|Year : 2016 | Volume
| Issue : 3 | Page : 325-329
Human albumin 4% versus hydroxyethyl starch 6% for fluid resuscitation in sepsis
Heba F Toulan MD , Eman M Kamal
Department of Anesthesiology, Intensive Care, and Pain Management, Faculty of Medicine, Ain-Shams University, Cairo, Egypt
|Date of Submission||06-Aug-2015|
|Date of Acceptance||22-Oct-2015|
|Date of Web Publication||31-Aug-2016|
Heba F Toulan
Department of Anesthesiology, Intensive Care, and Pain Management, Faculty of Medicine, Ain-Shams University, 11566 Cairo
Source of Support: None, Conflict of Interest: None
Early fluid resuscitation is vital to patients with sepsis. However, the choice of fluid has been a hot topic of discussion. The objective of this study was to compare hydroxyethyl starch (HES) 6% (130/0.4) with albumin 4% as a resuscitation fluid in septic patients.
Patients and methods
In this prospective randomized study, 80 patients aged 20–60 years of both sexes with sepsis were assigned to receive either HES (130/0.4) in 0.9% saline or human albumin 4% as a resuscitation fluid. Mortality rate after 28 days, need for renal replacement therapy, and duration of ICU stay were compared between the two groups.
The mortality rate in the albumin group (22.5%) was lower than in the HES 6% group (40%) with significant P value (0.033). Also, the need for renal replacement therapy (RRT) and length of ICU stay were significantly higher in the HES 6% group compared with the albumin group.
Use of human albumin 4% has a significant effect in reducing mortality rates in the ICU in patients with severe sepsis compared with HES 6%.
Keywords: albumin, colloid, sepsis
|How to cite this article:|
Toulan HF, Kamal EM. Human albumin 4% versus hydroxyethyl starch 6% for fluid resuscitation in sepsis. Ain-Shams J Anaesthesiol 2016;9:325-9
|How to cite this URL:|
Toulan HF, Kamal EM. Human albumin 4% versus hydroxyethyl starch 6% for fluid resuscitation in sepsis. Ain-Shams J Anaesthesiol [serial online] 2016 [cited 2021 Apr 11];9:325-9. Available from: http://www.asja.eg.net/text.asp?2016/9/3/325/189097
| Introduction|| |
Sepsis is a syndrome that is clinically defined as the body's systemic inflammatory response to infection . Mortality rates with severe sepsis and septic shock range from 25 to over 75%, with higher rates of death in patients with multiorgan dysfunction and prolonged hypoperfusion ,. Early fluid resuscitation is one of the key interventions for patients with sepsis that has been widely accepted by clinicians. However, the optimal choice of fluid remains inconclusive ,. Albumin has been used as one type of resuscitation fluid since the Second World War . However, until recently, the pragmatic value of albumin in sepsis has been under debate ,. Synthetic colloids include hydroxyethyl starches (HES), which have been used in a range of clinical application . Recent large randomized clinical trials provide insight into the efficacy of the fluids and have compared albumin with crystalloid ,, and HES with crystalloid ,, but no large head-to-head randomized controlled trials comparing the two colloids have been reported. As several large studies on which fluid should be used for resuscitation have been published recently, the purpose of this study was to compare and determine the effect of resuscitation fluid type on patients with severe sepsis with HES 6% (130/0.4) versus human albumin 4% in terms of survival rate and organ functions during ICU stay.
| Patients and methods|| |
After obtaining approval from the local ethical committee of the Anesthesia and Intensive Care Department, Faculty of Medicine, Ain-Shams University, informed consent was taken from the patients or from their first-degree relative.
This prospective, randomized controlled comparative study was conducted in the ICU Department of Ain-Shams University Hospitals during the period from January 2014 to March 2015.
The eligible patients were between 20 and 60 years old, of both sexes, admitted to the ICU because of severe sepsis, with presence of documented infection by either defined focus or positive culture, together with one or more of these general conditions: fever, hypothermia, tachycardia, tachypnea respiratory rate (RR) > 20, generalized edema, hyperglycemia in the absence of diabetes mellitus, leukocytosis, or leukopenia. Organ dysfunction may or may not be present.
