Case 1
A 36-year-old woman with no past medical history and taking no
conventional medications ingested a herbal preparation marketed
for “internal cleansing.” Its ingredients were neither
known to the patient nor listed on the product's accompanying
literature. The product claimed to be an herbal product created
from plants picked from the Amazon jungle. She purchased the product
from a street vendor in an urban area and consumed the entire
contents of the package, although the insert stated it should
be divided into 4 doses. This appeared to be an actual product
with a marketing strategy and not a home-packaged herbal product.
The next morning, nausea, vomiting, and weakness developed. In
the emergency department, her blood pressure was 86/30 mm Hg,
and her pulse rate was 30 beats/min. Here is her rhythm strip/ECG:
Her pupils were 3 mm, equal, and reactive to light. Her oral mucosa
was moist, and her lungs were clear to auscultation. Her cardiovascular
examination revealed a slow and irregular pulse rate with no murmurs,
gallops, or rubs. Her abdomen was nontender, with normal bowel
sounds. Neurologic examination was nonfocal, but she was globally
weak.
Serum chemistry showed sodium concentration of 138 mEq/L, potassium concentration of 6.3 mEq/L, chloride concentration of 101 mEq/L, bicarbonate concentration of 21 mg/dL, blood urea nitrogen concentration of 15 mg/dL, creatinine concentration of 1.0 mg/dL, and glucose concentration of 110 mg/dL. A CBC count and a chest radiograph revealed no abnormalities.
1. What does the ECG/rhythm strip show?
2. If you suspect the patient is poisoned, detail
a directed physical exam and list findings for the specific toxidromes.
3. If you suspect the patient is poisoned, detail
what screening ancillary/lab testing is indicated?
4. Given the physical exam and lab testing above,
what, if any, specific lab testing is indicated?
5. In addition to supportive care, what, if any,
empiric antidotal therapy is indicated and how should it be administered?
6. What is the risk, if any, in giving an empiric
antidote.
7. Is this patient poisoned, and if so, with what?
ANSWERS:
1. What does the ECG/rhythm strip show?
ANSWER: Her ECG revealed a junctional rhythm at a rate of 30 beats/min
and a digitalis effect on the ST segments (the so-called "Salvador
Dali" sign).
2. If you suspect the patient is poisoned,
detail a directed physical exam and list findings for the specific
toxidrome.
ANSWER: Patients suspected of having been poisoned need a careful
evaluation of vital signs/SaO2, mental status, pupils for nystagmus/mydriasis/miosis
and reactivity, mucous membranes for dryness or salivation, skin
for diaphoresis or dryness (check the axilla), presence or absence
of bowel sounds, and a clinical determination for urinary retention
by palpation of the lower abdomen. In some cases, unusual odors
can provide clues to certain poisons. In addition, you should
look for signs of IV drug abuse.
Anticholinergic, sympathomimetic, opioid, anticholinesterase,
and sedative-hypnotic or barbiturate poisonings may be recognized
by their characteristic toxidromes. In the clinical setting when
the patient’s history is limited or nonexistent, characteristic
physical findings suggesting a specific dru class may be critical
in refining the diagnosis, focusing the management, and directing
the antidotal intervention, such as naloxone for opioids or physostigmine
for anticholinergic overdoses. Limitations of this approach include
the not infrequent occurrence of mixed intoxications and presentations
that manifest only a few of the “textbook” signs and
symptoms. Failure of the physical findings to be readily categorized
as a toxidrome certainly does not exclude a toxic etiology.
Anticholinergic Syndrome
Drugs and toxins that block acetylcholine at muscarinic
receptors cause the anticholinergic toxidrome. Physical findings
include elevated temperature; delirium; mumbling speech; tachycardia;
dry, flushed skin; dry mucous membranes; urinary retention; decreased
to absent bowel sounds; mydriasis; and blurred vision. Seizures
and coma may also occur. A simple mnemonic, “hot as a hare,
blind as a bat, dry as a bone, red as a beet, mad as a
hatter, bloated as a bladder,” describes many of the features
of the anticholinergic toxidrome.
