The Unit: A Cardiology Blog: heart failure

Showing posts with label heart failure. Show all posts

Saturday, January 11, 2014

Digoxin, digoxout: an appraisal of digoxin immune fab

Preface: The inspiration for this topic came from an exchange on Twitter between @PharmERToxGuy, @DavidJuurlink, and I, representing one of the things I love most about #hcsm -- the opportunity for dialogue across diverse backgrounds and practice settings. In this particular case, we debated the appropriate use of digoxin immune fab (DigiFab^®), which was certainly challenging to do in segments of 140 characters or less. Below I have outlined a more detailed rationale for why I advocate its conservative use in the management of digoxin toxicity.

My reasons for advocating the conservative use of digoxin immune fab (DigiFab^®) are unrelated to its efficacy, as it is undoubtedly the most effective antidote for digoxin toxicity. Instead, I contend that in many cases, it is an unnecessary and overly aggressive -- if not a costly -- approach to a scenario that may be just as effectively managed by thoughtful monitoring and supportive therapy. While it can be challenging to predict whether patients might require fab therapy at a later time, I believe a more judicious approach can be made possible by considering the severity of toxicity, the circumstances in which it occurred, and whether fab administration would substantially alter the clinical course of the patient.

Digoxin toxicity is difficult to characterize as a result of heterogeneity in the literature (e.g., study methods, definitions for toxicity) and how use of digoxin has evolved over time (i.e., patient populations, indications, dosing, target concentrations). As an example, a patient with a ventricular arrhythmia and serum digoxin concentration of 10.0 ng/mL in 1994 and one with symptomatic bradycardia and a serum digoxin concentration of 2.0 ng/mL in 2014 are both classified as having digoxin toxicity (and both cases often characterized simply as a dysrhythmia), although the severity of their presentations is vastly different. These and similar challenges may explain in part some of the discrepancies in the literature, as some studies demonstrate a decline in the prevalence of digoxin toxicity while others claim it has not changed [1-3].

What has changed considerably over the last several decades is how digoxin is used. In the late 1980s and early 1990s, it was not uncommon for the vast majority of patients with heart failure to be receiving digoxin therapy -- as many as 9 out of 10 in some studies [4]. Today those numbers are substantially fewer, as digoxin therapy is often reserved for those patients with advanced symptomatic disease. When it is used in this population, a lower serum concentration (i.e., 0.5 - 0.9 ng/mL) is targeted, ameliorating many of the more severe adverse effects observed in the setting of elevated concentrations in the past [5,6]. Additionally, patients with heart failure are likely to be on concomitant therapies (e.g., beta blockers, aldosterone antagonists, implantable defibrillators and other devices) that may confer protection from some of the more severe forms of digoxin toxicity or prevent it altogether (e.g., less hypokalemia as a result of aldosterone antagonist use). Similar trends, including a decline in overall digoxin use and reservation for only the most advanced cases, have also been observed in the atrial fibrillation population, where lenient rate control targets have obviated the need for digoxin in many patients [7-9].

Whether or not these differences impact the number of patients presenting with digoxin toxicity, they likely influence how, and perhaps more importantly, why patients present. In my practice setting, digoxin toxicity often manifests as a result of something more problematic (i.e., renal impairment as a result of worsening heart failure, emergence of underlying conduction abnormalities) rather than the consequence of a drug-drug interaction or acute overdose. In these latter cases, fab administration may be a reasonable approach for preventing hospital admission. However, for the 4 out of every 5 patients with digoxin toxicity who require hospitalization either way, fab administration may not confer substantial benefit over what would be provided by monitoring and symptomatic support [3].

