|Year : 2019 | Volume
| Issue : 2 | Page : 23-29
Comparative effects of human albumin versus modern hydroxyethyl starch in living-donor renal transplant
Nazmy E Seif, Ahmed K Mohammed
Department of Anesthesia, Surgical Intensive Care and Pain Management, Faculty of Medicine, Cairo University, Giza, Egypt
|Date of Submission||05-Jan-2019|
|Date of Decision||24-Apr-2019|
|Date of Acceptance||20-Jun-2019|
|Date of Web Publication||15-Nov-2019|
Ahmed K Mohammed
Department of Anesthesia, Surgical Intensive Care and Pain Management, Faculty of Medicine, Cairo University, Giza, 11562 Kasr Alaini
Source of Support: None, Conflict of Interest: None
Background Living-donor renal transplantation is considered the best therapy for renal failure patients. The outcome and graft function are affected by various perioperative variables. Fluid management remains a controversy whether to use crystalloids or colloids with the effect of either type of solution on graft function and overall morbidity.
Patients and methods We studied 120 patients with end-stage renal disease, who were on regular hemodialysis scheduled for living-related kidney transplantation. The patients were assigned to receive either 6% hydroxylethyl starch (HES) 130/0.4 (Voluven) (HES group: n=60) or albumin 5% (ALB group: n=60) for intraoperative use. In both groups, normal saline was administered at 10 ml/kg/h. In addition, patients received 250 ml boluses of either Voluven (HES group) with a maximum of 50 ml/kg/day or ALB 5% (ALB group) to maintain their central venous pressure between 12 and 15 mmHg. Blood transfusion was given based on the hemoglobin level (<7 g/dl). Hemodynamic variables (mean arterial pressure and central venous pressure) were recorded. We recorded the cold and warm ischemia times, the operative time and the time of start of graft diuresis. Urine output, serum creatinine, blood urea nitrogen (BUN), and International Normalized Ratio (INR) were recorded by the end of surgery, then every 24 h during the first 3 postoperative days and once again on day 7. Creatinine clearance was calculated on post-transplant days 1, 2, 3, and 7. The need for postoperative dialysis within the first week and the incidence of early graft rejection were noted.
Results There were no statistically significant differences between the two groups regarding hemodynamic variables, onset of diuresis, or need for postoperative dialysis. Perioperative laboratory workup (BUN, creatinine, creatinine clearance, and INR) were similar in both study groups.
Conclusion There are no statistically significant differences between the use of HES solutions and ALB 5% on the outcome of living-donor renal transplant recipients. Using either solutions is comparable to the other with no special side effects.
Keywords: anesthesia, complications, fluids, kidney, transplantation
|How to cite this article:|
Seif NE, Mohammed AK. Comparative effects of human albumin versus modern hydroxyethyl starch in living-donor renal transplant. Egypt J Cardiothorac Anesth 2019;13:23-9
|How to cite this URL:|
Seif NE, Mohammed AK. Comparative effects of human albumin versus modern hydroxyethyl starch in living-donor renal transplant. Egypt J Cardiothorac Anesth [serial online] 2019 [cited 2020 Feb 26];13:23-9. Available from: http://www.ejca.eg.net/text.asp?2019/13/2/23/271084
| Introduction|| |
Renal transplant (RT) is now considered the best therapeutic option for end-stage renal failure. It not only improves quality of life; it also prolongs life . Living-donor RT provides significant advantages compared with cadaveric donor RT .
A successful outcome after transplant is influenced by appropriate preoperative assessment and drug treatment, close intraoperative monitoring, optimization of intravascular fluid volume, and the appropriate use of anesthetic agents . Adequate fluid maintenance is essential in order to ensure restoration and maintenance of the intravascular volume so that an appropriate graft function can be obtained after RT .
Fluid management remains a controversial subject in perioperative medicine and organ transplantation. Colloids may be preferred to crystalloids to maintain effective cardiac output and tissue oxygenation . Artificial colloids such as gelatin and dextran are known to affect the kidneys adversely. Albumin (ALB) is a normal endogenous colloid with a wide safety margin. Furthermore, ALB also protects the kidney by scavenging the reactive oxygen species and inhibiting apoptosis . Hydroxylethyl starch (HES) is a widely used, inexpensive alternative to human ALB.
Multiple authors have expressed concerns about HES-associated renal dysfunction . Although some studies have found HES solutions to have little effect on renal function ,, others have shown cause for concern ,. It has been suggested that the modern generation HES solutions, for example, HES 130/0.4 may be less likely to induce nephrotoxicity .
