Resuscitation and Oxygenation: Do We Really Know Whats Best

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Resuscitation and Oxygenation Do We Really Know
Whats Best?

• Mike McEvoy, PhD, REMT-P, RN, CCRN
• Clinical Associate Professor of Critical Care
  Medicine
• Albany Medical College, New York
• EMS Coordinator Saratoga County, New York
• EMS Editor Fire Engineering Magazine
• EMS Director New York State Association of Fire
  Chiefs

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Disclosures

• I serve on the speakers bureau for Masimo Corp.
• I have no other financial relationships to
  disclose.
• I am the EMS editor for Fire Engineering
  magazine.
• I do not intend to discuss any unlabeled or
  unapproved uses of drugs or products.

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Mike McEvoy, PhD, RN, CCRN, REMT-P www.mikemcevoy.
com
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Goals for this talk

• Hypoxia
• Hyperoxia
• Oxidative stress
• Theory and research
• Implications
• Practice pearls
• Monitoring
• Standards of Care
• Unanswered questions

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Hypoxia
Mt. Kilimanjaro 5895 m
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Altitude And HypoxiaHecht, AJM 197150703

• Feet_ Meters Baro Press PiO2 PaO2
  SaO2 PaCO2
• 0 0 760
  149 94 97 41
• 5,000 1,500 630 122
  66 92 39
• 8,000 2,400 564 108
  60 89 37
• 10,000 3,000 523 100
  53 85 36
• 12,000 3,600 483 91
  42 83 35
• 15,000 4,600 412 76
  44 75 32
• 18,000 5,500 379 69
  40 71 29
• 20,000 6,100 349 63
  38 65 21
• 24,000 7,300 280 62
  34 50 16
• 29,029 8,848 253 43
  28 40 7.5

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Physics

• Hypobaric hypoxia
• Alveolar gas equation
• PAO2 (PB-PH2O) FiO2 - PaCO2 /R
  (0.003PaO2)
• PAO2 varies proportionally to PB, as it declines
  PaO2declines.

Himalayan Peaks over Kathmandu, Nepal
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Effects of sudden hypoxia(Removal of oxygen mask
at altitude or in a pressure chamber)

• Impaired mental function mean onset at SaO2 64
• No evidence of impairment above 84
• Loss of consciousness at mean saturation of 56
• SOB? (dyspnea)
• Notes
• absence of breathlessness when healthy resting
  subjects are exposed to sudden severe hypoxia
• mean SpO2 of airline passengers in a pressurised
  cabin falls from 97 to 93 (average nadir 88.6)
  with no symptoms and no apparent ill effects

Akero A et al Eur Respir J. 200525725-30
Cottrell JJ et al Aviat Space Environ Med.
199566126-30 Hoffman C, et al. Am J Physiol
1946145685-692
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Normal Oxygen Saturation
Normal range for healthy young adults is
approximately 96-98 (Crapo AJRCCM,
19991601525) Previous literature suggested a
gradual fall with advancing age However, a
recent Salford/SouthendUK audit of 320 stable
adultsaged gt70 found Mean SpO2 96.7 (2SD
range 93.1-100)

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Normal nocturnal SpO2

• Healthy subjects in all age groups routinely
  desaturate to an average nadir of 90.4 during
  the night(SD 3.1)
• (Gries RE et al Chest 1996 110 1489-92)
• Therefore, be cautious in interpreting a single
  oximetry measurement from a sleeping patient.
  Watch the oximeter for a few minutes if in any
  doubt (and the patient is otherwise stable) as
  normal overnight dips are of short duration.

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What happens at 9,000 metres (approximately
29,000 feet)?
It Depends
SUDDEN
ACCLIMATIZATION
Passengers unconscious in lt60 seconds if
depressurized
Everest has been climbed without oxygen
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Deaths at Extreme Altitude

• UIAA Mountain Medicine Study Himalayan peaks
  above 22,960 ft
• All British expeditions to peaks over 7000 m were
  collected from Mountain Magazine 1968 - 1987.
• 535 mountaineers, 23 deaths on 10 of 51 peaks
  visited, 4.3 overall mortality (1 fatality every
  5th expedition).
• Everest - 29,032 ft
• 121 individuals, 11 expeditions, 7 deaths, 5.8
  overall mortality.
• K2 - 28,250 ft
• 28 individuals, 5 expeditions, 3 deaths, 10.7
  overall mortality.

