Anesthesia Challenges During HITHOC: A Narrative Review with Institutional Experience

Bernard Marcel Barban^1*, Daniel Sousa Cesar¹, Gustavo Schvartsma², Ricardo Mingarini Terra^3,4

¹Department of Anesthesiology, Hospital Israelita Albert Einstein, São Paulo, Brazil

²Oncology, Hospital Israelita Albert Einstein, São Paulo, Brazil

³Thoracic Surgery, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil

⁴Thoracic Surgery, Instituto do Cancer de São Paulo, São Paulo, SP, Brazil

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Introduction

Hyperthermic intrathoracic chemotherapy (HITHOC) is an advanced multimodal therapeutic approach for malignant pleural diseases, particularly mesothelioma and advanced thymoma. This technique combines cytoreductive surgery with intrapleural perfusion of heated chemotherapeutic agents (approximately 42°C), resulting in significant physiological disturbances and substantial anesthetic challenges^1,2.

Despite its growing adoption in specialized centers, anesthetic management during HITHOC remains poorly standardized, with most available evidence derived from small case series.

At Hospital Israelita Albert Einstein, 15 procedures have been performed over the past two years, with perioperative findings consistent with those reported in the literature. This article is presented as a narrative review complemented by institutional experience. Its objective is to summarize the current evidence regarding perioperative anesthetic management during HITHOC while describing practical aspects of the protocol adopted at Hospital Israelita Albert Einstein.

Literature Search Strategy

A narrative literature review was performed using PubMed/MEDLINE and Google Scholar. The search included publications through 2025 using combinations of the terms HITHOC, hyperthermic intrathoracic chemotherapy, cytoreductive surgery, anesthesia, perioperative management, and thoracic oncology. Priority was given to clinical studies, narrative reviews, systematic reviews, and consensus publications addressing anesthetic and perioperative management. Because of the limited number of available studies, evidence from institutional case series was also considered.

Pathophysiology and Hemodynamic Challenges

Cardiovascular Instability

The intrathoracic instillation of 3–5 liters of heated perfusate leads to profound hemodynamic changes. Up to 50% of patients may experience significant reductions in arterial blood pressure, while tachycardia (>100 bpm) occurs in a subset of cases^1,3.

These alterations are primarily driven by increased intrathoracic pressure, resulting in mediastinal shift, elevated central venous pressure, and increased airway pressures. Consequently, venous return is impaired, cardiac chambers may be compressed, and cardiac output can decrease¹.

In parallel, a hyperdynamic circulatory state may develop, characterized by reduced systemic vascular resistance, increased cardiac index, and elevated end-tidal CO₂. Although often transient, severe events such as intraoperative asystole have been reported, underscoring the potential severity of these physiological disturbances^2,3.

Our institutional experience mirrors these findings and reinforces the importance of continuous invasive hemodynamic monitoring throughout all phases of the procedure.

Temperature Management Challenges

Thermoregulation during HITHOC presents a biphasic pattern. During cytoreductive surgery, patients are at risk of hypothermia, whereas the perfusion phase induces controlled hyperthermia¹.

Hyperthermia is associated with increased metabolic demand, elevated lactate levels, and metabolic acidosis, and may lead to neurological complications at extreme temperatures (>43°C)^1,2,3.

Anesthetic Management Strategies

Monitoring and Vascular Access

Comprehensive monitoring is mandatory and should include invasive arterial pressure monitoring, central venous access, continuous core temperature monitoring, capnography, and hourly urine output assessment.

Anesthetic Technique

A combined approach using general anesthesia and thoracic epidural analgesia is widely considered optimal.

Thoracic epidural analgesia provides effective intraoperative and postoperative pain control, reduces systemic opioid requirements, and may facilitate earlier recovery. General anesthesia may be maintained using either volatile agents or total intravenous anesthesia (TIVA), depending on institutional preference^4,5.

Fluid Management and Vasoactive Support

Perioperative fluid management requires a careful balance between maintaining adequate organ perfusion and avoiding fluid overload, particularly given the risk of pulmonary complications^3,4,5.

