Jakob Gubensek

Treatment of hyperlipidemic acute pancreatitis with plasma exchange: a single-center experience.

Of the cases of acute pancreatitis, 1–7% are caused by severe hypertriglyceridemia and can be treated with plasma exchange (PE). We report on a large series of patients with acute hyperlipidemic pancreatitis (HLP) treated with PE. In the 1992–2008 period, 50 patients (45 ± 8 years old, 92% male) with acute HLP were treated with PE, during which 1–2 plasma volumes were exchanged. Heparin was used as anticoagulant in 85% of the procedures, and citrate in the rest. Cholesterol and triglycerides were measured before and after PE. In the 2003–2008 cohort of 40 patients, we retrospectively recorded an Acute Physiology and Chronic Health Evaluation II (APACHE II) score at the first PE session, hospital mortality, and length of hospital stay. A total of 79 PE treatments were done, 1–5 per patient. The volume exchanged was 4890 ± 1300 mL over a duration of 3.5 ± 2 h. During the first PE, the triglycerides were lowered from 58.9 ± 40.8 to 10.8 ± 10.8 mmol/L, and the total cholesterol was lowered from 20.0 ± 7.6 to 5.7 ± 4.3 mmol/L. In 10% of the procedures the plasmafilter was replaced, and in 3% the filter was clotted. Hypotension occurred in 3% of PE and there was one case of gastrointestinal bleeding after PE with heparin anticoagulation. In the 2003–2008 cohort, the median APACHE II score was 5 (range 0–15), the median overall hospital stay was 18 days (range 3–142 days) and the hospital mortality was 15%. To conclude, in acute hyperlipidemic pancreatitis, one to two plasma exchanges effectively reduce the serum triglyceride level. There is a low rate of procedure‐related complications. A mortality rate of 15% is considerable.

Factors Affecting Outcome in Acute Hypertriglyceridemic Pancreatitis Treated with Plasma Exchange: An Observational Cohort Study

Objectives The optimal therapy for hypertriglyceridemic acute pancreatitis, especially the role of plasma exchange (PE), is not entirely clear. The aim of our large, single-center, observational, cohort study was to analyze the factors affecting outcome in hypertriglyceridemic pancreatitis treated with PE. Methods We included 111 episodes of hypertriglyceridemic pancreatitis treated with PE, which occurred in 103 different patients. The Acute Physiology and Chronic Health Evaluation (APACHE) II score, triglycerides, delay to first PE, and PE treatment details were retrospectively obtained from the patients’ records. The main outcome measures were length of hospitalization and in-hospital mortality. Results The patients were 47±9 years old and the median APACHE II score at first PE was 4 (inter-quartile range (IQR) 2–7). There was a seasonal variation in the incidence of hypertriglyceridemic pancreatitis, and the recurrence rate was 1.6% per year. Triglycerides at presentation did not correlate with APACHE II or influence the outcome. The mean reduction in triglycerides during PE was 59% (from 44±31 to 18±15 mmol/l), which was twice the reduction observed during conservative treatment (27% daily). The median hospital stay was 16 days (IQR 10–24) and in-hospital mortality was 5%. The median delay to first PE was 35 hours (IQR 24–52), and there was no difference in mortality in the early and late PE groups (7% vs. 6%, p = 0.79). The group with citrate anticoagulation during PE had a significantly lower mortality than the group with heparin anticoagulation (1% vs. 11%, p = 0.04), and citrate was an independent predictor also in the multivariate model (p = 0.049). Conclusions PE effectively reduced serum triglycerides faster than could be expected with conservative treatment. The delay in PE therapy did not influence survival. We found that citrate anticoagulation during PE was associated with reduced mortality, which should be confirmed in a randomized study.

Comparison of Citrate Anticoagulation During Plasma Exchange With Different Replacement Solutions

