Richa Shukla PGY5 Faculty Mentor Dr Suneal Agarwal September 4 2014 HPI Reason for consult pancreatitis 31F G2P1 24weeks pregnant patient who presented as an outside hospital transfer for management of pancreatitis ID: 780304
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Slide1
HypertriglyceridemiA-Induced Pancreatitis
Richa
Shukla
, PGY5
Faculty Mentor: Dr.
Suneal
Agarwal
September 4, 2014
Slide2HPI
Reason for consult: pancreatitis
31F G2P1, 24-weeks pregnant patient who presented as an outside hospital transfer for management of pancreatitis
Initially presented to a hospital in Odessa on 1/12/14 with complaints of 2-3 days of severe
epigastric
pain. No clear etiology found and patient was discharged after resolution of pain
Slide3Case Discussion (cont.)
Patient returned to the OSH on 1/26/14 with ~2-3 days of worsening
epigastric
pain radiating to the back
On admission, was found to be in diabetic
ketoacidosis
and had laboratory evidence of pancreatitis with a lipase of 2400.
Patient’s triglycerides were found to be >10,000
Was diagnosed with
hypertriglyceridemic
pancreatitis.
Slide4Case Discussion (cont.)
Managed for both DKA and
hypertriglyceridemic
pancreatitis with 2 days of
plasmapharesis
(1/27, 1/28), an insulin drip and aggressive IV fluid resuscitation.
Lipase improved to 1000, triglycerides to 1800 and DKA resolved
Transferred to the TCH
Pavillion
for Women on 1/28 for
dyspnea
, increased work of breathing and pulmonary edema
Slide5Case Discussion (cont.)
On admission reported persistent
epigastric
pain requiring IV opiates, nausea/vomiting and
dyspnea
Seen by Endocrinology and started on a subcutaneous insulin regimen.
Pancreatitis was managed conservatively with bowel rest and pain management.
Started on Omega-3-acid ethyl esters (
Lovaza
) on 1/31 and
Gemfibrozil
on 2/5
Slide6Case Discussion (cont.)
Past Medical History:
-?Type I v. Type IV v. Type V
hyperlipoproteinemia
diagnosed at age ~28
-Insulin-dependent Diabetes Mellitus diagnosed at age ~23
-Recurrent pancreatitis
Past Surgical History:
-
Cholecystectomy
2011
-complicated by abdominal wound infection requiring abdominal wall plasty-Pancreatic debridement for necrotizing pancreatitis 2011
Home Medications:
-Insulin
Glargine
32 units SQ daily
-Insulin
Novolog
8 units TID AC meals
-Previously on
fibrates
, self d/
c’ed
1 year PTA
Social history
-Denies smoking, alcohol or drug use
-Currently unemployed
Family History:
-No known family members with
hypertriglyceridemia
Slide7Physical Exam
T 99.7, BP 126/84, HR
113
, RR 22, O2 sat 96% 2L NC
Gen: NAD, AAOx4
HEENT:
anicteric
sclera, PERRL, EOMI, MMM, OP clear
CV: RRR no m/r/g
Chest:
bilateral crackles in lower lung fields
, no wheezesAbd: soft,
tender to palpation in
epigastric
region
, NABS, +gravid uterus
Ext: WWP, no clubbing or cyanosis,
trace LE edema
Neuro
: oriented x4, fatigued, conversational
Slide8Laboratory Results
Date
Prior
to admission
1/29
1/30
1/31
2/2
2/3
2/4
2/5
2/6
2/7
Lipase
2400
275
148156160259184195265262AmylaseN/A87N/AN/A8211810597125132Triglycerides>10000834883629562646606411494502
Gemfibrozil
started
Lovaza started
Slide9Severity of pancreatitis
Not all results from her outside hospital admission were available however notes from the OSH suggest BISAP score of 2 on admission
Slide10Imaging Results
Abdominal Ultrasound:
Liver:
21.9 cm in length at the right
midclavicular
line.
Normal
echogenicity
. No mass. Main portal vein diameter 1.3 cm.
