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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5851_Библиотеки_им_академика_М_И_Перельмана.pdf
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Table 11.2 Intravenous diuretics
Drug Dose Onset of action
Loop diuretics
Bumetanide 1mg IV load, then 0.5–2mg/h infusion 5min
Furosemide 40mg IV load, then 10–40mg/h infusion 5min
Torsemide 20mg IV load, then 5–20mg/h infusion 10min
Thiazide diuretics
Chlorothiazide 500mg—1000mg IV 15min
C. E. Kulig
Table 11.3
Equivalent doses
Furosemide 40mg PO
Furosemide 20mg IV
Torsemide 20mg PO/IV
Bumetanide 1mg PO/IV
valent doses of diuretics
Equi
11.8.2 Reassessing Diuresis andAdding Thiazides
If there is no response or the response is suboptimal, it is recommended to double
the dose of loop diuretic at 2-h intervals as needed until the maximum recommended
dose is reached [2]. For context, a furosemide bolus of up to 160–200mg may be
given. Higher doses of loop diuretics should be avoided due to the very real risk of
ototoxicity [2].
It is important to note that in patients with renal insufciency, higher doses of
loop diuretics may be required as less of the medication gets to the site of action in
the loop of Henle [2].
If diuretic resistance remains an issue despite escalating doses, thiazide diuretics
may be added on in combination to the existing loop diuretics [2]. These diuretics
work distal to the loop of Henle where additional sodium and water reabsorption
can take place, so by inhibiting this later step, the body does not have that opportunity and more water is excreted. This recommendation is supported by the 2022
AHA/ACC/HFSA guidelines as well [2]. Recently, data looking at the effect of oral
vs. IV adjuncts to loop diuretics in those with ADHF found no difference in weight
loss between oral metolazone and IV chlorothiazide [6].
11.8.3 Side Effects ofLoop Diuretics
Whenever a patient is undergoing diuresis, it is imperative that laboratory evaluation is conducted routinely, with particular attention to electrolytes and renal function. The most commonly seen electrolyte abnormalities with aggressive diuresis
are hypokalemia and hyponatremia. Diuretics can also cause acute kidney injury,
11 Acute Decompensated Heart Failure
and so blood urea nitrogen (BUN), serum creatinine (SCr), and overall urine output
should be assessed daily.
303
11.8.4 Adjuncts toLoop Diuretics
Though loop diuretics are the mainstay of diuresis, diuretic resistance can often be
an issue, and adjunct agents can be considered. As mentioned previously, the addition of thiazide diuretics in addition to loop diuretics is commonly used, and guideline endorsed [2].
If cardiac output and perfusion are an issue, diuresis may be augmented by the
use of inotropes [2]. Inotropes increase the force of contraction of the cardiac muscle and can increase perfusion, thus getting more blood to the kidneys and aiding in
diuresis. Other considerations may include plasma ultraltration, aquapheresis, or
renal dose dopamine [2]. Since the publication of the guidelines, new studies have
also been published investigating the role of SGLT2-is or acetazolamide in these
patients [7, 8].
11.8.5 Clinical Pearls Associated withDiuresis
11.8.5.1 Clinical Pearl #1: Always Look at theWhole I/Os Picture
It is a common scenario—you might be on rounds, and you nd out that your patient
has had “poor” diuresis overnight and is only net negative 250mL.
Before you go increasing their diuretic regimen, it is important to get the whole
picture, instead of being reactive to a suboptimal net negative number.
Ask Yourself the Following Questions
We know that the patient was only net negative 250mL.But what were the ins and
what were the outs?
For example, it is very possible that the patient had great diuresis, with an impressive urine output, but is getting a lot of uids in. Is the patient volume restricted?
How much uid are they getting through their medications? Is it possible to concentrate any of the medications or switch from IV to oral? Is this truly a diuresis issue
or is it an intake issue?
