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Hyperthermic intraperitoneal chemotherapy (HIPEC) on the electrolytes changes and nefropaty

Aslan Bilge

Anesthesiologist, Zekai Tahir Burak Training and Research Hospital, Anesthesia Clinic Department, Talatpa�a Bulvari, 06050, Turkey.

E-mail : aa

Aydin Feray

General Surgery, Zekai Tahir Burak Training and Research Hospital, Turkey.

Gungor Tayfun

Gynecological Oncologist , Prof. Dr. ,Zekai Tahir Burak Training and Research Hospital Oncology Gynecology Clinic Department Chief, Turkey.

DOI: 10.15761/SCRR.1000114

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Abstract

Background

Objective: Hyperthermia intraperitoneal chemoprophylaxis (HIPEC) is a treatment of peritoneal carcinomatosis with potential iatrogenic [1-4]. This study was designed to define the effects of HIPEC on renal functions, electrolytes, nefropaty.

Methods: We retrospectively reviewed the perioperative care of 20 patients. After cytoreductive surgery (CS), residual tumors were not present in all cases, or were less than or equal to 3 mm (measured in size). Cisplatin 50 mg / m 2 plus doxorubicin 15 mg / m 2 was used [5-8]. This is a retrospective study evaluating patients receiving cisplatin with doxorubicin during HIPEC [9-10].

Comorbidities and effects of nephrotoxic drugs were found. Renal function parameters, including serum magnesium levels, were also collected on preoperative and postoperative creatinine levels and on days 1, 5 and 21 post HIPEC. Perioperative urine output (UO) was also recorded.

Findings: 20 patients were identified. Based on the RIFLE classification, patients (2.0%) developed acute renal damage (AKI) with HIPEC after cisplatin. The other patient had renal damage. Comparable mean creatinine levels were observed at baseline and on postoperative 21th day after HIPEC (p > 0.05). The incidence of hypomagnesaemia increased to 10% (p = 0.02) on the 5th day and to 5% on the 21th day (p > 0.05) after HIPEC.

Conclusion: Nephrotoxicity and permanent renal dysfunction may rarely occur in cisplatin therapy with HIPEC. We should closely monitor postoperative Mg levels in patients who have undergone HIPEC administration. Doxsorubicin may have cardiotoxic side effects.

Keywords

Peritoneal Carcinomatosis, HIPEC, cisplatin, doxorubicin, electrolytes.

Method

All patients received HIPEC during general anesthesia. Standard induction was 8 mg/kg pentothal, 1 µ/kg fentanyl, and 6 mg/kg rocuronium intravenously. In the case of all patients in the place were opened as MAC:1 sevolurane and 40% Oxygen + 60% nitrogen was given. TOF and BIS moniterisations were standardized. After debalking operation, HIPEC was performed using a 0.9% isotonic solution of cisplatin + doxarubicin for 40 minutes at 41-42 ° C. All patients underwent open perfusion. Metabolic, electrolyte and hemodynamic changes were noted during chemo-fusion, as well as postoperative metabolic, electrolyte and hemodynamic changes recorded on days 3, 5 and 21.

Table 1. Demographic Datas

All patients n = 20

Patients with RIF 

p Value

Female, %

20 (94.3%)

2 (10%)

Age (years)

49.6 ± 10.1

47.50 ± 10

0.65

Weight (kg)

70.9 ± 14.7

75.1 ± 29

0.01

BSA (m2)

1.75 ± 0.6

2.06 ± 0.6

0.042

Co morbidities

Diabetes mellitus 

4(20%)

1 (50%)

0.43

Hypertension 

5 (25%)

2 (100%)

0.045

Table 2. Electrolytes datas

    

Pre-HIPEC(n=20)

Post-HIPEC (n=20)

Sodium(mmol/L)

135

135

Potassium(mmol/L)

4.2

4.3

Chloride(mmol/L)

108

104

Calcium

8.1

7.1

Bicarbonate(mmol/L)

19

21

Creatinine

0.39

0.45

BUN(mg/dL)

19

21

GFR (ml/min/1.73 m2)

90.50 ± 16.00

80.13 ± 23.02

Mg (1.2 - 2.6 mg/dL)

2.4 ± 0.37

1.78± 0.50

PH

7.42

7.33

Table 3. RIFLE classification for GFR: glomerular filtration rate; UO: urine output; ESRD: end-stage renal disease.

Category

GFR criteria

UO criteria

Risk (R)

Increased creatinine level × 1.5 or GFR decrease > 25%

UO < 0.5 mL/kg/h × 6 h

Injury (I)

Increased creatinine level × 2 or GFR decrease > 50%

UO < 0.5 mL/kg/h × 12 h

Failure (F)

Increased creatinine level × 3 or GFR decrease > 75% or creatinine level > 4 mg/dL

UO < 0.3 mL/kg/h × 24 h or anuria × 12 h

Loss (L)

Persistent acute renal failure or complete loss of renal function for > 4 weeks

ESRD (E)

ESRD for > 3 months

Results

From January 2010 to January 2016, 20 patients were treated. Chemofusion with 0.9% isotonic resulted in transient significant hyponatremia and metabolic acidosis. While major morbidity occurred in 5% of patients, there was no mortality for 6 months. .Chemical interaction with doxorubicin led to mild hepatic toxicity but not significant. Hipomagnesemia was found to be significant when serum magnesium levels were below 0.7 mmol / L. On the 2nd day after operation in one patient in V4, V5, V6 T negative. T negativity improved within a few days. Troponin I and CK-MB never elevated in this patient. Transient hypotension developed in two patients. Doxsorubicin may have cardiotoxic side effects.