There is moderate degree of
periportal
edema. Biliary tree: Common duct is 5 mm. No significant intrahepatic biliary dilatation. Gallbladder: Removed. Pancreas: Partially visualized and unremarkable.
Ascites
:
Small amount of
perihepatic
ascites. Spleen: 13.3 cm in length.
Slide11Imaging results
Chest x-ray 1/29/14
Bilateral central
perihilar
and basilar opacities which are nonspecific but may reflect a combination of edema and
atelectatic
lung.
Slide12Case discussion
Lipase and triglycerides stabilized on oral lipid-lowering regimen
Patient placed on low fat diet
Weaned off narcotics
Pain, nausea, vomiting and
dyspnea
resolved
Slide13Clinical Questions
What are the causes of acquired and inherited lipid disorders? How do they cause pancreatitis?
How is
hypertriglyceridemic
pancreatitis managed?
Is there any relationship of
hypertriglyceridemic
pancreatitis to pregnancy? If so, is there a specific treatment in pregnant women?
Slide14Clinical Questions
What are the causes of acquired and inherited lipid disorders? How do they cause pancreatitis?
How is
hypertriglyceridemic
pancreatitis managed?
Is there any relationship of
hypertriglyceridemic
pancreatitis to pregnancy? If so, is there a specific treatment in pregnant women?
Slide15Hyperlipidemia
Hyperlipidemia
/
dysplipidemia
results from abnormal levels (>90% percentile) of cholesterol OR triglycerides in the blood
Inherited and acquired disorders of lipid metabolism
Acquired causes of
hyperlipidemia
include: obesity, diabetes mellitus (especially DKA),
nephrotic
syndrome, hypothyroidism, pregnancy, drugs (
clomiphene, mirtazapine, tamoxifen, HAART, estrogen, beta-blockers, thiazide diuretics, steroids)
Slide16Fredrickson’s classification of inherited lipid disorders
Fredrickson DS, Lees RS. Editorial: A system of
phenotyping
hyperlipoproteinemia
. Circulation 1965;31:321-27.
Present in adulthood
Slide17Hypertriglyceridemic Pancreatitis
HTG: fasting serum triglyceride level of >150 mg/
dL
.
mild (150-199 mg/
dL
)
moderate (200-999 mg/
dL
)
severe (1000 to 1999 mg/
dL)very severe (>2000 mg/dL) 3
rd
most common cause of pancreatitis (~10% of all cases of acute pancreatitis and up to 56% of pancreatitis cases during pregnancy)
Risk of AP in patients with serum
triglycerides
>1000 and >2000 mg/dL is ∼5% and 10% to 20%, respectively.Speck et al. Arch Verin Wissenschaftl Heilkunde. 1865
Slide18Presentation of HTGP
Similar to that of acute pancreatitis (AP) from other causes: abdominal pain, nausea, and vomiting
Amylase may be falsely normal (due to high TG levels), lipase may also be unaffected
Labs may also show
pseudohyponatremia
Poorly controlled DM, alcoholism, obesity, pregnancy, prior pancreatitis, and a personal or family history of
hyperlipidemia
should suggest HTGP
Slide19Hypertriglyceridemia-induced Pancreatitis
Seen with secondary factors (ex. uncontrolled diabetes, alcoholism, medications, pregnancy) in patients with an underlying common genetic abnormality of lipoprotein metabolism (Fredrickson’s Type IIB and IV)
Less commonly, patients with rare genetic abnormalities of lipoprotein metabolism (i.e. Fredrickson’s Type I and V) will develop pancreatitis without additional inciting factors.
Scherer J, Singh VP,
Pitchumoni
CS,
Yadav
D. Issues in
hypertriglyceridemic
pancreatitis: an update. J
Clin
Gastroenterol
. 2014 Mar;48(3):195-203.