Let Us Solidify with a Case
Patient A is net positive 103 mL (not including insensible losses) in the past 24h.
The team would like to increase their diuretic regimen, but you rst look at their I/
Os. Table11.4 shows their I/Os in the past 24h. For reference, Patient A weighs 92kg.
The rst thing to assess is urine output for your given patient. A good rule of
thumb is to look at 24-h output and translate it in terms of mL/kg/h.
304
Table 11.4 I/Os
Outs Total: 2050mL
Urine output (24h) 2050mL
Ins
Oral intake (24h) 946mL
Medication A (24h) 432mL
Medication B (24h) 150mL
Medication C (24h) 250mL
Medication D (24h) 250mL
Medication E (24h) 125mL
Net (24h) +103mL
C. E. Kulig
In this patient—>2050mL total/92kg/24h=0.93mL/kg/h.
A urine output of >0.5/mL/kg/h is generally considered “good,” with values
closer to 1 or above being excellent. In this case, the patient appears to be having
adequate diuresis on their current regimen.
But why is the patient still net positive? The answer lies in the amount of volume
the patient is getting through medications and oral intake. Ensure that the patient is
on a volume-restricted diet. Next, assess the indications and concentrations of all
medications the patient is getting.
Do they truly need every IV medication? Is there an appropriate indication? Or
can we discontinue any IV medications in the interim?
Are you able to concentrate any of the current medications? Check with your
hospital IV room. Keep in mind that if concentrating any IV medications, make sure
that they are still compatible to run in the type of line that the patient has (e.g., if
currently running through a peripheral line, is a higher concentration still compatible with a peripheral line? Or would a central line be required?). These are all considerations to make.
11.8.5.2
Clinical P
earl #2: Keep inMind That It Is Possible toBeVolume
Overloaded asaWhole, But Still BeIntravascularly Dry
Another common scenario in these patients: they have a day or two of fantastic
diuresis, and then all of a sudden, urine output drops and serum creatinine and
BUN rise. What is going on here? Should we increase the diuretic regimen?
It is important to understand and be aware of the concept that even though a
patient still has volume overload—they still have pitting edema, are above their
euvolemic weight, etc.,—they can still be intravascularly dry.
This can happen if we are diuresing too aggressively, too quickly. When patients
diurese their excess volume, volume from the “third space” such as the tissues
slowly gets pulled back into the vasculature and into blood volume where it can be
11 Acute Decompensated Heart Failure
305
diuresed out. However, if we are too aggressive with our diuretic regimen, what can
happen is that we diurese these patients too quickly and do not allow enough time
for volume in the third space to reenter the vasculature. This can lead to decreased
blood volume, hypotension, and acute kidney injury.
In this case, you may see soft blood pressures, an increase in SCr and BUN (with
a BUN:SCr ratio>20), and, in the days/hours preceding, a very high urine output
(in this case, too high!).
The last thing we would want to do in this scenario is escalate the diuretics.
Instead, in this case, you would want to slow down the diuresing process, allowing
time for that volume to reenter the vasculature. The solution here would be to
increase the frequency and possibly decrease the dose of diuretics.
Remember that each patient has their own unique diuretic threshold at which
lower doses will not produce adequate diuresis. In these patients who are already on
their personal lowest dose, increasing the frequency would be effective at slowing
net diuresis.
11.9 Intravenous Vasodilators
Depending on a patient’s hemodynamics, intravenous vasodilators can be considered; however, the role for directed vasodilators in ADHF is still unclear and does
not affect outcomes in ADHF [2]. Vasodilators that cause venodilation and decrease
preload may target pulmonary congestion and help more acutely with symptoms
such as dyspnea while waiting for signicant diuresis [2].
Intravenous nitroglycerin and nitroprusside are commonly utilized in ADHF
(Table11.5).
Nitroglycerin can be considered in those with hypertension, signicant mitral
regurgitation, or coronary ischemia.
