The Lung - Artificial Organs - PDF

The Lung How to support or replace the lung Artificial Organs Content 2 1 Anatomy & Physiology 2 Pathology 3 Mechanical Ventilation 4 Extracorporeal Life Support 5 Research & Development Artificial Organs - Lung The Lung O2 External respiration CO2 Pulmonal gas exchange Gas transport in blood 3 Arti...

The Lung How to support or replace the lung Artificial Organs Content 2 1 Anatomy & Physiology 2 Pathology 3 Mechanical Ventilation 4 Extracorporeal Life Support 5 Research & Development Artificial Organs - Lung The Lung O2 External respiration CO2 Pulmonal gas exchange Gas transport in blood 3 Artificial Organs - Lung The Lung By BruceBlaus. When using this image in external sources it can be cited as:Blausen.com staff (2014). &quot;Medical gallery of Blausen Medical 2014&quot;. WikiJournal of Medicine 1 (2). DOI:10.15347/wjm/2014.010. ISSN 2002-4436. - Own work, CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=28761835 4 Artificial Organs - Lung The Lung By OpenStax College - Anatomy &amp; Physiology, Connexions Web site. http://cnx.org/content/col11496/1.6/, Jun 19, 2013., CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=30148380 5 Artificial Organs - Lung The Lung Lung lobes https://www.amboss.com/us/knowledge/Airways_and_lungs https://step1.medbullets.com/respiratory/117005/lung-relationships 6 Artificial Organs - Lung Bronchial system Alveoli Number of pulmonary alveoli is approx. 300 Mio. Alveoli have a diameter of 0.1 mm – 0.3 mm Each alveoli is surrounded by small blood vessels Inner surface of the lung ~ 100 m2 Outer surface of the lung < 1 m2 Alveoli https://images.app.goo.gl/zNrsd9JeTou5oKDv7 7 Artificial Organs - Lung Alveoli Young-Laplace-equation or Law of Laplace: ∆𝑝 = 2 ∗ 𝛾 𝑟 : surface tension r: bubble radius p: pressure Surfactant (surface-activating agent) reduces surface tension at alveoli-air-interface Colbert, Bruce J., James, Adam, Williams, Daniel. Integrated Cardiopulmonary Pharmacology. USA: BVT Publishing, 2022. 8 Artificial Organs - Lung External Respiration pH O2 minute-breathing volume (L/min) ! CO2 80 60 40 20 45 60 75 arterial pCO2 (mmHg) CO2-response curve Breath regulation https://www.inspiritvr.com/general-bio/human-biology/breathing-and-its-regulation-study-guide 9 Artificial Organs - Lung 100 mmHg = 13,333 Pa External Respiration Pleural Gap Pleura Visceral pleura Ribs Diaphragm Rest Inspiration plung < pout 10 Artificial Organs - Lung Expiration plung > pout External Respiration ♀ ♂ ♂ 20-30 y 50-60 y 20-30 y inspiration capacity totalcapacity vital capacity inspirat. reserve volume ~3L breath volume functional residual capacity expirat. reserve volume ~ 1.7 L residual volume https://www.sofia.medicalistes.fr 11 at rest ~ 0.5 L Artificial Organs - Lung 5.1 L 4.4 L 4.4 L Spirometric measurement of volumes and capacities of the lung 1.6 L 2.2 L 1.4 L External Respiration Breathing volume in rest: 5 L/min 83.4 years life expectation (women) → 219,000,000 L air/life Hindenburg Zeppelin, V  200.000 m³ https://www.de.wikipedia.org/wiki/LZ_129 12 Artificial Organs - Lung Reminder: Law of Fick Diffusion (1. Law of Fick) on walls 𝐽 = 𝑗 ′′ ∗ 𝐴 = −𝐷 14 𝜕𝑐 ∗𝐴 𝜕𝑥 𝐷 𝑑𝑒𝑝𝑒𝑛𝑑𝑠 𝑜𝑛 𝑚𝑒𝑚𝑏𝑟𝑎𝑛 𝑎𝑛𝑑 𝑝𝑎𝑟𝑡𝑖𝑐𝑎𝑙 𝑠𝑡𝑟𝑒𝑎𝑚 Parameter Unit J Particle stream mol s-1 𝑗′′ Area-related particle stream density mol m-2 s-1 A Diffusion surface m2 D Particle stream density m2 s-1 c Concentration mol m-3 x Diffusion distance m Artificial Organs - Lung 𝑗 ′′ 𝑐1 𝜕𝑐 𝑐2 𝜕𝑥 Pulmonal Gas Exchange breathing air O2 blood from the right heart alveolus blood to the left heart O2 alveolar pO2 O2-partial pressure capillary pO2 venous pO2 driving pressure difference contact distance 15 Artificial Organs - Lung Pulmonal Gas Exchange breathing air CO2 blood from the right heart alveolus blood to the left heart CO2 CO2-partial pressure venous pCO2 driving pressure difference capillary pCO2 alveolar pCO2 contact distance 16 Artificial Organs - Lung Pulmonal Gas Exchange Air contains ca. 21 % of oxygen and 0.3 % of carbon dioxide O2: 0.21 * 760 mmHg (ambient pressure) = ca. 160 mmHg CO2: 0.003 * 760 mmHg = ca. Inspiration Air (dry) Gases 2 mmHg Alveolar Air (humid) Expiration Air (humid) Venous Blood Arterial Blood O2 21 % 160 mmHg 14 % 104 mmHg 16 % 120 mmHg 40 mmHg 100 mmHg CO2 0.3 % 2 mmHg 5% 40 mmHg 4% 27 mmHg 46 mmHg 40 mmHg H2O 0 0 mmHg 6% 47 mmHg 6% 47 mmHg 47 mmHg 47 mmHg N2 + noble gases 78.7 % 598 mmHg 75 % 569 mmHg 74 % 566 mmHg - - Σ 100 % 760 mmHg 100 % 760 mmHg 100 % 760 mmHg doi: 10.1007/978-3-662-50444-4_52 17 Artificial Organs - Lung Gas Transport in Blood - Oxygen 280 million hemoglobin (Hb) molecules Red blood cell per RBC Iron 4 heme groups with O2 binding site Hb standard values for adults: male: 13.5 g/dL – 17.5 g/dL female: 12.0 g/dL – 16.0 g/dL Heme group O2 molecule Hemoglobin and Heme https://de.123rf.com 18 Artificial Organs - Lung Gas Transport in Blood - Oxygen Hüfner number: 1.34 mLO2/gHb (1 g hemoglobin can bind 1.34 mL oxygen) → In theory: 100 mL blood with Hb of 15 g/dL contain 20.1 vol.