Mechanical ventilation in special situations-ARDS Ashraf Al Tarifi, MD,FCCP Consultant Intensivist and Pulmonologist KFSH&RC-Riyadh Al Khortoum April 19, 2013

Case summary 45 year old male patient admitted with pancreatitis secondary to biliary disease. C/O SOB one day after admission Found to have Pulse oximetry of 70% on RA Placed on NRM –sat improved to 92%

HISTORICAL PERSPECTIVES Described by William Osler in the 1800’s Ashbaugh, Bigelow and Petty, Lancet – 1967 12 patients pathology similar to hyaline membrane disease in neonates

REVISION OF DEFINITIONS 1988: four-point lung injury score Level of PEEP PaO2 / FiO2 ratio Static lung compliance Degree of chest infiltrates 1994: consensus conference simplified the definition

American-European Consensus Conference (AECC) Definition of ARDS Risk factors, 3 criteria are required: Radiological Exclusion Oxygenation Bernard et al. Am J Respir Crit Care Med 1994;149:818-24.

1994-ARDS Definition (American European consensus) ARDS defined as Acute onset bilateral infiltrates PaO2:FiO2 < 200 No evidence Left heart failure Pcwp < 18 Clinical features Refractory hypoxemia Reduced compliance

The Berlin Definition of ARDS May 2012 Timing Within 1 week of a known clinical insult or new or worsening respiratory symptoms Chest imaging Bilateral opacities—not fully explained by effusions, lobar/lung collapse, or nodules Origin of edema Respiratory failure not fully explained by cardiac failure or fluid overload. Need objective assessment (eg, echocardiography) to exclude hydrostatic edema if no risk factor present Oxygenation (with PEEP > 5 cm H2O) Mild PaO2/FIO2 200-300 mm Hg Moderate 100- 200 mm Hg Severe <100 mm Hg JAMA. 2012;307(23) Published online May 21, 2012

The Berlin Definition of ARDS- May 2012 Timing Within 1 week of a known clinical insult or new or worsening respiratory symptoms Chest imaging Bilateral opacities—not fully explained by effusions, lobar/lung collapse, or nodules Origin of edema Respiratory failure not fully explained by cardiac failure or fluid overload. Need objective assessment (eg, echocardiography) to exclude hydrostatic edema if no risk factor present Oxygenation (with PEEP > 5 cm H2O) Mild PaO2/FIO2 200-300 mm Hg Moderate 100- 200 mm Hg Severe <100 mm Hg JAMA. 2012;307(23) Published online May 21, 2012

Berlin 2012 Definition of ARDS Mild 22% Moderate 50% Severe 28% ARDS 4% 14% 29%

Case summary 45 year old male patient admitted with pancreatitis secondary to biliary disease. C/O SOB one day after admission Found to have Pulse oximetry of 70% on RA Placed on NRM –sat improved to 92% Patient intubated and ventilated-sat 88%

Pt intubated and mechanically ventilated Initial settings PCV FIO2 100% Tv 550 ml RR 20 PEEP 5 Peak airway pressure 36 Initial ABG PH 7.33 PCO2 40 (5.1 Kpa) PO2 57 (7.2 Kpa) HCO3 20 Saturation 88% What would you do next

Factors Influencing Oxygenation FIO2 Mean Airway pressure Inspiratory Time (I:E ratio) PEEP

Vent settings to improve oxygenation: FIO2 Always start at 100% even if patient was not hypoxemic prior to intubation Patient might have Rt mainstem intubation Pneumothorax secondary to high pressures during bagging Use continuous pulse oximetry if available or check arterial blood gases Once ETT position confirmed and oxygenation stable start weaning FIO2 to keep sat > 92-94%

Permissive Hypoxemia – How Low Can We Accept? 92-96% 88-92% 86-88% 82-86% 78-82% Respir Care. 2010 Nov;55(11):1483-90.

