By Brent ArdaughResearchers from the

Harvard-MIT Division ofHealth Sciences and Tech-nology (HST) may soon havethousands of critical care pa-tients breathing easier. In theSeptember 12, 2007 issue ofPLoS ONE, an open-accessjournal from the Public Li-brary of Science, Dr. Chi-Sang Poon and his

colleagues at HST an-nounced a safer, more cost-effective approach to deliverbreaths to patients on venti-lators.

Patients with severe headtrauma, multiple broken ribs,or even a prolonged surgicalrecovery time are not alwayscapable of breathing on theirown. Therefore, cliniciansoften apply machines calledventilators to help patientsmove air in and out of theirlungs more effectively in aprocess called mechanical

ventilation.By supplementing me-

chanical ventilation withnonassociative learning, HSTresearchers can better syn-chronize the natural breath-ing rhythm of a patient withthe rhythm of a ventilator, aphenomenon called respira-tory entrainment.

Nonassociative learning isthe natural ability of thehuman body to adapt to a sin-gle, recurring stimulus. Forexample, when you unexpect-edly become startled by loud

fireworks on July 4th, yourbody has natural ways oflearning more about the char-acteristics of the fireworks.The loud booms recurringthroughout the day serve as atype of stimulus that promptsyour body to respond. Thesame idea applies to mechan-ical ventilation, where nonas-sociative learning enablescritical care patients tobreathe in a more natural, ef-ficient way.

Photo courtesy of Cleveland ClinicAn example of a critical care patient on a mechanical ventilator.

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“It is a new way of deliver-ing artificial ventilation thatexploits the patient's innateability to adapt one's sponta-neous respiratory rhythm tothe ventilator rhythm,” said Dr.Poon, a Principal Research Sci-entist at HST. “This allows saferand more cost-effective me-chanical ventilation and couldobviate the need for sedationand paralysis.”

Currently, the well-being ofa patient almost entirely de-pends on the ventilator’s set-tings and the patient’smoment-to-moment responseto the machine. If the breath-ing rhythm of the patient is notsynchronized with the ventila-tor rhythm, clinicians may in-duce sedation or paralysis.Otherwise, a patient’s bodycan fight the ventilator-deliv-ered breaths and cause severelung injuries. Although certainpatient-triggered ventilatorsare common in most hospitals,they are not always beneficialfor newborn babies or long-term patients because of theirability to trigger at unwantedtimes.

In the study, Poon and hiscolleagues use two types ofnonassociative learning calledhabituation and desensitiza-tion to promote a better pa-tient-ventilator interaction.Habituation refers to a person’sdecrease in responsiveness toa repeated stimulus. In termsof the fireworks example, youmay learn to successfully“block out” or become moreaccustomed to the loud, recur-ring noises over time. On theother hand, desensitization isa person’s diminished re-sponse to a second stimulus asa result of the first stimulus.For instance, if you becamemore accustomed to the loudfireworks through repeatedsounds, your ability to hearother noises might have de-creased, too.

Your vagus nerves, string-like bundles of sensory fibers,help let you know when yourlungs are full by responding tostretch receptors inside yourlungs. When you inhale, theexpansion of your lungs acti-vates these stretch receptors,which send electrical signalsvia the vagus nerves to yourbrain. This phenomenon,

called the Hering-Breuer re-flex, is important because itprevents over-inflation of yourlungs by letting you knowwhen to stop inhaling and startexhaling.

Most current mechanicalventilators can induce extrapressure (Positive End Expira-tory Pressure or PEEP) in thelungs of certain patients topromote better conditions forgas exchange. For example,PEEP commonly assists pa-tients who suffer from AcuteRespiratory Distress Syndromeby preventing their lungs fromcollapsing. This extra pressureapplied in other cases, how-ever, can activate the Hering-Breuer reflex by sustainingelevated lung volumes.

Poon explained how PEEPcompromises respiratory en-trainment when stating, “Therespiratory rhythm is en-trained to the ventilatorrhythm through feedback viathe vagus nerves that detectthe phasic expansion and re-coil of the lungs. This phasicfeedback signal may bemasked by constant feedbacksignals elicited by sustained el-evation of lung volume due tocontinuous positive airwaypressure that often comes withmechanical ventilation.”

If the electrical signals ofthe vagus nerve become hin-dered by opposing or conflict-

ing signals, the lungs of a pa-tient can remain inflated. A re-lated event takes place whenyou are listening to your fa-vorite song on the radio andstatic interference suddenlyinterrupts. Continuous lunginflation is responsible for pro-ducing the bad static signalthat distorts the vagal signal.When the vagal signal be-comes compromised, a lowerquality patient-ventilator in-teraction occurs because thebreathing rhythm of the pa-tient is no longer synchronizedwith the rhythm of the ventila-tor.

Habituation and desensiti-zation both aid mechanicalventilation by operating as afilter: they can block or maskthe static signal caused by sus-tained lung inflation while al-lowing the vagal signal to pass.Just as when you adjust the tre-ble and bass setting on yourstereo, if you pretend the vagalsignal is the treble (higher fre-quency) and the static signal isthe bass (lower frequency), youcan block certain frequencieswhile permitting others.

“Habituation and desensi-tization are two different formsof nonassociative learning,”said Poon. “They confer the‘differentiator’ or ‘high-pass fil-ter’ function to the respiratorysystem that is important forbuffering the adverse effects of

sustained lung inflation.”Habituation enables the

natural breathing rhythm ofthe patient to adapt to therhythm of the ventilator. Simi-lar to the fireworks example,the patient becomes more ac-customed to a single type ofstimulus: the breaths deliveredby the ventilator. Desensitiza-tion works by combating thestatic signal produced by PEEPand continuous lung inflation.The patient, therefore, be-comes less affected by chang-ing pressures (secondstimulus) as a result of theirability to naturally adapt to theventilator-delivered breaths.Most ventilators currentlyused in hospitals do not incor-porate such a learning capabil-ity.

“Previous mechanical ven-tilator designs do not considerthe possibility of respiratory-ventilator entrainment andthat the patient could ‘learn’ toadapt to changing ventilatorpressures,” said Poon. “Thenew design will make use ofrespiratory-ventilator entrain-ment and let the patient'snonassociative learning to dothe fine-tuning on the fly.”

Chi-Sang Poon, ShawnaMacDonald, and Gang Song allcontributed equally to thestudy and their research wasfunded by the National Insti-tutes of Health.

Photo courtesy of MIT News OfficeChi-Sang Poon, from left, Shawna MacDonald and Gang Song have discovered that nonassociativelearning, a natural capability of the human body, promotes a better patient-ventilator interaction.

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