SENIOR GRAND ROUND

1. SENIORGRAND ROUND PRASHANT BHARUCHA M.D.

2. CASE 1 DAY 1 • 47-year-old Hispanic female who presented to the ER complaining of SOB and chest pain as well as cough and cold-like symptoms for approximately 4-5 days. • Patient had recently been in Los Angeles and seen her PCP for same symptoms. • Patient had received prescription of zithromax from PCP. Despite of taking this medication for 5 days, the patient continued to have increasing difficulty breathing associated wheezing and chest congestion. • In the emergency department the patient was diagnosed with pneumonia based on chest x-ray which showed bilateral peri-hilar infiltrates. • Patient was admitted to medicine service, started on treatment for community –acquired PNA.

3. DAY 2 • Patient was complaining of worsening of SOB, started on oxygen through venti-mask 50%. ABG was ordered, showed severe hypoxia with PO2 of 52% . CTA of chest was done which showed no evidence of PE but Bilateral diffuse infiltrate. • Patient was transferred to ICU team for further management. • Patient was started on oxygen with 100% NRB mask in ICU, started on sepsis protocol with cefepime and vancomycin. Tests for H1N1 virus had been sent and triple antiviral regimen (Tamiflu + Ribavirin + Amantadine) was started. • Patient deteriorates on the same day, intubated and started on volume control ventilation with PEEP 5 and FiO2 100%. DAY 3-6 • Patient did well on volume control ventilation, ABG was done- showed good oxygenation , CXR was stable-showing bilateral infiltrate with no improvement.

4. DAY 7 • Patient became hypoxic with SaO2 of 85-86% on 100% FiO2. Peak pressure on ventilator was above 40, Patient was started on Pressure control ventilation with 100% FiO2. • CXR was showing worsening of Bilateral infiltrate with ARDS picture. • Patient was still hypoxic, Pressure control ventilation with inverse ratio tried --- didn’t work. • Trauma surgery team has been consulted for possible HFOV. • Patient was sedated, paralyzed and started on HFOV. DAY 8-12 • Patient was doing well on High frequency oscillators . • Developed Pneumothorax, chest tube had been placed by CVT surgery. • H1N1 PCR came back positive, but patient had already completed the course of triple antiviral medication.

5. DAY 15 • Patient became hypoxic again, oscillator setting had been changed to MAP of 45 and FiO2 100%. CXR showing complete opacification of both lung field. • Trauma surgery team decided to start patient on ECMO. Hospital Course: • Patient was on ECMO for almost 15-18 days. Weaned off again to HFOV (oscillator). • Patient remain on HFOV for more than 20 days again. Patient developed Pneumothorax multiple times while on oscillator and had 3 chest tube placed. • Patient developed hypotension and was on vasopressers on and off. • Family had been updated with patient’s prognosis multiple times and they want patient as CAT I. • Patient coded twice on the same day with PEA , resuscitated twice. • Family had been informed again, patient was categorized as CAT III. • Patient died after 2 months of complicated hospital course with H1N1 ARDS.

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7. CASE 2 • 53-year-old Caucasian male who presented with shortness of breath and cough with sputum of 5 days duration. • Initially sputum was clear but later on turned yellow, greenish, dark and patient had occasional blood-streaked with excessive cough. Cough was associated with pleuritic chest pain. • Patient had recently come back from Utah where his sister and kids were diagnosed with H1N1 flu. They were all treated with tamiflu and were currently recovering. • Patient never had immunization with regular flu vaccine or the H1N1 flu vaccine for this season. • Patient also had fever, chills and dizziness.

8. Hospital course: • Patient was initially admitted to medicine team, later on intubated and transferred to ICU team because of hypoxia and renal failure. • Started on sepsis protocol and triple antiviral medication. • Started on conventional ventilation initially, but could not oxygenate the patient. • Trauma surgery had been consulted for oscillator. Unfortunately oscillator was not available and patient was started on ECMO by trauma surgery team. • Patient was managed on ECMO with CRRT for less than 7 days. • Patient was coded and then categorized as CAT III • Patient died of possible H1N1 vs. viral ARDS.

9. ? • What are the different modality of ventilation for patient with severe ARDS? • Is there any survival benefit of using ECMO in patients with severe ARDS?

10. ARDS DEFINITION: • Severe, acute lung injury involving diffuse alveolar damage, increased micro vascular permeability and non cardiogenic pulmonary edema. • Acute refractory hypoxemia. • Annual incidence 150,000 cases per year in the US. • High mortality- 40%-60%. • First described in 1967.