Positive end expiratory pressure -PEEP reduces shunt by recruiting partially collapsed alveoli

PEEP

ARDS -10 10

ARDS after PEEP

Immediately post intubation

PEEP 15

The PEEP Effect (recruit-Derecruit) NEJM 2006;354:1839-1841

Higher Vs lower PEEP in ARDS 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 Average PEEP 8.3 Vs 13.3 No survival benefit The National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. N Engl J Med 2004;351:327-336

How much PEEP is enough? ARDSnet protocol: PEEP - FiO2 Combinations GOAL: PaO2 55-80 mm Hg or SpO2 88-95% Use these FiO2/PEEP combinations to achieve oxygenation goal. FIO2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 PEEP 5 8 10 12 14 16 18 20-24 New Eng J Med. 2000;342(18)1301-1308

So, PEEP titrated to 12 cm H2O Current settings PCV FIO2 100% Tv 550 ml RR 24 PEEP 12 Peak airway pressure 35 ABG PH 7.32 PCO2 48 PO2 75 HCO3 22 Saturation 95% What would you do next

Ventilator-Induced lung injury (VILI) Volutrauma Overdistention Atelectetrauma Repeated recruitment and collapse Bio trauma Inflammatory mediators Barotrauma High-pressure induced lung damage Oxygen toxic effect FiO2 29

The Problem of Heterogeneity in ARDS -10 10

The Problem of Heterogeneity Especially in ARDS Some lung units may be overstretched while others remain collapsed at the same airway pressure. Finding the right balance of TV and PEEP to keep the lung open without generating high pressures is the goal. This presents major difficulty for the clinician, who must apply only a single pressure to ventilate patients

Ventilator-induced Lung Injury (VILI) Collapse Over Distension

Ventilator-Induced Lung Injury Atelectotrauma Vs Volutrauma Atelectrauma: Repetitive alveolar collapse and reopening of the under-recruited alveoli Volutrauma: Over-distension of normally aerated alveoli due to excessive volume delivery Dreyfuss: J Appl Physiol 1992 33

Mechanisms of Airspace Injury Airway Trauma “Stretch” “Shear”

ARDS -10 10

ARDS after PEEP Preventing Atelectotrauma

Ventilator-induced Lung Injury (VILI) Barotrauma Volutrauma Atelectrauma Biotrauma Over Distension Collapse

Baro-trauma Etiology :Directly related to airway pressures/PEEP Incidence 4% - 15% Highest in ARDS Incidence now decreased secondary to lung protective ventilation

Barotrauma-Pathophysiology Some alveoli become more distended than others. Alveolar pressure increases and forms a pressure gradient between the alveoli and adjacent perivascular sheath. Air dissects into the perivascular sheath leading to perivascular interstitial emphysema (PIE) and further moves into areas of least resistance including subcutaneous tissue and tissue planes.

Barotrauma-Complications Pneumothorax Interstitial emphysema Pneumomediastinum-leads to PTX in 42% of patients in one study Pneumopericardium Subcutaneous emphysema Pneumoperitoneum

Gas Extravasation

Barotrauma

Oxygen Toxicity : FIO2 > 60 % for > 24h Absorptive atelectasis O2/N2 = 21/79 >>>>>> 50/50 Oxygen Carbon dioxide Water Vapour Nitrogen

Hyperoxia toxicity: mechanism Free radicals: lipid peroxidations, especially in the cell membranes, inhibit nucleic acids and protein synthesis, and inactivate cellular enzymes. Explosive free radical production leading to swamping of the anti-oxidant enzyme systems and as a result free radicals escape inactivation.

ARDSnet NIH NHLBI ARDS Clinical Trials Network

Lung-Protective Ventilation ARDS Network, 2000: Multicenter, randomized 861 patients Lung-protective ventilation Conventional ventilation Tidal Volume (ml/kg) 6 12 Pplateau <30 <50 PEEP Protocol Actual PEEP 8.1 9.1 Result (p<0.001) 31.0% 39.8% 用的是預期體重 Principle for FiO2 and PEEP Adjustment FiO2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 PEEP 5 5-8 8-10 10 10-14 14 14-18 18-24 NEJM 2000; 342: 1301-1308

Lower Tidal Volume and Pplat < 30 Mortality Before Hospital Discharge 10 20 30 40 50 Mortality (Percent) P=0.0054 ARDS Network NEJM 342: 1301-8, 2000 6 ml/kg 12 ml/kg

NIH ARDS Network Trial Mechanical Ventilation in ARDS 31% mortality 40% mortality

Lung-Protective Ventilation Result: Lower 22% mortality (31% vs 39.8%) Increase ventilator-free days NEJM 2000; 342: 1301-1308

Median # Ventilator-Free Days ARDSnet

Median Organ Failure Free Days NEJM 2000;342:1301-8 P = 0.004 P = 0.004 P = 0.005 = 6 ml/kg = 12 ml/kg

Effect of 45 cmH2O PIP Control 5 min 20 min Malhotra A. N Engl J Med 2007;357:1113-1120

