Sodium thiosulfate during cisplatin-based hyperthermic intraperitoneal chemotherapy is associated with transient hypernatraemia without clinical sequelae

Our plain-English summary of Sodium thiosulfate during cisplatin-based hyperthermic intraperitoneal chemotherapy is associated with transient hypernatraemia without clinical sequelae, by A. Alonso, W. Liauw, H. Kennedy, et al (Pleura and Peritoneum, 2022).

The study

• Authors: A. Alonso, W. Liauw, H. Kennedy, N.A. Alzahrani, D.L. Morris
• Journal: Pleura and Peritoneum
• Published: 2022;7(2):87-93
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Objectives: Cisplatin is commonly used during intraperitoneal chemotherapy however has well-established nephrotoxic side-effects. Sodium thiosulfate is often added to cisplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) protocols to mitigate this, however evidence regarding risk of hypernatraemia is scarce as of yet.

Methods: We retrospectively identified patients undergoing cytoreductive surgery (CRS) for peritoneal surface malignancies of any origin at a single high-volume unit between April 2018 and December 2020. Patients were included if they received cisplatin-based HIPEC with intravenous sodium thiosulfate. Blood tests were collected pre-surgery and then daily during admission. Hypernatraemia was defined as serum sodium >145 mmol/L. Renal impairment was defined using the RIFLE criteria.

Results: Eleven CRSs met inclusion criteria, the majority of which were indicated for ovarian cancer (72.7%). One (9.1%) patient with mesothelioma received mitomycin C as an additional chemotherapy agent. The incidence of hypernatraemia was 100% but all cases were transient, with no clinical sequelae observed. The rate of AKI was 36.4%, with three (27.3%) patients classified as risk and one (9.1%) instance of failure. No long-term renal impairment was observed.

Conclusions: Despite biochemical evidence of mild hypernatraemia but with the absence of clinical sequelae, sodium thiosulfate appears to be safe when used in adjunct to cisplatin-based HIPEC during CRS. These findings should be evaluated with further comparative studies. When describing renal impairment, it is important that standardisation in reporting occurs, with the RIFLE and Acute Kidney Injury Network criteria now the preferred consensus definitions.

© 2022 Anais Alonso et al., published by De Gruyter, Berlin/Boston.

In plain English

This single-hospital study from St George Hospital in Sydney, Australia, looked back at patients who had cytoreductive surgery (surgery to remove tumour from the abdominal lining) with heated cisplatin chemotherapy inside the abdomen (HIPEC) between April 2018 and December 2020, and who were given intravenous sodium thiosulfate to protect the kidneys. It did not study asbestos exposure. Eleven operations qualified. Most were for ovarian cancer, and one patient with mesothelioma also received mitomycin C. All 11 patients developed raised blood sodium (hypernatraemia) right after surgery. The mean highest level was 150.4 mmol/L, and it resolved by post-operative days 1 to 8. No clinical complications from it were seen. Acute kidney injury occurred in 4 of 11 patients (36.4%), and all cases resolved. An earlier comparison group was described but not compared statistically because the study was small. The authors concluded that sodium thiosulfate appears safe in this setting, and that further comparative studies are needed. They noted that post-operative urine output was not recorded in electronic medical records and that other causes of the raised sodium could not be ruled out.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective single-centre study of patients drawn from a prospectively maintained database, with a historical control group described only descriptively (no statistical comparison)
• Who was studied: 11 cytoreductive surgeries with cisplatin-based HIPEC and intravenous sodium thiosulfate at St George Hospital, Sydney, Australia, April 2018 to December 2020. Most were for ovarian cancer (72.7%), and one patient had mesothelioma. A control group was made up of the same number of the most recent patients treated before the sodium thiosulfate protocol began.
• Exposure: No asbestos exposure was studied. The treatment studied was intravenous sodium thiosulfate given during cisplatin-based HIPEC: a 9 g/m2 bolus at the start of HIPEC, then 12 g/m2 infused over 6 h. Cisplatin was given at 100 mg/m2 intra-abdominally at 41.5°C for 90 min. The patient with mesothelioma also received mitomycin C.
• Main results:
  • In the sodium thiosulfate group, hypernatraemia occurred in 100% of patients (n=11), all detected immediately after surgery. The mean of each patient's peak sodium was 150.4 mmol/L (SD 2.7).
  • In the sodium thiosulfate group, hypernatraemia resolved by post-operative days 1 to 8 (median day three).
  • In the control group, eight of the remaining patients (excluding one who was already hypernatraemic before surgery) developed hypernatraemia. Their mean peak sodium was 145.5 mmol/L (SD 2.4), lower than in the sodium thiosulfate group, though not compared statistically.
  • No clinical complications of hypernatraemia or its treatment were seen in either group.
  • In the sodium thiosulfate group, acute kidney injury occurred in 4/11 (36.4%) patients by the RIFLE criteria. Three (27.3%) were classified as Risk and one (9.1%) as Failure, and all resolved during admission.
  • Of the patients still in hospital one month after surgery, none had ongoing renal impairment.
• The authors' conclusion: The authors concluded that, despite mild biochemical hypernatraemia without clinical sequelae, sodium thiosulfate appears to be safe as an adjunct to cisplatin-based HIPEC during cytoreductive surgery. They said these findings should be evaluated in further comparative studies.
• Limitations the authors state:
  • The study could not account for other causes of hypernatraemia, such as intravenous sodium bicarbonate, because anaesthetic data and fluid orders were not documented.
  • Post-operative urine output was not recorded in the electronic medical records, so acute kidney injury may have been underestimated.
  • The small sample size made statistical comparison with the control group inappropriate. The data are preliminary.
  • The direction of the relationship between kidney injury and sodium disturbances cannot be established from retrospective data.
  • There was no long-term follow-up, so chronic kidney complications could not be considered.

Topics

Medical terms in this study, explained in our Lexicon: Cisplatin, HIPEC, Chemotherapy, Cytoreductive Surgery, Ovarian Cancer, Mesothelioma, Mitomycin C.

Related studies

• Cytoreductive surgery with intraperitoneal hyperthermic chemotherapy for malignant peritoneal mesothelioma: mitomycin versus cisplatin — A.U. Blackham, P. Shen, et al. (2010)
• Anesthetic management and renal function in pediatric patients undergoing cytoreductive surgery with continuous hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin — P. Owusu-Agyemang, R. Arunkumar, et al. (2012)
• Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin in pediatric patients with peritoneal mesothelioma: a single institution experience and long term follow up — P. Malekzadeh, M. Good, et al. (2021)
• Repeat cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for recurrent diffuse malignant peritoneal mesothelioma — Y. Huang, N.A. Alzahrani, et al. (2015)
• Indications for hyperthermic intraperitoneal chemotherapy with cytoreductive surgery: a clinical practice guideline — R.C. Auer, D. Sivajohanathan, et al. (2020)
• Adjuvant dendritic cell-based immunotherapy after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with malignant peritoneal mesothelioma: a phase II clinical trial — M.V. Dietz, K.L.A. Quintelier, et al. (2023)

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