Slide20Relationship between primary and secondary factors in inducing severe HTG and thus increasing the risk of pancreatitis
Slide21Lactescent serum seen in HTG
Chylomicrons
: TG-rich lipoprotein particles. Present in circulation when TG > 900 mg/dl
Large enough to occlude pancreatic capillaries, leading to ischemia and
acinar
structural alteration, and also release of pancreatic lipase
Photo adapted from
Tsuang
et al.
Hypertriglyceridemic
pancreatitis: presentation and management. Am J Gastroenterology 2009 Apr;104(4):984-91
Mechanism of HTGP
Kota et al. Indian J
Endocrinol
Metab
. 2012 Jan-Feb; 16(1): 141–143.
Slide23Severity and outcomes in HTGP
Unclear if the severity of pancreatitis is associated with triglyceride levels
Lloret
et al.
129 patients with types IV and V HTG
20% developed pancreatitis with risk increasing with TG levels.
Of patients with severe and very severe HTG, 71.5% had severe AP
Balachandra
et al.
Small case series of 43 patients
showed that the severity of HTGP did not seem to correlate directly with the triglyceride level
Pancreatic lipase activity, efficiency serum FFA clearance, and severity of underlying pancreatic injury important in determining overall outcomes
Lloret
Linares et al. Pancreas. 2008;37(1):13.
Balachandra
et al.
Int J Clin Pract. 2006;60(2):156.
Slide24Clinical Questions
What are the causes of acquired and inherited lipid disorders? How do they cause pancreatitis?
How is
hypertriglyceridemic
pancreatitis managed?
Is there any relationship of
hypertriglyceridemic
pancreatitis to pregnancy? If so, is there a specific treatment in pregnant women?
Slide25Management of HTGP
Conventional treatment of pancreatitis: aggressive fluid resuscitation, analgesia, bowel rest
Insulin infusion
Heparin
Plasmapharesis
Lipid lowering agents –
fibrates
, omega-3 fatty acids
Slide26Insulin
Decreases serum TG levels by enhancing lipoprotein lipase activity
Inhibits hormone-sensitive lipase in
adipocytes
HTGP often presents in poorly controlled diabetics and thus should be used both to manage hyperglycemia and HTG
Intravenous infusion of regular insulin in D5 at 0.1-0.3 units/kg/day to maintain blood glucose 150-200 mg/dl
Slide27Heparin
Usually used in
conjunction
with insulin to enhance lipoprotein lipase activity
One case report including 5 patients with HTGP with TG levels > 1000 showed decrease in TG levels to < 500 within 3 days in all cases with use of heparin and/or insulin
Use of heparin in management of HTGP is controversial
Berger et al. heparin and insulin treatment of acute pancreatitis caused by
hypertriglyceridemia
. Experience of 5 cases. Rev Med
Chil
. 2001;129(12):1373.
Slide28Plasmapharesis
First described in 1978 by
Betteridge
et al.
Rapidly removes plasma TG and reduces risk of recurrent pancreatitis. Also reduces inflammation by removal of excess proteases and replacement of protease inhibitors
Multiple studies showing success in reducing TG levels
Betteridge
et al. Lancet 1978,
Stefannuti
et al
Artif
Organs. 2009 Dec, Lennertz et al.
Ther
Apher
. 1999 Aug,
Yeh et al J Clin Apher. 2003, Szczepiorkowski et al Journal of Clinical Apharesis June 2010
Slide29Plasmapharesis
Reference
#
of Patients
Plasma exchange method
Significant
reduction in TG level
Stefanutti
et al.
17
Albumin
By 61%
Yeh
et al.
18
FFP and albumin, double membrane filtration
By 66% (first setting) and by 83% (second setting)Yeh et al. 17FFP and albuminSignificant reductionChen et al. 94FFP and albuminNo significant reductionGubensek et al. 50AlbuminSignificant reductionKyriakidis et al. 10FFPBy 62%Table adapted from Ewald et al. Clin Res Cardiol Suppl. 2012 June; 7(Suppl 1): 31–35.
Slide30Plasmapharesis
Severe HTG (TG > 1000 mg/dl) and lipase > 3 times upper limit of normal result in very high FFA levels which can result in high levels of systemic inflammation
Deng et al demonstrated positive correlation between high TG levels and 24-h APACHE II score
Plasmapharesis
is a useful and important tool in the setting of severe HTG and significantly elevated lipase levels
Deng et al.
