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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_3871_Библиотеки_им_академика_М_И_Перельмана
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Chapter 12: Relevant pharmacology
d.
Heparin
i.
12
Forms a complex with antithrombin III to inactivate FXa and inhibit the
formation of thrombin
ii.
Small amount of activity on factors IX, XI, and XII
iii.
Dosing
1.
DVT prophylaxis: 5000 units SUBQ three times a day
2.
IV – stroke (off-label)
a.
No bolus dose
b.
Initial infusion rate: 10–12 units/kg/hr
c.
Adjust dose to target aPTT (differs between institutions)
d.
Note: Most institutions have dosing and monitoring protocols
3.
Intra-arterial – stroke (off-label)
a.
Use caution in patients already receiving systemic anticoagulation
b.
Small doses may be considered for local effects
iv.
Effects can be partially reversed using protamine
1.
Administer 1 mg of protamine for every 100 mg of heparin
2.
Maximum dose of protamine is 50 mg
3.
Administer by slow IV infusion over 10 minutes
v.
HIT can be characterized by:
1.
Decrease in platelets by 50% from baseline
2.
Platelet count <150 × 10
vi.
To diagnose HIT, must consider the timing of platelet decrease as related to
3
/microliter
initiation of heparin and previous heparin exposure, as well as other possible
causes of thrombocytopenia
vii.
If HIT is suspected or confirmed with a platelet factor 4 (PF4) and/or serotonin
release assay (SRA), heparin should be discontinued and an alternative
anticoagulant started
e.
Low-molecular-weight heparins (LMWHs)
i.
Inhibits FXa with minimal direct effect on factor II
ii.
Enoxaparin (Lovenox
iii.
Used for DVT prophylaxis and treatment of acute thrombotic
®
) and dalteparin (Fragmin®)
conditions
iv.
Prophylaxis dosing
1.
Enoxaparin 40 mg SUBQ once a day
2.
Enoxaparin 30 mg SUBQ twice a day (hip or knee replacement surgery)
3.
Dalteparin 2500 or 5000 IU SUBQ once a day
v.
Acute thrombosis dosing
1.
Enoxaparin 1 mg/kg SUBQ twice a day
2.
Enoxaparin 1.5 mg/kg SUBQ once a day can be used for inpatient treatment
of acute DVT or PE
vi.
Doses may need adjustments for renal insufficiency
vii.
Effects of LMWHs can be partially reversed by protamine
1.
Enoxaparin
189
Chapter 12: Relevant pharmacology
a.
If ≤8 hours since last dose, administer 1 mg protamine per 1 mg
enoxaparin
b.
If >8 hours since last dose, administer 0.5 mg protamine per 1 mg
enoxaparin
2.
Dalteparin
a.
Administer 1 mg of protamine per 100 units of dalteparin
3.
If aPTT remains prolonged 2–4 hours after initial protamine dose, a second
dose of 0.5 mg protamine per 1 mg enoxaparin or per 100 units dalteparin
may be given
viii.
If HIT is suspected or confirmed with a PF4 and/or SRA, LMWHs should be
discontinued and an alternative anticoagulant started
III.
Antiplatelet agents
a.
ADP (adenosine diphosphate) inhibitors
18,19
i.
Bind to P2Y
1.
Irreversibly inhibit platelet activation and aggregation for the life of the
class of ADP receptors (thienopyridine inhibitor)
12
platelet (about 7 days)
2.
Platelet transfusion may restore some platelet function
ii.
Clopidogrel (Plavix
1.
Half-life: 6 hours
2.
Dosing
a.
Loading dose: 300 mg or 600 mg PO once
b.
Maintenance dose: 75 mg PO once a day
iii.
Ticagrelor (Brilinta
1.
Half-life: 7 hours
2.
Dosing
a.
Loading dose: 180 mg PO once
b.
Maintenance dose: 90 mg PO twice a day
iv.
Prasugrel (Effient
1.
Half-life: 7 hours
2.
Only approved for use in acute coronary syndrome
3.
Limited evidence suggests prasugrel may be an alternative agent for patients
®
)
®
)
®
)
who are clopidogrel-non-responders
4.
Patients may be at higher risk for hemorrhagic complications
5.
Dosing
a.
Loading dose: 60 mg PO once
b.
Maintenance dose: 10 mg PO once a day
190
b.
Aspirin (acetylsalicylic acid, ASA)
i.
Blocks cyclooxygenase-1(COX-1), leading to inhibition of thromboxane A
1.
Irreversibly inhibits platelet aggregation for the life of the platelet
18
(about 7 days)
ii.
Platelet transfusion may restore some platelet function
iii.
