ARDS ---------------------------------------------------------------------------------------------------------------------- Ventilator Management Nimesh Mehta, MD Pulmonary and Critical Care Salem Pulmonary Associates

AECC vs Berlin AECC def 1994

ARDS Berlin Definition

Ventilator induced lung injury (VILI) in ARDS The goal of ventilatory support in ARDS: “Buy time and Protect lungs” The injured lung is more susceptible to iatrogenic injury as a result of mechanical ventilation Barotrauma - result of excess intrathoracic pressure (pneumothorax, subcut. emphysema, pneumomediastium) Volutrauma - Over-inflation as a result of excess volume Atelectotrauma – repetitive alveolar collapse and recruitment Biotruama – stimulation of inflammatory response resulting from mechanic lung injury giving rise to further cytokine-mediated lung and other organ injury Oxygen toxicity * ATS International consensus conference in intensive care medicine: Ventilator associated lung injury in ARDS. Am J Respir Crit Care Med 1999; 160(18): 2118-24.

Slutsky AS, Lung injury caused by Mechanical Ventilaton Slutsky AS, Lung injury caused by Mechanical Ventilaton. Chest 1999; 116 (Suppl_1):9S-15S.

ARDS Areated Recruitable Non- recruitable

“Open Lung Ventilation” Strategy First described by Amato* Use of PEEP to over come lower inflation point and allowing ventilation at more favorable part of volume pressure relationship Use of low tidal volumes to prevent over-distension of air-spaces and to avoid high-end inspiratory pressures or volumes * Amato MBP, et al. Beneficial effects of the “open lung approach” in ARDS: a prospective randomized study. AJRCCM 1995; 152:1835.

ARMA Trial Low tidal Volume Strategy 861 patients randomized to Vt 10-12 mg/kg ideal body weight and plateau pressure ≤50cmH2O vs Vt 6-8 mg/kg IBW and plateau pressure ≤30cm H2O

ARMA Trial Low tidal Volume Strategy Decreased mortality by 22% NEJM 2000;342:1301-8.

LTVV – More evidence Eisner MD, et al. AJRCCM 2001; 164: 231-236

LTVV – Adherence to protocol Needham et al. BMJ 2012; 344:2124  When adherence to LTVV fell from 100% to 50% or 0%; two year mortality increased by 4% and 8%; respectively Needham et al. AJRCCM 2015; 191:177 Initial TV of 7 mL/kg PBW was associated with 23% increase in ICU mortality when compared to those receiving tidal volume of 6 mL/kg PBW. Later increases in tidal volume by 1 mL/kg PBW also resulted in a 15% increase in mortality.

Optimal “PEEP” Positive end-expiratory pressure should be high enough to shift the end-expiratory pressure above the lower inflection point by 2-3 cm H2O Allows maximal alveolar recruitment Decreases injury by repeated opening and closing of small airways

Low PEEP vs High PEEP ALVEOLI NEJM 2004 LOV JAMA 2008 EXPRESS In hospital Mortality 27.5 vs 25.1 (p=0.47) 40.4 vs 36.4 (p=0.19) 35.4 vs 39.0 (p=0.30) 28 days Mortality --- 32.3 vs 28.4 (p=0.33) 35.4 vs 31.2 (p=0.31) Ventilator free days 14.5 vs 13.8 (p=0.50) 7 vs 3 (p=0.04) Barotrauma 10 vs 11 (p=0.51) 9.1 vs 11.2 6.8 vs 5.8 (p=0.57) Rescue or adjuvant therapy 12 vs 7.8 (p=0.05) 18.7 vs 34.5 (p < 0.01)

PEEP Trials Incremental PEEP Strategy Vs Deremental PEEP Strategy Combination of PEEP and FiO2 level in incremental or decremental fashion with close monitoring of Mechanics: Compliance, Plateau pressure Gas exchange: SpO2, PaO2, PaCo2, P/F ratio Hemodynamics: HR, BP, CO Optimal PEEP by Tidal Compliance C = VT / (Pplat – PEEP) If using fix VT, then titrate PEEP to lowest Pplat – PEEP

Stress Index A tool to monitor tidal recruitment and overdistension. During inspiration with constant flow (with volume cycle mode) Resistance is constent All change in pressure-time curve depends on change in compliance during tidal breath. Pre-requisite Patient sedated and preferably paralysed Constant flow condition Low Vt – volume cycle mode

Stress Index Concave upward Overdistention Concave downward (Decrease PEEP) Concave downward Potential for recruitment (Increase PEEP)