The aim of this study was, therefore, to investigate the possible adverse effects on renal graft function in living-donor RT of fluid therapy with modern HES solutions (HES 6% 130/0.4), compared with human ALB 5%.
| Patients and methods|| |
Following approval of the local ethics committee, written informed consent was obtained from all patients enrolled in this prospective, randomized, double-blinded study.
We studied 120 patients aged 18–60 years with end-stage renal disease, who were on regular hemodialysis, ASA III and IV scheduled for living-related kidney transplantation. Exclusion criteria were retransplantation, severe cardiovascular disease, hepatic dysfunction, or coagulopathy.
Using sealed envelopes and computer-generated randomization, 120 patients were assigned to receive either 6% HES 130/0.4 (Voluven; Fresenius Kabi, Bad Homburg, Germany) (HES group: n=60) or ALB 5% (ALB group: n=60) as their colloid for intraoperative use.
Before transplantation, each patient was premedicated with oral diazepam (10 mg) and ranitidine (50 mg) and an intravenous access was secured and tested.
After preoxygenation, general anesthesia was induced with intravenous administration of fentanyl (2 µg/kg), propofol (1–2 mg/kg), atracurium (0.5 mg/kg), and lidocaine to reduce the pressor response to intubation (1.5 mg/kg). Maintenance was achieved with 0.8–1.5% isoflurane in an O2/air mixture, atracurium infusion at 0.5 mg/kg/h, and fentanyl infusion at 1 µg/kg/h.
Mechanical ventilation was provided using a tidal volume of 4–6 ml/kg with the respiratory rate adjusted to maintain a PaCO2 of between 30 and 35 mmHg, keeping the peak airway pressure at around 15 cm H2O.
A 20-G arterial cannula was inserted in the radial artery on the other side of the arteriovenous fistula if available, or else in the dorsalis pedis artery on the side not affected by intraoperative vascular clamping (the side where the iliac artery was clamped during arterial anastomosis of the graft). A central venous catheter was also inserted after induction of anesthesia.
All patients were monitored using a 5-lead ECG with ST segment analysis, pulse oximetry noninvasive and invasive blood pressure (BP), end-tidal capnography, esophageal temperature, and intraoperative hourly arterial blood gases (ABG) analysis (additional samples are available if needed and are managed accordingly; if it shows something that affects the overall morbidity, the patient is dropped out of the study); urinary output and central venous pressure (CVP) were also measured.
In both groups, normal saline solution was administered routinely at 10 ml/kg/h. In addition, intraoperatively, the patient received 250 ml boluses of either Voluven (HES group) with a maximum of 50 ml/kg/day or ALB 5% (ALB group) (maximum ALB 2 g/kg/day, average 40 ml/kg/day) to maintain their CVP between 12 and 15 mmHg. Blood transfusion was given based on a hemoglobin level less than 7 g/dl.
Intraoperative hypertension (increase of systolic BP<150 mmHg or>25% increase from the patient’s baseline systolic BP) was treated with intravenous nitroglycerin infusion (0.5–10 µg/kg/min), while keeping systolic BP at more than 130 mmHg.
Each recipient was given methylprednisolone 250 mg at the induction of anesthesia and another 250 mg during graft revascularization, and was placed on the same immunosuppressive protocol postoperatively. A measure 0.5–1 mg/kg of furosemide was given 10 min before revascularization to all recipients.
At the end of the surgery, after discontinuation of inhalational anesthesia and neuromuscular blocker infusion and reversal of the residual block with neostigmine (0.5 mg/kg) and atropine (0.02 mg/kg), the patients were uneventfully extubated.
Postoperatively, the recipients were nursed in a high-dependency setting on a renal ward. Study fluids were discontinued and all the patients received an infusion of dextrose 5/0.45% normal saline at a rate of 1 ml/kg/h, in addition to the replacement of the previous hour’s urine output with 0.45% normal saline.
Hemodynamic variables (mean arterial BP and CVP) were recorded after induction of anesthesia, before vascular declamping and at the end of surgery.
Total intraoperative colloid infusion given as intravascular volume replacement therapy, either volaven (HES group) or ALB 5% (ALB group), was calculated for each recipient.
We recorded the cold and warm ischemia times, the operative time, and the time of start of graft diuresis (categorized as immediate, when diuresis started in the operating room or during the initial 4 postoperative hours, or late if it started after 4 h).
Total volume of urine output, serum creatinine, blood urea nitrogen (BUN), and International Normalized Ratio (INR) were recorded by the end of surgery, then every 24 h during the first 3 postoperative days and once again on the seventh postoperative day. Creatinine clearance (CrCl) was calculated from samples of a complete 24-h urine collection on post-transplant days 1, 2, 3, and 7.
