OXYGEN:
FRIEND OR FOE?
LIHUA ZHANG, M.D.
Oxygen is a drug
• Oxygen plays a vital role in the breathing processes and in the
metabolism of the living organisms.
• Oxygen is one of the most widely used therapeutic agents.
• It is a drug in the true sense of the word, with specific biochemical
and physiologic actions, a distinct range of effective doses, and welldefined adverse effects at high doses.
Benefit a high-oxygen strategy could have
• oxygen-derived free radicals!
• High O2 increase tissue O2 tension
• Decrease in surgical site infection?
Biologically advantageous uses of Oxygenderived free radicals
• killing of bacterial;
• killing of malarial parasites;
• destruction of circulating tumor cells, particularly in the pulmonary
circulation where the oxygen tension is highest.
Supplemental Perioperative Oxygen To Reduce The
Incidence Of Surgical-wound Infection
• Background Destruction by oxidation, or oxidative killing, is the
most important defense against surgical pathogens and depends
on the partial pressure of O2 in contaminated tissue. An easy
method of improving O2 tension in adequately perfused tissue is
to increase the concentration of FiO2.
• Methods randomly, 500 pts, colorectal resection, FiO2 30% or
80% during the operation and for two hours afterward. GA, abx,
wound with culture-positive pus.
• Results Among 250 pts with FiO2 80%, 13 (5.2%) had surgicalwound infections, as compared with 28 of 250 pts 30% FiO2
(11.2% P=0.01). The absolute difference between groups was
6%, with a relative risk reduction of 54%.
N Engl J Med 2000; 342:161-7
Supplemental Perioperative O2 and the Risk of
Surgical Wound Infection
A Randomized Controlled Trial
• Background Supplemental perioperative oxygen has been
variously reported to halve or double the risk of surgical wound
infection. To test the hypothesis that supplemental oxygen
reduces infection risk in patients following colorectal surgery.
• Methods randomly, 300 pts, colorectal resection, FiO2 30% or
80% during the operation and for six hours afterward. GA, abx,
wound with culture-positive pus.
• Results Among 148 pts with FiO2 80%, 22 (14.9%) had surgicalwound infections, as compared with 35 of 143 pts with FiO2 30%
(24.4% P=0.04). The absolute risk reduction was 9%, with a
relative risk reduction of 39%.
JAMA 2005; 294:2035-2042
• Canadian Association of General Surgeons and
American College of Surgeons Evidence Based
Reviews in Surgery. 21. recommended that
• “In general, widespread adoption of clinical practice change
requires a preponderance of evidence.
• However, there is little cost and no risk to the administration
of perioperative supplemental oxygen. Given that the
intervention makes sense from a biological and scientific
perspective, being easy to perform and relatively
noninvasive, practical, and with an excellent risk:benefit
profile, incorporating it into current quality improvement
activities aimed at reducing surgical site infection should be
relatively straightforward. “
Can J Surg 2007; 50: 214-216
High-Concentration Supplemental
Perioperative O2 to Reduce the Incidence of
Post C-section SSI
A Randomized Controlled Trial
• Objective 1. anaerobic bacteria infections, oxidative killing; 2.
colorectal surgery with supplemental O2 decreased SSI by 50%.
• Method 143 women undergoing C-section under regional
anesthesia to receive 30% or 80% FiO2 via non re-breathing mask
during the operation and for 2 hours after.
• Results Post c-section infection occurred in 17/69 (25%) with 80%
O2 compared with 10/74 (14%) of women with 30% FiO2 (relative
risk 1.8, P=.13). The stopping P value for futility was P > 0.11,
suggesting these differences were unlikely to reach statistical
significance with continued recruitment.
Obstet Gynecol 2008; 112: 545–52
Effect of High Perioperative FiO2 on SSI and
Pulmonary Complications After Abdominal Surgery
The PROXI Randomized Clinical Trial
• Objective To assess whether use of 80% O2 reduces the
frequency of SSI without increasing the frequency of pulmonary
complications in pts undergoing abdominal surgery.
• Method a pt- and observer-blinded randomized clinical trial, 1400
pts undergoing acute or elective laparotomy. Pts receive FiO2
80% or 30% during and for 2 hours after surgery.
• Results SSI, atelectasis, pneumonia, respiratory failure, and
mortality within 30 days 80% O2 compared with 30% O2 did not
result in a difference in risk of SSI and of pulmonary
complications after abdominal surgery.
