Atrial fibrillation

Atrial fibrillation


Janet Wong, M.D.

Emergent/urgent Cardioversion Atrial fibrillation is the most frequently occurring cardiac arrhythmia,
and it is the main problem that we have to deal with when it comes

. Poorly tolerated atrial ablation:
Significant hypotension
Pulmonary edema
to cardiac arrhythmias. There is a 2% risk of atrial fibrillation over
20 years, and the risk increases with age. By the time people reach
75, there is a high prevalence of atrial fibrillation. The risk also
increases with other associated diseases like hypertension, coronary
disease, and diabetes.
Significant ischemia
The main thing we worry about is the risk of stroke in people with
. DC cardioversion: atrial fibrillation. People can be very symptomatic and have functional
limitations due to rapid ventricular rate, loss of AV synchrony,
Minimum 200 J. synchronized shock
variability of ventricular response, and tachycardia-induced
cardiomyopathy.
Poorly tolerated atrial fibrillation is characterized by significant
hypotension. If their BP is 50, you are going to want to treat it as an
emergency. So you have someone that comes in, their blood
pressure is maintained, but they are developing severe pulmonary
edema or they are complaining of crushing chest pain with ECG
changes, I think you are not wrong in that case to urgently DC
cardiovert those people.

Atrial fibrillation is probably the most difficult arrhythmia to electrically
cardiovert. Certainly harder than ventricular tachycardia, often
harder than ventricular fibrillation. It usually takes high energy.
There are two reasons to start with a higher energy. A shock of 50
joules externally stimulates skeletal muscle and that's what makes
it painful. A shock of 200 joules or 300 joules or even 360 joules
your patient any discomfort by using a lower energy. When youhurts just as much. It doesn't hurt any more. So, you are not saving

immediately because when you shock somebody there is always
shock somebody, you should always recharge the defibrillator
the risk you are going to put them into VF. The risk of causing VFwith the shock is related to the energy. The lower the energy, the
higher the risk of VF because you have incompletely depolarized
the heart.

You can decrease the number of shocks if you use a higher energy
and you can also reduce the risk of causing VF. I routinely start at

200 to 300 joules, and if I have a big barrel-chested person or an
obese person, I just start with 360.

3
Acute Rate Control
. IV calcium channel blockers
Diltiazem 20 - 25 mg bolus, then 10-15 mg/hour infusion
Verapamil 2.5 - 5 mg bolus
. IV Digoxin
What if the person is stable and you want to just control them
medically when they come in? The rate can be controlled with a
variety of agents. One group of agents is the IV calcium channel
blockers. IV diltiazem is the drug of choice because of the ease of
use. After you have loaded the patient with a bolus, which is usually
20 to 25 mg, you can start the patient on an infusion of 10 to 15
mg/hour, and you can titrate the infusion rate to achieve the appropriate
heart rate. This strategy is very effective in the short term at
controlling ventricular rate. You want to convert people over that
can take p.o. medications early on if you are going to continue to
need to rate control them.
IV beta blockers work very well. IV Inderal, IV metoprolol; the short-
acting one is esmolol which is difficult to dose. Diltiazem is easier
for that reason.
IV digoxin is not usually recommended for acute rate control because
the onset of action is very long; it can take hours before you
rate control someone. Digoxin is not good at rate control in somebody
with a high catecholamine state. IV digoxin is no longer used
for acute rate control. There is no difference in conversion rate with
IV digoxin.
Rate control that in atrial fibrillation in the setting of the WPW
syndrome. In WPW, there is an accessory pathway connecting the
atrium to the ventricle which bypasses the AV node. The problem
with that is that the AV node limits the number of impulses that can
reach the atrium from the ventricle, maybe in a young healthy
person, to 200 to 220 beats per minute. The accessory pathway
doesn't have that same function and can let 250, even 300, beats
per minute through to the ventricle. The hallmarks of WPW in atrial
fibrillation are a wide QRS complex that is an irregular tachycardia,
and you have changing amounts of preexcitation. So, the QRS is
almost changing beat to beat by the amount of excitation of the
ventricle.
If you give typical AV node blocking drugs in these patients, they
will block the AV node fine, but the ventricle is still going to be
activated rapidly over the accessory pathway. If you give a drug like
verapamil, you may increase conduction over the accessory pathway.
If you give these patients, digoxin, verapamil, or beta blockers,
you can degenerate them to ventricular fibrillation.
The treatment of choice for atrial fibrillation in the setting of WPW
is electrical cardioversion if the patient is unstable. Procainamide is
the drug of choice given intravenously because it may convert the
atrial fibrillation, and it suppresses conduction over the accessory
pathway, and it will limit the number of impulses getting to the
ventricle. A potentially life-threatening complication may occur with
the usual rate control medications.

4
Elective Cardioversion
. > 24 - 48 hours
. Pharmacologic
Intravenous: procainamide/ibutilide
Oral loading
. Electrical
External
Internal
Anticoagulation for three months after cardioversion is recommended
because of high-risk of embolic events during this
period.
Patients who have been in atrial fibrillation for less than 48 hours
can be safely cardioverted without anticoagulation. Elective cardioversion
can be accomplished pharmacologically with either intravenous
procainamide or ibutilide. Or you can use oral loading of
quinidine or disopyramide (Norpace). External electrical cardioversion
can be used. Internal cardioversions may also be effective in
the patients who are resistant to external DC cardioversions.
In atrial fibrillation that has been present for more than 48 hours,
after you cardiovert them, you need to maintain anticoagulation due
to the high risk of embolic events during that period. Patients that
have been in chronic atrial fibrillation, the atria are stunned and
they don't contract very well. Patients are at continued risk for
stroke even though they are in sinus rhythm for a period of three
months after conversion from atrial fibrillation.
The standard approach is you put them on Coumadin and wait four
to six weeks and then bring them in for an elective cardioversion.
The down side is there is a delay in cardioversion. You also end up
having more prolonged anticoagulation with the risks attendant with
warfarin and you delay the recovery of atrial function. The longer
you leave somebody in atrial fibrillation, the longer it takes the
atrium to recover. The quicker you get somebody out of atrial
fibrillation, the longer they will stay out of fibrillation.
Transesophageal echo should be used to select candidates for
early cardioversion. Heparin therapy should be instituted and the
rate should be controlled, and you do a TEE and you look for
thrombus. In patients who do not have a thrombus, you can go
ahead and cardiovert. So, you have an overall shorter duration of
warfarin therapy--four to six weeks less–and a more rapid return of
atrial function, and fewer incidents of thromboembolism. In patients
in whom left atrial thrombi was excluded, you can safely cardiovert
these people.
If you decide to cardiovert somebody you don't always have to
shock them right off. What we do in our hospital is often bring them
in for elective cardioversion, we will give them a load of intravenous
procainamide, and if they don't convert then we go ahead and do
the DC cardioversion. The standard dose of procainamide, 15
mg/kg over 20 to 30 minutes. It is probably more effective at this
faster rate because you get a higher peak plasma level of the
procainamide, and that is probably what accounts for the acute
conversions. The patient should be monitored for hypotension,
QRS widening and QT prolongation.
A new class III antiarrhythmic drug called ibutilide (Corvert) works
by prolonging the action potential duration. It works well for up to
50%. With atrial fibrillation, with a 30% conversion rate. There is a
significant risk of torsades de pointes with ibutilide. It is much
easier to give than procainamide - you can give it quicker. Patients
develop polymorphic VTs, sustained in almost 2%, 2.5% non-
sustained. Some people even developed monomorphic VT. You
can see a 9% incidence of ventricular proarrhythmia in these patients.
It is okay to use it; you just have to be aware of this and use
it in the proper setting. So, if you give this in the ER, patients have
to be monitored closely for 4 hours after you use it. If you use it in
the hospital, they have to be in a telemetry setting where you are
comfortable with the people on your telemetry floors that they can
recognize this and treat it very rapidly.
How do you convert somebody electrically? When external cardioversion
fails, internal cardioversion with a catheter may be success

5
Treatment of Atrial Fibrillation
. Treat underlying cause if present
. Rate control
. Anticoagulating
. Maintenance of sinus rhythm in selected patients
ful. The catheter has a platinum electrode on it is floated into the
right atrium, and then you shock between the tip of the catheter and
the back patch. So, you are actually shocking from inside the heart.
The results have been really encouraging. Significantly more people
were cardioverted with internal cardioversion than with external.
The long-term outcomes were no different. It is useful in the patients
who will benefit from sinus rhythm, but you can't get into
sinus rhythm with external shocks.
Treatment of atrial fibrillation includes treatment of underlying
causes. The most common disorders are thyrotoxicosis and
pericarditis.

