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Indian J Crit Care Med
Indian J Crit Care Med
IJCCM
Indian Journal of Critical Care Medicine : Peer-reviewed, Official Publication of Indian Society of Critical Care Medicine
0972-5229
1998-359X
Jaypee Brothers Medical Publishers

10.5005/jp-journals-10071-24598
Letter to the Editor
Postoperative Hyperbilirubinemia and Acute Liver Dysfunction after Cytoreductive Surgery and HIPEC
Kannancheeri Arya 1https://orcid.org/0009-0002-9222-5284

Solanki Sohan Lal 2https://orcid.org/0000-0003-4313-7659

Kazi Mufaddal 3https://orcid.org/0000-0002-3295-0006

Saklani Avanish 4https://orcid.org/0000-0003-4498-7612

1,2 Department of Anaesthesiology, Critical Care and Pain, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
3,4 Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
Sohan Lal Solanki, Department of Anaesthesiology, Critical Care and Pain, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India, Phone: +91 9869253201, e-mail: me_sohans@yahoo.co.in
1 2024
31 12 2023
28 1 8081
Copyright © 2024; The Author(s).
2024
https://creativecommons.org/licenses/by-nc/4.0/ © The Author(s). 2024 Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted use, distribution, and non-commercial reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
How to cite this article: Kannancheeri A, Solanki SL, Kazi M, Saklani A. Postoperative Hyperbilirubinemia and Acute Liver Dysfunction after Cytoreductive Surgery and HIPEC. Indian J Crit Care Med 2024;28(1):80–81.

Keywords

Acute liver failure
Cytoreduction
Hyperbilirubinemia
Hyperthermic chemotherapy
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pmc Dear Editor,

A 23-year-old-man weighing 53 kgs, with no comorbidities or addiction, who had been diagnosed with carcinoma of the appendix with pseudomyxoma peritonei was scheduled for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). Preoperative investigations had shown a Hb 10.1 gm%, bilirubin of 0.4 mg/dL with AST – 30 U/L and ALT – 30 U/L, alkaline phosphatase – 209 U/L, albumin 3.69 gm/dL, globulin – 5.47 gm/dL and INR – 1.24. A thoracic epidural was inserted and standard general anesthesia was induced. The radial artery was cannulated and cardiac output monitoring was done. The right internal jugular vein was cannulated. The cytoreduction was completed and the total blood loss was 9000 mL. A total of 10.5 L of crystalloids, 2000 mL of 4% albumin, 1500 mL of gelatin, 2633 mL of packed red blood cells, and 1638 mL of fresh frozen plasma were transfused. Intraoperatively, the noradrenaline requirement went up to 0.8 µg/kg/min for 30 minutes. After CRS, HIPEC was given for 90 minutes with 23.5 mg of doxorubicin and mitomycin-C each. The minimum temperature (end of CRS) was 34.5°C and the maximum temperature during HIPEC was 37.5°C. The total urine output was 700 mL and the duration of the surgical procedure was 780 minutes. At the end of HIPEC phase ABG showed a pH of 7.22, bicarbonates of 18.9, and lactates increased to 6.45.

After the surgery, the patient was shifted for elective postoperative ventilation. On postoperative day (POD) 1, his investigations showed a bilirubin of 4.6 mg/dL (direct 3.56 mg/dL and indirect 1.10 gm/dL) with AST – 187 U/L, ALT – 65 U/L, INR – 1.59, aPTT – 39.9 seconds. Keeping in mind the normal increase in liver enzyme after a major CRS-HIPEC, the trachea was extubated on POD 1. In the evening laboratory reports showed a bilirubin of 13.43 mg/dL, (direct bilirubin 9.19 mg/dL, indirect 4.26 mg/dL), AST 266U/L, ALT 75U/L, INR – 1.44. ABG showed pH – 7.44, PCO2 – 38.3 mm Hg, HCO3 – 25.5 mmoL/L, lactates – 1.49 mmoL/L on room air. The serum ammonia level was also sent, which was 72.9 µg/dL.

