Prosthetic Heart Valves

Dr. Mona Youssefhttp://www.cardiologylinks.webs.com/home

complications

• Primary valve failure• Prosthetic valve endocarditis (PVE)• Prosthetic valve thrombosis (PVT)• Thromboembolism• Mechanical hemolytic anemia• Anticoagulant-related hemorrhage

Make UP

• Composition: - Synthetic material (mechanical prosthesis) - Biological tissue (bioprosthesis). - Homografts or preserved human aortic valves

• Three main designs : - Caged ball valve - Tilting disc (single leaflet) valve - Bileaflet valve.

*The only Food and Drug Administration (FDA)–approved caged ball valve is the Starr-Edwards valve

Bioprosthetic (xenograft) valves

Made from:

• Porcine valves e.g. Carpentier-Edwards valves or

• Bovine pericardium e.g. Perimount series valves

Pathophysiology

Valve failure

• Abruptly: -Tearing e.g. suture line dehiscence or breakage of components with acute valvular regurgitation or embolization of the valve fragments -Thrombus suddenly impinging on leaflet mobility• Gradually: - Calcifications with stiffening of the leaflets - Thrombus / pannus formation

Stenosis or incompetence of prosthetic valves

Acute Mitral Valve Failure

• Sudden left atrial volume overload • Increased left atrial pressure• Pulmonary venous congestion • Pulmonary edema • Decreased left ventricular output due to regurgitatnt volume into

the left atrium• The compensatory mechanism of increased sympathetic tone: - Increases the heart rate and the systemic vascular resistance (SVR) - Decreases diastolic filling time - Impedes left ventricular outflow - Increases the regurgitant volume

Acute Aortic valve Failure

• Rapidly progressive left ventricular volume overload• Increased left ventricular diastolic pressure • Pulmonary congestion and edema• Decreased cardiac output• The compensatory mechanism of increased sympathetic tone: - Increases heart rate and yields a positive inotropic state, aiding in the maintenance of cardiac output BUT also: -increases SVR impeding forward flow -Increases systolic wall tension yielding a rise in myocardial oxygen consumption& Myocardial ischemia, even in the absence of coronary artery disease.

Bioprosthesis

• Mostly suffer from slow degeneration, calcification, or thrombus formation

• Asymptomatic• gradually worsening congestive heart failure, with increasing

dyspnea.• Unstable angina • Systemic embolization

Prosthetic Valve Endocarditis

Early PVE occurring within 60 days of implantation

Due to: perioperative contamination or hematogenous spread

• Charecteristic lesion in mechanical valves : ring abscesses *Ring abscess may lead to: - Valve dehiscence and perivalvular leakage - Local extension with formation of myocardial abscesses - Further extension to the conduction system producing a new atrioventricular block - Less frequently valve stenosis and purulent pericarditis

• Bioprosthetic valve PVE usually causes leaflet tears or perforations. Valve stenosis is more common with bioprosthetic valves than with mechanical valves. Ring abscess, purulent pericarditis, and myocardial abscesses are much less frequent in bioprosthetic valve PVE.

• Finally: glomerulonephritis, mycotic aneurysms, systemic embolization, and metastatic abscesses

Late PVE

occurrs after 60 days

usually caused by hematogenous spread

Prosthetic valve thrombosis

Incidence• Prosthetic valve thrombosis is more common in mechanical valves

• Thromboembolic complication rates: - Hightest in Caged ball valves - Lowest in bileaflet valves

• Valve thrombosis is increased with: - Valves in the mitral position - In patients with subtherapeutic anticoagulation.

• Anticoagulant-related hemorrhagic complications : - Major hemorrhage in 1-3% of patients per year - Minor hemorrhage in 4-8% of patients per year.

• hemolytic anemia - Low-grade in 70% of prosthetic heart valve recipients - Severe hemolytic anemia occurs in 3% *The incidence is increased with caged ball valves and in those with perivalvular leaks.• Primary valve failure occurs in: - 3-4% of patients with bioprostheses within 5 years of implantation and in up to 35% of patients within 15 years. - Mechanical valves have a much lower incidence of primary failure.• PVE occurs in 2-4% of patients: - 3% in the first postoperative year, then 0.5% for subsequent years. - The incidence is higher in mitral valves. - Mechanical and biological valves are equally susceptible.

Mortality/Morbidity

• Acute failure of a prosthetic aortic valve usually leads to sudden or near-sudden death.

