Hypoxaemia

What is the limit?

Dr. Koo Chi KwanDirector, Intensive Care

NTWC - Hong Kong

To begin with….

• As anaesthetist and/or intensivist, one of our most important tasks is to maintain normal oxygenation in our patients..

What is normal arterial oxygenation?

• Sp02 90%• Pa02 8 kPa

Are commonly accepted as cut-off points between hypoxaemia and normoxia

What is normal arterial oxygenation?

• Detectable compensatory mechanisms are triggered once the body dips below these set points– Increase cardiac output– Increase minute ventilation

Compensatory mechanism?

• Acute– Cardiac output

• Chronic– Structual changes in cardiovascular system– Hyperventilation – Polycythaemia

What is normal arterial oxygenation?

• In conditions where “ normal “ arterial oxygenation cannot be maintained by all conventional means, what is the lower limit of arterial oxygenation before permanent organ damage sets in?

Lower limit

• How much “ margin” the patient have below 90%?• Any hints or suggestions from science?

Experience in children with cyanotic heart disease

• Sensors were place in 10 children with cyanotic heart disease of median age 5.43 ( range 0.03 – 45) months, median weight 3.74 kg (2.79-15.4)

• Duration of monitor - 27 hours • P02 values were 2.5-8.2 kPa ( median 5.3)• Co-oximeter saturation ranged from 37.1%-90.6% ( medi

an 75.8%)British Journal of Anaesthesia 1997;79:665-7

Experience in children with cyanotic heart disease

• These figures did not tell us how safe these values were.• Though these patients did not have immediate danger,

many had shortened survival.• Cannot be used as reference for limit of hypoxia

Scaling the height

• Scientific study of hypoxaemia

The medical expeditions to Mt. Everest

Alveolar gas sampling at the summit of Mt Everest ( Oct 81)

At the end of a normal inspiration, AMREE team members would expire quickly and deeply through the mouthpiece and hold their breath for a second or so at residual volume. By pulling a lever on the alveolar gas sampler, the valve on the small pre-evacuated aluminum canister would open. Once the sample was collected, the valve could be closed by releasing the lever.

Who is this Guy ?

Pulmonary gas exchange on the summit of Mount Everest

Journal of Applied Physiology, Vol 55, Issue 3 678-687, 1983,

J. B. West, P. H. Hackett, K. H. Maret, J. S. Milledge, R. M. Peters Jr, C. J. Pizzo and R. M.

Winslow

Alveolar gas and estimated arterial blood values on the summit of Mt Everest (8848 m)

Caudwell Xtreme Everest 2007

• It is a large medical expedition to Mount Everest to study the physiology of hypoxaemia that took place in Summer 2007

• The main aim is to measure how individuals’ bodies change as they are exposed to lower and lower levels of oxygen.

Caudwell Xtreme Everest 2007

• The expectation is that there will be a difference between those that adapt well, and those that adapt poorly. If it can be determined what that difference is, then they can start to look at treatments that can help poor adaptors use oxygen more efficiently.

• This may have implications in intensive care unit to improve survival rates in patients.

Caudwell Xtreme Everest

• The Caudwell Xtreme Everest team climbed from the south, via the South East Ridge, setting up laboratories at Base Camp (5300m), in the Western Cwm (6400m) and even doing some experiments on the South Col (7950m).

• The climbing team sampled arterial blood on the Balcony at 8400m.

Caudwell Xtreme Everest

• The scientific yield will derive from more than 220 healthy volunteers progressively exposed to hypobaric hypoxia whilst trekking to Everest Base Camp

Base Camp(5300)

Exercise test at Base Camp (5,300m)

Muscle Biospy at Base Camp

Camp 2 – Erecting Drash Lab

Camp 2 (6400m)

Arterial blood sampling

Microcirculation test at Camp 2

South Col Lab ( 8000m)

Challenging the height – Mt Everest

• Above 8000m, it is called the Death Zone• In the “Death Zone", no human body can acclimatize.

The body uses up its store of oxygen faster than it can be replenished.

• An extended stay in the zone without supplementary oxygen will result in deterioration of body functions, loss of consciousness and, ultimately, death

• The mortality rate of climbing Mt Everest over the last 56

years is 9%

Death Zone

Summit

Summit

Blood Gas at 8400m

Arterial blood gas in the death zone

What can we learn?