6
Anticoagulation Recommendations
. Strong contraindication to warfarin: Aspirin 325 mg per day
. Lone atrial fibrillation, less than 65: No treatment or aspirin
. Low-risk: Aspirin
. One or more risk factors: Warfarin (INR 2.0-3.0)
. $70, low-risk: Warfarin (INR 2.0) or aspirin
People who have atrial fibrillation have a 6-fold increased risk of
stroke. The very high risk patients tend to be the older patients with
diabetes, hypertension, previous strokes and TIAs, CHF, coronary
disease, and mitral valve disease. High risk patients greater than
65, with one of these risk factors have a 5% per year risk. The low
risk patients are the patients less than 60 with normal hearts, with
normal blood pressures and glucoses, and the risk is probably even
less than 1% per year.
With Coumadin there is an overall 65% reduction in stroke presentations
with atrial fibrillation. Anticoagulation is important in atrial
fibrillation.
There is a significant reduction in the risk of stroke with Coumadin
over platelet inhibitors. So, in the general population, including the
high-risk patients, Coumadin is clearly better than aspirin alone. In
patients that are low-risk, who have essentially structural normal
hearts, that have no hypertension, no LV dysfunction, no prior
embolic events, even if they are older, aspirin is probably better
than warfarin in those patients. High risk patients should be on
Coumadin.
With strong contraindications to warfarin, you need to put them on
aspirin. In patients with lone atrial fibrillation that are relatively
young, either nothing or aspirin is recommended. If it is a male
patient that is 55 years old, having him take an aspirin a day may
have some added benefit in coronary disease, so I like to tell them
to take an aspirin anyway.
Low-risk patients can be treated with aspirin alone. If they have one
or more risk factors, warfarin is recommended with an INR between
2 and 3, usually shooting between 2 to 2.5. Greater than 70 puts
them in high-risk; however, those are the people that have a higher
incidence of bleeding. What I tend to do in people that have relatively
normal hearts even if they are older than 70, I will often use
aspirin alone, or if I do use Coumadin I will tend to shoot on the
lower side of the INR. You have to individualize it for each patient.

7
Treatment Goals
. Alleviate symptoms
. Prevent ischemia
. Improve hemodynamics
. Prolonge life in prevent sequelae
Maintenance of sinus rhythm with an antiarrhythmic has not
been proven to reduce risk of stroke or prolong life
Treatment goals in treating atrial fibrillation include alleviation of
symptoms, prevention of ischemia with high heart rates. Some
patients with atrial fibrillation due to the loss of AV synchrony and
the irregularness of their rate have more CHF and keeping them in
sinus will improve hemodynamics. You would like to prolong life
and prevent sequelae.
There is no data at present that supports reduction in stroke or
prolongation of life with antiarrhythmic maintenance of sinus
rhythm.
Antiarrhythmics in patients that had no history of CHF did not
cause a significant increase in mortality. Patients with a history of
CHF and no antiarrhythmics, clearly they did less well than those
patients that had no history of CHF, but the surprising finding was
that if you looked at the survival curve for the patients that both had
a history of CHF and were receiving antiarrhythmics to maintain
sinus rhythm, their survival is much worse than the other groups.

8
Rate Control
. Pharmacological
Calcium blockers
Beta-blockers
Digitalis
Amiodarone
. Non-pharmacological
AV node modification
AV node ablation plus physiologic pacing
Rate control in chronic atrial fibrillation. There are pharmacologic
agents, digitalis, beta blockers, calcium channel blockers and even
amiodarone for rate control and there are some non-pharmacologic
approaches such as AV node modification or ablation of the AV
node and physiologic pacing.

9
Pharmacologic Rate Control
. Digitalis is indicated if history of CHF
Poor choice in active patients
Excessive slowing during sinus rate or at rest
. Beta-blockers
Excellent in active patients
Using combination with and antiarrhythmics
First choice in thyrotoxicosis
First choice in ischemic patients
May not be tolerated in patients with CHF or lung disease
ISA in patients with tachy-bradycardia syndrome
. Calcium channel blockers
Good in active patients
First choice in patients with lung disease
Acceptable in patients with ischemia
May not be tolerated in patients with CHF
. Amiodarone
May work when nothing else does
Good in patients with enhanced AV conviction
May be beneficial in patients with LV dysfunction
and/or Nonsustained ventricular tachycardia
If you are going to go ahead with pharmacologic rate control it is
important to confirm that the patient is rate controlled. A significant
number of patients who their physicians thought were adequately
rate-controlled were in atrial fibrillation with rates of 140 to 150 at
rest. Before people leave the hospital, I will get them up and put
them on the stairs while they are still on telemetry and see what
their heart rate does. After I send them out, I will either get a treadmill
test, or it is even better to send them home with a Holter monitor
and tell them, "I want you to go do all of the things that you are
normally going to do." You really want to do surveillance Holters
when they are back doing the things that they do because when
these people get active, their heart rates often shoot up much
higher than you thought.
Beta blockers are an excellent choice for active patients. Use in
combination with antiarrhythmics is well tolerated. It is the first
choice in patients with thyrotoxicosis. It is the first choice in patients
with ischemia. It may not be tolerated in patients with moderate
CHF or lung disease, although patients with mild CHF should be
put on beta blockers. A beta blocker like Pindolol, with intrinsic
sympathomimetic activity, may be advantageous in patients with
tachy-bradycardia syndrome, where you could avoid a pacemaker.
But I am not sure how good that is.
Calcium channel blockers, I think, are very good agents for rate
control. They are good in the active patients. They are the first
choice of patients with lung disease who can't use beta blockers. I
think they are the first choice of patients with atrial fibrillation and
LVH because of the beneficial effects of calcium channel blockers
in these patients and the regression of LVH. It may not be tolerated
in patients with CHF. Negative inotropic effects.
Digitalis is only recommended in patients with a history of CHF
because you have the added benefit in those patients. It is very
poor in active patients. The problem with digoxin is that you have
excessive slowing of the sinus rate at rest but not good control
during exertion. So, you push the dig to a point where someone has
a heart rate of 60 at rest and then they get up and start doing things
like climbing stairs and stuff and their heart rate goes up to 170 or
140. Digoxin, especially in the active patient, is not recomended.
Amiodarone may work when nothing else can control the heart rate.
It is good in patients that have enhanced AV nodal conduction is a
very rare entity where people go into atrial fibrillation and go very
rapidly up to 250 or 350 beats per minute. It may be beneficial in
patients with LV dysfunction and/or nonsustained VT where you get
the added benefit of reducing the risk of sudden death.
AV junctional ablation for rate control of atrial fibrillation. The
response of patients is really dramatic, and people do really well
with this procedure. Indications include failure of the multiple AV
nodal blocking drugs. So, patients that you just can't rate control no
matter what you use. Patients in whom even though their rate is
controlled the irregularity of the atrial fibrillation still bothers them.
Drug intolerance. Patients that when they take the drugs that rate
control, they get admitted five times a year with CHF and their heart
rate is 150 because they never take their medications. Also, patient
preference.
What do we do with patients with atrial fibrillation and heart failure?
Twenty five percent of patients with heart failure may also have
atrial fibrillation. These are the patients that are at highest risk of
proarrhythmia from antiarrhythmic drugs. Congestive heart failure