11. CRITERIA FOR ARDS • Acute onset respiratory failure • Bilateral diffuse alveolar infiltrate on CXR. • PaO2/FiO2 <200. • PCWP should be <18, No Left atrial enlargement. If PaO2/FiO2 is between 200 – 299 Acute Lung Injury

12. IMAGINGS IN ARDS

13. STEPWISE APPROACH IN ARDS • Oxygenation. • Ventilation. • Fluid management. • Recruitment maneuver. • Steroid ? • Treatment of underlying cause. • Supportive care.

14. VENTILATOR MANAGEMENT IN ARDS VENTILATOR SETUP AND ADJUSTMENT 1. Calculate predicted body weight (PBW) Males = 50 + 2.3 [height (inches) - 60] Females = 45.5 + 2.3 [height (inches) -60] 2. Select any ventilator mode 3. Set ventilator settings to achieve initial VT = 8 ml/kg PBW 4. Reduce VT by 1 ml/kg at intervals ≤ 2 hours until VT = 6ml/kg PBW. 5. Set initial rate to approximate baseline minute ventilation (not > 35 bpm). 6. Adjust VT and RR to achieve pH and plateau pressure goals below NHLBI ARDS NETWORK

15. PEEP in ARDS OXYGENATION GOAL: PaO255-80 mmHg or SpO288-95% • Use a minimum PEEP of 5 cm H2O. Consider use of incremental FiO2/PEEP combinations such as shown below (not required) to achieve goal. • Lower PEEP/Higher FiO2 PLATEAU PRESSURE GOAL: ≤ 30 cm H2O Check Pplat (0.5 second inspiratory pause), at least q 4h and after each change in PEEP or VT. PH GOAL : 7.30 – 7.45 NHLBI ARDS NETWORK

16. DIFFERENT MODALITIES OF VENTILATION IN ARDS • Pressure –control ventilation. • Pressure –control with IRV (I:E=1:1 or 2:1). • Airway pressure release ventilation (Bivent). • HFOV. • ECMO.

17. ECMO What is ECMO ? • An alternate method of providing prolonged Cardiac and Pulmonary support. • Called extracorporeal membrane oxygenation (ECMO), extracorporeal life support, or extracorporeal lung assist. • Last resort for ventilation.

18. DR. JOHN H. GIBBON JR • ECMO originate from the first blood oxygenator developed in the 1950‘s. • In 1930 he started working on techniques for extracorporeal circulation after a patient died from pulmonary hemorrhage. • The first interest was to provide pulmonary support and not cardiac

19. MEMBRANE OXYGENATOR DEVELOPMENT • The first oxygenators sustained blood – air intervention but various complications and organ deteriorations had been noted after limited time. • Experiments showed the negative effects of blood-air interface. • The next goal was to develop the membrane oxygenator. • DR. CLOWES build the first membrane oxygenator using polyethylene. • 1956 this device was successfully applied in cardiac surgery.

20. IMPROVED MEMBRANE OXYGENATORS • DR. KAMMERMEYER discovered that dimethylpolysiloxane membranes allowed much better diffusion rates than polyethylene. • This became the membrane of choice, and the improved diffusion rates of this membrane made extended life support possible. • Bleeding was still a problem, and the numerous transfusion that would be needed for extended support made the therapy unfeasible

21. DR. BARTLETT – ‘FATHER OF ECMO’ • Robert Bartlett team in the mid 1960‘s showed that longer support times was possible by reducing the heparin dosage. • In 70’s he made a device with Extracorporeal oxygenation that could provide extended heart-lung bypass. • In the same year the first newborn infant was successfully sustained using ECMO under the care of Dr Bartlett.

22. ADULT ECMO HURDLE 1976 • The study included centers with no ECMO experience. • Patient population was dominated by the influenza epidemic. • Severe bleeding problems. • 300 patients was to perform for the study, at 92 patients the study was stopped; poor results. • ECMO success rate in adults was 10%.

23. NEONATAL ECMO – BARTLETT TEAM • By 1981 they treated 45 newborns with a success rate over 50% lead to establishment of more ECMO centers. • By 1986, 715 neonatal cases were reported at 18 centers, with favorable success rates of about 80%. • Overall success rate in Neonates was 50% in 1986.

24. 1986 - USA 18 centres ECMO • 1986 - GATTINONI - 50% survival in adult ECCO2R • 1989 – ELSO (Extracorporeal Life Support Organization) REGISTRY • 2001 - 120 centres world wide

25. EXTRACORPOREAL LIFE SUPPORT ORGANIZATION • The Extracorporeal Life Support Organization (ELSO) is an international organization of health care professionals and scientists who are dedicated to the development and evaluation of novel therapies for support of failing organ systems. • Crucial is the promotion of a broad multidisciplinary collaboration. • The primary mission of the Organization is to maintain a registry of, at least, use of extracorporeal membrane oxygenation in active ELSO centers.

