Ovid: Handbook of Critical Care Drug Therapy

Chapter 1

Acute Resuscitation

TABLE 1.1. Advanced Cardiac Life Support (ACLS) Drugs

Drug	Dosage	Indications/Comments
Antiarrhythmic Agents
Adenosine	Bolus: 6 mg (initial) If no response, bolus with 12 mg after 1–2 min	For conversion of PSVT unresponsive to vagal maneuvers
	May repeat 12 mg once	Give as rapid IV bolus over 1–3 s followed by rapid 10 ml fluid bolus May use lower bolus dose of 3 mg if central line available Be cautious of interactions with theophylline (inhibits adenosine), dipyridamole (potentiates adenosine), other drugs that prolong QT interval
Amiodarone	300 mg bolus IV 150 mg bolus IV followed by 1 mg/min for 6 h and then 0.5 mg/min for 18 h	For VF or pulseless VT refractory to shock; may repeat 150 mg bolus IV in 3–5 min For stable wide-complex tachycardia up to a total dose 2.2 g IV per 24 h May use for narrow complex atrial arrhythmias, as adjunct to cardioversion Monitor for bradycardia and hypotension
Atropine	Bolus: 0.5 mg IV (maximum dose 3 mg)	For either absolute (<60 beats/min) or “relative” symptomatic bradycardia
	Bolus: 1 mg IV	For bradycardia manifesting with lack of pulse, PEA or for asystole unresponsive to epinephrine May repeat dose every 3–5 min up to maximum dose 0.04 mg/kg or 3 mg
	ETT bolus: 2–3 mg	Dilute up to 10 ml in NS or sterile water (IV preferred)
Diltiazem	0.25 mg/kg IV bolus over 2 min (typically 15–20 mg)	For control of ventricular response rate in A fib or A flutter, or other narrow complex tachycardia
	May repeat once	Do not use in wide-complex tachycardia
	0.35 mg/kg IV bolus over 2 min (typically 25 mg)	Negative inotrope, so use cautiously if reduced LV function
	Maintenance infusion 5–15 mg/h
Epinephrine	Bolus: 1 mg IV (10 ml of 1:10,000 solution)	Therapy for refractory VF or pulseless VT; dose should be followed by CPR and defibrillation; may be repeated every 3–5 min
		Initial therapy for PEA; may repeat every 3–5 min
		Initial therapy for asystole; may repeat every 3–5 min
	ETT bolus: 2–2.5 mg	Dilute up to 10 ml NS or sterile water (IV preferred)
	Infusion: 2–10 µg/min	For treatment of symptomatic bradycardia unresponsive to atropine and transcutaneous pacing; alternative to dopamine
Ibutilide	1 mg IV infused over 10 min; may be repeated after 10 min Use 0.01 mg/kg if <60 kg	For treatment of atrial arrhythmias Monitor electrolytes and EKG Increased risk for torsade de pointes if elderly, abnormal LV function (EF <35%), or electrolyte abnormalities Monitor for 4–24 h
Isoproterenol	Infusion: 2–10 µg/min	May be used in torsade de pointes unresponsive to magnesium
		Use with extreme caution; at higher doses is considered harmful
		Not indicated for cardiac arrest, hypotension, or bradycardia
Lidocaine	Bolus: 1–1.5 mg/kg	For wide-complex tachycardia of uncertain type, stable VT, and control of PVCs May be followed by boluses of 0.5–0.75 mg/kg every 5–10 min up to a total of 3 mg/kg Only bolus therapy should be used in cardiac arrest
	Bolus: 1.5 mg/kg	Initial bolus dose suggested when VF is present and defibrillation and epinephrine have failed
	ETT bolus: 2–4 mg/kg	Diluted in 5–10 ml NS or sterile water (IV preferred)
	Infusion: 2–4 mg/min	Continuous infusion used after bolus dosing and following return of perfusion to prevent recurrent ventricular arrhythmias Because half-life of lidocaine increases after 24–48 h, the dose should be reduced after 24 h, or levels should be monitored Therapeutic levels 1–4 mg/L Full-loading dose but reduced infusion rate in patients with low cardiac output, hepatic dysfunction, or age over 70 years