10
Chemical Cardioversion
. Procainamide
15 mg/kg IV over 20-30 minutes (750-1500 mg)
Watch for hypotension, QRS widening, QT prolongation.
can lead to atrial fibrillation, and atrial fibrillation can lead to and
worsen congestive heart failure. Chronic tachycardia is associated
with the development of a cardiomyopathy and it appears to be
reversible.
Ablation and pacing results in an improvement in EF from 25% to
52%. Dramatic increases in injection fraction. With severe LV
dysfunction, after you ablate their AV node and put in a pacemaker;
it is almost back to normal. I think that is a really important point
that people don't fully understand yet. Patients with mean heart
rates of 60 to 100 beats per minute on a Holter that had depressed
LV function underwent AV junctional ablation and showed a significant
improvement in function after this.
Regularization of ventricular response. Even if you have somebody
rate controlled, the ventricle is being activated very irregularly.
Regularization of rhythm provides significant hemodynamic benefits.
In patients with AF, an increase in pulmonary capillary wedge
pressure were seen with irregular rhythm as opposed to regular
rhythm; therefore, both rapid rate and irregularity leads to decreased
LV function.
If you have patients that are difficult to manage and are having
repeated visits to the hospital with CHF and have chronic atrial
fibrillation, AV junctional ablation with pacing is something to
consider. It may help you manage their CHF.

11
Maintenance of Sinus to Rhythm
. Pharmacologic
. Preventive pacing
. Implantable defibrillator
. Ablative therapy
Surgical
Catheter
Maintenance of sinus rhythm. There is a subset of patients in whom
we are going to want to try and maintain sinus rhythm. There are
pharmacologic approaches, preventative pacing, implantable
defibrillators and ablative therapy.

12
Pharmacologic Maintenance of Sinus
to Rhythm
. Class IA
Quinidine: diarrhea
Procainamide: arthritis/rash/lupus
Disopyramide: urinary retention
..Class IC
Flecainide: avoided in ischemia/poor LV function
Propafenone: avoided in ischemia/poor LV function
. Class III
Sotalol: CHF, asthma, bradycardia
. Amiodarone: end organ toxicity
Pharmacologic agents. The class-I agents are sodium channel
blockers. There is quinidine, procainamide, disopyramide.
Quinidine is a drug that has been used for years and years, but 40
to 50% of patients can't take it because of the diarrhea.
Procainamide maintenance is not recommended because of arthritis,
rash, and lupus-like syndromes. Disopyramide (Norpace) is not
good in older men because of urinary retention, but it is very well-
tolerated in younger patients, and in patients with vagally mediated
atrial fibrillation.
The class 1C agents. Flecainide got a very bad name because of
the excess mortality in patients post MI. But I think in patients with
structurally normal hearts, it is probably one of the most effective
agents that we have for controlling atrial fibrillation. It should be
avoided it in patients with ischemia or poor LV function. The same
thing with propafenone (Rythmol). A newer agent, Sotalol can be
very effective because it offers both rate control and an
antiarrhythmic properties, but the beta blocking properties can
cause problems in patients with CHF, asthma, and it can cause
bradycardia.
Amiodarone is a very good drug for controlling atrial fibrillation, but
the end organ toxicities are something to be concerned about. Over
one year's time on quinidine, about 50% are maintained in sinus
rhythm. Propafenone and Sotalol, 50%. With the exception of
amiodarone, the antiarrhythmic drugs are all about 50% effective at
one year. Amiodarone appears to be the most effective
antiarrhythmic at maintaining sinus rhythm. It is 78% effective at
maintaining sinus rhythm in people who had failed a type-I
antiarrhythmic. Amiodarone versus quinidine, again right around
50% versus 79%. Same thing for amiodarone versus Norpace.
Amiodarone is the best drug available for maintaining sinus rhythm.
We have had a lot of good success with using amiodarone, and we
use it in a lot of patients. Toxicity tends to be dose related. So, in
the doses we use in ventricular tachycardia, 400 to 600 mg/day,
there is a significant incidence of pulmonary fibrosis and other end
organ toxicities. At the dose we use for atrial fibrillation, it is 200
mg/day, which is one pill, or even 200 mg every other day, the
incidence of these side effects are very low. The side effects are
reversible. In patients that have failed other drugs and patients that
have LV dysfunction, amiodarone is the drug of choice.
Amiodarone is a very unique drug. The half-life is one month to five
months. It is a very lipophilic drug so when you give it to people it
immediately gets sucked up into their fat stores. Start with a much
higher dose and then we cut the dose back. Start them on 800
mg/day for about two weeks, then I will put them on 400 mg/day for
about a month, then cut them back down to 200 mg/day. Results
have been very good. Patients have tolerated it well and it clearly
works much better than other agents. Anybody over 70 who presents
with atrial fibrillation or who has any LV dysfunction, should be
started on amiodarone as a first line agent.

13
No Structural Heart Disease
. First-line agents
Class IC (flecainide, propafenone)
Disopyramide (especially if vagally mediated)
. Second-line
Sotalol
. Third line
Amiodarone
If you have a patient that has no structural heart disease with lone
AF, they are very symptomatic, you don't want to leave these
people in AF all the time and make them take aspirin and have
them in atrial fibrillation. You can give them drugs to try to maintain
sinus rhythm. We have had a lot of success with flecainide in this
population. Norpace is very good especially in vagally mediated AF.
There is a group of patients who get atrial fibrillation after they eat
big meals or they wake up in the middle of the night. Vagal surges
change the electrophysiologic properties of the atrium and make it
more susceptible to atrial fibrillation. Norpace has some vagolytic
effects and may be effective in those patients. Second line, Sotalol
is often good in these patients, and you can use amiodarone.

14
Ischemic Heart Disease
. First-line:
Sotalol
. Second-line:
Amiodarone
. Avoid class IC
In patients with ischemic heart disease, the class 1C drugs should
be avoided. Sotalol may be a good drug. The beta blocking properties
are good for the ischemic patient, and amiodarone is a good
agent in those patients.

15
CHF/LV Dysfunction
. First-line:
Amiodarone
. Consider non-pharmacologic approach
. Avoid class IC
In the patients with CHF and LV dysfunction, you have to avoid
those drugs that are proarrhythmic. Amiodarone may be the best
drug in these patients because you get the added protection from
sudden death. You should also consider the non-pharmacologic
approach in these patients because you may see an increase in LV
function after you control their rate with ablation and regularize their
ventricular response with pacing.

16
LVH/HCM
. First-line
Class 1C (flecainide, propafenone)
. Second-line:
Sotalol
Amiodarone
. Consider nonpharmacologic management (HCM)
In patients that have left ventricular hypertrophy or hypertrophic
cardiomyopathy, class 1C agents are also good. Disopyramide is
specifically good in patients with hypertrophic cardiomyopathy
because of the negative inotropic effects. It may decrease the
gradient. Sotalol also is very good in these patients, and
amiodarone is good. In patients with hypertrophic cardiomyopathy,
you should consider non-pharmacologic management, such as
ablation, because dual-chamber pacing will decrease the pressure
gradient so you get the added benefit of those two things.