Nitroprusside has the ability to cause potent blood pressure reduction, and so
invasive hemodynamic monitoring (such as with an arterial line) is often required
and used in an intensive care setting only. It can be considered in those with hypertension or severe mitral valve regurgitation complicating left ventricle dysfunction.
An issue with both nitroglycerin and nitroprusside is that tachyphylaxis can
occur within a period of 24h, and 1in 5 patients may be resistant even at high doses.
Nitroprusside has an additional concern of thiocyanate and cyanide toxicity,
especially in those with renal or hepatic disease and so caution should be taken in
these patients.
Importantly, there is no data suggesting that IV vasodilators improve outcomes
in these patients; therefore, their use is limited to relieving dyspnea in those with
intact or high blood pressure [2].
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Table 11.5 IV vasodilator comparison in ADHF
IV nitroglycerin IV sodium nitroprusside
Clinical
effect
Dosing Initial: 5–10mcg/min; titrate as
Adverse
effects
Clinical
pearls
Venous dilation>>arterial dilation;
arterial dilation can be seen at high
doses
Has more preload reduction than
afterload reduction
needed based on response and
tolerability in increments of
5–10mcg/min every 3–5min up to
200mcg/min
Hypotension, tachyphylaxis (within
24–48h of continuous infusion),
headache, reex tachycardia
Duration of therapy is usually short
term due to tachyphylaxis
C. E. Kulig
Potent venous and arterial dilator=potent
preload and afterload reduction
Initial: 0.1–0.3mcg/kg/min; titrate as needed
every 5–15min to achieve desired
hemodynamic effect; usual dosage range:
1–3mcg/kg/min; maximum dose: 5mcg/kg/
min for an 80kg patient
Hypotension (more potent than seen with
nitroglycerin), tachyphylaxis, reex
tachycardia, cyanide toxicity
Caution in renal dysfunction—Can
accumulate. Patients with renal impairment
are at higher risk of cyanide toxicity
Invasive monitoring generally required due to
risk of hypotension (potent afterload reducer)
May be particularly useful in an ADHF
patient with HFrEF and dyspnea who is
hemodynamically stable due to afterload
reduction
Duration of therapy is usually short term due
to tachyphylaxis and the risk of cyanide
toxicity
11.10 Cardiogenic Shock
Cardiogenic shock has a high mortality rate and is characterized by low cardiac
output and hypotension.
In those who have progressed from ADHF to cardiogenic shock, intravenous
inotropic support should be utilized to preserve end-organ function and maintain
perfusion [2].
Despite their common use, there are few prospective trials or randomized controlled evidence to guide their use. Additionally, there is also a lack of robust data to
guide the choice of one agent over another; factors such as blood pressure and presence of concomitant arrhythmia tend to guide agent selection [2].
Although all agents that have beta-1 agonism can be considered inotropes, in the
context of heart failure, generally the “true” inotrope agents include milrinone and
dobutamine (Table11.6).
Key factors to consider between the agents are their effects on blood pressure and
their route of elimination. Milrinone is renally excreted and can accumulate in those
with renal failure. Table11.6 reviews key differences between these agents.
11 Acute Decompensated Heart Failure
Table 11.6 Inotrope comparison in ADHF
IV dobutamine IV milrinone
Mechanism of
action
Renally cleared/
renal dose
adjustment
Side effects Tachyarrhythmias Tachyarrhythmias and hypotension
Effect on cardiac
output
Effect on SVR Minimal Decrease
Clinical pearls Do not co-administer with beta-
Beta-1 agonist PDE-3 inhibitor
No Yes
Increase Increase
Caution in renal dysfunction as
ers as mechanisms of action
block
cancel each other out
accumulation and prolonged
hypotension can occur
307
11.10.1 Inotrope Clinical Pearl
Oftentimes, patients in ADHF may require vasopressors in addition to inotropes due
to hypotension. A commonly seen scenario is a patient with ADHF in acute kidney
injury on milrinone who has become hypotensive and was started on a vasopressor
such as norepinephrine to keep mean arterial pressures (MAP) up. Because milrinone can cause hypotension and is renally eliminated, it can accumulate in those
with renal dysfunction. Oftentimes, this accumulation can be part of the reason why
hypotension occurs. Instead of relying on the addition of vasopressors which can
increase afterload making it harder for a struggling HFrEF heart to push blood out,
switching from milrinone to dobutamine may eliminate the need for pressors.