Patients were randomly assigned on encrypted computer randomization basis to receive either 6% HES (130/0.4) in 0.9% saline (Voluven; Fresenius Kabi, Berlin, Germany) or 4% human albumin (all fluid resuscitation in the ICU until discharge, death, or 28 days after randomization). Study fluid was administered to a maximum dose of 30 ml/kg of body weight per day, followed by open-label 0.9% saline for the remainder of the 24-h period.
All included septic patients were subjected to the measurements of standard parameters to define and follow up septic patients, including hemodyanmic parameters such as mean arterial pressure, heart rate, urine output (UOP), CVP, and RR at the start of the study (baseline) and then every hour, before resuscitation and daily.
All patients were followed up for a total of 28 days from the date of ICU admission, or until discharge from the ICU or until death.
Patients were excluded if: more than 8 h had passed from the first hypotensive episode; they had received more than 250 ml of colloid fluid (albumin or HES); they had other forms of shock (e.g. hemorrhagic, obstructive, or cardiogenic); they had had a previous admission to the ICU with severe sepsis or septic shock during the current hospitalization; they had a burn or traumatic brain injury before the current hospitalization; they had a history of chronic liver disease; they had a religious objection to the use of albumin; they had known previous severe reaction to albumin; there was lack of commitment from the patient, family, or clinical team to full therapeutic management; or they were pregnant or were enrolled in another related interventional trial.
Primary outcome was mortality rate after 28 days, whereas secondary outcomes were duration of mechanical ventilation, need for replacement therapy, and duration of ICU stay.
Statistical analysis was conducted on a personal computer using the Statistical Package for Social Sciences, version 3.0.1 (IBM© Corp., Armonk, New York, USA). Qualitative data were analyzed with the χ2-test and quantitative data were analyzed using the Student t-test and the Mann–Whitney test. Data were presented as mean and SD. A two-sided P value less than 0.05 was considered statistically significant.
Sample size calculations
The required sample size has been calculated using IMB© SPSS© SamplePower© version 3.0.1 (IBM© Corp.,). Thus, it has been estimated that a sample size of 40 patients in each study group (total 80 patients) will have a power of 80% (type II error = 0.2) to detect a reduction of 50% in the mortality rate in association with either of the interventions of interest. The test used was the two-sided χ2-test with 2 degrees of freedom, and significance was targeted at the 95% confidence level corresponding to a type I error of 0.05.
| Results|| |
There were no statistically significant differences in baseline patient characteristics (age, sex) among the three groups, as shown in [Table 1].
Also, there were no statistically significant differences in the baseline mean arterial pressure, heart rate, CVP, and urinary output, as shown in [Table 2] and [Figure 1].
|Table 2 Baseline hemodynamic variables and urine output in the two study groups|
Click here to view
|Figure 1 Baseline hemodyanmic variables and urine output in the two study groups. Data presented as mean ± SD.|
Click here to view
In the present study, there was a significant lower mortality rate in the albumin 4% group compared with the HES 6% group with significant P value (0.033), as shown in [Table 3] and [Figure 2].
Also, there was a higher need for renal replacement therapy in the HES 6% group compared with the albumin 4% group, but the difference was not statistically significant (P = 0.098).
There was no statistically significant difference between the two groups regarding the rate of hemodynamic support or mechanical ventilation, as shown in [Table 3] and [Figure 2].
The length of ICU stay was significantly higher in the HES 6% group compared with the albumin 4% group (P = 0.027; [Table 4].
|Table 4 Duration of organ system support and length of ICU stay in the two study groups|
Click here to view
No statistically significant difference was found between the two groups as regards duration of mechanical ventilation, renal replacement therapy, or duration of hemodynamic support, as shown in [Table 4] and [Figure 3].
|Figure 3 Duration of organ system support and length of ICU stay in the two study groups. Data are presented as median and interquartile range (IQR).|
Click here to view
There was no statistically significant difference between the two groups regarding international normalized ratio (P = 0.148).