17
Outpatient loading of antiarrhythmic medications utilizing a monitoring device is probably safe and cost-effective. Patients get their
first dose of the drug in the hospital, and then were sent out with a loop recorder for 10 days. Every day they transmit a tracing of
their heart rate and their QT interval and they also transmit any palpitations or any adverse effects that they had.
Prophylactic pacing for atrial fibrillation. It is thought that atrial fibrillation is due to multiple re-entrant wave fronts throughout the
atria. Excitation and therefore prolongation of the refractoriness of the tissue in the critical regions of the atrium may prevent the
initiation or maintenance of atrial fibrillation. If you stimulate the heart in more than one place, you may be able to prevent these reentrant
wave fronts and prevent atrial fibrillation. There are trials that have looked at patients with sick sinus syndrome that got either
dual chamber pacers or ventricular pacers alone. The studies showed that in patients that had atrial pacing, it was a significantly
much lower incidence of atrial fibrillation that had active atrial pacing suggesting that somehow pacing the atrium will decrease the
incidence of atrial fibrillation.
Implantable ventricular defibrillators. This is a device that goes in the pectoral region, has two leads in the right atrium. One in the
right atrium, one in the coronary sinus and one for R-wave synchronization in the RV apex. It is used to cardiovert people out of atrial
fibrillation. It can be done when you have two leads inside the heart like this and you are not shocking externally and you are not
stimulating skeletal muscle. The amount of energy required is only in some patients 0.5 Joule or 1 or 2 Joule. So, although in some
patients that causes a fair amount of discomfort, in some patients it doesn't and the idea of atrial defibrillators are being tested right
now. The big questions are safety. The first patient that has an atrial defibrillator that gets shocked or it fails and they get put into VF
and then dies, that will be the end of the whole idea.
Surgical treatment of atrial fibrillation. The Maze procedure consists of multiple atriotomies which interrupt all the potential re-entrant
circuits. This will restore control of the heartbeat to the atrial pacemaker, which is the sinus node, and it allows activation of the entire
atrial myocardium. The long term results are unclear.
Atrial flutter. Typical atrial flutter is characterized by the typical saw-tooth flutter wave in the inferior leads beneath the positive flutter
wave in lead V1. It is a macroreentrant electrical rhythm confined to the right atrium. So, the electrical wave front goes around the
right atrium, up the septum, down the lateral wall and through this isthmus of tissue between the opening of the IVC and the tricuspid
annulus and the coronary sinus. If we can create a line of conduction block, the patient should not have atrial flutter anymore.
We are now able to terminate atrial flutter and cure people that have typical atrial flutter in about 95% of cases. Antiarrhythmic drugs
are not very effective for atrial flutter, and rate control is much more difficult in atrial flutter than atrial fibrillation because it is hard to
get a reasonable rate control. When somebody presents with atrial flutter for the first time, cardioversion is recommended, and then
the patients are discharged and observed to determine what the natural history is going to be. If they are not going to have atrial
flutter for the next five years, no treatment is necessary. The first time they return with atrial flutter, if it is early on, the first line of
therapy now is ablative therapy and our success rate is very good and the risk is low.

18

Antimicrobial Prophylaxis

1
Antimicrobial Prophylaxis Against Acute Rheumatic Fever and Spontaneous
Bacterial Endocarditis
David Kramer, M.D.

2
Rheumatic Fever: Secondary Prophylaxis
. Indicated for patients with previous acute rheumatic fever (ARF) and/or
rheumatic heart disease (RHD)
. Prophylaxis is continuous because subclinical Group A beta-hemolytic
streptococcal pharyngitis can trigger recurrent ARF
. Risk of recurrence is greatest in first 5 years after ARF and in those with
RHD; the risk is 50% per episode of streptococcal pharyngitis
Secondary rheumatic fever prophylaxis. You all should know what
primary rheumatic fever prophylaxis is. That occurs of course to
accurate diagnosis and treatment of acute streptococcal pharyngitis
to prevent a first episode of rheumatic fever. However, secondary
rheumatic fever prophylaxis, that is which is for patients who
have been identified of having had a previous episode of rheumatic
fever and/or have been identified to have the presence of rheumatic
heart disease. So that if you identify someone who appears to have
rheumatic heart disease, but don’t have a clear history of rheumatic
episodes, you still want to institute rheumatic prophylaxis. Rheumatic
fever prophylaxis is continuous and the reason is because
you can not really rely only upon prior treatment of clinically
apparent strep pharyngitis in order to prevent rheumatic fever. One
third of rheumatic fever episodes may follow subclinical, in
clinically apparent streptococcal pharyngitis, and therefore this
should be continued prophylaxis to prevent all those streptococcal
infections. The risk of recurring episodes of rheumatic fever is
greatest in the first five years after a rheumatic fever episode. And
it also greatest in the first five years after a rheumatic fever
episode, and it also greatest in individuals who have had heart
disease. And if you take individuals at risk who have developed a
streptococcal pharyngitis. I gather in time another episode of
rheumatic fever will assume, all odds of sorts with increased heart
disease, or other developments of first-time heart disease. And that
is why this is such an important intervention. A common question
is how long do you get rheumatic fever prophylaxis? The best and
most considerate opinion is that the Committee of the American
Heart Association has recommended, and it’s recommendations
published in 1995, and contained in the Red Book. Patients who
have persistent rheumatic heart disease should receive at least ten
years of prophylaxis and should be at least until they are 40 years
of age, because that gets them through the period of time when
they are most likely to encounter young children who have streptococcal
pharyngitis. And I think really that a patient who has
significant rheumatic heart disease, doesn’t mean he has a life
long list of recurrent episodes of rheumatic fever after streptococcal
pharyngitis infection and lifelong infection ought to be considered
in those individuals.

3
Rheumatic Fever Prophylaxis Duration
. Persistent RHD: Prophylaxis is provided for at least 10 years
and at least until age 40; lifelong prophylaxis
should be considered
. RF with carditis 10 years, or well into adulthood
without residual RHD: (whichever is longer)
. RF without carditis: 5 years, or until age 21
(whichever is longer)
The patient who has an episode of acute rheumatic fever with
cardiac involvement, but then the cardiac involvement has resolved
and echo findings are no longer apparent in those patients. The
recommendation is that ten years of prophylaxis. And the reason
that these are long recommendations is that the consequences are
more obviously severe in the categories of patients considering an
episode of rheumatic fever. In patients who have had an episode of
rheumatic fever without any cardiac involvement, their recommendation
is that they should receive five years of therapy or at least
until the age of 21. The specifically recommended regimens for
rheumatic fever prophylaxis are Penicillin given monthly, the dose
is 600,000 units for children under 60 pounds or 1.2 million units
for individuals over 60 pounds, and then some kind of a regimen
every 3 week or every 4 week should be recommended. In the
United States every 4 week administration is perfectly fine. There
are of course, three acceptable oral agents, the third recommended
is Penicillin G at 250 mg twice daily. But for the individual
who can not tolerate these drugs, erythromycin seems to be the
idea for the standard recommendation.

4
Rheumatic Fever Prophylaxis Regimens
. IM Benzathine Pen G 1.2 M units IM Q3-4 wk
or
. P.O. Penicillin V 250 mg BID
or
. P.O. Sulfadiazine 0.5-1.0 gm QD
or
. P.O. Erythromycin 250 mg BID
Cardiac conditions that the Heart Association has recommended.
I think it would be a good idea to have a clear idea of this group of
patients. Clearly we all know that patients with prosthetic heart
valves are at very high risk. There is also a group of patients who
have other kinds of prosthetic material in their heart. And one of the
reasons that we have seen the highest patients is that they are
probably more likely given this. The consequences in these kinds
of patients are much more serious, and therefore it behooves us to
be as aggressive as we can to try to prevent this. An individual who
has had a previous episode of endocarditis is considered to be a
high risk for future episodes.

