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1. Zohair Al Aseri MD,FRCPC EM & CCM
 Cardiovascular
BB & CCB
Intoxication

2. Introduction
a 64-year-old man in the critical bay who took
an overdose of his medications.
Zohair Al Aseri MD,FRCPC EM & CCM

3. has a history of hypertension, atrial fibrillation, and
depression.
lethargic but arousable
reports he took about 40 tablets of immediate-release
metoprolol three hours ago in an attempt to “end it all.”
Zohair Al Aseri MD,FRCPC EM & CCM

4. “Is it too late for gastric decontamination?
If he is symptomatic, which therapy will you
try first, and what are your options?”
Zohair Al Aseri MD,FRCPC EM & CCM

5. a 2-year-old child in the pediatric area who was
found playing with grandma’s bottle of verapamil
controlled release 15 minutes ago.
The grandmother thinks that at most there are
three tablets missing.
Zohair Al Aseri MD,FRCPC EM & CCM

6. Child looks great
“Are three tablets a big deal?
Can we just watch the child for a couple of
hours?
Do we need an IV and blood work?
Zohair Al Aseri MD,FRCPC EM & CCM

7. Overdose of propranolol is the most deadly,
followed by acebutolol, oxprenolol, and alprenolol
Zohair Al Aseri MD,FRCPC EM & CCM
Perspective
BETA-ADRENERGIC BLOCKERS

8. inhibit endogenous catecholamines such as
epinephrine at the beta-receptor.
Zohair Al Aseri MD,FRCPC EM & CCM
Principles of Disease
Pathophysiology

9. Equally important properties, which vary from
one beta-blocker to another, include
cardioselectivity, membrane-stabilizing effect,
lipophilicity, and intrinsic sympathomimetic
activity.
Although cardioselectivity is lost in overdose,
cardioselective beta-blockers such as atenolol,
metoprolol, and esmolol are associated with a
lower mortality rate than propranolol, the oldest
beta-blocker.
Zohair Al Aseri MD,FRCPC EM & CCM
Principles of Disease
Pathophysiology

10. Selected Characteristics of Common Beta-Blockers
Zohair Al Aseri MD,FRCPC EM & CCM

11. Beta-blockers are rapidly absorbed after oral
ingestion, and the peak effect of normal-release
preparations occurs in 1 to 4 hours.
 
Hepatic metabolism on first pass results in
significantly less bioavailability after oral dosing
than with IV injection (1
 : 40 for propranolol).
Volume of distribution for various beta-blockers
generally exceeds 1
 L/kg, meaning tissue
concentrations exceed those of serum.
Zohair Al Aseri MD,FRCPC EM & CCM
Principles of Disease
Pathophysiology

12. Therefore, hemodialysis is not efficacious for
most beta-blockers.
Protein binding varies from 0% for sotalol to 93%
for propranolol.
Elimination half-lives vary from 8 to 9 minutes for
esmolol to as long as 24 hours for nadolol and
others
 
Zohair Al Aseri MD,FRCPC EM & CCM
Principles of Disease
Pathophysiology

13. Bradycardia the most common
Hypotension and unconsciousness are the
second and third most common signs.
Much of propranolol's toxicity derives from its
lipophilic nature and membrane-stabilizing effect
that allow it to penetrate the CNS, leading to
obtundation, respiratory depression, and
seizures. Other beta-blockers do not have these
effects.
Zohair Al Aseri MD,FRCPC EM & CCM
Clinical Features

14. Seizures probably result from a combination of
hypotension, hypoglycemia, hypoxia, and direct
CNS toxicity.
Surprisingly, bronchospasm is not problematic in
cases of beta-blocker overdose, even with
nonselective beta-blockers.
Zohair Al Aseri MD,FRCPC EM & CCM
Clinical Features

15. Zohair Al Aseri MD,FRCPC EM & CCM
MANIFESTATIONS AND COMPLICATIONS OF
BETA-BLOCKER OVERDOSEIN ORDER OF
DECREASING FREQUENCY

16. Propranolol's membrane-stabilizing effect impairs
SA and AV node function and leads to bradycardia
and AV block.
Ventricular conduction is also depressed, leading to
QRS widening and occasional ventricular
dysrhythmias.
Nadolol and acebutolol also have a significant
membrane-stabilizing effect.
These BB, like the TCA, can cause ventricular
dysrhythmias such as VT, VF and torsades de
pointes as well as the bradydysrhythmias more
characteristic of beta-blockers in general.
Zohair Al Aseri MD,FRCPC EM & CCM
Clinical Features