26. ECMO CIRCUITS TYPES: • VV -Veno-Venous. (no hemodynamic support, preferred for respiratory support). • VA -Veno-Arterial. (required for cardiac support). • AV -Arteriovenous. (limited to low blood flow, specifically for CO2 removal)

27. VENO-VENOUS ECMO • More common. • Provides only pulmonary support and allows lungs to heal. • Pulmonary support and hygiene are required to improve gas exchange. • Can provide sufficient oxygenation for several weeks.

28. PATIENT SELECTION CRITERIA • Vary widely from institution to institution. • ECMO is indicated for selected neonatal, pediatric and adult patients with severe, acute cardiac and/or respiratory failure who have failed to respond to conventional medical management.

29. INDICATION OF ECMO CARDIAC CASES • During Cardiopulmonary bypass surgery. • Postoperative cardiac failure in operative room(after bypass). • Cardiac arrest from any cause with response to CPR in less than 5 min but still unstable. • Myocardial failure secondary to myocardiopathy, myocarditis, toxic drug overdose. • Bridge to Transplant for Unrevascularizable acute MI, Chronic heart failure. Implantable circulatory support : VAD, TAH ELSO Guidelines April 2009

30. RESPIRATORY CASES • Hypoxic respiratory failure due to any cause (primary or secondary) ECLS should be considered when risk of mortality is 50 % or greater and is indicated when risk is 80 % or greater. • 50 % mortality can be identified as PaO2/FiO2 < 150 on FiO2 > 90% and/or Murray score 2-3. • 80 % mortality can be identified as PaO2/FiO2 < 80 on FiO2 > 90% and/or Murray score 3-4. • CO2 retention due to asthma or permissive hypercapnia with PaCO2>80. • Severe Air Leak syndromes. ESLO Guidelines April 2009

31. CONTRAINDICATION OF ECMO ABSOLUTE • Unlikely to be reversed in 10 – 14 days • Multi-organ failure • Severe reversible brain injury • Significant pre-ECMO CPR • Contraindication to anticoagulation and HIT syndrome • Uncontrolled metabolic acidosis • Terminal disease /malignancy • Chronic lung disease(underlying) • Chronic myocardial dysfunction • Immunosuppression RELATIVE • Mechanical ventilation >6 days • Septic shock • Severe pulmonary hypertension (MPAP >45 or >75% systolic) • Cardiac arrest > 5 min • Acute, potentially irreversible myocardial dysfunction • >35 years of age ELSO Guidelines April 2009

32. MONITORING ON ECMO • Multidisciplinary team approach is used. (Critical care, Anesthetist, CVT surgeon, Respiratory therapist, Nursing staff). • Patient is connected to ECMO circuit. • Blood flow is increased until respiratory and hemodynamic parameters are satisfactory.

33. OXYGENATION • Goal : VV access can supply all metabolic oxygen requirements, but PaO2 could be low between 80-85%. HEMODYNAMICS • On VA, SVO2 can be used as guide for hemodynamic support. • On VV, No Hemodynamic support provided. Echocardiogram is excellent tool to measure hemodynamics on VV ECMO. VENTILATOR MANAGEMENT Key aspect to consider • The lungs are not used for gas exchange. • Avoid high PEEP, High inflation pressure. • Ideal RR - 4 to 6 /min, Modest PEEP < 10 mm H2O, Inflations pressure should be low (e.g. 10 mm above PEEP). • Once patient stabilized, sedation should be lightened, spontaneous ventilation with pressure control ventilation should be started. ELSO Guidelines April 2009

34. COMPLICATION OF ECMO • Cannula dislodgement. • Bleeding. • Sepsis. • Air emboli. • Thromboembolism. • Risk of disseminated intravascular coagulation (DIC) & heparin induced thrombocytopenia (HIT). • Renal failure. • Decubitus ulcers. • Neurologic damage. • VA ECMO – Pulmonary hemorrhage, Infarction, cerebral infraction

35. WEANING / ENDPOINT THERAPY WEANING: • Extracorporeal support is decreased byreducing the blood flow through circuit as native organ function improves. • ECC support is less than 30% of total, native heart or lung function may be adequate to allow coming off ECLS, and a trial off is indicated. • Adjust ventilator to optimal settings, Maintain blood flow and anti-coagulation, turn off the oxygenator. Follow the patient SaO2 and pCO2. • If lung function is adequate at acceptable ventilator settings for >1 hour – Time for Decannualtion.

36. STOPPING SUPPORT FOR FUTILITY • No hope for healthy survival (severe brain damage, no heart or lung recovery, and no hope of organ replacement by VAD or transplant). • Three days of no cardiac function. • Two weeks of no lung function in a patient who is not a transplant candidate.

37. SURVIVAL BENEFIT OF ECMO IN ADULT WITH ARDS

38. RCTs OF ECMO IN ADULT • NIH Adult ECMO Trial Zapol et al JAMA 242:2193-96,1979 • PCIRV vs. ECCO2R Morris et al, Am J Respiratory Critical Care Med 1994;149:295-305.

