Acute Carbon Monoxide Intoxication (Cyanide poisoning) 2015-11-15T15:53:26+00:00

Pathophysiology and Hyperbaric Effects

Carbon monoxide (CO) remains among the most common poisons in the industrialized world and a leading cause of poison-related deaths. A survey of death certificate reports in the United States for a 10 year period ending in 1988 indicated that CO exposure contributed to the deaths of more than 56,000 people. Estimates of mortality and morbidity risk from carbon monoxide poisoning vary widely. The major reason for variability is an absence of a standardized method for defining the severity of a particular exposure. Different methods are also used to detect neurological dysfunction, the predominant form of morbidity. Acute mortality appears to be due to ventricular dysrhythmias caused by carbon monoxide-induced hypoxic stress. Morbidity can be related to cardiac, pulmonary and even to renal injuries, on occasion. However, the most common site of injury is the nervous system. Acute neurological changes following CO poisoning include hyperactivity, lethargy, disorientation, coma, dementia, psychosis, chorea, amnesic and confabulatory syndromes, apraxias, and a Parkinson-like syndrome. Rarely, cortical blindness, incontinence, and peripheral neuropathies occur. Neurological and psychiatric abnormalities also occur in delayed fashion after patients are acutely treated for CO poisoning and, seemingly, have recovered. These delayed neurological sequelae (DNS) occur from two to 40 days after CO exposure. Manifestations of DNS include disorientation, apathy, bradykinesia, gait disturbances, aphasia, apraxia, incontinence, personality changes, and rarely, seizures and coma.

Clinical observations and historical data currently provide the most useful guidelines for stratifying the risk of mortality and morbidity. Risk is greater when a “soaking,” or exposure to CO for a relatively long span of time (of an hour or more) has occurred. “Soaking” appears to confer greater risk compared to a shorter exposure, even when both exposures terminate with the same endpoints. The second clinical event associated with higher risk is an interval of unconsciousness. Although unconsciousness is not universally linked to a poor outcome, the duration of coma is proportional to the risk of morbidity. Poor outcome also appears to be more common among patients with cardiovascular disease and those over 60 years of age.

There is no prevailing symptom complex for CO intoxication and, even among patients exposed in the same incident, presenting complaints can vary widely. The measurement of carboxyhemoglobin (COHb) has been a keystone for diagnosing CO poisoning. Nevertheless, COHb is not a reliable indicator of either the severity of intoxication or prognosis. Performance measurements based on a battery of neuropsychiatric tests have been used in some investigations to quantify cortical dysfunction.

The toxicity of CO is based on a number of overlapping pathophysiological mechanisms. Clearly, one of the main aspects involves interference with the transport of oxygen from alveoli to tissues due to the binding of CO to hemoglobin. CO rapidly diffuses across the alveolar capillary membrane and binds to hemoglobin with an affinity more than 200 times greater than that of oxygen. The degree of CO uptake depends on ventilatory rate, the duration of exposure, and the relative concentrations of CO and oxygen. Hemoglobin saturation tends to remain in the normal range during CO poisoning until arterial oxygen tension becomes severely depressed. Oxygen tension at the tissue level is decreased due to the presence of COHb. This is caused by both a decrease in the arterial oxygen tension and also because of a leftward shift of the oxyhemoglobin dissociation curve. Approximately ten to 15 percent of the total amount of absorbed CO is bound to extravascular proteins. Binding of CO to myoglobin, reduced cytochromes, guanylate cyclase, and nitric oxide synthase has been documented. The affinity of CO for cytochrome oxidase is relatively low, but due to irregularities regarding the kinetics of binding and dissociation, CO can cause impairment of oxidative metabolism. This phenomena can cause the electron transport chain to become fully reduced, leading to generation of oxygen-based free radicals. Oxygen and nitrogen-based free radicals from vascular endothelial cells, platelets, and possibly neurons, appear to cause a perivascular oxidative stress immediately after CO poisoning. This subtle injury, coupled with transient cardiac dysfunction associated with CO-induced hypoxic stress, precipitates adherence of white blood cells to the vasculature in the brain and to subsequent tissue injury. These events, all elucidated in animal studies, are supported by clinical neurological imaging studies. The latter investigations indicate that the earliest evidence of injury in the brain follows a perivascular distribution.

