Hyperdiuresis involves combining hypertonic saline with a loop diuretic for management of diuretic-resistant volume overload. This may seem a bit counter-intuitive, but there are several reasons why it might work:
- Hypochloremia promotes sodium retention; this could be reversed with hypertonic saline.
- Hypertonic saline could osmotically pull fluid into the intravascular space, thereby promoting diuresis without intravascular volume depletion.
- Increasing the intravascular volume prior to diuresis could temporarily reduce neurohormonal sodium retention (e.g. renin/angiotensin/aldosterone and sympathetic nervous system stimulation), thereby facilitating diuresis.
- Hypertonic saline alone reduces renin production (which is helpful), but causes renal vasoconstriction via tubuloglomerular feedback. Loop diuretics block tubuloglomerular feedback – so the combination of hypertonic saline plus loop diuretics could reduce renin levels without triggering renal vasoconstriction.
There is already a fair body of evidence supporting hyperdiuresis (reviewed in a recent blog here). Nonetheless, this remains controversial, so additional evidence is needed.
Griffin et al: Real world use of hypertonic saline in refractory acute decompensated heart failure
This is a retrospective cohort study of patients at Yale New Haven Hospital with acute decompensated heart failure who received hyperdiuresis between 2013-2017.1 Forty patients were identified, including a total of 50 admissions and 58 episodes of hyperdiuresis therapy (in eight cases, repeat therapy was needed during a single admission).
Baseline data are shown below. This is an impressively sick cohort of heart failure patients. 64% of patients were on inotropes and/or vasopressors. Patients were refractory to large doses of furosemide (mean of 400 mg/day) – which by itself is a poor prognostic sign (equivalent to failing a furosemide stress test). On average, patients had soft blood pressure (mean MAP 72 mm) with poor cardiac function (mean LVEF 35%) and poor renal function (mean GFR 36 ml/min). Mortality was high.
treatment details
Treatment consisted of 150 ml 3% NaCl infused over 30 minutes, repeated up to twice daily. Loop diuretic was given simultaneously with hypertonic saline. Patients received a median of 3 treatments (with an interquartile range of 2-7).
efficacy data
Hyperdiuresis caused an increase in urine output, leading to weight loss. Most notably, this achieved a net fluid loss (which was not attainable before starting hyperdiuresis):
Perhaps most notable is a suggestion that hyperdiuresis may have decreased the serum creatinine (figure below). This replicates prior results from an RCT by Issa et al.2 These are small changes in creatinine, of dubious clinical significance. Nonetheless, this is a reassuring indication that hyperdiuresis doesn’t cause acute kidney injury (rather, it probably improves renal function due to effective decongestion).
safety data
One concern with hyperdiuresis might be causing cardiogenic pulmonary edema. Given the exuberant diuretic response, this doesn’t seem to be an issue (i.e. administered fluid is rapidly excreted). Overall, hyperdiuresis didn’t affect oxygenation:
Another concern with hyperdiuresis is that it could cause dangerous elevations of sodium level (since both 3% NaCl and loop diuretics do this independently). Increases in sodium level were observed, but the effects were generally moderate (figure below). Notably, 59% of patients were on thiazide diuretics at baseline, which may have tended to brake the rise in sodium.
Most patients were mildly hyponatremic at baseline. Thus, this increase in sodium tended to push patients back to normonatremia and normochloremia:
limitations
Substantial limitations are inevitable with any retrospective cohort study, no matter how well it is executed.
The patients were chosen based on clinician judgement, rather than any pre-specified criteria. Thus, these patients may not reflect the entire population of patients with decompensated heart failure and diuretic resistance. In particular, it’s likely that patients with baseline hypernatremia weren’t treated with hyperdiuresis – so these findings may not apply to such patients.
The dose of loop diuretic used wasn’t reported. Theoretically it is possible that the dose of furosemide used during hyperdiuresis could have been larger than the baseline dosing of furosemide – so increased efficacy might be explained solely by differences in furosemide doses. However, doses of furosemide were already prodigious at baseline, so I strongly doubt this is a real problem.
This is a single-center study, performed within two units specialized in the care of cardiac patients (the cardiac ICU and the cardiac step-down unit). The reported safety of hyperdiuresis could partially reflect close monitoring and high-level expertise within these units. Thus, it cannot be assumed that hyperdiuresis would be equally safe if administered in units with less intensive monitoring.
- Hyperdiuresis involves a combination of hypertonic saline and loop diuretic, for management of refractory volume overload.
- This retrospective cohort study describes 58 episodes of hyperdiuresis among a cohort of profoundly ill patients with decompensated heart failure and diuretic resistance (most of whom had severely impaired cardiac and renal function).
- Hyperdiuresis was successful in achieving volume removal, with a simultaneous improvement in renal function.
- Hyperdiuresis was well tolerated. There was no signal of increasing pulmonary edema. Hyperdiuresis did tend to increase the sodium and chloride levels, but these shifts were moderate (and tended to push patients towards normal values).
- Further investigation of hyperdiuresis is needed (ideally in the form of a RCT). In the interim, this seems to be a very reasonable treatment consideration for patients who are refractory to other therapies.
going further
- Hyperdiuresis (PulmCrit)
- Deresuscitation: Dominating the diuresis (IBCC)
references
- 1.Griffin M, Soufer A, Goljo E, et al. Real World Use of Hypertonic Saline in Refractory Acute Decompensated Heart Failure. JACC: Heart Failure. February 2020. doi:10.1016/j.jchf.2019.10.012
- 2.Issa VS, Andrade L, Ayub-Ferreira SM, et al. Hypertonic saline solution for prevention of renal dysfunction in patients with decompensated heart failure. International Journal of Cardiology. July 2013:34-40. doi:10.1016/j.ijcard.2011.11.087
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Thank you for your excellent comment on this interesting study. According to the recent study of Hodson DZ: Natriuretic Response Is Highly Variable and Associated With 6-Month Survival Insights From the ROSE-AHF Trial (JACC Heart Failure 2019) it would be of interest how hyperdiuresis influences renal sodium excretion and sodium balance and not only weight loss or urine volume. What does the rising of serum sodium 24 hours after treatment mean? Is this an effect of a positive sodium balance ? or is this based on the enhanced elimination of electrolyte free water? Maybe sodium chloride 3% (beside its hemodynamic… Read more »