Download Prosthetic Heart Valves

Prosthetic Heart
Valves
Dr. Mona Youssef
http://www.cardiologylinks.webs.com/home
complications
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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 StarrEdwards 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
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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
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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
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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.
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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)
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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
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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
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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.
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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.
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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
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In patients with acute valvular failure, diagnostic studies must be performed
simultaneously with resuscitative efforts.
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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.
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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
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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.
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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
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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
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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
Antibiotics
Amoxicillin:
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.
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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
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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
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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 612 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…