Update: What is the evidence for the use of albumin for treatment of intradialytic hypotension?

Introduction

Intradialytic hypotension is a complication that frequently affects patients undergoing hemodialysis and can lead to increases in failure of vascular access devices, cardiovascular complications, cerebral, mesenteric, and hepatic ischemia, and mortality.1 Although the true prevalence of intradialytic hypotension is unknown, it has been estimated to complicate between 15 and 50% of hemodialysis sessions.2 The most recent guidelines available with recommendations regarding management of intradialytic hypotension were published in 2005 by the National Kidney Foundation Disease Outcomes Quality Initiative (K/DOQI).3 These guidelines suggest several nonpharmacologic (eg, temperature modeling, isothermic dialysis, dialysate calcium or sodium modeling) and pharmacologic (eg, midodrine, carnitine) methods to control intradialytic hypotension. However, in an acute setting, intradialytic hypotension is often managed by volume expansion via administration of intravenous fluids.4 The 2005 K/DOQI guidelines do not identify a preferred method for control of intradialytic hypotension, and do not discuss volume expansion as a strategy.3 In an attempt to elucidate the role of volume expansion in the management of intradialytic hypotension, specifically with the use of intravenous albumin, a frequently asked question (FAQ) was published in March 2014 to further describe intradialytic hypotension, its management, and to summarize the available literature on the use of albumin to treat it (available here).5 The literature available at that time did not find a benefit associated with using albumin over normal saline (NS). Although it has been several years since the publication of the previous FAQ, no new guidelines have been published to describe the role of volume expansion with albumin (or other fluids) in the treatment of intradialytic hypotension. Therefore, the purpose of this FAQ is to summarize any new available literature describing use of albumin for this purpose.

Considerations when using albumin for intradialytic hypotension

There are several factors that should be considered when determining whether albumin is appropriate for use in a patient with intradialytic hypotension. While intravenous albumin is highly effective for volume expansion, intradialytic hypotension is not always caused by volume depletion.6 Since the ultimate goal of hemodialysis is fluid removal, fluid expansion may not be an appropriate management strategy depending on the source of hypotension. Since albumin is very effective at fluid expansion, it has the potential risk of limiting the net fluid removed during hemodialysis if administered. Additionally, albumin is an expensive fluid replacement option; a recent study estimated that albumin was 27 times more expensive than 100 mL of an equivalent crystalloid.7 Patients with renal impairment may develop hypoalbuminemia due to numerous factors, such as decreased hepatic albumin production and increased permeability of the capillaries.6 Low albumin levels have shown to be independently associated with development of intradialytic hypotension; further, some studies have suggested that hypoalbuminemia is associated with increased morbidity and mortality among patients receiving hemodialysis. The potential cause of hypotension, cost, and patient’s albumin level are important considerations when determining the most appropriate course of action for correction of hypotension.

Literature review

A literature search was performed to identify new literature published since the 2014 FAQ assessing use of albumin to treat intradialytic hypotension; 2 studies, published in 2019 and 2021, were identified.

In 2021, Macedo et al. published the results of a prospective, crossover, randomized controlled trial comparing use of albumin to normal saline for prevention of intradialytic hypotension in 65 adult patients undergoing intermittent hemodialysis with serum albumin levels less than 3 g/dL.8 Patients with impaired renal function undergoing hemodialysis were administered 100 mL of either 25% albumin or 0.9% NS intravenously at the start of hemodialysis to prevent intradialytic hypotension. Study participants were administered either albumin or normal saline, then alternated to the opposite solution at their next dialysis session for a maximum of 6 separate sessions; a total of 249 sessions were included in this study. The primary efficacy endpoint, delivered fluid removal, was significantly reduced with administration of normal saline (median, -8.25 ml/kg/hour [interquartile range, -11.32 to 5.65 mL/kg/hour] compared to albumin (median, -8.27 mL/kg/hour [interquartile range, -12.22 to 5.53]; p=0.011. However, this difference is not clinically significant and additional fluid removal parameters, including prescribed and delivered time, total prescribed and delivered ultrafiltration, delta weight in kg, and prescribed removal rate, were not different between groups. The primary safety endpoint assessed cardiovascular complications, including episodes of hypotension. Results showed that administration of albumin was associated with significant reductions in the frequency of development of hypotension across several different definitions of intradialytic hypotension, including: systolic blood pressure (SBP) decrease of 20 mmHg (35.8% with albumin vs 48% with NS; p=0.26), or 30 mmHg (23.6% vs 32.5%; p=0.041), composite decline of 20 mmHg SBP plus minimal SBP of 90 mmHg (3.3% vs 11.4%; p=0.016), and the K/DOQI definition (7.3% vs 15.4%; p=0.0002). Based on these results, the authors concluded that administration of albumin prior to hemodialysis is associated with improved fluid removal rates and reduced occurrence of hypotension among high-risk patients with hypoalbuminemia.