5
Infective Endocarditis Prophylaxis
. Goal is to prevent infective endocarditis in susceptible patients (with
underlying structural cardiac disease) when undergoing procedures that are
likely to induce transient bacteremia
. Coverage is provided for the procedure
. No controlled data support efficacy; recommendations are based on in vitro
susceptibility data
Then we have identified the moderate risk group of patients who
have unreformed heart disease, in whom prophylaxis is recommended,
and we will get to some of the new odds between this
group when we are ready. It is a moderate group of patients in that
they have acquired valvular heart disease, such as rheumatic heart
disease where the patients are getting continuous rheumatic fever
prophylaxis that needs in addition while ongoing a procedure for
example. We have ultimately decided that these patients should be
divided into those that have micro-prolapse with regurgitation, and
those that have micro-prolapse that may be associated with thicker
leaflets, this is something that occurs as folks get older, in the 50s
and 60s. So from the pediatric perspective, the findings of micro-
regurgitation is really once you determine whether a MVP patient
is one from whom you should recommend prophylaxis. Now what
we have done this time as a recommendation is to try to spell out
a group of negligible risk patients who have prophylaxis, and these
are patients we have considered to have no measurable risk over
that of the general population in individuals who do not have any
kind of heart disease. So these are kids who are supposed to have
ASD, VSD or PDA presurgical repairs, who do not have any
residual, cardiac disease, six months postoperative. To give it time
for all the patches to become epithelialized, for every 6 months, no
residual shunts.
Cardiac conditions the procedures that individuals are undergoing
where we need to consider whether they should give prophylaxis.
Some general principals are that procedures that are performed
through surgically scrubbed skin, including cardiac catheter,
angiography, are unlikely to be associated with bacteremia and
therefore, are generally not situations where we recommend
prophylaxis. In contrast, procedures that are done across mucosal
surfaces are much more likely to induce bacteremia. Bacteremia
is more common in the presence of poor dental hygiene than it is
in patients who have good dental hygiene, and the intensity of the
bacteremia in terms of the colony forming units, is much greater in
those that have poor dental hygiene. A very good rule of thumb
when it comes to speaking about dental procedures, is that
procedures that induce bleeding, that is that there is significant
trauma to the gingiva, are the ones that are most associated with
bacteremia.

6
Conditions Requiring Infective Endocarditis Prophylaxis
. Cardiac Conditions
Highest-Risk Patients (Recommended)
Prosthetic heart valves
Previous IE
Complex cyanotic congenital lesions
Surgical systemic-pulmonary shunts or conduits
. Moderate-Risk Patients (Recommended)
Acquired valve dysfunction (eg, RHD)
Hypertrophic cardiomyopathy
Most other congenital heart disease not included in categories I or III
Mitral prolapse with MR and/or thickened leaflets
. Negligible-Risk Patients (Not recommended)
Isolated secundum ASD
Surgically repaired ASD, VSD or PDA (without residua >6 months
post-op)
Previous CABG
Mitral prolapse without regurgitation
Functional murmurs; previous Kawasaki disease or rheumatic fever
without valve dysfunction
Pacemakers and defibrillators
So recommended prophylaxis includes extracting, cleaning with
bleeding. Cleaning typically induce bleeding, because then you can
really get down into the gum line and there is scraping and
bleeding. Very important to pediatrics, is the initial placement of
orthodontic bands with associated bleeding, and lots of trauma,
and as in contrast to the adjustment of orthodontic appliances. So
that the general rule is patients who have first time placement of
their orthodontia, they should be prophylaxis. Root canal surgery,
if it extended beyond the apex, is associated with bacteremia.
Periodontal procedures are associated with bacteremia.
Intraligamentary injections. Prophylaxis is not recommended for
shedding of primary teeth. As I said it is the adjustment of the
orthodontia, taking x-rays, fluoride treatments, and oral impressions.
Local anesthesia, placement of a kind of rubber dam and
suture removal interestingly, has not been associated with
bacteremia, and therefore we would not generally recommend
prophylaxis. In addition to dental procedures, there are a number
of nondental procedures involving the oral cavity and upper
respiratory tract, and of course the GI and GU tract.

7
IE Prophylaxis: Procedures
. Procedures (AHA, 1997)
Procedures through surgically scrubbed skin including routine cardiac cath and
angiography are unlikely to induce bacteremia
Trans-mucosal procedures more often induce bacteremia
Bacteremia is more common in the presence of poor dental hygiene
Procedures that induce bleeding are most commonly associated with bacteremia
. Dental Procedures
Prophylaxis Recommended
Extractions
Cleaning (with bleeding)
Initial placement of orthodontic bands
Root canal surgery (only beyond the apex)
Periodontal procedures
Intraligamentary injections
Prophylaxis Not Recommended
Shedding of primary teeth
Adjustment of orthodontic appliances
X-rays, fluoride treatments, oral impressions
Restorative dentistry (filling cavities)
Local anesthetic; placement of dams
Suture removal
..Non-dental Procedures
Prophylaxis Recommended
Respiratory: Tonsillectomy and/or adenoidectomy surgery involving mucosa,
rigid bronchoscopy
GI*: sclerotherapy for varices, esophageal dilatation, endoscopic retrograde
cholangiography with biliary obstruction, biliary tract surgery, surgery involving
GI mucosa
GU: prostatic surgery, cystoscopy, urethral dilatation
*Recommended for high-risk patients, optional for moderate risk
Prophylaxis Not Recommended
Respiratory: endotracheal intubation, flexible scope bronchoscopy (with or
without biopsy*), tympanostomy tube placement
GI: Transesophageal echocardiography*, endoscopy (with or without biopsy)
Genitourinary: Vaginal* or Cesarean delivery, hysterectomy*; in uninfected tissues:
urethral catheterization, dilation and curettage, therapeutic abortion, sterilization
procedures, insertion or removal of intrauterine devices, circumcision
Miscellaneous: cardiac catheterization, balloon angioplasty, placement of pacemakers,
defibrillators, or coronary stents, incision or biopsy of prepped skin
* Prophylaxis optional for high-risk patients
Prophylaxis is clearly recommending for the group of patients at
high risk undergoing these kinds of procedures and will be optional
for the much larger group of individuals who are on that list of
moderateness. So you can see here that the compromise that was
achieved was to make prophylaxis optional for the GI procedures,
accept for the very high-risk patients where we thought the risk
really justified without a doubt, the treatment of prophylaxis. So in
this category then are recommended patients undergoing T&A.
Under the GI procedures, for high-risk patients it is definitely
recommended that optional moderate infection, esophageal
dilatation, endoscopic retroperitoneal endoscopy. Under GU
procedures recommended for patients undergoing prostatic
surgery, got too many kids. So in this book we have simple
endotracheal intubation, flexible bronchoscopy, and that gets an
asterisk. GI procedures: Transesophageal echoes, only optional for
certain patients otherwise they really are not any cases of hepatitis
associated with this procedure, although almost all of your patients
have heart disease. Endoscopy. GU procedures: Vaginal delivery
is actually a higher risk for bacteremia than C-sections, so that gets
an asterisk. Hysterectomy gets an asterisk. If the patients have
nose infection, undergoing GU procedures such as urethral
catheterization of D&C, or circumcision, I strongly suspect that we
would not recommend prophylaxis. Then we have this latest group
of situations where we will not recommend prophylaxis:
angioplasty, placement of a pacemaker, coronary stents.

8
IE Prophylaxis for Dental, Oral, Respiratory
Tract or Esophageal Procedures (AHA, 1997)
Standard PO Amoxicillin 50 mg/kg 1 hour before
(adults=2 gm)
Unable to take orally IM or IV Ampicillin 50 mg/kg 30 min before
(adults=2 gm)
Penicillin-allergic PO Clindamycin 20 mg/kg 1 hour before
(adults=600 gm)
or
PO Cephalexin* or
Cefadroxil* 50 mg/kg 1 hour before
(adults=2 gm)
or
PO Azithromycin or 15 mg/kg 1 hour before
Clarithromycin (adults=500 mg)
Penicillin-allergic and IV Clindamycin 20 mg/kg within 30 min
unable to take orally before (adults=600mg)
or
IV or IM Cefazolin* 25 mg/kg within 30 min
before (adults=1gm)
* Avoid with immediate penicillin hypersensitivity
All Regimens are Single Dose
What are the now recommended prophylactic regimens? For
dental, oral, respiratory or esophageal procedures. Prevents
everything except lower GI and GU procedures, things have been
simplified to the bottom line here, single dose, no second doses.
Standard recommendation is single dose therapy. The standard
here is a single oral amoxicillin dose. For adults it is 2 grams. For
children it is 50 mg per kg. For patients that can not take oral
medication, a single dose of Ampicillin, same dosage, given 30
minutes before food. Now we have had a problem with patients
who are penicillin allergic, and you may remember that
Erythromycin has gotten in the past, standard recommendation. In
the larger group of moderate risk patients undergoing the
nonesophageal, GI plus GU procedures, we can give single dose
oral amoxicillin.

