Letter to the Editor:
To the Editor:
I read Dr. Stoelting’s recent editorial entitled “Dangers of Postoperative Opioids—Is There A Cure?” I believe that iatrogenic hyperventilation during anesthesia is an important factor in postsurgical opioid hypersensitivity.
Hyperventilation during anesthesia was founded on the questionable assumptions and observations of an earlier era. It does not increase oxygen stores. It increases morbidity and mortality in polio victims in iron lungs.1 It causes drowning in unsuspecting underwater swimmers.2 During anesthesia it impairs tissue perfusion and oxygenation, causes lung “stretch injury,” decreases opioid clearance, “traps” opioids in brain tissues, and undermines respiratory drive. In contrast, carbon dioxide is benign, and mild respiratory acidosis is beneficial.3,4 “Permissive hypercarbia” combined with anesthesia enhances respiratory drive, increases cardiac output, improves perfusion and oxygenation, protects lung tissues, prevents opioid “trapping” in brain tissues,5 and provides advance warning of inadequate analgesia and muscle relaxation via spontaneous respiratory efforts.6
Many clinicians misunderstand the complex relationships between opioids, controlled ventilation, and respiratory drive. Carbon dioxide is continuously produced by metabolic activity throughout the vertebrate body. It dissolves into tissues in large quantities and slowly equilibrates with fluctuating environmental concentrations. Respiratory drive mechanisms adjust to maintain this equilibrium.7 In the presence of conscious awareness, respiratory drive is primarily regulated by blood bicarbonate that determines pH in brain ventricles. This form of respiratory drive is amplified by pain perception. Respiratory drive is secondarily regulated by carotid body chemoreceptors that detect hypercarbia and hypoxemia in blood. During normal sleep and anesthesia, these become primary. Hypercarbia causes the chemoreceptors to become exponentially hypersensitive to hypoxemia, but hypocarbia disables them.8-10
Mechanical hyperventilation rapidly and abnormally depletes CO2 tissue reserves and blood bicarbonate. This can undermine respiratory drive for hours, until metabolic activity can replenish CO2 levels.7 Hyperventilated patients usually breathe and oxygenate effectively, but their respiratory drive precariously depends on their conscious awareness of surgical pain and psychological stimulation that provides an artificial stimulus to breathe. During this vulnerable period, even very small doses of opioids can unexpectedly obliterate the sole remaining source of respiratory drive, whereupon seemingly awake, alert, and fully recovered patients unpredictably stop breathing. The results can be devastating, because brain hypoxemia begins sooner than systemic hypoxemia. The danger may be greatest soon after surgical patients leave the recovery room and return to the conventional ward, where they are no longer closely monitored and stimulated. Monitors designed to detect the problem would likely generate so many “false alarms” as to be impractical.
Critical Care specialists have already embraced permissive hypercarbia. Anesthesiologists could profit from their example. The simple remedy of replacing hyperventilation with permissive hypercarbia that enhances respiratory drive can improve safety and outcome by preventing unexpected respiratory depression, rendering opioids more predictable, and facilitating greater opioid dosage to control stress.
Lewis S. Coleman, MD
Jaffe MB. Infrared measurement of carbon dioxide in the human breath: "breathe-through" devices from Tyndall to the present day. Anesth Analg 2008;107:890-904.
Wikipedia. Shallow Water Blackout. Available at: http://en.wikipedia.org/wiki/Shallow_water_blackout. Accessed November 30, 2009.
Fothergill DM, Hedges D, Morrison JB. Effects of CO2 and N2 partial pressures on cognitive and psychomotor performance. Undersea Biomed Res 1991;18:1-19.
Kavanagh B. Normocapnia vs hypercapnia. Minerva Anestesiol 2002;68:346-50.
Ainslie SG, Eisele JH Jr, Corkill G. Fentanyl concentrations in brain and serum during respiratory acid–base changes in the dog. Anesthesiology 1979;51:293-7.
Akça O. Optimizing the intraoperative management of carbon dioxide concentration. Curr Opin Anaesthesiol 2006;19:19-25.
Nichols G Jr. Serial changes in tissue carbon dioxide content during acute respiratory acidosis. J Clin Invest 1958;37:1111-22.
Corne S, Webster K, Younes M. Hypoxic respiratory response during acute stable hypocapnia. Am J Respir Crit Care Med 2003;167:1193-9.
Lahiri S, DeLaney RG. Stimulus interaction in the responses of carotid body chemoreceptor single afferent fibers. Respir Physiol 1975;24:249-66.
Prabhakar NR. O2 sensing at the mammalian carotid body: why multiple O2 sensors and multiple transmitters? Exp Physiol 2006;91:17-23.