Typical dose: 75–325 mg PO once a day
(TXA2)
2
Chapter 12: Relevant pharmacology
c. Glycoprotein (GP) IIb/IIIa inhibitors
i. Block the binding site for fibrinogen and vonWillebrand factor on GP IIb/IIIa
ii. Inhibit platelet aggregation
iii. Only approved for cardiovascular indications, including acute coronary
syndrome and percutaneous coronary intervention
iv. Both eptifibatide and Abciximab have shown to be effective when used as
adjunctive therapy for the management of thromboembolic complications in
neuroendovascular procedures
v. Eptifibatide (Integrilin
®)20
1. Half-life: 2.5 hours
2. Dosing
a. Loading dose: 180 μg/kg
b. Continuous infusion: 2 μg/kg/min
c. Reduce continuous infusion to 1 μg/kg/min if CrCl <50 ml/min
vi. Abcix imab (Reopro
®)21,22
1. Half-life: 10 to 30 minutes
2. Dosing
a. Loading dose: 0.25 mg/kg
b. Continuous infusion: 0.125 μg/kg/min (max 10 μg/min) for 12 hours
3. High rate of intracranial hemorrhage with Abciximab has been observed
4. Platelet transfusion may partially restore platelet function
IV. Thrombolytic agents
23
a. Alteplase (Activase®)
i. Tissue plasminogen activator (tPA)
ii. Binds to fibrin, enhances conversion of plasminogen to plasmin, and creates
local fibrinolysis
iii. Half-life <5 minutes
iv. Dosin g – stroke
1. Intravenous
a. Alteplase 0.9 mg/kg (not to exceed 90 mg total dose)
i. Administer 10% of total dose as IV bolus over 1 minute
ii. Administer the remaining dose as IV infusion over 60 minutes
b. Approved for use within 3 hours of onset of stroke symptoms
c. In some clinical conditions, may consider extending the time frame to
4.5 hours from the onset of stroke symptoms (off-label)
2. Intra-arterial (off-label)
a. Usually patients have received IV tPA prior to intervention
b. Small doses (i.e. 1–5 mg) may be considered for local thrombolysis
v. Reversal
1. Reversal of tPA may result in thrombosis
2. No reversal needed 2 hours post tPA infusion
3. If fibrinogen <100 mg/dl administer cryoprecipitate 0.10 units/kg
IV once
191
Chapter 12: Relevant pharmacology
4. Repeat fibrinogen in 1 hour; if <100 again, repeat cryoprecipitate dose
IV once
5. Administer aminocaproic acid (Amicar
1 hour
®
) 1 g/10 kg IV in 250 cc NS over
Calcium channel blockers
24
I. Nicardipine (Cardene®)
a. Cerebral vasospasm – intra-arterial (off-label)
i. Wide range of doses used in clinical studi es
ii. Usual total doses of 5 to 40 mg
iii. Onset of action: 1 minute
iv. Duration of action
1. Initial redistribution: 2 to 5 minute effective half-life after bolus of 0.25–2mg
2. Elimination half-life: 14.4 hours
b. Warning: Use with caution in patients with coronary artery disease, heart failure, or
aortic stenosis (contraindicated in advanced aortic stenosis)
II. Verapamil
25,26
a. Radial Artery Cocktail (off-label to prevent arterial vasospasm with radial artery access)
i. Usual dose: 2.5 mg diluted in NS and administered slowly IV
ii. Onset of action: 1 to 5 minutes
iii. Duration of action: 10 to 20 minutes
iv. Half-life after single dose: 3 to 7 hours
b. Cerebral vasospasm – intra-arterial (off-label)
i. Usual dose: 1 to 20 mg per arterial distribution
III. Toxicology
192
c. Warning: Use with caution in patients with poor left ventricular function or
conduction disturbances
27,28
a. Treatment for either nicardipine or verapamil poisoning
b. Mild hypotension (treatment)
i. IV fluids
c. Hypotension and bradycardia (treatment)
i. Standard ACLS treatment (O
, IV line, and fluids)
2
ii. Atropine 0.5–1 mg IV every 2 to 3 minutes (max 3 mg)
iii. Calcium (off-label to improve hemodynamics in calcium channel blocker
toxicity)
1. 10 ml calcium chloride 10% IV or 30 ml calcium gluconate 10% IV over 10
minutes. May repeat dose every 15–20 minutes
a. Monitor ionized calcium after three doses IV calcium
Chapter 12: Relevant pharmacology
iv. Vasopressors29: See “Vasopressors” section for standard dosing
recommendations. Much higher doses than standard recommendations
(i.e. standard references) may be required
v. Glucagon (off-label for calcium channel blocker and beta-blocker toxicity)
1. 50–150 μg/kg (3–10 mg) IV up to cumulative dose of 10 mg. Repeat every
3 to 5 minutes as necessary
2. If there is a favorable result, place on IV continuous infusion at 5–10 mg/hr
(diluted in D5W)
3. Rapid onset of action (rarely longer than 15 minutes)
4. A potent emetic which increases aspiration risk with bolus doses greater than
50 μg/kg
a. Metoclopramide and serotonin antagonists are often used
b. Hyperglycemia and hypokalemia can be expected
30
vi. High-dose insulin and dextrose
(off-label for calcium channel blocker and beta-
blocker toxicity)