• PVE has an overall mortality rate of 50%. • In early PVE, the mortality rate is 74%. • In late PVE, the mortality rate is 43%.• The mortality rate with a fungal etiology is 93%.• The mortality rate for staphylococcal infections is 86%.• Fatal anticoagulant-induced hemorrhage occurs in 0.5%

of patients per year.

Age

• The incidence of having any prosthetic valve complication decreases with age.

• In children, bioprostheses rapidly calcify and undergo rapid degeneration and valve dysfunction.

• Bioprosthetic failure is much higher in patients younger than 40 years.

Clinical

History

• Sources include a wallet-sized identification card (typically given to the patient at the time of surgery) and/or a review of medical records.

• Symptoms depend on the type of valve, its location, and the nature of the complication.

-With valvular breakage or dehiscence, failure often occurs acutely with rapid hemodynamic deterioration. -Failure occurs more gradually with valve thrombosis, calcification, or degeneration.• Heavily calcified or infected valvular annulus is suggestive of a

perivalvular leak• Acute prosthetic valve failure often present with the sudden onset

of dyspnea, syncope, or precordial pain.

• Subacute valvular failure maybe asymptomatic/ present with: - Gradually worsening congestive heart failure. (increasing dyspnea with exertion, orthopnea, paroxysmal nocturnal dyspnea, and fatigue) - Unstable angina • Embolic complications have symptoms related to the site of

embolization: - Stroke -Myocardial infarction (MI) - Sudden death - Symptoms of visceral or peripheral embolization.• Anticoagulant-related hemorrhage symptoms are related to the

site of hemorrhage.• PVE: Fever

Physical Exam• Normal prosthetic heart valve sounds

– Mechanical valves: .Tilting disc and bileaflet valves: *A loud, high-frequency, metallic closing sound. Can frequently be heard without a stethoscope Absence of this distinct closing sound is abnormal and implies valve dysfunction * +/- a soft opening sound .Caged ball valves (Starr-Edwards) have low-frequency opening and closing sounds of nearly equal intensity.

– Tissue valves: Closing sounds are similar to those of native valves. A low-frequency early opening sound may present in the mitral position.

*Muffled or absent normal prosthetic heart sounds may be a clue to valve failure or thrombosis.

• Prosthetic heart valve murmurs – Aortic prosthetic valves -Smaller orifice size always yields some degree of outflow obstruction producing a systolic ejection murmur - The intensity of the murmur increases with rising cardiac output - Caged ball and small porcine valves produce the loudest murmurs - Tilting disc valves and bileaflet valves upon closure do not occlude their outflow tract competely allowing for back flow producing a low-intensity diastolic murmur, but never more than 2/6 (suspect valvular failure) - Caged ball and tissue valves cause no diastolic murmur since they completely occlude their outflow tract in the closed position (any degree of diastolic is pathologic unless proven otherwise.

- Mitral prosthetic valves - A low-grade systolic murmur maybe heard with Caged ball valves due to the turbulent flow caused by the cage projecting into the left ventricle

- Any holosystolic murmur greater than 2/6 is pathologic in a patient with an artificial mitral valve.

-Short diastolic murmurs - best heard at the apex with the patient in the left lateral decubitus position -may be heard with bioprostheses and, the St. Jude bileaflet valve

• Acute valvular failure results in cardiogenic shock and severe hypotension: – Evidence of poor tissue perfusion : diminished peripheral pulses, cool or

mottled extremities, confusion or unresponsiveness, and decreased urine output.

– A hyperdynamic precordium and right ventricular impulse is present in 50% of patients

– Absence of a normal valve closure sound or presence of an abnormal regurgitant murmur

• Subacute valvular failure may present with signs of gradually worsening left-sided congestive heart failure. – Rales and jugular venous distention– A new regurgitant murmur– Absence of normal closing sounds.– A new or worsening hemolytic anemia (may be the only presention)

• PVE (often obscure)– Fever occurs in 97% of patients– A new or changing murmur is present in 56% of patients .produced by valvular dehiscence, stenosis, or perforation . May not occur early in the course of the illness & its absence does not exclude the diagnosis – Classic signs for native valve endocarditis, including petechiae, Roth spots, Osler nodes,

and Janeway lesions are often absent – Splenomegaly present in only 26% of early PVE cases and in 44% of late PVE cases.– PVE may present as congestive heart failure, septic shock, or primary valvular failure.– Systemic emboli may be the presenting symptom in 7-33% of cases of PVE(more

common with fungal etiologies)• Thromboembolic complications: signs related to the site of embolization. . Stroke ,MI, sudden death, or visceral or peripheral embolization . Systemic embolization should alert the physician to suspect valve thrombosis/ PVE• Anticoagulant-related hemorrhage: Signs depend on the site of hemorrhage

Causes• Prosthetic valve endocarditis (PVE) has been divided into 2

subcategories in accordance with differences in clinical features, microbial patterns, and mortality:

– Early PVE occuring within 60 days of valve insertion . is usually the result of perioperative contamination . Causative organisms include - Staphylococcus epidermidis (25-30%) -Staphylococcus aureus (15-20%) - gram-negative aerobes (20%) - fungi (10-12%) - streptococci (5-10%) - diphtheroids (8-10%).

