Toxicology represent a clinical dilemma for clinicians worldwide and impart a diagnostic challenge, particularly in the intensive care unit (ICU) setting. A poisoned patient typically cannot provide a history; therefore, an adequate diagnosis relies on laboratory data and an astute clinician identifying specific toxidromes and having a high index of suspicion.

Poisoning is the leading cause of injury-related death in the United States.¹ In 2015, 47% of exposure cases involved children younger than 6 years of age, but as in previous years, many of the more serious cases occurred among adolescents and adults. A total of 57% of human exposures involved medications or pharmaceuticals. Other exposures were to household products, plants, mushrooms, pesticides, animal bites and stings, carbon monoxide, and many other types of nonpharmaceutical substances.² The majority of exposures were ingestions or aspirations in 79% (Fig. 30-1) and were unintentional (Fig. 30-2). The categories of substances or toxins with the largest number of exposures in all ages included analgesics (11.1%), cleaning substances (7.6%), and sedative–hypnotics (5.8%).²

Pharmacologic Considerations

1. 
   

   Absorption: The degree of absorption of medications is highly dependent on the environment at the site of administration. Shock states decrease perfusion and shunt blood to the vital organs reduce systemic absorption of drugs from the intestines and intramuscular and subcutaneous tissues.³ Intestinal atrophy can begin after only 3 days of starvation and is not prevented by parenteral nutrition (see Figure 30-3).⁴

   
   
2. 
   

   Distribution: Sepsis, shock, burn injury, pancreatitis, and alterations in plasma protein binding are just a few examples of disease entities influencing the volume of distribution (Vd). Alternatively, fluid resuscitation, as frequently necessary in critically ill patients, will also lead to increased Vd.

   
   
3. 
   

   Metabolism: Drug metabolism occurs predominantly in the liver and is driven mainly by the cytochrome P450 enzyme system. Critical illness affects metabolic activity by alterations in plasma protein concentration, hepatic enzymatic activity, and blood flow. Many drugs used in critically ill patients may either induce or inhibit the activity of the various isoenzymes included in the cytochrome P450 complex.

   
   
4. 
   

   Elimination: Augmented renal clearance can be driven by sepsis, burn injury, or use of inotropic agents. On the other hand, acute kidney injury may complicate clearance of drugs, necessitating renal replacement therapy or dialysis.⁵

The diagnosis is often clinical, and it is common that multiple toxicities occur at the same time.^6-10 (Tables 30-1, 30-2, 30-3, 30-4)^7,11-16 Treatment is not necessarily dependent on confirmation of the diagnosis because it may delay an opportunity to prevent further damage.