The aim of our retrospective study was to compare the application of regional citrate anticoagulation and citrate‐related side‐effects in plasma exchange (PE) with different replacement solutions. We included 35 patients treated with PE with regional citrate anticoagulation and divided them into three groups according to the replacement solution used: human albumin (HA) group (40 PE treatments), fresh frozen plasma (FFP) group (86 PE treatments), or a combination of the two (63 PE treatments). The citrate anticoagulation parameters, ionized calcium and metabolic consequences of citrate were compared. The blood flow and citrate infusion rates were similar in all groups. To maintain comparable values of ionized calcium during PE, significantly more calcium was replaced in the combination group (7.6 ± 1.3 vs. 6.2 ± 2.7 mL/h, P < 0.001) and even more in the FFP group (10.8 ± 1.7 vs. 6.2 ± 2.7 mL/h, P < 0.001) as compared to the HA group. The pH increased significantly and comparably in all groups, but the increase in bicarbonate was significantly higher in the FFP group (4.4 ± 3.0 vs. 2.6 ± 2.1 mmol/L, P = 0.01). A short, heparin‐free hemodialysis session was performed after the PE treatment, because of significant metabolic alkalosis (mainly with pH ≥ 7.5), significantly more often in the FFP group (14/86 PE, P < 0.01) as compared to the HA group (0/40), and only rarely in the combination group (2/63). To conclude, when FFP is used as a replacement solution during PE with citrate anticoagulation, significantly more calcium needs to be replaced and the increase in bicarbonate is greater during PE. The additional citrate contained in FFP, combined with frequent PE treatments, often causes significant metabolic alkalosis, which can be efficiently corrected with a short heparin‐free hemodialysis.

Citrate anticoagulation for single-needle hemodialysis: safety and efficacy.

Abstract:  Single‐needle hemodialysis can be the only option in some patients and requires full heparinization. The aim of our retrospective clinical study was to evaluate the safety and efficacy of regional citrate anticoagulation for single‐needle hemodialysis. Citrate anticoagulation was performed during 41 single‐needle hemodialysis procedures in 24 patients at risk of bleeding, using 4% trisodium citrate, 1 M CaCl2 and calcium‐free dialysate. Safety was assessed by the percentage of procedures that were terminated prematurely or changed to another modality due to citrate‐related complications and by incidence of important hypocalcemia. Efficacy was evaluated by visually assessing  clot  formation  in  the  circuit.  Five  per  cent  of  the procedures were terminated prematurely. Important hypocalcemia was recorded in 34% of the procedures. Anticoagulation was suboptimal in 17% of the procedures, but none of the systems clotted. The median dialyzer assessment grade was excellent. The average protocol parameters  were:  blood  flow  244 ± 27 mL/min,  starting  rate of citrate 191 ± 19 mL/h, starting rate of calcium 6.7 ± 1.1 mL/h. In the first hour, ionized calcium decreased in 67% of the procedures by 0.08 ± 0.05 mmol/L. During the entire procedure, ionized calcium decreased in 80% of the cases by 0.17 ± 0.09 mmol/L. There was a significant, but small increase in sodium (135 ± 4 vs 137 ± 4 mmol/L) and no increase in bicarbonate. Citrate anticoagulation during single‐needle hemodialysis, according to our protocol, is safe and effective. Close monitoring of ionized calcium is mandatory. The calcium infusion rate should frequently be increased to correct hypocalcemia. The increased starting rate of calcium should be evaluated.

Standard citrate versus sequential citrate/anticoagulant-free anticoagulation during hemodialysis: a randomized trial.

In a randomized study, sequential anticoagulation for hemodialysis (citrate for the first 3.5 h, switching to 30-min anticoagulation-free hemodialysis) was compared to standard citrate anticoagulation. Fifty-two hemodialysis procedures were randomized either to sequential (n = 27) or standard citrate group (n = 25). The antithrombotic effect in the circuit was visually assessed after hemodialysis using a score from 1 (total clotting) to 5 (no clotting). The antithrombotic score for sequential versus standard group was as follows: dialyzer, 4.0 +/- 1.1 versus 4.8 +/- 0.4 (P < 0.01); arterial bubble trap, 4.0 +/- 1.2 versus 4.7 +/- 0.6 (P = 0.013); venous bubble trap, 4.0 +/- 1.3 versus 4.8 +/- 0.6 (P < 0.01). Serum citrate levels during sequential versus standard citrate anticoagulation (micromol/L) were as follows: at the beginning, 143 +/- 65 versus 148 +/- 77 (not significant [NS]); after 2 h, 317 +/- 157 versus 354 +/- 111 (NS); at the end, 125 +/- 81 versus 405 +/- 133 (P < 0.01). Sequential anticoagulation reduces the final serum citrate concentration to predialysis level. It can be a good anticoagulation strategy for patients in whom the reduction of citrate load is desired.

