BYDR.SOLIMAN M .M. ALI ASSITANT PROFESSOR ANESTHESIA AL AZHAR UNIVERSITY (Assiut)
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.
•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.
Ventilator-induced Lung InjuryLung 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.
Conclusions Search for ventilatory “lung protective” strategies Positive pressure ventilation may injure the lung via several different mechanismsAlveolar distension Repeated closing and opening Oxygen toxicity “VOLUTRAUMA” of collapsed alveolar units “ATELECTRAUMA” Lung inflammation “BIOTRAUMA” VILI Multiple organ dysfunction syndrome
End-Expiration Pathways to VILIExtreme 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
Recognized Mechanisms of Airspace Injury Airway Trauma “Stretch” “Shear”
Links Between VILI and MSOF Biotrauma and Mediator De-compartmentalization Slutsky, Chest 116(1):9S-16S
Protective Lung StrategyLow Tidal Volume 4-8 ml/kgP plat < 30 cmH2OBest PEEPPermissive HypercarbiaRecruitment maneuvers to open lung
AtelectasisIntroduction 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
Effects of atelectasisDecreased complianceImpaired oxygenationPulmonary vascular resistance increaseLung injury
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
Prevention / reversal of atelectasis Healthy lungsReversible 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 collapseNo evidence of barotrauma or pulmonary complications occurred in the high initial airway pressure
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)
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. 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
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
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
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;63:665-668Kennedy TP, Johnson KJ, Kunkel RG, Ward PA, Knight PR, Finch JS. Acute acid aspiration lung injury in the rat: biphasic pathogenesis. Anesth Analg 1989;69:87-92Knight 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
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
Prevention/TreatmentCricoid 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.
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: 453–460Practice 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
Ventilatory-based Strategies inthe Management of ARDS/ALI
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
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 .
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 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]
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.
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 al10 AJRCCM 2001.0 0 5 10 15 20 25 30 35 40 45 50 Paw [cmH2O]
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 4–10 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): i108–i116 (2010) doi:10.1093/bja/aeq299
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): i108–i116 (2010) doi:10.1093/bja/aeq299
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
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 ischaemia–reperfusion 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. Drew–Anderson Continuous perfusion of lungstechnique) Avoid use of oxygenator Reduced pro-inflammatory cytokinesMeticulous myocardial protection Limit ischaemia–reperfusion injury to lungs
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 α-2- agonists(dexmedetomidine) have shown potential anti-inflammatory effects.This work is still very preliminary and its clinical significanceand application are unknown.
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
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.
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 toFlow 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
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.
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
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
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
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
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.