Authors

  1. Fasolka, Brian J. PhD, RN, CEN
  2. Chen, Leon L. DNP, AGACNP-BC, FCCP, FAANP

Abstract

Chest pain is a common and high-risk chief complaint in the emergency department. There is an array of cardiac and non-cardiac-related conditions that could lead to this symptom. It is important for the clinician to have a broad perspective when treating patients complaining of chest pain so that dangerous and potentially life-threatening conditions are not overlooked. Here, we present one such cause of chest pain that can be detrimental if the clinician fails to correctly identify the underlying condition. A brief review of hypertriglyceridemia-induced acute pancreatitis is provided, and challenges faced by the treatment team are discussed.

 

Article Content

CASE STUDY

A 40-year-old man presented to the emergency department (ED) with a chief complaint of chest pain. He reported no significant medical or surgical history. Although the patient denied tobacco use, he admitted to occasional use of marijuana; the last incident was 3 weeks ago. He also consumed 4 to 5 beers per week, with last alcohol intake 3 days ago. Upon initial general survey, the patient appeared anxious and uncomfortable, and his skin was pale and diaphoretic. The patient described the pain as squeezing and rated the pain as 10 on a 0 to 10 rating scale. The pain was midline across the mid to lower sternum, radiating to the middle back. Reportedly, the pain started 2 hours prior to arrival and was associated with mild shortness of breath. He denied fevers, chills, nausea, or vomiting, and his vital signs in triage were temperature 37.1[degrees]C, heart rate 102 beats per minute/regular, respiratory rate 22 per minute, blood pressure 142/92 mm Hg, and pulse oximetry 97% on room air. The triage nurse assigned the patient as an Emergency Severity Index (ESI) level 2 (ESI levels range from 1 to 5), which indicated that this patient required immediate evaluation because he presented in severe pain and his symptoms made him a "high-risk" situation (ie, chest pain suggestive of acute coronary syndrome [ACS]). The patient was transferred to the acute care section of the ED as a clinical upgrade, pending an expedited attending physician evaluation.

 

An emergent 12-lead electrocardiogram was obtained, and it revealed sinus tachycardia with no ST-segment elevation and no ectopy. A large-bore peripheral intravenous catheter was established, and initial laboratory samples drawn from the intravenous site were only significant for a slightly elevated white blood cell count of 12 500/[mu]L. Initial troponin T was negative, and the comprehensive metabolic panel was within normal limits except that the potassium and liver function tests (LFTs) were reportedly hemolyzed and not reported. Given the suspicion for ACS, the patient was administered aspirin 325 mg by mouth and nitroglycerin 0.4 mg sublingual every 5 minutes for 3 doses. His chest pain was unchanged after the initial 2 doses of nitroglycerin, but after the third dose it reportedly decreased from a 10/10 to a 9/10. A STAT one view anteroposterior portable chest radiograph revealed a normal-sized heart and no acute pathologies.

 

The physician ordered a STAT computed tomographic study of the chest and abdomen/pelvis area with arterial contrast enhancement to rule out thoracic/abdominal aortic aneurysm or dissection and pulmonary embolism (PE). The initial imaging report was negative for these abnormalities. Repeat serum potassium and LFTs from a blood specimen drawn with a butterfly needle were once again not resulted due to hemolysis. Upon consultation with the laboratory technician, it was reported that the hemolysis was secondary to a lipemic blood sample. A serum lipase and serum lipid panel was requested, and the results indicated a serum lipase level of 498 units/L and a critically high triglyceride level of 2930 mg/dL. The Critical Care Medicine staff was consulted for admission into the medical intensive care unit (MICU) for hypertriglyceridemia-induced acute pancreatitis (HAP).

 

In the meantime, intravenous morphine was administered, which decreased the chest pain from 9/10 to 3/10, and the patient reported satisfaction with this degree of pain relief. An intravenous infusion of lactated Ringer's solution was initiated, and ondansetron was added for management of nausea and vomiting. An insulin infusion was initiated in the ED to treat hypertriglyceridemia. The patient remained on continuous cardiac and pulse oximetry monitoring and blood pressures were evaluated every 30 minutes until his transfer to the MICU.