17. The intrinsic sympathomimetic activity of some
beta-blockers such as pindolol and carteolol has
led to some unusual manifestations such as
sinus tachycardia instead of bradycardia and
ventricular dysrhythmias.
Labetalol is unique in that it also blocks alpha-
adrenergic receptors, yielding an additional
mechanism for hypotension.
However, labetalol's beta-blockade is three to
seven times more potent than its alpha-blockade.
Zohair Al Aseri MD,FRCPC EM & CCM
Clinical Features

18. In contrast to digitalis, beta-blocker toxicity has a
more rapid onset: life-threatening CNS and
cardiovascular effects can occur 30 minutes after
oral overdose.
Patients ingesting delayed-release preparations
may remain asymptomatic for several hours,
affording a valuable therapeutic window.
Zohair Al Aseri MD,FRCPC EM & CCM
Clinical Features

19. Diagnosis and management depend on the
clinical picture
Hypoglycemia is common in children
Zohair Al Aseri MD,FRCPC EM & CCM
Diagnostic Strategies

20. Known access of the patient to a beta-blocker
and consistent clinical features such as
obtundation, seizures, bradydysrhythmias, and
occasionally tachydysrhythmias should lead the
clinician to consider beta-blocker intoxication.
Zohair Al Aseri MD,FRCPC EM & CCM
Diagnostic Strategies

21. IV fluids
Oxygen
Monitoring of card for rhythm and respirations.
Activated charcoal is unproven treatment.
Multiple-dose charcoal without supporting
evidence for an improvement in outcome.
Zohair Al Aseri MD,FRCPC EM & CCM
Management

22. Evidence for improved outcome is also lacking
but whole-bowel irrigation has been advocated
for sustained-release preparations with a
polyethylene glycol solution (OCL, GoLytely,
CoLyte), administered orally or via nasogastric
tube at 1 to 2
 L/hour in adults or 20 mL/kg initially
in children.
Zohair Al Aseri MD,FRCPC EM & CCM
Management

23. Onset of toxicity is so uniformly early that
absence of symptoms 4 hours after ingestion
implies a low risk for subsequent morbidity
unless a delayed-release preparation is involved.
Zohair Al Aseri MD,FRCPC EM & CCM
Management

24. Hypotension, Bradycardia, and Atrioventricular
Block
Catecholamines with chronotropic and
dromotropic as well as inotropic and vasopressor
effects should be chosen.
Zohair Al Aseri MD,FRCPC EM & CCM
Management

25. It is rare for one catecholamine to be equally
effective against all four toxic effects, so
combinations of drugs are often used in severe
cases.
Zohair Al Aseri MD,FRCPC EM & CCM
Management

26. The first step in the treatment of beta-blocker
overdose is
Atropine
Glucagon
Crystalloid fluids.
Zohair Al Aseri MD,FRCPC EM & CCM
Management

27. A dose of atropine may quickly wear off or be
ineffective, so infusion of more potent drugs or
cardiac pacing is usually necessary.
Atropine (0.5
 mg for adults, 0.02 mg/kg for
children, minimum 0.10
 mg) should be given
before vagal stimuli such as tracheal or gastric
intubation.
Zohair Al Aseri MD,FRCPC EM & CCM
Management

28. Glucagon
Does not depend on beta-receptors for its action,
has both inotropic and chronotropic effects.
it helps to counteract the hypoglycemia induced
by beta-blocker overdose.
is given as a 5- to 10-mg IV bolus
Zohair Al Aseri MD,FRCPC EM & CCM
Management

29. Because of its short (20-minute) half-life, an
infusion of 2 to 5
 mg/hr (or for children, 0.05–
0.1
 mg/kg bolus, then 0.05–0.1 mg/kg/hr) should
be started immediately after the bolus.
With cumulative large doses, glucagon should be
diluted in 5% glucose in water for constant
infusion.
Zohair Al Aseri MD,FRCPC EM & CCM
Management
Glucagon

30. Side effects include nausea and vomiting in most
patients, mild hyperglycemia, hypokalemia, and
allergic reactions.
The response to glucagon alone is often
inadequate.
Zohair Al Aseri MD,FRCPC EM & CCM
Management
Glucagon

31. Sodium channel blockade, manifested by QRS
widening, occasionally occurs with beta-blocker
intoxication and may respond to infusion of
sodium bicarbonate.
Zohair Al Aseri MD,FRCPC EM & CCM
Management
sodium bicarbonate

32. In hypotensive patients, 20 to 40
 mL/kg of normal
saline or Ringer's lactate solution can be infused
and repeated.
If hypotension or bradycardia persists, other
cardioactive drugs are indicated.
dopamine, or epinephrine.
Zohair Al Aseri MD,FRCPC EM & CCM
Management

