Comparable Triglyceride Reduction With Plasma Exchange and Insulin in Acute Pancreatitis - A Randomized Trial
Jakob Gubensek, Milena Andonova, Alexander Jerman, Vanja Persic, Barbara Vajdic-Trampuz, Ana Zupunski-Cede, Nejc Sever, Samo Plut, Jakob Gubensek, Milena Andonova, Alexander Jerman, Vanja Persic, Barbara Vajdic-Trampuz, Ana Zupunski-Cede, Nejc Sever, Samo Plut
Abstract
Background and aims: Both insulin and plasma exchange (PE) are used in hypertriglyceridemic acute pancreatitis (HTG-AP). Our aim was to compare the efficacy of both treatments.
Methods: A randomized, parallel group study performed in a tertiary hospital in 22 HTG-AP patients with non-severe prognosis and triglycerides between 15 and 40 mmol/L. Patients were randomized to daily PE or insulin infusion until triglycerides were <10 mmol/L. Primary outcome was % reduction in triglycerides within 24 h. Secondary outcomes were days needed to lower triglycerides <10 mmol/L, highest CRP and percentage of patients with a severe course of pancreatitis.
Results: There was a trend toward a greater decrease in triglycerides within the first 24 h in the PE group (67 ± 17% vs. 53 ± 17%, p = 0.07), but the absolute difference was modest [mean difference of 6 mmol/L (14% of initial value)]. Triglycerides fell below 10 mmol/L in a median (IQR) of 1 (1-2) and 2 (1-2) days, respectively (p = 0.25). Secondary outcomes related to disease severity were also comparable: highest CRP 229 vs. 211 mg/L (p = 0.69) and severe course of pancreatitis in 2/11 cases in both groups (p = 1.0). Regarding treatment complications, there was one mild hypoglycemia and one allergic reaction during PE. Survival was 100% in both groups.
Conclusion: There was no significant difference, but only a trend toward a greater decrease in triglycerides with PE, and the clinical course was also comparable. These results do not support universal use of PE in patients with HTG-AP.
Clinical trial registration: [ClinicalTrials.gov], identifier [NCT02622854].
Keywords: acute hypertriglyceridemic pancreatitis; apheresis – therapeutic; conservative treatment; free fatty acids; hypertriglyceridemia.
Conflict of interest statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Copyright © 2022 Gubensek, Andonova, Jerman, Persic, Vajdic-Trampuz, Zupunski-Cede, Sever and Plut.
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References
- Forsmark CE, Vege SS, Wilcox CM. Acute pancreatitis. N Engl J Med. (2016) 375:1972–81. 10.1056/NEJMra1505202
- de Pretis N, Amodio A, Frulloni L. Hypertriglyceridemic pancreatitis: epidemiology, pathophysiology and clinical management. United Eur Gastroenterol J. (2018) 6:649–55. 10.1177/2050640618755002
- Anderson F, Thomson SR, Clarke DL, Buccimazza I. Dyslipidaemic pancreatitis clinical assessment and analysis of disease severity and outcomes. Pancreatology. (2009) 9:252–7. 10.1159/000212091
- Huang C, Liu J, Lu Y, Fan J, Wang X, Liu J, et al. Clinical features and treatment of hypertriglyceridemia induced acute pancreatitis during pregnancy: a retrospective study. J Clin Apher. (2016) 31:571–8. 10.1002/jca.21453
- Pedersen SB, Langsted A, Nordestgaard BG. Nonfasting mild-to-moderate hypertriglyceridemia and risk of acute pancreatitis. JAMA Intern Med. (2016) 176:1834–42. 10.1001/jamainternmed.2016.6875
- Garg PK, Singh VP. Organ failure due to systemic injury in acute pancreatitis. Gastroenterology. (2019) 156:2008–23. 10.1053/j.gastro.2018.12.041