– Late PVE appearing after 60 days of valve insertion . is usually the result of transient bacteremia from dental or genitourinary sources, GI manipulation, or intravenous drug abuse . The causative organisms -are similar to those causing native valve endocarditis -Include Streptococcus viridans (25-30%) S epidermidis (23-38%) S aureus (10-12%) gram-negative bacilli (10-12%) group D streptococci (10-12%) fungi (5-8%) and diphtheroids (4-5%).

*Multiple negative blood culture maybe seen with infections by - The (HACEK) group: Haemophilus aphrophilus Actinobacillus actinomycetemcomitans Cardiobacterium hominis Eikenella corrodens and Kingella kingae - Serratia and Rickettsia species - Aspergillus - Histoplasma - and Candida species. **Brucella :rare

Workup

Differential Diagnoses

• Chronic anemia• Peripheral vascular disease• Aortic regurgitation/ stenosis• Mitral regurgitation/ stenosis• Pulmonary embolism• Cardiogenic shock / septic shock• CHF & Pulmonary edema• Endocarditis• stroke Hemorrhagic/ ischemic• Myocardial infarction

Imaging Studies• An overpenetrated anteroposterior chest radiograph could aid in delineating the valvular

morphology and whether or not the valve and occluder are intact. In more stable patients, a lateral chest film helps identify the valve position and type.

• Radiographic appearance of the more commonly seen valves– Starr-Edwards caged ball valve

• Radiopaque base ring• Radiopaque cage• Three struts for the aortic valve; 4 struts for the mitral or tricuspid valve• Silastic ball impregnated with barium that is mildly radiopaque (but not in all models)

– Bjork-Shiley tilting disc valve (discontinued, but many patients still have these valves implanted) • Base ring and struts are radiopaque.• Two U-shaped struts project into base ring.• Edge of occluder disc is also radiopaque.

– Medtronic-Hall tilting disc valve • Radiopaque base ring• Radiopaque struts that project into base ring: 3 small ones and 1 large hook-shaped

one• Occluder disc that is mildly opaque but often cannot be seen

– Alliance Monostrut valve • Occluder has a radiopaque rim.• The base ring and two struts are radiopaque.

– St. Jude medical bileaflet valve • Mildly radiopaque leaflets are best seen when viewed on end. Seen as radiopaque

lines when the leaflets are fully open.• Base ring is not visualized on most models.• The valve may not be visualized on some radiographs.

– CarboMedics bileaflet valves: Valve housing and leaflets are radiopaque and easily visible.– Carpentier-Edwards porcine valve: The tall serpiginous wire support is the only visualized

portion.– Hancock porcine valve

• The radiopaque base ring is the only visible part in some models.• Other models have radiopaque stent markers with or without a visible base ring.

– Ionescu-Shiley bovine pericardial valve: Base ring and wide fenestrated stents are one piece.

Laboratory Studies• Complete blood count

– Microscopic evidence of hemolysis should be present. – A sudden increase in hemolysis may signal a perivalvular leak.6

– A hematocrit lower than 34% is present in 74% of patients and is the most common hematologic finding.

– A WBC count lower than 12,000 is present in as many as 54% of patients with PVE.

• Urinalysis: Hematuria is present in 57% of patients with PVE.• Blood cultures

– Culture results are positive in multiple samples in 97% of patients with PVE.

– Blood cultures should be held for 3 weeks. *Multiple blood cultures should be taken.

• Prothrombin time (PT)/international normalized ratio (INR) general guideline( but therapy must be individualized) – Bioprosthetic valves: INR 2-3 for 3 months following implantation; may then be discontinued unless otherwise indicated e.g. AF or development of prosthetic valve thrombosis.– Mechanical valves: . INR 2.5-3.5 . patients with AF and those with valves in the mitral position should be kept at the higher end of this range . Patients with bileaflet valves may be kept at the lower end of this range– Subtherapeutic values should raise the suspicion of valve thrombosis or

systemic embolization.

