Perioperative Outcomes and Challenges in Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy: A single-institution case series

Summary

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a high-risk, but potentially curative, treatment for peritoneal surface malignancies. This retrospective analysis was conducted between March 2023 and September 2025 at Sultan Qaboos Comprehensive Cancer Care and Research Centre, Muscat, Oman, with the objective of analysing perioperative outcomes and challenges in patients undergoing CRS with HIPEC. Data on demographics, intraoperative variables and postoperative outcomes were collected and statistically analysed. A total of 25 consecutive patients were included. The cohort had significant comorbidities (American Society of Anesthesiologists II/III = 84%). Significant metabolic stress was evidenced by increased lactate (P <0.001) and base deficit (P <0.05). Haemodynamic instability necessitated frequent vasopressor use (noradrenaline = 48%). Postoperatively, 20% developed coagulopathy and 16% renal impairment. Thoracic epidural analgesia was primary in 76% of cases. Prolonged ventilation (>5 days) was needed in 12% and the mortality rate was 8% (n = 2); however, this finding should be interpreted with caution given the limited sample size. Meticulous management of haemodynamics, metabolic stress and tailored multimodal analgesia is crucial. Outcomes align with established literature, underscoring the procedure's complexity and the need for optimised protocols to enhance patient safety.

1. Introduction

Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has emerged as an important treatment strategy for peritoneal surface malignancies, offering improved survival outcomes for selected patients. This aggressive surgical approach, while potentially curative, presents significant perioperative challenges due to the extensive nature of the surgery, prolonged anaesthesia duration and systemic effects of hyperthermic chemotherapy. The procedure is associated with complex physiological derangements, including major fluid shifts, haemodynamic instability, metabolic acidosis and coagulopathy. Despite advances in surgical and anaesthetic techniques, CRS-HIPEC remains a high-risk procedure with considerable morbidity. This report aimed to describe the perioperative course, quantify the incidence of key complications and analyse intraoperative physiological trends in patients undergoing CRS-HIPEC at a tertiary care cancer centre in Muscat, Oman. The authors' hypothesise that the procedure induces significant metabolic stress and haemodynamic instability correlating with surgical complexity. While previous studies have detailed outcomes in larger, mixed cohorts, there is a paucity of literature focusing on the granular intraoperative anaesthetic challenges and detailed postoperative complication profile from the perspective of a nascent programme in the region. As a newly established tertiary cancer centre in Oman, reporting this initial experience is valuable for benchmarking, identifying local challenges, and contributing to the global understanding of perioperative management in diverse settings.

2. Methods

This retrospective report analysed consecutive adult patients (≥18 years old) who underwent CRS-HIPEC at Sultan Qaboos Comprehensive Cancer Care and Research Centre, a tertiary care oncology institution in Muscat, Oman between March 2023 and September 2025. This report included all consecutive patients who underwent CRS-HIPEC during the defined study period, representing the total experience of our nascent programme. A formal sample size calculation was not performed as this is an exploratory analysis of initial outcomes. Patients who had aborted procedures prior to chemotherapy perfusion were excluded. Consecutive patients were identified from the institutional surgical database. Data were systematically collected from electronic medical records, anaesthesia charts and surgical reports to ensure comprehensive capture of all relevant perioperative variables; data extraction followed a standardised protocol. Variables with >10% missing were excluded from analysis. Demographic characteristics, including age, gender, American Society of Anesthesiologists (ASA) physical status and comorbidities, were recorded. Intraoperative data collection focused on surgical duration, peritoneal cancer index (PCI), estimated blood loss, fluid administration parameters, vasopressor requirements and physiological measurements taken at four critical time points: start of CRS, end of CRS, start of HIPEC and end of HIPEC. These time points are standard in HIPEC anaesthesia literature to capture physiologic changes specific to each surgical and chemoperfusion phase. Postoperative outcomes, including complications, intensive care unit length of stay and mechanical ventilation requirements, were documented.