9
Prophylaxis for Genitourinary/gastrointestinal
(Non-esophageal) Procedures (AHA, 1997)
. High-risk Patients IV or IM Ampicillin (50 mg/kg up to 2 gin) plus IV or
IM Gentamicin (1.5 mg/kg up to 120 mg) within 30
min of starting procedure; 6 hours later, ampicillin
(25 mg/kg IV or IM) or amoxicillin (25 mg/kg PO)
. High Risk IV Vancomycin (20 mg/kg up to 1 gm) over 1-2 hr
(Pen-allergic) (1.5 mg/kg up to 120 mg) plus IV or IM Gentamicin
within 30 min of starting procedure
. Moderate Risk PO Amoxicillin or IM or IV Ampicillin (50 mg/kg up
to 2 gm) within 30 min. of starting procedure
. Moderate Risk IV Vancomycin (20 mg/kg up to 1 gm) over 1-2 hrs.,
(Pen-allergic) within 30 min of starting procedure

10
Prophylaxis for Surgical Wounds
. Generally not indicated for clean wounds that do not involve mucosal
surfaces (exceptions: open heart surgery, placement of prosthetic device,
immunocompromise?, neonate?)
. Often utilized for clean-contaminated wounds (across mucosal surface)
. Universally utilized for contaminated or dirty/infected wounds (treatment,
not prophylaxis)
. A single dose shortly before surgery is generally adequate
. Directed against the most likely bacteria (staph for skin; gut flora, etc.)
Other circumstances of antibiotic prophylaxis. One of those is
prophylaxis of surgical wounds. Surgical wounds are divided into
clean, clean contaminated, and infected kinds of wounds. This is
preoperative, not postoperative. Generally surgical prophylaxis is
not indicated for cleaning wounds that do not involve mucosal
surfaces. There are specific exceptions. I think all of us would
agree that I think all of us would agree that patients undergoing
open-heart surgery, placement of a prosthetic device either cardiac
or orthopedic or some other device, is perhaps in compromised
individuals. For clean contaminated surgery across mucosal
surfaces, a surgical incision is going to be across a normal
mucosal surface, it clearly cannot be prepped in the same way that
skin can be, and therefore is going to be contaminated. Most
surgeons would use antibiotics and most time that is the reasonable
thing to do. In individuals who have contaminated or dirty
infected wounds, that incision has to be made, that is a third
compound fracture contaminated with dirt. I think the key is to try to
individualize surgical colleagues that when surgical wound
prophylaxis is given, and is appropriately in judgement of the
surgeon, it really should be a single dose, and should be given
shortly before surgery because it is really critical to have a substantial
level of antibiotics in the patients blood stream at the time of
incision. Antibiotic surgical prophylaxis should be directed against
the most likely bacteria, which would be staphylococci of the skin.

11
Prophylaxis for H Influenzae: Principles
. Observation of exposed household or child care/nursery contacts, with
prompt evaluation if fever develops
. Increased risk of invasive Hib in unvaccinated household contacts <4 years
old (perhaps also in child care contacts)
. Increased risk of Hib colonization among household contacts of all ages
(probably also in child care contacts)
. Risk for secondary cases among child care contacts is less than age-
susceptible household contacts: 2Ecases are rare when all contacts are >2
years old
. Prophylaxis is given as soon as possible because best prevention occurs
in first week after index case
Prophylaxis against H flu. There are some general principals that
is that if a case of invasive AIDS flu and we have exposed individuals,
those exposed are household and childcare and nursery
contact should be observed. There is an increased risk of invasive
HIb in unvaccinated, this really should be incompletely vaccinated,
household contact who are under 40 years of age, and perhaps
there is an increased risk also in childcare contact. Among
household contacts of an invasive case of HIb, there is an increased
risk of HIb colonization among household contacts of all
ages. That is also probably true in daycare and childcare contact
as well. The risk for secondary cases occurring among childcare
contact is definitely less than the risk for aids through susceptible
household contact.
In a household setting, all household members of all ages should
be prophylaxed where there is at least one incompletely vaccinated
contact for those of 48 months of age. For a definition of who is
considered to be completely vaccinated, that is a child who has
received at least one conjugated dose at the age of 15 months or
greater, or has had two doses of vaccine if the child is between 1214
months. In any case, I think the key point is that if you have any
one who is incompletely vaccinated under 4 years of age in a
household, you should really give vaccines to everybody in the
household, because of the concern about carriage. If you have a
child under 12 months of age in the household, all the household
members again of all ages ought to be prophylaxed, and the reason
is because this child may be colonized because of the booster
dose beyond 12 months. If it is in a childcare situation, it really gets
sort of confusing. I have to admit this is not my major field of
interest, but I will relay to you what the Red Book says. It indicates
clearly that the risks in a childcare setting is lower than in households
and secondary cases are less likely to occur in childcare
settings than in households. Secondary cases are rare when all the
people in the childcare center are over 2 years of age. And they
have a definition of what is contact? What is sufficient contact?
They define it as 25 hours of the week. In addition, the identification
of a first case, whether or not they give prophylaxis is certainly
enough to take the opportunity to bring everyone to a vaccine center
today. Now if there is a second case of invasive HIb that occurs
within 60 days in one of these centers, and there are many
unvaccinated or incompletely vaccinated children present, the
families should be given and all personnel, a dose as well. Unless,
we have pregnant personnel, and there is a specific exclusion in
the Red Book for pregnant personnel.
Prophylaxis is recommended for household and childcare and
nursery contacts. You do not need a second case. If you have a
case of pneumococcal disease. Whenever there is sharing of oral
secretions, food, drink, kissing, household and childbed nursery
contacts, clearly prophylaxis is indicated. Then, of course, medical
personnel. It should be everyone in the hospital who has passed
within 25 feet of the case, that is really where prophylaxis is
recommend or medical personnel who have been exposed such as
mouth-to-mouth resuscitation.

12
Meningococcal Vaccine
. Indications for Vaccine
Control of outbreak
Travel to epidemic area
Military recruits
Functional or anatomic asplenia, terminal complement deficiency state
. Immunogenicity
Group A >3 months old
Groups C, Y, W-135 >18-24 months old
Protection lasts 3-5 years (or less)
Revaccination is probably indicated for those <4 years if still at risk

Treatment of Acute Renal Failure

General Therapy for Acute Renal Failure


Treatment of acute renal failure usually should be conservative and largely supportive. It requires careful and precise management. All patients will require close monitoring, many of them within intensive care settings.

Supportive care includes stabilizing the patient, monitoring input and output strictly, weighing daily, determining electrolyte values frequently, preventing sepsis via reducing the number of intravenous lines and removing an indwelling urinary catheter, culturing periodically, and using antibiotics when indicated clinically. It is important to adjust medication dosage according to renal function and to avoid nephrotoxins whenever possible. Because serum creatinine values increase daily, it is best to calculate drug doses based on GFR <10 mL/min per

1.73 m², rather than on the serum creatinine level.

Conservative therapy may be symptomatic or specific. Symptomatic therapy consists of treating the underlying prerenal conditions that led to renal failure; maintaining the fluid and electrolyte balance; initiating therapy for complications such as hyperkalemia, hypertension, acidosis, and infection; and instituting appropriate nutrition. Specific therapy consists of using medications for specific underlying causes and may include steroids (conventional or high-dose pulse steroid therapy) and other immunosuppressive agents, anticoagulation agents, plasmapheresis, or intravenous immunoglobulin.