Source UIAA Mountain Medicine Centre, June 1997
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Pete 41
Mike 73
Godlisten 84
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High Altitude

• Physiological challenges of ascent
• Acclimatization
• Ventilatory response to exercise
• Hypoxic Ventilatory Response (HVR)
• When acclimatization fails
• Acute mountain sickness
• High altitude pulmonary edema
• High altitude cerebral edema

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Everest Ascent Its Dangerous Up There
Base Camp 5380 m (17,700)
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Acclimatization

• Process by which people gradually adjust to high
  altitude
• Determines survival and performance at high
  altitude
• Series of physiological changes
• ? O2 delivery
• hypoxic tolerance
• Acclimatization depends on
• severity of the high-altitude hypoxic stress
• rate of onset of the hypoxia
• individuals physiological response to hypoxia

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Ventilatory Acclimatization

• Hypoxic ventilatory response ? VE
• Starts within 1 3 hours of exposure ? 1500m
• Mechanism

Degree of HVR Performance improvement
Ascent to altitude
Hypoxia
Carotid body stimulation
Respiratory center stimulation
Increased ventilation
Improved hypoxia
CO2 H2O  H2CO3  HCO3- H
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Lung Gas Diffusion

• High altitude ? O2 diffusion
• Lower O2 driving pressure (atmospheric air to
  blood)
• Lower Hb affinity for O2 (on the steep portion of
  the O2/Hb curve)
• Inadequate time for equilibration

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O2 Hgb Dissociation Curve
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Consequence ? O2 Saturation
West et al., 1983
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V/Q Mismatch aka Va/Q Heterogeneity

• At rest

• With hypoxia (hypo or normobaric)
• interstitial edema
• V/Q mismatching

O2

• Inhaled air not evenly distributed to alveoli
• Gas composition not uniform throughout lungs
• Different lungs zones have different perfusion
• Differences are less in recumbent position

Hopkins et al., 1997 Pascoe et al., 1981
Seaman et al., 1995 Whitwell and Greet, 1984
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Circular break of the epithelium
Full break of the blood-gas barrier
Leaks?
Costello et al., 1992
West et al., 1995
Red cell moving out of the capillary lumen (c)
into an alveolus (a)
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Why Pulmonary Edema?

• Theories
• Pulmonary Hypertension
• Related, but not causal (Sartori et al. 2002)
• Pulmonary endothelial barrier fragility
• Inflammation
• But which came first? not causal (Schoene et
  al. 1986, 1998 Swenson et al. 2002)
• Stress failure theory
• Most plausible, correlated with other hypoxic
  etiologies
• Purturbation of alveolar fluid clearance
• Contributory, not primary (Dada et al., 2003)

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Stress Failure Theory
And Exercise Induced PE Theory
West et al., Mathieu-Costello, 1998, 1999 Powers
et al. 1998
Alveolar hypoxia
Hypoxic pulmonary vasoconstriction (uneven)
? V/Q mismatch
? capillary pressure (some capillaries)
Damage to capillary wall (stress failure)
EDEMA
Exposed basement membrane
Inflammatory mediators
Seen in about ½ endurance athletes (Powers et
al., 1988)
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AMSAcuteMountainSickness
Trekkers on the Annapurna Circuit
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AMS - Signs Symptoms

• Lake Louise Consensus 1993
• Headache in an unacclimatized individual who
  recently arrived at gt 2500m plus one or more
• n/v, anorexia, insomnia, dizziness or fatigue.
• 1-10h after ascent, remits in 4-8days.
• No diagnostic physical findings except low SpO2.
• (Hackett Roach, 2001, Forwand et al. 1968)

Machhapuchhre, 6993m
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AMS - Signs Symptoms

• Risk factors
• Prior history
• Residence below 900m
• Exertion
• Preexisting cardiopulmonary disorders
• Younger individuals (lt50)
• Men more susceptible to HAPE but not AMS
• Dehydration
• (Hackett Roach, 2001, Basnyat, 1999)

