Critical Care Update: Pressure

1. Critical Care Update:Pressure Michelle Harkins

2. Outline • Blood Pressure: • Norepinephrine versus Dopamine • Lung Pressure: ARDS ventilation • Standard Protocols • Perflurocarbons • Prone positioning • Jet Ventilation • ECMO

3. Vasoactive Support of Shock • Septic shock accounts for predominate ICU mortality • Fluid resuscitation and pressors main tx • Multiple choices: dopamine, dobutamine, epinephrine, norepinephrine, phenylephrine, vasopressin • Is there a preferred agent?

4. NE vs. DA • 1679 patients randomized from 12/03-10/07 • Belgium, Spain, Austria • Endpoints: Death at 28 days • Number of days without need for organ support • Adverse events • DA associated with increased rate of death among cardiogenic shock patients (N=280) • DA associated with more arrhythmias • De Backer, et al; SOAP II investigators. Comparison of dopamine and norepinephrine in the treatment of shock. NEJM 2010 362: 779-89.

5. Figure 1. Screening and Enrollment

6. Methods • Dose determined by patient’s body weight • Target BP determined by MD in charge for each individual patient • If patient was still hypotensive after max dose of either agent, open-label norepinephrine was added • Open-label dopamine was not allowed at any time • Epinephrine and vasopressin were used only as rescue therapy • Inotropic agents could be used prn to increase CO

7. Figure 2. Kaplan-Meier Curves for 28-Day Survival in the Intention-to-Treat Population.

8. Primary endpoint: death at 28d

12. Conclusion • Equal mortality outcomes and less than half the incidence of arrhythmias put norepinephrine preferentially ahead of DA for treatment of shock. • Fluid resuscitation protocol limited • ? tachyarrhythmia as a mechanism for increased mortality in cardiogenic shock subgroup treated with DA, especially in first 4 days

13. Case • 50 yo female presents with altered mental status, hypotension and leg ulcers / cellulitis. • Goes to the OR for wet gangrene. • Treated for septic shock with fluids and pressors.

14. Case (cont’d) • Develops progressive respiratory failure. • Intubated.

15. What is ARDS • Acute Lung Injury • Acute onset • Bilateral infiltrates consistent with pulmonary edema • A ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2/FiO2) between 201 and 300 mmHg. (The PaO2 is measured in mmHg and the FiO2 is expressed as a decimal between 0.21 and 1.00.) • No clinical evidence for an elevated left atrial pressure. If measured, the pulmonary capillary wedge pressure is 18 mmHg or less. • ARDS : Above + P/F ratio <200

16. Clinical Manifestations • Usually present with progressive dyspnea, over a short time frame. • History more relevant to precipitant and ruling out other conditions than ARDS. • Exam: Tachypnea, cyanosis, use of accessory muscles, occasional crackles, absence of signs of heart failure. • Hypoxic respiratory failure

17. Precipitants of ARDS • Pulmonary • Pneumonia • Toxic Inhalation • Aspiration of Gastric acid • Negative Pressure Pulmonary Edema • Extra-Pulmonary • Sepsis • Pancreatitis • Burns / Trauma • TRALI • Medications … • Obstetric Catastrophies • Narcotic induced pulmonary edema

18. Mortality and Morbidity of ARDS • Case fatality rate has decreased over time • 1970s 90%, 1991 55%, 1997 35% • 2004-05 26% • factors increasing mortality: number of organs failing, severity of lung injury, nature of underlying disease • High cost to healthcare system • Erickson, et al Crit Care Med 2009 37:1574-79

19. Outcomes among ARDS survivors Herridge et al. NEJM 2003

20. Standard Treatment for ARDS • Conventional mechanical ventilation • PEEP • Treating underlying cause, infection • Supportive care with nutrition, antibiotics, judicious fluid management

21. Fluid and ARDS ARDSnet NEJM 2006

22. Drug Therapy of ARDS

23. Alternate Modes of Mechanical Ventilation • Inverse Ratio Ventilation • Pressure Control • Volume Control • High Frequency Jet Ventilation • Low Frequency Ventilation

