What is the literature on use of albumin for intradialytic hypotension?

What is the literature on use of albumin for intradialytic hypotension?

Comment by InpharmD Researcher

Available literature evaluating use of albumin for hypotension during renal replacement therapy is limited to studies with small sample sizes and considerable variations in albumin formulations (iso- versus hyperoncotic) and dosing regimens (see Tables 1-6). Some studies reported no additional benefits of 5% albumin compared to normal saline in restoring blood pressure during hemodialysis, whereas others demonstrated the superiority of hyperoncotic albumin to normal saline in preventing intradialytic hypotension and improving ultrafiltration. A recent randomized controlled trial suggests that albumin administration prior to dialysis may be beneficial for hypoalbuminemic patients who need hemodialysis.

Background

Intradialytic hypotension (IDH) can result from an excessive rate or ultrafiltration. Acute management involves volume expansion through intravenous fluids (e.g. normal saline, hypertonic saline, albumin). A 2010 Cochrane review evaluating the benefits and harms of volume expansion with albumin for the treatment of intradialytic hypotension only identified one randomized, double-blind trial (see Table 1). The study demonstrated no statistical difference between 5% albumin and normal saline for the treatment of symptomatic hypotension in hemodialysis patients. The authors of the review state saline should be the first line of therapy for the treatment of IDH in stable dialysis patients due to the cost and relative rarity of albumin use. Overall, there appears to be a lack of randomized controlled trials comparing albumin to crystalloids or non-protein colloids, or a combination of both, in the treatment of symptomatic hypotension during dialysis. [1], [2]

A 2021 review evaluating the safety and efficacy of albumin for patients receiving kidney replacement therapy in preventing IDH noted the small sample size and considerable heterogeneity of interventions and outcomes assessed among available clinical trials. Specifically, studies used various formulations (5%, 17.5%, 20% and 25%) and dosing regimens of albumin, ranging from 100 mL to 300 mL via intravenous (IV) administration or priming hemodialysis circuit (see Table 4). The author further noted the lack of robust data on utilizing IV albumin in critically ill individuals, besides the recently published results from Clark et al. (see Table 5). [3]

Literature Review

A search of the published medical literature revealed 6 studies investigating the researchable question:

What is the literature on use of albumin for intradialytic hypotension?

Level of evidence

C - Multiple studies with limitations or conflicting results Read more→

Please see Tables 1-6 for your response.

A randomized, controlled trial of albumin versus saline for the treatment of intradialytic hypotension
Design	Randomized, double-blinded, crossover trial N= 45
Objective	To determine whether 5% albumin was more effective than normal saline for the treatment of intradialytic hypotension (IDH)
Study Groups	5% albumin (n= 23) Normal saline (n= 22)
Inclusion Criteria	Adult patients undergoing hemodialysis treatments for a minimum of 3 months, at least three symptomatic episodes of intradialytic hypotension in the 60-day preceding enrollment, two or fewer hypotensive episodes during the study period
Exclusion Criteria	Known sensitivity to albumin
Methods	Patients were randomized to receive 5% albumin to treat the first episode of hypotension followed by normal saline for the second and third dialysis sessions with hypotension or normal saline to treat the first episode of hypotension followed by 5% albumin for the second and third dialysis sessions with hypotension. The protocol for symptomatic hypotension was similar. Ultrafiltration was stopped and the patient was given 250 mL of albumin 12.5 g or saline 0.9%. If blood pressure was not restored after 5 mins, a second 250 mL of the same fluid was given. A third bottle of solution could be given if blood pressure had not been restored after another 5 mins. If by 5 mins later there was still no resolution, the protocol was discontinued and a treatment failure was recorded.
Outcome Measures	Percentage of target ultrafiltration achieved, post-dialysis blood pressure, time to restore blood pressure, treatment failure, recurrent hypotension
Baseline Characteristics		5% albumin (n= 23)	Normal saline (n= 22)
	Age, year	65.4 ± 14.9	64.5 ± 14.0
	Female	48%	32%
	Time on dialysis, months	41.1 ± 35.9	50.5 ± 57.0
	Diabetes	35%	36%
	Previous myocardial infarction	26%	14%
	Dry weight, kg	69.7 ± 15.8	71.6 ± 21.5
	Body mass index, kg/m²	26.6 ± 5.3	26.6 ± 7.5
Results		5% albumin (N= 45)	Normal saline (N=45)	p-value
	Actual ultrafiltration, L	2.6 ± 1.4	2.6 ± 1.2	0.58
	% target ultrafiltration achieved	0.84 ± 0.17	0.80 ± 0.16	0.14
	Post-dialysis blood pressure, mm Hg Systolic Diastolic	121 ± 19 63 ± 9	117 ± 19 61 ± 9	0.32 0.33
	Time to restore blood pressure, min	7.9 ± 6.6	9.9 ± 7.5	0.09
	Treatment failure	22%	24%	1.0
	Recurrent hypotension	36%	36%	1.0
Adverse Events	None reported
Study Author Conclusions	This study showed 5% albumin is no more effective than normal saline for the treatment of IDH in chronic hemodialysis patients. Normal saline should be used as the initial fluid for the treatment of intradialytic hypotension.
InpharmD Researcher Critique	The strengths of this study included the randomized, crossover design and proper blinding of intervention arms. However, the sample population was mostly older patients and may not reflect the same response compared to younger patients. Only patients with at least 3 incidences of hypotension were included in the final analysis, which may influence the generalizability of the results.