World J Gastroenterol. 2008 Jul
Slide31Other pharmacologic therapy
Oral lipid
lowering
agents should be initiated when tolerated by the patient as adjuvant therapy in HTGP
Fibrates
lower TG levels by 40-60% and raise HDL levels. Should be used as first line therapy for primary HTG
Omega-3 fatty acids studied in a prospective, double-blind, placebo-controlled trial proved capable of lowering high TG (500 – 2,000 mg / dl) by 45 %
Tsuang
et al.
Hypertriglyceridemic
pancreatitis: presentation and management. Am J Gastroenterology 2009 Apr;104(4):984-91
Slide32Clinical Questions
What are the causes of acquired and inherited lipid disorders? How do they cause pancreatitis?
How is
hypertriglyceridemic
pancreatitis managed?
Is there any relationship of
hypertriglyceridemic
pancreatitis to pregnancy? If so, is there a specific treatment in pregnant women?
Slide33Pregnancy and HTGP
Lipid profile changes in normal
pregnancy: marked
elevations of total plasma cholesterol and triglyceride levels, primarily through increased liver synthesis of triglyceride and VLDL-C in response to elevated estrogen levels
Pregnancy causes an increase in serum TG (peaks in 3
rd
trimester) but total serum TG rarely exceeds 300 mg/dl – a concentration that is not sufficient to cause pancreatitis
Slide34Pregnancy and HTGP
Responsible for ~56% of cases of AP occurring during pregnancy with an estimated overall frequency of 1 in 6790 pregnancies over a 15-year period
Most causes of HTGP in pregnancy are attributable to familial HTG however non-genetic, non-familial pregnancy-induced HTGP has been reported
Several case reports describe gestational HTGP in patients with underlying
hyperchylomicronemia
Gursoy
et al. Severe
Hypertriglyceridemia
-Induced Pancreatitis during Pregnancy. Journal of the National Medical Association. VOL. 98, NO. 4, APRIL 2006
Slide35Management of HTGP in pregnancy
Treatment generally does not differ in pregnancy
Case reports have shown success of
apharesis
in management of HTGP in pregnancy
Initiation of
fibrates
and omega-3 fatty acids reduce risk of recurrent pancreatitis
Dietary fat restriction also reduces chance of recurrence of HTGP
Achard
et al. Pancreatitis related to severe acute
hypertriglyceridemia during pregnancy: treatment with lipoprotein apheresis. Intensive Care Med. 1991;17(4):236.
Slide36Complications of HTGP in pregnancy
Some reports suggest up to 20% increased mortality in pregnancies complicated by pancreatitis
One of the most common reasons for maternal and fetal mortality are acute pancreatitis itself
Very rarely, acute pancreatitis associated with preeclampsia-
eclampsia
or HELLP syndrome
No guidelines exist about the need for early delivery in patients with acute pancreatitis
Slide37Conclusion
Both inherited and acquired causes of
hyperlipidemia
HTGP usually
multifactorial
(underlying lipid disorder exacerbated by secondary factor)
Pregnancy itself can cause
hypertriglyceridemia
Several management strategies for HTGP including
plasmapharesis
, insulin infusion and oral therapy. Management is similar in pregnant patientsImportant to recognize this disorder early in pregnant patient to improve overall outcomes
Slide38THANK YOU!
Slide39References
Sunil K. Kota
,
Siva K.
Kota
,
Sruti
Jammula
,
S. V. S. Krishna
, and Kirtikumar D. Modi. Hypertriglyceridemia-induced recurrent acute pancreatitis: a case-based review. Indian J Endocrinol Metab
. 2012 Jan-Feb; 16(1): 141–143.