The need for postoperative dialysis within the first week and the incidence of early graft rejection were noted (within 1 week postoperatively).
Power analysis was performed using Student’s t-test for independent samples on CrCl 24 h after surgery because it was the main outcome variable in this study. A previous study showed that the SD of CrCl in post-transplant patients was nearly 20 ml/min . On the assumption that a mean difference of 20 ml/min was considered a clinically significant difference between groups and taking power 0.8 and α error 0.05, a minimum sample size of 48 patients was calculated for each group. The number was increased up to 60 to compensate for dropouts.
Data were coded and entered using the statistical package statistical package for the social sciences (SPSS) version 24 (2016), IBM Corp., Armonk, NY, USA. Data were summarized using mean, SD, median, minimum and maximum in quantitative data and using frequency (count) and relative frequency (percentage) for categorical data. Comparisons between quantitative variables were done using unpaired t-test. For comparing categorical data, χ2-test was performed. Exact test was used instead when the expected frequency is less than 5. P values of less than 0.05 were considered as statistically significant.
| Results|| |
In all,120 patients, meeting our inclusion criteria, were enrolled in the study and were randomly allocated into one of the two groups: Tetraspan (FRESENIUS KABI, Bad Homburg, Germany) (HES) group and ALB group. All 120 enrolled patients completed the study.
Demographic data (age, sex, BMI, and ASA class) ([Table 1]) and the preoperative laboratory work were similar in both groups. The intraoperative graft characteristics (cold ischemic time, warm ischemic time. and the total operative time) were also comparable in the two groups ([Table 2],[Table 3],[Table 4],[Table 5],[Table 6],[Table 7]).
There was no statistical difference in the study colloid volume required intraoperatively for each group (700±128.65 ml in the HES group vs. 728.33±139.38 ml in the ALB group, P=0.417) as well as concerning the intraoperative blood loss ([Table 2]). The use of crystalloids, packed red blood cells (RBCs) and fresh frozen plasma and the diuretics consumption did not vary in between the two groups.
The hemodynamic variables remained stable and did not show a significant difference between the study groups at any of the measuring points, in terms of the mean BP and the CVP ([Figure 1] and [Figure 2]).
Start of diuresis was immediate in all patients except for four (6.7%) in the HES group and six (10%) in the ALB group. In respect of later graft function, it was evaluated using postoperative BUN, creatinine (Cr), CrCl, and 24-h urine volume. We did not observe differences in all these parameters throughout the entire study period being measured on the first, second, third, and seventh post-transplant days, irrespective of whether Tetraspan or ALB was infused (Figs 3–6). Regarding the coagulopathic effect, both groups showed comparable results in their postcolloid infusion INR (Fig. 7).
Dialysis was needed for six patients in the ALB group and four patients in the HES group (P=1). No cases suffering a graft rejection episode were reported for the 1-week duration of the study following transplantation.
| Discussion|| |
In this study, we compared the RT outcomes of patients receiving HES 130/0.4, as an intraoperative colloid solution, with those of patients receiving ALB 5%. No differences were detectable, suggesting that modern HES exerts no adverse effects in living-donor kidney transplantation and does not negatively influence graft function or transplant results.
Acute tubular necrosis (ATN) is the most common cause of delayed graft function and acute kidney failure in the early postoperative period and diminishes graft survival . Therefore, the ultimate goal of anesthetic management is the prevention of ATN . ATN has been reported to be lower in patients who are profoundly hydrated ,. Hyperhydration is known to dilate the atria, leading to the release of atrial natriuretic peptide . It also leads to increased renal perfusion .
This study found no deleterious effects on renal graft function with the use of HES 130/0.4 as a primary colloid therapy during surgery compared with 5% ALB, as measured by serum creatinine, urea nitrogen, and CrCl. Evaluating post-transplant kidney functions, we observed that there were no significant differences between the groups. Sufficient amounts of crystalloids should, however, be infused together with HES .
Cittanova et al. , noted, in their retrospective study involving kidney transplant patients, that osmotic nephrosis occurred after using the less-metabolizable HES specification (HES 200/0.62). In the Cittanova et al.  study, immediate renal function was found to be impaired in RT recipients whose donors were infused with the higher molecular weight HES (200/0.62). However, another retrospective study, done by Deman et al. , concluded that HES given at a maximum dosage of 15 ml/kg/day to the donors had no detrimental effect on renal function in the recipients; and suggested that the nephrotoxicity noted by Legendre et al. , might have resulted from the use of a particular preservation agent.