1. Insulin 1 unit/kg IV bolus followed by an IV infusion of 0.5 to 1 unit/kg/hr;
titrate in 1 to 2 unit/kg/hr increments every 10 to 15 minutes up to10 units/
kg/hr to achieve clinical response
2. Administer 50 ml dextrose 50% IV bolus if initial blood glucose < 200 mg/dl.
In all patients, administer 10% dextrose infusion IV starting at 100–250
ml/hr. Maintain blood glucose greater than 100 mg/dl
a. If central line available, may use 50% dextrose infusion IV to avoid fluid
overload
b. Monitor blood glucose every 10 minutes initially, then every 30 to 60
minutes once glucose is stable
3. Onset: 5 to 45 minutes
4. Maintain serum potassium >3 mmol/l and <4.5 mmol/l
5. Monitor magnesium and phosphorus concentrations
6. Dextrose supplementation may be needed for up to 24 hours after insulin
therapy stopped due to elevated insulin levels
7. An attempt to wean off vasopressors should be considered while on
high-dose insulin therapy
3
vii. Lipid emulsion
(off-label for local anesthetic, calcium channel blocker, and
beta-blocker toxicity)
1. See dosing and administration information in “Anesthetics, local” section
above, under lipid emulsion
viii. Extracorporeal life support
Contrast media (IV)
31
Management of acute reactions to contrast media
I. All reactions
a. Maintain IV access
b. Monitor vital signs
c. Provide supplemental oxygen as needed
193
Chapter 12: Relevant pharmacology
II. Bronchospasm
a. Albuterol
i. Two puffs via metered-dose inhaler (90 μg/inhalation)
ii. 2.5 mg via nebulizer (2.5 mg/0.5 ml)
iii. May repeat every 15 minutes for three doses
b. Epinephrine (1:1,000 dilution) 0.3 mg IM (moderate)
c. Epinephrine (1:10,000 dilution) 0.3 mg IV (severe)
i. Administer slowly into a running saline infusion
ii. May repeat every 5 to 15 minutes up to a total dose of 1 mg
III. Erythema (diffuse)
a. Normotensive
i. No additional treatment usually required
b. Hypotensive
i. NS or LR IV bolus 500–1000 ml
ii. Epinephrine (1:10,000 dilution) 0.3 mg IV
1. Administer slowly into a running saline infusion
2. May repeat every 5 to 15 minutes up to a total dose of 1 mg
iii. Epinephrine (1:1000 dilution) 0.3 mg IM (if no IV access)
IV. Hives
a. Diphenhydramine 50 mg PO, IV (over 1 to 2 minutes), or IM
b. Epinephrine (1:1000 dilution) 0.3 mg IM
V. Hypoglycemia
a. If patient can safely swallow, administer 15 g oral glucose
b. If patient cannot safely swallow
VI. Hypotension
a. Elevate legs at least 60 degrees
b. NS or LR IV bolus 500–1000 ml
c. Bradycardia with continued hypotension
d. Tachycardia with continued hypotension
194
i. 50% dextrose 25 g IV over 2 minutes
ii. Glucagon 1 mg IM or SUBQ
i. Consider atropine 1 mg IV
i. Consider epinephrine (1:10,000 dilution) 0.3 mg IV
1. Administer slowly into a running saline infusion
2. May repeat every 5 to 15 minutes up to a total dose of 1 mg
ii. IM administration is not preferred in patients with hypotension as absorption
may be inadequate due to decreased perfusion in the extremities
Chapter 12: Relevant pharmacology
VII.
Laryngeal edema
a.
Epinephrine (1:10,000 dilution) 0.3 mg IV
i.
Administer slowly into a running saline infusion
ii.
May repeat every 5 to 15 minutes up to a total dose of 1 mg
b.
Epinephrine (1:1000 dilution) 0.3 mg IM
VIII.
Pulmonary edema
a.
Elevate head of bed
b.
Furosemide 40 mg IV over 2 minutes
IX.
