Carbon Monoxide Poisoning and Smoke Inhalation

By Lisa Murphy DACVECC


Carbon Monoxide Poisoning

Carbon monoxide (CO) is a colourless, odourless gas which is produced by combustion of hydrocarbons from fires, car exhausts, charcoal grills and also endogenously via erythrocyte and haem catabolism. A normal carboxyhaemoglobin (COHb) level in dogs and cats is approximately 1-3%. In the normal environment, CO has a concentration of 0.001%; however inhalation of air containing 0.1% CO can result in COHb levels > 50%. The most common routes of exposure to CO in small animal patients include smoke inhalation, gas heaters and running generators. 

Following inhalation, CO is absorbed rapidly at the level of the alveoli. The amount of CO absorbed will depend on several factors including the patient’s minute ventilation (respiratory rate x tidal volume), duration of exposure and the concentration of CO in the environment. Once absorbed, a small amount will be oxidised into carbon dioxide and the remainder is bound to haem proteins. 

Carbon monoxide interacts with haemoglobin. It has 200x the affinity for haemoglobin when compared to oxygen. It, therefore, displaces oxygen from haemoglobin affecting normal haemoglobin release of oxygen to the tissues. Carbon monoxide binds 2/4 of the available haem groups within each molecule of haemoglobin. This reduces the oxygen-carrying capacity of the haemoglobin by 50% shifting the oxyhaemoglobin dissociation curve, see below. Furthermore, any oxygen which is bound by haemoglobin finds it more difficult to dissociate due to changes in the chemical equilibrium following CO binding. This leads to subsequent tissue hypoxia and cellular shock.

 
Hb-O2-dissociation-curve.jpg
 

Carbon monoxide also has direct toxic effects on cells. In the case of cardiac and skeletal muscle, CO binds to myoglobin and reduces the contractile functions. In the case of cardiac cells, this can decrease cardiac output worsening tissue hypoxia. Finally, CO may also cause:

  • sequestration of white blood cells
  • increased nitric oxide production (which can affect blood pressure regulation)
  • reperfusion injury
  • lipid peroxidation (which leads to damaged cell membranes), and
  • direct neurotoxicity as it can act as a stimulatory neurotransmitter

Clinical signs of CO poisoning will depend on the amount inhaled but can include lethargy, depression, disorientation, seizures, tachypneic, nausea and vomiting. Severe poisoning in people may also cherry-coloured mucous membranes. Veterinary retrospective studies have reported hyperaemic mucous membranes in a minority of dogs and cats.

Diagnosis of CO poisoning requires measurement of COHb levels via a co-oximetry machine. Pulse oximetry is inaccurate and will falsely elevate SpO2 levels in these cases. Pulse oximetry is based on the ratio of light absorbed by tissues at two different wavelengths (660nm to 940nm) and only measures oxyhaemoglobin and deoxyhaemoglobin. Carboxyhaemoglobin and oxyhaemoglobin have similar light absorption and are indistinguishable via a pulse oximeter. In contrast, a co-oximetry machine can give specific levels of oxyhaemoglobin, COHb and methaemoglobin. Venous samples are adequate for measurement of COHb although arterial samples will give more information regarding the patient’s oxygenation status. 

The most important aspect of treatment in these cases is oxygen supplementation. Elimination of COHb depends on minute ventilation and the fraction of inspired oxygen (FiO2). Increasing FiO2 will decrease the half-life of COHb as dissolved oxygen competes with CO for binding sites on haemoglobin. Once displaced from haemoglobin, CO is exhaled via the lungs.

In a patient breathing room air with a FiO2 of 21%, the half-life of CO is 4-6 hours. This decreases to 40-80 min at a FiO2 of 100% which can only be achieved with mechanical ventilation. Less invasive options for oxygen therapy include oxygen cages, nasal prongs and nasal cannulas among others. In animals with concurrent airway damage from smoke inhalation, the half-life may be slightly longer due to reduced efficiency of gas exchange. Hyperbaric oxygen chambers, which are not commonly available in veterinary medicine, can further reduce the CO half-life to 15-30 minutes. Human studies have not conclusively proven however that hyperbaric oxygen therapy offers significantly improved outcomes when compared to normobaric oxygen therapy. 

Care of the Smoke Inhalation Patient 

Regardless of whether or not they have significant CO poisoning, smoke inhalation patients may be dyspnoeic for multiple reasons. Reduced lung compliance from atelectasis and impaired lung surfactant function is common and leads to significant pulmonary oedema. The normal mucociliary escalator which acts to aid in the removal of irritant substances from the airway is impaired. This can lead to mucosal oedema, sloughing and damage to the tracheal and bronchial epithelium in the ensuing hours.