In the considerable body of clinical data on the third generation HES 130/0.4, there have been no reports of adverse effects on renal function over and above those seen in control groups in patients who are considered to be at particular risk, such as those with previous mild to severe renal dysfunction , the elderly , and those receiving high-dose therapy .
Hemodynamics in both groups in this study were similar over the entire study period. We did not also need a higher total volume of HES than ALB to maintain the desired intravascular volume in the target population. This is contrary to the results of Persson and Grande , who demonstrated that the plasma-expanding effects after hemorrhage were significantly greater with 20 ml/kg of 5% ALB than with the same amount of 6% HES 130/0.4.
One major concern about the use of HES preparations is the potential for inducing disorders in coagulation . In this study, routine anticoagulation tests did not show any differences between the two study arms.
Tetrastarch solutions appear less likely to impair platelet function and plasmatic coagulation as compared with first-generation or second-generation HES products ,.
Hanart et al.  showed that intraoperative volume replacement with 50 ml/kg of 6% HES 130/0.4 versus the same amount of 4% ALB for children undergoing cardiac surgery resulted in the transfusion of allogenic blood in fewer subjects and a significantly lower intraoperative fluid balance, whereas both measured and calculated intraoperative and postoperative blood loss were not different among groups.
Wilkes et al.  published the results of a meta-analysis, including a total of 653 randomized patients, comparing the influence of ALB versus different HES preparations with high molecular weight (HMWs) of 450 or 200 KD (Kilodalton) on postoperative bleeding after Cardio-Pulmonary Bypass (CPB) surgery, the analysis indicated that the amount of postoperative blood loss was significantly lower in patients treated with ALB versus high-HMW HES but not versus medium-medium molecular weight (MMW) HES.
Another meta-analysis including 73 randomized trials compared the clinical outcome in adult patients receiving colloids in the perioperative period . It was found that tetrastarches were associated with a 15% reduction in blood loss compared with gelatin and pentastarches. Pentastarches were associated with larger perioperative blood loss (10%) as compared with ALB; all other clinical outcome variables were similar between groups.
The worth to mention limitation of this study is that we did not gather long-term follow-up data, beyond the seventh day post-transplantation.
| Conclusion|| |
As for a short-term outcome, intraoperative administration of HES 130/0.4 (≤50 ml/kg/day) did not alter the renal graft function or recipient outcome and consequently can be safely used in the perioperative period during kidney transplants.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Jankovic Z, Sri-Chandana C. Anaesthesia for renal transplant: recent developments and recommendations. Curr Anaesth Crit Care 2008; 19:247–253.
Jankovic Z. Anaesthesia for living-donor renal transplant. Curr Anaesth Crit Care 2008; 19:175–180.
Sarinkapoor H, Kaur R, Kaur H. Anaesthesia for renal transplant surgery. Acta Anaesthesiol Scand 2007; 51:1354–1367.
Schnuelle P, Johannes van der Woude F. Perioperative fluid management in renal transplantation: a narrative review of the literature. Transpl Int 2006; 19:947–959.
Mukhtar A, Aboulfetouh F, Obayah G, Salah M, Emam M, Khater Y et al.
The safety of modern hydroxyethyl starch in living donor liver transplantation: a comparison with human albumin. Anesth Analg 2009; 109:924–930.
Davidson IJ. Renal impact of fluid management with colloids: a comparative review. Eur J Anesthesiol 2006; 23:721–738.
Wiedermann CJ. Renal impairment in cardiac surgery patients receiving hydroxyethyl starch. Intensive Care Med 2004; 30:519–520.
Boldt J, Brosch C, Ducke M, Papsdorf M, Lehmann A. Influence of volume therapy with a modern hydroxyethylstarch preparation on kidney function in cardiac surgery patients with compromised renal function: a comparison with human albumin. Crit Care Med 2007; 35:2740–2746.
Sakr Y, Payen D, Reinhart K, Sipmann FS, Zavala E, Bewley J et al.
Effects of hydroxyethyl starch administration on renal function in critically ill patients. Br J Anaesth 2007; 98:216–224.
Winkelmayer WC, Glynn RJ, Levin R, Avorn J. Hydroxyethyl starch and change in renal function in patients undergoing coronary artery bypass graft surgery. Kidney Int 2003; 64:1046–1049.
Mahmood A, Gosling P, Vohra RK. Randomized clinical trial comparing the effects on renal function of hydroxyethyl starch or gelatine during aortic aneurysm surgery. Br J Surg 2007; 94:427–433.
Schabinski F, Oishi J, Tuche F, Luy A, Sakr Y, Bredle D et al.
Effects of a predominantly hydroxyethyl starch (HES)-based and a predominantly non HES-based fluid therapy on renal function in surgical ICU patients. Intensive Care Med 2009; 35:1539–1547.