Hemodialysis Catheters With Citrate Locking in Critically Ill Patients With Acute Kidney Injury Treated With Intermittent Online Hemofiltration or Hemodialysis

The purpose of the study was to compare the long‐term catheter‐related complications associated with temporary untunneled hemodialysis catheters, locked with citrate in the interdialysis period, inserted in critically ill patients with acute kidney injury, between different catheter insertion sites (femoral vs. jugular and subclavian) and catheter types (single‐lumen [SL] vs. double‐lumen [DL]). In a retrospective clinical study, the long‐term catheter‐related complications in 290 critically ill patients treated with intermittent high‐volume online hemofiltration or hemodialysis between December 2004 and January 2008 were analyzed. Among 534 inserted catheters, 493 (92.3%) were femoral, 29 (5.4%) jugular, and 12 (2.3%) subclavian; 304 (56.9%) were SL and 230 (43.1%) were DL. There were 125 (20.3/1000 catheter days [c.d.]) thrombotic complications, while infectious complications were exceptionally rare, that is, only 13 (2.1/1000 c.d.), of which 10 (1.6/1000 c.d.) were possible catheter‐related bloodstream infections and 3 (0.5/1000 c.d.) exit‐site infections. The incidence rate of all thrombotic complications was significantly lower in all jugular and subclavian vs. all femoral catheters (7.7/1000 c.d. vs. 21.8/1000 c.d., P = 0.01), and in all SL vs. DL catheters (11.4/1000 c.d. vs. 32.2/1000 c.d., P < 0.001). The incidence rate of any possible catheter‐related bloodstream and exit‐site infections was not significantly different in all jugular and subclavian vs. all femoral catheters, neither in femoral SL vs. DL catheters. The major long‐term catheter‐related complications were thrombotic, and significantly more frequent in DL vs. SL catheters. Infectious complications were exceptionally rare, most probably due to the strict catheter care protocol, as well as the routine use of a citrate catheter lock and antibiotic ointment at the catheter exit‐site.

Dialysis Patients Refusing Kidney Transplantation: Data From the Slovenian Renal Replacement Therapy Registry

Kidney transplantation is considered the best renal replacement therapy (RRT) for patients with end‐stage renal disease; nevertheless, some dialysis patients refuse to be transplanted. The aim of our registry‐based, cross‐sectional study was to compare kidney transplant candidates to dialysis patients refusing transplantation. Data were collected from the Slovenian Renal Replacement Therapy Registry database, as of 31 December 2008. Demographic and some RRT data were compared between the groups. There were 1448 dialysis patients, of whom 1343 were treated by hemodialysis and 105 by peritoneal dialysis (PD); 132 (9%) were on the waiting list for transplantation, 208 (14%) were preparing for enrollment (altogether 340 [23%] dialysis patients were kidney transplant candidates); 200 (13.7%) patients were reported to refuse transplantation, all ≤65 years of age; 345 (24%) were not enrolled due to medical contraindications, 482 (33%) due to age, and 82 (6%) due to other or unknown reasons. No significant difference was found in age, gender, or presence of diabetes between kidney transplant candidates vs. patients refusing transplantation (mean age 50.5 ± 13.9 vs. 51.3 ± 9.6 years, males 61% vs. 63%, diabetics 18% vs. 17%). The proportion of patients ≤ 65 years old who were refusing transplantation was 28% (187/661) for hemodialysis and 17% (13/79) for PD patients (P = 0.03). There is a considerable group of dialysis patients in Slovenia refusing kidney transplantation. Compared to the kidney transplant candidates, they are similar in age, gender and prevalence of diabetes. Patients treated by peritoneal dialysis refuse kidney transplantation less often than hemodialysis patients.

Regional Citrate Anticoagulation for Single-Needle Hemodialysis: A Prospective Clinical Study

Aim: Regional citrate anticoagulation protocol for single-needle hemodialysis was tested prospectively for safety and efficacy. Methods: 15 chronic dialysis patients at risk of bleeding were included. 4 % trisodium citrate (200 ml/h), calcium-free dialysate and 1 mol/l calcium chloride (7 ml/h) were used. After dialysis the antithrombotic effect in the circuit was assessed visually (grade 5, no clotting, to 1, total occlusion) and serum citrate was measured. Results: Of 32 dialyses performed, 94% were uneventful and in 2 cases (6%) there was severe (ionized calcium ≤0.8 mmol/l) but asymptomatic hypocalcemia. Mean anticoagulation score after dialysis was 4.8 ± 0.7 for the arterial bubble trap, 4.6 ± 0.8 for the dialyzer and 4.8 ± 0.7 for the venous bubble trap. Serum citrate after dialysis was 158 ± 60 µmol/l. Conclusion: Regional citrate anticoagulation in single-needle dialysis is safe and efficient.