- Carr RA, Rejowski BJ, Cote GA, Pitt HA, Zyromski NJ. Systematic review of hypertriglyceridemia-induced acute pancreatitis: a more virulent etiology? Pancreatology. (2016) 16:469–76. 10.1016/j.pan.2016.02.011
- Gubensek J, Buturovic-Ponikvar J, Romozi K, Ponikvar R. Factors affecting outcome in acute hypertriglyceridemic pancreatitis treated with plasma exchange: an observational cohort study. PLoS One. (2014) 9:e102748. 10.1371/journal.pone.0102748
- Hutchison B, Collins J, Makar RS, Dzik W. Retrospective analysis of outcomes in patients with acute hypertriglyceridemic pancreatitis treated without therapeutic plasma exchange. Transfusion. (2021) 61:537–45. 10.1111/trf.16214
- Zhang XL, Li F, Zhen YM, Li A, Fang Y. Clinical study of 224 patients with hypertriglyceridemia pancreatitis. Chin Med J. (2015) 128:2045–9. 10.4103/0366-6999.161361
- Betteridge D, Bakowski M, Taylor K, Reckless J, De Silva S, Galton D. Treatment of severe diabetic hypertriglyceridemia by plasma exchange. Lancet. (1978) 311:1368. 10.1016/s0140-6736(78)92450-9
- Gubensek J, Buturović-Ponikvar J, Marn-Pernat A, Kovac J, Knap B, Premru V, et al. Treatment of hyperlipidemic acute pancreatitis with plasma exchange: a single-center experience. Ther Apher Dial. (2009) 13:314–7. 10.1111/j.1744-9987.2009.00731.x
- Lu Z, Chen Y, Wu Y, Lin Y, Yang N, Wang X, et al. The role of double filtration plasmapheresis in hypertriglyceridemic pancreatitis: a propensity score matching analysis. J Clin Apher. (2020) 35:388–97. 10.1002/jca.21811
- Henderson SR, Maitland R, Mustafa OG, Miell J, Crook MA, Kottegoda SR. Severe hypertriglyceridaemia in type 2 diabetes mellitus: beneficial effect of continuous insulin infusion. QJM. (2013) 106:355–9. 10.1093/qjmed/hcs238
- Mikhail N, Trivedi K, Page C, Wali S, Cope D. Treatment of severe hypertriglyceridemia in nondiabetic patients with insulin. Am J Emerg Med. (2005) 23:415–7. 10.1016/j.ajem.2005.02.036
- Inayat F, Zafar F, Baig AS, Chaudhry NA, Aslam A, Khan ZH, et al. Hypertriglyceridemic pancreatitis treated with insulin therapy: a comparative review of 34 cases. Cureus. (2018) 10:e3501. 10.7759/cureus.3501
- Araz F, Bakiner OS, Bagir GS, Chaudhry NA, Aslam A, Khan ZH, et al. Continuous insulin therapy versus apheresis in patients with hypertriglyceridemia-associated pancreatitis. Eur J Gastroenterol Hepatol. Ther Apher Dial. (2021) 25:681–6. 10.1111/1744-9987.13603
- Dhindsa S, Sharma A, Al-Khazaali A, Sitaula S, Nadella S, McKee A, et al. Intravenous insulin versus conservative management in hypertriglyceridemia-associated acute pancreatitis. J Endocr Soc. (2019) 4:bvz019. 10.1210/jendso/bvz019
- Weintraub M, Rassin T, Eisenberg S, Ringel Y, Grosskopf I, Iaina A, et al. Continuous intravenous heparin administration in humans causes a decrease in serum lipolytic activity and accumulation of chylomicrons in circulation. J Lipid Res. (1994) 35:229–38. 10.1016/s0022-2275(20)41211-8
- Tsuang W, Navaneethan U, Ruiz L, Palascak JB, Gelrud A. Hypertriglyceridemic pancreatitis: presentation and management. Am J Gastroenterol. (2009) 104:984–91. 10.1038/ajg.2009.27
- Chen JH, Yeh JH, Lai HW, Liao CS. Therapeutic plasma exchange in patients with hyperlipidemic pancreatitis. World J Gastroenterol. (2004) 10:2272–4. 10.3748/wjg.v10.i15.2272
- Chen Z, Huang X, Zhang M, Han N, Ning Y. Rapid reduction in triglyceride levels by therapeutic plasma exchange in patients with hypertriglyceridemic pancreatitis. J Clin Apher. (2022) 37:82–90. 10.1002/jca.21954