33. Other catecholamines include norepinephrine,
dobutamine, and phenylephrine.
Often, norepinephrine or dopamine is added to
beta-agonists such as isoproterenol that lack
vasopressor activity.
Zohair Al Aseri MD,FRCPC EM & CCM
Management

34. Because patients are resistant to these drugs,
the initial dose should be high and the infusion
rates should be rapidly titrated to effect.
A common mistake with cases of beta-blocker
overdose is to timidly titrate catecholamine
infusions within previously familiar ranges. In the
setting of massive beta-blockade, much higher
doses are usually needed and the drug is titrated
to effect.
Zohair Al Aseri MD,FRCPC EM & CCM
Management

35. There are no randomized controlled human trials.
There are multiple case reports of the hemodynamic
improvement after institution of HDIE.
Zohair Al Aseri MD,FRCPC EM & CCM
Stellpflug SJ, Harris CR, Engebretsen KM, et al. Intentional overdose with cardiac arrest treated with
intravenous fat emulsion and high-dose insulin. Clin Toxicol 2010;48: 227-229.42
Treatment
High-Dose
Insulin Euglycemia (HDIE)
Therapy

36. Kerns W. Antidotes in Depth: Insulin- Euglycemia Therapy. In: Nelson LS, et al eds. Goldfrank’s
Toxicologic Emergencies
9
th
ed. New York: McGraw Hill; 2010: 893-5
It can take up to 60 minutes to see improvement.
It is given along with a dextrose infusion of 0.5
g/kg/hr.
It is important to follow glucose and potassium
levels closely during HDIE and avoid
hypoglycemia and hypokalemia.
Zohair Al Aseri MD,FRCPC EM & CCM
Treatment
High-Dose
Insulin Euglycemia (HDIE)
Therapy

37. High-dose (0.5–1 unit/kg/hr) insulin infusion for
hemodynamically significant toxicity is often
given before traditional pressors.
Beta-blocker toxicity shifts myocardial energy
preferences from free fatty acids to
carbohydrates, and insulin increases myocardial
carbohydrate uptake.
Recent canine and porcine models showed the
benefit of insulin infusion up to 10
 units/kg/hr.
Zohair Al Aseri MD,FRCPC EM & CCM
Management
Insulin

38. Glucose, usually in 5 to 10% solutions, is infused
to maintain a serum glucose of approximately
100
 mg/dL.
The combination of glucose and high-dose
insulin augments myocardial contraction
independent of beta-receptors.
Glucose and potassium should be monitored
frequently during infusion and supplemented as
needed to maintain euglycemia and eukalemia.
Zohair Al Aseri MD,FRCPC EM & CCM
Management
Insulin

39. Refractory cases of bradycardia may respond to
an external or transvenous pacemaker.
Zohair Al Aseri MD,FRCPC EM & CCM
Management

40. Because deleterious effects on calcium transport
may contribute to beta-blocker toxicity, IV
calcium salts have been suggested for treating
hypotension.
calcium should be given cautiously and less
aggressively than for cases of calcium channel
blocker overdose.
Constant infusions are safer than boluses.
Give 1 to 2
 g over 5 to 10 minutes, monitoring
closely for effect.
Zohair Al Aseri MD,FRCPC EM & CCM
Calcium
Management

41. Although uncharacteristic, ventricular
tachydysrhythmias do occur sometimes.
Cardioversion and defibrillation are indicated for
ventricular tachycardia and ventricular fibrillation,
respectively, following American Heart
Association guidelines.
Pulsatile ventricular tachycardia or frequent
ventricular ectopy can most safely be treated
with lidocaine.
Zohair Al Aseri MD,FRCPC EM & CCM
Ventricular Dysrhythmias
Management

42. Other antidysrhythmic drugs, especially of
classes IA and IC, should be avoided because
they may potentiate AV block or be
prodysrhythmic because of an additive
membrane stabilizing effect.
Zohair Al Aseri MD,FRCPC EM & CCM
Ventricular Dysrhythmias
Management

43. Sotalol, unlike other beta-blockers, has class III
as well as class II effects; that is, it prolongs the
QT interval and can cause torsades de pointes
and other ventricular dysrhythmias.
Overdrive pacing with isoproterenol or a
pacemaker and magnesium sulfate are specific
therapies for torsades de pointes.
Zohair Al Aseri MD,FRCPC EM & CCM
Ventricular Dysrhythmias
Management

44. Hemodialysis or hemoperfusion may be
beneficial for atenolol, nadolol, sotalol, and
timolol, the beta-blockers with lower V
d
, lower
protein binding, and greater hydrophilicity.
Zohair Al Aseri MD,FRCPC EM & CCM
Extracorporeal Elimination and
Circulatory Assistance
Management

45. can be lifesaving in cases of refractory
hypotension.
 