Machhapuchhre, 6993m
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AMSEpidemiology

• Maggiorini et al. 1990 visitors to Swiss
  mountain huts 34
• 2850-3050m 9-13
• 3650m 34
• 4559m 52 (11 with HAPE or HACE)
• Houston. 1985 and Hackett et al. 2001 Colorado
  skiers
• 1850-2800m 12 - 22
• Montgomery et al. 1989 Rocky Mountains
• 2000m 25
• Hackett et al. 1976 Trekkers in Nepal
• 4200m 43-52 AMS

Trekkers on the Annapurna Circuit
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AMS - Pathophysiology
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AMS - Signs Symptoms

• Fitness is NOT protective
• Roach et al. 2000
• Cross-over design, n7, exposed to simulated
  alt.(4800m) x10h.
• Symptom scores of AMS 4.4 ( 1.0) with exercise
  (50 max workload) vs. 1.3 ( 0.4) when
  sedentary.
• Normoxic controls who exercised had no symptoms
  of AMS.
• Sa O2 during exercise 76 vs 81.
• C Does exercise-induced exaggeration of
  hypoxemia worsen AMS?
• (Roach et al, 2000 Hackett Roach, 2001)

Machhapuchhre, 6993m
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AMS - Signs Symptoms

• Is there a way to predict individual
  susceptibility?
• Prior history of AMS/HAPE is most reliable.
• Low HVR too much overlap with the range of
  normal.
• High PAP with exposure to hypoxia or exercise
  poor sensitivity and specificity.
• Avoid by prevention and ascent rates to lt
  300m/day above 2000m in first exposure to
  altitude or susceptible individuals.
• (Bärtsch P et al. 2001)

Machhapuchhre, 6993m
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HAPE - Epidemiology

• Most common fatal manifestation of altitude
  illness
• 1-2 of healthy individuals which ascending over
  4000m
• 150 McKinley climbers succumb (Hackett et al.,
  1990)
• 10 of HAPE-R and 60 of HAPE-S individuals who
  ascend to over 4000m in 24h develop HAPE
• Risk factors
• Strenuous exercise - Absence of pulmonary artery
• Cold - Pulmonary hypertension
• Recent URI - Reentry
• Prior HAPE
• (Bärtsch et at. 1991)

On the way to Thorung La 5000m
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HAPE - signs symptoms

• Symptoms most often superimposed on AMS
• Cough - Tachypnea - DOE, SOB rest
• Tachycardia - Orthopnea - Fever
• Cyanosis - Rales - Watery sputum
• 2-4d after rapid ascent, often during the night.
• CXR fluffly patchy perihilar infiltrates,
  sparing of lung bases periphery, usually
  affects RML first.
• ECG RBBB, RAD, tall R precordial leads, S
  lateral leads.
• (Jerome Severinghaus, 1996)

On the way to Thorung La 5000m
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HAPE - signs symptoms

• In those with HAPE severe hypoxemia can lead to
  the rapid progression of AMS to HACE.
• Mortality
• 11 with treatment.
• when descent impossible and no supplemental O2
  available, mortality rate 44 - 50.
• An effective portable medical regimen for the
  treatment of HAPE is desirable when immediate
  descent is not an option.
• (Oelz et al. 1989 Bärtsch et al. 1991, Hackett
  Roach, 2001)

On the way to Thorung La 5000m
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HAPE - prevention

• Slow ascent (HAPE-S lt300m/day over 2000m)
  (Dumont et al. BMJ 2000)
• Steroids (Keller et al. BMJ, 1995 Reid et al. J
  Wild Med, 1994 Johnson et al. NEJM, 1984)
• Pulmonary vasodilators NO inhibitors (Dumont et
  al. BMJ 2000 Hohenhaus et al. Am J Resp Crit
  Care Med, 1994 Fallon et al. Amer J Physiol,
  1998 Oelz et al. Lancet, 1989)
• PCO2 reducers (acetazolamide) (Grissom et al. Ann
  Int Med, 1992 Reid et al. J Wild Med, 1994
  Forwand et al. NEJM, 1968)
• CPAP (Schoene et al. Chest, 1985)