For statistical analysis, continuous variables were expressed as mean ± standard deviation with ranges, while categorical variables were presented as frequencies and percentages. The normality of distribution was assessed using the Shapiro-Wilk test. The Shapiro-Wilk test confirmed normality for key continuous variables (e.g., temperature), justifying the use of parametric tests. Comparisons of repeated measures across different time points were performed using paired t-tests or Wilcoxon signed-rank tests, as appropriate, based on the data distribution characteristics. Paired t-tests were used for normally distributed repeated measures (e.g., temperature), while the Wilcoxon signed-rank test was used for non-normally distributed data (e.g., lactate). Normality was assessed using the Shapiro-Wilk test. Intergroup comparisons for categorical outcomes were conducted using the Chi-square test or Fisher's exact test. Correlation analyses were conducted to examine the relationships between key variables, including PCI and intraoperative blood loss. All statistical analyses were performed using Statistical Package for Social Sciences (SPSS) software, Version 29 (IBM Corp., Armonk, New York, USA) with a P value of <0.05 considered statistically significant. Graphical representations were generated to illustrate trends in physiological parameters throughout the procedure.

3. Results

A total of 25 patients were included in this report. The demographic profile of the patients revealed a predominance of ASA Grade II (52%) and III (32%), with a slight majority of males (56%) over females (44%). Comorbidities were prevalent, with hypertension (32%), diabetes mellitus (28%) and ascites (28%) being the most common. The primary tumours included appendix mucinous adenocarcinoma (44%), colorectal (24%) and mesothelioma (12%) among others. A significant proportion of patients had undergone previous abdominal surgery (64%) or peritonectomy (56%) [Table 1]. The relatively young mean age in this cohort may reflect the prevalence of appendiceal malignancies and specific referral patterns to the cancer centre.

Table 1.

Demographic characteristics of patients who underwent cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (N = 25).

Characteristic	n (%)
ASA Grade
I	4 (16)
II	13 (52)
III	8 (32)
Gender
Male	14 (56)
Female	11 (44)
Comorbidities
Ascites	7 (28)
Coronary artery disease	1 (4)
Diabetes mellitus	7 (28)
Thyroid disorders	1 (4)
Hypertension	8 (32)
Dysrhythmias	1 (4)
Primar tumour
Colorectal	6 (24)
Appendix mucinous adenocarcinoma	11 (44)
Mesothelioma	3 (12)
Primary peritoneal carcinoma	2 (8)
Gastric carcinoma	2 (8)
Renal cell carcinoma	1 (4)
Previous peritonectomy	14 (56)
Previous abdominal surgery	16 (64)

ASA = American Society of Anesthesiologists.

Intra-operative variables indicated a mean body mass index of 27.4 ± 4.8 kg/m², with an average age of 32.6 ± 7.9 years. The mean duration of surgery was 825 ± 29.8 minutes and the peritoneal cancer index score averaged 18.2 ± 3.67. Estimated blood loss was substantial, averaging 1,876 ± 86.4 mL with significant crystalloid (8,750 ± 356.67 mL) and blood product administration. The completeness of cytoreduction (CC) score at the end of surgery was CC-0/1 in 88% of cases. Notably, all patients maintained a urine output greater than 1 mL/kg. Temperature fluctuations were observed, with a significant increase at the end of HIPEC (37.4 ± 1.4; P <0.001). Haemodynamic parameters such as mean blood pressure and heart rate showed variability, with significant changes in lactate levels (P <0.001) and base deficit (P <0.05) during the procedure [Table 2].

Table 2.

Intra-operative variables of the cohort.