It is important to note that while these patients may be at risk of secondary bacterial pneumonia, signs of infection will not be seen for at least 12-24 hours; moreover, the risk of clinically significant infection is thought to be low. The empirical use of antibiotics in similar human patients has not been conclusively shown to improve outcomes so prophylactic antibiotics are not recommended for these patients. 

Other important treatment considerations include:

  • Judicious intravenous fluid therapy especially in patients with severe dermal burn injuries.
  • Steroid use has been associated with an increased incidence of bacterial pneumonia and is not recommended.
  • Diuretics are also controversial. While diuretics are of benefit in hydrostatic oedema associated with congestive heart failure, there is less evidence supporting their use in cases of oedema due to increased permeability as in the case of smoke inhalation injury. They should be avoided in hypovolaemic or dehydrated patients.
  • Bronchodilators including the methylxanthines (aminophylline, theophylline) and beta-adrenergic agonists (terbutaline) can also be used. Many human studies recommend nebulised bronchodilators, see below.
  • N-Acetylcysteine (NAC) is used for its mucolytic properties and as a free radical (reactive oxygen species) scavenger, it may reduce reperfusion injury. Several human studies have shown benefit to using it in nebulised form to attenuate the lung injury associated with smoke inhalation and burns. 

Several drugs can be administered in aerosolised form. Most notably, bronchodilators like albuterol are recommended in human patients. Furthermore, several adult and paediatric human studies have reported benefit of aerosolised heparin which has anti-inflammatory effects. One veterinary study evaluating aerosolised heparin in research dogs did not report any benefit. While N-acetylcysteine can be administered in nebulised form, it can be irritant to the airways and cause bronchospasm when given via this route. It is important to note that dyspnoeic veterinary patients are easily stressed, and some could worsen with the restraint involved in administering aerosolised medications. 

In addition to the above, some of these patients can sustain corneal injuries from exposure to high temperatures and will require ophthalmic medications to promote healing.  

Delayed Neurological Sequelae

Delayed neuropsychiatric syndrome (DNS) has been described in humans who have experienced significant CO toxicity. Typically, signs develop within 3-240 days post exposure and can lead to cognitive dysfunction, personality changes, ataxia and deafness. The risk of DNS is highest with COHb levels > 25%. The exact mechanism of DNS is not known but it is not believed to be solely from hypoxia.

In a retrospective evaluation of dogs who had experienced CO poisoning, neurological dysfunction was noted to occur 2-6 days following exposure in 5/11 dogs evaluated. Anecdotally, in the author’s experience, 2 dogs who had been treated for CO poisoning following house fires developed suspect DNS with one dog developing behavioural changes and aggression and the other developing seizures. While seizures in these cases can be managed with standard anticonvulsive medications, therapy for behavioural changes is more difficult to recommend at this time. 

References:

Beasley, V.R., 1990. Smoke inhalation. Veterinary Clinics of North America: Small Animal Practice, 20(2), pp.545-556.

Vaughn, L., Beckel, N. and Walters, P., 2012. Severe burn injury, burn shock, and smoke inhalation injury in small animals. Part 2: diagnosis, therapy, complications, and prognosis. Journal of Veterinary Emergency and Critical Care, 22(2), pp.187-200.

Berent, A.C., Todd, J., Sergeeff, J. and Powell, L.L., 2005. Carbon monoxide toxicity: a case series. Journal of veterinary emergency and critical care, 15(2), pp.128-135.

Mariani, C.L., 2003. Full recovery following delayed neurologic signs after smoke inhalation in a dog. Journal of Veterinary Emergency and Critical Care, 13(4), pp.235-239.

Norkool, D.M. and Kirkpatrick, J.N., 1985. Treatment of acute carbon monoxide poisoning with hyperbaric oxygen: a review of 115 cases. Annals of emergency medicine, 14(12), pp.1168-1171.

Weaver, L.K., Hopkins, R.O., Chan, K.J., Churchill, S., Elliott, C.G., Clemmer, T.P., Orme Jr, J.F., Thomas, F.O. and Morris, A.H., 2002. Hyperbaric oxygen for acute carbon monoxide poisoning. New England Journal of Medicine, 347(14), pp.1057-1067.

Weaver, L.K., 2009. Carbon monoxide poisoning. New England Journal of Medicine, 360(12), pp.1217-1225.