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

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