Thorung La, 5415m
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HAPE what doesnt work

• Simulated descent (Bärtsch et al. BMJ, 1993
  Pollard et al, BMJ, 1995)
• Practice (repeated exposures) (Burse et al. Aviat
  Space Environ Med, 1988)
• ? Antioxidants (Bailey et al. High Alt Med Biol,
  2001)

Thorung La, 5415m
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Bottom Line prevent/correct hypoxia and you will
prevent/correct PE !
Heading towards Muktinath, 5000m
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Is Hypoxia Bad?

• Hypoxia not only stops the motor, it wrecks the
  engine.
• - John Scott Haldane, 1917

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Chemistry Warning O2
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Oxygen

• Not all chemicals are bad. Without chemicals
  such as hydrogen and oxygen, for example, there
  would be no water, a vital ingredient for beer.
• -Dave Barry

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Oxygen

• Diatomic gas
• Atomic weight 15.9994 g-1
• Invisible
• Odorless, tasteless
• Third most abundant element in the universe
• Present in Earths atmosphere at 20.95

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Oxygen

• Essential for animal life.

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Oxygen

• Oxygen therapy has always been a major component
  emergency care
• Health care providers believe oxygen alleviates
  breathlessness

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Oxygen
We began giving oxygen because it seemed like the
right thing to do

• Documented benefits
• Hypoxia
• Nausea/vomiting
• Motion sickness

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Oxygen

• Today, there are numerous textbooks on the
  reactive oxygen species.

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Oxygen

• We are learning that oxygen is a two-edged sword
• It can be beneficial
• It can be harmful

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The Chemistry of Oxygen

• Oxygen is a highly reactive substance
• It shares electrons between two atoms in order to
  maintain stability
• Overall, diatomic oxygen has 2 unpaired electrons

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The Chemistry of Oxygen

• Molecules/atoms with unpaired electrons are
  extremely unstable and highly-reactive
• Referred to as free radicals

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The Chemistry of Oxygen

• Free radicals, in normal concentrations, are
  important in intracellular bacteria and
  cell-signaling
• Most important free radicals (both produced by
  oxygen)
• Superoxide (?O2-)
• Hydroxyl radical (?OH)

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The Chemistry of Oxygen

• Changes associated with aging are actually due to
  effects of free-radicals
• As we age, the antioxidant enzyme systems work
  less efficiently

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The Chemistry of Oxygen
Lifespan 3.5 years
Lifespan 21 years
Lifespan 24 years
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The Chemistry of Oxygen

• Most cells receive approximately 10,000
  free-radical hits a day
• Enzyme systems (anti-oxidants) can normally
  process these

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The Chemistry of Oxygen

• Accumulation of free-radicals is called oxidative
  stress
• It results from an imbalance between
• Number of free-radicals present
• Number of anti-oxidants present

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Oxygen free radicals

• Produced when O2 is introduced into damaged cell
  environment
• Production directly proportionate to amount of O2
  introduced

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Oxidative Stress

• Occurs during reperfusionnot during hypoxia
• Flooding ischemic cells with oxygen during
  reperfusion worsens oxidative stress.

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Not a new concept

• ACLS Guidelines 2000
• Supplemental oxygen only for saturations lt 90

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Stroke

• Brain vulnerable to oxidative stress
• More fatty acids
• Fewer antioxidants
• High oxygen consumption
• High levels of ironand ascorbate
  (worsensoxidative stress)
• Dopamine and glutamine oxidation

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Stroke

• Lactic acid accumulates in neurons in ischemic
  stroke.
• Acidic environment has pro-oxidant effect
• Increased H2O2 conversion
• Superoxide anion converted to hydroperoxyl
  radical (HO2)
• Increased iron available for free radical
  formation

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Stroke
No oxygen
Oxygen
Ronning OM, Guldvog B. Should Stroke Victims
Routinely Receive Supplemental Oxygen? A
Quasi-Randomized Controlled Trial. Stroke.
1999302033-2037.
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Stroke

• 1994 AHA Stroke Council concluded no data
  support routine use of supplemental oxygen in
  stroke patients
• More recently, oxygen has been suggested to be
  detrimental

Panciolli AM, et al. Supplemental oxygen use in
ischemic stroke patients does utilization
correspond to need for oxygen therapy. Arch
Intern Med. 200216249-52.
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Stroke

• In non-hypoxic patients with minor or moderate
  strokes, supplemental oxygen is of no clinical
  benefit.

