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Refractory Hypoxemia in the ICU

Refractory Hypoxemia in the ICU. Gordon D. Rubenfeld, MD MSc Associate Professor of Medicine University of Washington Harborview Medical Center. Disclosures. NIH grant funding to study implementation strategies for lung protective ventilation in the community

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Refractory Hypoxemia in the ICU

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  1. Refractory Hypoxemia in the ICU Gordon D. Rubenfeld, MD MSc Associate Professor of Medicine University of Washington Harborview Medical Center

  2. Disclosures • NIH grant funding to study implementation strategies for lung protective ventilation in the community • Speaking fees from KCI – usually speak on the con side of prone ventilation • No funding from the ARDS Network – but some of my best friends do • I think that medicine should be evidence based – most of the time

  3. What is Refractory Hypoxemia? • No official definition • PaO2 < 50 on an FIO2 = 1.0 • Persistent for > 1 hour • Despite PEEP trial of up to 20 - 25 cm H2O • Despite ruling out readily reversible causes • Mucus plugging/lobar or greater collapse • Pneumothorax • Systemic vasodilators enhancing shunt • Pulmonary embolism • Intra-cardiac R > L shunt • Circulatory collapse (low SvO2)

  4. But first, a note from our sponsor • ALI • Common • Frequently missed • Lethal • Easily treatable with evidence based life saving interventions • Refractory hypoxemia in ALI • Extremely rare • Never missed • Not that much more lethal than regular ALI • All treatments are experimental (but very cool and sexy)

  5. ALI is common and 3-5x more lethal than a heart attack • 383,000 and 190,000 cases of sepsis and acute lung injury respectively in US • Mortality rates of 30-60% • 540,000 people die following ICU admission each year • 58% of hospital deaths in or following ICU admission

  6. ALI cases are frequently missed N=76 N=32 N=28 Mahoney AM, et al, American Thoracic Society Abstract. 2002 ALI not documented even in patients with significant risk factors for ALI

  7. Easily treatable with evidence based life saving intervention –that isnt used! Tidal Volume ml/kg Not PBW International International Scandinavia Scandinavia Scandinavia Australia ARF ALI ARDS COPD Luhr OR, et al. Incidence and mortality after acute respiratory failure and acute respiratory distress syndrome in Sweden, Denmark, and Iceland. AJRCCM. 1999;159(6):1849-1861. Bersten AD, et al. Incidence and Mortality of Acute Lung Injury and the Acute Respiratory Distress Syndrome in Three Australian States. AJRCCM. 2002;165(4):443-448. Esteban A,, et al. How is mechanical ventilation employed in the intensive care unit? An international utilization review. AJRCCM. 2000;161(5):1450-1458.

  8. Community physicians [a little]more likely to use injurious tidal volumes Academic Community Biased toward underestimating ml/kg PBW as BW used if height not recorded and height generally less recorded in community hospitals

  9. No obvious “safe” PplatTidal volume reduction lowers mortality at every Pplat Patients with Ppl<30 on 12/kg Hager, etal AJRCCM 2005 Quartile of Pplat

  10. Hypoxemia associated with increased mortality but is a rare cause of death • < 10% of ALI deaths • Montgomery AB, et al. ARRD 1985; 146:486-9 • Estenssorro E, et al. CCM 2002; 30:2450-56 • Stapleton RD, et al. Chest 2005; 128:525-32

  11. How harmful is hypoxemia? • Unclear • Rare cause of death in ALI • Associated with some cognitive abnormalities in 1 study Your pO2 here is ??

  12. How harmful is hypoxemia? • Unclear • Rare cause of death in ALI • Associated with some cognitive abnormalities in 1 study Your pO2 here is 47

  13. Refractory hypoxemia therapyConclusions • Refractory hypoxemia is never missed • None of the treatments that improve oxygenation have been shown to affect mortality • Deaths from hypoxemia are very rare – and side effects of hypoxemia unclear • While cool - some have harmful side effects • There is no evidence that one is better than others – have several in your bag of tricks

  14. Routine Approaches to Severe Hypoxemia • Rule out readily reversible causes • Mucus plugging/lobar or greater collapse • Pneumothorax • Systemic vasodilators enhancing shunt • Pulmonary embolism • Intra-cardiac R > L shunt • Circulatory collapse (low SvO2) • Positive end-expiratory pressure (PEEP) • Diuresis • Permissive hypoxemia

  15. Routine Approaches to Severe Hypoxemia • What about transfusion? • DO2 directly proportional to Hgb • Unfortunately, transfused blood is not ‘normal’ • Transfusion from Hgb 7-9 to > 10 does not clearly improve (and may actually worsen) DO2 • Serum free hemoglobin may worsen VQ • Do not ‘routinely’ transfuse patients above Hgb 7 just because they have severe hypoxemia Crit Care Med. 2004 Feb;32(2):364-71 JAMA. 1993 Jun 16;269(23):3024-9

