Handbook of Critical Care Drug Therapy

• All patients with ACS are candidates for antiplatelet and antithrombin therapies.
• STEMI are candidates for reperfusion therapy (fibrinolytic or catheter-based).
• NSTEMI are not candidates for fibrinolytic reperfusion agents but should receive catheter-based therapy when applicable.
• In treating ACS attention should also be paid to exacerbating factors such as fever, anemia, hypoxemia, hypertension, hypotension, and arrhythmias.
• If chest pain or hypotension remains refractory, intra-aortic balloon counterpulsation should be considered.
• In general, patients with ACS should undergo diagnostic coronary arteriography to evaluate for left main disease, triple vessel disease, proximal LAD disease or lesions amenable to PCI.
• Cocaine-induced ACS should be treated with intravenous nitroglycerin and a calcium channel blocker (e.g., diltiazem, verapamil) and coronary arteriography should be considered. There is evidence that -adrenergic blockade can enhance cocaine-induced coronary artery vasoconstriction.

Spray: 1 2 metered sprays (0.4 mg NTG/spray) onto or under the tongue; may repeat in 3 5 min, 3

IV: 20 g/min then titrate to effect (pain relief and/or to lower BP 10% to 20% if not hypotensive)

Topical: 1 2 inches of 2% ointment q6h or equivalent patches

PCI: 75 325 mg prior to (300 325 mg at least 2 h and preferably 24 h before PCI if not on daily ASA) then 325 mg qd for at least 1 m if BMS, 3 m if sirolimus-eluting and 6 m if paclitaxel- eluting then 75 162 mg indefinitely

Effective for primary and secondary MI prevention

Immediate antiplatelet effect; reduces mortality

PCI: 300 mg PO before PCI (preferably 6 h prior), then 75 mg PO qd for at least 1 m if BMS, 3 m if sirolimus-eluting and 6 m if paclitaxel-eluting and ideally up to 12 m if bleeding risk not high

May be beneficial when added to daily ASA in NSTEMI (CURE trial)

In addition to ASA for planned PCI

May be associated with increased risk of bleeding in patients undergoing CABG within 5 7 d of receiving clopidogrel

otherwise

60 70 U/kg IV bolus (max, 5,000 U) then 12 15 U/kg/h infusion (max 1,000 U/h) for at least 48 h (maintain aPTT 1.5 2.0 control)

Should be avoided in cases of known HIT or whenever a pre-existing coagulopathy would increase risk over perceived benefit

With provisional use of GPI IIb/IIIa (given for complications) as an alternative to UFH + GPI IIb/IIIa in patients undergoing PCI

Except in the setting of PCI there are limited data on efficacy and safety

Use in conjunction with ASA (325 mg PO); safety and

As a substitute for UFH with known HIT in patients undergoing PCI

Avoid if pre-existing coagulopathy would increase risk over perceived benefit

• Only for STEMI, including true posterior MI, or presumed new left bundle branch block and <12 hours from onset (ideally 3 h from symptom onset; goal: door to drug <30 minutes).
• Consider PCI as an alternative based on local resources. In general PCI preferred if door to balloon <90 minutes, or cardiogenic shock present or late presentation (>3 hours) or contraindication to fibrinolysis. If 3 hours from symptom onset and PCI without delay then no preference for either strategy.
• Reteplase and alteplase are not known to be antigenic nor hypotensive-inducing. Tenecteplase has shown infrequent development of antibody titer at 30 days and reuse should be undertaken with precaution. It is also not hypotensive-inducing.
• Tenecteplase, reteplase, and alteplase should be used in conjunction with ASA 162 325 mg PO and heparin bolus of 60 U/kg (max 4,000 U) then 12 U/kg/h infusion (max 1,000 U/h) for at least 48 hours (maintain aPTT of 1.5 2.0 times control).

<60 kg: 30 mg

60 69 kg: 35 mg

70 79 kg: 40 mg

80 89 kg: 45 mg

90 kg: 50 mg

Give with ASA and heparin (see above)

Give with ASA and heparin (see above)

>67 kg: 15 mg IV bolus, then 0.75 mg/kg over 30 min, then 0.5 mg/kg over 60 min

Give with ASA and heparin (see above)

• Platelet aggregation inhibitor; inhibits the integrin GP IIb/IIIa receptor in the platelet membrane; contraindications include active bleeding, bleeding diathesis (past 30 days), intracranial tumor, hemorrhage arteriovenous malformation, aneurysm, recent stroke or major surgery or trauma (past month), severe hypertension, aortic dissection, pericarditis, platelets <100,000.
• Major benefit in NSTEMI troponin positive group with signs of persistent or recurrent ischemia (used in addition to aspirin or heparin).
• Can be used as adjunctive therapy with PCI strategy.
• Eptifibatide and tirofiban preferred in patients with USA/NSTEMI managed medically and abciximab and eptifibatide preferred in patients with USA/NSTEMI undergoing PCI. For planned PCI start treatment prior to procedure as early as feasible.