Magnesium sulfate	Bolus: 1–2 g (8–16 mEq)	Drug of choice in patients with torsade de pointes For recurrent/refractory VT or VF For hypomagnesemia For ventricular dysrhythmias, administer over 1–2 min For magnesium deficiency, administer over 60 min
	Infusion: 0.5–1 g/h (4–8 mEq/h)	Rate and duration of infusion determine clinically or by magnitude of magnesium deficiency
Naloxone	0.4 mg IV is typical	Onset of action 2 min IV and <5 min IM/SC
	May give 0.4–2 mg IV every 2–3 min (maximum dose is 10 mg)	Duration of action ~45 min Give 0.4 mg diluted in 10 ml NS or sterile water slowly to avoid abrupt narcotic withdrawal
	0.8 mg IM/SC	Hypertension/hypotension, cardiac arrhythmias, pulmonary edema may occur Monitor for reoccurring respiratory depression because narcotics typically last longer than naloxone
	ETT: 2 mg diluted in 5–10 ml NS or sterile water	(IV preferred)
Procainamide	12–17 mg/kg; administer at rate of 20–30 mg/min (maximum 50 mg/min)	Infrequently used Recommended when lidocaine is contraindicated or has failed to suppress ventricular ectopy Use higher dose for more urgent situations (VF or pulseless VT) Maximum total dose of 17 mg/kg Continue bolus dosing until arrhythmia suppressed, hypotension, QRS complex widens by 50% of original width, or maximum total dose given Rapid infusion may cause precipitous hypotension Avoid in patients with QT prolongation (>30% above baseline) or torsade de pointes
	Infusion: 1–4 mg/min	Continuous maintenance infusion, after return of perfusion, to prevent recurrent arrhythmias Reduce dosage in renal failure Monitor blood levels in patients with renal failure or with >24-h infusion Therapeutic levels: procainamide 4–10 mg/L, N-acetyl-procainamide (NAPA) 10–20 mg/L
Vasopressin	40 U IV push, one dose only	As an alternative to 1st or 2nd dose epinephrine in refractory VF, asystole, or PEA resume epinephrine after 3–5 min
Verapamil	Bolus: 2.5–10 mg over 2–3 min	Only give to patients with narrow complex PSVT unresponsive to adenosine
	May repeat in 15–30 min prn Max. cumulative = 20 mg	Diltiazem (0.25 mg/kg) is an alternative to verapamil because it has less negative inotropy
Vasopressor Agents
Dopamine (For other vasopressors, Table 3.8)	Infusion: 2–20 µg/kg/min	For treatment of symptomatic bradycardia unresponsive to atropine and transcutaneous pacing For treatment of hypotension that is unresponsive to volume
Electrolyte Agents
Sodium bicarbonate	Bolus: 1 mEq/kg	Helpful in limited clinical conditions: hyperkalemia, bicarbonate responsive acidosis, tricyclic antidepressant overdose Not recommended in the majority of arrest cases (hypoxic lactic acidosis) Guide therapy by blood gas analyses and calculated base deficit to minimize iatrogenic alkalosis
A fib, atrial fibrillation; A flutter, atrial flutter; CPR, cardiopulmonary resuscitation; EF, ejection fraction; EKG, electrocardiogram; ETT, endotracheal tube; IM, intramuscular; IV, intravenous; LV, left ventricular; MI, myocardial infarction; NS, normal saline; PEA, pulseless electrical activity; PSVT, paroxysmal supraventricular tachycardia; PVC, premature ventricular contraction; SC, subcutaneous; VF, ventricular fibrillation; VT, ventricular tachycardia