To be successful, such heroic measures must be
taken before prolonged hypotension leads to
multiorgan ischemic injury.
Zohair Al Aseri MD,FRCPC EM & CCM
Management
Extracorporeal Elimination and
Circulatory Assistance

46. Because most patients recover with just
supportive care, these expensive and invasive
interventions should be reserved for drugs and
circumstances, such as propranolol, verapamil,
and mixed cardiotoxic overdoses, that are
associated with higher rates of mortality.
Zohair Al Aseri MD,FRCPC EM & CCM
Management
Extracorporeal Elimination and
Circulatory Assistance

47. Zohair Al Aseri MD,FRCPC EM & CCM
TREATMENT OF BETA-BLOCKER POISONING

48. At this time, given the potential benefit and
despite no human randomized controlled trials
performed to date, IFE may be considered for
patients who are failing other modalities or
during cardiac arrest.
Zohair Al Aseri MD,FRCPC EM & CCM
Intravenous
Fat Emulsion Rescue Therapy.

49. Reported adverse effects include acute
reactions such as an anaphylactoid reaction,
and subacute reactions or the “fat overload
syndrome” (i.e., coagulopathy, jaundice, lipid
accumulation in the liver).
Zohair Al Aseri MD,FRCPC EM & CCM
Driscoll DF. Lipid injectable emulsions: Pharmacopeial and safety issues. Pharm Res 2006;23:1959-
69
Intravenous
Fat Emulsion Rescue Therapy.

50. Weinberg GL. Treatment of Local Anesthetic Systemic Toxicity (LAST). Reg Anesth Pain Med
2010;35:188-93
Based on previous use of intralipid for local
anesthetic toxicity, the accepted dosing for IFE
is a 20% lipid emulsion given as a 1.5 mL/ kg
bolus, followed by an infusion of 0.25 mL/kg/min
for 30 minutes (not to exceed 8 mL/kg total initial
dose).
Zohair Al Aseri MD,FRCPC EM & CCM
Intravenous
Fat Emulsion Rescue Therapy.

51. may be useful in severe cases of atenolol overdoses
because atenolol is less than 5% protein bound and 40-
50% is excreted unchanged in urine.
Nadolol, sotalol, and atenolol, which have low lipid
solubility and low protein binding, reportedly are removed
by hemodialysis. Acebutolol is dialyzable.
Propranolol, metoprolol, and timolol are not removed by
hemodialysis.
Consider hemodialysis or hemoperfusion only when
treatment with glucagon and other pharmacotherapy fails.

Zohair Al Aseri MD,FRCPC EM & CCM
Hemodialysis

52. Zohair Al Aseri MD,FRCPC EM & CCM

53. symptomatic hypoglycemia is much more
common in children, especially in those who
have been fasting, and occurs even after
therapeutic doses.
Zohair Al Aseri MD,FRCPC EM & CCM
Pediatric Considerations

54. Obtunded children should receive empirical
glucose, 1 to 2
 mL/kg of 25% glucose IV.
Generally, 5% glucose infusions have been
sufficient to maintain euglycemia, especially with
concomitant use of glucagon and
catecholamines, which stimulate glucose
release.
Because glycogen mobilization is a beta
2 
effect,
hypoglycemia may be less common with the
cardioselective (beta
1) blockers.
Zohair Al Aseri MD,FRCPC EM & CCM
Pediatric Considerations

55. Seizures also occur in cases of pediatric beta-
blocker overdose, but hypoglycemia is probably
an important contributing factor.
Diazepam is effective.
Zohair Al Aseri MD,FRCPC EM & CCM
Pediatric Considerations

56. Patients who remain completely asymptomatic for
6 hours after an oral overdose of normal-release
preparations can be safely referred for psychiatric
evaluation, with medical consultation for the first
24 hours.
Zohair Al Aseri MD,FRCPC EM & CCM
Disposition

57. Patients ingesting sustained-release preparations
should be admitted to a monitored bed, but those
who remain asymptomatic 8 hours after ingestion
are very unlikely to develop toxicity.
Those who have been hypotensive, who have
more than first-degree heart block, or who have
hemodynamically significant dysrhythmias should
be admitted to the intensive care unit.
Zohair Al Aseri MD,FRCPC EM & CCM
Disposition