Adjunct to ASA and heparin in high risk USA/NSTEMI managed medically

• Beneficial in setting of MI regardless of ejection fraction or presence of HF (oral route preferred).
• Avoid IV ACE-I within the first 24 hours of symptom onset due to risk of hypotension.

-Blocking Agents (Refer to Table 3.5)

• Indicated as treatment in the setting of ACS.

Statins(Refer to Table 3.6)

• For all patients with ACS without contraindication in first 24 hours. May reduce ACS associated inflammation, and increase nitric oxide level and thus may be useful irrespective of LDL-C level.

Antiarrhythmic Agents (Refer to Tables 3.9 and 3.10)

• Do not give prophylactically and avoid Class IC agents.

Some studies suggest reduction in mortality while others do not

Please see the following tables:

• Cardiogenic pulmonary edema and shock (Therapy; Table 3.3)
• Heart failure (Tables 3.3, 3.4, 3.5)
• Arrhythmia (antiarrhythmic agents Tables 3.9 and 3.10)

Secondary Prevention After Acute MI

• ASA 75 162 mg PO qd indefinitely
• ACE inhibitor indefinitely (Table 3.4)
• -blocker indefinitely (Table 3.5)
• Statin indefinitely if LDL-C 100 mg/dl (Table 3.6)

• Active bleeding or recent bleeding diathesis (excluding menses).
• Intracranial/cerebral vascular legion (e.g., malignant intracranial neoplasm, arteriovenous malformation, or aneurysm).
• Prior intracranial hemorrhage.
• Major closed head or facial trauma within 3 months.
• Ischemic stroke within 3 months (except acute ischemic stroke <3 hours).
• Suspicion of aortic dissection.

• Chronic hypertension severe and poorly controlled.
• Presentation with severe uncontrolled hypertension (SBP >180 or DBP >110 mm Hg, consider absolute in low risk patients with STEMI).
• Prior ischemic stroke >3 months, dementia, or known intracranial pathology not covered under absolute.
• Recent internal bleeding (preceding 2 4 weeks) or active peptic ulcer disease.
• Noncompressible vascular punctures.
• Current anticoagulant use (bleeding risk proportional to INR).
• Pregnancy.
• Traumatic or prolonged cardiopulmonary resuscitation (>10 minutes) or major surgery (<3 weeks).

• Assess BP, heart rhythm, adequacy of oxygenation, mentation, heart and lung sounds. Cardiovert for VT or rapid AF; initiate anti-ischemic (coronary arteriography referral in appropriate individuals), antihypertensive, or inotropic therapies as indicated.
• Consideration should be given to guiding management with continuous arterial monitoring and RHC determined hemodynamics, especially in patients not responding to initial therapies.
• Management of compensated chronic HF associated with systolic dysfunction should routinely include oral vasodilator therapy (Table 3.4), -blockade (Table 3.5), and symptom relief with diuretics. In addition in selective patients with moderate to severe HF aldosterone antagonists (spironolactone [25 50 mg q24h for NYHA Class III IV] or eplerenone [25 50 mg for HF post-MI]) and digoxin (adjusted to serum levels of 0.5 0.9 ng/ml) can be beneficial. Cardiac resynchronization therapy should be considered in appropriate candidates on optimal medical therapy with NYHA Class III IV symptoms and LVEF 35%, QRS duration 0.12 s, and LV end diastolic dimension 30 mm (indexed to height). An implantable cardioverter defibrillator should be considered in selective HF patients per guidelines.

• If patient not hypotensive then put head of bed at 60 90 . If patient is hypotensive then also refer to Table 3.8.
• For patients with hypoxemia, consider noninvasive ventilatory support with CPAP.
• For pulmonary edema associated with hypertensive crisis also see Table 3.11. If aortic dissection is a concern then -blockade should be instituted prior to starting other antihypertensive agents.
• For patients with decompensated HF the goal would be to obtain PCWP <18 and preferably 15 mm Hg while avoiding symptomatic hypotension and organ hypoperfusion.

Topical: 1 2 inches of 2% ointment q6h or equivalent patches

Useful in patients with ischemia because of direct coronary vasodilation

Causes headache and contraindicated in RV infarction or in patients on sildenafil or other PDE 5 inhibitors

• Reduce circulating blood volume; improve oxygenation; goal is to relieve symptoms without producing hypotension or azotemia.
• Initial therapy with IV loop diuretics is recommended for patients with pulmonary edema or anasarca or suspected GI edema, others may be tried on oral therapy.
• If GFR <30 cc/min then initial doses may need to be doubled.
• Poor response to traditional oral or IV bolus diuretic regimens may respond to IV infusions or sequential nephron blockade with a loop diuretic used in combination with either metolazone or hydrochlorothiazide or chlorothiazide.
• Diuretic refractory patients may be considered for ultrafiltration.

