PULMONARY BOARD REVIEW:
OVERDOSES AND POISONINGS
Carbon Monoxide
 Non-irritating, colorless, tasteless and odorless gas
 Poisoning occurs in the setting of smoke inhalation, attempted suicide from auto
exhaust and poorly ventilated burning charcoal or gas stoves
 Also generated from the metabolism of methylene chloride, a component of paint and
varnish removers
 Pathophysiology
-Binds to hemoglobin with an affinity that is 240 times greater than oxygen 
decreases O2 saturation and blood carrying capacity
-Directly inhibits cellular respiration through cytochrome oxidase blockade
 Diagnosis
-Index of suspicion during cold weather
-Carboxyhemoglobin levels  determined by co-oximetry on ABG (pulse
oximetry cannot distinguish between carboxyHB and oxyHB; pulse oximetry
may be “normal” despite high [CO]
 Clinical Manifestations  severity depends on [CO], duration of exposure and
minute ventilation
-5-10%  headache, mild dyspnea
-10-30%  headache, dizziness, weakness, dyspnea, irritability, nausea and
vomiting
->50%  coma, seizures, cardiovascular collapse, death
-Delayed neuropsychiatric sequelae (DNS) are noted in 10-30% of survivors
 variable manifestations include Parkinsonism, short-term memory loss,
behavorial changes, hearing loss and psychosis
 Treatment
-100% FIO2 decreases the ½ life of CO from 5-6 hrs to 40-90 min
-Hyperbaric oxygen further decreases the ½ life to 15-30 min  role has been
debated; patients with life-threatening exposures should receive at least one
hyperbaric oxygen treatment
Ethylene Glycol
 Colorless, odorless, sweet tasting alcohol
 Found in antifreeze, de-icers and industrial solvents
 Pathophysiology
-Metabolized by alcohol dehydrogenase to oxalic acid which precipitates to
calcium in the renal tubules  produces calcium oxalate crystals  leads to
ATN and hypocalcemia
-Production of oxalic acid also leads to an anion gap metabolic acidosis with
an elevated osmolar gap
 Diagnosis  check serum levels
 Clinical Manifestations

-Stage 1 (30 min-12 hrs)  inebriation, ataxia, seizures
-Stage 2 (12 hrs-24 hrs)  myocardial dysfunction, pulmonary edema
-Stage 3 (2-3 days)  acute renal failure
Treatment  need to inhibit formation of toxic metabolites
-Supportive measures  Gastric lavage in the first hour post-ingestions,
administration of calcium, folate, thiamine and B6
-Ethanol infusion  supplied as a 10% solution in D5W containing 10g of
ethanol per 100 cc of solution
Target level 100-200 mg/dL
Loading dose 0.6g/kg
Maintainence dose 66 mg/kg/hr (non-alcoholics)
154 mg/kg/hr (alcoholics)
-Fomepizole  directly inhibits alcohol dehydrogenase
Used until toxic levels fall to < 20
Loading dose 15 mg/kg IV
Maintenance dose 10 mg/kg IV q 12
-Hemodialysis  indications include:
Levels > 50
Significant and refractory metabolic acidosis
Evidence of end-organ damage
Methanol
 Colorless, odorless, bitter tasting alcohol
 Found in paint removers, duplicator fluid and windshield washing fluid
 Pathophysiology
-Metabolized by alcohol dehydrogenase to formic acid which leads to visual
symptoms secondary to optic nerve swelling
-Production of formic acid also leads to an anion gap metabolic acidosis with
an elevated osmolar gap
 Diagnosis  check serum levels
 Clinical Manifestations
-Up to 6 hrs  headache, dizziness, ataxia, confusion
-6 hrs-3 days  visual symptoms, acidosis, pancreatitis
 Treatment  same as ethylene glycol
-Hemodialysis  indications include
Levels > 50
Lethal dose ingested
Significant and refractory metabolic acidosis
Evidence of end-organ damage
Isopropanol
 Colorless, bitter tasting alcohol which smells like acetone
 Found in rubbing alcohol, skin lotions, hair tonics, aftershave, de-icers
 Pathophysiology
-Metabolized by alcohol dehydrogenase to acetone
-Does not lead to anion gap metabolic acidosis


Clinical Manifestations
-Sweet smelling breath
-Urinary ketones
-Elevated osmolar gap without metabolic acidosis
-Hemorrhagic gastritis
Treatment
-Gastric lavage if performed within 1 hour of ingestions
-Supportive measures are usually sufficient
-Hemodialysis  indications include
Lethal dose ingested
Levels >400
Refractory shock
Prolonged coma
Theophylline Toxicity:
1. Theophylline has a low therapeutic index. The usual recommended therapeutic plasma
concentration is 10 to 20 mg/L
2. Theophylline is extensively metabolized by hepatic cytochrome P450, as only a small
fraction is excreted in the urine - The half-life of theophylline in a healthy adult
nonsmoker averages 8 hours, but increases to 30 hours or more in the presence of chronic
liver disease
3. Decreased theophylline clearance - when metabolism of the drug is slowed by the
presence of concomitant disease (such as heart failure or liver disease) or by the
concurrent administration of other drugs (including erythromycin, cimetidine,
ciprofloxacin, cephalexin, tetracycline, birth control pills, allopurinol, propranolol, and
thiabendazole). Age above 60 years and early infancy.