• Echocardiography – Acoustic shadowing originating from the components of the prosthetic valve

especially the mitral can severely limit the image interpretation– Two-dimensional and Doppler echocardiography may demonstrate : perivalvular leaks vegetations inadequate valve/occluder movement.

– Two-dimensional echocardiography and Doppler echocardiography can detect the presence of acute valvular regurgitation and grade the severity.

– Transesophageal echocardiography is the imaging study of choice in patients with a suspected prosthetic valve complication.

– A normal transthoracic echocardiogram does not rule out a pathologic process.

• Cinefluorography may detect impaired occluder movement but often cannot readily determine the etiology.

Other Tests

• Electrocardiography – An atrioventricular (AV) block may indicate the

presence of a myocardial abscess. – A fever and new AV block is considered PVE until

proven otherwise.– Atrial fibrillation is common in mitral valve

replacement and may cause hemodynamic compromise.

Treatment

Emergency Department Care• In patients with acute valvular failure, diagnostic studies must be performed

simultaneously with resuscitative efforts.

• Primary valve failure: due to breakage or abrupt tearing of the components usually present with acute hemodynamic deterioration and needs immediate valve replacement, meanwhile:

– Reduce the impedance to forward flow and improve peripheral perfusion via afterload reduction and inotropic support .

-If the mean arterial pressure is higher than 70 mm Hg: sodium nitroprusside - If the mean arterial pressure is lower than 70 mm Hg:

dobutamine alone or in combination with inamrinone

– Avoid inotropic agents with vasoconstricting properties.

– In cases of acute mitral regurgitation and surgical facilities are not immediately available: Intra-aortic balloon counterpulsation

– Intra-aortic balloon counterpulsation is relatively contraindicated in the presence of an incompetent aortic valve.

• Prosthetic valve endocarditis – Administer intravenous antibiotics . after 2 sets of blood cultures are drawn . Vancomycin and gentamicin may be used empirically pending blood cultures and determination of methicillin resistance– Consider anticoagulation , the incidence of systemic embolization is as

high as 40%.– Consider emergency surgery in . patients with moderate-to-severe heart failure . patients with an unstable prosthesis noted on echocardiography or fluoroscopy

• Thromboembolic complications – Patients presenting with embolization need to be anticoagulated if they

are not already taking anticoagulants or have a subtherapeutic INR.– Assessment of valve function is needed.

• Prosthetic valve thrombosis – Surgery . the mainstay of treatment . associated with a high mortality rate: 20-40% in NYHA class IV

– Thrombolytic therapy may be used to treat select patients with thrombosed prosthetic valves.

– Patients with right/left -sided prosthetic valve thrombosis and NYHA class III and IV, pulmonary edema, or hypotension may benefit from thrombolysis due to the higher operative mortality.

– Contraindications to thrombolysis of left-sided prosthetic valve thrombosis :

. presence of a large left atrial thrombus . ischemic CVA less than 6 weeks ago . <4 d postoperative

– Thrombolytic therapy should always be done in conjunction with cardiovascular surgical consultation.

– Thrombolysis is emerging as the treatment of choice in obstructing prosthetic valvular thrombosis.

– The chance of a successful thrombolysis is inversely related to: . the size of the thrombus . the amount of time that has elapsed since the onset of symptoms

• Anticoagulant-related hemorrhage – Major anticoagulant-related hemorrhage require reversal of

their anticoagulation with fresh frozen plasma and vitamin K.– The time off anticoagulants should be as short as possible to

avoid valve thrombosis.– Use of recombinant factor VIIa or prothrombin complex

concentrate should not be used to reverse excessive anticoagulation in patients with prosthetic heart valves

Medication

• Antibiotics• Vasodilators• Inotropic agents• Anticoagulants

Vasodilators

• Role: - in acute mitral or aortic valve failure ,a significant portion of the cardiac output is regurgitated through the incompetent valve

- catecholamines worsen this effect by increasing peripheral vascular resistance

- Vasodilators reduce SVR allowing forward flow, improving cardiac output.

