HypertriglyceridemiA -Induced Pancreatitis - PowerPoint Presentation

Slide1

HypertriglyceridemiA-Induced Pancreatitis

Richa

Shukla

, PGY5

Faculty Mentor: Dr.

Suneal

Agarwal

September 4, 2014

Slide2

HPI

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

Slide3

Case 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.

Slide4

Case 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

Slide5

Case 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

Slide6

Case 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

Slide7

Physical 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

Slide8

Laboratory 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

Slide9

Severity of pancreatitis

Not all results from her outside hospital admission were available however notes from the OSH suggest BISAP score of 2 on admission

Slide10

Imaging 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.

Slide11

Imaging 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.

Slide12

Case 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

Slide13

Clinical 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?

Slide14

Clinical 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?

Slide15

Hyperlipidemia

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)

Slide16

Fredrickson’s classification of inherited lipid disorders

Fredrickson DS, Lees RS. Editorial: A system of

phenotyping

hyperlipoproteinemia

. Circulation 1965;31:321-27.

Present in adulthood

Slide17

Hypertriglyceridemic 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

Slide18

Presentation 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

Slide19

Hypertriglyceridemia-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.

Slide20

Relationship between primary and secondary factors in inducing severe HTG and thus increasing the risk of pancreatitis

Slide21

Lactescent 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

Slide22

Mechanism of HTGP

Kota et al. Indian J

Endocrinol

Metab

. 2012 Jan-Feb; 16(1): 141–143.

Slide23

Severity 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.

Slide24

Clinical 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?

Slide25

Management of HTGP

Conventional treatment of pancreatitis: aggressive fluid resuscitation, analgesia, bowel rest

Insulin infusion

Heparin

Plasmapharesis

Lipid lowering agents –

fibrates

, omega-3 fatty acids

Slide26

Insulin

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

Slide27

Heparin

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.

Slide28

Plasmapharesis

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

Slide29

Plasmapharesis

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.

Slide30

Plasmapharesis

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

Slide31

Other 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

Slide32

Clinical 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?

Slide33

Pregnancy 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

Slide34

Pregnancy 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

Slide35

Management 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.

Slide36

Complications 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

Slide37

Conclusion

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

Slide38

THANK YOU!

Slide39

References

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

.

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

. 2008 Jul;14(28):4558-61.

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.

Slide40

References

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.