Beta-Blocker and Calcium Channel Blocker Key Concepts
Introduction: BB and CCBs are some of the more dangerous ingestions frequently
encountered.
The most dangerous BB is propranolol. Due to its ability to block sodium channels it can
cause QRS widening and ventricular dysrhythmias similar to tricyclic antidepressants.
Furthermore, its lipid solubility allows it to cross the blood brain barrier where it blocks
cerebral sodium channels thereby causing seizures.
The most dangerous CCBs are the non-dihydropyridines verapamil and diltiazem
(verapamil is worse). Non-dihydropyridines are more dangerous because they have a
higher affinity for cardiac calcium channels and “poison the pump” (causing bradycardia),
while the dihydropyridines have higher affinity for vascular cardiac channels and “poison
the pipes” (causing vasodilation and a potential reflex tachycardia). Humans can only
vasodilate so much, and the heart can compensate via increased cardiac output, but no one can
tolerate the cardiac output of zero that can result from too much cardiac calcium channel
blockade. Having said that, as the dose of a dihydropyridine increases it loses its selectivity and
blocks both cardiac and vascular calcium channels.
Signs/symptoms:
Generally, the signs and symptoms of BB and CCB ODs are pretty simple. Patients will be
bradycardic and hypotensive (unless that have reflex tachycardia from lower doses of
dihydropyridines. What is often impressive is how awake and alert the patient is despite profound
bradycardia and hypotension. Do not be fooled by the patient’s appearance. They could be
minutes away from death. Propranolol patients typically experience more CNS sedation due to
its high lipid solubility resulting in increased CNS concentrations.
Labs: CCB ODs frequently are hyperglycemic since blockade of pancreatic calcium channels
inhibits insulin release. Textbooks frequently state that BB ODs are hypoglycemic, but in reality
they are typically euglycemic.
Decon: If the patient ingested a large overdose (especially of nondihdropyridine CCBs or
propranolol) within the last hour or two, they should receive gastric lavage. 50 grams of
activated charcoal should be given. In the event they took an extended release
formulation, whole bowel irrigation may be appropriate.
Treatment:
1) Give intravenous fluid but avoid more than 2-3 liters of NS since these patients tend to
die from profound pulmonary edema that results from an extremely low cardiac output
and ejection fraction.
2) Glucagon: Glucagon is used in beta-blocker overdose because it activates the Breceptor at a different location farther down the pathway than where the BB binds.
Glucagon increases intracellular concentration of cyclic AMP, thereby improving
myocardial contractility. A typical dose is 5-10mg IV (not the mere 1-2 mg you would use
for a food bolus) followed by a 5-10 mg/hr infusion. Generally, in a large OD, it will not be
sufficiently effective.
3) Calcium is used in CCB overdose and causes an increased extracellular gradient that
forces more calcium into the cell. Intravenous calcium infusions have been shown to be
helpful, although response is often short lived. Initial bolus should be 10-20 mL of 10%
calcium chloride (i.e., 1-2 grams) (CHILD: 10 to 30 mg/kg over 5 minutes) or 20-40 mL of
10% calcium gluconate solution (2-4 grams) that can be repeated every 3-5 minutes up
to 3-4 doses. Patients that respond to calcium infusion can be placed on a continuous
infusion at 1-2 grams/hour.
4) Vasopressors: Epinephrine is usually the pressor of choice, but use whatever you can
get your hands on quickly.
5) High-dose Insulin Euglycemia: During times of stress the myocardial cells switch from
fatty acid metabolism to glucose metabolism. The blockade of pancreatic insulin cells
inhibits the calcium-dependent release of insulin. Without insulin, myocardial cells are
unable to transport glucose intracellularly, resulting in the heart cells’ lacking fuel with
which to function. Providing insulin (at least in theory) enables the cardiac cells to get the
glucose they need. Insulin is also a direct inotrope, which may explain why it also
appears to be effective in BB OD. Remember it is HIGH dose insulin (1 U/kg push,
the 1-10 U/kg/hr infusion). Do not use DKA doses. Go big or go home! With CCB ODs
the pt is typically hyperglycemic and will not require much D50. BB ODs will likely require
intermittent pushes of D50. Avoid running a D5 or D10 drip too fast or too long due to the
volume overload issue mentioned before. Insulin is a vasodilator so it will help the
cardiac output, but it will not raise the SBP all the way to 120. Just try to keep the MAP
above 60. There is growing evidence to indicate that insulin is more effective than
pressor, so try and get patients onto insulin and off of pressors as soon as you can.
6) Intralipid: Verapamil, propranolol, and several other CCB/BB are lipid soluble, and there
are case reports of it being effective. It is generally reserved as a last ditch effort for the
crashing patient.