Mukhtar A, EL Masry A, Moniem AA, Metini M, Fayez A, Khater YH. The impact of maintaining normal serum albumin level following living related liver transplantation: does serum albumin level affect the course? A pilot study.Transplant Proc 2007; 39:3214–3218.
Koehntop DE, Beebe DS, Belani KG. Kidney transplantation. In: Klinck JR, Lindop MJ, editors. Anesthesia and intensive care for organ transplantation. London: Chapman & Hall 1998. pp. 253–280.
Visser WA. Anaesthesia for renal transplantation. Curr Anaesth Crit Care 1999; 10:286–290.
Thomsen HS, Lokkegaard H, Munck O. Influence of normal central venous pressure on onset of function in renal allografts. Scand J Urol Nephrol 1987; 21:143–145.
Carlier M, Squifflet JP, Pirson Y, Gribomont B, Alexandre GP. Maximal hydration during anaesthesia increases pulmonary arterial pressures and improves early function of human renal transplants. Transplantation 1982; 34:201–204.
Hestin D, Mertes PM, Hubert J, Claudon M, Mejat E, Renoult E et al.
Relationship between blood pressure and renin, angiotensin II and atrial natriuretic factor after renal transplantation. Clin Nephrol 1997; 48:98–103.
Cittanova ML, Leblanc I, Legendre C, Mouquet C, Riou B, Coriat P. Effect of hydroxyethyl starch in brain-dead kidney donors on renal function in kidney-transplant recipients. Lancet 1996; 348:1620–1622.
Pillebout E, Nochy D, Hill G, Conti F, Antoine C, Calmus Y, Glotz D. Renal histopathological lesions after orthotopic liver transplantation (OLT). Am J Transplant 2005; 5:1120–1129.
Deman A, Peeters P, Sennesael J. Hydroxyethyl starch does not impair immediate renal function in kidney transplant recipients: a retrospective multicentre analysis. Nephrol Dial Transplant 1999; 14:1517–1520.
Jungheinrich C, Scharpf R, Wargenau M, Bepperling F, Baron JF. The pharmacokinetics and tolerability of an intravenous infusion of the new hydroxyethyl starch 130/0.4 (6%, 500 ml) in mild-to-severe renal impairment. Anesth Analg 2002; 95:544–551.
Fenger-Eriksen C, Hartig Rasmussen C, Kappel Jensen T, Anker-Møller E, Heslop J, Frøkiaer J, Tønnesen E. Renal effects of hypotensive anaesthesia in combination with acute normovolaemic haemodilution with hydroxyethyl starch 130/0.4 or isotonic saline. Acta Anaesthesiol Scand 2005; 49:969–974.
Neff TA, Doelberg M, Jungheinrich C, Sauerland A, Spahn DR, Stocker R. Repetitive large-dose infusion of the novel hydroxyethyl starch 130/0.4 in patients with severe head injury. Anesth Analg 2003; 96:1453–1459.
Persson J, Grande PO. Volume expansion of albumin, gelatin, hydroxyethyl starch, saline and erythrocytes after haemorrhage in the rat. Intensive Care Med 2005; 31:296–301.
Treib J, Haass A, Pindur G. Coagulation disorders caused by hydroxyethyl starch. Thromb Haemost 1997; 78:974–983.
Treib J, Haass A, Pindur G, Seyfert UT, Treib W, Grauer MT et al.
HES 200/0.5 is not HES 200/0.5. Influence of the C2/C6 hydroxyethylation ratio of hydroxyethyl starch (HES) on hemorheology, coagulation and elimination kinetics. Thromb Haemost 1995; 74:1452–1456.
Treib J, Haass A, Pindur G, Treib W, Wenzel E, Schimrigk K. Influence of intravascular molecular weight of hydroxyethyl starch on platelets. Eur J Haematol 1996; 56:168–172.
Hanart C, Khalife M, De Ville A, Otte F, De Hert S, Van der Linden P. Perioperative volume replacement in children undergoing cardiac surgery: albumin versus hydroxyethyl starch 130/0. 4. Crit Care Med 2009; 37:696–701.
Wilkes MM, Navickis RJ, Sibbald WJ. Albumin versus hydroxyethyl starch in cardiopulmonary bypass surgery: a meta-analysis of postoperative bleeding. Ann Thorac Surg 2001; 72:527–533.
Cheng D, Belisle S, Giffin M, Karkouti K, Martin J, James M et al.
Colloids for perioperative plasma volume expansion: systematic review with meta-analysis of controlled trials (Abstract). Transfus Altern Transfus Med 2007; 9:S3.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]