Platelet count was significantly lower in the HES 6% group compared with the albumin 4% group (P = 0.039), as shown in [Table 5].
|Table 5 International normalized ratio and platelet count in the two groups|
Click here to view
| Discussion|| |
This study randomized 80 patients into two groups: group A consisted of 40 patients with severe sepsis who received HES 6% (130–0.4) and standard medical therapy, and group B consisted of 40 patients with severe sepsis who received human albumin 4% and standard medical therapy.
Human albumin is a natural protein that accounts for 50–60% of all plasma proteins and nearly 80% of plasma colloid osmotic pressure .
Human albumin also has multiple roles other than its oncotic properties:
- Transporting other biologically active molecules;
- Acting as an antioxidant;
- Anti-inflammatory action;
- Inhibition of platelet aggregation;
- Capacity for reducing capillary permeability and maintaining endothelial cell integrity; and
- Buffering the acid–base equilibrium ,,.
It has been reported that hypoalbuminemia, which is common in critically ill patients (including septic patients), is associated with poor clinical outcomes . Chou et al.  reported that, for patients with severe sepsis due to secondary peritonitis, albumin administration may reduce 28-day mortality; however, this mortality benefit was limited to patients whose baseline serum albumin is 20 g/l or lower.
HES 130/0.4 (tetrastarch) is a third-generation HES developed to provide better pharmacokinetic and safety profiles. When compared with albumin, tetrastarch may be a more cost-effective alternative with a comparable degree of volume expansion . The osmotic pressure obtained with tetrastarch is equivalent to that of albumin and results in 100% volume expansion.
Potential side effects due to administration of HES include pruritis, renal dysfunction, and coagulopathies ,.
Renal impairment in the critically ill is associated with a 60% mortality rate . It is generally thought that low-molecular-weight HES solutions carry lower risks of renal failure and coagulopathies when compared with high-molecular-weight HES and dextrans . The VISEP study, which used a pentastarch solution, was halted early because of increased incidences of acute kidney injury .
In the present study mortality at 28 days was lower in the albumin group (22.5%) compared with the HES group (40%), with significant P value (0.033).
The need for renal replacement therapy was also higher in the HES group compared with the albumin group, but the difference was not statistically significant.
Gattas et al.  concluded that with HES there is a 6% increase in relative risk of death and a significant 25% increase in relative risk of being treated with RRT. Zarychanski et al.  showed a clear survival benefit with other control fluids in critically ill patients. Patel et al.  conducted a meta-analysis on trials with severe septic patients treated with 6% HES (130/0.4 or 130/0.42). The control fluid showed a higher survival benefit in the 90-day follow-up period. Delaney et al.  compared albumin with any control fluid and found albumin to be superior in reducing the risk for mortality.
In the present study, there was significant reduction in platelet count in the HES group in contrast with a study that showed marginal decrease in platelet count in the albumin group.
Haase et al.  found a higher rate of RRT and blood transfusion in patients treated with HES 130/0.38–0.45 but no significant difference in the risk of death.
In contrast to the present study results, which showed increase in ICU stay with HES, the CHEST trial CRYSTMAS study demonstrated no differences in ICU length of stay in the HES group ,.
In the present study, there were no statistically significant differences as regards duration of mechanical ventilation or renal replacement therapy or duration of hemodyanmic support between the two groups.
Limitations of the study
A major limitation was the inability to assess the definitive outcome at 90 days and follow up the patients outside the ICU; another limitation was the complexity of the medical treatment and many parameters to be measured with a large volume of data.
| Conclusion|| |
Use of human albumin 4% for fluid resuscitation in patients with severe sepsis in the ICU seems to lower the mortality rates, together with reducing the ICU length of stay and the need for renal replacement therapy, when compared with the use of HES 6%.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008; 36: 296-327.
Annane D, Aegerter P, Jars-Guincestre MC, Guidet B. Current epidemiology of septic shock: the CUB-R a Network. Am J Respir Crit Care Med 2003; 168:165-172.
Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, et al.
Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med 2013; 41:580-637.
Perner A, Haase N, Guttormsen AB, Tenhunen J, Klemenzson G, et al.
Hydroxyethyl starth 130/0.42 versus Ringer′s acetate in severe sepsis. N Engl J Med 2012; 367:124-134.