4. Clinical:
a. Seizures can occur at a plasma theophylline concentration as low as 25 mg/L.
They are, however, more common at levels above 40 mg/L and, with chronic
dosing, are almost universal above 100 mg/L - The risk is less with an acute OD
b. Arrhythmias can begin when the plasma theophylline level is greater than 20 to
30 mg/L, but cardiovascular collapse and respiratory arrest are rare unless the
concentration is greater than 50 mg/L with chronic therapy or above 100 mg/L
with an acute overdose
c. Hypokalemia, hypomagnesemia, hypophosphatemia, hypercalcemia,
hyperglycemia, and respiratory alkalosis
d. Rhabdomyolysis occurs in selected cases
5. Treatment:
a. Decreased intestinal absorption - gastric lavage, activated charcoal given with a
cathartic such as sorbitol
b. Beta blockers and anti-arrhythmic agents
c. Control of seizures – benzo > dilantin
d. Renal Replacement Indications:
i. If the patient is clinically unstable or has seizures, life-threatening
hypotension, and/or arrhythmias
ii. If the acutely intoxicated patient has a plasma theophylline concentration
above 100 mg/L
iii. If a chronically intoxicated patient is over age 60 and has a plasma
theophylline level above 40 mg/dL
iv. If a younger chronically intoxicated patient has a plasma concentration
above 60 mg/L. If the plasma level is just above this value and the patient
is stable, dialysis can be delayed for two hours pending a second plasma
level in those patients who can tolerate repeated oral charcoal
v. If the plasma theophylline level is above 60 mg/L in a patient at high risk
for seizures or one or more of the following problems:
1. Impaired metabolism of theophylline due to chronic liver disease,
heart failure, or hypoxemia (PO2 40 mmHg).
2. Inability to tolerate repeated dose oral charcoal because of
intractable vomiting or intestinal ileus.
3. Increased susceptibility to severe toxicity, which occurs in patients
who are elderly or who have ischemic heart disease, severe chronic
lung disease, or a history of epilepsy
vi. HD = net effect is removal of 40 percent of the administered dose in three
hours, added advantage of correcting the electrolyte abnormalities
vii. HP = Hemoperfusion is even more effective, HP cartridges are prone to
saturation – may have to change the cartridge every two hours
Clostridium:
1. Botulinum:
a. Food Botulism:
i. descending muscle weakness – upper extremities to lower extremities
ii. CN – blurred vision, diplopia, ptosis, urinary retention
b. Wound Botulism: like food
c. D/D: MG (no autonomic findings), LEMS, Tick Paralysis, GBS (ascending
paralysis), Polio, CVA
d. Think botulism: no fever, symmetrical neurological findings, responsive, normal
to decreased heart rate, normal BP, no sensory deficits
e. Treatment: Botulism anti-toxin (SE: serum sickness), PCN G or Flagyl
2. Tetani:
a. Tetanus toxin blocks neurotransmission  disinhibits neuron (ant. Horn cells) 
increased muscle tone, spasms, autonomic instability
b. Clinical: lockjaw, sweating, tachycardia, fever, increased or decreased BP,
Aware!, stiff neck, opisthotonus, sardonic smile, rigid abdomen, periods of apnea,
dysphagia
c. Treatment:
i. wound debridement
ii. PCN G or Cephalosporin or Flagyl
iii. Tetanus immune globulin
iv. Active immunization – TD x 3 every 2 weeks
v. Benzos, baclofen, b-blocker, MgSO4