-% O2 0.5 % - 1 % Hb as MetHb (Fe3+) 1 % - 2 % Hb as COHb (non-smoker) | ~10 % COHb (smoker) 𝑆𝑎 𝑂2 = 𝑐𝑂2 𝐻𝑏 ~ 97 % 𝑐𝑂2 𝐻𝑏 + 𝑐𝐷𝑒𝑠𝑜𝑥𝑦𝐻𝑏 + 𝑐𝐶𝑂𝐻𝑏 + 𝑐𝑀𝑒𝑡𝐻𝑏 Bunsen Coefficient 𝑐𝑎 𝑂2 = 1.34 𝑚𝐿 𝑆𝑎 𝑂2 𝑚𝐿𝑂2 ∗ 𝐻𝑏 ∗ + (𝑝𝑂2 ) ∗ 0.003 𝑔𝐻𝑏 100 𝑑𝐿𝑏𝑙𝑜𝑜𝑑 𝑚𝑚𝐻𝑔 bound 19 Artificial Organs - Lung dissolved Gas Transport in Blood - Oxygen Oxygen Saturation SaO2 in % 100 Left Shift ↓ pCO2, Temp. ↑ pH a Bohr Effect: shift of oxygen saturation curve v Right Shift ↑ pCO2, Temp. ↓ pH O2 physically dissolved 40 pvenous 20 Saturation Plateau O2 chemically bound Artificial Organs - Lung 100 parterial 150 pO2 in mmHg Henry’s Law: dissolved gas proportional to partial pressure Gas Transport in Blood - Oxygen Arterial pO2 depends on age and physique 98 paO2 /mmHg 95 BrocaIndex 90 Broca index = body weight × 100 height−100 75 85 95 105 115 85 125 135 145 80 n = 1100 75 21 Artificial Organs - Lung 15 20 30 40 50 60 70 Age/years Gas Transport in Blood – CO2 Physically dissolved in plasma: up to 7 % RBC Iron Bound to CO2Hb (Carbaminohemoglobin): ~23 % Globin chain Conversion to hydrogen carbonate (HCO3¯): ~ 70 % Heme group CO2 CO2 + H2O Carbonic anhydrase H2CO3 O2 molecule H+ + HCO3Hamburger phenomenon/ Chloride shift Clhttps://de.123rf.com 22 Artificial Organs - Lung Gas Transport in Blood – CO2 a-v: physiological CO2 binding curve 30 Haldane Effect: O2 saturation dependent on CO2 concentration v 25 O2 saturation = 97 % 20 a 15 10 CO2 physically dissolved Henry’s Law 5 10 20 30 40 50 60 70 parteriel pmixed-venous CO2 partial pressure pCO2 (mmHg) 23 CO2 chemically bound CO2 concentration in the blood (mmol/L) O2 saturation = 0 % Artificial Organs - Lung 80 Gas Blood Values venous arterial pH 7.4 7.4 pCO2/mmHg 37 - 50 32 - 45 pO2/mmHg 36 - 44 65 - 100 SO2/% 65 97 https://www.amboss.com/de/wissen/Pulsoxymetrie_und_Blutgasanalyse 24 Artificial Organs - Lung Gas Blood Values comp. resp. acidosis or comp. metab. alkalosis resp. acidosis metab. partially compensated 100 90 80 70 pCO2 /mmHg 60 metab. and resp. acidosis 1 50 40 5 metab. acidosis resp. not compensated 3 comp. metab. acidosis or comp. resp. alkalosis metab. acidosis resp. partially compensated 7.1 7.2 Acidosis Artificial Organs - Lung metab. alkalosis resp. not compensated 2 4 7.0 25 6 30 20 metab. alkalosis resp. partially compensated 7.4 7.3 pH BE ± 2 mmol/L 7.5 7.6 Alkalosis 7.7 1. 2. 3. 4. 5. 6. BE slightly increased pH value slightly increased Slight hypocapnia BE slightly lowered pH-value slightly lowered Light hypercapnia Content 1 Anatomy & Physiology 2 Pathology 3 Mechanical Ventilation 4 Extracorporeal Life Support 5 Research & Development 27 Artificial Organs - Lung Lung Diseases Obstructive lung diseases Restrictive lung diseases Respiratory tract infections External respiration Tumors Pleural cavity diseases Pulmonal gas exchange Gas transport in blood 28 Artificial Organs - Lung External Respiratory Diseases Acute/chronic rhinitis Acute/chronic sinusitis Laryngitis Tonsillitis Sleep apnea Allergies 29 Artificial Organs - Lung Pulmonal Gas Exchange Disorders Acute/chronic bronchitis Asthma Pneumonia Pneumothorax Atelectasis Lung cancer Cystic fibrosis Chronic obstructive pulmonary disease (COPD) Acute respiratory distress syndrome (ARDS) Covid … 30 Artificial Organs - Lung Blood Gas Transport Disorders Carbon monoxide poisoning Decompression illness Pulmonary embolism Anemia 31 Artificial Organs - Lung Lung Diseases Acute/chronic rhinitis Cystic fibrosis Acute/chronic sinusitis Chronic obstructive pulmonary disease Laryngitis (COPD) Tonsillitis Acute respiratory distress syndrome (ARDS) Sleep apnea Covid-19 Allergies Carbon monoxide poisoning Acute/chronic bronchitis Decompression illness Asthma Pulmonary embolism Pneumonia Anemia Pneumothorax … Atelectasis Lung cancer 32 Artificial Organs - Lung Sleep Apnea Obstructive lung disease pCO2 ↑ & pO2 ↓ Awakening as safety mechanism → Chronic fatigue → Reduced life expectation → Cardiac diseases (e.g. cardiac arrhythmias) Therapy: mechanical ventilation https://www.drugwatch.com/health/sleep-apnea/ 33 Artificial Organs - Lung Pneumothorax Collapse of one lung lobe due to air in the pleural cavity − Rupture of an alveoli (spontaneous PT) − Physical trauma (traumatic PT) − Ongoing air inflow to pleural cavity (tension PT) → Chest pain → Reduced breathing capacity → Cardiac and circulatory complications Therapy: removal of air, sealing of rupture Collapsed lung (yellow arrow) due to air in the pleural cavity (blue arrow) https://www.uniklinik-freiburg.de/thoraxchirurgie/krankheitsbilder/pneumothorax.html 34 Artificial Organs - Lung Atelectasis Collapsed region of lung due to lack of ventilation − Surfactant-deficiency of newborns (mainly pre-terms) − Obstruction of (part of) lung − Suppression of respiration (OP, pain,…) − External compression → Reduced breathing capacity up to respiratory distress Therapy: Re-ventilation of collapsed lung, mechanical ventilation Deflated right lung https://commons.wikimedia.org/w/index.php?curid=1753377, CC BY-SA 3.0 35 Artificial Organs - Lung Chronic Obstructive Pulmonary Disease Obstructive lung disease Chronic inflammatory response to inhaled irritants − Chronic-obstructive bronchitis − Lung emphysema pCO2 ↑ & pO2 ↓ https://www.livingwellwithcopd.com/en/what-is-copd.html https://www.healthcentral.com/condition/copd/copd-lungs-vs-normal-lungs 36 Artificial Organs - Lung Chronic Obstructive Pulmonary Disease 8 % – 15 % of population (smokers: 10 % – 20 %) → Shortness of breath Risk factors: − Smoking − Air pollution − Genetics (predisposition, AAT deficiency) No cure of COPD 37 Artificial Organs - Lung FEV1 → Chronic cough (% of target value of a 25-year-old) → Reduced expiration volume Non-smoker or insensitive to smoke 100 Quit at 45 Regular smoking and sensitive to smoke 75 50 Onset of symptoms 25 Serious disability Quit at 65 Death 0 25 50 age/years Fletscher-Peto curve 75 Acute Respiratory Distress Syndrome Acute lung failure due to lung oedema End-stage of acute inflammation-caused lung injury → Impaired gas exchange: pO2 & SO2 ↓ → Surfactant degradation & atelectasis https://www.frontiersin.org/articles/10.3389/fphar.2022.930593/full 38 Artificial Organs - Lung Acute Respiratory Distress Syndrome Incidence: 3 – 75 per 100.000 people Mortality: 50 % – 70 % Pulmonal causes Systemic causes Aspiration of stomach contents or water (drowning) Sepsis Inhalation of toxic gases (smoke intoxication) Pneumonia or systemic inflammation Ventilation with high cO2 Polytrauma Interstitial negative pressure (severe upper airway obstruction) Operations with lengthy cardiac bypass Therapy: treatment of cause + mechanical ventilation/extracorporeal life support, abdominal positioning 39 Artificial Organs - Lung CO poisoning Most common accidental lethal poisoning in Germany O2 Inhalation of CO, e.g. defective gas boiler, fire CO is 300 times more binding-affine than O2 − Blocks heme binding sites for O2, O2 CO CO CO CO O2 SO2 ↓ Therapy: 100 % oxygen inhalation/ventilation, in severe cases hyperbaric oxygen therapy https://de.123rf.com 40 Artificial Organs - Lung Decompression Illness Too fast decompression after exposure to increased pressure (e.g. diving) ambient air: 78 % N2 pN2 ~ 600 mmHg alveoli N2 blood tissue 41 Artificial Organs - Lung increased pressure + 5 bar pN2 ~ 2925 mmHg fast decompression pN2 ~ 600 mmHg N2 bubble Decompression Illness Gas bubbles can cause − Emboli − Oedema − Muscle pain − Circulatory collapse − Respiratory failure Therapy: hyperbaric oxygen therapy 42 Artificial Organs - Lung N2 bubble Pulmonary Embolism Blood clot that obstructs lung artery 80 % of clots have origin in deep vein thrombosis − Decreased oxygen transport and blood supply in the lung − Increased pressure in lung circulation, − Cardiogenic shock Therapy: anticoagulation, thrombolysis, pulmonary thrombectomy https://www.informedhealth.org/pulmonary-embolism.html 43 Artificial Organs - Lung Therapy Options Mechanical Ventilation Drugs Lung Transplantation Positioning Therapy 44 Artificial Organs - Lung Extra Corporeal Life Support (ECLS) Content 1 Anatomy & Physiology 2 Pathology 3 Mechanical Ventilation 3.1 History 3.2 Non-invasive Therapies 3.3 Invasive Therapies 4 Extracorporeal Life Support 5 Research & Development 45 Artificial Organs - Lung Ventilation Goals Maintain sufficient ventilation Obtain tissue oxygenation Decrease the work of breathing (WOB) and improve patient’s comfort No cure, but gives time to survive and treat the underlaying problem 1 mmH2O = 0.073 mmHg Mechanical ventilator 100 mmH2O = 980.64 Pa https://rajnursing.blogspot.com/2018/04/introduction-to-mechanical-ventilator.html 46 Artificial Organs - Lung Ventilation Modes Volume-limited ventilation (VC) − Pressure results from inspired volume Pressure-limited ventilation (PC) − Inhaled volume may change from breath to breath Depends on lung compliance − Ability of lung to stretch and expand 𝐶𝐿𝑢𝑛𝑔 Δ𝑉 = Δ𝑝 https://www.statpearls.com/ArticleLibrary/viewarticle/24496 47 Artificial Organs - Lung Lung compliance Ventilation Modes Negative pressure ventilation https://slideplayer.com/slide/8979033/ https://en.wikipedia.org/wiki/Negative_pressure_ventilator#/media/File:Iron_lung_action_diagrams.png 48 Artificial Organs - Lung Positive pressure ventilation Content 1 Anatomy & Physiology 2 Pathology 3 Mechanical Ventilation 3.1 History 3.2 Non-invasive Therapies 3.3 Invasive Therapies 4 Extracorporeal Life Support 5 Research & Development 49 Artificial Organs - Lung Historical Overview Mouth to mouth resuscitation “Secret of the midwives” Invasive ventilation of dog, Andreas Vesalius since biblic times https://www.zhb.uni-luebeck.de/epubs/ediss1082.pdf 50 Artificial Organs - Lung 1543 Repetition of experiments with continuous lung inflation, Hook & Lower 1667 Several reports and recommendations concerning mouth-tomouth resuscitation Mid 18th century Translation to human resuscitation, recommendation as first method-of-choice after drowning with bellow, John Hunter 1776 Manual & Negative-Pressure Ventilation Manual ventilation with positioning First description of a negative-pressure ventilator: full-body type ventilator John Dalziel Spirophore, Eugene Woillez Apparatus for producing artificial respiration, Karl Anton Fries “Biomotor” as emergency ventilator, Rudolf Eisenmenger reports about barotrauma, end of hyperbaric ventilation beginning of 1800‘s 1838 https://www.welt.de/english-news/article3725062/Martha-s-iron-courage.html http://rc.rcjournal.com/content/56/8/1170 https://www.zhb.uni-luebeck.de/epubs/ediss1082.pdf 51 Artificial Organs - Lung 1876 1913 1920‘s Manual & Negative-Pressure Ventilation Iron Lung Drinker and Shaw, modified by