JAMA, 2009; 302: 15431550
Disadvantage of hyperoxia
• Negative effect on pulmonary function: atelectasis, shunt
• May promote development of acute lung injury and increase
mortality
• After re-expansion of previously atelectatic lung, upregulation of
pro-inflammatory cytokines
• Tissue damage arising from oxygen-derived free radicals
• Cause arterial vasoconstriction
O2 and Anesthesia
• Preoperative:
• Preoxygenation, denitrogenization, optimal O2 concentration for
induction
• Intraoperative:
• FiO2 used in ventilation, optimal O2 concentration for extubation
• Postoperative:
• Supplemental O2 through nasal cannula, face mask; shunt and PA
equation
What is the function of Nitrogen to human?
• Nitrogen is a non-reactive gas. It helps to reduce the effect of O2 by
controlling the rate of combustion, oxidation (rusting of iron and
corrosion of metals).
• There is so much nitrogen in our atmosphere that it adds extra mass
to the air.
• During inspiration, air is inhaled, oxygen is absorbed, and nitrogen
keeps our lung alveoli open.
•If nitrogen is replaced by another gas, that is if it
is actively “washed out” of the lung by either
breathing high concentrations of oxygen, or
combining oxygen with more soluble nitrous
oxide in anesthesia, the process of absorption
atelectasis is accelerated. It is important to
realize that alveoli in dependent regions, with
low V/Q ratios, are particularly vulnerable to
collapse.
Optimal Oxygen Concentration during
Induction of General Anesthesia
• Background: The use of 100% oxygen during induction of
anesthesia may produce atelectasis.
• Methods: 36 healthy, nonsmoking women, randomized, FiO2
100, 80, or 60% for 5 min during the induction of GA.
Ventilation was then withheld until the oxygen saturation,
assessed by pulse oximetry, decreased to 90%. Atelectasis
formation was studied with CT.
Anesthesiology 2003; 98:28 –33
• Results: Atelectasis 5.6±3.4% of the total lung area, 0.6±0.7%, and
0.2±0.2% in the groups breathing 100, 80, and 60% O2, (P < 0.01).
The corresponding times to reach SpO2 90% were 411±84, 303±59,
and 213±69 s, (P < 0.01).
• Conclusion: During routine induction of general anesthesia, 80%
oxygen for oxygenation caused minimal atelectasis, but the time
margin before unacceptable desaturation occurred was
significantly shortened compared with 100% oxygen.
Examples of CT scans of a patient with healthy lungs, before and after induction of
anaesthesia.
Magnusson L , Spahn D R Br. J. Anaesth. 2003;91:61-72
©2003 by Oxford University Press
Two‐dimensional representation of a volume image from an anaesthetized subject.
Magnusson L , Spahn D R Br. J. Anaesth. 2003;91:61-72
©2003 by Oxford University Press
Measurement of atelectatic surface by CT of the lung at the level of the interventricular
septum and corresponding histograms.
Magnusson L , Spahn D R Br. J. Anaesth. 2003;91:61-72
©2003 by Oxford University Press
Samples of CT scans of a morbidly obese and a non‐obese patient before anaesthesia, after
extubation and 24 h later.
Magnusson L , Spahn D R Br. J. Anaesth. 2003;91:61-72
©2003 by Oxford University Press
The Effect of Increased FIO2 Before Tracheal
Extubation on Postop Atelectasis
• General anesthesia promotes pulmonary atelectasis, which can be
eliminated by a vital capacity (VC) maneuver (inflation of the lungs
to 40 cm H2O for 15 s).
• High-inspired O2 favors recurrence of atelectasis. Therefore, 100%
O2 before tracheal extubation may contribute to atelectasis.
• Results VC maneuver+FiO2=0.4 group, postoperative atelectasis
was smaller (2.6% ±1.1% of total lung surface, P<0.05) than in the
FiO2=1.0 group (8.3%±6.2%) and in the VC maneuver+Fio2=1.0
group (6.8%±3.4%).
Anesth Analg 2002, 95:1777–81
Supplemental Oxygen Impairs Detection of
Hypoventilation by Pulse Oximetry
• Hypoventilation can be detected reliably by pulse oximetry
only when patients breathe room air. In patients with
spontaneous ventilation, supplemental oxygen often
masked the ability to detect abnormalities in respiratory
function in the PACU. Without the need for capnography
and arterial blood gas analysis, pulse oximetry is a useful
tool to assess ventilatory abnormalities, but only in the
absence of supplemental inspired oxygen.