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TABLE 1.2. Shock—General Management

Type of Shock	Initial Therapy	Subsequent Therapy
Cardiogenic Shock
Massive myocardial infarction	Supplemental oxygen, aspirin, pain relief, venous access Therapy for ACS (see Table 3.1) Optimize volume status and ensure adequate preload Treat arrhythmias Consider RHC Determine need for inotropic agents; diuretics; vasodilators; vasopressors (see Tables 3.3 and 3.8) Consider mechanical ventilation	Early IAB, coronary arteriography, and revascularization by PCI or bypass grafting Consider thrombolytic agent if cardiac catheterization not possible
Nonischemic cardiomyopathy	Therapy as above, but omit therapy for ACS	Consider IAB or assist devices as bridge to transplantation Consider reversible causes (e.g., acute valvular regurgitation requiring emergent valve replacement, thyrotoxicosis)
Oligemic Shock
Massive hemorrhage, severe dehydration, etc.	For hemorrhage, large bore peripheral or central venous access Volume resuscitation with packed RBCs and 0.9% NaCl Consider use of blood warmer If large bleed, consider platelets, fresh frozen plasma, and supplemental calcium For dehydration, volume resuscitation with 0.9% NaCl or Ringer's lactate Monitor electrolytes and coagulation	If hypotension persists despite volume resuscitation, consider: possibility of coexisting sepsis, tamponade, or ACS; RHC; inotropic and/or vasopressor agents Consult GI and surgery for massive gastrointestinal hemorrhage (see Table 7.1)
Extracardiac Obstructive Shock
Tamponade	Confirm suspected diagnosis with echocardiography and/or RHC, temporize by increasing filling pressures with bolus 0.9% NaCl IV; support BP	Urgent percutaneous pericardiocentesis, surgical pericardiotomy, or pericardial window
Massive pulmonary embolism	Correct hypoxemia; administer heparin or LMWH; thrombolytic therapy (alteplase 100 mg IV over 2 h); give inotropic support such as dobutamine for right heart strain and failure	Consider percutaneous catheter suction thrombectomy or thoracotomy with embolectomy Consider IVC filter long term See Table 4.11
Tension pneumothorax	Emergent needle or tube thoracostomy	Tube thoracostomy
Distributive Shock
Septic shock	Emergent broad-spectrum antibiotics IV after blood cultures; IV crystalloid; if shock persists, consider RHC If shock persists despite adequate preload, add dopamine 2–20 µg/kg/min; or norepinephrine 2 µg/min	Consider vasopressin in refractory shock Stress dose steroids hydrocortisone 100 mg IV q8h; optional fludrocortisone 50 µg po qd Consider baseline cortisol level prior to glucocorticosteroid therapy and corticotropin stimulation test Role of drotrecogin alfa is not established^a
Anaphylaxis	Epinephrine 0.3–0.5 mg for severe symptoms of hypotension, bronchospasm, or laryngeal edema; given as 0.3–0.5 ml of 1:1,000 SC or 0.5–1.0 ml of 1:10,000 solution IV; also give diphenhydramine 50 mg IV; repeat 25–50 mg IV q4h prn; abnormal permeability causes intravascular depletion, which should be corrected with volume	Cautious administration prn of additional epinephrine; give corticosteroids (Methylprednisolone 60 mg IV or equivalent) and cimetidine 300 mg IV q12; these will have delayed rather than immediate effect For persistent symptoms and patient on β-blockers, give glucagon 1 mg IV
Hypoadren-alism	Administer dexamethasone 4 mg IV q6h together with fluids	To confirm diagnosis, perform corticotropin stimulation test (dexamethasone will not interfere); draw baseline cortisol level, give 250 µg IV cosyntropin, and repeat cortisol level 30 min later
Neurogenic	Trendelenburg position; fluids	If hypotension persists, consider vasopressors (e.g., phenylephrine or metaraminol)
ACS, acute coronary syndrome; BP, blood pressure; GI, gastroenterology; IAB, intra-aortic balloon; IV, intravenous; IVC, inferior vena cava; LMWH, low molecular weight heparin; PCI, percutaneous coronary intervention; RBCs, red blood cells; RHC, right heart catheterization ^aWhile some authors recommend drotrecogin alfa (recombinant activated protein C) in highly selected patients with a high risk of death (Apache score of ≥25) and a low risk of bleeding, the role of drotrecogin alfa in septic patients has not been clearly established. It has no effect or is harmful in septic patients with Apache score of <25, in surgical patients with single organ dysfunction, and in pediatric sepsis. The risk of serious bleeding including intracerebral hemorrhage is increased in patients receiving drotrecogin alfa.