• Nitroprusside (Nitropress) : • Action: . Produces vasodilation . increases inotropic activity . Causes peripheral vasodilation by direct action on venous and arteriolar smooth muscle, reducing peripheral resistance. . At higher dosages, may exacerbate myocardial ischemia by increasing heart rate.• Dosing Adult . Begin infusion at 0.3-0.5 mcg/kg/min IV . increase in increments of 0.5 mcg/kg/min, titrating to desired hemodynamic effects . average dose is 1-6 mcg/kg/min IV

*Infusion rates >10 mcg/kg/min IV may lead to cyanide toxicity Pediatric: as in adults• Interactions : additive effect when administered with other hypotensive agents

• Contraindications .Documented hypersensitivity .subaortic stenosis . atrial fibrillation or flutter• Pregnancy Fetal risk : not established in humans• Precautions increased intracranial pressure hepatic failure severe renal impairmen hypothyroidism sodium nitroprusside has the ability to lower blood pressure and thus should be used only in patients with mean arterial pressures >70 mm Hg * in renal or hepatic insufficiency, nitroprusside levels may increase leading to cyanide toxicity

Inotropic agents• Action: increase cardiac output. Avoid vasoconstricting agents

to avoid increases in valvular regurgitation.

• Dobutamine (Dobutrex) -A Synthetic direct-acting sympathomimetic ,catecholamine and beta-receptor agonist - Produces vasodilation and increases inotropic state. - At higher dosages: . may increase heart rate, excerbating myocardial ischemia -Does not significantly increase myocardial oxygen demands: its major advantage over other direct-acting catecholamines.

-Dosing Adults -Start at low rate (1 mcg/kg/min IV infusion) -titrated at intervals of few minutes guided by: patient's response including : systemic blood pressure urine flow frequency of ectopic activity heart rate and if possible: measurement of cardiac output central venous pressure and/or pulmonary capillary

wedge pressure

- usual range :2-20 mcg/kg/min IV dictated by clinical response Pediatrics: as in adults

-Interactions: Beta-adrenergic blockers antagonize effects of dobutamine; general anesthetics may increase toxicity

-Contraindications Documented hypersensitivity subaortic stenosis atrial fibrillation or flutter - Pregnancy: Fetal risk not confirmed -Precautions Increased intracranial pressure severe renal / hepatic impairment: increased evels may cause cyanide toxicity hypothyroidism following MI correct hypovolemic state before using this drug

• Inamrinone (Inocor): Formerly amrinone A Phosphodiesterase inhibitor with positive inotropic and vasodilator activity More likely to cause tachycardia than dobutamine exacerbating myocardial ischemia.

-Dosing Adult 0.75 mg/kg IV bolus slowly over 2-3 min maintenance infusion is 5-10 mcg/kg/min IV do not to exceed 10 mg/kg

dose adjusted according to patient's response Pediatric Not established; may administer as in adults

-Interactions Diuretics may cause significant hypovolemia and a decrease in filling pressure additive effects to cardiac glycosides• Contraindications:Documented hypersensitivity• Pregnancy: Fetal risk not established • Precautions liver toxicity correct hypokalemic states before inamrinone

Anticoagulants• Indications: -bioprosthetic valves need anticoagulants for 3 months - mechanical valves and in patients with atrial fibrillation need lifelong anticoagulation - Any patients presenting with thromboembolic complications must be promptly anticoagulated if they do not have a therapeutic INR of 2.5-3.5.

Heparin: - Augments activity of antithrombin III and prevents conversion of fibrinogen to fibrin

- Does not actively lyse but is able to inhibit further thrombogenesis - Prevents reaccumulation of clot after spontaneous fibrinolysis.• Dosing - Adult : Initial dose: 40-170 U/kg IV

Maintenance infusion: 18 U/kg/h IV Alternatively:50 U/kg/h IV initially, followed by continuous infusion of

15-25U/kg/h and increase dose by 5 U/kg/h q4h prn using aPTT results

-Pediatric : Initial dose: 50 U/kg IV Maintenance infusion: 15-25 U/kg/h IV Increase dose by 2-4 U/kg/h IV q6-8h prn using aPTT results

• Interactions : Effect decreased by: Digoxin nicotine tetracycline antihistamines Toxicity may be increased by: NSAIDs aspirin dextran dipyridamole hydroxychloroquine• Contraindications: Documented hypersensitivity subacute bacterial endocarditis active bleeding history of heparin-induced thrombocytopenia• Pregnancy : safety not established• Precautions : In neonates: preservative-free heparin is recommended to avoid possible toxicity (gasping syndrome) by benzyl alcohol caution in severe hypotension and shock

AntibioticsAmoxicillin:

Derivative of ampicillin Active against certain gram-positive and gram-negative organisms Superior bioavailability and stability to gastric acid broader spectrum of activity than penicillin. less active against Streptococcus pneumococcus Penicillin-resistant strains also resistant to amoxicillin less so at higher doses More effective against gram-negative organisms (eg, N meningitidis, H influenzae) bactericidal : interferes with synthesis of cell wall mucopeptides during active multiplication DOC for prophylaxis in nonallergic patients undergoing dental, oral, or respiratory tract procedures.

