12/18/2012
Intubation/Hyperventilation
Paradox: Implications for
Traumatic Brain Injury
Joshua Gaither, MD, FACEP
Assistant Professor of Emergency Medicine
Daniel Spaite, MD, FACEP
Professor and Distinguished Chair
of Emergency Medicine
Disclosures


We will refer to the EPIC Study
multiple times
Funded by the NIH-NINDS
 1R01NS071049-01A1 (Adults)
 3R01NS071049-S1 (EPIC4Kids)
Objectives
Understand the physiological changes that
occur with hyperventilation
 Recognize “inadvertent ventilatory
inattentiveness”
 Become aware of the impact of hyperventilation
on TBI outcomes
 Understand the shift from focus on ETI as a
procedure to proper post-intubation ventilation
 Be able to prevent the
intubation/hyperventilation paradox

1
12/18/2012
Impact
Leading cause of death / disability
worldwide
 In USA - TBI

 5.3 million Americans or 2% of the population
○ have moderate to severe disability
○ require long term assistance with daily activities
 DIRECT cost
○ 60 billion/year (2000)
Physiology & Pathophysiology

Normal CNS & cardiac physiology

Cardiac changes after hyperventilation

Vascular changes after hyperventilation

Cellular changes after hyperventilation
Normal Physiology
Global CNS Perfusion
CPP = MAP – (ICP or JVP)
CNS Perfusion
Vaso-dilation
Hypovent or
CO2/H+  vasodilation 
Perfusion
Vaso-constriction
Hypervent or
CO2/H+  vasoconstriction
Perfusion
2
12/18/2012
Pathophys: 1° Brain Injury

Tissue Damage
 Occurs at the moment of impact
 Essentially irreversible

No known treatments, many attempted:
 Beta-hydroxybutyrate
 Hypothermia
 Etc.
Pathophys: 2° Brain Injury

Tissue Damage
 Occurs after the initial trauma
 Possibly reversible
 Often preventable

Result of cellular hypoxia
 Systemic hypoxia
 Systemic hypoperfusion
○ Blood loss, spinal shock, etc.
 Local hypoperfusion:
○ High ICP or JVP
○ Changes in local CNS perfusion
The Historical Ironies:
It’s ALL About Cerebral Blood Flow
Irony #1:
 Decreasing ICP by “keeping them dry” does so by decreasing cerebral blood flow
 Irony #2:  Decreasing ICP by hyperventilating does do by decreasing cerebral blood flow


Net effect: You feel good about lowering ICP… but you’ve done so by causing CNS ischemia
3
12/18/2012
The Historical Ironies:
All About CBF

Irony #1: Decreasing ICP by “keeping them dry”
does so by decreasing cerebral blood flow
 Dry = Low Central Venous Pressure (preload)

Pathophysiology: hyperventilation/PPV
 Increase interthorasic pressure
Preload
MAP
CPP



The Historical Ironies:
ALL About CBF

Irony #2: Hyperventilation decreases ICP by
decreasing cerebral blood flow!!!

CO2

Vasoconstriction

Cerebral Blood Flow
CPP = MAP –
ICP
CNS Vasoconstriction

How could something that decreases ICP cause
an increase in mortality
Hypervent 
CO2/ H+ 
Vasoconstriction 
Perfusion

But that’s not All
4
12/18/2012
Hypocarbia Damages Cells


Ca++ influx into cells  depolarization  release
of glutamate  initiation of apoptosis
CO2 or
pH
 increase cell membrane
permeability  protein shifts
 loss of membrane
potential, mitochondrial
rupture.
 left shift of the oxygenhemoglobin  local
hypoxia
What does hyperventilation after ETI do?
From Pathophysiology
to Patient Outcomes

Moderate hyperventilation:
 OR of mortality when arrival pCO2 <30
 1.8 (CI: 1.1-3.0)

More severe hyperventilation = greater mortality
 Patients with severe hyperventilation had a higher
mortality rate 56% vs 30% (OR 2.9, CI 1.3-6.6)
 One study showed a six‐fold increase
5
12/18/2012
Why is Hyperventilation So Bad??
 How could something that decreases
ICP cause a six‐fold increase in mortality?
 The decreased ICP occurs because of
profound cerebral vasoconstriction
 All advantages gained from lower ICP are overwhelmed by the CNS ischemia And Now…on to the Fistfight
 Our opinion:  Much of the EMS intubation controversy has been fought on an overly‐simple
battleground. Controversy: Should TBI Patients
Be Intubated… At All?