Finfer S. Reappraising the role of albumin for resuscitation. Curr Opin Crit Care 2013; 19:315-320.
Human albumin administration in critically ill patients: systematic review of randomized controlled trials. BMJ 1998; 317:235-240.
Human albumin solution for resuscitation and volume expansion in critically ill patients. Cochrane Database Syst Rev 2011; 6:CD001208.
K Berman. Albumin 2015: a market profile and forecast of albumin in the United States through the year 2015
. USA: The Marketing Research Bureau Inc.; 2011.
Finfer S, Bellomo R, McEvoy S, et al.
Effect of baseline serum albumin concentration on outcome of resuscitation with albumin or saline in patients in intensive care units: analysis of data from the saline versus albumin fluid evaluation (SAFE) study. BMJ 2006; 333:1044.
Maitland K, Kiguli S, Opoka RO, et al.
Mortality after fluid bolus in African children with severe infection. N Engl J Med 2011; 364:2483-2495.
Mira JP. Facts or myths: early albumin resuscitation during septic shock (the EARSS trial) [Internet]. Berlin; 2011. Available at: http://www.esicm.org/flash
Conference/2011/Berlin/10438/swf/player.swf. [Accessed 17 June 2013]
Guidet B, Martinet O, Boulain T, et al.
Assessment of hemodyanmic efficacy and safety of 6% hydroxyethyl starch sepsis. The CRYSTMAX study. Crit Care 2012; 16:1-33.
Myburgh JA, Finfer S, Bellomo R, et al.
Hydroethyl starch or saline for fluid resuscitation in intensive care. N Engl J Med 2012; 367:1901-1911.
Karakala N, Raghunathan K, Shaw AD. Intravenous fluids in sepsis: what to use and what to avoid. Curr Opin Crit Care 2013; 19:537-543.
Delaney AP, Dan A, McCaffrey J, Finfer S. The role of albumin as a resuscitation fluid for patients with sepsis: a systematic review and meta-anslysis. Crit Care Med 2011; 39:386-391.
Caironi P, Tognoni G, Masson S, Fumagalli R, Pesenti A, et al.
Albumin replacement in patients with severe sepsis or septic shock. N Engl J Med 2014; 370:1412-1421.
Vincent JL, Dubois MJ, Navickis RJ, Wilkes MM. Hypoalbuminemia in acute illness: is there a rationale for intervention? A meta-analysis of cohort studies and controlled trials. Ann Surg 2003; 237:319-334.
Chou CD, Yien HW, Wu DM, Kuo CD. Albumin administration in patients with severe sepsis due to secondary peritonitis. J Chin Med Assoc 2009; 72:243-250.
Gattas DJ, Dan A, Myburgh J, Billot L, Lo S, Finfer S. Fluid resuscitation with 6% hydroxyethyl starch (130/0.4 and 130/0.42) in acutely ill patients: systematic review of effects on mortality and treatment with renal replacement therapy. Intensive Care Med 2013; 9:782-783.
Zarychanski R, Abou-Setta AM, Turgeon AF, et al.
Association of hydroxyethyl starch administration with mortality and acute kidney injury in critically ill patients requiring volume resuscitation: a systematic review and meta-analysis. JAMA 2013; 309:678-688.
Patel A, Waheed U, Brett SJ. Randomized trials of 6% tetrastarch (hydroxyethyl starch 130/0.4 or 0.42) for severe sepsis reporting mortality: systematic review and meta-analysis. Intensive Care Med 2013; 39:811-822.
Haase N, Perner A, Hennings LI, et al.
Hydroxyethyl starch 130/0.38-0.45 versus crystalloid or albumin in patients with sepsis. Crit Care Med 2006;20:310-312.
Myburgh JA, Mythen MG. Fluid resuscitation. N Engl J Med 2013; 369:1243-1251.
Guidet B, Martinet O, Boulain T, et al
. Assessment of hemodynamic efficacy and safety of 6% hydroxyethyl starch 130/0.4 vs 0.9% NaCl fluid replacement in patients with severe sepsis: the CRYSTMAS study. Critical Care 2012; 16:R94.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]