Portier de la Morandiere KP, Walter D. Oxygen
therapy in acute stroke. Emergency Medicine
Journal. 200320547-553
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Stroke

• Supplemental oxygen should not routinely be
  given to non-hypoxic stroke victims with minor to
  moderate strokes.
• Further evidence is needed to give conclusive
  advice concerning oxygen supplementation for
  patients with severe strokes.

Ronning OM, Guldvog B. Should Stroke Victims
Routinely Receive Supplemental Oxygen? A
Quasi-Randomized Controlled Trial. Stroke.
1999302033-2037.
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Neonates

• Prevailing wisdom oxygen is harmful toneonates
• Transition fromintrauterine hypoxic environment
  to extrauterine normoxic environment leads to an
  acute increase in oxygenation and development of
  ROS

Sola A, Rogido MR, Deulofeut R. Oxygen as a
neonatal health hazard call for détente in
clinical practice. Acta Pediatrica.
200796801-812.
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Neonates

• 1,737 depressed neonates
• 881 resuscitated with room air
• 856 resuscitated with 100 oxygen
• Mortality
• Room air resuscitation 8.0
• 100 oxygen resuscitation 13.0
• Neonatal mortality reduced with room air
  resuscitation

Davis PG, Tan A, ODonnell CP, et al
Resuscitation of newborn infants with 100 oxygen
or air a systematic review and meta-analysis.
Lancet 3641329-1333, 2004
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Neonates

• Neonates resuscitated with room air had lower
  mortality in the first week of life (OR 0.70, 95
  CI 0.50-0.98) and at 1 month and beyond (OR 0.63,
  95 CI 0.42-0.94)
• Room air is superior to 100 oxygen for initial
  resuscitation.

Rabi Y, Rabi D, Yee W Room air resuscitation of
the depressed newborn a systematic review and
meta-analysis. Resuscitation 72353-363, 2007
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Neonates ECC

• Supplementary oxygen is recommended whenever
  positive-pressure ventilation is indicated for
  resuscitation
• Free-flow oxygen should be administered to
  breathing infants who have central cyanosis

American Heart Association. 2005 American Heart
Association guidelines for cardiopulmonary
resuscitation (CPR) and emergency cardiovascular
care (ECC) of pediatric and neonatal patients
pediatric basic life support. Circulation.
200513IV1-203.
69
Neonates - ECC

• Although the standard approach to resuscitation
  is to use 100 oxygen, it is reasonable to begin
  resuscitation with an oxygen concentration of
  less than 100 or to start with no supplementary
  oxygen (i.e., start with room air).

American Heart Association. 2005 American Heart
Association guidelines for cardiopulmonary
resuscitation (CPR) and emergency cardiovascular
care (ECC) of pediatric and neonatal patients
pediatric basic life support. Circulation.
200513IV1-203.
70
Acute Coronary Syndrome

• In acute uncomplicated MI, there is no evidence
  that supplemental oxygen reduces mortality.
  However, there is no evidence of harm. Further
  research is required before changes in clinical
  practice should be recommended.

Mackway-Jones K. Oxygen in uncomplicated
myocardial infarction. Emerg Med J.
20042175-81.
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Cardiac Arrest

• Emphasis on circulation
• Compression only CPR may be better
• Known dangers of oxidative stress
• Study on Room Air vs. FiO2 1.0
• In-hospital med/surgical wards
• Standard ACLS, change only FiO2 (30 days)
• Study halted by IRB use of 100 oxygen harmful
  to human subjects!