Variable	Mean ± SD (range)	P value
BMI	27.4 ± 4.8 (18.4–40)
Age in years	32.6 ± 7.9 (20–76)
Duration of surgery in min	825 ± 29.8 (420–2,340)
Peritoneal cancer index score	18.2 ± 3.67 (2–39)
Estimated blood loss in mL	1,876 ± 86.4 (200–9,000)
Total crystalloid in mL	8,750 ± 356.67 (4,500–22,000)
Total blood/blood products
Blood in units	2.46 ± 0.98 (0–14)
FFP in mL	131.5 ± 22.5 (0–500)
Platelet in units	0.38 ± 0.76 (0–8)
Cryoprecipitate in units	1.35 ± 0.97 (0–10)
Total colloids (albumin) in mL	131.25 ± 21.34 (0–250)
Net fluid balance in mL2	5,125 ± 1,245 (2,100–9,800)
Completeness of cytoreduction score (CC-0/1) in %	88
Number of patients with urine output in mL/kg
<0.5	0
0.5–1	0
>1	25
Temperature in °C		<0.001
At start of CRS	35.8 ± 1.2 (34.9–37.0)
At the end of CRS	35.4 ± 0.98 (32.0–37.0)
At the start of HIPEC	35.4 ± 0.76 (32–36.8)
At the end of HIPEC	37.4 ± 1.4 (35.0–38.5)
Mean blood pressure in mmHg		<0.05
At start of CRS	79.3 ± 11.4 (62–95)
At the end of CRS	76.2 ± 9.65 (60–91)
At the start of HIPEC	79.6 ± 9.14 (74–92)
At the end of HIPEC	79.6 ± 9.14 (74–92)
Heart rate in beats/min		0.117
At start of CRS	85.6 ± 13.2 (67–120)
At the end of CRS	93.2 ± 11.43 (65–126)
At the start of HIPEC	94.2 ± 10.75 (70–129)
At the end of HIPEC	94.1 ± 11.35 (72–130)
Lactates in mmol/L		<0.001
At start of CRS	1.1 ± 0.62 (0.3–2.2)
At the end of CRS	3.3 ± 1.24 (0.9–8.9)
At the start of HIPEC	3.5 ± 1.32 (0.9–8.2)
At the end of HIPEC	3.8 ± 1.97 (1.0–9.4)
Ph		0.109
At start of CRS	7.39 ± 0.67 (7.29–7.52)
At the end of CRS	7.34 ± 0.74 (7.20–7.47)
At the start of HIPEC	7.32 ± 0.98 (7.2–7.47)
At the end of HIPEC	7.31 ± 0.78 (7.19–7.44)
Base deficit		<0.05
At start of CRS	–1.8 ± 1.1 (–1.3 to –8.0)
At the end of CRS	–1.2 ± 1.24 (–6.4 to –8.4)
At the start of HIPEC	–1.9 ± 1.53 (–6.4 to –15)
At the end of HIPEC	–2.3 ± 1.46 (–5.8 to –17)
Airway pressure in cm of water		0.135
At start of CRS	17 ± 3.2 (12–27)
At the end of CRS	17.5 ± 3.6 (12–26)
At the start of HIPEC	17.6 ± 4.2 (12–28)
At the end of HIPEC	17.3 ± 4.3 (12–25)
End-tidal carbon dioxide in mmHg		0.148
At start of CRS	35.4 ± 2.35 (32–39)
At the end of CRS	35.1 ± 2.24 (32–38)
At the start of HIPEC	35.4 ± 2.1 (32–38)
At the end of HIPEC	35.9 ± 3.2 (31–41)

SD = standard deviation; BMI = body mass index; FFP = fresh frozen plasma; CRS = cytoreductive surgery; HIPEC = hyperthermic intraperitoneal chemotherapy.

Postoperative outcomes included a 32% incidence of chest tube placement, with an average duration of 4.2 ± 1.56 days. Mean length of stay was 18.4 ± 9.6 days (range: 7–45 days). Coagulopathy occurred in 20% of patients and renal impairment was noted in 16%. A Clavien-Dindo grade (I–V) was assigned to each complication [Table 3,Table 4]. The overall major complication rate (Grade ≥III) was 48%. Pain management predominantly involved epidural analgesia (76%), with a smaller subset requiring intravenous (IV) patient-controlled analgesia (PCA; 28%). Vasopressor use was common, with noradrenaline (48%) and phenylephrine (44%) frequently administered. Postoperative ventilation was required in most patients, with 64% ventilated for less than 2 days, 24% for 2–5 days and 12% for more than 5 days. The mortality rate was 8% (95% confidence interval: 1.0–26.0%). Table 5 details the characteristics of 5 patients with the longest surgical durations (>1,000 mins), highlighting extensive multi-visceral resections and the association with multiple major postoperative complications. HIPEC regimens were specified as oxaliplatin-based (84%), cisplatin/doxorubicin (16%).

Table 3.

Further clinical variables of the current cohort.

