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Intubation/Hyperventilation Paradox: Implications for

Traumatic Brain Injury

Joshua Gaither, MD, FACEPAssistant Professor of Emergency Medicine

Daniel Spaite, MD, FACEPProfessor 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 ventilatoryinattentiveness”

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

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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 PerfusionCPP = MAP – (ICP or JVP)

CNS Perfusion

Vaso-dilationHypovent or CO2/H+ vasodilation Perfusion

Vaso-constrictionHypervent or CO2/H+ vasoconstriction Perfusion

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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

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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

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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 oxygen-hemoglobin 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

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Why is Hyperventilation So Bad??

How could something that decreases ICP cause a six‐fold increase in mortality?

The decreased ICP occurs because ofprofound 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‐simplebattleground.  

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.

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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

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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

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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 sixseconds (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

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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…everyoneinevitably gets distracted and hyper/over-ventilates.

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!!!!”

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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!!!

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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

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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 TBINOT ACCEPTABLE:

- Manual ventilation without a cadence device and PC bag

- Unfortunately, most agencies that intubate have neither of these devices

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.

Beware: ETCO2 That ISN’T!!!

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Early findings in EPIC Study: Don’t let ETCO2 monitoring be a tool that

simply documents you’re killing TBI patients!!!

Beware: ETCO2 That ISN’T!!!

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 worseoutcomes than BLS

With ventilation adjuncts and meticulous attention to preventing hyper- and over-ventilation…ETI may improve TBI outcomes in the setting of a busy EMS system, active medical direction, and high success rates

SUMMARY

The days when it was acceptable to intubate TBI patients without the adjuncts that preventhyper/over-ventilation are gone!!!

ETI without meticulously-controlled post-intubation 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.

Take Home Messages

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www.EPIC.Arizona.edu

Special thanks to the EPIC Partners

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