• Primary diuretic agents used intravenously for patients with pulmonary edema or anasarca.
• Ototoxicity during therapy is most frequently associated with high doses and elevated blood concentrations.
• Furosemide 40 mg & torsemide 10 20 mg & bumetanide 1 mg.

Initial bolus: 0.5 1.0 mg

Range: 0.5 6 mg titrate to effect q2 3 prn

Infusion: 1 mg load then 0.5 2 mg/h

Oral:

Initial: 0.5 1.0 mg

Range: 0.5 10 mg q24h, 12h, 8h, prn

Max daily dose: 10 mg

Maintenance doses should be given on an intermittent schedule, i.e., QOD or every 3 4 d alternating with a 1 2-d interval without drug

Initial bolus: 20 40 mg

Range: 20 250 mg titrate to effect q1 2 prn

Infusion: 40 80 mg load then 5 20 mg/h

Oral:

Initial: 20 40 mg

Range: 20 600 mg q12h, 8h, 6h, prn

Max daily dose: 600 mg

IV boluses are usually doubled until desired effect is obtained or maximal single dose range reached (250 400 mg)

Initial bolus: 10 20 mg

Range: 10 200 mg q24h titrate to effect

Infusion: 20 mg load then 3 15 mg/h

Oral:

Initial: 10 20 mg q24h

Range: 10 200 mg q24h

Max daily dose: 200 mg

Doses can be up-titrated by doubling until desired effect is obtained or maximal single dose reached (200 mg)

IV dose = PO dose

• Primarily effects distal renal tubular mechanism of electrolyte reabsorption.
• Adjunctive diuretic agents for treatment of pulmonary edema or anasarca. May be used with loop diuretics to provide sequential nephron blockade.

Initial: 250 mg q24h or q12h

Range: 250 1,000 mg q24h, 12h

Max daily dose: 1,000 mg

Range: PO 25 100 mg q24h, 12 h

Max daily dose: 200 mg

Range: PO 2.5 20 mg q24h

Max daily dose: 20 mg

(If with loop diuretic for sequential nephron blockade then 2.5 10 mg 60 min before loop diuretic)

Thiazide-like diuretic although primarily acts by inhibiting sodium reabsorption at the cortical diluting site

• Adjunctive diuretic agents for treatment of pulmonary edema or anasarca. May be used with loop diuretics in patients with refractory hypokalemia.
• Beneficial in the treatment of chronic HF associated with systolic dysfunction.
• These agents combined with ACE inhibitors may lead to hyperkalemia (monitor potassium levels). Risk increases progressively with serum Cr >1.6 mg/dl. If baseline K 5.0 mg/dl then avoid aldosterone antagonists.

Range: PO 25 100 mg q24h

Max daily dose: 100 mg

Max daily dose for chronic HF: 50 mg

Selective aldosterone antagonist blocks mineralocorticoid but not glucocorticoid, androgen, or progesterone receptors

Range: PO 12.5 200 mg q24h, 12h

Max daily dose: 200 mg

Max daily dose for chronic HF: 50 mg

In severe HF, 25 50 mg q24h added to therapy with ACE-I and loop diuretics reduced risk of death or hospitalization (RALES).

Initial: 5 mg/kg (250 375 mg)

Range: 250 500 mg q24h, 12h

(Maintenance doses should be given on an intermittent schedule, i.e., qod or 2 out of every 3 d)

Carbonic anhydrase inhibitor, causes bicarbonaturia

Adjunctive diuretic agent for treatment of pulmonary edema or anasarca; may be used with loop diuretics in patients with metabolic alkalosis

• For patients refractory to medical therapy consideration should be given to intra-aortic balloon counterpulsation (contraindications include severe aortic insufficiency, abdominal or aortic aneurysm, and severe calcific aortic-iliac disease or peripheral vascular disease).
• For patients with HF the goal would be to obtain SVR 1,200 while avoiding symptomatic hypotension and organ hypoperfusion.
• In appropriate medically refractory HF patients consideration should be given to referral for transplantation and/or evaluation for ventricular assist device placement.

• In chronic HF, scheduled intermittent (i.e., 48 72 hours once a week) or continuous prolonged inotrope infusions may palliate symptoms but do not improve survival and can have an adverse impact on survival.