Emerson Both-Respirator, Edwards & Both Poliomyelitis epidemic USA Movement away from negative-pressure ventilation late 1920‘s 1937 https://www.welt.de/english-news/article3725062/Martha-s-iron-courage.html http://rc.rcjournal.com/content/56/8/1170 52 Artificial Organs - Lung 1950s 1960s Positive-Pressure Invasive Ventilators 1. generation Only volume control ventilation Pulmomat, Dräger, 1952 Pulmotor, Dräger, 1907 today 1900 http://rc.rcjournal.com/content/56/8/1170 53 Artificial Organs - Lung Positive-Pressure Invasive Ventilators 1. generation 2. generation Only volume control ventilation First appearance of patient-triggered inspiration 1900 1975 http://rc.rcjournal.com/content/56/8/1170 54 Artificial Organs - Lung 1980 today Positive-Pressure Invasive Ventilators 1. generation 2. generation 3. generation Only volume control ventilation First appearance of patient-triggered inspiration Microprocessor control 1900 1975 http://rc.rcjournal.com/content/56/8/1170 55 Artificial Organs - Lung 1980 ca. 2000 today Positive-Pressure Invasive Ventilators 1. generation 2. generation 3. generation Only volume control ventilation First appearance of patient-triggered inspiration Microprocessor control 4. generation Plethora of ventilation modes Dräger Evita V800 1900 1975 http://rc.rcjournal.com/content/56/8/1170 56 Artificial Organs - Lung 1980 ca. 2000 today Content 1 Anatomy & Physiology 2 Pathology 3 Mechanical Ventilation 3.1 History 3.2 Non-invasive Therapies 3.3 Invasive Therapies 4 Extracorporeal Life Support 5 Research & Development 58 Artificial Organs - Lung Non-invasive Ventilation (NIV) Awake and partly mobile patient without intubation Ventilation support by increased fraction of inspired O2 (FiO2) & positive pressure Indication: Nasal cannula for NIV − (acute phase of) COPD − Acute respiratory insufficiency (e.g. lung oedema, hypercapnia) − Weaning from intubation/ECLS − Sleep apnea −… https://www.medicalexpo.de/prod/galemed-corporation/product-68550-510847.html https://www.medicalexpo.de/prod/flexicare-medical/product-68503-605573.html https://www.lecturio.de/magazin/atemwegsmanagement/ 59 Artificial Organs - Lung Mask for NIV Non-invasive Ventilation (NIV) Contraindication − No spontaneous breathing activity − Obstruction of airways − Gastrointestinal bleeding Pros/cons Helmet for NIV + Low risk of ventilation-related injuries or pneumonia + Eating, drinking, talking, short breaks − Leakage of ventilation air https://de.intersurgical.com/produkte/intensiv-therapie/starmed-castar-r-helmfur-nicht-invasive-beatmung-niv 60 Artificial Organs - Lung Continuous Positive Airway Pressure (CPAP) Holds continuous level of positive pressure (5 cmH2O – 30 cmH2O) p/mmH2O t/min − lung/alveoli open up − more surface area available for gas exchange Adapted from: DOI: 10.1177/0897190010388145 Indication − Sleep apnea − Atelectasis, rib fractures, pneumonia,… − congestive heart failure (↑ intrathoracic pressure, ↓cardiac preload) CPAP sleep mask https://www.aerztezeitung.de/Medizin/Sauerstoff-CPAP-Wer-braucht-was-oder-auch-beides-443760.html 61 Artificial Organs - Lung Bi-level Positive Airway Pressure (BPAP) Alternating pressure for inspiration and expiration − Determines tidal breathing volume − Reduces breathing work during exhalation https://www.google.com/search?client=firefox-bd&sca_esv=578099941&q=BPAP&tbm=isch&source=lnms&sa=X&ved=2ahUKEwi6_YiTjqCCAxXNm_0HHSUeDiQQ 0pQJegQIDBAB&biw=1920&bih=1019&dpr=1#imgrc=o-0HRMfnhgDkTM 62 Artificial Organs - Lung Hyperbaric Oxygenation (HBO) 100 % O2 ventilation plus high ambient pressure (~ 3 bar = 2280 mmHg) − ↑ pO2, ↑ physically dissolved O2 − ↓ gas bubble volume Indication − CO intoxication − Gas emboli − Decompression accident − Wound healing disorder − Tissue oedema https://www.uniklinik-duesseldorf.de/patienten-besucher/klinikeninstitutezentren/hyperbare-sauerstofftherapie-hbo 63 Artificial Organs - Lung Reminder – Oxygen Dissociation Curve Saturation Plateau Oxygen Saturation SaO2 in % 100 𝑚𝐿 𝑆𝑎 𝑂2 𝑚𝐿𝑂2 𝑐𝑎 𝑂2 = 1.34 ∗ 𝐻𝑏 ∗ + (𝑝𝑂2 ) ∗ 0.003 𝑔𝐻𝑏 100 𝑑𝐿𝑏𝑙𝑜𝑜𝑑 𝑚𝑚𝐻𝑔 bound dissolved O2 physically dissolved 40 pvenous 64 O2 chemically bound Artificial Organs - Lung 100 parterial 150 pO2 in mmHg Hyperbaric Oxygenation (HBO) 100 % O2 ventilation plus high ambient pressure − ↑ pO2, ↑ physically dissolved O2 𝑐𝑑𝑖𝑠 𝑂2 = (𝑝𝑂2 ) ∗ 0.003 𝑚𝐿𝑂2 𝑑𝐿𝑏𝑙𝑜𝑜𝑑 𝑚𝑚𝐻𝑔 𝑐𝑐𝑜𝑛𝑠 𝑂2 = 1.34 𝑚𝐿 𝑆𝑎−𝑣 𝑂2 ∗ 𝐻𝑏 ∗ 𝑔𝐻𝑏 100 = 6.432 𝑚𝐿𝑂2 /𝑑𝐿𝑏𝑙𝑜𝑜𝑑 pO2/mmHg cdisO2/(mLO2/dLblood) 100 0.3 760 2.28 2,280 65 6.84 Artificial Organs - Lung SaO2 = 97 % x 18 SvO2 = 65 % Sa-vO2 = 32 % Hb = 15 g/dL Hyperbaric Oxygenation (HBO) 100 % O2 ventilation plus high ambient pressure − ↑ pO2, ↑ physically dissolved O2 − ↓ gas bubble volume N2 bubble 𝑝 ∗ 𝑉 = 𝑐𝑜𝑛𝑠𝑡. p = 760 mmHg 66 Artificial Organs - Lung (Boyle-Mariotte Law) p = 2280 mmHg Hyperbaric Oxygenation (HBO) 100 % O2 ventilation plus high ambient pressure − ↑ pO2, ↑ physically dissolved O2 − ↓ gas bubble volume − Vasoconstriction − Trigger of growth factors Adapted from: DOI: 10.2147/CWCMR.S60319 67 Artificial Organs - Lung Content 1 Anatomy & Physiology 2 Pathology 3 Mechanical Ventilation 3.1 History 3.2 Non-invasive Therapies 3.3 Invasive Therapies 4 Extracorporeal Life Support 5 Research & Development 68 Artificial