Numerous studies:
 Poorer outcomes in TBI patients intubated in the
field

Severity-adjusted outcomes (field vs. ED ETI)
 Death: aOR 3.99
 Poor neuro outcome: aOR 1.61
 Moderate/severe functional impairment: aOR
1.92
Wang, Peitzman, Cassidy: Ann Emerg Med 2004.
6
12/18/2012
Should TBI Patients Be
Intubated… At All?

San Diego RSI Trial
 Field ETI vs. non-intubated EMS controls
 Risk of death: 33.0% vs. 24.2% (RI = 36.4%)
 Trial was terminated early by the DSMB due
to increased mortality with RSI
Davis, Hoyt, Ochs: J Trauma; 2003
Should TBI Patients Be
Intubated… At All?
 So…is
prehospital ETI bad for TBI
patients?
 Many experts believe ETI should be
delayed until arrival at the ED
ETI is Bad???

Studies showing worse outcomes with ETI











Stiell: CMAJ 2008;178:1141-52
Davis: J Trauma 2003;54:444-53
Davis: J Trauma 2005;58:933-9
Davis: J Trauma 2005;59:486-90
Denninghoff: West J Emerg Med 2008;9:184-9
Murray: J Trauma 2000;49:1065-70
Wang: Ann Emerg Med 2004;44:439-50
Wang: Prehosp Emerg Care 2006;10:261-71
Eckstein: Ann Emerg Med 2005;45:504-9
Bochicchio: J Trauma 2003;54:307-11
Arbabi: J Trauma 2004;56:1029-32
7
12/18/2012
But….Wait a Minute!!!
 Studies
showing better outcomes with ETI
 Winchell: Arch Surg 1997;132:592-7
 Klemen: Acta Anaesthesiol Scand 2006;50:1250-4
 Warner: Trauma 2007;9:283-89
 Davis: Resuscitation 2007;73:354-61
 Davis: Ann Emerg Med 2005;46:115-22
 Bulger: J Trauma 2005;58:718-23
 Bernard: Ann Surg 2010;252:959-965
So…Should TBI Patients Be
Intubated in the Field???
 The
question isn’t nearly that simple!!!
 Focusing solely on the procedure
ignores an incredibly important factor
Should TBI Patients Be
Intubated… At All?
Randomized: PM RSI Vs. ED intubation
 Meticulous ETCO2 management post‐ETI
 Favorable Neuro Outcome (GOS‐E 5–8)

 PM RSI: 51% (80/157)  ED ETI: 39% (56/142 )
 aOR 1.28
Bernard, Nguyen, Cameron. Ann Surg; 2010
8
12/18/2012
So…Why the Dramatic Differences
in the Studies???

The “Intubation-Hyperventilation Paradox”
 If done well, intubation has the potential to:
-Protect the airway
-Provide good ventilation and oxygenation
 Ironically…it also makes it much easier to:
-Over-ventilate
-Hyper-ventilate
Gaither, Spaite, Bobrow: Ann Emerg Med; 2012
Three Major Problems
With Manual Ventilation
1.
Hyperventilation:
-Bagging faster than one breath every six
seconds (10 bpm)
-Even moderate hyperventilation kills brain
cells and causes major, debilitating morbidity
or death
-Davis: ETCO2 increments of 3 mmHg <32
Three Major Problems
With Manual Ventilation
2.
Over-ventilation: Squeezing the bag too
hard/too aggressively/too deeply 
-High airway pressure 
-Increased JVP and ICP
-Decreases venous return 
-Cardiac output/Cerebral perfusion
-Alveolar damage  ARDS
9
12/18/2012
Three Major Problems
With Manual Ventilation
3.
Inadvertent Ventilatory Inattentiveness:
-A recent landmark discovery:
-Every healthcare provider has this
neuro-psychiatric disorder
Inadvertent Ventilatory
Inattentiveness (IVI)