Srinivasa
P
Munigoti
, Alan Rees. Hypertriglyceridaemia, LPL Deficiency and Pancreatitis. British Journal of Diabetes and Vascular Disease. 2011;11(3):107-112. Betteridge DJ, Bakowski M, Taylor KG, Reckless JP, de Silva SR, Galton DJ. Treatment of severe diabetic hypertriglyceridaemia by plasma exchange. Lancet. 1978 Jun 24; 1(8078):1368.Iskandar SB, Olive KE. Plasmapheresis as an adjuvant therapy for hypertriglyceridemia-induced pancreatitis. Am J Med Sci. 2004 Nov;328(5):290-4.Stefanutti C, Di Giacomo S, Vivenzio A, Labbadia G, Mazza F, D'Alessandri G, Russi G, De Silvestro G, Marson P. Therapeutic plasma exchange in patients with severe hypertriglyceridemia: a multicenter study. Artif Organs. 2009 Dec; 33(12):1096-102.Lennertz A, Parhofer KG, Samtleben W, Bosch T. Therapeutic plasma exchange in patients with chylomicronemia syndrome complicated by acute pancreatitis. Ther Apher. 1999 Aug; 3(3):227-33.Yeh JH, Chen JH, Chiu HC. Plasmapheresis for hyperlipidemic pancreatitis. J Clin Apher. 2003; 18(4):181-5.Yeh JH, Lee MF, Chiu HC. Plasmapheresis for severe lipemia: comparison of serum-lipid clearance rates for the plasma-exchange and double-filtration variants. J Clin Apher. 2003; 18(1):32-6.Gubensek J, Buturović-Ponikvar J, Marn-Pernat A, Kovac J, Knap B, Premru V, Ponikvar R. Treatment of
hyperlipidemic acute pancreatitis with plasma exchange: a single-center experience. Ther Apher Dial. 2009;13(4):314–317.Chen JH,
Yeh JH, Lai HW, Liao CS. Therapeutic plasma exchange in patients with hyperlipidemic pancreatitis. World J Gastroenterol. 2004;10(15):2272–2274.
Ewald N, Kloer HU
. Treatment options for severe
hypertriglyceridemia
(SHTG): the role of
apheresis
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Clin
Res
Cardiol
Suppl.
2012 Jun;7(
Suppl
1):31-5.
Deng LH,
Xue
P, Xia Q, Yang XN, Wan MH. Effect of admission
hypertriglyceridemia
on the episodes of severe acute pancreatitis. World J
Gastroenterol
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Speck L. Fall von
lipamia
. Arch
Verin
Wissenschaftl
Heilkunde
. 1865: 1:232.
Quoated
in
Thannhauser
SJ, Ed.
Lipidoses
, disease of intracellular lipid metabolism, 1958, 3
rd
ed. New York,
Grune
& Stratton, 307.
Slide40References
Lloret
Linares C, Pelletier AL,
Czernichow
S,
Vergnaud
AC,
Bonnefont-Rousselot
D, Levy P,
Ruszniewski
P,
Bruckert E. Acute pancreatitis in a cohort of 129 patients referred for severe hypertriglyceridemia. Pancreas. 2008;37(1):13.Balachandra S, Virlos IT, King NK, Siriwardana HP, France MW, Siriwardena AK. Hyperlipidaemia and outcome in acute pancreatitis.
Int
J
Clin
Pract. 2006;60(2):156.Berger Z, Quera R, Poniachik J, Oksenberg D, Guerrero J. [heparin and insulin treatment of acute pancreatitis caused by hypertriglyceridemia. Experience of 5 cases]. Rev Med Chil. 2001;129(12):1373.Tsuang W, Navaneethan U, Ruiz L, Palascak JB, Gelrud A. Hypertriglyceridemic pancreatitis: presentation and management. Am J Gastroenterol. 2009 Apr;104(4):984-91. doi: 10.1038/ajg.2009.27. Epub 2009 Mar 17.Achard JM, Westeel PF, Moriniere P, Lalau JD, de Cagny B, Fournier A. Pancreatitis related to severe acute hypertriglyceridemia during pregnancy: treatment with lipoprotein apheresis. Intensive Care Med. 1991;17(4):236.