Traditional One-Lung Ventilation & ALI;Have we been killing our Patients?

Philip M. Hartigan, MDBrigham & Women’s Hospital

Harvard Medical School

Case Report:

• 54 y/o male• Smoking History• COPD• Persistent cough

• CXR - Large RUL mass• Cytology = NSCCA• Metastatic w/u Negative• Scheduled for a Right

Pneumonectomy

Case Report:

CASE REPORT:

General Anesthetic:• Thoracic Epidural• A-Line• TIVA• L-DLT

• VT =10 ml/kg• PEEP = O

CASE REPORT:

Hospital Course – POD # 2:

Dyspnea Hypoxemia Pulmonary Edema

CASE REPORT:

Hospital Course (cont.):

Respiratory Failure Reintubation

PCWP < 16 cmH2O Diuretics Fluid Restriction

ARDS MSOF Death

What Just Happened ?

“Traditional” OLV “Protective” OLVVT = 10 ml/kg VT = 6 ml/kgPEEP = 0 PEEP = 5 cmH2O

Impact: Incidence: 2 - 9%

Mortality: 35 – 72%

“ALI/ARDS is emerging as the most prominent cause of perioperative mortality following pulmonary resection as other complications have become better controlled”

Peter Slinger 2006

Known Causes of ALI / ARDS:

InfectionAspirationBPFCardiac FailurePulmonary Embolic eventsTRALIOther (pancreatitis, trauma, CPB…)

Post-Pneumonectomy Pulmonary Edema

ALI following Pulmonary Resection

Primary ALI following Thoracic Surgery

Idiopathic ALI following Pulm Resection

Nomenclature

Hypothesis:

“Traditional OLV Causes ALI “ Extrapolated Evidence Retrospective Studies Animal Studies Clinical Studies

Extrapolated Evidence:

ARDS Literature:Reduced ARDS Mortality with Protective Ventilation

VILI Literature:VolutraumaAtelectraumaInflammatory Response

AlveolarSystemic

“The finding of small changes in cytokine concentrations is in no way indicative of a causal link with outcome”

Dreyfuss Didier, 2003

Hypothesis:

“Traditional OLV Causes ALI “ Extrapolated Evidence – (Weak) Retrospective Studies Animal Studies Clinical Studies

Retrospective Studies;Factors Associated w/ ALI:

High Perioperative Fluid Balance Extent of Surgery Side of Surgery (R > L) Duration of Surgery Alcoholism / Chemotherapy Increased Vent Pressures/Volumes

Retrospective Studies:

Van der Werff ‘97 190 Pts PIPs > 40 assoc.w/ Pulm Edema

Licker ‘03 879 Pts Ventilatory Hyperpressure

Index

Fernandez - 170 Pts VT assoc with-Perez ‘06 Resp Failure

8.3 vs 6.7 ml/kg

Risk Factors for Primary ALILicker, et al: Anesth Analg 2003;97:1558

Pneumonectomy

Excessive Fluid

Alcoholism

Ventilatory Hyperpressure Index

Risk Factors for Primary ALILicker, et al: Anesth Analg 2003;97:1558

Pneumonectomy

Excessive Fluid

Alcoholism

Ventilatory Hyperpressure Index(P-Plateau > 10 cmH20 x Duration OLV)

Hypothesis:

“Traditional OLV Causes ALI “ Extrapolated Evidence - (weak) Retrospective Studies – (weak) Animal Studies Clinical Studies

Animal Studies:

De Abreu , et al. Anesth Analg 2003

Control – 2LV @ 8 mlPEEP = 2

Protect - OLV @ 4 mlPEEP = 2

Tradit’l – OLV @ 8 mlPEEP = 0

OLV in the Rabbit Lung ModelDe Abreu, et al. Anesth Analg 2003; 96:220

PIP MPAP

TXB2WG

2-LV (CTRL) Protect OLV Traditional OLV

Hypothesis:

“Traditional OLV Causes ALI “ Extrapolated Evidence – (weak) Retrospective Studies – (weak) Animal Studies – (suggestive) Clinical Studies

Clinical Studies:

• Schilling, et al 2005• Schilling, et al 2007• Schilling, et al 2011

Traditional vs Protective OLV:

Proinflammatory CytokinesInhalational Agents are protective

Schilling T, et al. Anesth Analg 2005;101:957Protective OLV and Inflammatory Mediators

Design:32 Pts for thoracotomyOLV @ 5 vs 10 ml/kgPEEP = 0 BAL at 3 time points

Findings:Traditional OLV was associated with:

Proinflammatory cytokinesAntiinflammatory cytokines

I

IL-8 TNF-a

sICAM IL-10

VT = 10 ml/kg VT = 5 ml/kg Schilling ‘05

Schilling T, et al. Anesthesiology 2011;115:65

Effect of Volatile Anesthetics on Systemic and Alveolar Inflammatory Response

Design:63 Pts for thoracotomy

21 – Propofol (4mg/kg/hr)21 – Desflurane (1 MAC)21 – Sevoflurane (1 MAC)

OLV @ 7 ml/kgPEEP = 5 BAL before & after OLV

Findings:Desfl & Sevo attenuate proinflammatory changes evenwith protective OLV compared to Propofol.

III

Hypothesis:

“Traditional OLV Causes ALI “ Extrapolated Evidence – (weak) Retrospective Studies – (weak) Animal Studies – (suggestive) Clinical Studies – (suggestive)

Death

OLV

InflammatoryResponse

ALI / ARDS

Death

Unbalance DrainageChemo / XRTExtent of SurgeryDuration of SurgAlcoholismGeneticUnrecognized:InfectionAspirationEmboliTRALICardiac

PneumonectomyImpaired LymphaticsExcessive Fluids

OLV

InflammatoryResponse

ALI / ARDS

Death

Unbalance DrainageChemo / XRTExtent of SurgeryDuration of SurgAlcoholismGeneticUnrecognized:InfectionAspirationEmboliTRALICardiac

PneumonectomyImpaired LymphaticsExcessive Fluids

Low VTPEEPSevofluraneDesflurane

Low FiO2

OLV

InflammatoryResponse

ALI / ARDS

CO2

Injury

The Balancing Act of OLV

O2

Schilling T, et al. Br J Anaesth 2007;99:368

OLV & Inflammatory Mediators:Propofol vs Desflurane

Design:30 Pts for thoracotomy

15 – Propofol (4mg/kg/hr)15 – Desflurane (1 MAC)

OLV @ 10 ml/kgPEEP = 0 BAL at 3 time points

Findings:Desflurane attenuates the proinflammatory changesof non-protective OLV

II

TNF-aIL-8

IL-10 sICAM-1

Propofol Desflurane Schilling ‘07

Postulated Causes

VILI from “Traditional” OLV Oxygen Toxicity Hyperperfusion Stress Injury Inflammatory Response to Surgery Postoperative Hyperexpansion Unrecognized, Known Etiologies

Known Causes of ALI / ARDS:

InfectionAspirationBPFCardiac FailurePulmonary Embolic eventsTRALIVILIOther (pancreatitis, trauma, CPB…)

Factors Associated with ALI High Perioperative Fluid Balance Extent of Surgery Side of Surgery (R > L) Duration of Surgery Alcoholism / Chemotherapy

Idiopathic ALI following Pulm Resection

2-9% following pneumonectomy

35 – 50% Mortality

Clinical / Histology resembles ALI/ARDS

Low PCWP, high alveolar protein

Diagnosis of Exclusion

Acute Lung Injury• Bilateral Pulmonary Infiltrates• PCWP < 18 mmHg• PaO2/FiO2 < 300 mmHg

ARDS• PaO2/FiO2 < 200 mmHg

Definitions: ALI & ARDS

Hypothesis:

“Traditional OLV Causes ALI “ Extrapolated Evidence Retrospective Studies Animal Studies Clinical Studies

OLV

Mech StressInjury

ALI

ARDS

DEATH

InflammMediators

Perspective

Does Traditional OLV Cause ALI ?

Potential contributing factorTheoretical riskNot currently strongly supported by evidence

Recommendations:

Initial VT = 5-6 ml/kgPEEP = 5