  16. Experimental Approaches to Refractory Hypoxemia • HFO • Inhaled vasodilators (iNO and prostacyclin) • ECMO • Prone ventilation

  17. How much of an improvement in oxygenation is significant? • Variation in ABG and SaO2 in respiratory cycle • Noise • Tendency to over-interpret 5-10 mm Hg transient differences • I look for 20-30 mm Hg differences • Be prepared to be flexible

  18. Mode of Ventilation • When VT, PEEP, I:E ratio are held constant, PCV does not improve oxygenation or lower plateau pressure (does ‘lower’ peak pressure - but who cares …) • Lessard MR et al. Anesthesiology 1994;80:983-1 • Mang H, et al. AJRCCM 1995; 151:731-6 • Zavala E, et al. Anesthesiology 1998;88:35-42 • When VT and PEEPTOT are held constant, PC-IRV at 2:1 does not improve oxygenation • Mercat A et al. AJRCCM 1997;155:1637-42

  19. PEEPimproves oxygenation but no effect on mortality • ARDSNet ALVEOLI study • Assessment of Low tidal Volume and elevated End-expiratory volume to Obviate Lung Injury • 6 ml/kg PBW tidal volumes • Plateau pressure limit of 30 cm H2O • High PEEP/low FiO2 protocol vs. Low PEEP/high FiO2 • N = 549 patients with ALI/ARDS • Similar findings in LOVES and EXPRESS

  20. Adverse Effects of PEEP • Overdistends recruited lung • Decreased cardiac output • Increased physiologic dead space • Increased shunt fraction and worsen oxygenation • Redirects pulmonary blood flow to atelectatic regions of lung • Increases RAP which can lead to intra-cardiac, right-to-left shunting across a PFO

  21. Paralysis improves oxygenation Crit Care Med. 2004 Jan;32(1):113-9

  22. But … • The reason why is unclear • Anti-inflammatory -  compliance  recruitment •  SvO2 by  VO2 • The effect is highly variable • Paralytics increase risk for delayed neuromuscular complications • Save for rescue - Avoid steroidal (-uronium) • Therapeutic trial - Look for big effect • Monitor train-of-4 titrate to effect Anaesth Intensive Care. 2002 Apr;30(2):192-7.

  23. Clearance of Alveolar Edema • ß - agonists • Inhaled • Intravenous • Lasix plus albumin • Atrial natriuretic peptide

  24. Beta-agonists • Clearance of alveolar edema • Stimulates Na+-K+-ATPase activity • Increases secretion of surfactant from Type II pneumocytes • Anti-inflammatory? • Appealing • No serious side effects • Easy to use • inexpensive

  25. Furosemide Plus Albumin • Martin GS, et al. Crit Care Med 2002;30:2175 • Randomized controlled trial • N = 37 adults with acute lung injury and total protein < 5 g/dL • Treatment (N = 19) • 25 g human serum albumin q8h • Continuous IVI furosemide • Placebo (N = 18) • Placebo + placebo

  26. Furosemide Plus AlbuminImprovement in Gas Exchange Reversal of ARDS Change in PaO2/FiO2 Ratio p = 0.03 p = 0.01 Martin GS, et al. Crit Care Med 2002;30:2175

  27. Recruitment Maneuvers • Designed to open collapsed alveoli and shift the volume-pressure curve up and to the right • Most common methodology • 40 cm H2O CPAP • 40 seconds • Often possible to reverse hypoxemia and completely recruit the lung in early ARDS • 24/26 patients; transient  BP and  PaCO2 • Borges JB, et al. AJRCCM 2006;174:268-78

  28. Recruitment Maneuvers • A decremental PEEP trial can then identify the PEEP level needed to maintain oxygenation after a recruitment maneuver • Girgis K, et al. Respir Care 2006;51:1132-39 • But, RMs are generally not associated with sustained effects in early ARDS • Brower RG, et al. CCM 2003;31:2592-97 • SPO2 was higher 10 minutes after the RM • Highly variable response; not sustained • Oczenski W, et al. Anesthesiology 2004;101:620-5

  29. Prone ventilation –Takes the heart off the lungs Supine Ppl - - - + + + Prone Ppl - Gattinoni L. et al. Intens Care Med 1986; 92:137 +

  30. Prone Positioning • Implications of observations • Less overinflation of non-dependent lung • Less airspace opening/closing of dependent lung • Speculation • Less ventilator-induced lung injury

  31. Effect of prone ventilation can be transient SupineProne  Improving Oxygenation Gattinoni L, et al.N Engl J Med. 2001;345(8):568-73.