7) Pacemaker: Everyone likes to try the pacemaker but they rarely ever work. Pacemakers
are good for when the electrical system of the heart is broken but the left ventricle still
works well (i.e., an inferior MI). In the case of a BB or a CCB OD, many cardiac cells are
poisoned. Flogging a poisoned cell with electricity will not suddenly make it work.
8) Bypass/ECMO: The tox patient is the ideal candidate for bypass/ECMO because if you
can sustain them through the next few days, they will metabolize the drug and recover
completely. Convincing the surgeon to hook the patient up to the machine is the difficult
part.
9) Intra-aortic balloon pumps have also been effective.
Salicylate Overdose Key Concepts
Introduction: Talk to old ED docs, and they will remember people dying of ASA OD on a regular
basis, but these days we rarely see it. Due to the current lack of familiarity, people frequently fail
to recognize the severity of this toxicity. These patients end up dying when aggressive care may
have saved them. If you don’t fear ASA ODs, you should!
Signs/Sxs: The first symptom is typically vomiting. Patients may or may not have tinnitus or
just decreased hearing. Auditory changes tend to resolve as the serum concentration increases.
Initially patients develop a respiratory alkalosis secondary to the hyperpnea (deep, rapid
respirations similar to Kussmaul respirations), which is a result of direct stimulation of the brain’s
respiratory center. This can be inhibited if the patient co-ingests a drug that causes respiratory
depression (i.e., an opioid like morphine). The patient’s tachypnea is often missed by the person
getting triage vitals, so count the respirations on your own.
As serum ASA levels rise the patient develops a metabolic acidosis (ASA is an acid). ASA
uncouples oxidative phosphorylation in muscles (decreased ATP production, excess heat
generated may result in fever), and disrupts gluconeogenesis, fatty acid metabolism, and Krebs
cycle (hypoglycemia may occur, inorganic acids such as lactate, pyruvate may build up).
Depending upon how shortly after overdose the patient presents, he may be normal, have a
respiratory alkalosis, or have a combined respiratory alkalosis and metabolic acidosis (this
is the most common presentation). Common lab findings would be . . .
pH = 7.5, pCO2 =22 (respiratory alkalosis), serum bicarb =12 (metabolic acidosis), anion
gap = 18
As serum and brain concentrations rise, the pt may become jittery, agitated, confused, and
eventually comatose. Seizures may occur. Hyperthermia can occur in severe cases and is
considered a pre-terminal event.
Chronic toxicity (pt taking too much for several days for a toothache) tends to be more subtle and
can be mistaken for pneumonia or sepsis. Pulmonary edema tends to occur in older patients who
have chronically overdosed. If you have a patient that seems a little altered and appears to have
sepsis but you aren’t quite sure, send an ASA level.
Treatment:
First, these patients are always dehydrated from their vomiting and hyperventilation. Give 2L of
NS bolus.
Give multi-dose activated charcoal.
A key concept to understand about ASA toxicity is that patients die when too much ASA gets into
their brain causing cerebral edema and herniation. Two things determine how much salicylate
gets into the brain: 1) the serum concentration of ASA, and 2) the serum pH. The more acidemic
a patient is, the more ASA that is in the non-ionized form and able to cross the blood-brain
barrier. Your job as a nEM doc is to keep the ASA out of the brain! You accomplish this in 2
ways:
1) Alkalinize the urine. You alkalinize the urine by giving IV sodium bicarb. Add 3 amps of
sodium bicarb and 40 meq of potassium to 1L of D5W, and then infuse it at a rate
of 200-250 mL/hour. Alkalinizing the urine traps ASA in the urine, thereby creating a
concentration gradient and decreasing the serum and brain levels.
2) Alkalinize the serum. You alkalinize the serum via the bicarb that was just discussed.
This help to keep ASA in the ionized form and prevent it from crossing the blood-brain
barrier. The patient should also be alkalinizing his own serum by the respiratory alkalosis
he has induced with his hyperpnea. Do not take away this very important respiratory
alkalosis by intubation. Sometimes the patient will take a co-ingestant that prevents him
from hyperventilating (i.e. opioids) or he will have developed so much cerebral edema
from the ASA that he is no longer hyperventilating. In each of these cases you need to
hyperventilate the patient by intubation and mechanical ventilation. DO NOT USE
ARDS-NET PROTOCOLS. If you ventilate these patients at a respiratory rate of
10/min and a tidal volume of 6-8 mL/kg you will be guilty of a clean kill. Put them
on a tidal volume of 10-12 mL/kg and a rate > 20 breaths per minute. Check VBGs
frequently. If the pt is becoming increasingly acidemic, ventilate more.