• Dramatic “ depth “ of hypoxaemia have been reached in these settings

• They are possible because “time” has been allowed for various compensatory process (Acclimatization)– Respiratory– Cardiovascular – Haematological

Physiology of hypoxaemia

• Adaptive responses to sub-lethal hypoxia are believed to enhance tissue tolerance during subsequent stress

• Mechanism includes increase expression of – Heme-oxygenase ( HO)-1– Heat-shock protein (HSP)– Growth factors : vascular endothelial factor,

erythroprotein• Hypoxic pre-conditioning

Hypoxia inducible factors ( HIF)

Prolyl-4-hydroxylases( PHDs) serves as oxygen sensors and under normoxic conditions promote degradation of HIF-1a following binding with ubiquitin ligase, Von-Hippel-Lindau protein ( VHL)

Physiology of hypoxaemia

• Potential therapeutic interventions:– PHDs( Prolyl hydroxylase domain enzyme) inhibition

by induction of cellular hypoxia, eg. Carbon monoxide admixture to ambient air

– Chemical inhibitions of PHDs, e.g.CoCl2, Mimosine– Molecular biology techniques, e.g. Von-Hippel-Lindau

knockout

What is the implication to daily clinical practice?

• But in our day-to-day practice, many of our patients suffer from hypoxaemia acutely without any time for adaptation..or pre-conditioning..

What is the implication to daily clinical practice?

• What if severe hypoxaemia occurs acutely for the first time?– As in many day-to-day clinical scenario; one lung

ventilation, airway surgery, ARDS

A patient with severe hypoxaemia

• Ms LYC, F/39, Lives with family• Merchandiser, frequent travel to Shenzhen• Good past health, nonsmoker• Presented to A&E with shortness of breath and admitted

to ICU for respiratory failure• History: URI symptoms and fever for one week without i

mprovement after being given steroid and theophylline by General Practitioner

A patient with severe hypoxaemia

• Found to have severe desaturation in A&E ( SaO2 50% despite high flow O2 )and was intubated. Remained hypoxemic despite mechanical ventilation with FiO2 1.0

• Started on: tamiflu, rocephin, azithromycin

A patient with severe hypoxaemia

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VV-ECMO establishedLowest recorded Sp02 – 49%Highest – 72 %

A patient with severe hypoxaemia

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Lowest recorded PaO2 – 2.9 kPa

Highest – 8.06 kPa

A patient with severe hypoxaemia

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The first 3 Chest X-Ray

On admission2 hours later

4 hours later

A patient with severe hypoxaemia

• Started on Venous-venous Extracorporal Membranous Oxygenation (VV-ECMO) about 12 hours after hospital admission

• Oxygenation improved immediately after ECMO

The Chest X-Ray while on ECMO

Immediately after ECMO

2 days after ECMO6 days after ECMO

Weaning off ECMO

8 days post ECMO

off ECMO 10 days after admission Extubated 11 days

after admission

A patient with severe hypoxaemia

• On ECMO for 9 days• Extubated the next day after ECMO was off

Recovery

4 days after extubation On discharged from hospital

A patient with severe hypoxaemia

Sequelae• Noted occasional disorientation & irrelevant speech 4

days after extubation• Psychiatric assessment → ?organic psychosis, ?

tamiflu psychosis• CT Brain - bilateral frontal hypo-densities • EEG - Fair amount of general slow wave over frontal

area.• CSF - clear & colorless, Gram Stain & AFB smear -ve, • WBC 2, RBC 55, Prot/Glu normal

A patient with severe hypoxaemia

SequelaeMRI (D21 since initial admission, D9 after extubation) : • Widespread haemorrhagic signals in the white matters

of bilateral cerebral hemispheres, pons and cerebellum. The haemorrhagic changes are most severe at the corpus callosum.

• Small subacute haemorrhages at the subcortical white matters of both frontal lobes with perifocal oedema.

A patient with severe hypoxaemia

Sequelae• Clinical Psychology (D22 after initial admission, D10

after extubation)– Patient's attention, verbal fluency, visua-spatial

functions, verbal and visual memory, set-shifting and inhibitory control were all impaired to different levels

A patient with severe hypoxaemia

Sequelae• Patient seen on D25 after admission. She has no

memory of being in ICU• She was discharged home on D35. The MMSE on

discharged was 27/30

Conclusions:

• Survival with reasonable cerebral function has been documented in subjects with Pa02 of– 2.51 kPa at Mt Everest – 2.9 kPa in our patient with pneumonia

• We are still unsure whether these are the limits of hypoxia ( though they are quite alarming).

• The therapeutic role of HIF( hypoxia-inducible factor) signal enhancement in the management of hypoxia or attenuation of hypoxic injuries remained undefined.