Organs - Lung Invasive Ventilation (IV) Endotracheal/nasotracheal intubation Sedation, sometimes neuromuscular blocking agents Indications: A: endotracheal tube B: inflation tube with pilot balloon C: trachea D: esophagus − NIV failed to improve oxygenation or ventilation − Acute physiological impairments (Apnea, ventilation failure, cardiogenic shock, …) Goal − Guarantee delivery of high O2 − Provide work of breathing for patient https://www.doccheck.com/de/detail/photos/2317-endotracheale-intubation-schema 69 Artificial Organs - Lung Invasive ventilation: Endotracheal intubation Ventilation Parameters Vt (L/min) I E Vt Pressure, flow & volume during physiological respiration https://www.slideshare.net/subodhchaturvedi1/basic-ventilatory-modes 70 Artificial Organs - Lung Vt Tidal Volume RR Respiratory Rate FiO2 Fraction of Inspired Oxygen I/E Inspiration-Expiration Ratio Ventilation Parameters PIP Airway pressure cycle during mechanical ventilation 71 Artificial Organs - Lung PIP Peak Inspiration Pressure PEEP Positive End-Expiratory Pressure Pplat Plateau Pressure Volume-cycled Modes (VC) Set Vt + set flow Varying pressures depending on pulmonary compliance (pplat) and airway resistance (PIP) Modes: − Assisted = patient-triggered − Controlled = machine-triggered Common for initial ventilation in emergency situations High risk for barotrauma https://thoracickey.com/mechanical-ventilation-2/ 72 Artificial Organs - Lung Pressure-cycled Modes (PC) Set PIP + inspiration time Varying Vt depending on patient Flow decreases with increasing inhalation → more homogeneous gas distribution Modes: − Assisted/Supported = patient-triggered − Controlled = machine-triggered Popular for ARDS Adapted from: https://thoracickey.com/mechanical-ventilation-2/ 73 Artificial Organs - Lung Assist Control (AC) Most common in ICUs Breaths are − Patient- or time-triggered (assisted/controlled) PEEP, RR, FiO2 set Complications − Increasing residual volume − Hyperventilation − Barotrauma 74 Artificial Organs - Lung Assist Control Pressure-Cycled (AC-PC) Breaths are − Patient- or time-triggered (assisted/controlled) − Pressure targeted − Time cycled PIP & Ti set Flow pattern results from parameters https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6284234/ 75 Artificial Organs - Lung Assist Control Volume-Cycled (AC-VC) Breaths are − Patient- or time-triggered (assisted/controlled) − Flow targeted − Volume cycled Vt & flow pattern set https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6284234/ 76 Artificial Organs - Lung Pressure-Regulated Volume Control (PRVC) Breaths are − Patient- or time-triggered (assisted/controlled) − Pressure targeted − Time cycled Goal Vt & Ti set PIP is constantly adapted in relation to goal Vt Increases work of breathing https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6284234/ 77 Artificial Organs - Lung Pressure Support (PS) Spontaneous mode of ventilation →Weaning & spontaneous breathing trials Breaths are − Patient-triggered − Pressure targeted − Flow cycled PEEP, PIP, FiO2 set Volume-assured pressure-cycled ventilation − Increases pressure limit if minimum Vt not reached https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6284234/ 78 Artificial Organs - Lung Synchronized Intermittent Mandatory Ventilation (SIMV) Breaths are − Patient- or time-triggered (assisted/controlled) − PC, VC or PRVC mode possible PEEP, RR, FiO2 set Spontaneous breaths are − Unsupported − Slightly pressure-supported Recent studies show pro-longed weaning times compared to other modes Adapted from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6284234/ 79 Artificial Organs - Lung Ventilator-Induced Lung Injury Uneven ventilation Lung and vocal cord damage Muscle weakness Barotrauma (high PIP) Volutrauma (overdistension of alveoli) Atelectotrauma Biotrauma (e.g. pneumonia, O2-intoxication) https://thoracickey.com/mechanical-ventilation-2/ 80 Artificial Organs - Lung Lung Protection Strategies ARDS: Lung protective ventilation − Low Vt to achieve low pplat, therefore increase RR − “high” PEEP Severe obstructive lung diseases: − Increase exhalation time (prevent auto-PEEP) 81 Artificial Organs - Lung Weaning Discontinuation of invasive ventilation − Abrupt termination possible in 75 % cases − Spontaneous breathing trials: PS, CPAP, T-trial Extubation Possibly non-invasive ventilation afterwards 82 Artificial Organs - Lung Future of IV Smart alarm systems Decision support Ventilator management protocols incorporated in the basic operation of the ventilator Ability to effectively ventilate all patients in all settings, invasively or noninvasively Ventilator graphics (Dräger) http://rc.rcjournal.com/content/56/8/1170 83 Artificial Organs - Lung Content 1 Anatomy & Physiology 2 Pathology 3 Mechanical Ventilation 4 Extracorporeal Life Support 4.1 Oxygenators 4.2 Cannulation 4.3 Therapy Models 5 Research & Development 84 Artificial Organs - Lung ECLS Blood Pump Oxygenator https://www.sofia.medicalistes.fr 85 Artificial Organs - Lung Heat Exchanger Tubing Components of extracorporeal life support Cannulae ECLS Cardiohelp, Maquet Cardiopulmonary https://www.jems.com/patient-care/how-physicians-perform-prehospital-ecmo-on-the-streets-of-paris/ 86 