1. BYDR.SOLIMAN M .M. ALI ASSITANT PROFESSOR ANESTHESIAAL AZHAR UNIVERSITY (Assiut)

2. Introduction:DURING General Anesthesia Patients are at risk forseveral types of lung injury in the perioperative periodincluding:- >Atelectasis. >Pneumonia.>Pneumothorax,>ALI, ARDS.>This review discusses ventilator-induced lung injury. >Lung protective ventilatory strategies to specific clinicalsituations such as CPB and one-lung ventilation alongwith newer novel lung protective strategies are discussed. 3. Key points on# Mechaniical ventilation can have adverse effectson pulmonary function by several mechanisms.# Patients undergoing one-lung ventilation orcardiopulmonary bypass are at increased risk ofdeveloping acute lung injury (ALI).# Protective ventilatory strategies may prevent orreduce ALI.# There is a lack of randomized controlled trials toguide optimal intra-operative ventilation. 4. Ventilator-induced Lung InjuryLung inflammation biotrauma Lung overinflation or overstretching produces regional and systemicinflammatory response that may generate or amplify multiple-system organfailure. Factors converting the shear stress applied to an injured lung into regionaland systemic inflammation are still incompletely elucidated but couldinclude: - 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. 5. Conclusions Search for ventilatory lung protective strategiesPositive pressure ventilation may injure the lungvia several different mechanismsAlveolar distensionRepeated closing and opening Oxygen toxicity VOLUTRAUMA of collapsed alveolar unitsATELECTRAUMA Lung inflammationBIOTRAUMA VILI Multiple organ dysfunction syndrome 6. End-ExpirationPathways to VILIExtreme Stress/StrainTidal Forces Moderate Stress/Strain(Transpulmonary andMicrovascular Pressures) Rupture Signaling Mechano signaling viaintegrins, cytoskeleton, ion channelsinflammatory cascadeCellular Infiltration and InflammationMarini / Gattinoni CCM 2004 7. Recognized Mechanisms of Airspace Injury Airway TraumaStretch Shear 8. Links Between VILI and MSOFBiotrauma and MediatorDe-compartmentalizationSlutsky, Chest 116(1):9S-16S 9. Protective Lung StrategyLow Tidal Volume 4-8 ml/kgP plat < 30 cmH2OBest PEEPPermissive HypercarbiaRecruitment maneuvers to open lung 10. AtelectasisIntroduction General anesthesia is associated with impairedoxygenation pulmonary atelectasis wassuspected as the major cause Decrease in lung compliance and the partialpressure of arterial oxygen (PaO2) Atelectasis occurs in the most dependent parts ofthe lung of 90% of patients who are anesthetized gas exchange abnormalities and reduced static compliance associated with acute lung injury perioperative morbidity 11. Pathogenic mechanisms todevelopment atelectasis 12. Effects of atelectasisDecreased complianceImpaired oxygenationPulmonary vascular resistance increaseLung injury 13. Postoperative period Atelectasis can persist for 2 days after major surgery The lung dysfunction is often transient; may berelated to reduction in FRC Postoperative mechanical respiratory abnormalityafter abdominal or thoracic surgery is a restrictivepattern with severely reduced inspiratorycapacity, vital capacity, and FRC pain control inpreventing postoperative atelectasis Atelectasis and pneumonia are often consideredtogether because the changes associated with atelectasis may predispose to pneumonia 14. Prevention / reversal of atelectasis Healthy lungsReversible by passive hyperinflation (i.e., threesuccessive inflations: a pressure of 20cmH2O for10s; 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 theanesthesia-induced collapse and that PEEP of 5cmH2O or more is required to prevent collapseNo evidence of barotrauma or pulmonarycomplications occurred in the high initial airwaypressure 15. Spectrum of Regional Opening Pressures (Supine Position)OpeningPressure SuperimposedPressureInflated0Small Airway10-20 cmH2O CollapseAlveolar Collapse(Reabsorption)20-60 cmH2O Consolidation l= Units at Risk for TidalLung Opening & Closure(from Gattinoni) 16. Recruitment Maneuvers (RMs)Proposed for improving arterial oxygenation and enhancing alveolarrecruitmentAll 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. IntensiveCare Med. 1999. Amato MB. N Engl J Med. 1998.) Increasing the ventilatory pressures to a plateau pressure of 50 cmH2O 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 17. Treating atelectasis in the postoperativeperiod 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 18. Aspiration Defined as the inhalation of material into theairway below the level of the true vocal cords Two primary mechanisms of injury may ensue: Aspiration pneumonitis