Patients with worsening heart failure often require days of clinical evaluation whether or not they have signs or symptoms consistent with digoxin toxicity (which can often mimic those of worsening heart failure). Furthermore, complete digoxin withdrawal may actually worsen outcomes in this population [6, 10]. In the case of renal impairment, digoxin immune fab may not be an ideal strategy if renal impairment is advanced or does not improve substantially, as it too requires renal clearance and is not removed by hemodialysis. Although an earlier review substantiates fab use in patients with mild to moderate renal impairment, several limitations make it difficult to derive similar conclusions when renal impairment is severe [11]. Although manifestations of digoxin toxicity may initially improve in this latter population, recrudescent toxicity may occur days to weeks later as digoxin redistributes from peripheral tissues, a phenomenon that has been well-documented in the literature [12, 13]. For patients on chronic digoxin therapy, this may occur even in the absence of severe renal impairment. In these scenarios, fab use may provide clinicians with a false sense of security, resulting in less frequent monitoring or premature discharge when the patient should be observed for recrudescent toxicity or worsening signs and symptoms of heart failure.

Finally, as I alluded to in several instances above, digoxin immune fab may not be the most cost-effective strategy in a given patient. Notably, many cost-effectiveness analyses are a decade or more older, making them subject to the same limitations as the epidemiological studies described above. Given the financial woes of today's health care environment, cost-effectiveness should be a factor in determining whether a therapy is indicated, especially when less expensive alternatives exist or if the therapy is unlikely to alter the long-term outcome of the patient. Otherwise, we endanger our ability to use these more expensive therapies in patients who have no alternatives. In the US, a single vial of digoxin immune fab costs between $1200-1500 (or more), and most patients require multiple vials based on their body weight and/or serum digoxin concentration. Unless hospitalization can be substantially shortened or avoided altogether, the cost of fab therapy may quickly outpace reimbursement. For example, the average reimbursement for a drug overdose at my institution runs about $6500, whereas a heart failure admission runs around $8300 [14].

That being said, the following are situations where I would definitely recommend the use of digoxin immune fab:

Ventricular arrhythmias, accelerated junctional rhythms
Life-threatening bradyarrhythmias unresponsive to chronotropic agents (and when temporary pacing is not readily available)
Acute mental status changes
Acute overdose

I generally avoid recommending fab on the basis of a specific serum digoxin concentration alone, as these are often open to interpretation (e.g., timing of ingestion, laboratory draw). Furthermore, a toxic concentration is any concentration that results in clinically meaningful adverse sequelae in a given patient. A serum digoxin concentration of 2.0 ng/mL resulting in a ventricular arrhythmia is toxic and requires emergent treatment, while a patient with a serum concentration of 4.0 ng/mL and no adverse sequelae requires close observation but emergent therapy is not warranted.

Outside the indications outlined above, the strategy I most commonly recommend for managing digoxin toxicity is to simply facilitate urine output (e.g., intravenous fluids), provide supportive therapy when necessary, and monitor closely should a need for fab arise. If the patient has symptomatic bradycardia, this may require intermittent use of a chronotropic agent. Although atropine is often recommended in this scenario, its half life makes it less than ideal for counteracting a drug that may require hours to days to clear. Instead, I prefer the use of a dopamine infusion in this setting, as it may be turned on or off (or titrated) based on patient need. Importantly, dopamine and other catecholamine-based therapies should be monitored closely so as not to exacerbate other rhythm disturbances commonly associated with digoxin toxicity.

Peer review: Special thanks goes to Jo Ellen Rodgers, PharmD, FCCP, BCPS (AQ Cardiology), a clinical associate professor at the University of North Carolina Eshelman School of Pharmacy, and Jonathan Cicci, PharmD, BCPS, a clinical pharmacy specialist in cardiology at the University of North Carolina Health Care for their review of this entry.

References

Saturday, November 23, 2013

TOPCAT: not purrfect, but a signal of benefit with spironolactone in heart failure with preserved ejection fraction

This entry is the second part of a series on late-breaking clinical trials from the American Heart Association Scientific Sessions 2013. For a list of all reviewed trials, click here.

Note: details of this trial have not yet been published, so the following has been compiled from ClinicalTrials.gov and results presented at AHA13.