Range: 2.5 20 g/kg/min IV titrate to effect

Usual: (in HF) 2.5 7.5 g/kg/min

Wean: taper slowly (i.e., 1 g/kg/min q1h or slower)

In HF patients with CAD or associated secondary pulmonary HTN, consider using with NTG

In HF, if hypoperfusion and elevated SVR persist then consider adding nitroprusside or milrinone

May precipitate or worsen dysrhythmias

(Controversial in HF several advocate no load, realizing initial effect will be delayed several h) then 0.25 or 0.375 g/kg/min IV

Range: 0.25 or 0.375 or 0.5 or 0.75 g/kg/min IV

Wean: taper slowly (i.e., adjust dose downward q2 3h or slower elimination half-life is &2.3h)

In refractory HF patients can be combined with dobutamine

May precipitate or worsen dysrhythmias

Can cause a lupuslike syndrome

For oral dosing in HF see Table 3.4

Initial: 0.01 g/kg/min IV

Range: 0.01 0.03 g/kg/min IV

Titration: Increase by 0.005 g/kg/min (after a bolus of 1 g/kg IV) no more frequently than every 3 h up to a max dose of 0.03 g/kg/min IV (limited experience with infusion durations >48 h)

Limit use to acutely decompensated HF with dyspnea at rest or with minimal activity (VMAC trial); sufficient evidence does not exist to recommend its use as an agent to replace diuretics or enhance diuresis

Should not be used as primary therapy for cardiogenic shock or in patients with systolic BP <90 mm Hg

May be associated with a dose-dependent increase in serum Cr

Useful in patients with ischemia because of direct coronary vasodilation

Increase venous capacitance; reduces preload (predominant) and afterload

Causes headache and contraindicated in RV infarction and in patients on sildenafil and other PDE 5 inhibitors

For dosing of isosorbide dinitrate in CAD see Table 3.1 and in HF see Table 3.4

Usual: 1 4 g/kg/min IV

Titrate to effect in increments of 0.2 0.5 g/kg/min IV q10 30min or slower

Max: 10 g/kg/min IV

Wean: Taper slowly to prevent rebound increase in filling pressures and decrease in cardiac output

Preload and afterload reduction (balanced venous and arterial vasodilation); very effective for decreasing pulmonary congestion and increasing CI

Methemoglobin levels should be monitored and elevated or rising levels are indications for discontinuing

Be alert for thiocyanate toxicity (confusion, nausea, weakness, anion-gap acidosis, seizures), especially in renal insufficiency. Monitor thiocyanate levels if infusion >48 h

Solution is light-sensitive

• ACE-I are considered first line therapy with ARB a suitable alternative in patients intolerant of ACE-I, particularly in those with ACE-I induced incessant cough.
• For HF associated with systolic dysfunction in patients intolerant of ACE-I and ARB, the combination of HYZ and ISDN is a reasonable alternative. In addition the combination of HYZ and ISDN when added to standard HF therapy that includes ACE-I (or ARB), -blocker, and diuretic (many also received digoxin) has been shown to produce a further survival benefit in black patients with NYHA Class III IV HF.

• Survival benefit in NYHA Class II IV HF patients and quality-of-life benefit in NYHA Class I patients (asymptomatic LV dysfunction).
• Beneficial in setting of MI regardless of ejection fraction or presence of HF.
• Cautiously begin low doses in setting of hypovolemia, hyper K, azotemia, or serum Na <130.
• In patients with uni or bilateral renal artery stenosis, ACE-I can increase serum Cr or BUN.
• Has been associated with angioedema, rash, hyperkalemia, and incessant cough.

Range: PO 12.5 50 mg q8h (advance over 24 72 h to max tolerated dose)

Beneficial in patients with LV dysfunction and prior or current HF symptoms

Range: PO 5 20 mg q12h

Range: PO 10 40 mg qd

Range: PO 5 40 mg qd

Beneficial in patients with LV dysfunction and prior or current HF symptoms

Range: PO 10 20 mg q12h

Range: PO 2.5 5 mg q12h

Range: PO 1 4 mg qd

• Use cautiously and start in low doses in setting of hypovolemia, hyperkalemia, and azotemia.