11.11 Management ofPatients withADHF andAtrial
Fibrillation (AF)
As heart failure progresses and the heart continues to remodel, arrhythmias can
become increasingly prominent. Chronic atrial brillation can become increasingly
common in these patients as these structural changes occur. However, even in those
without chronic AF and mild structural changes, ADHF may precipitate acute episodes of AF due to volume overload. As a patient becomes volume overloaded, the
volume of blood that the left atrium needs to handle increases, and may cause stretching of the atrial wall, thus precipitating acute atrial brillation. In this patient, the
need for diuresis is the underlying treatment of the acute atrial brillation episode.
In general, cardioversion should be considered in those with new-onset atrial
brillation and in those with hemodynamic instability.
308
However, in patients with long-standing heart failure and chronic atrial brillation, cardiac structural changes are advanced and the chance of meaningful and
successful rhythm control is oftentimes low; oftentimes, these patients are best managed with rate control strategies such as beta-blockers and/or digoxin. Keep in mind
that any medications such as non-DHP calcium channel blockers should be avoided
in those with systolic heart failure due to their negative inotropic properties [2].
Other precipitating causes for atrial brillation should also be investigated such
as hormonal (e.g., hyperthyroidism), toxicologic, acute infection, or other medications (e.g., inotropes) [2].
C. E. Kulig
11.12 Digoxin
11.12.1 The Role ofDigoxin
The role of digoxin in heart failure is somewhat controversial, as there is conicting
data on whether or not it benets patients with heart failure, and it is not included in
the “pillars” of guideline-directed medical therapy (GDMT) management for these
patients [2]. However, digoxin is often considered as a rate control agent, especially
in those in the intensive care setting who cannot tolerate the potential blood pressurelowering effects of other rate control agents, such as beta-blockers, and who are not
candidates for non-dihydropyridine calcium channel blockers (e.g., those with HFrEF).
Digoxin can be theoretically benecial to patients with heart failure given its
positive inotropic properties and has two main mechanisms of action. For rate control, digoxin has an indirect effect on both the sinoatrial and atrioventricular nodes
by stimulating the vagus nerve and vagal tone, thus decreasing the heart rate.
11.12.2 Mechanism ofAction
Digoxin exerts its positive inotropic activity indirectly by inhibiting the Na+/K+
ATPase pump on the surface of the myocytes. To truly understand its action, you
must rst understand the function of two key pumps on the surface of the myocytes.
The Na+/K+ ATPase is present on the surface of myocytes (Fig.11.4). As the
name “ATPase” suggests, this pump requires energy (in the form of ATP) to actively
pump ions across its channel. In other words, this pump must move ions against a
concentration gradient.
At baseline, there is a high level of sodium extracellularly (aka outside the cells)
and a high level of potassium intracellularly (within the cells) (this is why if blood
samples are shaken or mishandled and the red blood cells lyse, you can end up with
false hyperkalemia).
The Na+/K+ ATPase pumps 3Na+ out of the cell for every 2K+ it pumps into the
cell, thus leaving the cellular membrane with a net negative charge.
11 Acute Decompensated Heart Failure
309
Fig. 11.4 Digoxin’s mechanism of action
310
Meanwhile, there is also a Na+/Ca+2 exchanger pump located on the surface of
these cells. This pump is not an ATPase and therefore does not require energy to
work. In other words, this pump works with the concentration gradient and pumps
Ca+2 out of the cell in exchange for Na+ based on the concentration gradient.