58. Most fatalities occur with verapamil, but severe
toxicity and death have been reported for most
drugs of this class.
Zohair Al Aseri MD,FRCPC EM & CCM
CALCIUM CHANNEL BLOCKERS
Perspective

59. Calcium channel antagonists
block the slow calcium channels in the myocardium
and vascular smooth muscle, leading to coronary
and peripheral vasodilation.
reduce cardiac contractility
depress SA nodal activity
slow AV conduction.
Zohair Al Aseri MD,FRCPC EM & CCM
Pathophysiology

60. Both verapamil and diltiazem act on the heart and
blood vessels, whereas nifedipine causes primarily
vasodilation.
In the pancreas, calcium channel blockade inhibits
insulin release, resulting in hyperglycemia.
As with beta-blockers, selectivity is lost in cases of
overdose
Zohair Al Aseri MD,FRCPC EM & CCM
Pathophysiology

61. All calcium channel blockers are rapidly
absorbed
Onset of action and toxicity ranges from less
than 30 minutes to 60 minutes
Peak effect of nifedipine can occur as early as
20 minutes after ingestion,
Zohair Al Aseri MD,FRCPC EM & CCM
Pathophysiology

62. Peak effect of sustained-release verapamil can
be delayed for many hours.
High protein binding and V
d greater than 1 to
2
 L/kg make hemodialysis or hemoperfusion
ineffective.
Fortunately (except with sustained-release
preparations), their half-lives are relatively short,
limiting toxicity to 24 to 36 hours.
Zohair Al Aseri MD,FRCPC EM & CCM
Pathophysiology

63. Zohair Al Aseri MD,FRCPC EM & CCM
Selected Characteristics of Some Calcium Channel
Blockers

64. Cardiovascular toxicity is primarily responsible for
morbidity and mortality.
Hypotension and bradycardia occur early
AV block
Sinus arrest
Junctional rhythm
Asystole.
Reflex sinus tachycardia mainly by nifedipine
overdose
Zohair Al Aseri MD,FRCPC EM & CCM
Clinical Features

65. Calcium channel blockade has little effect on
ventricular conduction, so QRS widening is not
seen commonly.
Ventricular dysrhythmias are also uncommon
except
Bepridil, which has class I antidysrhythmic
properties and prolongs the QT with
increased risk of ventricular tachycardia,
especially torsades de pointes
Zohair Al Aseri MD,FRCPC EM & CCM
Clinical Features

66. Unlike beta-blockers, calcium antagonists
seldom induce seizures.
Pulmonary effects include noncardiogenic
pulmonary edema and apnea can also occur.
As with digitalis and beta-blocker overdose,
nausea and vomiting are common.
Zohair Al Aseri MD,FRCPC EM & CCM
Clinical Features

67. Zohair Al Aseri MD,FRCPC EM & CCM
MANIFESTATIONS AND COMPLICATIONS OF CALCIUM
CHANNEL BLOCKER POISONING

68. Serum levels of calcium antagonists are not
available
Glucose and Electrolytes (including calcium and
magnesium). Hyperglycemia secondary to
insulin inhibition occurs occasionally, but mild
and short-lived requires no treatment.
Lactic acidosis occurs with hypotension and
hypoperfusion.
Zohair Al Aseri MD,FRCPC EM & CCM
Diagnostic Strategies

69. ECG
A prolonged QRS or QT interval suggests
bepridil or a co-ingested cardiac toxin such as a
TCA.
Zohair Al Aseri MD,FRCPC EM & CCM
Diagnostic Strategies

70. IV
O2
Cardiac monitoring
Vomiting is a powerful vagal stimulus that can
exacerbate bradycardia and heart block.
Zohair Al Aseri MD,FRCPC EM & CCM
Management

71. No evidence for activated charcoal.
Sorbitol should be avoided because hypotension
frequently causes an ileus where residual
sorbitol is metabolized to cause abdominal
distension.
Zohair Al Aseri MD,FRCPC EM & CCM
Management

72. Atropine (0.5–1
 mg, up to 3 mg for adults, and
0.02
 mg/kg for children, minimum 0.1 mg).
Atropine's effect is short-lived
If symptomatic bradycardia or heart block
persists, the next step is a pacemaker or
chronotrope such as isoproterenol.
Zohair Al Aseri MD,FRCPC EM & CCM
Hypotension and Bradycardia

73. A bolus of crystalloid fluid (20
 mL/kg
or more) should also be infused early.
Zohair Al Aseri MD,FRCPC EM & CCM
Hypotension and Bradycardia