Pulseless and unresponsive
a.
Follow standard ACLS protocols
X.
Reaction rebound prevention
a.
IV corticosteroids are not useful for the acute treatment of allergic reactions, but
may help to prevent short-term recurrence
b.
Hydrocortisone 5 mg/kg (max 200 mg) IV over 1 to 2 minutes
c.
Methylprednisolone 1 mg/kg (max 40 mg) IV over 1 to 2 minutes
Magnesium sulfate
Intra-arterial in combination with nicardipine for cerebral vasospasm (off-label)
I.
Dilute magnesium sulfate 1 g (2 ml) in 28 ml of NS (final concentration 33.3 mg/ml)
II.
Inject 0.25 to 1 g intra-arterially through microcatheter per vessel
a.
Usual recommended max infusion rate: 150 mg/min
III.
Monitoring parameters: magnesium serum levels and respiratory rate
IV.
Use with caution in patients with renal impairment, myasthenia gravis, or other
neuromuscular diseases
V.
Treat magnesium-induced hypotension with IV fluids, and dopamine or
norepinephrine if unresponsive to fluids
32
Osmotic agents
For intracranial hypertension or cerebral edema
I.
Mannitol 20% or 25%
a.
Administer 0.25–1 g/kg dose IV over 20 to 30 minutes
b.
May repeat every 6 hours
c.
Maintain serum osmolality <300–320 mOsm/kg
d.
Monitor renal function
II.
Sodium chloride 23.4%
a.
Administer 30 ml IV through a central line over 20 minutes
b.
May cause hypotension if injected too rapidly
33
(off-label)
195
Chapter 12: Relevant pharmacology
Sedation
I. Benzodiazepines
a. Lorazepam (Ativan
i. Usual initial IV dose: 2 mg, or 0.044 mg/kg, whichever is smaller
1. Administer 15 minutes prior to procedure for optimal effect, measured as
lack of recall
2. Larger doses of up to 0.05 mg/kg, up to a total of 4 mg, IV may be
administered in those patients in whom a greater likelihood of lack of recall
would be beneficial
3. Doses of other injectable central nervous system (CNS) depressant drugs
ordinarily should be reduced
ii. IV administration
1. Must be diluted with equal volume of compatible diluent (sterile water for
injection, NS, D5W)
2. Do not inject IV faster than 2 mg/min
iii. Elimination half-life: 14 hours
iv. Pregnancy Category D
b. Midazolam (Versed
®
)
®
)
i. Preprocedural sedation in healthy adults below 60 years of age
1. Midazolam 1 to 2.5 mg IV over at least 2 minutes
a. Reduce dose by 30% if narcotics or other CNS depressants are also used
ii. Preprocedural sedation in patients age 60 or older, and debilitated or chronically
ill patients
1. Midazolam 1 to 1.5 mg IV over at least 2 minutes
a. Reduce dose by 50% if narcotics or other CNS depressants are also used
iii. Administration: Dilute to 0.5 mg/ml in D5W or NS for IV use
iv. Pharmacokinetics
1. Amnestic onset within 1 to 5 minutes
2. Duration of action: usually less than 2 hours
3. Elimination half-life: 1.8 to 6.4 hours (mean approximately 3 hours)
4. Clearance reduced in elderly, congestive heart failure, liver disease, or
conditions which diminish cardiac output and hepatic outflow
v. Pregnancy Category D
c. Paradoxical reactions to benzodiazepines
34
i. Agitation, emotional release, excitement, excessive movement
ii. Occurs in less than 1% of patients
iii. Predisposing factors include young and advanced age, alcoholism, and
psychiatric disorders
iv. Flumazenil can reverse this effect
d. Antidote: Flumazenil rapidly reverses the sedation effect (See dosing information in
“Anticonvulsants for status epilepticus” section under Benzodiazepines, Toxicology)
196
Chapter 12: Relevant pharmacology
II. Propofol
a. Procedural sedation
b. See contraindications, warnings, and administration instructions in
Vasopressors
I. Dobutamine (direct-acting positive inotrope, mild chronotrope)
a. Cardiac decompensation: 0.5 to 20 μg/kg/min IV (max 40 μg/kg/min)
b. Post cardiac arrest (American Heart Association [AHA] ACLS Guidelines, off-label)
c. Onset of action: 1 to 2 minutes
d. Plasma half-life: 2 minutes
e. May increase heart rate
f. May exacerbate ventricular ectopy
g. Ineffective therapeutically in the presence of severe aortic stenosis
II. Dopamine (positive inotrope and chronotrope; vasopressor)