The physiological benefits of hyperbaric oxygen therapy (HBOT) are: improvement of oxygenation and hastened COHb dissociation, restoration of mitochondrial function, and inhibition of adherence of leukocytes to the microvascular endothelium. Clinical efficacy of hyperbaric oxygen is severely diminished when administered more than six hours after the patient is removed from the CO-contaminated environment. Goulon, et al., reported in a retrospective study that mortality was 13.5 percent if HBOT treatment was begun within six hours and 30.1 percent if HBOT was delayed for more than six hours. The incidence of DNS was 35.8 percent for those patients treated with either ambient pressure oxygen or with HBOT at greater than six hours. In contrast, the incidence of DNS among patients treated with HBOT in less than six hours was .7 percent. A high incidence of DNS, 47 percent, was also reported in a recent prospective randomized study, despite use of HBOT. However, the mean time for randomization in the study was six hours, thus the poor patient outcome is consistent with Goulon’s earlier findings. Thom, et al., recently reported a prospective randomized trial in which the incidence of DNS was compared with patients treated with ambient pressure and hyperbaric oxygen. In all cases, treatment was begun within six hours of poisoning. Twenty three percent (seven of 30 patients) treated with ambient pressure oxygen developed sequelae, whereas none of 30 (zero percent) treated with HBOT develop DNS


Bour H, Pasquier P, Bertrand-Handy J: Le coma oxycarbone. Semaine des Hospitaux de Paris 1966;40:1839-1861.

Broome JR, Skrine H, Person RR: Carbon monoxide poisoning: forgotten not gone. Br J Hosp Med 1988;39:298-305. Brown, DB, Mueller GL, Golich FC: Hyperbaric oxygen treatment for carbon monoxide poisoning in pregnancy: a case report. Aviat Space Environ Med 1992;63:1011-1014.

Brown SD, Piantadosi CA: In vivo binding of carbon monoxide to cytochrome C oxidase in rat brain. J Appl Physiol 1990;68:604-610.

Cho SH, Yun DR: The experimental study on the effect of the hyperbaric oxygenation on the pregnancy wastage of the rats in acute carbon monoxide poisoning. Seoul J Med 1982;23:66-75.

Choi IS: Delayed neurologic sequelae in carbon monoxide intoxication. Arch Neurol 1983;40:433-435.

Cobb N, Etzel RA: Unintentional carbon monoxide-related deaths in the United States, 1979 through 1988. JAMA 1991;266:659-663.

Coburn RF: The carbon monoxide body stores. Ann NY Acad Sci 1970;174:11-22.

Coric V, Oren DA: Carbon monoxide poisoning and treatment with hyperbaric oxygen in the subacute phase. J Neurol Neurosurg Psychiatry 1998;65(2):245-247.

Cramlet SH, Erickson HH, Gorman HA: Ventricular function following acute carbon monoxide exposure. J Appl Physiol 1975;39:482-486.

Elkharrat D, Raphael JC, Korach JM, et al.: Acute carbon monoxide intoxication and hyperbaric oxygen in pregnancy. Inten Care Med 1991;17:289-292.

Ernst A; Zibrak JD: Carbon monoxide poisoning. N Engl J Med 1998;339(22)1603-1608.

Ferm VH: Teratogenic effects of hyperbaric oxygen. Proc Soc Exp Biol Med 1964;116:975-976.

Forbes WH, Sargent F, Roughton FJW: The rate of carbon monoxide uptake in normal men. Am J Physiol 1945;143:594.

Gilman SC, Bradley ME, Greene KM, Fischer GJ: Fetal development: effects of decompression sickness and treatment. Aviat Space Environ Med 1983;54:1040-1042.

Gorman DF, Clayton D, Gilligan JE, Webb RK: A longitudinal study of 100 consecutive admissions for carbon monoxide poisoning to the Royal Adelaide Hospital. Anaesth Intens Care 1992;20:311-316.

Goulon M, Barois A, Rapin M, Nouailhat F, Grosbuis S, Labrousse J: Carbon monoxide poisoning and acute anoxia due to breathing coal gas and hydrocarbons. Ann Med Int (Paris) 120:335-349, 1969, translated in J Hyperbaric Med 1986;1:23-41.

Hampson NB, Kramer CC: Carbon monoxide poisoning from indoor burning of charcoal briquets. JAMA 1994;271(1):52-53.

Hardy KR, Thom SR: Pathophysiology and treatment of carbon monoxide poisoning. Clin Toxicol 1994;32:613-629.

Ischiropoulos H, Duran D, Nelson J, Beers MF, Abrams WR, Ohnishi ST, Fisher D, and Thom SR: Nitrotyrosine as a marker of in vivo peroxynitrite formation and oxidative stress. J Biol Chem (in press).

Ishimaru H, Katoh A, Suzuki H, Fukuta T, Kameyama T, Nabeshima T: Effects of N-methyl-D-aspartate receptor antagonists on carbon monoxide-induced brain damage in mice. J. Pharmacol Exp Ther 1992;261:349-352.

Jay GD, McKindley DS: Alterations in pharmacokinetics of carboxyhemoglobin produced by oxygen under pressure. Undersea Hyperb Med 1997;24(3):165-173.