THERAPY FOR PRERENAL FAILURE

Rapid volume replacement and treatment of the underlying condition that resulted in prerenal failure are the cornerstones of therapy. Initial fluid administration of isotonic saline (0.9%) or 5% albumin (10 to 20 mL/kg per dose) should be used to restore intravascular volume. This can be both a diagnostic and a therapeutic trial. Fluid administration also can convert oliguric to nonoliguric renal failure in its early stage.

Unless a patient is suffering congestive heart failure (CHF), fluid administration should be repeated, followed by the use of loop diuretics, including furosemide (2 to 5 mg/kg per dose) or bumetanide (0.25 to 0.5 mg/dose IV). After each bolus, the patient's volume needs to be reevaluated. Response to the therapy will be indicated by a urine output of greater than 1 to 3

D:\FILES\A_Journals\Pediatrics 5 Minute Review\Unused\Acute Renal Failure Therapy.wpd 1 mL/kg per hour.

Patients who have CHF will need inotropic support, such as dopamine (5 µg/kg per minute IV), dobutamine (5 to 20 µg/kg per minute), or digoxin. Therapeutic digitalis values should be achieved slowly and the maintenance dose reduced as dictated by renal function (Table 6).

THERAPY FOR POSTRENAL FAILURE

Therapy for postrenal failure includes removal of obstruction by decompression or diversion of the urinary tract, stabilization of electrolyte abnormalities, management of postobstructive diuresis, and therapy for voiding dysfunction and for urinary tract infection. Surgical intervention will require urologic consultation. The site of the obstruction will determine the approach: placement of a Foley catheter, vesicostomy, ureteral catheters (stents), or nephrostomy tubes. Prompt relief of a partial obstruction is indicated in cases of severe pain, where the possibilities for severe renal damage predominate, and whenever there is a history of frequent urinary tract infections.

Postobstructive diuresis is characterized by marked polyuria. The excessive excretions of salt and water may result in hypokalemia, hyponatremia, and hypotension and lead to collapse. Fluid replacement should be guided by what is excreted and based on frequent measurements of urine volume, urinary electrolytes, and serum electrolytes, including calcium and phosphorus.

THERAPY FOR ESTABLISHED RENAL FAILURE

Maintaining Balance of Fluid and Electrolytes

In a euvolemic state, fluid intake, including water generated from endogenous metabolism (insensible fluid gain), is balanced by fluid output. Most of the fluid output involves sensible fluid losses by urine, stool, and sweat and insensible losses by water evaporation from the skin and respiratory tract. Only small amounts of water normally are lost in the stool (100 to 150 mL/d), and fluid loss by sweat is minimal. Therefore, patients who are in ARF should have fluid restricted to net insensible water loss (insensible losses minus endogenous water production, which is 400 mL/m² per day or 25% to 30% of caloric expenditure) plus all measured fluid losses (urine output, gastrointestinal losses, chest tube drainage). Net insensible loss should be restored with 5% to 10% dextrose in water (D5%W - D10%W). Urine output should be replaced with fluid that has the composition and quantity of these losses. Usually, normal saline (0.45% NS) mL for mL of losses every 4 to 6 hours is appropriate. If this therapy is sufficient, the patient will lose

2 0.5% to 1% of body weight per day over the initial few days. The patient should be weighed at leastonce daily, and input and output should be monitored strictly, with clinical status assessed constantly. Once urine output begins to rise, fluid intake should be increased. Fluid balance is easier to manage in children who have nonoliguric renal failure. Dialysis is indicated in the case of a severe fluid overload (Table 6).

Metabolic acidosis will change the activity of cellular enzymes and depress cardiac function. A serum bicarbonate (HCO3) of less than 12 mEq/L may require correction. The goal is to keep the serum pH greater than 7.2 or serum bicarbonate level above 16 mEq/L. The amount of NaHCO3 needed to correct metabolic acidosis can be estimated by using this formula:

Base deficit (BD) = 0.6×BW (kg) × (desired - observed serum HCO3)

The base deficit can be added to the urine output or maintenance fluid. Half of the replacement can be given within the first 2 to 3 hours and the rest evenly over 24 hours. Caution must be taken to avoid salt and fluid overload. In the patient who has hypocalcemia, sodium bicarbonate must be administered cautiously because it may lead to tetany.

Patients who have CHF will not tolerate a large sodium load, and the use of intravenous tromethamine (THAM) can be considered; it is available as a 0.3 M solution. The dose of THAM in mL can be calculated as:

mL of 0.3 M THAM = BW (kg) × base deficit (mEq/L)

THAM can be given only in intensive care settings. If the patient has respiratory acidosis (increased pCO2), administration of base will not be effective and it is not indicated.

Hyponatremia can lead to cerebral overhydration and neurologic symptoms. It is necessary to keep the serum sodium in the range of 130 to 135 mEq/L, restricting excessive free water.

Hyperkalemia is the most life-threatening condition in ARF, resulting in muscular weakness and abnormal cardiac conduction, which can lead to fatal arrhythmias. Potassium must be monitored by serial determination and electrocardiogram. A peaked T wave, prolongation of the PR interval, widening of the QRS, disappearance of the P wave, and ventricular fibrillation are electrocardiographic (EKG) changes associated with an elevated serum potassium level.

The effects of hyperkalemia can be reversed by direct antagonism of its membrane actions and by lowering of the serum K^+ concentration either by promoting K^+ uptake into the cells or by removing K^+ from the body. Severe symptoms usually do not occur until the serum

3 level is above 7.5 mEq/L, but acid-base disbalance and a low serum Ca^++ level can modify the toxicity of hyperkalemia. In the absence of obvious artifactual changes (extravascular hemolysis, thrombocytosis, leukocytosis), an asymptomatic elevation of the serum K^++ to >5.8 mEq/L should be treated via a cation exchange resin (sodium polystyrene sulfonate). All sources of potassium should be eliminated in ARF. Usually ignored sources of K^+ are blood transfusions and drugs (penicillin).

If serum K+ is greater than 6.5 mEq/L and is accompanied by EKG changes, emergency steps must be instituted to lower the potassium level (Table 6).

1 Calcium gluconate--10% solution (0.5 to 1.0 mL/kg per dose) will oppose the effect of hyperkalemia on the heart and stabilize myocardial membranes. It should first be given intraveneously (IV) slowly over 10 to 15 minutes under careful EKG monitoring. The protective effect of Ca++ is relatively short and can be repeated within 5 minutes if indicated by EKG.

2 Glucose and insulin will promote the cellular uptake of potassium by increasing the Na+-glucose cotransport and Na+-K+ ATP-ase. Regular insulin in a dose of 0.1 to 0.2 U/kg and dextrose 0.5 to 1.0 g/kg are given after calcium gluconate. One can mix 100 mL D25%W with 6 U of regular insulin and administer slowly (1 to 2 mL/kg per dose IV).

3 Sodium bicarbonate (NaHCO3 7.5% 1 to 2 mEq/kg per dose IV slow push or fast drip) will raise the blood pH and shift potassium into cells. An increase of serum pH by 0.1 will lower serum K+ by 0.6 to 1 mEq/L, but this effect in ARF is transient; there is only a moderate, unpredictable response on the serum potassium concentration, which often is accompanied by significant volume expansion.

4 Albuterol aerosol and other beta2-adrenergic agonists can be given in an emergency. Like insulin, the beta2-adrenergic agents will cause a shift of potassium from the extracellular space into the cells. In some patients, albuterol aerosol can lower the serum K+ level by 1.0 to



1.5 mEq/L within 30 minutes. This measure is safer than giving sodium bicarbonate. All of these steps are only temporizing measures and must be accompanied by removal of potassium from the body.