Range: PO 8 32 mg qd

Range: PO 25 50 mg q12h

Range: PO 40 160 mg q12h

Beneficial in patients with LV dysfunction and prior or current HF symptoms

HYZ 10 20 mg PO q6 8h

ISDN 10 20 mg PO q6 8h

Range:

HYZ 25 75 mg PO q6 8h

ISDN 20 40 mg PO q6 8h

Use cautiously and start in low doses in setting of hypovolemia

Also available in a fixed dosage form of HYZ 37.5 mg and ISDN 20 mg. Starting dose to 1 tablet tid with max dose 2 tablets tid

HYZ can cause a lupuslike syndrome; ISDN can cause headache and is contraindicated with sildenafil and other PDE 5 inhibitors

• -blockade is indicated as treatment in the setting of ACS and for secondary prevention post-MI. It is beneficial in the setting of MI regardless of EF or presence of HF.
• -blockade with either carvedilol or bisoprolol or metoprolol (CR/XL) is indicated for HF associated with systolic dysfunction. There is sufficient evidence from multiple randomized trials to recommend these agents in NYHA Class II IV HF. Many experts would also advocate these agents in NYHA Class I HF. Appropriate candidates should be in a relatively compensated state with resting HR >60, and absence of 2nd- or 3rd-degree AV block or bronchospastic disease.
• -blockers can cause bradycardia, hypotension, bronchospasm, worsened conduction disturbances, worsened HF in a decompensated HF patient, and rebound ischemia after discontinuation.
• There is evidence that -adrenergic blockade augments cocaine-induced coronary artery vasoconstriction.

Range PO: 25 100 mg qd

1 cardioselective at usual dose; long half-life allows qd dosing

Initial: PO 1.25 mg qd

Range: PO 1.25 10 mg qd

(Initial dose doubled after 1 wk then titrate over 1 4 wk intervals to max tolerated)

Anti-ischemic range: PO 5 20 mg qd

1 cardioselective

Initial: PO: 3.125 mg q12h

Range: PO: 6.25 25 mg q12h (max dose 50 mg q12h if wt >85 kg)

(Initial dose doubled after 1 2 wk then titrated as tolerated every 2 wk)

Anti-ischemic range: PO 25 50 mg qd

Reduction in HF or cardiac events following MI

Not cardioselective

Consider reducing loading dose in marginally or poorly compensated patients

Use 100 mg vial for loading dose

Initial: (NYHA II) PO 25 mg qd

Initial: (NYHA III IV) PO 12.5 mg qd

Range: PO 25 200 mg qd

(Initial dose doubled after 1 2 wk then titrated as tolerated every 2 wk)

Anti-ischemic range: PO 100 400 mg qd

Tartrate (ACS therapy):

IV: 5 mg q5min up to 15 mg then begin PO therapy 15 min after final IV dose

Initial: PO 25 50 mg PO q6h for 48 h

Range: PO 50 200 mg q12h

Tartrate form associated with reduction in HF or cardiac events following MI

1 selective at daily doses totaling 200 mg

Range: PO: 10 80 mg q6h

Long acting:

Range: PO: 80 320 mg qd

Prototype -blocker; not cardioselective

• For all patients with ACS without contraindication in first 24 hours. May reduce ACS associated inflammation, and increase nitric oxide level and thus may be useful irrespective of LDL-C level.
• For secondary prevention in patients with LDL-C >100 mg/dl.
• Reduction in LDL-C 18% to 55%, TG 7% to 30%, and increase in HDL-C 5% to 15%.
• Contraindicated in active or chronic liver disease.
• Side effects: Myopathy (monitor CK) or increased liver enzymes (monitor AST and ALT).
• Liver enzyme tests should be performed before and at 2 3 months following both the initiation of therapy and dose elevations, and periodically (e.g., semiannually) on chronic therapy.
• Reduce dose or discontinue if serum transaminase levels of 3 times the upper normal limit persist.
• Temporarily hold or discontinue if a condition suggestive of or predisposing to myopathy or renal failure develops.
• Concomitant therapy with cyclosporine, macrolides, protease inhibitors, azole antifungals, nefazodone, fibrates, or niacin may increase the risk of myopathy.

• In general, calcium channel antagonists are not used in the treatment of acute coronary syndromes.
• Used for treatment of hypertension.
• Nondihydropyridine forms are used for treatment of atrial arrhythmias.

PO: 30 90 mg q6h

Max cumulative = 20 mg

PO: 40 160 mg q6h

Titrate: 2.5 mg/h every 5 15 min

Range: 5 15 mg/h IV

PO: 20 40 mg tid

• Vasoconstrictors usually are administered by central vein and should be used in conjunction with adequate volume repletion. All can precipitate myocardial ischemia. All except phenylephrine can cause tachyarrhythmias.
• Cautions should be used to avoid extravasation of vasoconstrictors. If extravasation occurs, 10 15 ml of 0.9% NaCl containing 5 10 mg of phentolamine should be infiltrated liberally throughout the affected area.