non-infectious acuteinflammatory reaction characterized by infiltration onradiography Aspiration pneumonia parenchymal inflammatoryreaction to an infectious agent characterized by aninfiltrate on chest radiographMcClave 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: S8085Marom EM, McAdams HP, Erasmus JJ. The many faces of pulmonary aspiration. AJR Am Roentgenol. Jan 1999;172(1):121-8 19. Aspiration Pneumonitis Severity of lung injury is primarily based on threefactors; the pH, volume, and particulate nature ofaspirated contents. A pH of 0.3ml/kg (20-25ml in average adult) and thepresence of particulate matter result in moresignificant 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;63:665-668Kennedy TP, Johnson KJ, Kunkel RG, Ward PA, Knight PR, Finch JS. Acute acid aspiration lung injury in the rat: biphasic pathogenesis. AnesthAnalg 1989;69:87-92Knight PR, Rutter T, Tait AR, Coleman E, Johnson K. Pathogenesis of gastric particulate lung injury: a comparison andinteraction with acidic pneumonitis. Anesth Analg 1993;77:754-760 20. Aspiration Pneumonitis The chemical pneumonitis and lung injury was firstdescribed by Mendelson in 1946. Characterized by a biphasic injury pattern based on animalmodels Initial phase: peaks within 1 hour; increase in capillary permeabilitysecondary to direct chemical burn. Second phase: peaks at 4 hours; acute inflammatory response withinfiltration of inflammatory mediators into lung interstitium andalveoli.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 21. Prevention/TreatmentCricoid Pressure Described by Sellick in 1961 as a means to preventregurgitation and aspiration on induction of anesthesia byapplying backward pressure of the cricoid cartilage againstthe 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: 404406. 22. Prevention/Treatment 23. Prevention/Treatment Antacids, prokinetic agentsH2-blockers have beenshown to decrease gastricvolume and or pH, but nostudies have been shown toimprove outcome. The ASA does notrecommend the routineadministration of thesedrugs.Engelhardt T &Webster NR. Pulmonary aspiration of gastric contents. British Journal of Anaesthesia 1999; 83: 453460Practice 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 24. Ventilatory-based Strategies inthe Management of ARDS/ALI 25. Recommendations in PracticeLimited VT 6 mL/kg PBW to avoid alveolar distensionEnd-inspiratory plateau pressure < 30 - 32 cm H2OAdequate end-expiratory lung volumes utilizing PEEP and higher mean airwaypressures to minimize atelectrauma and improve oxygenationConsider recruitment maneuversAvoid oxygen toxicity: FiO2 < 0.7 whenever possibleMonitor hemodynamics, mechanics, and gas exchangeAddress deficits of intravascular volume 26. 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 . 27. How Much Collapse Is DangerousDepends on the Plateau 100 Less Extensive Collapse But Total Lung Capacity [%] Greater PPLAT R = 100%R = 93% R = 81% Some potentially 60More Extensive recruitable units Collapse But open only at Lower PPLAT high pressureR = 59% From Pelosi et al 20AJRCCM 2001R = 22% 0020 4060R = 0%Pressure [cmH2O] 28. PEEP in ARDSHow much is enough ?Optimal PEEP: Allowing for a given ARDS an optimization ofarterial oxygenation without introducing a risk of oxygen toxicityand VILI, while having the least detrimental effect onhemodynamics, oxygen delivery, and airway pressures.There has never been a consensus regarding the optimum level ofPEEP for a given patient with ARDS.The potential for recruitment may largely vary among the ALI/ARDSpopulation.PEEP may increase PaO2 without any lung recruitment because of adecrease 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. 29. 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.5040 Opening30 pressure Closing%20 pressure From Crotti et al10AJRCCM 2001.005 10 15 20 25 30 35 40 45 50Paw [cmH2O] 30. 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 ,6ml kg1 predicted body weight, pressure control ventilation.PIPs ,35 cm H2O, external PEEP of 410 cm H2O ).Recruitment manoeuvres showed a decreased incidence ofALI ,atelectasis , ICU admissions, and shorter hospital stay. Avoiding overhydration .The use of a balanced chest drainage system afterpneumonectomy has been suggested to decrease ALI.British Journal of Anaesthesia 105 (S1): i108i116 (2010) doi:10.1093/bja/aeq299 31. 