References:

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

A randomized trial of albumin infusion to prevent intradialytic hypotension in hospitalized hypoalbuminemic patients
Design	Prospective, randomized, controlled, crossover trial N= 65 patients (249 dialysis sessions)
Objective	To assess if the concurrent use of intravenous albumin during dialysis would result in higher quantities of fluid removal per unit time and be associated with a reduced incidence of intradialytic hypotension (IDH)
Study Groups	0.9% sodium chloride (n= 65) 25% albumin (n= 65)
Inclusion Criteria	> 18 years old; acute kidney injury (AKI), AKI on chronic kidney disease (CKD), and end-stage kidney disease (ESKD); required fluid removal with dialysis; serum albumin level < 3 g/dL at the initiation of dialysis
Exclusion Criteria	Renal transplant; not expected to be on dialysis for less than 24 hours
Methods	Eligible patients scheduled to receive intermittent hemodialysis (IHD) were randomized to receive either a single dose of 25 g albumin (100 mL of Grifols 25%) or 100 mL of 0.9% sodium chloride administered intravenously at the start of IHD. Patients alternated between both intervention solutions administered prior to the start of their IHD for a maximum of six sessions for each patient. Ultrafiltration removal, vital signs, and symptoms of hypotension were monitored. Hypotension was assessed based on the lowest systolic blood pressure, changes in systolic blood pressure, symptoms, and need for intervention during each dialysis session. Management of hypotensive episodes included pausing the ultrafiltration, placing the patient in Trendelenburg position, giving 0.9% sodium chloride boluses, adjusting the dialysate temperature to 35^oC, and shortening treatment time.
Duration	Follow-up duration: duration of dialysis session
Outcome Measures	Primary: delivered fluid volume, hypotension Secondary: ultrafiltration rates to achieve target fluid removal in each session, urea reduction rate, and dialysis dose based on Kt/V per session
Baseline Characteristics		Total population (N= 65)
	Age, years	58.09
	Female	29.2%
	Race White Hispanic	35.4% 36.9%
	AKI ESKD	84.6% 15.4%
	Number of sessions completed 1 2 3 4 5 6	21.5% 12.3% 13.8% 6.2% 9.2% 36.9%
	Serum albumin at dialysis initiation, g/L	2.69
Results	Endpoint	0.9% sodium chloride (n= 65)	25% albumin (n= 65)	p-value
	Fluid removal parameters Total delivered ultrafiltration, mL Delivered removal rate, mL/kg/h	-2,500 (-3,000 to -1,700) -8.25 (-11.8 to -5.8)	-2,500 (-3,100 to -1,675) -8.27 (-12.22 to -5.53)	0.156 0.011
	Hypotension Systolic blood pressure (SBP) reduction ≥ 20 mmHg SBP reduction ≥ 30 mmHg Kidney Disease Outcomes Quality Initiative (KDOQI)^* Hypotension episodes resulting in interventions^* Hypotension episodes	59 (48%) 40 (32.5%) 19 (15.4%) 26 (20.8%) 42 (33.6%)	44 (35.8%) 29 (23.6%) 9 (7.3%) 16 (12.9%) 39 (31.5%)	0.026 0.041 0.002 0.072 0.718
	Urea reduction rate	69.23 ± 8.36	69.60 ± 8.58	0.67
	Dialysis dose based on Kt/V	1.26 ± 0.34	1.29 ± 0.38	0.063
	^*KDOQI defined as change in SBP ≥20 mmHg and symptoms of cramping, headache, light-headedness, vomiting, or chest pain during hemodialysis; Interventions included ultrafiltration reduction, blood flow reduction, or 0.9% sodium chloride administration
Adverse Events	Not disclosed
Study Author Conclusions	In hypoalbuminemic patients who need hemodialysis, albumin administration before the dialysis results in fewer episodes of hypotension and improves fluid removal. Albumin infusion may be of benefit to improve the safety of hemodialysis and achievement of fluid balance in these high-risk patients.
InpharmD Researcher Critique	The study is limited by its small sample size. Additionally, although there was a difference in overall hypotension episodes and total delivered ultrafiltration, these differences were not statistically significant.

