxicity: FiO2 < 0.7 whenever possible
Monitor hemodynamics, mechanics, and gas exchange
Address deficits of intravascular volume

28. Recruitment Maneuvers in ARDS
The purpose of a recruitment maneuver is to open
collapsed lung tissue so it can remain open during tidal
ventilation with lower pressures and PEEP, thereby
improving gas exchange and helping to eliminate high
stress interfaces.
Although applying high pressure is fundamental to
recruitment, sustaining high pressure is also important.
Methods of performing a recruiting maneuver include
single sustained inflations and ventilation with high
PEEP .

29. How Much Collapse Is Dangerous
Depends on the Plateau
100 Less Extensive
Collapse But
Total Lung Capacity [%]
Greater PPLAT R = 100%
R = 93%
R = 81% Some potentially
60 More Extensive
recruitable units
Collapse But
open only at
Lower PPLAT
high pressure
R = 59%
From Pelosi et al
20 AJRCCM 2001
R = 22%
0
0 20 40 60
R = 0% Pressure [cmH2O]

30. PEEP in ARDS
How much is enough ?
“Optimal PEEP”: Allowing for a given ARDS an optimization of
arterial oxygenation without introducing a risk of oxygen toxicity
and VILI, while having the least detrimental effect on
hemodynamics, oxygen delivery, and airway pressures.
There has never been a consensus regarding the optimum level of
PEEP for a given patient with ARDS.
The potential for recruitment may largely vary among the ALI/ARDS
population.
PEEP may increase PaO2 without any lung recruitment because of a
decrease in and/or a different distribution of pulmonary perfusion.
Levy MM. N Engl J Med. 2004.
Rouby JJ, et al. Am J Respir Crit Care Med. 2002.
Gattinoni L, et al. Curr Opin Crit Care. 2005.

31. Opening and Closing Pressures in ARDS
High pressures may be needed to open some lung units, but once open,
many units stay open at lower pressure.
50
40
Opening
30 pressure
Closing
%
20 pressure
From Crotti et al
10 AJRCCM 2001.
0
0 5 10 15 20 25 30 35 40 45 50
Paw [cmH2O]

32. OLV- management strategies to minimize
lung injury:
FIo2 as low as possible.
Variable tidal volumes, begin inspiration at FRC.
 Avoid atelectasis with frequent recruitment manoeuvres.
 Using a protective lung ventilation strategy (tidal volume ,6
ml kg1 predicted body weight, pressure control ventilation.
PIPs ,35 cm H2O, external PEEP of 4–10 cm H2O ).
Recruitment manoeuvres showed a decreased incidence of
ALI ,atelectasis , ICU admissions, and shorter hospital stay.
 Avoiding overhydration .
The use of a balanced chest drainage system after
pneumonectomy has been suggested to decrease ALI.
British Journal of Anaesthesia 105 (S1): i108–i116 (2010) doi:10.1093/bja/aeq299

33. Impact of intraoperative lung protective strategies in lung cancer surgery.
Kilpatrick B , Slinger P Br. J. Anaesth. 2010;105:i108-i116
© The Author [2010]. Published by Oxford University Press on behalf of the British Journal of
Anaesthesia. All rights reserved. For Permissions, please email:
journals.permissions@oxfordjournal.org

34. Permissive hypercapnia, or hypercapnic acidosis (HCA)
HCA is an accepted consequence of lung protective ventilation in
patients with ALI/ARDS.
•Attenuation of lung PMN recruitments.
• Pulmonary and systemic cytokine concentrations.
•Cell apoptosis, and free radical injury by inhibiting endogenous
xanthine oxidase .
•Attenuated lung injury in both early and prolonged sepsis.
attenuation •
British Journal of Anaesthesia 105 (S1): i108–i116 (2010) doi:10.1093/bja/aeq299

35. Pulmonary dysfunction after CPB
 Pulmonary dysfunction after CPB is well described but
poorly understood. Although the incidence of ARDS after
CPB is low (<2%), the mortality associated with it is high
(>50%).
 Pulmonary insult is multifactorial and not all related to
CPB itself.
 Additional factors are general anaesthesia, sternotomy,
and breaching of the pleura.
 CPB-related factors include hypothermia, blood contact
with artificial surfaces, ischemia–reperfusion injury,
administration of blood products, and ventilatory arrest.
British Journal of Anaesthesia 105 (S1): i108–i116 (2010)
doi:10.1093/bja/aeq299

36. Strategies to limit lung injury during CPB
Intervention Mechanism of action
Off-pump surgery Reduced cytokine and SIRS response
Drugs (steroids, aprotinin) Reduced pro-inflammatory cytokine release
Mimics endothelial surface. Reduces complement
Biocompatible circuits
activation and inflammatory response
Preferentially removes activated leucocytes, attenuates
Leucocyte filters
ischaemia–reperfusion injury
Removal of destructive and inflammatory substances
Ultrafiltration
reducing SIRS response
Prevents atelectasis, development of hydrostatic
Protective ventilation strategies
oedema, and pulmonary ischaemia
Pulmonary perfusion techniques (e.g. Drew–Anderson
Continuous perfusion of lungs
technique)
Avoid use of oxygenator
Reduced pro-inflammatory cytokines
Meticulous myocardial protection Limit ischaemia–reperfusion injury to lungs

37. Role of anaesthetic agents in lung
protection
Volatile agents have immune modulatory effects recent 
studies in models of ALI , OLV and cases of lung ischemia
reperfusion injury found that volatile anaesthetics might
induce lung protection by the inhibition of the expresstion
of pro inflammatory mediators.
Induction agents(I.V) 
(ketamine, propofol, and thiopental), and α-2- 
agonists(dexmedetomidine) have shown potential anti-
inflammatory effects.
This work is still very preliminary and its clinical significance
and application are unknown.