Summary:
In the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial, 3445 patients with heart failure with preserved ejection fraction (HFpEF) were randomized in a double-blind fashion to spironolactone (15 mg titrated to 30-45 mg per day) or placebo. Investigators defined HFpEF as the presence of at least one sign and symptom of heart failure and EF > 45%. Patients were also required to have controlled systolic blood pressure (SBP < 140 mmHg or < 160 mmHg if taking > 3 antihypertensive medications) and serum potassium < 5.0 mEq/L. The mean systolic blood pressure at enrollment was 129.2±14.0 mmHg and potassium was 4.3±0.4 mEq/L. Other notable characteristics at baseline included the presence of hypertension in 91% of patients and chronic kidney disease in 39%. Additionally, 84% of patients were taking an ACE inhibitor (ACEi) or angiotensin receptor blocker (ARB), and 82% were taking a diuretic.

After an average follow-up of 3.3 years, spironolactone failed to reduce the primary endpoint, a composite of cardiovascular mortality, cardiac arrest, or heart failure hospitalizations (18.6% vs. 20.4%, HR 0.89 (95% CI 0.77-1.04), p = 0.138). Spironolactone was more effective at reducing heart failure hospitalizations alone (12.0% vs. 14.2% with placebo, HR 0.83 (95% CI 0.69-0.99), p = 0.042), but it also doubled the rate of hyperkalemia (defined as serum potassium > 5.5 mEq/L) (18.7% vs. 9.1% with placebo, p < 0.001) and increased the incidence of renal failure (data not available at the time of writing). In a post-hoc analysis of TOPCAT, regional variability was observed, as patients in the Eastern Hemisphere (primarily Russia and the Republic of Georgia) did not benefit from the addition of spironolactone while a slight benefit was observed among patients in the Americas (HR 0.82 (95% CI 0.69-0.98)).

Commentary:
The results of TOPCAT follow a consistent theme in patients with HFpEF – no therapies have been shown to have a substantial impact on disease progression and it remains an incredibly difficult condition to treat. Optimism for spironolactone had been high due in part to the results of Aldo-DHF, where its use resulted in improvements in left ventricular function, although no differences in clinical endpoints were observe [1]. Authors attributed this lack of benefit to the short duration of the study and its relatively young, healthy population. However, as TOPCAT revealed, spironolactone does not appear to confer significant benefit even when a larger and sicker population is followed for a longer period of time.

Several findings from TOPCAT are worth further comment. Although the results were largely negative, the fact that spironolactone reduced heart failure hospitalizations may be a signal of benefit in carefully selected patients, such as those who can be monitored closely for hyperkalemia and changes in renal function. Although some experts have heralded it as the first study to show a benefit in HFpEF, this is not entirely accurate, as candesartan demonstrated similar improvements in heart failure hospitalizations as a secondary endpoint of the CHARM-Preserved trial [2]. Nonetheless, it does represent another potential approach in a patient population with so few therapeutic options.

Some of the baseline characteristics of patients in TOPCAT also warrant further discussion. The vast majority had hypertension, which is not altogether unsurprising given its role in the pathophysiology of HFpEF. However, the fact that patients were required to have controlled hypertension may have limited the impact of spironolactone. I recognize this probably had to be done to assess whether the potential impact of spironolactone was independent of its effects on blood pressure. However, given the number of trials showing benefit with spironolactone in refractory hypertension (as well as the role of hypertension in HFpEF), perhaps spironolactone would have been better than the medication therapies patients were required to be on in order to meet inclusion criteria. For example, the incidence of hyperkalemia (and the results this may have had on the primary endpoint) may not have been so high had so many patients not been taking ACEi or ARB therapy.