24. The Baby Lung and Ventilator-Induced Lung Injury • Several animal models of ARDS demonstrated that high VT or shearing alveoli lead to increased ARDS and increased generation of pro-inflammatory mediators Gattinoni, ICM 2005

25. Baby Lung is not an anatomical unit, but a result of Lung Edema and compressive forces that are dependant Baby lung or Sponge Lung Gattinoni, ICM 2005

26. Low tidal volume • Amato 38 vs 71 % • 3 smaller studies 7 vs 10 ml/kg no difference ARDSnet NEJM 2000

27. Low Vt protocol ARDSnet website

28. Pressure Volume Curves Albaiceta GM et al. Current Opinion in Crtical Care 2008;14:80-86

29. PEEP • Initial high PEEP studies also had control and intervention groups with different Vt. • Alveoli study compared aggressive PEEP increase versus FiO2 increase. ARDSnet NEJM 2004

30. Recruitment Maneuvers • Part of Alveoli trial, showed only modest, transient benefit and were dropped afterward. • More severe ARDS has more recruitable lung. Gattinoni et al., NEJM 2006

31. Prone Positioning • In spite of large trials, no improvement in mortality is seen although proning does consistently cause improvements in oxygenation

32. Two trials of “jet” ventilation in ARDS. Derdak had a trend toward reduction in mortality. This was mitigated by the high Vt in the control group (8ml/kg) High Frequency Oscillatory Ventilation

33. Other Vent Modalities • APRV – Poorly studied • Perflurocarbon – Partial liquid Ventilation (over 400 patients studied…no benefit) • Non- invasive: Poorly studied, no evidence of benefit.

34. ECMO for ARDS • Early study demonstrated no benefit in adults. (Zapol, JAMA 1979!). • 10% survival in each group • Many small series since then VV and VA. (Morris et al. 1994)

35. Adult ECMO

36. Modes of ECMO

37. Role of ECMO • No controlled studies in H1N1 • JAMA 2009: Australia, NZ experience • Reported use in Michigan, Taiwan • UNM also • CESAR trial (Lancet 16 Sept 09) • RCT Conventional ventilatory support vs. ECMO • 180 patients and randomly assigned to consideration of ECMO (n=90) vs. conventional (n=90)

38. CESAR • Exclusion criteria: Pip > 30 or FiO2>80% for more than 7 days, ICH, heparin contraindication • Primary outcome = death or severe disability at 6 months • Power calculations were based on a 70% mortality in the conventional group

39. Randomized to ECMO • Patients hemodynamically stable  put on standard ARDSnet-like protocol • Pplateau < 30, optimize peep to PaO2, diuresis to dry weight, Hct 40%, prone positioning, nutrition • If didn’t respond to above within 12 hours (FiO2> 90 still needed to obtain SaO2>90%), pH < 7.2 either respiratory or metabolic, or became hemodynamically unstable, then was put on ECMO

40. CESAR • 90 patients considered for ECMO • 68 received ECMO • Other patients received ARDSnet-like protocol • 1 contraindication to heparin • 2 died during transfer • 3 died within 48hr of transfer • Overall 47 died • Peek et al, Efficacy and economic assessment of conventional ventilatory support vs ECMO for severe adult respiratory failure (CESAR). Lancet. September 2009

41. 57 who received ECMO (63%) survived to 6 months without disability • vs. 47% (41/87) of those with conventional tx

45. ECMO is not THE answer • Very expensive treatment: longer stay, more expense • ECMO centers will have better outcomes: CESAR was a referral to ECMO centers in the UK • NM has the capacity to have 4 machines up and running at one time for Hanta, neonates and ARDS

46. Other Proven Strategies • Sedation Vacation: Improves liberation from ventilator and mortality • Daily Weaning Trials: Decrease Ventilator days and improve mortality • Awake and Breath protocols also improve cognitive outcomes months later • Jackson, et. al. Am J Respir Crit Care Med 2010