Chest 2004; 126;1552-1558
Alveolar gas equation and clinical use
•PAO2= (PB - PH2O) x FiO2 – PaCO2/RQ
= (760 - 47) x 0.21 – 40/0.8 = 149.7 – 50 = 99.7
= (760 - 47) x 0.21 – 50/0.8 = 149.7 – 62.5 = 87.2
= (760 - 47) x 0.3 - 50/0.8 = 213.9 – 62.5 = 151.4
= (760 - 47) x 0.3 - 70/0.8 = 213.9 – 87.5 = 126.4
Isoshunt curves showing the effect of varying amounts of shunt on PaO2.
Note: there is little benefit in increasing inspired oxygen concentration in
patients with very large shunts.
Major causes of hypoxemia
1. Alveolar Hypoventilation.
2. Ventilation perfusion (V/Q) mismatch: common causes of
V/Q mismatch are atelectasis, patient positioning, bronchial
intubation, one-lung ventilation, bronchospasm, pneumonia,
mucus plugging, acute respiratory distress syndrome (ARDS)
and airway obstruction.
3. Shunt (normal shunt about 2%): hypoxemia caused by shunt
can not be overcome by increasing the inspired oxygen
concentration.
4. Diffusion abnormalities.
5. Low barometric pressure
6. Low inspired oxygen concentration (decreased FiO2).
Specific treatment for arterial hypoxemia
• Hypoventilation
• Low ventilation/perfusion ratio
• Intrapulmonary shunt
• Diffusion defect
• Low barometric pressure
• Low inspired oxygen
concentration (<21%)
Increase alveolar ventilation
CPAP
CPAP
Steroids (?)
Return to sea level pressure
Oxygen!
Although oxygen supplementation will increase oxygen tension in
every instance, oxygen is the specific treatment for reversal of the
pathologic condition causing arterial hypoxemia in only 1 instance: low
inspired oxygen concentration (<21%).
• Summary and grading of recommendation for perioperative management
Preoxygenation
Use of high FiO2, (0.8)
CPAP 6cmH20
25 ' Head-up tilt
Reduces atelectasis
Reduces atelectasis
Improves artenal oxygenation
Prolongs nonhypoxic apnea time
Reduces atelectasis
Improves artenal oxygenation
Prolongs nonhypoxic apnea time
Grade B
Grade B
Grade B
Grade B
Grade B
Grade B
Grade B
Does not improve gas exchanges
Reduces peak airway pressure
Reduces alveolar inflammation
Reduces postoperative pulmonary dysfunction
Reduces alveolar inflammation in association with low
tidal volume ventilation
Improves arterial oxygenation in morbidly obese
Improves arterial oxygenation during one-lung ventilation
Prevents atelectasis relapse after a vital capacity maneuvre
Reduces wound infection in major abdominal surgery
Does not reduce PONV
Protects cardiovascular system
Grade B
Grade A
Grade B
Grade C
Intraoperative management
Use of PCV
Reduce VT to 5-8 ml kg- 1
Use 5-1 0 cmH2O PEEP
Set Fi0 2 to 0.8
Grade B
Grade B
Grade B
Grade B
Grade A
Grade B
NO
Eur J Anaesthesiol 2009; 26: 1-8
• As early as 1775, Joseph Priestley suggested that oxygen might not
be an entirely unmixed blessing:
• “….though pure dephlogisticated air might be very useful as a
medicine, it might not be so proper for us in the usual healthy
state of the body: for, as a candle burns so much faster in
dephlogisticated than in common air, so we might, as may be said,
live out too fast, and the animal powers be too soon exhausted in
this pure kind of air.”
References
• Rothen HU. Oxygen: avoid too much of a good thing! . European Journal
of Anaesthesiology 2010, 27:493–494 ;
• Downs JB. Has Oxygen Administration Delayed Appropriate Respiratory
Care? Fallacies Regarding Oxygen Therapy. RESPIRATORY CARE 2003, 48:
611-620;
• Downs JB. Is Supplemental Oxygen Necessary? Journal of Cardiothoracic
and Vascular Anesthesia, 2006, 20: 133-135;
• Nunn JF. Oxygen-friend and foe Journal of the Royal Society of Medicine,
1985, 78: 618 – 622.
Thank you.
Questions?