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TABLE 1.3. Hypovolemic Shock

	Mild	Moderate	Severe	Life-threatening
% loss of intravascular volume	≤10–15%	15–30%	30–40%	>40%
Loss of intravascular volume (cc)	<700–800	800–1500	1500–2000	>2000
Mean arterial pressure	WNL	WNL	Reduced	Reduced
Heart rate	80–100	101–119	120–140	>140
Pulse pressure	WNL/increased	101–119 Reduced	120–140 Reduced	>140 Reduced
Respirations (breaths/min)	15–20	21–29	30–35	>35
Capillary refill test^a	≤2 s	>3 s	>3 s	>3 s
Urine output (cc/h)	≥30	20–30	5–15	Oliguria
Mental status	Uneasy	Mild anxiety	Anxiety or confusion	Confusion or lethargy
Volume replacement	Crystalloid	Crystalloid	Crystalloid or blood if indicated	Crystalloid or blood if indicated
^aThe capillary refill test is performed by pressing on the fingernail or the hypothenar eminence. The test is not valid in hypothermic patients. WNL = within normal limits.

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TABLE 1.4. Crystalloids and Colloids

Fluid	Dosage	Comments
0.9% NaCl	≥500 ml^a	Hyperchloremic metabolic acidosis secondary to vigorous NaCl replacement may occur
Lactated Ringer's	≥500 ml^a	Balanced electrolyte composition (mEq/L): Na⁺ 130, K⁺ 4, Ca⁺⁺ 3, Cl^- 110, lactate 28 Not compatible with blood products
5% albumin	0.25–1 g/kg^b	Each 250 ml contains 12.5 g albumin
25% albumin	0.25–1 g/kg^b	Each 100 ml contains 25 g albumin
6% hetastarch	≥500 ml^a	Chemically modified glucose polymer Large doses, especially >1500 ml, can lead to coagulopathies (factor VIII deficiency) and platelet abnormalities Can cause artifactual hyperamylasemia Anaphylactoid reactions have occurred Total amount should not exceed 1,500 ml/d (20 ml/kg) Cautious use in cardiac bypass and septic patients
6% hetastarch in lactated electrolyte injection	500–1,000 ml	Chemically modified glucose polymer Balanced electrolyte composition (mEq/L): Na⁺ 143, K⁺ 3, Ca⁺⁺ 5, Cl^- 124, Mg⁺⁺ 0.9, lactate 28, dextrose 0.99 g/L A volume expander used to support oncotic pressure and provide electrolytes Doses >1,500 ml are rarely required Can cause artifactual hyperamylasemia Use with caution in anticoagulated patients
^aMost crystalloids are given in 500 ml aliquots as quickly as possible (i.e., over 10–15 minutes) to increase blood pressure or perfusion. If initial aliquot is not successful in increasing blood pressure, then repeat until hemodynamic stability or the addition of a vasopressor agent occur. ^bColloid has no proven outcome benefit in general ICU patients; it may have a role in hypotensive patients. Dextrans and gelatins are rarely used plasma expanders.

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FIGURE 1.1. Universal Algorithm for Adult Emergency Cardiac Care AED, automatic external defibrillator; CPR, cardiopulmonary resuscitation; ECG, electro-cardiogram; EMS Emergency Management Service; IV, intravenous; MI, myocardial infarction

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The American Heart Association in collaboration with the International Liaison Committee on Resuscitation: Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Circulation 2000; 102: 8 Suppl I with permission; also adapted from Circulation 2005;Suppl III:1–130.