The higher rate of renal failure observed in the spironolactone arm is also intriguing, as a similar result was observed in Aldo-DHF, but this finding is not consistent with trials of aldosterone antagonists in patients with heart failure with reduced ejection fraction (HFrEF). Many patients with HFpEF are notoriously preload dependent, which can complicate strategies for maintaining appropriate volume status. Spironolactone is a weak diuretic at the low doses commonly used in HFrEF and usually has only minimal impact on volume status in most patients, even when combined with loop diuretics. However, could it have had a more substantial impact in patients with HFpEF given the more tenuous nature of their volume status? In TOPCAT, 4 out of every 5 patients were already on a diuretic at baseline – could the addition of spironolactone have been enough to tip the balance toward hypovolemia and subsequent renal failure?

All in all, I would still consider spironolactone in select patients with HFpEF (i.e., those who can be monitored for changes in serum potassium concentrations and renal function). I would especially consider its use in patients with HFpEF and refractory hypertension as well as those for whom only minor diuresis is necessary to maintain volume status. That being said, I am definitely cautious about its use in combination with diuretics or ACEi or ARB therapy. In fact, given the lack of benefit shown with these other agents, I think it would be reasonable to consider spironolactone first based on its potential for reducing heart failure hospitalizations (and potential for adverse events when combined with other agents).

Bottom line:
Similar to the agents studied before it, spironolactone does not substantially impact clinical outcomes in patients with HFpEF. It appears to reduce heart failure hospitalizations, but does so at the expense of increased rates of hyperkalemia and renal failure. Accordingly, its use should only be considered in select patients.

References

Thursday, November 21, 2013

ROSE AHF: Mostly thorns for low-dose dopamine, nesiritide in acute decompensated heart failure and renal impairment

This entry is the first part of a series on late-breaking clinical trials from the American Heart Association Scientific Sessions 2013. For a list of all reviewed trials, click here.

Summary:
In the Renal Optimization Strategies Evaluation in Acute Heart Failure (ROSE AHF) trial [1], patients with acute decompensated heart failure (ADHF) and renal impairment were randomized in a double-blind fashion to 72 hours of low-dose dopamine (2 mcg/kg/min), low-dose nesiritide (0.005 mcg/kg/min), or placebo. Patients were eligible for enrollment if they had at least one sign and symptom of ADHF (irrespective of ejection fraction) and an estimated glomerular filtration rate (eGFR) of 15-60 mL/min/1.73 m². Baseline characteristics were similar between the three groups with a median systolic blood pressure of 115 mmHg, median ejection fraction (EF) of 33% (over two-thirds with EF < 50%), and eGFR of 42 mL/min/1.73 m².

Low-dose dopamine failed to produce a difference in the co-primary endpoints of cumulative urine output (UOP) or change in cystatin C at 72 hours compared to placebo (differences in UOP of 8254 mL and 8296 mL, respectively, p = 0.59). Drug discontinuation was similar between the two groups, although low-dose dopamine was more likely to be discontinued for tachycardia (7.2% vs. 0.9% with placebo, p < 0.001) while placebo was discontinued more frequently for hypotension (10.4% vs. 0.9% with low-dose dopamine, p < 0.001). Likewise, low-dose nesiritide also failed to confer significant differences in the co-primary endpoint (differences in UOP of 8574 mL and 8296 mL with placebo, p < 0.49). Compared to placebo, hypotension was more common in the low-dose nesiritide group (18.8% vs. 10.4% with placebo, p = 0.07). Results for the co-primary endpoints were similar across subgroups with the exception of EF. Compared to dopamine, patients with preserved EF tended to do better with placebo (p = 0.01 for interaction). In contrast, nesiritide appeared to benefit those with reduced EF, although this difference was not statistically significant. No differences in clinical endpoints (e.g., symptom relief, death, rehospitalization) were observed between any of the groups.