a. Hypotension, low cardiac output, poor perfusion of vital organs, or shock: Initiate at
b. Symptomati c bradycardia (AHA ACLS Guidelines, off-label): 2–10 μg/kg/min;
c. Inotropic and chronotropic effects predominate at 2–10 μg/kg/min IV infusion rates
d. Vasopressor effects predominate at 10–20 μg/kg/min IV infusion rates
e. Onset of action: within 5 minutes
f. Plasma half-life: 2 minutes
g. May exacerbate ventricular ectopy
h. Initiate with 1/10 the usual dopamine dose in patients taking monoamine oxidase
i. Hypotension may occur at lower IV infusion rates
j. Infuse into a central line or large vein whenever possible to prevent extravasation
35–38
i. Recommended initial dose: 1 mg/kg IV followed by 0.5 mg/kg every 3 to
5 minutes as needed for sedation
ii. Intubation may be necessary
“Anticonvulsants for status epilepticus” section under Propofol
39,40
5–10 μg/kg/min; titrate as needed
2to5μg/kg/min; titrate up to 20–50 μg/kg/min as needed
titrate to response
inhibitors within 2–3 weeks prior to dopamine initiation
into adjacent tissue
i. If tissue ischemia occurs, mix 5–10 mg phentolamine (adrenergic blocking
agent) in 10–15 ml NS and infiltrate ischemic area with phentolamine solution
as soon as possible. Use a fine hypodermic needle. Do not exceed 0.1 to
0.2 mg/kg (5 mg total). If dose is effective, normal skin color should return to
the blanched area within 1 hour
III. Epinephrine (positive inotrope, vasopressor; when given by slow IV injection,
vasodilation of the skeletal muscle vasculature occurs)
a. Asystole, pulseless arrest, pulseless VT/VF (AHA ACLS Guidelines, off-label):
Epinephrine 1 mg IV every 3 to 5 minutes until return of spontaneous circulation
197
Chapter 12: Relevant pharmacology
b. Via endotracheal tube (off-label): 2 to 2.5 mg diluted in 5 to 10 ml sterile water or NS
c. Usual IV infusion dose: 2 to 10 μg/min
d. Anaphylaxis:
i. 0.3 to 0.5 mg IM or SUBQ (1 mg/ml concentration), repeated every 5 to 10
minutes as needed
ii. AHA ACLS Guidelines (off-label): 0.2 to 0.5 mg IM every 5 to 15 minutes as needed
iii. For anaphylactic shock where patient is not in cardiac arrest: 0.05 to 0.1 mg IV
has been used. An IV infusion of 5 to 15 μg/min may also be considered
e. Asthma (AHA ACLS dosing, off-label): 0.01 mg/kg divided into three doses of
approximately 0.3 mg SUBQ at 20 minute intervals (1 mg/ml concentration)
f. Symptomatic bradycardia as a second line treatment (AHA off-label dosing): Initial
dose 2–10 μg/min IV and titrate to response
g. Symptomatic hypotension (AHA ACLS Guidelines, off-label): 0.1 to 0.5 μg/kg/min
IV for severe hypotension. Titrate to response
h. May exacerbate ventricular ectopy
i. Use caution in patients taking monoamine oxidase inhibitors
j. Infuse into a central line or large vein whenever possible to prevent extravasation
into adjacent tissue
i. See phentolamine dosing under dopamine section (section II above)
IV. Norepinephrine (positive inotrope, strong vasopressor)
a. Hypotension, acute
i. Norepinephrine 8 to 12 μg/min IV
ii. AHA AC LS Guidelines (off-label): Initial dose 0.1 to 0.5 μg/kg/min (as base) IV;
titrate to desired effect
b. Post cardiac arrest (AHA ACLS Guidelines, off-label): 0.1 to 0.5 μg/kg/min (as base)
IV; titrate to desired effect
c. Should be diluted in D5W or D5W-NS. Dextrose solutions reduce drug oxidation.
Administration in NS alone is not recommended
d. Reduce infusions of norepinephrine gradually; avoid abrupt withdrawal
e. Use extreme caution if patient receiving monoamine oxidase inhibitors or
antidepressants of the triptyline or imipramine types. Severe, prolonged
hypertension may result
f. Infuse into a central line or large vein whenever possible to prevent extravasation
into adjacent tissue
i. See phentolamine dosing under dopamine section (section II above)
V. Phenylephrine (vasopressor)
a. Severe hypotension and shock
i. Initiate IV infusion at 0.5 μg/kg/min. Titrate to desired response, up to
6 μg/kg/min IV
ii. AHA ACLS Guidelines (off-label): phenylephrine 0.5 to 2 μg/kg/min IV
198
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