In 2019, Yin and colleagues published a single-center, retrospective chart review study comparing management of intradialytic hypotension within their facility before and after implementation of an algorithm designed to spare use of albumin.9 The study compared 180 patients (90 pre-intervention and 90 post-intervention) with at least 1 episode of intradialytic hypotension (defined as SBP <90 mmHg or mean arterial pressure [MAP] <60 mmHg) and with or without hypotensive symptoms to assess albumin use as a result of the algorithm. The pre-intervention period occurred between November 10, 2016 and December 14, 2016 and the post-intervention period took place between January 4 and March 11, 2017. The implemented algorithm required patients with intradialytic hypotension to be managed first by receiving 200 mL of NS intravenously over 10 minutes, followed by 100 mL of albumin 25% if they remained hypotensive within 10 minutes after receiving NS. If participants remained hypotensive 10 minutes after receiving IV albumin, they were allowed to receive a repeat dose 10 minutes later, followed by nephrologist consultation. The primary endpoint compared use of albumin in the pre- and post-intervention groups; implementation of the algorithm led to significant reductions in albumin use (4700 mL total) compared to pre-intervention (11,400 mL total; p<0.001). Reversal of hypotensive episodes was assessed as a secondary endpoint, and was found to be similar in the pre- and post-intervention groups (90% pre-intervention vs 93% post-intervention; p=0.99). Cost of albumin was also assessed as a secondary endpoint, and was significantly reduced after implementation of the algorithm ($4343 vs $10534; p<0.001). The authors concluded that management of intradialytic hypotension following the proposed algorithm was effective for management of intradialytic hypotension while limiting the use (and thus, associated cost) of albumin.

Discussion

Although 2 additional studies have been published since the 2014 FAQ, data supporting administration of albumin for intradialytic hypotension is somewhat conflicting and still very limited. Published studies describing use of intravenous albumin to treat intradialytic hypotension generally utilize a dose of 100 mL of 25% albumin (25 grams of albumin)8-10; the 2004 study by Knoll et al, described in the 2014 FAQ, was the only study which used a 250 mL 5% albumin solution (12.5 grams).11 The 2019 study by Yin and colleagues was designed in order to limit administration of intravenous albumin, and generally showed that use of NS first-line prior to albumin was both a clinically and economically effective strategy.9 The 2021 study published by Macedo et al. is the first to show a statistically significant improvement in intradialytic hypotension when compared to normal saline.8 Patients included in this trial were required to have hypoalbuminemia, which likely contributed to these findings. While most studies have shown no difference in intradialytic hypotension between patients administered albumin or NS, albumin could potentially be an effective option in patients with low albumin levels prior to dialysis.

References

  1. Kanbay M, Ertuglu LA, Afsar B, et al. An update review of intradialytic hypotension: concept, risk factors, clinical implications and management. Clin Kidney J. 2020;13(6):981-993. doi: 10.1093/ckj/sfaa078
  2. See EJ, Polkinghorne KR. Volume management in haemodialysis patients. Curr Opin Nephrol Hypertens. 2020;29(6):663-670. doi: 10.1097/MNH.0000000000000642
  3. K/DOQI Workgroup. K/DOQI clinical practice guidelines for cardiovascular disease in dialysis patients. Am J Kidney Dis. 2005;45(4 Suppl 3):S1-S153.
  4. Fortin PM, Bassett K, Musinin VM. Human albumin for intradialytic hypotension in haemodialysis patients. Cochrane Database Syst Rev. 2010;(11):CD006758. doi: 10.1002/14651858.CD006758.pub2
  5. Derlet A. What is the evidence for the use of albumin for treatment of intradialytic hypotension? University of Illinois at Chicago Drug Information Group. Published March 2014. Accessed January 20, 2021. https://dig.pharmacy.uic.edu/faqs/2014-2/march-2014-faqs/
  6. Hryciw N, Joannidis M, Hiremath S, Callum J, Clark EG. Intravenous albumin for mitigating hypotension and augmenting ultrafiltration during kidney replacement therapy. Clin J Am Soc Nephrol. Published online October 28, 2020. doi: 10.2215/CJN.09670620
  7. Taylor C, Yang L, Finfer S, et al; Fluid-TRIPS and Fluidos Investigators, The George Institute for Global Health, The ANZICS Clinical Trials Group, BRICNet, and the REVA Research Network. An international comparison of the cost of fluid resuscitation therapies. Aust Crit Care. Published online August 10, 2020. doi: 10.1016/j.aucc.2020.06.001
  8. Macedo E, Karl B, Lee E, Mehta RL. A randomized trial of albumin infusion to prevent intradialytic hypotension in hospitalized hypoalbuminemic patients. Crit Care. 2021;25(1):18. doi: 10.1186/s13054-020-03441-0
  9. Yin L, Dubovetsky D, Louzon-Lynch P. Implementation of an algorithm utilizing saline versus albumin for the treatment of intradialytic hypotension. Ann Pharmacother. 2019;53(2):159-164. doi: 10.1177/1060028018801024
  10. Emili S, Black NA, Paul RV, Rexing CJ, Ullian ME. A protocol-based treatment for intradialytic hypotension in hospitalized hemodialysis patients. Am J Kidney Dis. 1999;33(6):1107-1114. doi: 10.1016/S0272-6386(99)70148-4
  11. Knoll GA, Grabowski JA, Dervin GF, O’Rourke K. A randomized, controlled trial of albumin versus saline for the treatment of intradialytic hypotension. J Am Soc Nephrol. 2004;15(2):487-492. doi: 10.1097/01.asn.0000108971.98071.f2

Prepared by:

Jessica Elste, PharmD, BCPS
Clinical Assistant Professor, Drug Information Specialist
University of Illinois at Chicago College of Pharmacy

February 2021

The information presented is current as of January 14, 2021. This information is intended as an educational piece and should not be used as the sole source for clinical decision-making.