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 ofAnaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournal.org 32. Permissive hypercapnia, or hypercapnic acidosis (HCA)HCA is an accepted consequence of lung protective ventilation inpatients 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): i108i116 (2010) doi:10.1093/bja/aeq299 33. Pulmonary dysfunction after CPB Pulmonary dysfunction after CPB is well described butpoorly understood. Although the incidence of ARDS afterCPB is low (50%). Pulmonary insult is multifactorial and not all related toCPB itself. Additional factors are general anaesthesia, sternotomy,and breaching of the pleura. CPB-related factors include hypothermia, blood contactwith artificial surfaces, ischemiareperfusion injury,administration of blood products, and ventilatory arrest.British Journal of Anaesthesia 105 (S1): i108i116 (2010)doi:10.1093/bja/aeq299 34. Strategies to limit lung injury during CPBIntervention Mechanism of actionOff-pump surgery Reduced cytokine and SIRS responseDrugs (steroids, aprotinin)Reduced pro-inflammatory cytokine release Mimics endothelial surface. Reduces complementBiocompatible circuits activation and inflammatory response Preferentially removes activated leucocytes, attenuatesLeucocyte filters ischaemiareperfusion injury Removal of destructive and inflammatory substancesUltrafiltration reducing SIRS response Prevents atelectasis, development of hydrostaticProtective ventilation strategies oedema, and pulmonary ischaemiaPulmonary perfusion techniques (e.g. DrewAnderson Continuous perfusion of lungstechnique) Avoid use of oxygenator Reduced pro-inflammatory cytokinesMeticulous myocardial protection Limit ischaemiareperfusion injury to lungs 35. Role of anaesthetic agents in lungprotection Volatile agents have immune modulatory effects recent studies in models of ALI , OLV and cases of lung ischemiareperfusion injury found that volatile anaesthetics mightinduce lung protection by the inhibition of the expresstionof pro inflammatory mediators. Induction agents(I.V) (ketamine, propofol, and thiopental), and -2- agonists(dexmedetomidine) have shown potential anti-inflammatory effects.This work is still very preliminary and its clinical significanceand application are unknown. 36. 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: 10926 37. Inhaled Nitric OxidePhysiology of inhaled nitric oxide therapy Selective pulmonary vasodilatation(decreases arterial and venous resistances) Decreases pulmonary capillary pressure Selective vasodilatation of ventilated lungareas Bronchodilator action Inhibition of neutrophil adhesion Protects against tissue injury by neutrophiloxidantsSteudel W, et al. Anesthesiology. 1999. 38. Alternative lung protective strategiesNovalung membrane ventilator.Extracorporeal membrane oxygenation.High-frequency oscillatory ventilation. 39. NovaLung functionSweep gas O2High CO2 gradient betweenblood and sweep gas allows Cannula in Femoral vein diffusion across themembrane, allowing efficientCO2 removalOxygenation limited due toFlow monitor Novalung arterial inflowCannula in membrane Low resistance to blood flowFemoral 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 oxygenationHeparin coated(MAP & cannula size)biocompatible surfaceCardiothoracic Transplant ProgrammeFreeman Hospital Newcastle Upon Tyne Hospitals NHS Trust 40. Novalung membrane Comparedwithconventional extracorporealmembrane oxygenation (ECMO), the Novalung is asimple, pumpless, and, very importantly, portabledevice. Anti-coagulation requirements are much reducedblood product requirements are less. Tidal volumes 3 ml kg1, low inspiratory plateaupressure, high PEEP, and low ventilatory (6 b/min)areall possible with the NovalungVILI. 41. 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 42. High-frequency Oscillatory VentilationCharacterized by rapid oscillations of a reciprocating diaphragm, leading tohigh-respiratory cycle frequencies, usually between 3 and 9 Hz in adults, andvery low V T. Ventilation in HFOV is primarily achieved by oscillations of the airaround 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 43. Future lung protection therapies Several therapies that could play a future role in lungprotection. Inhaled hydrogen sulphide shows beneficial effects ina model of VILI via inhibition of inflammatory andapoptotic responses Inhaled, aerosolized, activated protein C. The use of -adrenergic agonists has potential benefitsby increasing the rate of alveolar fluid clearance andanti-inflammatory effects.79 44. PROTEIN- Ci)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 45. ENHANCED RESOLUTION OF ALVEOLAR EDEMAAlveolar clearance of edema depends on active sodiumtransport across the alveolar epitheliumb2 adrenergic stimulation :1.Salmetrol2.Dopamine3.DobutamineENHANCED REPAIR :Mitogen for type-II pneumatocyte :1. Hepatocyte growth factor2. Keratinocyte growth factor.