Atropine and atropine-like agents cause this syndrome. Atropine-like
agents include a number of commonly used over-the-counter cold
medications containing antihistamines, antiparkinson medications
such as benztropine and trihexyphenidyl, topical mydriatics, antispasmodics
such as Donnatal and dicyclomine, muscle relaxants such as cyclobenzaprine
and orphenadrine, and belladonna alkaloids such as scopolamine
and hyoscyamine. Cyclic antidepressants also cause anticholinergic
symptoms. Plants that contain belladonna alkaloids include jimson
weed (Datura stramonium), deadly
nightshade (Atropa belladonna), and henbane (Hyoscyamus niger).
Sympathomimetic Syndrome
Sympathetic agonists such as cocaine and amphetamine produce
hypertension,
diaphoresis, tachycardia, tachypnea, hyperthermia, and mydriasis.
Restlessness, agitation, excessive speech, tremors, and insomnia
also occur. Severe cases are associated with dysrhythmias and
seizures. Other agents that may cause sympathomimetic effects
include over-the-counter decongestants such as phenylpropanolamine,
ephedrine, and pseudoephedrine. Theophylline and caffeine may
cause many of these findings by enhancing catecholamine release.
Overdoses with (F×2 -adrenergic receptor agonists,
methylphenidate, and Ephedra species such as ma huang cause sympathomimetic
symptoms.
This symptom complex may be difficult to distinguish from the
anticholinergic syndrome. Whereas sweating and normal to hyperactive
bowel sounds are associated with sympathomimetic overdose, the
anticholinergic toxidrome is manifested by dry skin and diminished
bowel sounds.
Opioid Syndrome
The classic triad of opioid intoxication is mental status depression,
respiratory depression, and pinpoint pupils. Bradycardia, hypotension
(rare), hypothermia, hyporeflexia, and needle marks may be present.
Opioids commonly associated with this toxidrome include morphine,
heroin, designer fentanyls, oxycodone, hydromorphone, and propoxyphene.
Meperidine,
pentazocine, and dextromethorphan may cause CNS and respiratory
depression but are often associated with dilated pupils. Central
¥2 -receptor agonists such as clonidine, guanabenz, guanfacine,
and imidazoline derivatives that act on the locus ceruleus of
the CNS cause many of these same symptoms in the overdose setting.
Anticholinesterase Syndrome
Organophosphates are commonly available as insecticides.
They are readily absorbed through the skin, mucous membranes,
and respiratory and gastrointestinal tracts. Organophosphates
inactivate cholinesterase enzymes, resulting in accumulation of
acetylcholine at receptor sites and overstimulation of muscarinic,
nicotinic, and central acetylcholine receptors. Other causes of
cholinesterase inhibition include carbamates and
therapeutic cholinesterase inhibitors such as physostigmine, pyridostigmine,
neostigmine, and edrophonium. Clinical findings suggestive of
acute anticholinesterase intoxication
include muscarinic effects as well as muscle weakness, fasciculations,
altered mental status, seizures, and coma. DUMBELS is a mnemonic
used to recall many of the muscarinic effects: defecation, urination,
miosis, bronchorrhea, bronchospasm, bradycardia, emesis, lacrimation,
and salivation.
Sedative-Hypnotic Syndrome
Sedative-hypnotic overdoses are associated with hypotension,
bradypnea, hypothermia, mental status depression, slurred speech,
ataxia, and hyporeflexia. The sedative-hypnotic group includes
barbiturates, benzodiazepines, buspirone, paraldehyde, chloral
hydrate, meprobamate, methaqualone, ethchlorvynol, glutethimide,
and zolpidem. Of course, ethanol
intoxication may also present with many of these symptoms. Ingestion
of neuroleptics, cyclic antidepressants, and skeletal muscle relaxants
may also cause significant sedation. Bullous lesions have been
reported in some patients with sedative-hypnotic overdoses. Paradoxical
excitement is seen with some of the sedative-hypnotics, especially
in very young and elderly
patients.
3. If you suspect the patient is poisoned,
detail what screening ancillary/lab is testing indicated?
ANSWER: Patients suspected of having been poisoned should get
a minimum screening to include an ECG, fingerstick glucose, BMP/Anion
Gap, and APAP level. Other random serum or toxicological testing
is expensive, time consuming, and generally not clinically helpful.
Specific toxicological testing is based on the history, physical
exam findings, and
abnormalities found on ECG, electrolytes, glucose, or anion gap.
4. Given the physical exam and lab testing
above, what, if any, specific lab testing is indicated?
ANSWER: This patient needs a digoxin level. Unfortunately the
result is delayed and, depending on the type of assay used, routine
hospital laboratory may be false-negative for other digoxin-like
cardiac glycosides for which the antidote will effectively cross-react.