Commentary:
Those who follow my blog know that I am no fan of using low-dose dopamine for the purposes of renoprotection in ADHF (previous entries here and here). While I am not opposed to its use as a mixed inotrope/vasopressor (i.e., for patients in whom peripheral vasodilation from a traditional inotrope might compromise hemodynamics), the renoprotective properties of low-dose dopamine have been widely discredited [2]. Given the lack of benefit observed in ROSE AHF, hopefully this myth has been debunked once and for all. Importantly, dopamine not only failed to produce a significant difference in the co-primary endpoints; it also resulted in lower rates of hypotension and higher rates of tachycardia, indicating that even at doses as low as 2 mcg/kg/min, dopamine is not entirely selective for renal vascular beds.

Unfortunately, a signal of differential response between those with reduced versus preserved EF was observed (although not statistically significant), which may provide just enough justification to continue evaluating this approach in select subgroups. Although the inclusion of a low-dose nesiritide arm in this study was an interesting hypothesis, the fact that it did not produce a meaningful difference in outcomes is not altogether unsurprising.

Bottom line:
Neither low-dose dopamine nor low-dose nesiritide provide renoprotective effects in patients with ADHF and renal impairment.

References

Sunday, September 22, 2013

Should tolvaptan be used routinely for hyponatremia in patients with heart failure? Na.

One can hardly open a medical publication without seeing an advertisement for Otsuka's tolvaptan (Samsca^®), an oral vasopressin antagonist approved for the management of hyponatremia in the setting of heart failure. Despite only minimal improvements in clinical trials and new warnings issued by the US Food & Drug Administration (FDA), the use of tolvaptan remains a topic of interest.

Hyponatremia is common among hospitalized patients and is associated with poor prognosis among those with heart failure [1]. What is less clear, however, is whether this relationship is a result of cause-and-effect or merely correlation. The latter is worth investigating, as this has been observed with other surrogate markers that were once considered potential therapeutic targets, with hemoglobin being one of the most recent to be called into question [2].

To date, the available evidence suggests that, while serum sodium concentrations can be improved with vasopressin antagonist therapy, these changes do not appear to confer meaningful differences in clinical outcomes. In SALT, a trial evaluating the use of tolvaptan in patients with hyponatremia (a third of whom had heart failure), patients randomized to tolvaptan experienced improvements in urine output and serum sodium concentrations, but this only persisted while patients were on therapy; in less than a week after discontinuing tolvaptan, serum sodium concentrations returned to baseline [3]. In EVEREST, a trial specifically enrolling patients with acute decompensated heart failure (irrespective of serum sodium concentrations), those randomized to tolvaptan experienced greater reductions in body weight (although less than a kg difference versus placebo) and improvements in some but not all heart failure signs and symptoms [4]. Tolvaptan failed to impart any clinically meaningful differences in mortality, hospitalizations, worsening heart failure, or quality of life [5]. Serum sodium concentrations improved initially but these differences dissipated with time.

In other words, tolvaptan and other vasopressin antagonists appear to have no appreciable effect on the underlying pathophysiology of heart failure. While serum sodium concentrations can be improved, recurrence of hyponatremia should be expected following cessation of therapy if underlying causes (e.g., reduced renal perfusion, hypervolemia, etc.) are not addressed. Coupled with emerging evidence of liver injury that eventually prompted FDA to limit its use to less than 30 days (and avoid it altogether in patients with evidence of liver impairment), tolvaptan has only limited utility in patients with heart failure.

There are a couple of scenarios where a short course of tolvaptan may be considered:

Patients with symptomatic hyponatremia at any serum sodium concentration; or,
As a temporizing measure (i.e., up to 5 days or so) to stabilize critically low serum sodium concentrations (< 125 mEq/L, to prevent patients from becoming symptomatic) while underlying causes are corrected, i.e., discontinuation of potentially offending drugs (select antipsychotics and antidepressants, thiazide diuretics), optimization of standard heart failure therapies, addition of vasodilators or inotropes to improve renal perfusion, or aggressive diuresis to correct hypervolemia.

That being said, there is evidence that suggests small boluses of hypertonic saline can improve hyponatremia in these scenarios without worsening fluid balance [6].