Artificial Organs - Lung https://www.getinge.com/en-in/products/hls-set-advanced/ Content 1 Anatomy & Physiology 2 Pathology 3 Mechanical Ventilation 4 Extracorporeal Life Support 4.1 Oxygenators 4.2 Cannulation 4.3 Therapy Models 5 Research & Development 87 Artificial Organs - Lung History First successful operation with total CPD 1953 by John Gibbon − HLM pre-primed with heparinized donor blood (25 medical students) − Film oxygenator with variable surface area − Gold-coated to improve hemocompatibility https://www.dhzb.de/fileadmin/user_upload/deutsche_Seite/wissenschaft_forschung/Historie/Gibbon.pdf 88 Artificial Organs - Lung History – Film Oxygenator + high partial pressure gradient + easy control of blood gases – high coagulation activation – no independent pCO2 control Blood in O2 + CO2 O2 CO2 O2 https://americanhistory.si.edu/collections/search/object/nmah_1213039 89 Artificial Organs - Lung CO2 O2 Oxygenated blood out Rotation screen oxygenator from Dennis and colleagues, 1947 History – Bubble Oxygenator + high exchange surface area + efficient gas exchange + simple handling – risk of gas emboli, use of defoamer – high rate of hemolysis – no independent pCO2 control O2 + CO2 Bubble elimination CO2 O2 Oxygenated blood out Blood in O2 90 Artificial Organs - Lung Bubble oxygenator Bubble oxygenator according to Lillehei & DeWall History – Foil Membrane Oxygenator + safe long-term use + no direct blood-air contact – large exchange surface = large volume – indirect exchange contact – high equipment costs Blood in Semi-permeable membrane O2 + CO2 CO₂ O₂ O2 Foil membrane oxygenator [3.1] 91 Artificial Organs - Lung Oxygenated blood out History – Hollow Fiber Membrane + + + + very large exchange area low filling volume safe long-term use no direct blood-air contact – indirect exchange contact – high equipment costs O2 Blood in O₂ O2 + CO2 Oxygenated blood out Gas exchange on hollow fiber [3.1] 92 Artificial Organs - Lung History – Hollow Fiber Membrane + plasma sealing Solid membrane – high mass transfer resistance material: e.g. silicone rubber + low mass transfer resistance + plasma sealing material: polymethylpenthen (PMP) + low mass transfer resistance Mikroporous membrane 93 Artificial Organs - Lung – risk of plasma leakage material: polypropylene (PP) Types of hollow fiber membranes Mikroporous membrane with solid outer layer PMP Hollow Fiber Membrane Woven with defined distances (warp threads) 5 µm 380 µm 200 µm PMP hollow fiber membrane: microporous membrane with solid outer layer Microscopic image of a PMP hollow fiber membrane https://www.sofia.medicalistes.fr 94 Artificial Organs - Lung Hollow Fiber Membrane O2 O2 O2 Venous Blood O2 O2 O2 O2 O2 O2 O2 O2 O2 O2 O2 O2 O2 O2 O2 O2 O2 O2 O2 O2 Artificial Organs - Lung O2 O2 O2 O2 O2 95 O2 O2 O2 O2 O2 O2 Oxygenated Blood O2 O2 O2 Hollow Fiber Membrane Blood flow Gas flow Water flow Venous Blood Legend: O2 O2 O2 O2 O2 O2 O2 O2 O2 O2 O2 O2 O2 O2 O2 O2 O2 O2 O2 O2 O2 O2 O2 O2 O2 O2 O2 O2 O2 O2 O2 O2 O2 O2 O2 O2 Oxygenated Blood Flow Paths Cold Blood H2O H2O H2O 96 Artificial Organs - Lung H2O H2O H2O H2O H2O Fluid flow within an oxygenator H2O H2O H2O H2O H2O Blood flow in heat exchanger fiber bundle Warm Blood Blood flow in oxygenator fiber bundle Membrane Configurations Flow along the fibers 98 Artificial Organs - Lung Flow perpendicular to the fibers Membrane Configurations Membrane is rolled Flow along the fibers 99 Artificial Organs - Lung Membrane is stacked Flow perpendicular to the fibers Membrane Configurations Wound oxygenator https://www.sofia.medicalistes.fr 100 Artificial Organs - Lung Stacked oxygenator Membrane Configurations long fibers , rolled + uniform flow distribution perpendicular to fibers , stacked + low pressure loss + identical flow distribution for all flow + high surface area efficiency rates + exchange in counterflow principle 101 Artificial Organs - Lung + good bubble elimination Fiber Bundle Manufacturing 2x 1x  Separation of blood and gas phase  Centrifugal force > capillary forces 4x Manufacturing of oxygenators 102 Artificial Organs - Lung Limitations Large artificial surface area → hemocompatibility issues Configurations geometrically restricted → new membrane technologies Long-term use restricted 103 Artificial Organs - Lung Content 1 Anatomy & Physiology 2 Pathology 3 Mechanical Ventilation 4 Extracorporeal Life Support 4.1 Oxygenators 4.2 Cannulation 4.3 Therapy Models 5 104 Research & Development Artificial Organs - Lung Cannulation https://www.jems.com/patient-care/how-physicians-perform-prehospital-ecmo-on-the-streets-of-paris/ 105 Artificial Organs - Lung Cannulas Single-lumen HLS cannula (single-lumen), Getinge Smartcanula. U: Uncovered, C: Covered, T: Tubing https://www.getinge.com/de/produktkatalog/hls-kan%C3%BClen/ Strunina et al. 2019. The peripheral cannulas in extracorporeal life support. Biomed. Eng.-Biomed. Tech. 2019; 64(2): 127–133 106 Artificial Organs - Lung Dual-lumen Dual-lumen cannula Cannula materials biocompatible silicone polyurethane polymer high material strength at room temperature, more flexible at body temperature reinforced stainless steel wire − prevents kinking or collapse Cannulas Strunina et al. 2019. The peripheral cannulas in extracorporeal life support. Biomed. Eng.