74. have considerable effect on contractility but their
effect on bradycardia, AV block, and peripheral
vasodilation is often poor.
A reasonable dose is 6
 g of calcium chloride, but
some have given much higher calcium infusions,
administering up to 30
 g and raising the total
serum calcium level to as high as 23.8
 mg/dL.
Zohair Al Aseri MD,FRCPC EM & CCM
Hypotension and Bradycardia
Intravenous calcium

75. With rapid IV injection bradycardia, AV block, AV
dissociation, junctional tachycardia, ventricular
ectopy, and VF have been reported.
Extravasation can cause severe tissue necrosis.
Administration through a central venous catheter
is safer.
Infiltration of calcium gluconate is less
destructive than calcium chloride, but larger
doses are necessary
Zohair Al Aseri MD,FRCPC EM & CCM
Hypotension and Bradycardia
Intravenous calcium

76. It is prudent to raise the total serum calcium
level no higher than 14
 mg/dL, which the
endocrine and oncology literature define as the
threshold of “severe” hypercalcemia.
If ionized calcium levels are followed, it is
probably wise not to exceed twice-normal levels.
Zohair Al Aseri MD,FRCPC EM & CCM
Hypotension and Bradycardia
Intravenous calcium

77. Adults should receive 10 to 20
 mL of 10%
calcium chloride slowly over 5 to 10 minutes,
followed by a constant infusion of 5 to
10
 mL/hour.
Children can receive 10 to 30
 mg/kg (0.1–
0.3
 mL/kg) of 10% calcium chloride initially.
calcium level can be as high as 18.2
 mg/dL
within 15 minutes after a bolus of just 5
 mL of
10% calcium chloride, so levels should be
measured later during the constant infusion.
Zohair Al Aseri MD,FRCPC EM & CCM
Hypotension and Bradycardia

78. Most severely poisoned patients require addition
of catecholamines to accelerate the heart rate
(chronotropy), enhance AV conduction
(dromotropy), and restore tone to peripheral
vessels (vasotropy).
Most experience and success have been reported
with isoproterenol and dopamine, often in
combination.
Isoproterenol infusion can begin at 2 to 10
 ?g/min
(0.1
 ?g/kg/min in children), but much higher rates
may be needed.
Zohair Al Aseri MD,FRCPC EM & CCM
Hypotension and Bradycardia

79. Epinephrine, norepinephrine, and dobutamine
have also led to successful outcomes.
Zohair Al Aseri MD,FRCPC EM & CCM
Hypotension and Bradycardia

80. Glucagon has also been used for its inotropic
and chronotropic effects.
Zohair Al Aseri MD,FRCPC EM & CCM
Hypotension and Bradycardia

81. (0.5–1
 iu/kg/hr) infusion has been effective in
both animal trials and human cases.
Glucose (5–10% solutions usually suffice) is
infused concurrently to maintain serum glucose
at 100
 mg/dL (usually 10–30 g/hr).
Insulin euglycemia is thought to act by improving
myocardial carbohydrate metabolism, thereby
augmenting myocardial contraction.
Zohair Al Aseri MD,FRCPC EM & CCM
Hypotension and Bradycardia
Insulin

82. Serum glucose and potassium levels should be
checked frequently to ensure that normal levels
are maintained.
Zohair Al Aseri MD,FRCPC EM & CCM
Hypotension and Bradycardia
Insulin

83. Megarbane B, Karyo S, Baud FJ. The role of insulin and glucose (hyperinsulinaemie/ euglycaemia)
therapy in acute calcium channel antagonist and beta-blocker poisoning. Toxicol Rev 2004;23:215-222
Kline JA, Leonova E, Raymond R. Beneficial myocardial metabolic effects of insuin during verapamil
toxicity in the anesthetized canine. Crit Care Med 1995;3:1251-63
Tune JD, Mallet RT, Downey HF. Insulin improves contractile function during moderate ischemia in
canine left ventricle.
Am J Physiol 1998;274:1574-81
High-Dose
Insulin Euglycemia (HDIE) Therapy
may be administered to increase inotropy.
Its proposed mechanism of action is by improving
calcium use in the myocytes, although the exact
mechanism is unclear.
Zohair Al Aseri MD,FRCPC EM & CCM
Treatment

84. Zohair Al Aseri MD,FRCPC EM & CCM
TREATMENT OF CALCIUM CHANNEL BLOCKER
INTOXICATION

85. Zohair Al Aseri MD,FRCPC EM & CCM

86. Nifedipine, can kill a child with ingestion of a
single tablet.
Seizures may be more common in children than
adults and should be treated with diazepam,
lorazepam, or calcium.
Recommendations for calcium chloride
administration in children range from 10 to
30
 mg/kg (0.1–0.3 mL/kg of 10% calcium
chloride) over 5 to 10 minutes, followed by an
infusion.
Zohair Al Aseri MD,FRCPC EM & CCM
Pediatric Considerations