In summary, routine use of tolvaptan should be avoided, as it both fails to improve long-term clinical outcomes and represents an incredibly expensive strategy for improving symptoms and/or treating a surrogate marker that has yet to be associated with improved clinical endpoints. Although the price of tolvaptan has likely come down since its introduction to the market, at one time its use represented spending about $50 for each mEq/L increase in serum sodium concentration per day, and about $3 for each additional mL of urine output per day.

Note: I borrowed the title for this entry from an old Chemistry Cat meme, so let me end by giving credit (or blame?) to whomever it is due.

References

Sunday, August 11, 2013

The trouble with diltiazem infusions

This post has been updated, and moved to a new blog at the following URL:
http://blogs.pharmacy.umaryland.edu/atrium/2016/03/18/the-trouble-with-diltiazem-infusions/

Sunday, May 5, 2013

Cocaine and beta blockers: all it's cracked up to be?

This post has been updated, and moved to a new blog at the following URL:
http://blogs.pharmacy.umaryland.edu/atrium/2017/08/29/cocaine-and-beta-blockers-all-its-cracked-up-to-be/

Monday, June 4, 2012

Innovation or impersonation: low-dose dopamine in heart failure

Although renal dysfunction is commonly associated with the use of aggressive diuretic therapy in patients with acute decompensated heart failure (ADHF), strategies for preventing or overcoming this phenomenon remain a considerable challenge. Low-dose dopamine has been proposed as a novel approach for promoting diuresis in patients with ADHF, but its use in this setting remains controversial. Enthusiasm for this strategy was renewed when preliminary results from the DAD-HF trial were announced in early 2010; however, when full details of the trial became available later that year [1], many clinicians felt that the trial's limitations outweighed many of its proposed benefits.

In DAD-HF, 60 patients with ADHF of New York Heart Association (NYHA) Class IV severity were randomized to one of two treatment arms: (1) a high-dose furosemide infusion (20 mg/hour), or (2) a low-dose furosemide infusion (5 mg/hour) plus dopamine infusion (5 mcg/kg/min). Patients with severe renal impairment (GFR < 30 mL/min) were excluded. Prior to being allocated to one of the two treatment arms, all patients received a 40-mg intravenous bolus of furosemide. All study infusions were discontinued after a total of 8 hours and further management was left to the discretion of the attending physician.

No differences in total urine output (UOP) or dyspnea symptoms were observed at 8 hours. Significant differences in the incidence of worsening renal function (defined as > 0.3 mg/dL rise in serum creatinine at 24 hours) were observed in the high-dose furosemide group (30%, compared to 6.7% in the low-dose furosemide plus dopamine group, p = 0.042); however, a difference was not observed when a second definition for worsening renal function was used (> 20% decrease in GFR at 24 hours). When patients were observed for the duration of hospitalization, results were reversed; no differences were observed when the change in serum creatinine was used to define renal dysfunction, whereas a greater percentage of patients in the high-dose furosemide group had worsening renal function when GFR was used (69.2% versus 34.6%, p = 0.025). No differences in length of stay, readmission rate, or mortality were observed.

Although the results of DAD-HF are not exactly compelling, the authors go on to make several bold statements about the proposed renoprotective benefits of dopamine. However, the limitations of this trial do warrant further discussion, as I believe they significantly influence how the results should be interpreted and applied to clinical practice.