- Dichtwald S, Meyer A, Zohar E, Ifrach N, Rotlevi G, Fredman B. Hypertriglyceridemia induced pancreatitis: plasmapheresis or conservative management? J Intensive Care Med. (2021) (in press). 10.1177/08850666211054365
- Miyamoto K, Horibe M, Sanui M, Sasaki M, Sugiyama D, Kato S, et al. Plasmapheresis therapy has no triglyceride−lowering effect in patients with hypertriglyceridemic pancreatitis. Intensive Care Med. (2017) 43:949–51. 10.1007/s00134-017-4722-3
- Banks PA, Bollen TL, Dervenis C, Gooszen HG, Johnson CD, Sarr MG, et al. Classification of acute pancreatitis–2012: revision of the Atlanta classification and definitions by international consensus. Gut. (2013) 62:102–11. 10.1136/gutjnl-2012-302779
- Coskun A, Erkan N, Yakan S, Yildirim M, Carti E, Ucar D, et al. Treatment of hypertriglyceridemia-induced acute pancreatitis with insulin. Prz Gastroenterol. (2015) 10:18–22. 10.5114/pg.2014.45412
- Antonic M, Gubensek J, Buturovic-Ponikvar J, Ponikvar R. Treatment efficacy and safety during plasma exchange with citrate anticoagulation: a randomized study of 4 versus 15% citrate. Artif Organs. (2016) 40:368–75. 10.1111/aor.12559
- Padmanabhan A, Connelly-Smith L, Aqui N, Balogun RA, Klingel R, Meyer E, et al. Guidelines on the use of therapeutic apheresis in clinical practice - evidence-based approach from the writing committee of the American society for apheresis: the eighth special issue. J Clin Apher. (2019) 34:171–354. 10.1002/jca.21705
- Abe T, Matsuo H, Abe R, Abe S, Asada H, Ashida A, et al. The Japanese society for apheresis clinical practice guideline for therapeutic apheresis. Ther Apher Dial. (2021) 25:728–876. 10.1111/1744-9987.13749
- Zadori N, Gede N, Antal J, Szentesi A, Alizadeh H, Vincze A, et al. EarLy elimination of fatty acids iN hypertriglyceridemia-induced acuTe pancreatitis (ELEFANT trial): protocol of an open-label, multicenter, adaptive randomized clinical trial. Pancreatology. (2020) 20:369–76. 10.1016/j.pan.2019.12.018
- Song X, Shi D, Cui Q, Yu S, Yang J, Song P, et al. Intensive insulin therapy versus plasmapheresis in the management of hypertriglyceridemia-induced acute pancreatitis (Bi-TPAI trial): study protocol for a randomized controlled trial. Trials. (2019) 20:365. 10.1186/s13063-019-3498-x
- Gubensek J. Potential differences between double-filtration plasmapheresis and therapeutic plasma exchange in the treatment of acute hypertriglyceridemic pancreatitis. J Clin Apher. (2021) 36:223–4. 10.1002/jca.21843
- David S, Bode C, Putensen C, Welte T, Stahl K. EXCHANGE study group. Adjuvant therapeutic plasma exchange in septic shock. Intensive Care Med. (2021) 47:352–4. 10.1007/s00134-020-06339-1
- Hong S, Qiwen B, Ying J, Wei A, Chaoyang T. Body mass index and the risk and prognosis of acute pancreatitis: a meta-analysis. Eur J Gastroenterol Hepatol. (2011) 23:1136–43. 10.1097/MEG.0b013e32834b0e0e
- Domschke S, Malfertheiner P, Uhl W, Büchler M, Domschke W. Free fatty acids in serum of patients with acute necrotizing or edematous pancreatitis. Int J Pancreatol. (1993) 13:105–10. 10.1007/BF02786078
- Sztefko K, Panek J. Serum free fatty acid concentration in patients with acute pancreatitis. Pancreatology. (2001) 1:230–6. 10.1159/000055816
- Navina S, Acharya C, DeLany JP, Orlichenko LS, Baty CJ, Shiva SS, et al. Lipotoxicity causes multisystem organ failure and exacerbates acute pancreatitis in obesity. Sci Transl Med. (2011) 3:107ra110. 10.1126/scitranslmed.3002573
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