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Acute postoperative pancreatitis after craniotomy for excision of insular glioma: A classic case of whodunit

1 Department of Neurosurgery, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
2 Department of Anaesthesiology and Critical Care, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
3 Department of Surgical Gastroenterology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
4 Department of Diagnostic and Interventional Radiology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India

Date of Submission03-Feb-2021
Date of Decision13-Mar-2021
Date of Acceptance24-Mar-2021
Date of Web Publication07-Jan-2022

Correspondence Address:
Suryanarayanan Bhaskar,
All India Institute of Medical Sciences (AIIMS), Jodhpur 342005, Rajasthan.
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jpn.JPN_31_21



Acute pancreatitis (AP) has been reported following abdominal surgeries. There are rare reports of AP developing following operations remote to the pancreas. We report a case of postoperative AP following craniotomy for tumor excision. A 15-year-old girl presented with a history of one episode of seizure, headache, and recent left-sided hemiparesis. She was found to have a right frontal glial lesion with extensive white matter tract edema. Craniotomy and excision was done. On the first postoperative day, she developed acute abdominal pain, with guarding and tenderness on examination. Radiological and biochemical evidence for AP was found. AP is a rare, but life-threatening complication. A number of drugs commonly used in neurosurgical practice can cause AP, which include steroids, antiepileptics, and propofol which are extensively used during surgery and for sedation in the intensive care area.

Keywords: Complication – acute pancreatitis, drugs – propofol, surgery – craniotomy, tumor – insular glioma, valproate

How to cite this URL:
Ruparelia J, Singh Gosal J, Kumari K, Varshney VK, Sureka B, Bhaskar S, Kaur M. Acute postoperative pancreatitis after craniotomy for excision of insular glioma: A classic case of whodunit. J Pediatr Neurosci [Epub ahead of print] [cited 2023 Dec 1]. Available from: https://www.pediatricneurosciences.com/preprintarticle.asp?id=335201

   Introduction Top

Any major or life-threatening postoperative complications, particularly following neurosurgery, are distressing to both the patient and the surgeon, and significantly affect morbidity and mortality. Even a minor focal neurological deficit may be a grave predictor of a stormy postoperative period. Clinical alertness and regular neurological examination can, hence, never be overstated.[1] To such a vigilant neurosurgeon, a postoperative complication that is both rare and remote from the usual anatomical region of observation, is perplexing as well as interesting.

Acute pancreatitis (AP) has been well-recognized as a complication of surgeries on organs close to the pancreas for many years.[2] AP causes significant pain and distress to the patient and has a significant mortality. Although direct injury to the pancreas or the vessels supplying it has generally been held responsible, pancreatitis has sometimes also been reported in surgeries remote from the pancreas and variety of drugs commonly used in the neurosurgical patients.[3],[4] Diagnosis is based on clinical, biochemical, and radiological findings, and evaluation includes ruling out a number of common causes to provide appropriate care.

We report a patient who underwent craniotomy for excision of an insular glioma and later developed AP on the first postoperative day. Prompt diagnosis and appropriate immediate management helped in bringing relief to the patient, and avoiding further complications of this life-threatening condition.

   Case Report Top

A 15-year-old-girl presented with a history of one episode of left focal seizure. She had since been on oral antiepileptic drugs (sodium valproate and levetiracetam) and her seizures had been well-controlled. She complained of mild headache on the right side, which progressively increased and became holo-cranial over the last few weeks. She had occasional vomiting and her mother had noticed recent learning difficulties at school. Prior to presentation, she had developed a left-sided weakness (motor power 4/5), associated with difficulty in walking, for which oral steroid (prednisolone 20 mg per day) was started a week before admission. She was otherwise conscious, oriented, and communicating normally. Babinski sign was positive on both sides. Bilateral papilledema was present.

Contrast-enhanced magnetic resonance imaging (MRI) showed a right frontal non-enhancing space-occupying lesion, primarily in the region of the inferior frontal gyrus, with extensive white matter tract edema extending through both cerebral hemispheres [[Figure 1]A, [Figure 1]B, [Figure 1]C]. A provisional diagnosis of an intermediate-grade astrocytoma was made based on radiological findings and she was planned for surgery.
Figure 1: Preoperative MRI T1 (A), T2 (B), and contrast enhanced T1 (C) axial sequences showing a non-enhancing lesion in right inferior frontal gyrus, with mass effect and perilesional white matter tract oedema

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A routine anesthesia and analgesia protocol was followed, with 100 mg propofol as the induction agent. Anesthesia was maintained using an inhalational agent (isoflurane). A right frontotemporal craniotomy was done and the tumor was excised. Her immediate postoperative recovery was uneventful; she was extubated in the operation room and shifted to the neurosurgical ward. Oral feeds were started 6 h after surgery.