When digoxin inhibits the Na+/K+ ATPase, the pump no longer pumps Na+ out
of the cell—thus, intracellular concentrations of sodium increase.
As mentioned above, usually the Na+/Ca+2 exchanger pumps Ca+2 out of cell
and Na+ in to the cell with the concentration gradient—in other words, when intracellular Na+ levels are high, this pump will become less active, and as a result,
intracellular calcium concentrations will increase.
This is how digoxin can exert a positive inotropic effect and increase force of
contraction. By inhibiting the Na+/K+ ATPase, intracellular calcium levels rise
indirectly causing a higher force of contraction.
C. E. Kulig
11.12.3 Loading Dose
A loading dose can be considered for digoxin for the management of atrial brillation in patients with heart failure. It should be noted that loads are generally not
given in heart failure patients in the absence of atrial brillation. Dosing varies but
is often given intravenously at a dose of 0.25–0.5mg over several minutes. Repeat
doses of 0.25mg IV may be given every 6h, not to exceed 1.5 mg within 24 h
(though often in practice 1mg is used as the cap).
11.12.4 Maintenance Dosing
After initial loading, maintenance dosing is initiated. Oral doses range from
62.5mcg to 250mcg daily; however, renal function must be considered when selecting doses as digoxin is renally cleared and is a narrow therapeutic index drug. In
patients with chronic kidney disease (CKD) or acute kidney injury (AKI), maintenance doses should be decreased. Likewise, if a patient has been on digoxin prior to
admission and presents in AKI, maintenance doses should still be adjusted or even
stopped depending on the degree of AKI.As with other medications in the critically
ill, oftentimes urine output may be the best marker of real-time kidney function.
11.12.5 Monitoring
As mentioned above, digoxin is a narrow therapeutic index drug—this means that
small differences in dose or blood concentrations may lead to either drug failures
(subtherapeutic) or toxicities (supratherapeutic).
11 Acute Decompensated Heart Failure
Digoxin levels should be taken as troughs, ideally immediately prior to the next
dose; however, levels at least 6h after an oral dose can be considered acceptable. Prior
to 6h after dosing, digoxin is still undergoing redistribution into target tissues (e.g., it
will likely be falsely high). It is important to note that in patients with heart failure as
a comorbidity, goal digoxin levels are 0.5–0.9ng/mL, which are signicantly lower
than goal ranges for patients without heart failure (e.g., 0.8–2.0ng/mL) [2].
311
11.12.6 When toGet aLevel?
The half-life of digoxin is fairly long, 36–48h in adults with healthy renal function,
and can be as high as 3.5–5days in those with renal impairment. Because it takes
four to ve half-lives for a drug to reach steady state, this means that digoxin levels
will not represent steady-state levels for a minimum of 6days. Early levels can be
considered if toxicity is expected but, in general, will be falsely low if taken prior
unless loading doses have been given recently.
11.12.7 Distribution
Digoxin primarily distributes into the heart, liver, kidneys, and skeletal muscle.
Therefore, caution should be taken in giving high doses to obese patients, and
digoxin does not distribute extensively into fat. Patients with extremes of skeletal
muscle (e.g., elderly malnourished patients vs. bodybuilders) may require different doses.
11.12.8 Drug-Drug Interactions
Digoxin has multiple drug-drug interactions and is a substrate of p-glycoprotein.
Always assess a patient’s prole for drug-drug interactions when starting digoxin or
when starting new medications.
11.12.9 Digoxin Toxicity
Aside from renal function, potassium levels are important to monitor during digoxin
therapy. Hypokalemia may predispose a patient to digoxin toxicity; once digoxin
toxicity occurs, hyperkalemia may occur. Other signs and symptoms of digoxin
toxicity include bradycardia, GI upset and diarrhea (these are the most common
symptoms), visual disturbances (yellow-green disturbances), and syncope.