His Hepato-portal Doppler study showed normal portal vein diameter with normal color flow and respiratory phasic variation [peak systolic velocity (PSV) = 20]. The hepatic artery showed normal Doppler perceptible color flow and spectral indices (PSV = 35–40). The liver appeared normal in size and echotexture. Blood and urine were also sent for blood crossmatching-related reaction which came back negative. A negative Coombs test also suggested no transfusion-related reactions. On POD 2, his total bilirubin decreased to 5.84 mg/dL and indirect bilirubin to 1.96 mg/dL, direct bilirubin to 3.88 mg/dL. Bilirubin was on a decreasing trend thereafter.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy is well established but associated with higher postoperative mortality and morbidity.1 Transient changes in liver function are common after major surgery due to surgical stress and reduced hepatic blood flow from anesthesia and multiple blood transfusions.2 Postoperative acute liver dysfunction leading to a very high value of serum bilirubin as in our case, after CRS-HIPEC is rare and not reported.

Evidence has shown that a long duration of anesthesia leading to the reduction in hepatic blood flow can cause an increase in the level of abnormal aminotransferases in conjunction with a normal abdominal ultrasound scan suggesting ischemic liver injury. The majority of anesthetics lead to a decrease in portal blood flow, which can cause a decrease in clearance of both endogenous and exogenous substances which have a high hepatic extraction ratio due to a decrease in flow. Even though there is an increase in hepatic arterial blood flow, it fails to maintain adequate oxygen supply during anesthesia along with blood loss and hypotension during surgery causing ischemic injury which can impair its normal function.3 There are also cases of hyperammonemia reported after HIPEC. These are mostly seen with liver decompensation and can cause neurological deterioration which did not happen in our case.4

Less frequently reported were the warm chemotherapeutic drugs used during HIPEC as a cause of hepatotoxicity.5 Warm chemotherapeutic agents along with their manipulation in proximity to the biliary tree can also be a contributory factor. Thermal injury may be caused by the direct placement of an inflow pump over the liver or the long duration of the HIPEC phase causing necrosis of the hepatocytes secondary to heat.5 The use of chemotherapeutic agents like adriamycin and mitomycin during HIPEC can cause local toxicity and necrosis of liver tissues by entrapment in the Glisson capsules. A rise in aminotransferases can occur with adriamycin but elevation of bilirubin and coagulopathy is rare.6

In this case, the preoperative clinical course showed no evidence of preoperative liver disease or extra or intrahepatic obstruction. Hemolytic reaction due to multiple blood transfusions was ruled out by a negative Coombs test. Intraoperative massive blood loss and the use of high doses of vasopressors for a short duration of time might have triggered the hypoxic injury to the hepatic tissues. The use of doxorubicin and mitomycin during the HIPEC phase might have added to the chances of liver dysfunction. Given the multifactorial nature of liver dysfunction, it can be challenging to pinpoint a single causative factor. Treatment and management would then be tailored based on the specific circumstances of the case.

Oricd

Arya Kannancheeri https://orcid.org/0009-0002-9222-5284

Sohan Lal Solanki https://orcid.org/0000-0003-4313-7659

Mufaddal Kazi https://orcid.org/0000-0002-3295-0006

Avanish Saklani https://orcid.org/0000-0003-4498-7612

Source of support: Nil

Conflict of interest: None
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References

1. Solanki SL Mukherjee S Agarwal V Thota RS Balakrishnan K Shah SB et al. Society of Onco-Anaesthesia and Perioperative Care consensus guidelines for perioperative management of patients for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) Indian J Anaesth 2019 63 12 972 987 10.4103/ija.IJA_765_19 31879421
2. Nandi R Das S Nag A Datta A Jaundice after cytoreductive surgery along with hyperthermic intra-peritoneal chemotherapy in an ovarian cancer patient: A case report Indian J Anaesth 2020 64 11 997 999 10.4103/ija.IJA_418_20 33487694
3. Gelman S General anesthesia and hepatic circulation Can J Physiol Pharmacol 1987 65 8 1762 1779 10.1139/y87-276 3319112
4. Sharma V Solanki SL Saklani AP Hyperammonemia after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: A report of three cases with unusual presentation Indian J Crit Care Med 2021 25 5 590 593 10.5005/jp-journals-10071-23821 34177182
5. Zheng Z Yu H Xiong B Shen S Yang H Zhou Y The incidence and risk factors of hepatotoxicity induced by perioperative hyperthermic intraperitoneal chemotherapy in gastrointestinal carcinoma patients: A retrospective study Onco Targets Ther 2018 11 5715 5722 10.2147/OTT.S170398 30254464
6. Kohli P Penumadu P Subramaniam R Acute liver failure following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: A case report Cureus 2019 11 e5026 10.7759/cureus.5026 31497453