Variable	n (%)	Mean days ± SD (range)	Clavien-Dindo grade for complications
LOS in days		18.4 ± 9.6
Chest tube	8 (32)	4.2 ± 1.56 (3–10)	II (n = 5)
			IIIa (n = 3)
Postoperative coagulopathy	5 (20)	3.8 ± 0.32 (2–4)	II (n = 3)
			IVa (n = 2)
Post-operative renal impairment	4 (16)	4.35 ± 1.32 (2–8)	I (n = 1)
			II (n = 2)
			III (n = 1)
Post-operative pain management
Epidural	19 (76)	4.2 ± 0.76 (3–8)
IV PCA	7 (28)	4.6 ± 0.95 (3–9)
Regional	1 (4)	2.6 ± 0.48 (1–4)
Medications
Noradrenaline	12 (48)	2.3 ± 0.79 (1–5)
Phenylephrine	11 (44)	1.2 ± 0.56 (1–3)
Lasix	7 (28)	4.3 ± 1.2 (2–8)
Ephedrine	10 (40)	6.74 ± 3.8 (7–13)
Postoperative ventilation in days
<2	16 (64)
2–5	6 (24)
>5	3 (12)
Mortality	2 (8)

SD = standard deviation; LOS = length of stay; IV PCA = intravenous patient-controlled analgesia.

Table 4.

Profile of patients with long duration of surgery.

Patient number	Time in mins	Medical history	Surgical resection	Perioperative complications	Clavien-Dindo grade	LOS in days
1	1,140	Ascites	Cytoreductive surgery and HIPEC; complete peritonectomy, ileocecectomy, splenectomy, thermo-ablation of liver. HIPEC: Oxaliplatin 300 mg/m2 for 60 min.	Coagulopathy, AKI, deranged liver function, hypotension	IVa	20
2	1,055	Diabetes, hypertension	Laparotomy, cytoreductive surgery (peritonectomy, right hemicolectomy, splenectomy, omentectomy, cholecystectomy, anterior resection) + HIPEC with oxaliplatin for 60 min.	AKI, nosocomial pneumonia, liver failure, hypotension, arrhythmias, coagulopathy	IVb	40
3	1,880	Ascites, previous surgery	Cytoreduction; total parietal peritonectomy, sub-total colectomy, hysterectomy, left oophorectomy, splenectomy, total greater and lesser omentectomy, cholecystectomy, peri-hepatic pedicle dissection. HIPEC: Oxaliplatin 200 mg/m$ for 60 min.	AKI, coagulopathy, hypotension, liver failure, nosocomial pneumonia, stress cardiomyopathy	V	100
4	1,200	Ascites, diabetes	Laparotomy, cytoreductive surgery, right hemicolectomy, total peritectomy, splenectomy, hysterectomy, bilateral salpingo-oophorectomy. HIPEC: Oxaliplatin 250 mg/m2 for 60 min.	Coagulopathy, nosocomial pneumonia, AKI, Hypotension, arrhythmias	IIIb	40
5	2,340	Diabetes, hypertension	Laparotomy, adhesion lysis, en-block resection of left/right paracolic gutter peritonectomy, extensive small and large bowel deposits removal, excision of paraaortic/retroportal nodes, intraoperative liver ultrasound, temporary closure of abdomen. HIPEC: Cisplatin + Doxorubicin for 1 hour.	Nosocomial pneumonia, hypotension, hypertension, coagulopathy, AKI, deranged liver function, stress cardiomyopathy	V	45

LOS = length of stay; HIPEC = hyperthermic intraperitoneal chemotherapy; AKI = acute kidney injury.

Table 5.

Procedure and outcome summary by primary tumour type.

Primary tumour type	n	Mean PCI (range)	Mean surgery duration in mins (range)	Mean EBL in mL (range)	Patients with major complications (grade ≥III), n (%)
Appendiceal adenocarcinoma	11	15.8 (2–28)	745 (420–1,140)	1,450 (200–3,500)	4 (36.4)
Colorectal cancer	6	22.4 (10–39)	890 (600–1,200)	2,100 (800–5,000)	4 (66.7)
Mesothelioma	3	26.7 (18–35)	1,010 (850–1,200)	2,400 (1,500–4,000)	2 (66.7)
Other	5	16.0 (8–25)	780 (550–1,055)	1,800 (700–3,000)	2 (40.0)
Total/average	25	18.2 (2–39)	825 (420–2,340)	1,876 (200–9,000)	12 (48.0)

PCI = peritoneal cancer index; EBL = estimated blood loss.

