Cardiovascular Therapies



Cardiovascular Therapies

















TABLE 3.1. Treatment of Acute Coronary Syndromes (Unstable Angina, Non-ST Segment Elevation, and ST Segment Elevation Myocardial Infarction)
















































































































  • 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 β-adrenergic blockade can enhance cocaine-induced coronary artery vasoconstriction.
Agent Dosage Indications Comments
MONA(Morphine, O2, NTG, ASA) See below All patients with ACS. Bedrest, IV access, telemetry, obtain serial ECGs and cardiac enzymes
Morphine sulfate Initially 2–4 mg IV then increments of 2–8 mg IV q5–15 min prn pain If pain not relieved with NTG then give until pain and anxiety relief is obtained or hypotension occurs Reduces sympathetic tone; reduces preload; reduces myocardial O2 demand
Oxygen Initially 4 L/min by nasal cannula or 28% by venti-mask (adjust to maintain SaO2 >90%) Maximize O2 delivery to ischemic myocardium SaO2 should be maintained over 90% and preferably over 95%
Nitrates (Contraindicated in patients on sildenafil or other PDE 5 inhibitors and patients with RV infarctions)
Nitroglycerin SL: 0.4 mg q5min ×3
Spray: 1–2 metered sprays (0.4 mg NTG/spray) onto or under the tongue; may repeat in 3–5 min, ×3
IV: 20 μg/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		 Nitrate preparations for acute use; initial pain relief; coronary vasodilation; reduces preload (predominant) and afterload Causes headache; may increase myocardial O2 demand by causing unintended tachycardia or hypotension; rapid tachyphylaxis
Isosorbide dinitrate 10–60 mg PO q4–6h Useful for chronic management Daily nitrate-free interval may ameliorate tachyphylaxis to antianginal effects
Aspirin (ASA) Immediate: 162–325 mg tablet (chewed or ground up) then 75–162 mg PO qd
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		 All patients with ACS without ASA allergy
Effective for primary and secondary MI prevention		 Irreversibly inhibits prostaglandin cyclo-oxygenase, preventing formation of platelet aggregating factor thromboxane A2
Immediate antiplatelet effect; reduces mortality
Clopidogrel ACS: Initially 300 mg PO then 75 mg PO qd
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		 As a substitute for ASA in individuals with true ASA allergy
May be beneficial when added to daily ASA in NSTEMI (CURE trial)
In addition to ASA for planned PCI		 Inhibitor of ADP-induced platelet aggregation
May be associated with increased risk of bleeding in patients undergoing CABG within 5–7 d of receiving clopidogrel
Heparin (UFH) If adjunct to fibrinolytic agents: 60 U/kg IV bolus (max 4,000 U) then 12 U/kg/h infusion (max 1,000 U/h) for at least 48 h (maintain aPTT 1.5–2.0 × control)
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)		 For persistent or recurrent angina; for fibrin-specific lytics; for increased risk of systemic emboli (e.g., coexisting atrial fibrillation, LV thrombus, large or anterior MI) Enhances the action of antithrombin III
Should be avoided in cases of known HIT or whenever a pre-existing coagulopathy would increase risk over perceived benefit
Bivalirudin PCI: 0.75 mg/kg IV bolus immediately before the procedure then 1.75 mg/kg/h infusion for the duration of the procedure. Five min after bolus, an ACT should be done, and if needed an additional bolus of 0.3 mg/kg may be given. As an alternative to UFH in patients with ACS undergoing PCI
With “provisional use” of GPI IIb/IIIa (given for complications) as an alternative to UFH + GPI IIb/IIIa in patients undergoing PCI		 Direct thrombin inhibitor (synthetic analogue of recombinant hirudin)
Except in the setting of PCI there are limited data on efficacy and safety
Use in conjunction with ASA (325 mg PO); safety and
Bivalirudin (continued) Continuation of the infusion for up to 4 h postprocedure is optional (after 4 h, an additional infusion may be continued at 0.2 mg/kg/h for up to 20 h) (REPLACE-2 Trial)
As a substitute for UFH with known HIT in patients undergoing PCI		 efficacy have not been established when used in conjunction with platelet inhibitors other than ASA
Enoxaparin (LMWH) 30 mg IV bolus, then 1 mg/kg sq bid for 2–8 d (use with ASA 325 mg PO); avoid if age ≥75, serum Cr > 2 mg/dl in women or >2.5 mg/dl in men Adjunctive therapy in ACS (age <75, and without clinically significant renal insufficiency) as an alternative to UFH Direct thrombin inhibitor through complex with antithrombin III
Avoid if pre-existing coagulopathy would increase risk over perceived benefit
Fibrinolytic Agents(For contraindications refer to Table 3.2)


