Systemic Inflammatory
Response and Protective
Ventilation Strategies
Daniel R. Brown, PhD, MD, FCCM
Chair, Division of Critical Care Medicine
Associate Professor
Department of Anesthesiology
Rochester, Minnesota USA
Director, Critical Care Practice
Mayo Clinic
brown.daniel@mayo.edu
Conflict of Interest
• None
• ARDSNet Investigator
Learning Objectives
• Identify ventilator management
strategies associated with improved
outcomes
• Describe the association between
mechanical ventilation and
inflammation
• Discuss strategies to provide optimal
mechanical ventilation
Why be concerned about
perioperative inflammation?
• Dysregulation of inflammation may
have a profound impact on morbidity
and mortality
• An inexact science; genetic factors
likely play a role
• Inflammatory risk from anesthesia
and surgery may be modified
Time, Feb 23, 2004
Dysregulation of inflammation
• Too little inflammation
• Increase susceptibility to infection
• Concerns regarding tissue
remodeling and tissue repair
• Cancer recurrence?
• Too much inflammation
• End-organ dysfunction
• May lead to permanent dysfunction
• Cancer recurrence?
• BALF IL-6
PC 20 cm H2O
VT ~15 mL/kg
J Surg Research 2013; 180: 125-32
Some points to consider...
• Mechanical ventilation in and of itself
may harm people (VILI)
• Many observations in ICU patients
likely apply to OR patients
• Many observations in patients with
acute lung injury may apply to
patients with healthy lungs
Back in the day…
• Supraphysiologic tidal volumes
thought necessary to prevent
hypoxemia
• Bendixen HH et al. NEJM 1963; 269: 991-6
• High airway pressures shown in
animal models to be injurious to lung
parenchyma
Dreyfuss 1985
Balancing Ventilation Priorities
Derecruitment
Consequences:
• Atelectasis
• Hypoxemia
• Hypercapnia
• Inflammation
Overdistention
Consequences:
• VQ mismatch
• Barotrauma
• Alveolar-capillary injury
• Inflammation
Predicted Body Weight
Predicted body weight for men (IBW) = 50 +[2.3x (ht. in inches –60)]
Ht/in
Htcm
IBW
Vt
64
163
59.2
355
65
165
61.5
369
66
168
63.8
383
67
170
66.1
397
68
173
68.4
410
69
175
70.7
424
70
178
73
438
71
180
75.3
452
72
183
77.6
466
73
185
79.9
479
74
188
82.2
493
75
191
84.5
507
70
180
68.5
411
71
183
70.8
425
72
185
73.1
439
Predicted body weight for women (IBW) = 45.5+[2.3x(ht. in inches-60)]
Ht/in
Htcm
IBW
Vt
61
155
47.8
287
62
157
50
301
63
160
52.4
314
64
163
54.7
328
65
165
57
342
66
168
59.3
356
67
170
61.6
370
68
173
63.9
383
69
175
66.2
397
ARDSNET NEJM 2000; 342: 1301-8
Cytokine, Inflammation and Tidal
Volumes
Parsons PE et al. Crit Care Med 2005; 33: 1-6
Talmor D et al. NEJM 2008; 359: 2095-104
•332 ICU patients without lung injury at onset
of mechanical ventilation
•80 developed acute lung injury within 5 days
•Risk factors included tidal volume, blood
product transfusion, acidosis and restrictive
lung disease
Crit Care Med 2004; 32: 1817-24
•Higher myeloperoxidase
implies activation of
polymorphonuclear cells
•Supported by increased BALF
IL-8 concentrations at 5 h
•Higher nucleosome levels
suggest pulmonary apoptotic
cell death
Anesthesiology 2008; 108: 46-54
Things we think we know
about ventilating ICU patients
• Supraphysiologic VT are bad
• Negative end-expiratory
transpulmonary pressure is not good
• Protective ventilation appears to benefit
both healthy and diseased lungs
Villar J et al. Acta Anaesthesiol Scand 2004; 267-71
•3,434 cardiac surgery patients
•Higher tidal volumes were independent
risk factors for organ failure, multiple organ
failure and prolonged ICU stay
•Organ failures were associated with
increased ICU length of stay as well as
hospital and long-term mortality
Anesthesiology 2012; 116: 1072-82
Anesthesiology 2012; 116: 1072-82
•40 elective CABG patients studied postCPB
•10-12 ml/kg + 2-3 cm H2O PEEP
•8 ml/kg + 10 cm H2O PEEP
•Plasma and BAL IL-6 and IL-8 measured
before sternotomy, immediately after
CPB separation and 6 h after mechanical
ventilation
J Thorac Cardiovasc Surg 2005; 130: 378-83
BAL IL-6 and IL-8
J Thorac Cardiovasc Surg 2005; 130: 378-83
Plasma IL-6 and IL-8
J Thorac Cardiovasc Surg 2005; 130: 378-83
•52 esophagectomy patients with protective
strategy during one-lung ventilation
•9 ml/kg during 2 lung ventilation
•9 ml/kg vs. 5 ml/kg during one-lung
ventilation
•Blood IL-1β, IL-6, IL-8 and TNF-α before,
during and 18 hours after surgery
Ventilator Management
During Esophagectomy
• Lower IL-1β, IL-6, and
IL-8 after one-lung
ventilation and 18 h
post-op with lower onelung VT
• No difference in TNF-α
Anesthesiology 2006; 105: 911-9
Ventilator Management
During Esophagectomy
• Higher PaO2/FIO2 during one-lung
ventilation and following surgery in
protective group
• Shorter time to extubation in protective
group (115 vs. 171 min)
• Less extravascular lung water increase
Anesthesiology 2006; 105: 911-9
•32 elective thoracic surgery patients
•VT 10 ml/kg vs. 5 ml/kg during and after OLV
•BAL fluid of ventilated lung 30 minutes after
intubation, after OLV and 2 h postoperatively
•Proinflammatory variables increased in all
patients; increases were less in some cytokines
with smaller OLV VT
Anesth Analg 2005; 101: 957-65
• 400 prospective,
randomized abdominal
surgery patients
• Less major pulmonary
and extrapulmonary
complications
• Shorter ICU LOS
Futier E et al. 2013; 369: 428-37
Data would suggest during
mechanical ventilation in the OR
• Mechanical ventilation contributes to
inflammation
• How a patient is ventilated modifies
the inflammatory response
• Intraoperative mechanical ventilation
strategy impacts postoperative
outcome
Does it make a difference if we
use a volume or pressure
regulated mode?
Lower tidal volumes and plateau
pressures seem to be protective
P Plat 30 23 21 16
Frank JA, et al. AJRCCM 2002; 165: 242-9
Day 1 plateau pressure and
mortality in ARDSNET study
Hager DN, et al. AJRCCM 2005; 172: 1241-4
Should PPlat target be < 30?
• 30 ARDS pts
receiving low 6 mL/kg
IBW
• CT evaluation for
hyperinflation
• Solid circles indicate
hyperinflation
• Cytokines lower and
ventilator-free days
greater in protected
group
Terragni PP, et al. AJRCCM 2007; 175: 160-6
Neonatal Systematic Review
Favors volume over pressure controlled mode
Peng WS et al. doi:10.1136/archdischild-2013-304613
Goals of Ventilator Management
Overdistension Injury
Risk
PEEP
Airway Closure
Risk