4. Discussion

The findings of this report provide a comprehensive overview of the perioperative characteristics and outcomes of patients undergoing CRS-HIPEC. The observed mortality (8%) and major complication rates (coagulopathy = 20%, renal impairment = 16%) fall within the wide ranges reported in larger series (mortality: 2–10%); this should be taken with caution because of this report's small sample size. The demographic profile revealed that the majority of patients were classified as ASA II (52%) or ASA III (32%), indicating a population with significant comorbidities, which is consistent with previous reports highlighting the high-risk nature of patients selected for HIPEC procedures.¹ The gender distribution showed a slight male predominance (56%) and common comorbidities included hypertension (32%) and diabetes mellitus (28%), underscoring the importance of preoperative optimisation to mitigate perioperative risks.² The most frequent primary tumours were appendix mucinous adenocarcinoma (44%) and colorectal cancer (24%), aligning with other studies that identify these malignancies as common indications for CRS/HIPEC.³ The young mean age of the current cohort, primarily driven by appendiceal primaries, may influence physiological reserve and complication profiles compared to older cohorts with colorectal primaries, warranting age-stratified analysis in larger studies. The high prevalence of previous abdominal surgery (64%) and peritonectomy (56%) further emphasises that these patients often present with advanced or recurrent disease, necessitating aggressive surgical and chemotherapeutic approaches.⁴

Intraoperative variables demonstrated the complexity of CRS/HIPEC, with a mean surgical duration of 825 minutes and substantial blood loss (1,876 mL), findings that are comparable to other large series.^1,3 In the current report, the mean operative time and blood loss are comparable to those reported by other authors.^3,5,6 The significant rise in lactate levels (from 1.1 to 3.8; P <0.001) and worsening base deficit (from –1.8 to –2.3; P <0.05) reflect the metabolic stress induced by the procedure, likely due to surgical trauma and the systemic effects of hyperthermic chemotherapy.⁶ Serial lactate measurement was a useful marker of evolving metabolic stress, correlating with surgical duration and blood loss. However, its limitations are acknowledged; transient elevations are expected during HIPEC due to regional hyperthermia and may not solely reflect hypoperfusion, necessitating integration with other clinical parameters. The marked increase in temperature during HIPEC (37.4°C; P <0.001) confirms effective hyperthermia delivery, though careful monitoring is required to avoid complications such as systemic hyperthermia or organ dysfunction.⁷ Haemodynamic parameters, including mean blood pressure and heart rate, remained relatively stable. Still, the frequent use of vasopressors (48% noradrenaline, 44% phenylephrine) suggests that haemodynamic support is often necessary to maintain perfusion during and after the procedure.

Postoperative outcomes revealed a range of complications, including coagulopathy (20%) and renal impairment (16%), which are well-documented challenges in HIPEC patients.⁸ The high incidence of chest tube placement (32%), coagulopathy (20%) and renal impairment (16%) signals the need for proactive strategies. This supports routine pleural cavity assessment during surgery, protocolised post-HIPEC coagulation studies with timely factor repletion and vigilant fluid balance monitoring to avoid nephrotoxicity. Pain management was primarily achieved with epidural analgesia (76%). However, a subset of patients required transition to IV PCA (28%), indicating variability in pain control needs and potential gaps in epidural efficacy for some individuals. The current institutional protocol incorporates several enhanced recovery after surgery (ERAS) principles: preoperative carbohydrate loading, avoidance of long-acting sedatives, goal-directed fluid therapy using stroke volume variation, mandatory epidural analgesia and early enteral nutrition. Deviations include routine intensive care unit admission postoperatively and variable use of non-opioid adjuncts, highlighting areas for protocol strengthening. Ventilation requirements were notable, with 64% of patients extubated within 2 days, while 12% required prolonged ventilation, likely due to the systemic inflammatory response syndrome or other postoperative complications.^9,10 The mortality rate of 8% is within the range reported in other HIPEC series, where rates vary from 2% to 10% depending on patient selection and institutional experience.⁹ These findings have directly altered the current institute's protocol, leading to the pre-emptive involvement of nephrology, stricter coagulation monitoring post-HIPEC and the development of a standardised multimodal analgesia bundle.