  • 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).
Tenecteplase IV bolus over 5–15 s
<60 kg: 30 mg
60–69 kg: 35 mg
70–79 kg: 40 mg
80–89 kg: 45 mg
≥90 kg: 50 mg		 Greater fibrin specificity then rtPA
Give with ASA and heparin (see above)
Reteplase 10 U IV over 2 min, then repeat, 30 min later, 10 U IV over 2 min Low fibrinolysis (relatively clot-selective)
Give with ASA and heparin (see above)
Alteplase (rtPA) >67 kg: 15 mg IV bolus, then 50 mg over 30 min, then 35 mg over 60 min
>67 kg: 15 mg IV bolus, then 0.75 mg/kg over 30 min, then 0.5 mg/kg over 60 min		 Low fibrinolysis (relatively clot-selective)
Give with ASA and heparin (see above)
Glycoprotein IIb/IIIa Receptor Inhibitors (GPI IIb/IIIa)


  • 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.
Abciximab 0.25 mg/kg IV bolus (over 5 min) then 0.125 μg/kg/min (max 10 μg/min) infusion for 12–24 h Consider for USA/NSTEMI undergoing PCI A murine monoclonal antibody; readministration may result in hypersensitivity, thrombocytopenia, or diminished benefit due to formation of human antichimeric antibodies
Eptifibatide 0.18 mg/kg IV bolus (max 22.6 mg) then 2 μg/kg/min (max 15 mg/h) infusion up to 72 h Consider for USA/NSTEMI undergoing PCI
Adjunct to ASA and heparin in high risk USA/NSTEMI managed medically		 If CrCl <50 mL/min or Cr >2 mg/dL, decrease infusion to 1 μg/kg/min (maximum 7.5 mg/h), contraindicated in renal dialysis
Tirofiban 0.4 μg/kg/min IV for 30 min then 0.1 μg/kg/min for 12–48 h Adjunct to ASA and heparin in high risk USA/NSTEMI managed medically CrCl <30 mL/min, decrease dose by half (0.2 μg/kg/min IV for 30 min, then 0.05 μg/kg/min)
Angiotensin Converting Enzyme—Inhibitors (Refer to Table 3.4)


  • 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.

β-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.
Magnesium sulfate 1–2 g IV over 30–60 min, then 0.5–1 g IV q1–2 h for up to 24 h Prophylactic use in ICU patients with ACS not recommended
Some studies suggest reduction in mortality while others do not		 Can cause conduction disturbances; mild hypotension; flaccidity; optimal dose unknown
Treatment of Complications of ACS
Please see the following tables:


Secondary Prevention After Acute MI


  • ASA 75–162 mg PO qd indefinitely
  • ACE inhibitor indefinitely (Table 3.4)
  • β-blocker indefinitely (Table 3.5)
  • Statin indefinitely if LDL-C ≥100 mg/dl (Table 3.6)
ACS, acute coronary syndromes; ADP, adenosine diphosphate; aPTT, activated partial thromboplastin time; ASA, aspirin; BMS, bare metal stent; BP, blood pressure; CABG, coronary artery bypass graft; CURE, clopidogrel in unstable angina to prevent recurrent events; ECG, electrocardiogram; GPI IIb/IIIa, glycoprotein IIb/IIIa receptor inhibitor; HF, heart failure; HIT, heparin-induced thrombocytopenia; INR, international normalized ratio; IV, intravenous; LAD, left anterior descending coronary artery; LDL-C, low-density lipoprotein-cholesterol; LMWH, low molecular weight heparin; LV, left ventricle; NSTEMI, non-ST segment elevation myocardial infarction; NTG, nitroglycerin; O2, oxygen; PCI, percutaneous coronary intervention; PDE, phosphodiesterase; PO, by mouth; REPLACE-2, Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events-2; RV, right ventricle; SaO2, arterial oxygen saturation; STEMI, ST segment elevation myocardial infarction; UFH, unfractionated heparin; USA, unstable angina









TABLE 3.2. Fibrinolytic Therapy for ST-Segment Elevation Acute Coronary Syndrome: Contraindications




Absolute Contraindications to Fibrinolytic Therapy


  • 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.
Relative Contraindications to Fibrinolytic Therapy


  • 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).