The trial was small (n = 60) and included a considerably homogenous patient population. The hemodynamic effects of dopamine in ADHF are a function of disease severity [2], so it is unknown how patients of other NYHA classes would respond to this management strategy;
The study protocol only ran for a total of 8 hours. Given the pharmacokinetics of intravenous furosemide, a significant portion of the clinical response at 8 hours (i.e., when urine output was recorded) can attributed to the initial intravenous bolus dose (which was administered to all patients), and perhaps the first several hours of the continuous furosemide infusion. Given the impaired clearance in patients with ADHF, it is unlikely that many patients were at steady state when the infusions were discontinued and the 8-hour assessment of urine output was performed.
Assessments of efficacy were performed after 8 hours while assessments of safety were made after 24 hours (and throughout the course of hospitalization). However, no information was provided on how patients were managed after their 8-hour protocols were completed (left to the discretion of the attending physician), which could have influenced these results.
The investigators did not include a low-dose furosemide only group (i.e., no dopamine), so it is unknown whether the differences observed in DAD-HF can be attributed to dopamine per se, or the lower dose of furosemide used in this group. As the authors note in their discussion, the results of the DOSE trial demonstrated that higher doses of furosemide (whether administered as an intermittent intravenous bolus or continuous infusion) are clearly associated with worsening renal function in patients with ADHF [3]. The authors attempt to discount the possibility that their findings was due to lower doses of furosemide alone by claiming that the addition of dopamine provided a comparable degree of diuresis as high-dose furosemide but without the subsequent worsening of renal function. However, as described above, assessments of efficacy in DAD-HF were performed at 8 hours (versus 72 hours in DOSE), so this hardly seems like a fair comparison.
The dose of dopamine (5 mcg/kg/min) used in DAD-HF is hardly "low-dose" by any definition. In previous studies, the doses of dopamine thought to confer renoprotection are < 2 mcg/kg/min, where activation of renal dopaminergic receptors predominate. However, at doses of 3-5 mcg/kg/min, dopamine is known to exert positive inotropic effects, where improvements in renal blood flow can also be attributed to improved cardiac output. Even in the studies cited by the authors, the doses at which dopamine improved renal hemodynamics were also those at which cardiac index was highest [2]. In other words, it cannot be said from the present study that dopamine at 5 mcg/kg/min offers any greater degree of renoprotection than if a traditional inotrope (e.g., dobutamine, milrinone) had been used.
Finally, only surrogate markers (e.g., serum creatinine, GFR calculations) were used to determine changes in renal function. While these markers are certainly the most practical to measure and have been correlated with clinical endpoints in other investigations, it seems difficult to justify their use in some of the bold statements made by the authors of DAD-HF. No comments are made on more clinically relevant measures of renal dysfunction (e.g., time to continuous renal replacement therapy [CRRT]), or whether changes in serum creatinine or GFR were still present at 30 or 60 days after randomization. While the authors present an excellent review on the pharmacologic effects of dopamine, if these effects do not translate into meaningful improvements in clinical outcomes, what difference dose it make?

Therefore, based on the limitations highlighted above (and no additional evidence to the contrary), I tend to recommend against using dopamine as a strategy for preventing or ameliorating the renal dysfunction associated with aggressive diuretic therapy. While the adverse effects of dopamine at doses of < 5 mcg/kg/min are arguably low, I do believe it often delays initiation of more appropriate management strategies when necessary (i.e., inotropes, CRRT) while we wait to see if it will work. That being said, I am not entirely opposed to the use of dopamine in patients with ADHF, as there are some scenarios where it has its advantages:

Patients with mixed cardiogenic/septic shock or in whom the primary contributor to shock is unknown;
Patients who require inotrope therapy but have labile or tenuous blood pressures and in whom central hemodynamic parameters are unknown (i.e., scenarios in which dobutamine or milrinone may be a riskier choice); in this situation, dopamine may serve as a temporary measure until blood pressures improve (or a pulmonary artery catheter can be placed), or as a bridge to initiating a traditional inotrope;
Patients whose hemodynamics are especially sensitive to changes in intravascular fluid volume, such as those associated with aggressive diuresis or intermittent hemodialysis.

Otherwise, I am not sure that DAD-HF contributes much to our knowledge on the management of patients with ADHF or how we might avoid renal injury in the context of aggressive diuretic therapy. Additionally, based on the reasons outlined above, I am not sure it is an appropriate strategy to attempt in patients with ADHF simply because we do not yet have a more proven alternative.

For a discussion on the myths of low-dose dopamine in critically ill patients with renal dysfunction (i.e., in the absence of ADHF), please see this post.

References