References:

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. Published 2021 Jan 6. doi:10.1186/s13054-020-03441-0

Implementation of an Algorithm Utilizing Saline Versus Albumin for the Treatment of Intradialytic Hypotension
Design	Retrospective, observational, single-center, pre-post study N= 180
Objective	To determine the effect of an algorithm for intradialytic hypotension (IDH) management
Study Groups	Preintervention (n= 90) Postintervention (n= 90)
Inclusion Criteria	Age >18 years, underwent intermittent hemodialysis, diagnosed with intradialytic hypotension
Exclusion Criteria	Sensitivity to albumin, hemodynamic instability, pregnant
Methods	A protocol to treat IDH was implemented in 2017 where patients with IDH were first given 400 mL of normal saline. If blood pressure was not restored, they were given 100 mL of 25% albumin. These patients were compared to a historical cohort where IDH was treated without an algorithm.
Duration	Preintervention: November to December 2016 Postintervention: January to March 2017
Outcome Measures	Albumin use, reversal of hypotension (mean arterial pressure ≥60 mm Hg), time to restore systolic blood pressure ≥90 mm Hg, treatment failure
Baseline Characteristics		Preintervention (n= 90)	Postintervention (n= 90)	p-value
	Age, years	65.5 ± 12.8	62.6 ± 13.4	Not significant (NS)
	Women	47 (52%)	62 (69%)	0.02
	Body mass index, kg/m²	28.9 ± 6.6	36.2 ± 42.1	NS
	Serum albumin, g/dL	3.36 ± 0.87	3.14 ± 0.74	NS
	Predialysis blood pressure, mm Hg Systolic blood pressure Diastolic blood pressure	115 ± 19 58 ± 15	121 ± 22 50 ± 12	NS < 0.001
	Total dialysis time, min	218 ± 39	195 ± 45	< 0.001
	Predialysis systolic blood pressure < 90 mm Hg	6 (7%)	4 (4%)	NS
	Predialysis mean arterial pressure < 60 mm Hg	10 (11%)	3 (3%)	NS
Results		Preintervention (n= 90)	Postintervention (n= 90)	p-value
	Total albumin use, mL	11,400	4,700	<0.001
	First line fluid Normal saline Albumin	19 (21%) 71 (79%)	74 (87%) 5 (6%)	<0.001 <0.001
	Reversal of hypotension	81 (90%)	84 (93%)	0.99
	Time to restore blood pressure, min	22 ± 10	22 ± 15	0.28
	Treatment failure	3 (3%)	4 (4%)	0.99
Adverse Events	Not discussed
Study Author Conclusions	An algorithm-based approach to the management of IDH by expanding volume was effective in correcting hypotension and was associated with a significant reduction in albumin use and associated drug costs.
InpharmD Researcher Critique	The role of IDH treatment in the setting of hemodynamic instability was not evaluated limiting the extrapolation of these results to the patient population defined by the exclusion criteria. Additionally, this was a retrospective chart review that is limited by confounding factors and human error.

References:

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

Summaries of other trials assessing intravenous albumin for intradialytic hypotension (IDH)
Author/Study design	Study population	Intervention	Main results/Conclusions
Rostoker et al., 2011 Randomized, single-blind, crossover study	N= 10 (HD sessions not specified) Outpatients on maintenance HD “prone to IDH”	20% albumin (200 mL) versus 4% gelatin (200 mL) given throughout HD	Fewer episodes of SBP < 100 mm Hg in six patients (60%) with albumin 20% albumin improved hemodynamic parameters
van der Sande et al., 2000 Randomized, nonblinded, crossover study	N= 9 (27 HD sessions) Outpatients on maintenance HD with recurrent IDH and CHF	20% albumin (100 mL) versus 3% saline (33 mL) versus 10% HES (100 mL) for BP drop	20% albumin (and HES) sessions: lower drop in BV and lower drop in end treatment SBP versus 3% saline 20% albumin was superior to 3% saline for preventing IDH
van der Sande et al., 1999 Randomized, nonblinded, crossover study	N= 10 (30 HD sessions) Outpatients on maintenance HD; CHF excluded	20% albumin (100 mL) versus NS (100 mL) versus 10% HES (100 mL) for 10% BV decline	Albumin and HES both maintained a significantly smaller change in BV than NS (p= 0.05). No significant differences in SBP 20% albumin was superior to NS for preserving BV during HD
Jardin et al., 1982 Nonblinded, crossover study	N= 8 (53 HD sessions) Inpatients with sepsis and anuric AKI	HD circuit primed with either 300 mL 17.5% albumin or 300 mL NS	Albumin sessions: more UF achieved and higher MAP during treatment versus NS Priming HD circuit with 17.5% albumin limited IDH, facilitated ultrafiltration
All included trials were single-center studies. AKI, acute kidney injury; HD, hemodialysis; NS, normal saline; IDH, intradialytic hypotension; SBP, systolic BP; UF, ultrafiltration; CHF, congestive heart failure; HES, hydroxyethyl starch; BV, blood volume; MAP, mean arterial pressure.