Conclusion

Cytoreduction with HIPEC using high dose cisplatin and leads to manageable metabolic and electrolyte disturbances, rarely nephrotoxicity and frequent mild hepatic toxicity without noticable impact on postoperative morbidity. Doxsorubicin may have cardiotoxic side effects.

References

  1. Armstrong DK, Bundy B, Wenzel L (2006) Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med 354: 34–43. [Crossref]
  2. Flessner MF (2005) The transport barrier in intraperitoneal therapy. Am J Physiol Renal Physiol 288: 433–442. [Crossref]
  3. Tannock IF, Lee CM, Tunggal JK (2002) Limited penetration of anticancer drugs through tumor tissue: A potential cause of resistance of solid tumors to chemotherapy. Clin Cancer Res 8: 878–884. [Crossref]
  4. Verwaal VJ, van Ruth S, de Bree E (2003) Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer. J Clin Oncol 21: 3737–3743. [Crossref]
  5. Yan TD, Black D, Savady R (2006). Systematic review on the efficacy of cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for peritoneal carcinomatosis from colorectal carcinoma. J Clin Oncol 24: 4011-4019. [Crossref]
  6. Van Ruth S, Mathot RAA, Sparidans RW (2004) Population pharmacokinetics and pharmacodynamics of mitomycin during intraoperative hyperthermic intraperitoneal chemotherapy. Clin Pharmacokin 43: 131-143. [Crossref]
  7. Chau I, Cunningham D (2006) Adjuvant therapy in colon cancer – what, when and how? Ann Oncol 17: 1347–1359.
  8. Elkas JC, Winter WE, Chernofsky MR (2007) A phase I trial of oxaliplatin and topotecan in recurrent ovarian carcinoma. Gynecol Oncol 104: 422-427. [Crossref]
  9. Zorzi D, Laurent A, Pawlik TM (2007) Chemotherapy-associated hepatotoxicity and surgery for colorectal liver metastases. Br J Surg 94:274–286. [Crossref]
  10. Stephens AD, Alderman R, Chang D (1999) Morbidity and mortality analysis of 200 treatments with cytoreductive surgery and hyperthermic intraoperative intraperitoneal chemotherapy using the Coliseum technique. Ann Surg Oncol 6: 790-796. [Crossref]

Editorial Information

Editor-in-Chief

Article Type

Review Article

Publication History

Received: March 05, 2018
Accepted: March 16, 2018
Published: March 20, 2018

Copyright

©2018 Aslan Bilge. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Citation

Aslan Bilge (2018) Hyperthermic intraperitoneal chemotherapy (HIPEC) on the electrolytes changes and nefropaty. Surg Case Rep Rev, 2 DOI: 10.15761/SCRR.1000114

Corresponding author

Aslan Bilge

Anesthesiologist, Zekai Tahir Burak Training and Research Hospital, Anesthesia Clinic Department, Talatpasa Bulvari, 06050, Ankara/TURKEY. Tel: +90 312 3065184

Table 1. Demographic Datas

All patients n = 20

Patients with RIF 

p Value

Female, %

20 (94.3%)

2 (10%)

Age (years)

49.6 ± 10.1

47.50 ± 10

0.65

Weight (kg)

70.9 ± 14.7

75.1 ± 29

0.01

BSA (m2)

1.75 ± 0.6

2.06 ± 0.6

0.042

Co morbidities

Diabetes mellitus 

4(20%)

1 (50%)

0.43

Hypertension 

5 (25%)

2 (100%)

0.045

Table 2. Electrolytes datas

    

Pre-HIPEC(n=20)

Post-HIPEC (n=20)

Sodium(mmol/L)

135

135

Potassium(mmol/L)

4.2

4.3

Chloride(mmol/L)

108

104

Calcium

8.1

7.1

Bicarbonate(mmol/L)

19

21

Creatinine

0.39

0.45

BUN(mg/dL)

19

21

GFR (ml/min/1.73 m2)

90.50 ± 16.00

80.13 ± 23.02

Mg (1.2 - 2.6 mg/dL)

2.4 ± 0.37

1.78± 0.50

PH

7.42

7.33

Table 3. RIFLE classification for GFR: glomerular filtration rate; UO: urine output; ESRD: end-stage renal disease.

Category

GFR criteria

UO criteria

Risk (R)

Increased creatinine level × 1.5 or GFR decrease > 25%

UO < 0.5 mL/kg/h × 6 h

Injury (I)

Increased creatinine level × 2 or GFR decrease > 50%

UO < 0.5 mL/kg/h × 12 h

Failure (F)

Increased creatinine level × 3 or GFR decrease > 75% or creatinine level > 4 mg/dL

UO < 0.3 mL/kg/h × 24 h or anuria × 12 h

Loss (L)

Persistent acute renal failure or complete loss of renal function for > 4 weeks

ESRD (E)

ESRD for > 3 months