 

DISCUSSION

Chest pain is one of the most common presenting complaints to the ED. While cardiopulmonary abnormalities account for a significant number of underlying causes, gastrointestinal conditions such as acute pancreatitis can often present with chest pain as the first symptom.1 Hypertriglyceridemia is the third most common cause of acute pancreatitis behind alcohol and biliary obstruction, accounting for approximately 2% to 10% of all cases.2,3 Although the association between hypertriglyceridemia and pancreatitis has been established since the 1800s, there is no established triglyceride level above that which definitively leads to acute pancreatitis. The current data and recommendations indicate a triglyceride level of greater than 1000 mg/dL places a patient at a higher risk for developing acute pancreatitis.3,4 The exact mechanism of injury to pancreatic cells during hypertriglyceridemia is unclear, but several existing hypotheses help explain the phenomenon. One explanation is that excessive triglycerides undergo lipolysis by pancreatic lipase, and this process induces overwhelming fatty acid formation and results in inflammatory changes to the pancreatic vasculature. These pathological changes ultimately lead to pancreatitis.5 Another theory postulates that hyperviscosity due to hypertriglyceridemia directly induces ischemic changes in the pancreas and results in gross inflammation.5 Regardless of the underlying process, the result is pancreatitis along with associated morbidities and mortality.2

 

Absent of secondary inciting factors such as uncontrolled diabetes, alcohol abuse, and pregnancy, patients with severe hypertriglyceridemia often have primary genetic disorders with lipid metabolism such as familial combined hyperlipidemia or familial dysbetalipoproteinemia. Medications have also been implicated in inducing hypertriglyceridemia. The list includes, but not limited to, oral contraceptives, valproic acid, protease inhibitors, antipsychotics, and certain antidepressants. In the intensive care unit setting, the medication commonly associated with hypertriglyceridemia is propofol due to its high lipid content.6 Our presenting patient did not have diabetes and was not taking medications that are classically associated with hypertriglyceridemia. While he denied chronic alcohol abuse, it could be possible that he might be underreporting his usage. He could also have a genetic abnormality that placed him at a high risk of hypertriglyceridemia, but he nor our team had that information at hand and he likely would need additional testing.

 

Our patient also demonstrated the diagnostic challenge presented by severe hypertriglyceridemia because laboratory results were unable to be processed because of persistent lipemia. This is caused by excessive triglycerides interfering with the calorimetric reading of the sampled serum.7 While blood samples that visibly contain lipids can direct the clinician to suspect hypertriglyceridemia, the sample may not always be obvious. There have been case reports of hypertriglyceridemia inducing spurious laboratory values including falsely low serum lipase, amylase, and sodium levels even after repeated testing.7 This can confound the clinician and delay diagnosis and treatment. HAP should be suspected if a patient presents with the fitting clinical picture and has predisposing risk factors such as diabetes or is taking an associated medication. However, our patient proved to be difficult diagnostically, given lack of risk factors and a nonspecific chief complaint.

 

EMERGENCY DEPARTMENT CARE

High-risk patients presenting to the ED with chest pain and other associated cardiac symptoms should receive initial diagnostics and treatments for ACS until that diagnosis is ruled out. Other life-threatening cardiovascular diseases including aortic aneurysm/dissection and PE should also be carefully considered. Gastrointestinal and biliary disorders such as gastritis, peptic ulcer disease, gastroesophageal reflux disease, and acute pancreatitis might also be considered as differential diagnoses. Initial treatment of HAP in the ED focuses on minimizing pancreatic stimulation, providing symptom relief, and maintaining fluid electrolyte balance.3 The patient should be given nothing by mouth to minimize production of pancreatic enzymes. Pain should be controlled with intravenous analgesics, and intravenous infusions of crystalloids are used to correct fluid imbalance.3 Additional symptom management might include antiemetics if nausea or vomiting is reported.