. Dosing: Adult: 2 g PO 1 h before procedure Alternatively, 3 g PO 1 h before procedure, followed by 1.5 g PO 6 h after initial dose

Pediatric : 50 mg/kg PO 1 h before procedure

. Interactions: May reduce efficacy of oral contraceptives

. Contraindications : Documented hypersensitivity

. Pregnancy : safety unestablished

. Precautions: Renal impairment

Ampicillin : - Broad-spectrum bactericidal - Interferes with bacterial cell wall synthesis during active replication - Alternative to amoxicillin when unable to take medication orally.

- prophylaxis in patients undergoing dental, oral, or respiratory tract procedures. - Coadministered with gentamicin for prophylaxis in GI or genitourinary procedures.

• Dosing Adult : 2 g IV/IM 30 min prior to procedure

High-risk patients: 2 g ampicillin IV/IM followed 6 h later by 1 g IV/IM

Pediatric : 50 mg/kg IV/IM 30 min prior to procedure High-risk patients: 50 mg/kg IV/IM ampicillin

followed 6 h later by 25 mg/kg IV/IM

• Interactions -ampicillin level elevated by Probenecid and disulfiram -allopurinol decreases ampicillin effects and has additive effects on ampicillin rash -may decrease effects of oral contraceptives

• Contraindications : Documented hypersensitivity

• Pregnancy: safety not established

• Precautions :Adjust dose in renal failure evaluate rash and differentiate from hypersensitivity reaction

Azithromycin : -Acts by: binding to 50S ribosomal subunit of susceptible microorganisms and blocks dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. -Nucleic acid synthesis is not affected. -Concentrates in phagocytes and fibroblasts contributing to drug distribution to inflamed tissues -Treats mild-to-moderate microbial infections.

- tissue concentrations are higher than Plasma concentrations giving it value in treating intracellular organisms. -Has a long tissue half-life.

-Used in penicillin-allergic patients undergoing dental, esophageal, and upper respiratory procedures.

. Dosing : Adult : 500 mg PO 1 h before procedure Pediatric : 15 mg/kg PO 1 h before procedure; not to exceed 500 mg .Interactions : May increase toxicity of : theophylline warfarin digoxin effects are reduced with coadministration of aluminum and/or magnesium antacids nephrotoxicity and neurotoxicity may occur when coadministered with cyclosporine .Contraindications : Documented hypersensitivity hepatic impairment: do not administer with pimozide .Pregnancy : not established .Precautions : Site reactions can occur with IV route bacterial or fungal overgrowth may result from prolonged antibiotic use may increase hepatic enzymes and cholestatic jaundice prolonged QT intervals pneumonia hospitalized geriatric or debilitated patients

Cefazolin: -First-generation semisynthetic cephalosporin that -arrests bacterial cell wall synthesis and inhibits bacterial replication by binding to 1 or more penicillin-binding proteins - Poor capacity to cross blood-brain barrier -Primarily active against skin flora, including S aureus -typically used alone for skin and skin-structure coverage

.Dosing: Adult: 1 g IV/IM 30-60 min before procedure Pediatric: 50 mg/kg IV/IM 30-60 min before procedure Do not to exceed 1 g/dose

.Interactions: Probenecid prolongs effect of cefazolin coadministration with aminoglycosides may increase renal toxicity and yield false-positive urine-dip test results for glucose

.Contraindications : Documented hypersensitivity

.Pregnancy :safety not established

.Precautions: high doses may cause CNS toxicity ,Adjust dose in severe renal insufficiency prolonged use or repeated therapy may yield superinfections and promotion of nonsusceptible

• Ceftriaxone: -Third-generation Bactericidal cephalosporin - Acts by inhibiting cell wall synthesis -broad-spectrum gram-negative activity -lower efficacy against gram-positive organisms -Highly stable in presence of beta-lactamases, both penicillinase and cephalosporinase, of gram-negative and gram-positive bacteria. - 33-67% excreted unchanged in urine, remainder secreted in bile and then feces as microbiologically inactive compounds. - Reversibly binds to human plasma proteins