McEvoy et al. (Unpublished) Comparison of
Normoxic to hyperoxic ventilation during
In-Hospital Cardiac Arrest. Germany 2008.
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Post-Cardiac Arrest

• Post-cardiac arrest brain injury is a common
  cause of morbidity and mortality
• 68 of out-of-hospital cardiac arrests
• 23 of in-hospital cardiac arrests
• Causes
• Limited tolerance of ischemia
• Unique response to reperfusion

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Post-Cardiac Arrest

• Burst of ROS has been observed in cardiomyocytes
  in the first few minutes of reperfusion
• Antioxidants and other cardioprotective measures
  diminish during the reperfusion burst

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Therapuetic Hypothermia

• Post ROSC Survival
• Post cardiac arrest hypothermia
• 58 patients, all ROSC in OOH CPA
• Cooling protocol keep sat 92-96
• Survival ? by 50 when sats lt 92
• Survival ? by 83 when sats gt 96

Unpubished data. Albany Medical Center, Albany,
New York, USA. Division of Cardiothoracic
Surgery 2009.
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Trauma

• Charity Hospital (1/1?9/30/2002)
• 5,549 trauma patients by EMS
• 459 received assisted ventilation were excluded
• 5,090 remaining prehospital patients
• 2,203 (43.3) received prehospital oxygen
• 2,887 (56.7) did not receive prehospital oxygen

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Trauma
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Trauma

• MORTALITY

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Trauma

• Our analysis suggest that there is no survival
  benefit to the use of supplemental oxygen in the
  prehospital setting in traumatized patients who
  do not require mechanical ventilation or airway
  protection.

Stockinger ZT, McSwain NE. Prehospital
Supplemental Oxygen in Trauma Patients Its
Efficacy and Implications for Military Medical
Care. Mil Med. 2004169609-612.
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Where to from here?
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British Thoracic Society

• Issued an O2 therapy guideline 2008
• All this and more
• Routine administration can be harmful
• O2 does not affect dyspnea unless hypoxic
• Hyperoxia may decrease target organ perfusion
  (when given needlessly)
• Unnecessary O2 delays recognition of
  deterioration by providing false reassurances
  with high O2 saturations

www.brit-thoracic.org.uk
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British Thoracic Society

• and more
• Absorption atelectasis _at_ FiO2 0.3-0.5
• O2 risk to some COPD patients
• ? SVR, coronary vasospasm
• No demonstrated clinical benefit of keeping O2
  sat gt 90 in any patient

Harten JM et al. J Cardiothoracic Vasc Anaesth
2005 19 173-5 Kaneda T et al. Jpn Circ J 2001
213-8 Frobert O et al. Cardiovasc Ultrasound
2004 2 22 Haque WA et al. J Am Coll Cardiol
1996 2 353-7 Thomaon AJ et al. BMJ 2002
1406-7 Ronning OM et al. Stroke 1999 30 Murphy R
et al. Emerg Med J 2001 18333-9 Plant et al.
Thorax 2000 55550 Downs JB. Respiratory Care
2003 48611-20
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British Thoracic Society

• O2 therapy guideline (everywhere)
• Keep normal/near-normal O2 sats
• All patients except hypercapnic resp. failure and
  terminal palliative care
• Keep sat 92-96, tx only if hypoxic
• Use pulse oximetry to guide tx max 98

www.brit-thoracic.org.uk
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Implications R U there?
84
Got oxygen?
85
Oxygen?
86
Implications Oximetry mandatory
87
Implications Venturi Comeback
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Prehospital Implications

• Pulse oximetry guided supplemental oxygen
• Protocols needed!

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Can We Attenuate Oxidative Stress?

• Perhaps
• Clues lie with Carbon Monoxide
• Known in vitro and in vivo antioxidant and
  anti-inflammatory properties
• Critically ill patients ? CO production
• Survivors produce more CO
• Non-survivors produce less or no CO
• Multiple human studies now using CO to attenuate
  oxidative pulmonary stress

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Implications of CO

• Need to monitor COHb
• CO-oximetry measures COHb non-invasively and
  continously

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Take Home Messages

• Oxygen can hurt
• CO may help
• Empiric use is nota good practice - O2 tx must
  befocused
• Use oximetry toguide care prevent hypoxia and
  hyperoxia

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Questions?
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