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FIGURE 1.2. Algorithm for Ventricular Fibrillation (VF) and Pulseless Ventricular Tachycardia (VT) ABC, airway breathing circulation; CPR, cardiopulmonary resuscitation; IV, intravenous; PEA, pulseless electrical activity

Give drugs typically at 3–5 minute intervals: Vasopressin 40 U IV single dose (wait 10 minutes before giving epinephrine)

(

The American Heart Association in collaboration with the International Liaison Committee on Resuscitation: Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2000; 102: 8 Suppl I, with permission; also adapted from Circulation 2005;Suppl III:1–130.

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FIGURE 1.3. Algorithm for Pulseless Electrical Activity (PEA) CPR, cardiopulmonary resuscitation; EMD, electromechanical dissociation; IV, intravenous Class I: definitely helpful. Class IIa: acceptable, probably helpful. Class IIb: acceptable, possibly helpful. Class III: not indicated, may be harmful.

*Sodium bicarbonate 1 mEq/kg: is Class I: if patient has known pre-existing hyperkalemia.

†Sodium bicarbonate 1 mEq/kg: Class IIa: if known pre-existing bicarbonate-responsive acidosis; if overdose with tricyclic antidepressants; to alkalinize the urine in drug overdoses. Class IIb: if intubated and long arrest interval; upon return to spontaneous circulation after long arrest interval. Class III: hypoxic lactic acidosis.

(

The American Heart Association in collaboration with the International Liaison Committee on Resuscitation: Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2000; 102: 8 Suppl I with permission; also adapted from Circulation 2005;Suppl III:1–130.

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FIGURE 1.4. Asystole Treatment Algorithm CPR, cardiopulmonary resuscitation; IV, intravenous; TCP, transcutaneous pacing

(

The American Heart Association in collaboration with the International Liaison Committee on Resuscitation: Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2000; 102: 8 Suppl I, with permission; also adapted from Circulation 2005;Suppl III:1–130.

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FIGURE 1.5. Bradycardia Algorithm (Patient not in Cardiac Arrest) ABC, airway breathing circulation; AV, atrioventricular; BP, blood pressure; ECG, electrocardiogram; HF, heart failure; IV, intravenous; MI, myocardial infarction; TCP, transcutaneous pacemaker

*Serious signs or symptoms must be related to the slow rate. Clinical manifestations include: symptoms (chest pain, shortness of breath, decreased level of consciousness) and signs (low BP, shock, pulmonary congestion, HF, acute MI).

†Do not delay TCP while awaiting IV access or for atropine to take effect if patient is symptomatic.

§Atropine should be given in repeat doses in 3–5 minutes up to total of 0.04 mg/kg.

¶Never treat third-degree heart block plus ventricular escape beats with lidocaine.

#Verify patient tolerance and mechanical capture. Use analgesia and sedation as needed.

(

The American Heart Association in Collaboration with the International Liaison Committee on Resuscitation: Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2000; 102: 8 Suppl I, with permission; also adapted from Circulation 2005;Suppl III:1–130.

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FIGURE 1.6. Tachycardia Algorithm ABC, airway breathing circulation; AV, atrioventricular; BP, blood pressure; DC, direct current; ECG, electrocardiogram; LV, left ventricular; PSVT, paroxysmal supraventricular tachycardia; VT, ventricular tachycardia

(

The American Heart Association in collaboration with the International Liaison Committee on Resuscitation: Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2000; 102: 8 Suppl I, with permission; also adapted from Circulation 2005;Suppl III:1–130.

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FIGURE 1.7. Electrical Cardioversion Algorithm (Patient not in Cardiac Arrest) IV, intravenous; VT, ventricular tachycardia

*PSVT (paroxysmal supraventricular tachycardia) and atrial flutter often respond to lower energy levels (start with 50 J)

(

The American Heart Association in collaboration with the International Liaison Committee on Resuscitation: Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2000; 102: 8 Suppl I, with permission; also adapted from Circulation 2005;Suppl III:1–130.

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