Check ASA levels and pH every hour! Too many patients die because the lab is checked
every 4-6 hours. If the VBG reveals the patient is becoming acidemic or the ASA is
increasing despite therapy, dialysis may be necessary. Keep in mind that individual patients
may have severe toxicity at lower levels and may require dialysis due to underlying physiology
and pathology. Generally accepted recommendations for hemodialysis in textbooks include the
following:
1) ASA level>100mg/dL in acute ingestions
2) altered mental status
3) medical management with urinary alkalinization not effective (serum ASA level
increasing or pH decreasing)
4) patient unable to handle fluid load due to congestive heart failure or renal
insufficiency
5) patient unable to urinate due to renal insufficiency
6) severe acidosis pH < 7.3
When to stop therapy Treatment may be stopped when the salicylate level is trending down and
has fallen below 30mg/dL in the clinically stable patient.
Salicylate Toxicity Do’s and Don’ts
DO check an acetaminophen level in a patient with a toxic aspirin level because a patient may
confuse types of analgesic medications.
DO check serial aspirin levels to establish a trend.
DO check the units of the aspirin level (e.g. mg/L vs. mg/dL).
DO NOT suppress a patient’s respiration (e.g. sedation or decreasing respiratory rate on
ventilator) because acidosis may worsen.
Tricyclic Antidepressant OD Key Concepts
Introduction: Tricyclic antidepressants are prescribed for many indications including depression
and chronic pain. In overdose (OD), they represent a major cause of poisoning, hospitalizations
and deaths.
Mechanism of Toxicity
A. Cardiovascular (CV) – Several mechanisms contribute
1. Anticholinergic effects and inhibition of neuronal reuptake of catecholamines
both result in tachycardia. Generally, the greater the tachycardia the
greater the overdose.
2. Alpha-adrenergic blockade results in vasodilation  hypotension.
3. Membrane depressant (quinidine-like) effects cause myocardial
depression and cardiac conduction disturbances by inhibition of fast
Na channels that initiate the cardiac action potential. Metabolic acidosis
or respiratory acidosis can contribute to cardiotoxicity by inhibiting the
fast Na channels.
B. Central Nervous System (CNS) – Partially due to anticholinergic effects like sedation
and coma, but seizures may occur from inhibition of serotonin and norepinephrine
reuptake.
Clinical Presentation – Depending on the specific drug and dose, the patient may exhibit none
or all of the effects listed below. Symptom onset usually begins 30-40 min after ingestion.
Patients may deteriorate very rapidly. Those with life-threatening ingestions (i.e., > 1 gm)
generally deteriorate within the first couple of hours.
A. CV
1. Typical ECG findings include the cardiac conduction delays of
a. Prolonged PR
b. Prolonged QRS (In a prospective study by Boehnert & Lovejoy
[NEJM 1985], QRS > 100ms was associated with 34% seizure rate,
and a QRS of >160ms was associated with ventricular
dysrhythmias.)
c. Prolonged QTc
d. AV block
e. Other findings suggestive of TCA ingestion likelihood (but not
necessarily the extent of sodium channel poisoning) include the
terminal 40-ms axis of the QRS complex.
i. Common abnormalities seen in TCA-poisoned Pts are an R
wave (positive deflection) in aVR and an S wave (negative
deflection) in leads I and aVL.
ii. The combination of a rightward axis shift in the terminal
40ms of the QRS, along with a prolonged QTc and sinus
tachycardia, is highly sensitive and specific for TCA
poisoning.
iii. One prospective study (Liebelt) suggested that an absolute
height of the terminal aVR that is > 3mm was 81% sensitive
in predicting seizures or dysrhythmias in TCA-poisoned Pts.
2. Dysrhythmias: Sinus tachycardia with QRS prolongation may resemble VT,
but true VT or VF may also occur. Torsade de pointes may occur in OD.
3. Hypotension by venodilation is common. Hypotension can also result from
myocardial depression, leading to shock and pulmonary edema.
4. CNS: Can have rapid transition from alert to sedated to seizing to dead.
B. Seizures
1. Common with TCA OD
2. May be recurrent or persistent
Muscular hyperactivity from myoclonic jerking or seizures can lead to
hyperthermia  rhabdomyolysis, multiorgan failure, brain damage, death
4. The acidosis caused by the seizure increases the risk of V-fib/V-tach.
C. Death- With large OD death usually occurs within 1-2 hours of ingestion. Often
results from VF, cardiogenic shock, or status epilepticus with hyperthermia.
3.
The classic presentation of a significant TCA overdose in tachycardia, then hypotension,
then seizure causing a worsening acidosis resulting in cardiac dysrhythmia and death
within 6 hours after the overdose.
If the patients is asymptomatic a 6 hours with a normal ECG, they are unlikely to develop
toxicity and can be medically cleared. There are no extended release formulations of
TCAs.
Diagnosis – Should be suspected in any patient with hypotension, tachycardia, lethargy, coma,
seizures, and ↑QRS on ECG (QRS > 100 ms, terminal R in aVR > 3mm, R to S ratio in aVR >
0.6). Check ECGs every 15-30 minutes for the first few hours, monitoring closely for QRS
prolongation.