87. Overall, death following calcium antagonist
ingestion in children is rare.
Zohair Al Aseri MD,FRCPC EM & CCM
Pediatric Considerations

88. Hyperglycemia occasionally occurs in children,
but the elevation is usually short-lived.
Insulin it is generally not necessary, because the
hyperglycemia usually resolves spontaneously
within 24 to 36 hours.
Zohair Al Aseri MD,FRCPC EM & CCM
Pediatric Considerations

89. Because the peak effect occurs in 90 minutes to
6 hours, patients who are totally asymptomatic
for 6 hours can be safely discharged
For delayed-release preparations should be
admitted for at least 24 hours of continuous
cardiac monitoring.
Zohair Al Aseri MD,FRCPC EM & CCM
Disposition

90. Widely used as vasodilators in the treatment of
heart failure and ischemic heart disease.
augment coronary blood flow as well as reduce
myocardial oxygen consumption by reducing
afterload.
At lower doses nitrates primarily dilate veins
At higher doses they also dilate arteries.
Zohair Al Aseri MD,FRCPC EM & CCM
NITRATES AND NITRITES

91. Hypotension is a common complication, but
usually responds to supine positioning, IV fluids,
and reduction of dose.
Hypotension is usually transient.
Low-dose pressors are occasionally needed, but
it is best to avoid them in the setting of acute
coronary syndromes.
Zohair Al Aseri MD,FRCPC EM & CCM
NITRATES AND NITRITES

92. Intravenous nitroglycerin infusions are being
used commonly in patients with acute pulmonary
edema for afterload reduction.
Infusions are usually initiated at 5 to
10
 micg/min, but rates as high as 200 to
300
 micg/min may be used.
hypotension may develop suddenly
Zohair Al Aseri MD,FRCPC EM & CCM
NITRATES AND NITRITES

93. Excessive fall in blood pressure usually responds
to reducing or terminating the infusion.
Use of nitrates is contraindicated in patients who
have recently taken sildenafil (Viagra).
Zohair Al Aseri MD,FRCPC EM & CCM
NITRATES AND NITRITES

94. Sildenafil and related drugs (vardenafil/Levitra
and tadalafil/Cialis) inhibit type-5
phosphodiesterase, thereby relaxing vascular
smooth muscle.
These agents can prolong and intensify the
vasodilating effects of nitrates, resulting in severe
hypotension.
If blood pressure does not rise with IV fluids,
dopamine should be cautiously titrated, beginning
at 5
 micg/kg/min.
Zohair Al Aseri MD,FRCPC EM & CCM
NITRATES AND NITRITES

95. Nitrites are also oxidizing agents that convert
hemoglobin to methemoglobin, impairing oxygen
delivery.
Zohair Al Aseri MD,FRCPC EM & CCM
NITRATES AND NITRITES

96. Patients with g6pd deficiency are especially
susceptible to the oxidative stress of nitrite
exposure, and they may even develop
hemolysis.
When methemoglobin levels exceed 15%, a
venous blood sample appears chocolate brown,
and the skin appears blue even while patients
look remarkably comfortable.
Unlike most cases of cyanosis, supplemental
oxygen does not improve the patient's color.
Zohair Al Aseri MD,FRCPC EM & CCM
NITRATES AND NITRITES

97. Pulse oximetry is not reliable, and the partial
pressure of oxygen remains normal in mild to
moderate cases.
This rare complication can be treated with IV
methylene blue, but this antidote is usually not
needed unless methemoglobinemia approaches
30% or the patient develops more reliable signs
of distress, such as tachypnea, tachycardia,
acidosis, and hypotension.
The usual dose of methylene blue in adults is 1
to 2
 mg IV over 5 minutes.
Zohair Al Aseri MD,FRCPC EM & CCM
NITRATES AND NITRITES

98. Zohair Al Aseri MD,FRCPC EM & CCM

99. time of ingestion
specific name of the medication
number of pills ingested
formulation
(i.e., immediate release vs. sustained release)
dose per tablet
co-ingestants
chronic medications taken as prescribed
alcohol, or illicit drugs.
Zohair Al Aseri MD,FRCPC EM & CCM
ED
Evaluation
Important to know:

100. Intravenous
Fat Emulsion Rescue Therapy.
its use has been reported in betablocker and calcium
channel blocker toxicity.
Zohair Al Aseri MD,FRCPC EM & CCM
Controversies