She complained of nausea and severe abdominal pain on postoperative day (POD) 1. Examination revealed a tense and rigid abdomen. An abdominal radiograph showed gas-filled bowel loops [Figure 2]A and abdominal ultrasound revealed free fluid in abdomen with left pleural effusion. A contrast-enhanced computed tomography (CT) scan of the abdomen was done which showed a bulky pancreas with necrotic areas in the pancreatic parenchyma and peri-pancreatic fluid collection [Figure 2]B and C. Serum amylase and lipase levels were found to be elevated (2002 IU/L and 2548 IU/L, respectively). Other biochemical tests, including liver function, calcium levels, and serum triglycerides were normal except leucocytosis [Table 1].
Figure 2: CT Topogram (A) image showing gas-filled bowel loops, with “colon cut-off sign” at splenic flexure and contrast enhanced CT images of axial (B) and coronal (C) sections showing bulky pancreas with few non-enhancing areas, peri-pancreatic fluid, suggestive of acute interstitial oedematous pancreatitis

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Table 1: Relevant biochemical investigation reports for our patient on postoperative day 1 and 15, and reference values

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AP was managed conservatively using a standard treatment regimen which included placement of nasogastric tube, keeping the patient nil-by-mouth, intravenous fluid administration, and continuing supportive medication. Intravenous paracetamol was given for analgesia. Dexamethasone (4 mg 8-hourly, started postoperatively, and given for 1 day) and sodium valproate were immediately stopped. Abdominal girth charting was done and vital parameters were regularly monitored. Over the next 3 days, the patient had significant symptomatic improvement. She was able to pass stools and flatus and her abdominal pain and guarding reduced. Serum amylase and lipase levels returned close to the normal range (141 IU/L and 136 IU/L, respectively). She was able to tolerate oral feeds and had an uneventful recovery thereafter. She was discharged 7 days after surgery.

Histopathology report of the excised tumor showed diffuse astrocytoma, WHO grade 2. She is undergoing chemo-radiotherapy as part of adjuvant treatment and is under regular follow up.

   Discussion Top

AP is a highly painful condition with life-threatening complications. Patients develop rapidly worsening abdominal pain, nausea, vomiting, abdominal distension, and respiratory distress. Diagnosis is based on radiological evidence of a bulky pancreas with or without non-enhancing necrotic areas. This is supplemented additionally with elevated lipase and amylase levels, as well as other biochemical parameters.[3],[4]

Our patient had developed acute abdominal pain, nausea, abdominal distension, guarding, and tenderness on the first postoperative day. Biochemical parameters showed elevated serum amylase and lipase levels (>5 times the normal). Radiological investigations (contrast-enhanced CT) confirmed the diagnosis by showing a bulky pancreas with peri-pancreatic inflammatory changes, and non-enhancing necrotic areas within the pancreatic parenchyma. Additionally, the patient also had a reactionary left pleural effusion, which did not cause significant respiratory difficulty.

Postoperative AP is a well-recognized complication following abdominal surgeries and occasionally after surgeries performed on organs remote to the pancreas, such as spinal surgeries, joint replacements, ocular surgeries, and others.[3],[5],[6] Common etiologies include alcohol abuse, biliary stone disease, hypercalcemia, hypertriglyceridemia, and local trauma to the pancreas.[3],[6] Splanchnic hypoperfusion due to hemodynamic alterations in the perioperative period has been implicated as a potential cause of AP in surgeries remote from the pancreas. The literature search revealed one case report of AP following a cranial procedure where the inciting cause was not clearly delineated.[7]

Drugs are responsible for 0.1–2% of AP.[4] Diagnosis of drug-induced pancreatitis requires evidence of AP, followed by ruling out of the more common causes. Our patient had received three drugs which have the potential to cause AP.[8] The first was corticosteroids which are classified as Class IB drugs.[8] Our patient had received Prednisolone (20 mg/day) for 1 week prior to surgery, and Dexamethasone (4 mg thrice a day) for 1 day post-operatively.

The second drug was propofol, which is listed as Class II drug to cause AP, is commonly used for sedation (in the intensive care units), induction and maintenance of anesthesia in the operating room.[8] Its association with AP is being reported with more frequency and is related to severe hypertriglyceridemia, although it is not necessarily the only mechanism.[9] Some observations support an idiosyncratic reaction.[9] Our patient received 100 mg Propofol as an induction agent prior to the surgery. However, she was found to have normal lipid levels postoperatively once pancreatitis had been diagnosed (serum triglycerides 87 mg/dL). An idiosyncratic reaction to propofol is still possible.

