Page 1750 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

CHAPTER 124: Toxicology in Adults 1219

of cyanide poisoning. Failure to respond to methylene blue suggests occurs within minutes of naloxone administration and lasts for 1 to
cytochrome b5 reductase deficiency, G6PD deficiency, or sulfhemo- 3 hours. Repeat boluses may be needed every 20 to 60 minutes to main-
globinemia. Exchange transfusion can be considered in severe cases tain an adequate clinical response. Alternatively, a continuous naloxone
unresponsive to methylene blue. infusion may be used particularly in longer acting opioids (0.4-0.8 mg/h,
■ OPIOIDS or two-thirds of the initial dose needed to achieve a response, given each
hour intravenously).
Opioid stimulation of opiate receptors causes generalized depression of Noncardiogenic pulmonary edema may be initially difficult to
the central nervous system. Symptoms of overdose range from lethargy to distinguish from aspiration pneumonitis and acute lung injury; how-
respiratory arrest and coma, depending on the dose, agent ingested, and ever, improvement is generally quicker in opioid-induced pulmonary
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patient tolerance. The majority of deaths occur from the use of IV heroin, edema. Supplemental oxygen, positive end-expiratory pressure, and
although death rates from prescription opioids (eg, methadone, oxyco- mechanical ventilation may all be required to achieve adequate gas
done, fentanyl) have increased more recently. 321,322 Ethanol appears to exchange. Since intravascular volume status may be reduced, diuresis
enhance the acute toxicity of heroin and may contribute to its mortality. 323 can aggravate hypotension.
Opioids cause respiratory failure through a number of mechanisms Seizures unresponsive to naloxone may be treated with intravenous
such as alveolar hypoventilation (with slow deep respirations), aspira- diazepam or lorazepam. Refractory seizures suggest either body packing
tion, and acute noncardiogenic pulmonary edema (which occurs most or a secondary process.
after successful resuscitation and administration of naloxone, from ■ ORGANOPHOSPHATE AND CARBAMATE INSECTICIDES
notably with heroin). Noncardiogenic pulmonary edema may occur
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either heroin or naloxone itself. By inhalation, heroin can trigger acute Organophosphates and carbamates are used extensively in the United
exacerbations of asthma. 325,326 States as insecticides. In addition, interest in these substances has
Other features of opioid intoxication include hypotension, bradycardia, grown in recent years because of their association with bioterrorism
decreased gut motility, rhabdomyolysis, muscle flaccidity, hypothermia, and potential for mass exposure. Organophosphates act as irrevers-
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and seizures. Seizures are most common with propoxyphene, tramadol, ible acetylcholinesterase (AChE) inhibitors. Carbamates are reversible
and meperidine. The meperidine metabolite normeperidine may cause AChE inhibitors. Insecticides can be absorbed through the mouth, skin,
seizures in the therapeutic dosing range, particularly if there is renal conjunctiva, gastrointestinal tract, or respiratory tract. Toxicity occurs
insufficiency. Propoxyphene was taken off the market because of its within 12 to 24 hours after exposure from excess acetylcholine at neural
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sodium-channel activity (similar to TCAs) and association with wide- end plates due to inhibition of AChE. 335
complex tachyarrhythmias and negative inotropy at therapeutic doses. The diagnosis of organophosphate poisoning is made on clinical
Patients classically present with small or pinpoint-sized pupils that grounds and by measurement of cholinesterase activity in the blood. The
respond to naloxone; however, the lack of miosis does not rule out opi- history may suggest attempted suicide, accidental ingestion, industrial/
oid poisoning, as coexisting toxins or other conditions such as anoxic agricultural exposure, terrorism, or rarely ingestion of contaminated
brain injury influence pupil size. food. 336,337 Emergency department personnel have also been inadvertently
The diagnosis of opioid overdose depends on a history of ingestion or poisoned through contact with patients. The signs and symptoms of
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a high index of suspicion for drug overdose, combined with compatible poisoning by both classes of insecticides are virtually identical except
clinical features. The combination of a Glasgow Coma Scale score ≤12 that carbamates do not readily cross the blood-brain barrier to cause CNS
with respiratory rate ≤12, miotic pupils, or circumstantial evidence of toxicity. Clinical features include miosis (85%), vomiting (58%), exces-
drug use has a sensitivity of 92% and a specificity of 76% for opioid sive salivation (58%), respiratory distress (48%), abdominal pain (42%),
overdose. Rapid response to naloxone corroborates the diagnosis. depressed mental status (42%), and muscle fasciculations (40%).
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Urine drug screens can support the diagnosis, but treatment is gener- In one case series, tachycardia occurred more often than bradycardia
ally required prior to results, limiting their usefulness. It should also be (21% vs 10% of cases). In early poisoning, there is a transient period of
noted that certain opioids such as fentanyl and methadone may not be intense sympathetic tone causing tachycardia, followed by heightened
detected by routine urine drug screening. parasympathetic tone and bradycardia, heart block, and ST- and T-wave
Treatment involves initial supportive measures and naloxone (see abnormalities. Breath or sweat may take on the odor of garlic.
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below). Gastric emptying may be helpful acutely, but extreme care must Clinical features of organophosphate poisoning result from overstim-
be taken not to empty the stomach in lethargic or comatose patients ulation of muscarinic, nicotinic, and central receptors (Table 124-25).
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unless the airway has been adequately protected. Although gastric lavage Muscarinic overstimulation results in sustained toxicity characterized
is most useful when it is performed within 1 hour of ingestion, this time
limit may be extended several hours because of decreased gut motility.
Activated charcoal should be administered up to 2 to 3 hours after oral
ingestion particularly with acetaminophen-containing combination TABLE 124-25 Classification of Signs and Symptoms of Acute
medications once the airway has been protected. There is a small risk Organophosphate Poisoning
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of small-bowel obstruction in the setting of decreased bowel motility. Muscarinic Nicotinic Central
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There is no role for hemodialysis.
Naloxone, a specific opioid antagonist with no opioid agonist prop- Salivation Fasciculations Anxiety
erties, reverses opioid-induced sedation, hypotension, and respi- Lacrimation Paresis/paralysis Confusion
ratory depression. The initial dose is 0.4 mg IV or 0.8 mg IM or Urination Hypertension Seizures
SC. Endotracheal and nebulized administration have both been
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18
described. Lower doses should be given when there is a concurrent Diarrhea Tachycardia Psychosis
stimulant overdose. Larger initial doses may be required when there GI cramps Ataxia
is abuse of naloxone-resistant opioids (eg, fentanyl, methadone, and Emesis
propoxyphene). If naloxone does not produce a clinical response after
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2 to 3 minutes, an additional 1 to 2 mg IV may be administered to a total Blurred vision
dose of 10 mg. In general, a lack of response to 6 to 10 mg naloxone is Miosis
required to exclude opioid toxicity. Continuing naloxone beyond a total Bradycardia
dose of 10 mg is reasonable if there is a very high index of suspicion
or a partial response has been achieved. In general, opioid antagonism Wheezing

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