• Dosing Adult: 1 g IV/IM 30-60 min before procedure Pediatric : 50 mg/kg IV/IM 30-60 min before procedure; not to exceed 1 g• Interactions: - Probenecid may increase ceftriaxone levels - coadministration with ethacrynic acid, furosemide, and aminoglycosides may increase nephrotoxicity - simultaneous administration with IV calcium-containing solutions may cause precipitation (thoroughly flush infusion lines between ceftriaxone and calcium)• Contraindications : Documented hypersensitivity hyperbilirubinemic neonates• Pregnancy : safety not established• Precautions : -Adjust dose in severe renal insufficiency (high doses may cause CNS toxicity) - superinfections and promotion of nonsusceptible organisms may occur with - prolonged use or repeated therapy - caution in breastfeeding women - may displace bilirubin from albumin-binding sites, increasing the risk of kernicterus - caution with gallbladder, biliary tract, liver, or pancreatic disease - caution in patients with history of colitis or penicillin hypersensitivity

Cephalexin: - First-generation Bactericidal cephalosporin that inhibits bacterial replication by inhibiting bacterial cell wall synthesis (effective against rapidly growing organisms forming cell walls)

-Resistance occurs by alteration of penicillin-binding proteins. -Effective against streptococcal & staphylococci, including penicillinase-producing staphylococci.

• Dosing Adult : 2 g PO 1 h before procedure Pediatric : 50 mg/kg PO 1 h before procedure; not to exceed 2 g/dose

• Interactions: Coadministration with aminoglycosides increases nephrotoxic potential

• Contraindications: Documented hypersensitivity

• Pregnancy : safety not established

• Precautions: Adjust dose in severe renal insufficiency (high doses may cause CNS toxicity) prolonged use or repeated therapy may yield superinfections and promotion of nonsusceptible organisms

• Clarithromycin: -Semisynthetic macrolide -reversibly binds to P site of 50S ribosomal subunit of susceptible organisms -may inhibit RNA-dependent protein synthesis by stimulating dissociation of peptidyl tRNA from ribosomes, causing bacterial growth inhibition.

-Used in penicillin-allergic patients undergoing dental, esophageal, and upper respiratory procedures.

• Dosing Adult : 500 mg PO 1 h before procedure Pediatric : 15 mg/kg PO 1 h before procedure; not to exceed 500 mg/dose• Interactions: Toxicity increases with fluconazole and pimozide effects decrease and GI adverse effects may increase with rifabutin or rifampin may increase toxicity of anticoagulants cyclosporine tacrolimus digoxin carbamazepine ergot alkaloids triazolam HMG-CoA reductase inhibitors

Plasma levels of certain benzodiazepines may increase, prolonging CNS depression arrhythmias and increases in QTc intervals occur with disopyramide coadministration with omeprazole may increase plasma levels of both agents decreases metabolism of repaglinide, thus increasing serum levels and effects• Contraindications : Documented hypersensitivity coadministration with pimozide• Pregnancy: safety not established• Precautions: Coadministration with ranitidine or bismuth citrate is not recommended with CrCl <25 mL/min give half dose or increase dosing interval if CrCl <30 mL/min diarrhea may be a sign of pseudomembranous colitis superinfections may occur with prolonged or repeated antibiotic therapies

Clindamycin: Semisynthetic antibiotic produced by 7(S)-chloro-substitution of 7(R)-hydroxyl group of parent compound lincomycin Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest Widely distributed in the body Does not penetrate the CNS Protein bound Excreted by the liver and kidneys Used in penicillin-allergic patients undergoing dental, oral, or respiratory tract procedures Useful for treatment against streptococcal and most staphylococcal infections

• Dosing Adult : 600 mg PO/IV 1 h prior to the procedure; 150 mg PO/IV 6 h after first dose Pediatric : 20 mg/kg PO 1 h or 20 mg/kg IV 30 min before procedure Do not to exceed 600 mg/dose• Interactions : Increases duration of neuromuscular blockade induced by

tubocurarine and pancuronium erythromycin may antagonize effects of clindamycin antidiarrheals may delay absorption of clindamycin• Contraindications: Documented hypersensitivity regional enteritis hepatic impairment ulcerative colitis antibiotic-associated colitis• Pregnancy : safety not established• Precautions: Adjust dose in severe hepatic dysfunction associated with severe and possibly fatal colitis

• Gentamicin: - Aminoglycoside antibiotic for gram-negative bacteria including Pseudomonas species - Synergistic with beta-lactamase against enterococci - Interferes with bacterial protein synthesis by binding to 30S and 50S ribosomal subunits.

- Dosing regimens are numerous and are adjusted based on: CrCl changes in volume of distribution body space into which the agent needs to distribute - may be given IV/IM - Each regimen must be followed by at least trough level drawn on third or fourth dose, 0.5 h before dosing; may draw peak level 0.5 h after 30-min infusion.