5. Sodium polystyrene sulfonate, an ion exchange resin, will bind potassium in the gut in exchange for sodium (1 mEq K+ for 1 mEq Na+) and remove excess potassium from the body. The usual dose is 1 g/kg orally or by nasogastric (NG) tube given with 70% sorbitol or rectally (1 g in 2 to 4 mL of 25% to 30% sorbitol or 10% dextrose in water) as a retention enema placed through a Foley catheter for 30 to 60 minutes. Doses can be repeated every 2 to 4 hours.

When all of the aforementioned therapies fail to control plasma K^+ excess adequately, dialysis, usually in the form of hemodialysis, should be initiated. Mild hyperphosphatemia does not require therapy. Higher levels of phosphate in serum

 4 can be controlled with calcium carbonate as a phosphate binding agent (300 to 400 mg/kg per day orally). The dose should be adjusted to maintain the serum phosphorus level in the 5- to 6-mg/dL range. In general, magnesium or aluminum phosphate binders should be avoided in ARF.

Hypocalcemia does not require therapy unless tetany is present. If the child has tetany, 10% Ca gluconate (0.5 to 1.0 mL/kg per dose IV) should be administered.

Treating Hypertension

ARF in any form can present as hypertension and hypertensive encephalopathy. It is essential to lower the blood pressure quickly and safely. The blood pressure should be reduced by at least 25% within 1 hour with an antihypertensive medicine whose onset of action is rapid. It is advisable to start with one antihypertensive medicine and increase the dose to its maximum recommended level. Therapy is individualized and needs titration (Table 6). In most cases, hypertension is the result of sodium and fluid retention, but other factors, such as activation of the renin-aldosterone-angiotensin II and/or the alpha-adrenergic system, may have roles as well.

For immediate control of blood pressure, orally administered medication is less feasible in severely sick patients. Rather, a dose of the following should be considered:

1 Nifedipine, a calcium channel blocker (0.25 to 1.0 mg/kg per dose sublingually intrabuccally) usually is very effective. The dose can be repeated within 30 minutes and then every 3 or 4 hours as needed. Maximum is 30 mg/dose or 180 mg/24 hours.

2 Diazoxide, a vasodilator, given as a rapid IV infusion (3 to 5 mg/kg per dose) will lower blood pressure effectively within a few minutes. Its effect lasts several hours. Slow infusion should be avoided because it allows diazoxide to bind to plasma proteins and lose its efficacy. If the first dose is ineffective, another higher dose (maximum 10 mg/kg per dose) can be given. Doses can be repeated every 30 minutes. The maximum dose is 150 mg.

3 Hydralazine is a peripheral vasodilator that acts within 5 to 20 minutes when administered as 0.1 to 0.5 mg/kg per dose IV bolus or IM. Doses can be given every 4 to 6 hours as needed, but subsequent doses usually will result in undesirable side effects, such as headache, flushing, and tachycardia. The maximum to be given is 3.5 mg/kg per 24 hours.

4 Labetalol, with its alpha1- and nonselective beta-adrenergic blocking characteristics, can be used in a single dose. The starting dose is 0.25 mg/kg IV. It should be increased by 0.5 mg/kg per dose after 10 minutes, if needed, to 1.0 mg/kg IV, or it should be given as a continuous infusion (1 to 5 mg/kg per hour). The maximal dose is 300 mg/day.

5 Sodium nitroprusside continuous IV infusion (0.5 to 10 µg/kg per minute) will correct the



 5 blood pressure rapidly, but close monitoring of vital signs, lactic acid, and the thiocyanate level are needed. This agent probably should be used only in an intensive care setting. The maximum dose to be used is 800 µg/min.

Treating Anemia

There is no need for transfusion unless the patient is symptomatic and the hematocrit falls below 25%.

Nutrition

The provision of adequate and appropriate nutrition is a fundamental part of the nondialytic therapy of ARF, regardless of the etiology. Generally, enteral nutrition is preferred, either by oral intake or gastric tube. In many cases, the oliguric phase of ARF is short and self-limited, and special nutritional support is not needed. Some experimental studies suggest that infusion of nutrients (amino acids) in the early phase of ARF may increase oxygen requirements and aggravate tissue injury. The goal is to provide sufficient nutrients and adequate caloric intake to restrain the catabolic response and to hasten renal recovery. About 400 kcal/m² per day (45 to 50 kcal/kg per day) are required mainly as simple carbohydrates (>70%) and fats (<20%) orally and/or glucose solution (10%) parenterally. A patient whose nutritional status is normal and in whom ARF is uncomplicated may resume a normal diet within 5 to 7 days. If renal function is below 30% of normal (GFR <50 mL/min per 1.73 m²), the nutritional requirement should be adapted to renal failure. There are special formulas designed for enteral feedings in patients who are in renal failure.

Hyperalimentation should be considered early in the hypercatabolic patient. With dialysis, daily protein and caloric intake can be more generous (0.5 to 1 g/kg per day high biologic value protein), but more frequent dialysis may be necessary to control azotemia. If the BUN is greater than 50 mg/dL, a patient can benefit from special "nephro" solutions (essential amino acids and various nonessential amino acids). Depending on serum electrolyte concentrations, solutions should contain minimal amounts of sodium and no potassium or phosphorus.

Nutritional therapy requires monitoring for potential metabolic complications, such as fluid and electrolyte derangements, excessive BUN accumulation, hyperglycemia, and hypertriglyceridemia.

Renal replacement therapy (dialysis) usually is needed in about 20% of patients. The use

 6 of dialysis always should be individualized, but in general, the indications include severe fluid overload resulting in severe hypertension, CHF, pulmonary edema, and/or metabolic derange¬ments refractory to therapy, such as severe acidosis, severe hyperkalemia, hyponatremia, hypernatremia, hyperuricemia, or hyperphosphatemia. Dialysis is indicated when the BUN is greater than 100 mg/dL and there are symptoms of uremia, usually manifested in children as central nervous system depression. Preemptive dialysis can be used to prevent rather than treat uremic symptoms, as in the case of rapidly decompensating hemolytic-uremic syndrome and acute uric acid nephropathy or for removal of toxins as in oxalate overload. Early dialysis can simplify management and help in the administration of a specific therapy (chemotherapy) or diet (hypercatabolic cases).

The choice between hemodialysis, continuous arteriovenous hemofiltration, continuous venovenous hemofiltration, continuous arteriovenous hemodialysis, and peritoneal dialysis will depend on the availability of the technique, the etiology of the renal failure, and specific indications and relative contraindications. In patients whose major problem is excess extracellular volume (eg, in patients who have cardiac problems), hemofiltration offers some distinct advantages because this technique removes excess fluid quickly.

Prevention

Prevention of ARF, obviously, is the best form of therapy. Certain clinical situations may predispose to the development of ARF and should be recognized. Some preventive measures include:

1 Monitor the patient at risk.

2 Provide adequate hydration and maintenance of extracellular fluid volume (ECV) prior to the administration of radiocontrast material, amphotericin B, or aminoglycosides.

3 Administer nephrotoxic drugs in appropriate doses and monitor drug levels carefully. If possible, use alternative medication and limit the length of patient exposure.

4 Alkalize urine (pH >6.5) and adequately hydrate patients who have hyperuricemia or pigmenturia.

5 Use xanthine oxidase inhibitors to prevent hyperuricemia, such as in tumor lysis syndrome.

6 Treat prerenal conditions promptly via intravenous fluid to expand ECV and via osmotic and loop diuretics to increase blood flow and decrease cast formation if cardiovascular status allows.

7 Administer low-dose dopamine infusion (3 to 5 µg/kg per minute) to patients who are in

8. Ameliorate ARF with nutrients and hormones; vasodilatators and cytoprotective agents can help. Experimental studies have indicated a role for the following agents in animal studies and limited clinical trials. However, the beneficial effects of thyroxine, atrial natriuretic factor, insulin growth factor, prostaglandin analogs, adenosine triphosphate-magnesium chloride, calcium channel blockers, and dopamine need to be established more firmly.