The management of postoperative pain following CRS-HIPEC presents unique challenges due to the extensive surgical trauma, prolonged operative duration and systemic effects of hyperthermic chemotherapy. The current report revealed that thoracic epidural analgesia (TEA) was the primary modality for pain control, used in 76% of cases, with a mean duration of 4.2 ± 0.76 days. This aligns with current literature advocating TEA as the gold standard for major abdominal surgeries, given its efficacy in reducing opioid consumption, facilitating early extubation and lowering pulmonary complications.^11,12 However, 28% of patients required transition to IV PCA suggesting limitations in epidural efficacy, potentially due to HIPEC-induced coagulopathy or inadequate coverage of visceral pain.^10,13

The high vasopressor requirements (noradrenaline in 48%, phenylephrine in 44%) underscore the haemodynamic instability during CRS-HIPEC, which may complicate TEA administration. Notably, 20% of patients developed coagulopathy, a known risk factor for epidural haematoma, though no such complications were reported in the current cohort. This supports Konkianitis et al.'s findings, who demonstrated the safety of TEA in CRS-HIPEC despite transient coagulation abnormalities.¹⁴

Alternative regional techniques, such as the transversus abdominis plane (TAP) block, were underutilised (4% in the current report). While TAP blocks offer advantages such as technical simplicity and lower bleeding risk, their efficacy in CRS-HIPEC remains debated. Deng et al., reported superior pain relief with quadratus lumborum blocks compared to TAP blocks in colorectal surgery, but data specific to CRS-HIPEC are limited.¹⁵ The high incidence of renal impairment (16%) further complicates pain management, as non-steroidal anti-inflammatory drugs are often contraindicated, narrowing analgesic options.

Multimodal analgesia was inconsistently applied, with only 8% of patients receiving adjuncts such as gabapentin. This contrasts with the ERAS protocols that emphasise multimodal approaches to reduce opioid dependence.¹⁴ The prolonged ventilation requirements (12% >5 days) highlight the interplay between pain control and respiratory outcomes, as poorly managed pain can impair pulmonary function.¹⁵

The retrospective design and selection of patients deemed suitable for this major surgery introduces unavoidable selection bias, limiting the generalisability of findings to all patients with peritoneal surface malignancies. The exploratory nature of multiple statistical comparisons increases the risk of Type I error; findings should be considered hypothesis-generating. The small sample size limits the statistical power to detect significant associations between variables and outcomes. The cohort size precluded meaningful multivariable regression to identify independent predictors of complications. As an initial case series, the results may reflect institutional learning curve effects in both surgical and anaesthetic management, which could improve over time. Other limitations include the single-centre nature and lack of long-term oncologic outcomes.

5. Conclusion

This report reinforces that CRS/HIPEC is a high-risk but viable treatment for peritoneal malignancies, with outcomes heavily influenced by patient selection, intraoperative management and postoperative care. The findings align with existing literature and highlight areas for further research, such as validating predictors of prolonged ventilation and renal injury in HIPEC patients, exploring protocolised fluid management strategies and assessing the impact of enhanced recovery pathways tailored to this population. Future studies should focus on identifying predictors of complications and long-term survival to refine patient selection and enhance outcomes.

Authors' Contribution

Parli Raghavan Ravi: Conceptualisation, Methodology, Formal Analysis, Data Curation, Writing - Original Draft. Maha Abdullah Naseer AlShaibi: Writing - Original Draft, Writing - Review & Editing, Visualisation. Raj Sahajanandan: Writing - Review & Editing, Formal analysis. Mohammed Abdullah Saif AlHosni: Writing - Review & Editing, Data Curation, Visualisation. Srinivas Shyam Mantha: Methodology, Data Curation.

Acknowledgement

We would like to acknowledge Sneha Parli for her valuable contribution to the statistical analysis and coding of this study.

Ethics Statement

Institutional ethical approval was obtained from the Sultan Qaboos Comprehensive Cancer Care and Research Centre (CCCRC-17-2024). The requirement for informed consent was waived due to the retrospective nature of the investigation.

Conflict of Interest

The authors declare no conflicts of interest.

Funding

No funding was received for this study.

Data Availability

Data are available upon reasonable request from the corresponding author.