Treatment
A. ABCs – If you think the patient got a significant exposure then consider intubating
in order to perform gastric lavage and give activated charcoal. Treating a
seizing TCA OD is much easier if they are already intubated.
B. Seizures – Treat aggressively with benzos. If seizures are not well controlled with
anticonvulsants, intubate and paralyze the patient with a nondepolarizing NM
blocker, like pancuronium, and monitor with constant EEG.
C. In patients with QRS prolongation and hypotension, give sodium bicarb, 1-2 mEq/
kg IV and repeat as needed to maintain arterial pH 7.45-7.55. Do not place on a
bicarb drip since it provides such a small dose of bicarb compared to bicarb pushes.
If you cannot give further doses of bicarb due to the pH, consider adjusting the
ventilatory rate or giving 3% hypertonic saline.
D. Treat hypotension with vasopressors and bicarb.
E. Hyperventilation can be used to induce a respiratory alkalosis thereby decreasing the
TCA’s affinity for the Na channel.
F. Mechanical support of circulation may be necessary (cardiopulmonary bypass).
G. Physostigmine is contraindicated. It has been associated with asystole.
Organophosphate Poisoning Key Concepts
Introduction: Organophosphates (OPs) are pesticides frequently involved in accidental and
suicidal poisonings throughout the world. They are also used in chemical warfare as “nerve
agents.”
Mechanism of toxicity: OPs inhibit the enzyme acetylcholinesterase (AChE) resulting in
excessive accumulation of the neurotransmitter at muscarinic receptors (cholinergic effector
cells), nicotinic receptors (skeletal neuromuscular junctions) and in the CNS.
Permanent inhibition of AChE can occur through covalent binding to OP (called “aging”).
Once aging has occurred the pt will not regain normal function until their body regenerates
sufficient AChE, which can take weeks to months.
Clinical Presentation:
1. Muscarinic Sxs: Vomiting, diarrhea, abdominal cramping,
bronchospasm, miosis (the most sensitive finding), bradycardia,
salivation, and lacrimation.
2. Nicotinic Sxs: Muscle fasciculations, tremor, and weakness potentially
leading to respiratory failure.
3. CNS Sxs: Agitation, seizures, and coma.
The following pneumonic may help:
S – Salivation, Seizures
L – Lacrimation
U – Urination
D – Defecation
G – GI irritation
E – Emesis
And the Killer B’s (these are the things that kill you): Bradycardia, Bronchorrhea,
Bradypnea, Brochospasm
Decontamination: Remove contaminated clothing. Wash skin thoroughly with soap and
water. Universal precautions and nitrile gloves protect staff from contamination. Systemic toxicity
can result from dermal exposure.
Activated charcoal is contraindicated because of possible respiratory depression,
seizures, and risk of aspiration. Consider nasogastric tube for aspiration of gastric contents, or
gastric lavage for recent large ingestions, if patient is intubated or able to protect airway.
Treatment: Treatment focuses on reversing the muscarinic effects with atropine (does not
reverse the nicotinic effects), preventing aging of AChE with pralidoxime, and treating
seizures with benzodiazepines.
1. Airway management: Immediately assess airway and respiratory function.
Administer oxygen. Suction secretions. Endotracheal intubation may be necessary
because of respiratory muscle weakness or bronchorrhea. Avoid succinylcholine
for rapid sequence intubation as prolonged paralysis may result.
2. Atropine: Atropine is used to treat muscarinic effects (e.g. salivation, lacrimation,
urination, defecation, GI effects, bronchorrhea). ADULT: 1 to 3 mg IV; CHILD: 0.02
mg/kg IV. If inadequate response in 3 to 5 minutes, double the dose. Continue
doubling the dose and administer atropine IV every 3 to 5 minutes as needed to
dry pulmonary secretions. Once secretions are dried, maintain with an infusion of
10% to 20% of the loading dose every hour. Monitor frequently for evidence of
cholinergic effects or atropine toxicity (e.g. delirium, hyperthermia, ileus) and titrate
dose accordingly. Large doses (hundreds of milligrams) are sometimes required.
Atropinization may be required for hours to days depending on severity. In the event
the patient develops excessive CNS toxicity from the atropine, glycopyrrolate
(an anticholinergic which does not cross the blood-brain barrier) may be used.
3. Pralidoxime (2-PAM): Treat moderate to severe poisoning (fasciculations, muscle
weakness, respiratory depression, coma, seizures) with pralidoxime in addition to
atropine; most effective if given within 48 hours. Administer for 24 hours after
cholinergic manifestations have resolved. May require prolonged administration.
4. Benzodiazepines: IV benzodiazepines are indicated for seizures or agitation
(diazepam 5 to 10 mg IV, lorazepam 2 to 4 mg IV). Repeat as needed.