Koren G, Sharav T, Pastuszak A, Garrettson LK, Hill K, Samson I, et al.: A multicenter, prospective study of fetal outcome following accidental carbon monoxide poisoning in pregnancy. Reprod Toxicol 1991;5:397-403.

Krantz T, Thisted B, Strom J, Sorensen MB: Acute carbon monoxide poisoning. Acta Anaesthesiol Scand 1988;32:278-282.

Lamy M, Hauguet M: Fifty patients with carbon monoxide intoxication treated with hyperbaric oxygen therapy. Acta Anes Belgica 1969;1:49-53

Mathieu D, Nolf M, Durocher A: Acute carbon monoxide poisoning: risk of late sequelae and treatment by hyperbaric oxygen. Clin Toxicol 1985;23:315-324.

Mayevsky A, Meilin S, Rogatsky GG, Zarchin N, Thom SR: Multiparametric monitoring of the awake brain exposed to carbon monoxide. J Appl Physiol (in press).

Min SK: A brain syndrome associated with delayed neuropsychiatric sequelae following acute carbon monoxide intoxication. Acta Psychiatr Scand 1986;173:80-86.

Murray LP, Hofrichter J, Henry ER, Eaton WA: Time-resolved optical spectroscopy and structural dynamics following photodissociation of carbon monoxyhemoglobin. Biophys Chem 1988;29:63-76.

Myers RAM, Snyder SK, Emhoff TA: Subacute sequelae of carbon monoxide poisoning. Ann Emerg Med 1985;14:1163-1167.

Norkool DM, Kirkpatrick JN: Treatment of acute carbon monoxide poisoning with hyperbaric oxygen: a review of 115 cases. Ann Emerg Med 1985;14:1168-1171.

Norman CA, Halton DM: Is carbon monoxide a workplace teratogen? A review and evaluation of the literature. Ann Occup Hyg 1990;34:335-347.

Raphael, JC, Elkharrat D, Jars-Guincestre MC, Chastang C, et al.: Trial of normobaric and hyperbaric oxygen for acute carbon monoxide intoxication. Lancet 1989;19:414-419.

Richardson JC, Chambers RA, Heywood PM: Encephalopathies of anoxia and hypoglycemia. Arch Neurol 1959;1:178-182.

Silverman CS, Brenner J, Murtagh FR: Hemorrhagic necrosis and vascular injury in carbon monoxide poisoning: MR demonstration. AJNR 1993;14:168-170.

Silverman RK, Montano J: Hyperbaric oxygen treatment during pregnancy in acute carbon monoxide poisoning. J Repro Med 1997;42(5)309-311.

Smith JS, Brandon S: Morbidity from acute carbon monoxide poisoning at three-year follow-up. Br Med J 1973;1:318-321.

Tabrah, FL, Tanner R: Baromedicie today–rational uses of hyperbaric oxygen therapy. Hawaii Med J 1994;53(4):112-115.Thom SR: Functional inhibition of leukocyte B2 integrins by hyperbaric oxygen in carbon monoxide-mediated brain injury in rats. Toxicol Appl Pharmacol 1993;123:248-256.

Thom SR: Leukocytes in carbon monoxide-mediated brain oxidative injury. Toxicol Appl Pharmacol 1993;123:234-247.

Thom SR, Mendiguren I, Nebolon M, Campbell D, Kilpatrick L: Temporary inhibition of human neutrophil B2 integrin function by hyperbaric oxygen (HBO). Clin Res 1994;42:130A.

Thom SR, Ischiropoulos H: Nitric oxide released by platelets inhibits neutrophil B2 integrin function following acute carbon monoxide poisoning. Toxicol Appl Pharmacol 1994;128:105-110.

Thom SR, Taber RL, Mendiguren II, Clark JM, Hardy KR, Fisher AB: Delayed neuropsychological sequelae following carbon monoxide poisoning and its prophylaxis by treatment with hyperbaric oxygen. Ann Emer Med 1995;25:474-480.

Tomaszewski C, Rudy J, Wathen J, Brent J, Rosenberg N: Prevention of neurologic sequelae from carbon monoxide by hyperbaric oxygen in rats. Ann Emer Med 1992;21:631-632.

Tomaszewski CA, Thom SR: Use of hyperbaric oxygen in toxicology. Emerg Med Clin North Am 1994;12(2);437-439.

VanHoesen KB, Camporesi EM, Moon RE, Hage ML, Piantadosi, CA: Should hyperbaric oxygen be used to treat the pregnant patient for acute carbon monoxide poisoning. JAMA 1989;261:1039-1043.

Wolfe E: Carbon monoxide poisoning with severe myonecrosis and acute renal failure. Am J Emerg Med 1994;12(3)347-349.

Zhang J, Piantadosi CA: Mitochondrial oxidative stress after carbon monoxide hypoxia in the rat brain. J Clin Invest 1991;90:1193-1199.