  32. Four Clinical Trials Disappointing • Gattinoni L, et al. NEJM 2001 • N = 304 • 6 hours per day x 10 days • Oxygenation (PaO2/FIO2) improved • No difference in survival • Mancebo J, et al. • N = 133 • No difference in survival

  33. Four Clinical Trials Disappointing • Guerin C, et al. JAMA 2004 • N = 791 (AHRF) • 8 hours per day • Oxygenation (PaO2/FIO2) improved • No difference in survival • More complications in prone group • Curley MAQ, et al. ATS 2005 (A294) • N = 102 (pediatric ALI) • 20 hours per day x 7d • No difference in VFD or survival (stopped for futility)

  34. Rationale for HFV-Based Lung Protective Strategies • HFV uses very small tidal volumes • Avoids excessive end-inspiratory lung volumes • Allows for higher end-expiratory lung volumes to achieve better recruitment • HFV uses much higher respiratory rates • Allows for maintenance of normal PaCO2 even with very small tidal volumes

  35. HFV gas transport mechanisms

  36. HFV vs CV: Adults AuthorDevicePatientsDesignMain outcomes (HFV vs CV) Carlon HFJV 300 ARF RCT Lower PeakP, same survival MacIntyre HFJV 58 ARF X-over Lower PeakP, same PO2 Gluck HFJV 90 ARDS X-over Lower PeakP, better PO2 Forte HFO 18 ARDS X-over Same gas exchange Mehta HFO 24 ARDS X-over Better PO2, higher mean Paw

  37. HFO in Adults with Severe ARDS • Appeared to be feasible • Appeared to be the most promising form of HFV • Prospective, controlled trials needed to test efficacy compared to low-stretch conventional ventilation with adequate recruitment

  38. MOAT Survival Curves P = 0.08 Derdak S, et al. AJRCCM 2002;166:801-808

  39. Extra-corporeal Life Support (ECLS) • Extra-corporeal membrane oxygenation (ECMO) • Veno-arterial ECMO (VA-ECMO) • Veno-venous ECMO (VV-ECMO) • Extra-corporeal CO2 Removal (ECCO2R) • IVOX (intra-venous oxygenator)

  40. ECMO - Problems • VA-ECMO has adverse cardiopulmonary effects • Bleeding is excessive • 1.76 - 2 L/day of blood loss

  41. Extracorporeal Life SupportThe University of Michigan Experience • N = 1000 patients as of 1998 • Techniques have evolved from 1979 & 1994 • VV-ECMO is now the standard • Bleeding complications have decreased • UK Multicenter RCT of ECMO completed enrollment at 180 ECMO compared to lung protective ventilation • Inclusion LIS > 3

  42. One Approach to Refractory Hypoxemia • Safety first • Use things in order of • Local experience, cost, and availability • Likelihood of worsening other organ failure or complications • Experimental trials with fixed endpoints • Finally, and most importantly, • If you are routinely using lung protective ventilation targeting tidal volumes of < 6 ml/kg PBW and Pplat<30 and diuresis • Do not feel like your patients are missing state-of-the-art care if you cannot provide (ECMO, iNO, HFO, prone, etc)

  43. Package 1 – ALWAYS Reassess goals of care Reassure self of outcomes of refractory hypoxemia Eliminate reversible causes of hypoxemia PEEP trial (UP? DOWN?) Consider diuresis Massive resusc – consider chest tubes and abdomen

  44. Package 1 – ALWAYS Reassess goals of care Reassure self of outcomes of refractory hypoxemia Eliminate reversible causes of hypoxemia PEEP trial (UP? DOWN?) Consider diuresis Massive resusc – consider chest tubes and abdomen Package 2 – Usually Recruitment maneuver Therapeutic trial of paralysis Prone Violate Pplat criteria for LPV

  45. Package 1 – ALWAYS Reassess goals of care Reassure self of outcomes of refractory hypoxemia Eliminate reversible causes of hypoxemia PEEP trial (UP? DOWN?) Consider diuresis Massive resusc – consider chest tubes and abdomen Package 2 – Usually Recruitment maneuver Therapeutic trial of paralysis Prone Violate Pplat criteria for LPV Package 3 – Rarely iNO or inhaled prostacyclin HFOV

  46. Refractory hypoxemia therapyConclusions • All patients with ALI should be on lung protective ventilation • Refractory hypoxemia is never missed • None of the treatments that improve oxygenation have been shown to affect mortality • Deaths from hypoxemia are very rare – and side effects of hypoxemia unclear (repeat)

  47. Refractory hypoxemia therapyConclusions • While cool – some of the treatments for refractory hypoxemia can be harmful particularly if you use them rarely • Paralysis • Recruitment • Inhaled prostacyclin • Prone • There is no evidence that one is better than others – have several in your bag of tricks

  48. The P’s of refractory hypoxemia • PEEP • Pee (diuresis) • Prone • Paralysis • Pleural evacuation • Prostacyclin (or iNO) • More Peep

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