The syndrome: During manual ventilation…
without meticulous prevention…everyone
inevitably gets distracted and hyper/overventilates.
 Studies: Typical rate: 24-40+ bpm
-Our epi level is higher than the patient’s
Inadvertent Ventilatory
Inattentiveness (IVI)

We cannot “wing it”
 Without adjuncts…everyone manually
ventilates…wrong
-Even anesthesiologists and RTs
 Three things are unavoidable:
-Death, Taxes…and IVI
 A recent hospital example:
-“Hey…pay attention…get bagging!!!!”
10
12/18/2012
Inadvertent Ventilatory
Inattentiveness (IVI)

The Cure: Meticulous, multifaceted,
active, adjuncts to prevent hyper- and
over-ventilation
 Cadence devices  RR = 10
 Pressure-controlled bags
 ETCO2 monitoring
 The “V-EMT”
EPIC Study’s Plan to Prevent IVI:
The “Ventilator EMT”
 The
V-EMT: Assigned to manual ventilation
 The most important person on the team!!
-Equivalent to the “Compressor” in MICR
EPIC’s Plan to Prevent IVI:
The “Ventilator EMT”
 The
V-EMT’s job:
 Maniacal about ventilatory rate/depth
 Meticulously uses ventilatory adjuncts
 Should not be disturbed
 If available, add a “spotter”
-Someone to watch the “watcher”
-That’s how important this is!!!
11
12/18/2012
Adjuncts for Preventing
Hyperventilation
 Until
patient on a ventilator (EMS/hospital):
 Cadence Device
-Timed flashing light
-10 bpm/20-peds <15
-1 sec breath
Adjuncts for Preventing
Hyperventilation
 Until
patient on a ventilator:
 Pressure-controlled bag
-Helps prevent hyper and over-ventilation
Adjuncts for Preventing
Hyperventilation

Continuous ETCO2 monitoring


Target: 40 mmHg
Range: 35-45 mmHg
12
12/18/2012
Optimal Ventilation for TBI
 Best:
- Initial cadence device/PC bag followed by…
- ETCO2 monitoring to modulate ventilation rate
asap followed by…
- Mechanical ventilator asap @ 7cc/kg (not 10)
 Next Best:
- Cadence device/PC bag
- ETCO2 monitoring
 Barely acceptable: CD/PCB
Ventilation for TBI
 NOT ACCEPTABLE:
- Manual ventilation without a cadence
device and PC bag
- Unfortunately, most agencies that
intubate have neither of these devices
Beware: ETCO2 That ISN’T!!!
 Early
findings in EPIC Study:
 Many systems with ETCO2 monitoring simply use
them to confirm tube placement…and then nicely
document that they are inadvertently
hyperventilating!!!
 Termed: “ETCO2 monitoring that isn’t”!!!
 If you have ETCO2 monitoring…use it…check
it…QI it…report it…ask about it…demand to see
the waveforms…be maniacal.
13
12/18/2012
Beware: ETCO2 That ISN’T!!!
 Early
findings in EPIC Study:
 Don’t let ETCO2 monitoring be a tool that
simply documents you’re killing TBI
patients!!!
SUMMARY

Because of the universal syndrome of
IVI…intubation with unaided manual ventilation
is always harmful!!!
 Prehospital and in-hospital
ETI/ventilation as we often do it gives worse
outcomes than BLS
 With ventilation adjuncts and meticulous
attention to preventing hyper- and overventilation…ETI may improve TBI outcomes in
the setting of a busy EMS system, active
medical direction, and high success rates

Take Home Messages
The days when it was acceptable to intubate TBI
patients without the adjuncts that prevent
hyper/over-ventilation are gone!!!
 ETI without meticulously-controlled postintubation ventilation is a downgrade from BLS
care.
 Many systems with ETCO2 monitoring simply
use them to confirm tube placement…and then
document that they’re inadvertently
hyperventilating!!!
 If your system doesn’t have at least CDs/PCBs,
you should not be intubating TBI patients.

14
12/18/2012
Special thanks to
the EPIC Partners
www.EPIC.Arizona.edu
Historical Perspective:
All About ICP
(josh…exactly redundant with slide #9)

Hyperventilation:
 Significantly decreases ICP…so…we thought it
MUST be good for TBI patients
15