5. In addition to supportive care, what,
if any, empiric antidotal therapy is indicated?
ANSWER: In general, following securing of the ABCs, altered and/or
poisoned patients should get oxygen, bedside determination of
blood glucose or empiric D50%, perhaps thiamine and consideration
for narcan if ventilatory embarrassment appears eminent (respiratory
rate < 6/min). The critical step for the clinician in this
case is to recognize the signs and symptoms of acute cardioactive
steroid poisoning, which includes nausea,
vomiting, abdominal pain, hyperkalemia (due to poisoning of the
Na+-K+-ATPase pump), bradycardia, and other appropriate digoxin-like
ECG changes. The ECG findings of the digoxin effect include a
scooping ST segment and a prolonged PR interval. As in digoxin
toxicity, this might progress to any dysrhythmia except an atrial
tachycardia with a rapidly
conducting ventricular response (i.e., atrial fibrillation with
a rapid ventricular response or supraventricular tachycardia).
Typically, premature ventricular contractions and atrioventricular
nodal dissociation can be seen. Once poisoning by a pharmacologically
active cardioactive steroid is suspected, serum electrolyte measurement,
particularly potassium measurement, and an ECG should be acquired.
To draw a comparison, this is
similar to an acute digoxin overdose in which the patient is showing
signs of toxicity and the dose ingested is unknown. If there are
signs of toxicity, 10 vials of digoxin-specific Fab should be
empirically administered because it will be impossible to quantify
the exposure from an herbal product. If there is no response after
30 minutes, another 10 vials
should be considered. Digoxin-specific Fab is a polyclonal product
and can cross-treat other cardioactive steroids with varying and
unknown specificity, which makes dosing of the antidotal therapy
difficult. Acquisition of the herbal product from the patient
should always be attempted to assist with the subsequent public
health investigation. The
combination of bradycardia with a normal blood pressure, the junctional
rhythm with the scooping ST segments, and the hyperkalemia was
enough to warrant administration of antidotal therapy in this
case.
6. What is the risk, if any, in giving
an empiric antidote?
ANSWER: Nothing is risk free and there in many cases, antidotes
themselves can be toxic. With regard to empiric use of digoxin-specific
antibody (Fab) fragments (Digibind), say in a patient already
on digoxin who is acutely or chronically accidentally poisoned,
the Digibind will remain active for weeks, preventing the patient
from being digitalized later once the poisoning episode has been
resolved. Otherwise, Digibind is generally safe despite a few
case reports of hypokalemia, rash, worsening of congestive heart
failure, and several other nonspecific functional symptoms.
7. Is this patient poisoned, and if so,
with what?
ANSWER: The patient is poisoned with cardioactive digitalis-like
steroids.
One hour after the 10 vials of digoxin-specific Fab were administered,
the nausea, vomiting, and weakness resolved. Her ECG also reverted
to sinus rhythm at a rate of 68 beats/min. She was admitted to
the telemetry unit for 24 hours and then was transferred to the
floor the following day. The patient was discharged home in normal
health after a 2-day hospitalization. Subsequently, serum analysis
with a more digoxin-specific immunoassay (Tina Quant, Roche Diagnostics,
Basel, Switzerland) than the fluorescence
polarization immunoassay found a digoxin concentration of 0.34
ng/mL. Further serum testing with an enzyme immunoassay for digitoxin
revealed a concentration of 20 ng/mL (therapeutic range 10 to
30 ng/mL). Serum high-performance liquid chromatography analysis
revealed the presence of digoxin (0.3 ng/mL) and active digitoxin
metabolites; the parent compound was not present. The active digitoxin
metabolites were in the following
proportions: digitoxin-monodigitoxoside, 11 ng/mL; digitoxigenin,
5 ng/mL; and digitoxin polar metabolites, 5 ng/mL.
REFERENCES:
Fermin Barrueto Jr., et al. Cardioactive steroid poisoning from
an herbal
cleansing preparation. Ann Emerg Med, 2003 Mar; 41(3):396.
Ford: Clinical Toxicology, 1st ed., 2001 W. B. Saunders, pp. 3, 51-57.
EDWARD L. FIEG
7 Maryland Plaza/ #201
St Louis MO 63108
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efieg@prodigy.net
elfieg@sbcglobal.net
fiege@msnotes.wustl.edu