Start at 30 g/min IV and titrate

Alpha

Doses up to 350 g/min may be required in some settings

Start at 0.01 U/min and titrate; doses should be limited to 0.04 U/min

Exact mechanism of BP increase is unknown

2 20 g/kg/min

Dopaminergic effects (++++)

Alpha

Beta

Increases in BP mainly due to increases in inotropy and HR

Start at 2 g/min and titrate

Alpha

Beta

Doses up to 0.5 g/kg/min may be required in some settings

Start at 2 g/min and titrate

Alpha

Beta

Doses up to 3 g/kg/min may be required in some settings

2.5 20 g/kg/min

Beta

Can be combined with nitroprusside, NTG, or milrinone

Can be combined with dobutamine

Load 2 g/kg bolus, then 0.01 g/kg/min and increase by 0.005 g/kg/min (after 1 g/kg bolus) no sooner than every 3 h

Range: 0.01 0.03 g/kg/min

Should not be used for intermittent outpatient infusion, scheduled repetitive use, to improve renal function, to enhance diuresis, or as primary therapy for cardiogenic shock

0.25 4 g/kg/min (20 300 g/min)

Useful in patients with ischemia due to direct coronary vasodilation

Contraindicated with sildenafil and other PDE 5 inhibitors

Initial: 0.2 g/kg/min (10 15 g/min)

Usual: 1 4 g/kg/min

Max: 10 g/kg/min

Useful for acute management of low cardiac output states

Methemoglobin levels should be monitored and elevated or rising levels are indications for discontinuing

May repeat 0.5 0.75 mg/kg IV to a max 3 mg/kg, then infusion 1 4 mg/min

IV formulation not available in the U.S.

Contraindicated if conduction abnormalities, coronary disease, HF

Avoid if electrolyte abnormalities or liver disease

Used for supraventricular arrhythmias

150 300 mg PO q8h

600 mg po single dose used for cardioversion of recent onset A fib

Avoid if structural heart disease, conduction abnormalities, or abnormal electrolytes

Use 100 mg vial for loading dose

Used for atrial arrhythmias

Drug of choice for reduced LV function

IV: 150 mg over 10 min, then 1 mg/min for 6 h, then 0.5 mg/min maintenance infusion; switch to PO when possible; for recurrent ventricular arrhythmias, supplement with infusions of 150 mg over 10 min

IV: 300 mg for VF refractory to 1 2 shock-CPR cycles and one vasopressor agent

ARDS has been reported

With IV administration, hypotension, bradycardia, and AV block can occur

Avoid if abnormal electrolytes, prolonged QT interval

Use with caution in patients with EF <35%

IV formulation not available in the U.S.

Monitor level

If stable

1st choice: vagal maneuvers such as carotid sinus massage

2nd choice: IV adenosine

Alternatives: IV verapamil; IV diltiazem; IV -blocker

If reduced LVEF, amiodarone preferred to calcium channel antagonists

Consider electrical cardioversion; rapid atrial pacing, or IV ibutilide if normal LVEF

1st choice: PO -blocker, PO verapamil, or PO diltiazem

2nd choice: PO digoxin

3rd choice: Class IA/C or Class III drugs

If reduced EF, amiodarone preferred

If stable

For rate control:

IV diltiazem, -blocker, amiodarone, or digoxin depending on clinical setting?

For restoring sinus rhythm:

1st choice: IV/PO Class IC or Class III drugs

Class IA drugs rarely used

If CAD, sotalol preferred over Class IC

If HF, amiodarone preferred over Class IC

Rate control with oral drugs: -blockade, verapamil, diltiazem, digoxin, or amiodarone

Rhythm control with oral drugs: Class III or Class IC or Class IA (rarely used) drugs depending on clinical setting

Prophylactic warfarin and/or aspirin should be prescribed for paroxysmal or chronic A fib/flutter unless contraindicated

Notes: (1) If A fib persists >24 48 h, anticoagulate prior to conversion; (2) use type IA antiarrhythmic agents only after blocking the AV node with digoxin or a calcium channel or -blocker; (3) prior to cardioversion, consider whether TEE or several weeks anticoagulation is necessary

2nd choice: IV diltiazem or IV verapamil

3rd choice: IV esmolol or IV metoprolol (use caution despite -1 selectivity)

-blockade may be contraindicated because of pulmonary disease

Note: Digitalis and electrical cardioversion are both ineffective for this rhythm

2nd choice: PO, Class IC, or Class III agents

Catheter ablation may be necessary

Initially 200 J unsynchronized monophasic or biphasic equivalent

If stable with pulse

Drug choices:

1st: IV amiodarone

2nd: IV lidocaine

3rd: IV procainamide

4th: -blockade, Mg

Electrical:

Synchronized cardioversion

Drug therapy should be tailored to circumstance. It may include -blockade, amiodarone, sotalol, or LV remodeling regimen in heart failure

Other antiarrhythmic agents may be proarrhythmic

Note: Symptomatic ventricular tachycardia requires evaluation and treatment. Asymptomatic ventricular arrhythmias may require evaluation especially if reduced LV function. Therapy is not usually needed for premature ventricular contractions.