The most worrying drug that our patient had received, which could have resulted in AP, was sodium valproate, a Class IA drug.[8] The possible association of AP with valproate led the United States Food and Drug Administration (USFDA) to issue a black-box warning for all valproate products in 2000.[10] The proposed mechanism for valproate-related AP includes a free radical-mediated, direct toxic effect; but could also be an idiosyncratic event.[10] It is most common during the first year of treatment, and whenever the dose of the drug is increased.

Our patient had been receiving sodium valproate for 9 months, since her first episode of seizures. Her dosage (25 mg/kg/day) was well within the prescribed dosage limit. The dose was not changed during the perioperative period, nor was she given any additional doses. However, to be safe, we stopped the drug once diagnosis of AP was established and levetiracetam was continued.

We excluded some other common causes of AP, like alcohol abuse, trauma, biliary stone disease, hypertriglyceridemia. She had been hemodynamically stable throughout the operative period, and hence, splanchnic hypoperfusion too was not suspected.

To establish a diagnosis of drug-induced pancreatitis, there must a temporal relationship between start of the drug and development of AP. Additionally, the subsidence of symptoms after stopping the offending drug, and reappearance of symptoms after a re-challenge, firmly establish the “guilt” of the drug.[4],[8] AP is classically managed conservatively and usually self-resolves over the course of a few days, once the offending factors are eliminated. We could safely stop all three drugs (Steroid, Propofol, and Valproate) in our patient. However, the ethical limitations of a re-challenge make it difficult to establish a causal relationship, and the possibility of “drug-coincident” or idiopathic postoperative pancreatitis has to be considered in this case, along with “drug-induced” pancreatitis.

We conclude that many drugs commonly used in neurosurgical practice are among etiological factors for AP, and thus it holds relevance for neurosurgeons. AP can become rapidly life-threatening, and its most effective management is by its prompt diagnosis and withdrawal of the offending agent. As discussed in this report, early diagnosis of this remote and rare complication helped achieve an uneventful recovery, and avoid further morbidity.



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Conflicts of interest

There are no conflicts of interest.

   References Top

Bhaskar S, Gosal JS, Garg M, Jha DK Letter: the neurological examination. Oper Neurosurg (Hagerstown) 2020;18:E262.  Back to cited text no. 1
Dunphy JE, Brooks JR, Archroyd F Acute postoperative pancreatitis. N Engl J Med 1952;248:445-51.  Back to cited text no. 2
Ponka JL, Landrum SE, Chaikof L Acute pancreatitis in the postoperative patient. Arch Surg 1961;83:475-90.  Back to cited text no. 3
Jones MR, Hall OM, Kaye AM, Kaye AD Drug-induced acute pancreatitis: a review. Ochsner J 2015;15:45-51.  Back to cited text no. 4
Tauchi R, Imagama S, Ito Z, Ando K, Hirano K, Ukai J, et al. Acute pancreatitis after spine surgery: a case report and review of literature. Eur J Orthop Surg Traumatol 2014;24(S1):S305-9.   Back to cited text no. 5
Liu TT, Chen CC, Yang YH, Wang SS, Chang FY, Lee SD Acute pancreatitis associated with temporal lobectomy and intractable seizure. Zhonghua Yi Xue Za Zhi (Taipei) 2000;63:226-9.   Back to cited text no. 6
White MT, Morgan A, Hopton D Postoperative pancreatitis. A study of seventy cases. Am J Surg 1970;120:132-7.  Back to cited text no. 7
Badalov N, Baradarian R, Iswara K, Li J, Steinberg W, Tenner S Drug-induced acute pancreatitis: an evidence-based review. Clin Gastroenterol Hepatol 2007;5:648-61.e3. doi:10.1016/j.cgh.2006.11.023  Back to cited text no. 8
Haffar S, Kaur RJ, Garg SK, Hyder JA, Murad MH, Abu Dayyeh BK, et al. Acute pancreatitis associated with intravenous administration of propofol: evaluation of causality in a systematic review of the literature. Gastroenterol Rep 2019;7:13-23.  Back to cited text no. 9
Pellock JM, Wilder BJ, Deaton R, Sommerville KW Acute pancreatitis coincident with valproate use: a critical review. Epilepsia 2002;43:1421-4. doi:10.1046/j.1528-1157.2002.18502.x  Back to cited text no. 10


  [Figure 1], [Figure 2]

  [Table 1]


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