-Biomed. Tech. 2019; 64(2): 127–133 https://sites.google.com/a/learnpicu.com/learnpicu/ecmo 107 Artificial Organs - Lung Cannulation Regions Central cannulation Peripheral cannulation Jugular vein (left) Subclavian vessel (left) Carotid artery (right) Superior Vena Carva Aorta Pulmonary Artery Right Atrium Left Atrium Femoral vessel (left) Femoral vessel (right) Vascular system including peripheral cannulation options Conrad et al. 2018. The Extracorporeal Life Support Organization Maastricht Treaty for Nomenclature in Extracorporeal Life Support – A Position Paper of the Extracorporeal Life Support Orgaization. Am J Respir Crit Care Med Vol 198, Iss 4:447–451 108 Artificial Organs - Lung Inferior Vena Carva Left Ventricle Anatomy of the human heart and central cannulation options https://focusedcollection.com/de/160287892/stock-photo-human-vascular-system.html Central Cannulation Via sternotomy − post open chest surgery − If peripheral cannulation not possible https://www.intechopen.com/chapters/51795 109 Artificial Organs - Lung Peripheral Cannulation Seldinger Technique Cut-down Method Dilators DOI: 10.1186/s13054-019-2334-8 http://cardiaccathpro.com/VascularAccess.html, https://obgynkey.com/venous-cutdown/ 110 Artificial Organs - Lung Central vs Peripheral Cannulation Central Cannluation 111 Peripheral Cannulation + good perfusion flow + less invasive than central cannulation + offload left ventricle + no surgery necessary - bleeding & infections - Watershed phenomenon - bypass of lung and heart → thrombosis - increased afterload → lung oedema Artificial Organs - Lung Pressure Loss Law of Hagen-Poiseuille: 4   R  p  V= 8   L 𝐿 𝑅 Parabolic velocity profile with laminar flow Cannulation: ↓ R → ↑ Δp − Higher pump work required − More shear stress and blood damage induced 112 Artificial Organs - Lung Complications in Cannulation Hemorrhage (Bleeding) Blood vessel − Vessel injury (puncturing, suction) − Bad cannula placement, dislodgement D D − Most frequent complication on ECMO, ~30 % Cannula http://scansect.org/wp-content/uploads/2015/05/Vilnius_Phillip-Option-and-Pitfalls-in-Cannulation-for-ECLS.pdf Jayakumar et al. 2017. Cannulation in ECMO. Journal of Pediatric Critical Care Vol 4, Iss 2: 48 Ganslmeier et al. 2011. Percutaneous cannulation for extracorporeal life support. The Thoracic and cardiovascular surgeon Vol 59, Iss 2: 103-107 Grigioni et al. 2000. A parametric model of cannula to investigate hemolysis by using CFD. Proceeding of the 22nd Annual EMBS International Conference, July 23-28,2000, Chicago IL. 113 Artificial Organs - Lung Complications in Cannulation Hemorrhage (Bleeding) Ischemia of adverted body parts − Inadequate distal perfusion, occlusion of access vessel − second most frequent complication in VA ECMO (10 % - 20 %) https://www.jpedsurg.org/article/S0022-3468%2820%2930197-4/pdf 114 Artificial Organs - Lung Complications in Cannulation Hemorrhage (Bleeding) Ischemia of adverted body parts Hemolysis − Incidence: 5 % - 18 % − Unphysiological flow, pressure difference, shear stresses 115 Artificial Organs - Lung Complications in Cannulation Hemorrhage (Bleeding) Ischemia of adverted body parts Hemolysis Infections − Site of puncture − Open chest 116 Artificial Organs - Lung Complications in Cannulation Hemorrhage (Bleeding) Ischemia of adverted body parts Hemolysis Infections North-South /Harlequin Syndrome − Undersupply of upper body with oxygenated blood DOI: 10.1161/CIRCHEARTFAILURE.118.004905 117 Artificial Organs - Lung North-South Syndrome Complications in Cannulation Hemorrhage (Bleeding) Ischemia of adverted body parts Hemolysis Infections North-South /Harlequin Syndrome Impaired/limited patient mobility − Not possible in femoral cannulation − long, rigid design of the cannulas causes pain (e.g. during kinking) Mobilization of VV ECMO patient DOI: 10.1111/petr.12907 118 Artificial Organs - Lung Content 1 Anatomy & Physiology 2 Pathology 3 Mechanical Ventilation 4 Extracorporeal Life Support 4.1 Oxygenators 4.2 Cannulation 4.3 Therapy Models 5 Research & Development 119 Artificial Organs - Lung Support Modes Extracorporeal Life Support (ECLS) Extracorporeal Membrane Oxygenation (ECMO) System Support Mode Condition Extracorporeal Carbon Dioxide Removal (ECCO2R) VA V-AV VV VV-A Cardiac failure Cardiorespiratory failure Respiratory failure Insufficient drainage in VV ECMO VV Conrad et al. 2018. The Extracorporeal Life Support Organization Maastricht Treaty for Nomenclature in Extracorporeal Life Support – A Position Paper of the Extracorporeal Life Support Orgaization. Am J Respir Crit Care Med Vol 198, Iss 4:447–451 120 Artificial Organs - Lung AV CO2 retention AV = arteriovenous VA = venoarterial VV = venovenous VVA = venovenoarterial VAV = venoarteriovenous Support Modes and Conditions Which support mode is suitable for which condition of the patient? AV VA VV VVA 121 Artificial Organs - Lung VA ECMO (“Cardiac ECMO”) Indication: − Myocardiac pump failure − heart index < 2.0 L/min/m2 Aim: − Hemodynamic support − Cardiac unloading → 5-7 L/min pump flow Problems: cannulation of artery Irreversible myocardial damage: rather long-term VAD Conrad et al. 2018. The Extracorporeal Life