Initially 200 J unsynchronized monophasic or biphasic equivalent

If stable

1st choice: IV magnesium sulfate

2nd choice: increase heart rate with atrial pacing, isoproterenol, or atropine

After 1 2 shocks, consider epinephrine 1 mg IV at 3 5 min intervals. May give vasopressin 40 U IV once, instead of 1st or 2nd dose epinephrine

Consider amiodarone 300 mg IV over 10 min

Other possible drugs include IV lidocaine, procainamide, or Mg

Onset: <1 min

Duration: 1 10 min

Methemoglobinemia

Cyanide toxicity

Onset: 1 2 min

Duration: 3 10 min

Onset: 5 min

Duration: 2 12 h

Onset: 1 2 min

Duration: 3 10 min

Tachycardia, GI stimulation, hypoglycemia

• Side-effects include bronchospasm, negative inotropy, HF, conductive disturbances

Range: 5 15 mg IV

Onset: 5 10 min

Duration: 3 6 h

Onset: 1 3 min

Duration: 1 2 min for -blockade

The bolus dose should be withdrawn from the 100-mg vial

Infusion doses >300 g/kg/min have not been studied

Onset: IV 2 3 min

Duration: 1 6 h

Onset: 15 min

Duration: 4 6 h

Initial dose in pt on diuretics: 0.625 mg

Titrate: 2.5 mg/h every 5 15 min

Range: 5 15 mg/h

Onset: 1 5 min

Duration: 30 min

30 mg PO q8h = 1.2 mg/h

40 mg PO q8h = 2.2 mg/h

Tachycardia; monitor for hypokalemia q6

Can worsen glaucoma; contains sulfites; effect of dialysis unknown; avoid in intracranial hypertension

Onset: 4 6 h

Duration: 10 16 h

• For hypertension associated with neurologic disorders, see chapter 9
• Rate of BP reduction and final BP goal depends on diagnosis. In general BP should not be reduced more than 10% to 15% over 4 6 hours and then a more gradual reduction over the ensuing days. Rapid control of BP is indicated in aortic dissection. Diuretic only for pa- tient with clinically evident fluid overload.

Alt: Labetalol

Alt: Calcium channel blocker

Alt: Labetalol

Drugs to avoid: hydralazine, minoxidil, nifedipine

Alt: Labetalol

Alt: Calcium channel blockers

(BP > 140/90 mm Hg, edema, proteinuria, seizures in pregnancy)

Alt: Labetalol

Alt: Calcium channel blockers

Renovascular hypertension;

Vasculitis

Alt: Calcium channel blockers

Alt: ACE inhibitors

-blockers after -blockade

Alt: Labetalol

Alt: Nitroprusside

Alt: Nitroprusside

Alt: Labetalol

Alt: Phentolamine

Alt: Nitroprusside

Alt: Nitroprusside

Alt: Phentolamine

Alt: Resume clonidine or -blocker

• This form includes familial and idiopathic ( primary ) PAH and PAH associated with congenital systemic-to-pulmonary shunts, portal hypertension, collagen vascular diseases (e.g., scleroderma), certain drugs and toxins (e.g., anorexic agents), HIV disease, and hemoglobinopathies (e.g., sickle cell disease). IPAH has a mPAP >25 mm Hg at rest and a PCWP or LA pressure 15 mm Hg.
• Treatments below are not being recommended for PH due to postcapillary etiologies (e.g., left-sided heart disease), hypoxic etiologies (e.g., sleep disordered breathing, chronic high altitude), airway or parenchymal lung diseases (e.g., COPD, ILD), and chronic thrombotic and embolic etiologies.
• Progressive evaluation may include EKG, chest x-ray, echocardiogram, 6-minute walk, pulmonary function studies, chest CT, polysomnogram, serologies (e.g., ANA, RF, Scl 70, HIV), liver sonogram, VQ scan, pulmonary angiography, and RHC.
• Anticoagulant therapy based on risk benefit analysis should be considered to reduce risk of pulmonary thrombo-embolism or systemic embolism.
• Consider lung transplant evaluation or balloon atrial septostomy in appropriate refractory candidates.

Monitor serum K and renal function

Vasoreactivity testing: 10 or 20 ppm inhaled (2 3 sets of baseline hemodynamics over 1 h then NO dose given over 6 10 min with hemodynamics determined)

Doses >20 ppm increase risk of methemoglobinemia; monitor methemoglobin levels prior to and at 1 and 6 h after initiating prolonged therapy and after each dose increase, otherwise daily. NO dose should be reduced for methemoglobin concentration 5%

Used to test pulmonary vasoreactivity in IPAH: Positive response = decrease of 10 mm Hg in mPAP to mPAP 40 mm Hg without a decrease in CO

May be useful as continuous inhalation therapy in ventilated patients with PH and right HF

Interruptions in delivery during chronic administration or large dose reductions may cause symptoms of rebound PAH

May increase bleeding risk due to inhibitory effects on platelet aggregation

• Reserved for IPAH with a positive vasodilator test (see NO above).
• Maintenance of response defined as NYHA Class I II and near normal resting hemodynamics should be re-evaluated in 6 months. If response not maintained then patient should be considered for therapy with prostanoids or an endothelin-1 receptor antagonist.
• There are limited data on dose ranges and optimal dosing.