References:

Adapted from:
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. 2021;16(5):820-828. doi:10.2215/CJN.09670620

Intravenous albumin for the prevention of hemodynamic instability during sustained low-efficiency dialysis: a randomized controlled feasibility trial (The SAFER-SLED Study)
Design	Single-center, blinded, placebo-controlled, randomized feasibility trial N= 60 (271 sustained low-efficiency dialysis [SLED] sessions)
Objective	To compare intravenous (IV) 25% albumin to 0.9% saline during SLED sessions initiated in intensive care unit (ICU) for patients with acute kidney injury (AKI)
Study Groups	Saline (n= 30; 123 SLED sessions) Albumin (n= 30; 148 SLED sessions)
Inclusion Criteria	ICU patients; aged ≥ 18 years; developed AKI; planned to receive SLED
Exclusion Criteria	SLED for a non-AKI indication (e.g., intoxication); kidney failure receiving dialysis treatment prior to admission; allergy to albumin; pregnancy; and any contraindication or known objection to blood-product transfusions
Methods	Eligible patients were randomly assigned (1:1) to receive 100 mL boluses of either 25% albumin or normal saline (0.9%) at the start and then midway (at 4 h) into SLED sessions (200 mL/session) for up to 10 SLED sessions. At the study center, only SLED was available as renal replacement therapy (RRT) modality used for hemodynamically unstable patients unable to tolerate intermittent hemodialysis (i.e., continuous renal replacement therapy [CRRT] is not used). Specifically, the SLED consisted of 8-h sessions using a dialysate temperature of 35.5 °C, maximum blood flow rate of 200 mL/min, maximum dialysate flow rate of 300 mL/min, and dialyzers with a surface area of 0.6 m². Default dialysate concentrations were sodium, potassium, bicarbonate, and calcium 140 mmol/L, 4 mmol/L, 34 mmol/L, and 1.25 mmol/L, respectively. Adjustments were made based on treating physicians' discretion.
Duration	Between April 1st, 2019, and January 14th
Outcome Measures	Primary: recruitment rate, adherence to the protocol and completeness of follow-up Exploratory outcomes: measures of ultrafiltration, hemodynamic stability during treatment, patient outcomes
Baseline Characteristics		Saline (n= 30)	Albumin (n= 30)
	Age, years	60	61
	Female	30%	20%
	APACHE II total score	29.9	30.3
	Comorbidities Diabetes mellitus Peripheral vascular disease Chronic kidney disease	43% 10% 20%	33% 20% 30%
	Primary ICU admission diagnosis Septic/distributive shock Respiratory failure	63% 13%	73% 17%
	Indications for SLED Initiation Pulmonary edema Uremia Hyperkalemia Acidosis	53% 3% 27% 43%	47% 0 57% 47%
	Laboratory parameters prior to SLED Albumin, g/L Creatinine, µmol/L Potassium, mmol/L Lactate, mmol/L	25 320 4.6 3.0	23 357 5.0 4.5
	Vital signs prior to SLED Systolic blood pressure, mmHg Mean arterial pressure, mmHg Vasopressor use	n= 123 118 ± 21 78 ± 13 99 (80%)	n= 148 116 ± 20 78 ± 12 91 (61%)
Results	Endpoint	Saline	Albumin
	Post-SLED vital signs Systolic blood pressure, mmHg Mean arterial pressure, mmHg Vasopressor use	119 ± 20 79 ± 12 95 (77%)	124 ± 20 83 ± 13 80 (54%)
	Unadjusted mortality In ICU In hospital	16 (53.3%) 19 (63.3%)	11 (36.7%) 11 (36.7%)
	Fluid removal parameter (interquartile range) Actual ultrafiltration Percentage achieved ultrafiltration	2,500 (1,760 to 3,480) 99.7% (83.3 to 100)	3,000 (2,000, 3,980) 99.8% (87.5, 100)
	In the cohort overall, both doses of the assigned fluid (either albumin or saline) were administered correctly (according to the study assignment) for 244 of the 271 SLED sessions, thereby achieving 90% adherence to the study protocol. No patients were lost to follow-up. The median length of ICU and hospital stay did not differ significantly between groups.
Adverse Events	No adverse events related to albumin or saline administration were encountered.
Study Author Conclusions	The efficacy of using hyperoncotic albumin to prevent hemodynamic instability in critically ill patients receiving SLED remains unclear. A larger trial to evaluate its impact in this setting, including evaluating clinically relevant outcomes, is feasible.
InpharmD Researcher Critique	Clinical outcomes reported in the current study remained exploratory and need to be further confirmed in future large-scale randomized controlled trials. As the study center specifically utilized SLED, findings may not be readily generalizable to other types of RRTs.