Treatment Efficacy and Safety During Plasma Exchange With Citrate Anticoagulation: A Randomized Study of 4 Versus 15% Citrate

In plasma exchange (PE), contrary to dialysis, there is no ultrafiltration, and the volume of anticoagulant contributes to volume overload of the patient and might also reduce PE efficiency through dilution. To reduce the volume of citrate, we compared 4 and 15% citrate anticoagulation protocols in PE in a randomized study, aiming to evaluate PE efficacy, anticoagulation efficiency, and overall safety. In addition to standard biochemical analyses during PE treatments, the elimination rate (ER) of immunoglobulins was calculated to evaluate PE efficacy. Anticoagulation was evaluated by postfilter ionized calcium, visual evaluation of the extracorporeal system, and change in the sieving coefficient (SC) during PE. Accumulation of citrate was determined by calculating the total-to-ionized calcium ratio and measuring the citrate concentration after PE. One hundred forty procedures (70 in each group) were performed in 37 patients. The mean citrate infusion rate was 197 ± 10 mL/h in the 4% and 59 ± 5.5 mL/h in the 15% groups, respectively; the total volume of infused citrate was 502 ± 77 mL versus 164 ± 52 mL (P < 0.001). ER for immunoglobulin G (0.57 ± 0.06 vs. 0.55 ± 0.1, P = 0.18), M, and A were comparable. Ionized calcium was stable during the procedures, and there were no significant side effects. Although postfilter ionized calcium was on the upper limit of the target range (0.41 ± 0.16 vs. 0.37 ± 0.14 mmol/L, P = 0.38), the visual assessment score was excellent, and even a rise in SC was observed during the procedures in both groups. The total-to-ionized calcium ratio was increased in 20 versus 22% of procedures, and citrate concentrations after PE were also similar (1306 ± 441 vs. 1263 ± 405 μmol/L). To conclude, we were unable to show superior PE efficacy in the 15% citrate group, but we significantly reduced the infused volume, which is important in patients with fluid overload. Both citrate protocols were found to provide excellent anticoagulation without significant metabolic disturbances or other side effects, confirming the safety of 15% citrate as anticoagulant during PE. 

Effect of Switching to Nocturnal Thrice‐Weekly Hemodialysis on Clinical and Laboratory Parameters: Our Experience

Long or frequent hemodialysis schedules are reported to improve clinical outcomes. We report here our experience with an in‐center, nocturnal, thrice‐weekly hemodialysis program. We retrospectively analyzed the effect of switching 10 patients (8 male, age 45 ± 11 years, renal replacement therapy vintage 12 ± 8 years) from regular, 4–5 h, thrice‐weekly hemodialysis to 8 h nocturnal, in‐center hemodialysis as regards dialysis efficiency, chronic kidney disease‐metabolic and bone disease (CKD‐MBD) parameters, blood pressure, and anemia. With more intense dialysis, the mean predialysis creatinine and urea decreased significantly (1092 ± 195 vs. 961 ± 154 μmol/L, P < 0.01 and 30.8 ± 4.6 vs. 25.5 ± 2.9 mmol/L, P < 0.01), while the decrease in potassium was insignificant (5.9 ± 0.7 vs. 5.6 ± 0.5 mmol/L), but in 3/10 patients, dialysate potassium was increased. Three months after starting nocturnal hemodialysis, no significant influence on pre‐dialysis blood pressure was observed (143/80 vs. 140/80 mmHg), but antihypertensive medications were reduced in two patients. The mean dry weight reduced (74 ± 12 to 72 ± 12 kg) and the mean ultrafiltration increased insignificantly (3123 ± 1174 to 3434 ± 1341 mL). Serum calcium was stable, while phosphate reduced insignificantly (1.5 ± 0.5 to 1.2 ± 0.2 mmol/L), but 6/10 patients were able to discontinue phosphate binders, the dose was reduced in one, and phosphate was added to dialysate in 3/10 patients. Intact parathyroid hormone values were within the target range, except in patients post‐parathyroidectomy. There were no differences in hemoglobin (121 ± 6 vs. 122 ± 8 g/L), and the mean epoetin dose decreased insignificantly (5950 ± 3947 vs. 5250 ± 4238 IU/week). To conclude, improved phosphate and potassium control and reduction in phosphate binders were observed after switching to nocturnal hemodialysis. There was an insignificant reduction of epoetin dose and antihypertensive medications.