 

The ED clinicians should carefully monitor the patient for potential organ damage associated with acute pancreatitis. Pulmonary complications include pleural effusion, pneumonia, and acute respiratory distress syndrome. Cardiovascular complications include hypovolemia secondary to hemorrhage or retroperitoneal fluid shifts. In addition, hypocalcemia and sepsis secondary to pancreatic pseudocyst formation are potential complications for which the patient should be monitored.

 

INTENSIVE CARE UNIT CARE

Once the ED has initiated targeted treatments of acute pancreatitis, the MICU care should be directed toward lowering the serum triglyceride level to limit further organ damage. There are oral medications available that will lower the triglyceride level. But with organ damage, it is more likely that the patient will need more aggressive therapies targeting rapid decrease of the serum triglyceride level such as intravenous insulin infusion or plasmapheresis. Despite the lack of large randomized studies demonstrating their impact on clinical outcome, both are mainstay therapies for HAP. Most of the supporting data come from small retrospective studies, case reports, and case series; therefore, larger randomized controlled studies are needed to further validate these therapies.

 

Insulin therapy has been shown to effectively reduce the serum triglyceride level through the stimulation of the lipoprotein lipase (LPL). With increase of LPL activity, there is an increased degradation of chylomicrons into free fatty acids and glycerol and this results in a decreased serum triglyceride level.8,9 Both insulin intravenous infusion and subcutaneous injection have demonstrated their efficacy in achieving a lower serum triglyceride level in cases of HAP, but continuous infusion is often favored because of titratability. Various case reports have shown that with insulin therapy alone, teams have been able to decrease patients' serum triglyceride levels significantly in the initial 24 hours. This effect was enhanced when the patient was given nothing by mouth in combination with the insulin infusion.9

 

Plasmapheresis or plasma exchange for patients with severe hypertriglyceridemia has been shown to be effective in rapidly decreasing the serum triglyceride level. The mechanism by which this is achieved is that it directly removes triglycerides from circulating chylomicrons and very low-density lipoprotein, thereby decreasing generation of proinflammatory free fatty acids.6 While effective, plasmapheresis is less favored because of several factors. It is more invasive since it requires the insertion of a hemodialysis catheter. It requires patients to receive systemic anticoagulation, which increases their risk for bleeding. Finally, it is more costly because it requires additional equipment and specialist consultation.10

 

Both insulin therapy and plasmapheresis alone are effective in decreasing serum triglycerides and reducing the potential complications of persistent hypertriglyceridemia. No studies have demonstrated superiority of either therapy or the combination of both therapies.9 When weighing the accessibility of therapy, relative risk, and complications, insulin therapy may be more advantageous than plasmapheresis as the initial therapy of choice in HAP. Heparin infusion has also been utilized in severe hypertriglyceridemia due to its activity on stimulating LPL function. However, multiple studies have shown that this effect is transient and the intended therapeutic effect may not be achieved. Furthermore, the action of heparin on LPL may increase the serum free fatty acid level and result in increased inflammation, which could be detrimental in HAP.11

 

CONCLUSION

Chest pain is a common but a high-risk chief complaint in EDs. Clinicians should expedite the initial assessments and diagnostics for at-risk patients and those presenting in acute distress, as was presented in this case. Astute clinical reasoning is vital to ensure that life-threatening conditions are not overlooked before considering alternative etiologies of chest pain. ACS is a common, life-threatening cause of chest pain and should be considered as a leading differential diagnosis, but other life-threatening cardiovascular, pulmonary, and gastrointestinal/hepatobiliary etiologies must be considered, particularly with atypical clinical presentations.