Usual IPAH range 30 180 mg q8h

Should be up titrated cautiously

Usual IPAH range: 120 720 mg q6 8h

Should be up titrated cautiously

Usual IPAH range: 2.5 30 mg PO qd

Limited data and should be up titrated cautiously

• Epoprostenol is produced in the vascular endothelium. Treprostinil and iloprost are stable analogues of epoprostenol. These agents are vasodilators with platelet antiaggregating properties.
• Adverse reactions associated with initiation and up titration of prostanoid therapy include jaw pain, flushing, headache, nausea, diarrhea, rash, anxiety, hypotension, and musculoskeletal pain. In addition epoprostenol therapy carries the risk of catheter-related infections and thromboembolic events, treprostinil can cause pain and induration at the infusion site, and iloprost has been associated with trismus and cough.

Average discharge dose after a 3-d initial titration was 6.5 ng/kg/min

Adjustments: Increases or decreases of 1 2 ng/kg/min are usually based on symptoms or excessive side effects

Plateau dose usually 20 40 ng/kg/min

Chronic overdosing can result in high-output HF

Requires a central venous catheter for administration; interruptions in delivery or large dose reductions may cause symptoms of rebound PAH

Adjustments: increase by >1.25 ng/kg/min per wk for the first 4 wk then 2.5ng/kg/min per wk based on symptoms; similar decreases are made based on excessive side effects

Limited data with >40 ng/kg/min

Avoid interruptions in delivery

Liver disease: initial dose should be decreased to 0.625 ng/kg/min and increased cautiously

Liver disease: give 2.5 g at intervals 3 h to max of 6 times daily; dose may be cautiously increased or given more frequently per patient response

• Endothelin-1 is a vasoconstrictor and smooth muscle mitogen.
• Bosentan may cause hepatotoxicity. If elevated AST or ALT with symptoms or Bili of 2 UNL, then stop. If AST or ALT >3 and 5 UNL, then reduce or hold and monitor AST/ALT; if levels return to pretherapy values, then continue or reintroduce (starting dose); and monitor levels. If ALT or AST >5 and 8 UNL, then stop and monitor levels; if levels return to pretherapy values, then consider reintroduction (starting dose) and monitor levels. If ALT or AST >8 UNL, then stop and should avoid reintroducing.

Maintenance, up to 125 mg PO q12h

Adults <40 kg: initial and maintenance, 62.5 mg PO q12h (monitor liver function [monthly] and hemoglobin [1 mo, 3 mo, every 3 mo])

Should avoid if elevated AST or ALT >3 the UNL at baseline

Adverse reactions include hepatotoxicity, anemia, edema, headache, hypotension, nausea, emesis, dyspepsia, palpitations, and flushing

• Limited data on long-term efficacy and safety alone or in combination with prostanoids or bosentan.

Dose increases of 25 mg q8 12h every 2 4 wk, based on symptoms (limited data on dosing, particularly maximal efficacious dose)

Increased plasma levels can occur in the elderly (age >65) and with renal impairment (Cr clearance <30 mL/min), hepatic impairment and concurrent use of cytochrome P450 inhibitors

Inhibitor of cGMP specific phosphodiesterase; lengthens and enhances effects of inhaled NO

Hypotension can result with the coadministration of nitrates

Adverse reactions include headache, flushing, periorbital edema, and priapism

Sotalol

Ibutilide, dofetilide, sematilide

Disopyramide

Procainamide

Quinidine

Amiodarone^b

Nonantiarrhythmic Agents

Erythromycin, clarithromycin, telithromycin, azithromycin

Ketoconazole, itraconazole

Quinolones (sparfloxacin, moxifloxacin, gatifloxacin, gemifloxacin, levofloxacin)

Phenothiazines (chlorpromazine, droperidol, haloperidol, thioridazine)

Fosphenytoin

Methadone

Pentamidine

Probucol

Quetiapine

Risperidone

Arsenic trioxide

Astemazole^c

Bepridil, mibefradil

SSRI (venlafaxine)

Terfinadine^c

Tricyclic antidepressants

Trimethoprim-sulfamethoxazole

^bRisk of torsade is low.

^cNot available in the U.S.