38. ion.59
Nitrous oxide
Owing to its relatively higher solubility compared with 
oxygen and nitrogen, nitrous oxide plays a role in
absorption atelectasis.
Although this may be helpful in aiding lung collapse in 
the setting of OLV, there is no strong evidence for or
against this agent for lung protection. 
 Anesth Analg 2009; 108: 1092–6

39. Inhaled Nitric Oxide
Physiology of inhaled nitric oxide therapy
• Selective pulmonary vasodilatation
(decreases arterial and venous resistances)
• Decreases pulmonary capillary pressure
• Selective vasodilatation of ventilated lung
areas
• Bronchodilator action
• Inhibition of neutrophil adhesion
• Protects against tissue injury by neutrophil
oxidants
Steudel W, et al. Anesthesiology. 1999.

40. Alternative lung protective strategies
Novalung membrane
ventilator.
Extracorporeal membrane
oxygenation.
High-frequency oscillatory
ventilation.

41. NovaLung function
Sweep gas O2
•High CO2 gradient between
blood and sweep gas allows
Cannula in
Femoral vein diffusion across the
membrane, allowing efficient
CO2 removal
•Oxygenation limited due to
Flow monitor
Novalung arterial inflow
Cannula in membrane •Low resistance to blood flow
Femoral artery
(7mmHg at 1.5l /minute)
allowing the heart to be the
Two variables: pump for the device
Sweep gas flow controls CO2 removal
Blood flow controls oxygenation •Heparin coated
(MAP & cannula size) biocompatible surface
Cardiothoracic Transplant Programme
Freeman Hospital
Newcastle Upon Tyne Hospitals NHS Trust

42. Novalung membrane
 Compared with conventional extracorporeal
membrane oxygenation (ECMO), the Novalung is a
simple, pumpless, and, very importantly, portable
device.
 Anti-coagulation requirements are much reduced
blood product requirements are less.
 Tidal volumes ≤3 ml kg−1, low inspiratory plateau
pressure, high PEEP, and low ventilatory (6 b/min)are
all possible with the Novalung® VILI.

43. TWO TYPES OF ECMO:
 Veno-arterial bypass - supports the heart and lungs
 Requires two cannulae-one in jugular vein and one in
the carotid artery
 Veno-venous bypass – supports the lungs only
 Requires one cannula- jugular vein

44. High-frequency Oscillatory Ventilation
Characterized by rapid oscillations of a reciprocating diaphragm, leading to
high-respiratory cycle frequencies, usually between 3 and 9 Hz in adults, and
very low V T. Ventilation in HFOV is primarily achieved by oscillations of the air
around the set mean airway pressure mPaw.
HFOV is conceptually very attractive, as it achieves many of the goal of lung-
protective ventilation.
• Constant mPaws: Maintains an “open lung” and optimizes lung
recruitment
• Lower V T than those achieved with controlled ventilation (CV), thus
theoretically avoiding alveolar distension.
• Expiration is active during HFOV: Prevents gas trapping
• Higher mPaws (compared to CV): Leads to higher end-expiratory lung
volumes and recruitment, then theoretically to improvements in
oxygenation and, in turn, a reduction of FiO2.
Chan KPW and Stewart TE, Crit Care Med 2005

45. Future lung protection therapies
 Several therapies that could play a future role in lung
protection.
 Inhaled hydrogen sulphide shows beneficial effects in
a model of VILI via inhibition of inflammatory and
apoptotic responses
 Inhaled, aerosolized, activated protein C.
 The use of β-adrenergic agonists has potential benefits
by increasing the rate of alveolar fluid clearance and
anti-inflammatory effects.79

46. PROTEIN- C
i) Inactivates Va & VIIa – limit thrombin generation.
ii)  fibrinolysis.
iii) Anti-inflam. -  cytokines, inhibit apoptosis.
In the PROWESS study APC administ. Improved survival.
28 days absolute risk reduction in mortality – 6.1%. 19.4%
reduction in relative risk.
 Risk of bleeding (3.5% vs 2.0%)
Faster resolution of respiratory dysfun.
 ventilatory free days (14.3 vs 13.2 days)
Bernad GR ; NEJM 2001; 344; 699-709

47. ENHANCED RESOLUTION OF ALVEOLAR EDEMA
Alveolar clearance of edema depends on active sodium
transport across the alveolar epithelium
b2 adrenergic stimulation :
1. Salmetrol
2. Dopamine
3. Dobutamine
ENHANCED REPAIR :
Mitogen for type-II pneumatocyte :
1. Hepatocyte growth factor
2. Keratinocyte growth factor.