 

HAP is a less common but serious type of acute pancreatitis that may mimic ACS and requires specialized treatment to address the root cause. In a busy hospital setting, clinicians may often assume that hemolyzed blood specimens are just secondary to trauma to the blood cells during peripheral blood sample collection. However, there are several pathologies that may result in spurious laboratory values or hemolysis of blood samples. The hemolyzed blood samples may be indicative of underlying hematologic or metabolic abnormalities and the patient will require additional testing and monitoring to prevent further clinical deterioration. It is particularly concerning if a blood sample is not due to lipemia since this often indicates a severe metabolic derangement. In our case, the clinician diligently sought out the cause of the repeatedly hemolyzed sample and was able to discover an unusual condition. Once a diagnosis of HAP is confirmed, patients should receive timely and targeted interventions to relieve symptoms and to lower serum triglyceride levels. Careful ongoing monitoring for potential complications is vital before a prompt transfer to an intensive care setting.

 

REFERENCES

 

1. Smulders MW, Bekkers SCAM, van Cauteren YJM, et al Risk stratification and role for additional diagnostic testing in patients with acute chest pain and normal high-sensitivity cardiac troponin levels. PLoS One. 2018;13(9):e0203506. doi:10.1371/journal.pone.0203506. [Context Link]

 

2. Samarasinghe S, Avari P, Meeran K, Cegla J. Management of hypertriglyceridaemic pancreatitis in the acute setting and review of literature. BMJ Case Rep. 2018;11(1):e227594. doi:10.1136/bcr-2018-227594. [Context Link]

 

3. Garg R, Rustagi T. Management of hypertriglyceridemia induced acute pancreatitis. Biomed Res Int. 2018;2018:4721357. doi:10.1155/2018/4721357. [Context Link]

 

4. Minhas J, Thakkar D, Dargin J. Hypertriglyceridemia-induced acute pancreatitis. J Emerg Med. 2017;52(3):e89-e90. doi:10.1016/j.jemermed.2016.10.018. [Context Link]

 

5. Valdivielso P, Ramirez-Bueno A, Ewald N. Current knowledge of hypertriglyceridemic pancreatitis. Eur J Intern Med. 2014;25(8):689-694. doi:10.1016/j.ejim.2014.08.008. [Context Link]

 

6. Scherer J, Singh VP, Pitchumoni CS, Yadav D. Issues in hypertriglyceridemic pancreatitis: an update. J Clin Gastroenterol. 2014;48(3):195-203. doi:10.1097/01.mcg.0000436438.60145.5a. [Context Link]

 

7. Melnick S, Nazir S, Gish D, Aryal MR. Hypertrigly-ceridemic pancreatitis associated with confounding laboratory abnormalities. J Community Hosp Intern Med Perspect. 2016;6(3):31808. doi:10.3402/jchimp.v6.31808. [Context Link]

 

8. Inayat F, Zafar F, Baig AS, et al Hypertriglyceridemic pancreatitis treated with insulin therapy: a comparative review of 34 cases. Cureus. 2018;10(10):e3501. doi:10.7759/cureus.3501. [Context Link]

 

9. Rawla P, Sunkara T, Thandra KC, et al Hypertrigly-ceridemia-induced pancreatitis: updated review of current treatment and preventive strategies. Clin J Gastroenterol. 2018;11(6):441-448. doi:10.1007/s12328-018-0881-1. [Context Link]

 

10. He WH, Yu M, Zhu Y, et al Emergent triglyceride-lowering therapy with early high-volume hemofiltration against low-molecular-weight heparin combined with insulin in hypertriglyceridemic pancreatitis: a prospective randomized controlled trial. J Clin Gastroenterol. 2016;50(9):772-778. doi:10.1097/MCG.0000000000000552. [Context Link]

 

11. Gubensek J, Buturovic-Ponikvar J, Romozi K, Ponikvar R. Factors affecting outcome in acute hyper-triglyceridemic pancreatitis treated with plasma exchange: an observational cohort study. PLoS One. 2014;9(7):e102748. doi:10.1371/journal.pone.0102748. [Context Link]

 

acute pancreatitis; hypertriglyceridemia; insulin infusion; lipemia