• Dosing Adult : -Penicillin-susceptible streptococcal endocarditis: 1 mg/kg IV q8h for 2 wk; used in combination with ceftriaxone

-Enterococcal: 1 mg/kg IV q8h for 4 wk; used in combination with ampicillin

-MSSA: 1 mg/kg IV q8h for 3-5 d; used in combination with nafcillin

Pediatric : as in adults• Interactions -Coadministration with other aminoglycosides, cephalosporins, penicillins, and amphotericin B may increase nephrotoxicity -aminoglycosides enhance effects of neuromuscular blocking agents prolonged respiratory depression may occur -coadministration with loop diuretics may increase auditory toxicity with possible irreversible hearing loss of varying degrees may occur (monitor regularly)

• Contraindications: Documented hypersensitivity; non – dialysis-dependent renal insufficiency• Pregnancy : safety not established• Precautions : - Narrow therapeutic index (not intended for long-term therapy) - caution in renal failure (not on dialysis) - adjust dose in renal impairment - myasthenia gravis - hypocalcemia -conditions that depress neuromuscular transmission

• Vancomycin: Potent antibiotic directed against gram-positive organisms and Enterococcus species treatment of septicemia and skin structure infections Indicated for patients who: -cannot receive or have failed to respond to penicillins and cephalosporins -have infections with resistant staphylococci adjust dose in patients with renal impairment.

• Dosing Adult : Dental, oral, upper respiratory tract, and genitourinary procedures: 1 g IV infused over 1 h, 1 h prior to procedure Pediatric: Dental, oral, upper respiratory tract, and genitourinary procedures: 20 mg/kg IV over 1 h, 1 h prior to procedure• Interactions: Erythema, histaminelike flushing, and anaphylactic reactions may occur when administered with anesthetic agents when taken concurrently with aminoglycosides, risk of nephrotoxicity may increase above that with aminoglycoside monotherapy effects in neuromuscular blockade may be enhanced when coadministered with nondepolarizing muscle relaxants• Contraindications: Documented hypersensitivity• Pregnancy: safety not established• Precautions: renal failure neutropenia red man syndrome is caused by too rapid IV infusion (dose given over a few min) but rarely happens when dose is given as 2-h administration or as PO or IP administration; red man syndrome is not an allergic reaction

Transfer

The mortality is related directly to the delay of surgical correction.

Prophylaxis• antibiotic prophylaxis :

– Dental and oral procedures– Respiratory procedures, particularly those which involve disruption of the

respiratory mucosal surface, or when a known infection is present • If a known infection caused by Staphylococcus aureus is present,

prophylaxis with an antistaphylococcal penicillin, cephalosporin, or vancomycin should be given.

• In cases of known or suspected methicillin-resistant Staphylococcus aureus, prophylaxis with vancomycin should be given.

– Sclerotherapy of bleeding esophageal varices– Routine prophylaxis for gastrointestinal or genitourinary procedures is no

longer recommended, unless in the presence of a known infection. • Urethral catheterization in the presence of a suspected urinary tract

infection• Vaginal delivery in the presence of infection

– Incision and drainage of infected tissues

• For dental, oral, or upper respiratory tract procedures, use amoxicillin 2 g PO 30-60 minutes before the procedure. – If unable to take PO medication, use ampicillin 2 g IM/IV OR

cefazolin 1 g IM/IV, OR ceftriaxone 1 g IM/IV 30-60 minutes before the procedure.

– For penicillin-allergic patients, use clindamycin 600 mg PO/IM/IV OR azithromycin 500 mg PO OR clarithromycin 500 mg PO OR cephalexin 2 g PO 30-60 minutes before the procedure.

– These are all single-dose regimens.– Do not use cephalexin in patients with a documented significant

allergy to penicillin unless there is documentation that the patient can tolerate cephalosporins.

Complications

• Glomerulonephritis• mycotic aneurysms• and metastatic abscesses

Special Concerns

• Pregnancy Some debate exists:– Warfarin increases the chance of spontaneous abortion

and stillbirths and is associated with teratogenicity from 6-12 weeks' gestation.

– Current recommendations are to use heparin from 6-12 weeks and from 38-40 weeks' gestation. Warfarin may be used for the remainder of pregnancy.

– The American College of Obstetrics and Gynecology have recommended that low molecular weight heparin not be used in pregnancy.

Heart Disease has been around as long as we have.Medications, surgery, PCI, Stents….. All cure the heart that we can see and physically touch.The essence of our heart, the one with the soul that is inconceivable to our physical science, has yet to be tackled.Love,hate, jealousy,lonlinless,and all the lost souls need mending too…