Back to our patient Protective lung strategy applied, so tidal volume was decreased to 420 ml (6ml/kg IBW) (Height-152 )x 0.9 +50 males (Height-152 )x 0.9 +45 females Current settings PCV FIO2 100% RR 32 PEEP PIP 28 ABG pH 7.21 PCO2 65 PO2 71 HCO3 25 Saturation 92% What would you do next

Permissive Hypercapnia Low Vt (6ml/kg) to prevent over-distention Increase respiratory rate to avoid very high level of hypercapnia PaCO2 allowed to rise Usually well tolerated-May be beneficial Potential Problems: tissue acidosis, autonomic dysregulation, CNS effect, and circulatory effects May need to start Bicarb infusion till the kidney starts to compensate (2-3 days)

Permissive Hypercapnia – When would you NOT do it? Renal failure High intracranial pressures Cardiovascular problems/Arrhythmia

Back to our patient What would you do next Protective lung strategy done, so tidal volume was decreased to 420 ml (6ml/kg IBW) (Height-152 )x 0.9 +50 males (Height-152 )x 0.9 +45 females Current settings PCV FIO2 100% RR 32 PEEP 12 PIP 28 ABG pH 7.21 PCO2 65 PO2 57 HCO3 25 Saturation 88% What would you do next

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

Paralysis in Early ARDS Papazian L et al. N Engl J Med 2010;363:1107-1116

Paralysis The reason why is unclear  recruitment  SvO2 by  VO2  compliance Anti-inflammatory The effect is highly variable Paralytics increase risk for delayed neuromuscular complications especially when given with steroids - Monitor train-of-4 titrate to avoid over paralysis Anaesth Intensive Care. 2002 Apr;30(2):192-7.

ARDS Recruitment Maneuvers Application of high airway pressure (35-40cmH2O) for approximately 40 seconds. Most common methodology 40 cm H2O CPAP 40 seconds Employed to open atelectatic alveolar units that occur with ARDS and particularly with any disconnection from ventilator If successful, PaO2 will increase by 20% or more. Must use PEEP after procedure to keep recruited alveoli open.

ARDSnet protocol Vs open lung protocol Tv 6 ml/kg Plateau pressure <30 Conventional PEEP (titrate for FIO2 <0.6) Experimental protocol Tv 6 ml/kg Plateau pressure <40 Recruitment maneuvers High PEEP (10-15) JAMA, February 2008

ARDSnet protocol Vs open lung protocol

ARDSnet protocol Vs open lung protocol JAMA, February 2008

Inhaled Nitric Oxide May be used as “rescue” therapy Most ARDS/ALI patient may have mild to moderate pulmonary HTN Improvement in oxygenation was small and not sustained No change on mortality or duration of mechanical ventilation Increased renal failure May be used as “rescue” therapy

Fluid management in ARDS

Pathogenesis of Pulmonary Edema & ALI/ARDS Alveolar edema fluid flooding Alveolar edema fluid clearance

Low flow by exam or CI <2.5 MAP < 60 Low flow by exam or CI <2.5 Conservative fluid strategy Furosemide UOP < 0.5 ml/kg/h & CVP or PAOP low KIDNEY CVP < 4 PAOP < 8 Favors Dry LUNG

Liberal fluid strategy CI > 4.5 FiO2 > 0.7 LUNG Favors Perfused KIDNEY (organs) CVP 10-14 PAOP 14-18

Ventilator free days to day 28 P=0.0002

ICU free days to day 28 P<0.001 Days

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

Proning May Benefit the Most Seriously ill ARDS Subset Supine 0.5 * p<0.05 Prone * 0.4 0.3 Mortality Rate 0.2 0.1 0.0 > 49 40- 49 31- 40 0 - 31 Quartiles of SAPS II SAPS II

High Frequency Ventilation in ARDS-Harmful Ferguson ND et al. N Engl J Med 2013;368:795-805

Steroids in ARDS To be answered in Debate session

Steroid therapy Increase the number of ventilator-free and shock-free days during the first 28 day Improve oxygenation, compliance and blood pressure No increase in the rate of infectious complications Higher rate of neuromuscular weakness Routine use of steroid is not supported Starting steroid more than 14 days after the onset of ARDS may increase mortality NEJM 2006;354:1671-1684

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

Take home messages Take ARDS seriously-it kills about 60000 patients per year in the US Use lower Tv (6ml/kg IBW) to keep plateau pressure <30 Permissive hypercapnea is safe and well tolerated Use enough PEEP to recruit lungs Keep lungs dry

Use ventilators safely! normal lungs 5 min of 45 cm H2O 20 min of 45 cm H2O Dreyfuss, Am J Respir Crit Care Med 1998;157:294-323