TABLE 3.3. Treatment of Hypervolemia, Pulmonary Edema, Cardiogenic Shock and Decompensated Heart Failure Associated with Systolic Dysfunction








































































Only gold members can continue reading. Log In or Register to continue

Related posts:

Default ThumbnailRenal, Electrolyte, and Acid Base Disturbances Default ThumbnailEndocrine Therapies Default ThumbnailGastroenterology, Liver, and Nutrition Therapies Default ThumbnailHematologic Therapies Default ThumbnailNeurologic and Psychiatric Therapeutics Default ThumbnailDrug Monitoring

Stay updated, free articles. Join our Telegram channel

Tags:
Jun 16, 2016 | Posted by in CRITICAL CARE | Comments Off on Cardiovascular Therapies

Full access? Get Clinical Tree

 Get Clinical Tree app for offline access


  • 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), β-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.
Agent Dosage Comments
3.3.1 Therapy of Pulmonary Edema or Significant Hypervolemia


  • 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 β-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.
Oxygen Initially 4 L/min by nasal cannula or 28% by venti-mask (Adjust to maintain SaO2 > 90%) SaO2 should be maintained over 90% and preferably over 95%
Morphine sulfate Initially 2–4 mg IV then increments of 2–8 mg IV q5–15min prn pain and anxiety (avoid if hypotensive) Reduces sympathetic tone; reduces preload; reduces myocardial oxygen demand
Nitroglycerin IV: 20 μg/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		 Increase venous capacitance; reduces preload (predominant) and afterload, and can reduce myocardial O2 demand; tachyphylaxis occurs
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
Diuretics


  • 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.
Diuretics—Loop of Henle


  • 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.
Bumetanide IV:
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		 Oral form duration of action 4–6 h; IV &4 h
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
Furosemide IV:
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		 Oral form duration of action 6–8 h; IV &2 h
IV boluses are usually doubled until desired effect is obtained or maximal single dose range reached (250–400 mg)
Torsemide IV:
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		 Oral and IV form duration of action &12 h
Doses can be up-titrated by doubling until desired effect is obtained or maximal single dose reached (200 mg)
IV dose = PO dose
Diuretics—Thiazide (Distal Tubule)


  • 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.
Chlorothiazide IV or oral:
Initial: 250 mg q24h or q12h
Range: 250–1,000 mg q24h, 12h
Max daily dose: 1,000 mg		 Oral or IV form duration of action 6–12 h
Hydrochlorothiazide Initial: PO 25 mg q24h or q12h
Range: PO 25–100 mg q24h, 12 h
Max daily dose: 200 mg		 Duration of action 6–12 h
Metolazone Initial: PO 2.5 mg q24h
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)		 Duration of action 12–24 h
Thiazide-like diuretic although primarily acts by inhibiting sodium reabsorption at the cortical diluting site
Diuretics—Potassium Sparing (Aldosterone Antagonists)


  • 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.
Eplerenone Initial: PO 25 mg q24h
Range: PO 25–100 mg q24h
Max daily dose: 100 mg
Max daily dose for chronic HF: 50 mg		 For HF after MI, initially 25 mg q24h, increasing to 50 mg q24h within 4 wk if tolerated (EPHESUS).
Selective aldosterone antagonist blocks mineralocorticoid but not glucocorticoid, androgen, or progesterone receptors
Spironolactone Initial: PO 12.5–25 mg q24h
Range: PO 12.5–200 mg q24h, 12h
Max daily dose: 200 mg
Max daily dose for chronic HF: 50 mg		 Duration of action 48–72 h
In severe HF, 25–50 mg q24h added to therapy with ACE-I and loop diuretics reduced risk of death or hospitalization (RALES).
Diuretics—Proximal Tubule
Acetazolamide IV or oral:
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)		 Oral form duration of action 6–12 h; IV & 4–5 h
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
3.3.2 Therapy of Hypoperfusion (characterized by low CI due to systolic dysfunction and abnormally high afterload [elevated SVR])

  • 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.
Inodilators (Inotropy and Afterload Reduction)