Support Organization Maastricht Treaty for Nomenclature in Extracorporeal Life Support – A Position Paper of the Extracorporeal Life Support Orgaization. Am J Respir Crit Care Med Vol 198, Iss 4:447–451 122 Artificial Organs - Lung VA ECMO in Vf-Af Configuration VV-A ECMO Indication − Insufficient venous drainage in VA ECMO − North-South/ Harlequin Syndrome Aim: − Increase cardiac unload − Improve upper body oxygenation https://www.intechopen.com/chapters/51211 123 Artificial Organs - Lung VV ECMO (“Respiratory ECMO”) Indication: − Respiratory failure (ARDS) − arterial pO2 < 60 mmHg Aim: − Lung support until recovery/transplant Pump speed: 2-3 L/min May allow for mobilization Conrad et al. 2018. The Extracorporeal Life Support Organization Maastricht Treaty for Nomenclature in Extracorporeal Life Support – A Position Paper of the Extracorporeal Life Support Orgaization. Am J Respir Crit Care Med Vol 198, Iss 4:447–451 124 Artificial Organs - Lung VV ECMO in Vf-Vj Configuration VV ECMO in (dl) Vj-V Configuration VAV ECMO Indication: − Cardiac and respiratory failure − Heart failure during VV ECMO − Lung failure during VA ECMO Aim: − Hemodynamic plus respiratory support Fine balancing of blood flow in return cannulas necessary VV-A ECMO in Vf-VjAf Configuration https://www.intechopen.com/chapters/51211 125 Artificial Organs - Lung AV ECCO2R Indication: − Respiratory failure → Gas exchange support − Good heart index > 3.0 L/min/m2 − Mean arterial pressure > 70 mmHg − pCO2 > 70 mmHg Aim: − Reduction of CO2 in lung protective manner → Pumpless system (1.5 L/min flow from arterial system) Conrad et al. 2018. The Extracorporeal Life Support Organization Maastricht Treaty for Nomenclature in Extracorporeal Life Support – A Position Paper of the Extracorporeal Life Support Orgaization. Am J Respir Crit Care Med Vol 198, Iss 4:447– 451 126 Artificial Organs - Lung AV ECCO2R in Af-Vf Configuration VV ECCO2R Less invasive than AV ECCO2R No arterial cannulation Potential for early mobilization Less complications But: more blood damage due to pump Conrad et al. 2018. The Extracorporeal Life Support Organization Maastricht Treaty for Nomenclature in Extracorporeal Life Support – A Position Paper of the Extracorporeal Life Support Orgaization. Am J Respir Crit Care Med Vol 198, Iss 4:447–451 Liu2016 127 Artificial Organs - Lung VV ECCO2R in (dl) Vj-V Configuration ECLS Pros and Cons Pros: Cons: + Lung saving - Bleeding + Fast recovery of the lung - Inflammation + Optional awake patient - High anticoagulation + Optional mobile patient - Ischema - extremely invasive 128 Artificial Organs - Lung Content 1 Anatomy & Physiology 2 Pathology 3 Mechanical Ventilation 4 Extracorporeal Life Support 5 Research & Development 129 Artificial Organs - Lung ECLS Research Topics Oxygenator − Long-term stability − Membrane performance − Priming volume Pump − Operation point optimization Cannula − Positioning (CFD) Artificial lung 130 Artificial Organs - Lung Fiber Configuration Target Rolled fiber bundle 131 Artificial Organs - Lung Priming Volume Pressure Loss Correlations in the fiber bundle Mass Transfer Fiber Configuration Fiber diameter Rolled fiber bundle 132 Artificial Organs - Lung Target Priming Volume Pressure Loss Mass Transfer ↓ ↑ ↓ ↓ Correlations in the fiber bundle Fiber Configuration Target Priming Volume Pressure Loss Mass Transfer Fiber diameter ↓ ↑ ↓ ↓ Bundle density ↑ ↓ ↑ ↑ Rolled fiber bundle 133 Artificial Organs - Lung Correlations in the fiber bundle Fiber Configuration Target Priming Volume Pressure Loss Mass Transfer Fiber diameter ↓ ↑ ↓ ↓ Bundle density ↑ ↓ ↑ ↑ Membrane surface area ↑ ↑ ↑ ↑ Rolled fiber bundle 134 Artificial Organs - Lung Correlations in the fiber bundle Fiber Configuration Variables: − Large fiber diameter − Small fiber diameter − Small fiber diameter + higher bundle density Correlations in the fiber bundle Mutual interaction: 135 Target Fiber Diameter Bundle Density Membrane surface area Fiber diameter ↓ - ↓ ↓ Bundle density ↑ -  Membrane surface area ↓    - Artificial Organs - Lung 3D Membranes Triply periodic minimal surfaces (TPMS) Passive mixing Arbitrary housing geometry Local membrane variation Membrane TPMS 136 Artificial Organs - Lung Blood Gas HFM 3D Membranes for Artificial Lungs Gas Isotropic Anisotropic Decreased cell size Blood Membrane Flow directions (Upscaled geometry) 50 mm 137 Artificial Organs - Lung 3D Membranes for Artificial Lungs Improved perfusion (stagnation volume reduced by 7.4 %) 22.3% Increased gas transfer rates (~14 % for O2) Decreased pressure loss (~20 %) Velocity [m/s] Vres [%] PO2 [mmHg] Isotropic 4e-2 100 64 14% 2e-02 50 49 0 0 34 Anisotropic 138 Artificial Organs - Lung Long-term Stability Different bioactive coatings/surface modifications 139 Artificial Organs - Lung Endothelialization of the oxygenator membrane Miniaturization Mini HLM − Intended use: open heart surgery of newborns 450 mm − Priming volume of complete extracorporeal circuit: 104 mL Mini HLM 140 Artificial Organs - Lung Miniaturization Mini HLM Artificial placenta oxygenator − Extremely pre-term infants − Oxygenator can adapt to growth of baby 141 Artificial Organs - Lung Thank you for your attention ! Johanna Clauser [email protected]