PV curve

PV curve - Limitations Requires sedation/paralysis No easily available No good correlation between different methods Difficult to identify “inflection points” Harris et al, AJRCCM 2000; 161:432 Unable to differentiate chest wall and lung compliance Mergoni et al, AJRCCM 1997; 156:846 Ranieri et al, AJRCCM 1997; 156:1082 Deflation limb may be more useful than inflation limb Holzapfel et al, Crit Care Med 1983;11:561 Hickling, AJRCCM 2001;163:69 Pressure-volume curves of individual lung units not known Hickling, AJRCCM 1998;158:194 No evidence, other than retrospective case reports

Esophageal balloon pressure monitoring Surrogate for pleural pressure

 Titrating applied PEEP to an end­-expiratory transpulmonary pressure (Tp-PEEP) between 0 and 10 cm H2O To reduce cyclic alveolar collapse Maintaining an end­-inspiratory transpulmonary pressure (Tp Plateau) ≤25 cm H2O To reduce alveolar overdistension 61 patients assigned to Adjustment of the FiO2 and applied PEEP to achieve specific end-expiratory transpulmonary pressures Adjustment of the FiO2 and applied PEEP according to a table similar to used in ARMA trial NEJM 2008; 359: 20

Esophageal balloon pressure monitoring Limitations Is it true representation of pleural pressure Supine position Weight of mediastinum Heterogeneity of lung pathology Focal rather than global pleural pressure Malpositioning and changing positions. Single trial to aim to look at only oxygenation Using merely high PEEP has already shown similar results Approximately trans-pulmonary end-inspiratory pressure to 25 cm H2O No evidence base.

Recruitment Maneuvers Hodgson C, et al. Recruitment manoeuvers in ALI. Cochrane Database Sys Rev 2009 7 trials reviewed, total patients = 1170 Fan E, et al. Recruitment maneuvers for ALI: a systematic review. AJRCCM. 2008:178;1156 40 studies, total patients 1185

Recruitment Maneuvers ~ Evidence based ~ Did not differentiate between different RM strategies Improved oxygenation (did not persist) No change in ventilator parameter, except higher PEEP after RM No significant difference on 28th day mortality No statistical difference in risk of barotrauma No significant changes in hemodynamic parameters after an RM. Hypotension (12%) and desaturation (9%) were the most common adverse events Only 1% patients had their RMs terminated prematurely due to adverse events. Current recommendation: to use after brief disconnection of patient from ventilator.

APRV Application of CPAP a relatively high level (Phigh) Time-cycled release phase to lower level of CPAP (Plow) Unrestricted spontaneous breathing is permitted in any phase of respiratory cycle.

APRV- Evidence Based Study Study design Groups Results Rasanen et al. 1991 Prospective Crossover trial 50 pts with ALI/ARDS APRV Vs CMV Lower peak airway pressure Similar oxygenation and hemodynamics Sydow et al. 1994 Randomized controlled trial 18 pts with ALI APRV Vs VC-IRV Better oxygenation Similar hemodynamics Kaplan LF, et al. 2001 12 pts with ALI APRV Vs PC-IRV Lower peak and mean airway pressure Better CO, CVP, Oxygen delivery Lower sedative and NMB Putensen et al. 2001 30 trauma pts with ALI/ARDS APRV Vs PCV High CO Less sedative and NMB Less MV and ICU days Required paralysis in control group for first 3 days Varpula et al. 2004 58 pts with ALI/ARDS APRV Vs SIMV-PS No diff. in term of gas exchange, sedation needs, ventilator free days and mortality Only study after ARDSNet low tidal volume study

Prone Ventilation

Prone Ventilation PROSEVA trial - NEJM 2014 466 patients with severe ARDS undergo prone-positioning sessions of at least 16 hours or to be left in the supine position. Severe ARDS was defined as PF ratio < 150 with FiO2 > 0.6 with PEEP > 5. Supine Group (n = 229) Prone Group (n = 237) Mortality at 28 days 75 38 < 0.001 Mortality at 90 days 94 56 Vent free days at 28 days 10 14 Vent free days at 90 days 43 57

Summary Identify ARDS early Low tidal volume – aim is 6 mL/kg (not 8 mL/kg) Aim to have plateau pressure minimum (not just < 30 cm H2O) with some degree of permissive hypercapnia PEEP titration based on FiO2 Recruitable ARDS vs non Decremental PEEP titration PV curve Recruitment Maneuvers – good only after any circuit disconnection Esophageal balloon – know limitation Rescue therapies: APRV; Prone Ventilation  ECMO

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