101. No human randomized control trials regarding
treatment with IFE are available.
A few animal studies of IFE in beta-blocker and
calcium channel blocker toxicity show
hemodynamic benefit.
Zohair Al Aseri MD,FRCPC EM & CCM
Jamaty C, Bailey B, Laroque A, et al. Lipid emulsions in the treatment of acute poisoning: A systematic
review of
human and animal studies. Clin Toxicol 2010;48:1-27
Tebbutt S, Harvey M, Nicholson T, et al. Intralipid prolongssurvival in a rat model of Verapamil Toxicity.
Acad Emerg Med 2006;13:134-139
Cave, G, Harvey M. Intravenous lipid emulsion as antidote beyond local anesthetic toxicity: A
systematic review. Acad
Emerg Med 2009;16:815-24
Cave G, Harvey M, Castle C. The role of fat emulsion therapy in a rodent model of propranolol toxicity:
A preliminary study.
J Med Toxicol 2006;2:4-7
Intravenous
Fat Emulsion Rescue Therapy.

102. There are multiple human case reports in which
IFE appears to have contributed to recovery
from cardiogenic shock or arrest.
Zohair Al Aseri MD,FRCPC EM & CCM
Stellpflug SJ, Harris CR, Engebretsen KM, et al. Intentional overdose with cardiac arrest treated with intravenous fat
emulsion and high-dose insulin. Clin Toxicol 2010;48: 227-229.42.
Jamaty C, Bailey B, Laroque A, et al. Lipid emulsions in the treatment of acute poisoning: A systematic review of
human and animal studies. Clin Toxicol 2010;48:1-27
Cave, G, Harvey M. Intravenous lipid emulsion as antidote beyond local anesthetic toxicity: A systematic review. Acad
Emerg Med 2009;16:815-24
Cave G, Harvey M, Castle C. The role of fat emulsion therapy in a rodent model of propranolol toxicity: A preliminary
study.
J Med Toxicol 2006;2:4-7
Dolcourt BA, Aaron CK. Intravenous fat emulsion for refractory verapamil and atenolol induced shock: A human case
report. Clin Toxicol 2008;46:619
Young AC, Velez LI, Kleinschmidt KC. Intravenous fat emulsion therapy for intentional sustained-release verapamil
overdose. Resuscitation 2009;80:591-3
Intravenous
Fat Emulsion Rescue Therapy.

103. As these are case reports, and there may exist
a bias against reporting or publishing negative
outcomes, human case-control studies are
needed to further elucidate the efficacy of IFE
in beta-blocker and calcium channel blocker
overdose.
Zohair Al Aseri MD,FRCPC EM & CCM
Intravenous
Fat Emulsion Rescue Therapy.

104. At this time, given the potential benefit and
despite no human randomized controlled trials
performed to date, IFE may be considered for
patients who are failing other modalities or
during cardiac arrest.
Zohair Al Aseri MD,FRCPC EM & CCM
Intravenous
Fat Emulsion Rescue Therapy.

105. Reported adverse effects include acute
reactions such as an anaphylactoid reaction,
and subacute reactions or the “fat overload
syndrome” (i.e., coagulopathy, jaundice, lipid
accumulation in the liver).
Zohair Al Aseri MD,FRCPC EM & CCM
Driscoll DF. Lipid injectable emulsions: Pharmacopeial and safety issues. Pharm Res 2006;23:1959-
69
Intravenous
Fat Emulsion Rescue Therapy.

106. West P, McKeown NJ, Hendrickson RG. Iatrogenic lipid emulsion overdose in a case of amlodipine
poisoning. Clin Toxicol 2010;48:393-6
One case report of iatrogenic IFE overdose
describes interference with laboratory studies,
but otherwise no other attributable adverse
effects were noted.
Zohair Al Aseri MD,FRCPC EM & CCM
Intravenous
Fat Emulsion Rescue Therapy.

107. Weinberg GL. Treatment of Local Anesthetic Systemic Toxicity (LAST). Reg Anesth Pain Med
2010;35:188-93
Based on previous use of intralipid for local
anesthetic toxicity, the accepted dosing for IFE
is a 20% lipid emulsion given as a 1.5 mL/ kg
bolus, followed by an infusion of 0.25 mL/kg/min
for 30 minutes (not to exceed 8 mL/kg total initial
dose).
Zohair Al Aseri MD,FRCPC EM & CCM
Intravenous
Fat Emulsion Rescue Therapy.

108. Thank you
Zohair Al Aseri MD,FRCPC EM & CCM
Main reference is Rosen Text book of EM