References:

Clark EG, McIntyre L, Watpool I, et al. Intravenous albumin for the prevention of hemodynamic instability during sustained low-efficiency dialysis: a randomized controlled feasibility trial (The SAFER-SLED Study). Ann Intensive Care. 2021;11(1):174. Published 2021 Dec 13. doi:10.1186/s13613-021-00962-x

Efficacy of Human Albumin in Prevention of Intradialytic Hypotension in Critically Ill Patients with Hypoalbuminemia Undergoing Haemodialysis – A Randomized Controlled Trial
Design	Open label parallel group randomized trial N= 78 patients, 205 sessions of HD
Objective	To evaluate the efficacy of human albumin in preventing intradialytic hypotension (IDH) in critically ill patients with hypoalbuminemia undergoing hemodialysis
Study Groups	Albumin group (n= 205 sessions) Standard of care group (n= 205 sessions)
Inclusion Criteria	Critically ill patients with hypoalbuminemia undergoing hemodialysis
Exclusion Criteria	Not specified
Methods	Hemodialysis sessions were randomized to receive either standard of care or 100 mL 20% human albumin at the initiation of hemodialysis along with standard of care. Vital signs, fluid removed, ultrafiltration removal rate, and blood flow rate were recorded every 15 minutes during HD. Vasopressor requirement and dose were noted. IDH was assessed as per the National Kidney Foundation Kidney Disease Outcomes Quality Initiative Guidelines
Duration	Not specified
Outcome Measures	Primary: Incidence of intradialytic hypotension Secondary: Fluid removal, vasopressor requirement
Baseline Characteristics		Albumin group (n= 205 sessions)	Standard of care group (n= 205 sessions)
	Incidence of IDH (SBP fall of 20 mm Hg)	51.5%	42.2%
	Incidence of IDH (MAP fall of 10 mm Hg)	64.1%	56.9%
	Vasopressor requirement	7.8%	28.4%
	Mean fluid removed, mL	2132.32 ± 1217.32	2240.88 ± 941.80
Results		Albumin group	Standard of care group	p-value
	Incidence of IDH (SBP fall of 20 mm Hg)	51.5%	42.2%	0.182
	Incidence of IDH (MAP fall of 10 mm Hg)	64.1%	56.9%	0.291
	Vasopressor requirement	7.8%	28.4%	<0.001
	Mean fluid removed, mL	2132.32 ± 1217.32	2240.88 ± 941.80	0.619
Adverse Events	Not specified
Study Author Conclusions	The incidence of intradialytic hypotension was not significantly decreased in the intervention group. Albumin administration is beneficial in reducing the need for vasopressors during HD, though it didn’t affect total fluid removal.
Critique	The study provides valuable insights into the role of albumin in reducing vasopressor requirements during hemodialysis in hypoalbuminemic patients. However, the lack of significant reduction in intradialytic hypotension incidence and the absence of detailed adverse event reporting are limitations. Due to the study being presented as an abstract, an in-depth analysis could not be conducted. Standard of care was not defined.

References:

Mohapatra RK, Sahoo D, Behera S, Kumarpanda S. Efficacy of Human Albumin in Prevention of Intradialytic Hypotension in Critically Ill Patients with Hypoalbuminemia Undergoing Haemodialysis – A Randomized Controlled Trial. Indian J Crit Care Med. 2025;29(Suppl 1):S182. doi:10.5005/jaypee-journals-10071-24933.132