39. NIH TRIAL • VA ECMO +Ventilation Vs Conventional Ventilation • Severe ARDS. A Randomized Prospective Study. JAMA 1979:242:2193-6). • 90 patients, 9 US centres, 1974 - 1977 • Survival < 10% in both arms • Criticism: • 1. VA ECMO used (prone to micro thrombi in lungs) • 2. High anticoagulation and bleeding complications • 3. High pressure ventilation used even DURING ECMO • 4. Mean duration of ventilation prior to ECMO was 9 days • Little experience, varying technique in different centres

40. PCIRV and ECCO2R Trial • Morris, et.al: Randomized Trial of PCIRV and ECCO2R in ARDS. AJRCCM,1994;149:295-305 • 40 patients, severe ARDS (paO2/FiO2 63 mmHg) in one US centre • 33% survival in 21 patients ECCO2R + LFPPV • 42% survival in 19 patients PCIRV • P = 0.8, no significant difference • Little previous experience in centre with technique in humans • High pressure ventilation before and DURING ECCO2R (PEEP > 20, Peak 45 - 55 cmH2) • Frequent severe bleeding complications (leading to discontinuation of ECCO2R in 7/19 cases).

41. BOTH TRIALS HAVE LITTLE RELEVANCE TO CURRENT ECMO REGIMENS

42. OBSERVATIONAL STUDIES • Cohort studies of ECMO-Leicester. • PaO2/FiO2 65 mm of Hg. • Murray score was 3.4.

43. MURRAY SCORE Murray score = Average score (all 4 parameters must be used): • PaO2/FIO2 : On 100% Oxygen, >300=0, 225-299=1, 175-224=2, 100-174=3, <100=4. • CXR: normal=0, 1 point per quadrant infiltrated. • PEEP: <5=0, 6-8=1, 9-11=2, 12-14=3, >15=4. • Compliance (ml/cmH2O): >80=0, 60-79=1, 40-59=2, 20-39=3, and <19=4. Compliance = Tidal volume/(PIP-PEEP). • Severe respiratory failure will be defined as a Murray Score >3.0, or uncompensated hypercapnoea with a pH < 7.20.

44. ECMO Vs. Non ECMOSurvival benefit from 51 studies Lewandowski Critical Care 2000 4:156   doi:10.1186/cc689

45. Multi-centre randomized controlled trial (2000-2007). • United Kingdom –multicenter, 180 patients • Respiratory tract diseases: Severe acute respiratory failure . Inclusion Criteria: • Adult patients (18-65 years in UK) • With severe, but potentially reversible respiratory failure. Severe respiratory failure will be defined as a Murray score >3.0, or uncompensated hypercapnoea with a pH <7.20 . Exclusion Criteria: • Duration of high pressure and/or high FiO2 ventilation >7 days • Intra-cranial bleeding • Any other contra-indication to limited heparinisation • Patients with other co morbid conditions.

46. OUTCOME OF STUDY Primary outcome: • Death or severe disability at six months. • Severe disability will be defined as, patient requiring full time nursing care at home, or continued residence in hospital. Secondary outcome: • Hospital Indices: duration of ventilation, length of ICU stay, length of hospital stay. Daily APACHE II score. • Cost-effectiveness Ratio • Follow up: Survivors will be contacted 6 months after randomization for a detailed examination by a chest physician using a structured data collection form.

47. RESULT OF CESAR TRIAL • Referral to consideration for treatment by ECMO led to a gain of 0.03 quality-adjusted life-years (QALYs) at 6-month follow-up. • (relative risk 0.69; 95% CI 0.05-0.97, p=0.03). • A lifetime model predicted the cost per QALY of ECMO to be pound 19252 (95% CI 7622-59 200) at a discount rate of 3.5%.

48. ECMO in H1N1 INFLUENZA ARDS • ECMO for 2009(H1N1) influenza ARDS. • JAMA. 2009;302(17):1888-1895. Published online October 12, 2009 (doi:10.1001/jama.2009.1535. • 201 Patients, in 15 ICU in Australia and New Zealand. • Observational study.

49. Flow Diagram of Patients Receiving Mechanical Ventilation for Suspected 2009 Influenza A(H1N1) Infection at ECMO Centres

50. OUTCOME • Patients treated with ECMO (n = 61)were compared with those without (n = 133). • ECMO had longer duration of mechanicalventilation (median [IQR], 18 [9-27] vs. 8 [4-14] days; P = .001). • ICU stay (median [IQR], 22 [13-32] vs. 12 [7-18] days; P = .001). • Greater ICU mortality (14 [23%] vs. 12 [9%]; P = .01). • Overall survival rate is 80 % in ECMO group Vs. 82 % in Non-ECMO.