Forced diuresis is commonly employed to reduce cisplatin-induced nephrotoxicity. However, this approach must be individualized based on hemodynamic status and renal function.

Vasoactive support is frequently necessary. In our experience, norepinephrine was required in all cases, with progressive dose escalation during the hyperthermic phase. In selected cases, vasopressin was added to achieve hemodynamic stability^1,2,3.

Blood Management

Significant intraoperative blood loss is common and often necessitates transfusion. However, in contrast to hyperthermic intraperitoneal chemotherapy (HIPEC), clinically significant coagulopathy appears to be less frequent during HITHOC^1,2.

Pain Management

Thoracic epidural analgesia remains the gold standard for postoperative pain control. It provides superior analgesia compared to systemic strategies, reduces opioid consumption, and may contribute to earlier extubation and improved respiratory outcomes^3,4.

Respiratory Management

One-lung ventilation is required and should follow lung-protective strategies, including low tidal volumes (approximately 5 mL/kg), limitation of plateau pressures, and moderate levels of PEEP (5–10 cmH₂O)^1,4,5.

During the perfusion phase, appropriate PEEP may help prevent atelectasis and improve distribution of chemotherapeutic agents.

Postoperative Considerations

Extubation and Recovery

Early extubation is feasible in most patients, provided that hemodynamic and respiratory stability are achieved. ICU stay typically ranges from 1 to 4 days, with overall hospital stay varying between 2 and 4 weeks^1,4.

Complications

Although severe complications are relatively uncommon, they may require surgical reintervention. Renal toxicity remains a major concern but can be minimized through optimized fluid management and protective strategies^1,4,6.

Institutional Experience

Between 2024 and 2026, 15 patients underwent HITHOC at Hospital Israelita Albert Einstein.

All procedures were performed using combined thoracic epidural anesthesia and TIVA with target-controlled infusion of propofol and remifentanil. The epidural solution consisted of ropivacaine 0.375% (20 mL), fentanyl (100 μg), and morphine (2 mg).

Norepinephrine infusion was required during all procedures, with progressive dose escalation during the hyperthermic phase. Vasopressin was added in selected patients presenting persistent vasodilatory hypotension.

Based on our institutional protocol, perfusion was initiated with a target core temperature of approximately 35°C, allowing gradual warming to approximately 37°C by the end of perfusion. Although this strategy has provided satisfactory temperature control in our experience, it represents an institutional practice and has not been validated in comparative clinical studies.

Overall, the physiological responses observed at our institution were consistent with those reported in published case series.

Although complete perioperative data were not available for all patients who underwent HITHOC at our institution, we included a concise summary of our institutional experience to illustrate that the overall perioperative characteristics and anesthetic challenges observed in our practice are consistent with those reported in the published literature. This section is intended to provide clinical context rather than to present a comprehensive case series or comparative analysis.

Proposed Perioperative Management Algorithm

The proposed management algorithm was developed by integrating findings from the available literature with the institutional protocol currently employed at Hospital Israelita Albert Einstein. It is intended as a practical framework rather than an evidence-based guideline and should be adapted according to institutional resources, surgical technique, and patient characteristics. (Figure A)

Figure A

Safety Considerations

Strict safety protocols are essential to protect healthcare personnel from exposure to cytotoxic agents. The use of appropriate personal protective equipment and adherence to safe handling protocols are mandatory, as patient body fluids may remain contaminated for up to 48 hours post-procedure^1,3,4.

Conclusion

HITHOC is a highly complex procedure requiring comprehensive perioperative planning, meticulous monitoring, individualized hemodynamic management, and close multidisciplinary collaboration.

Current recommendations are supported primarily by observational studies and institutional experiences. Our institutional findings are consistent with the published literature but should be interpreted as complementary clinical experience rather than confirmatory evidence.

Our experience at Hospital Israelita Albert Einstein aligns with the existing literature and highlights the need for further research aimed at standardizing anesthetic protocols and improving perioperative outcomes.

References

1. Kerscher C, Ried M, Hofmann HS, et al. Anaesthetic management of cytoreductive surgery followed by hyperthermic intrathoracic chemotherapy perfusion. J Cardiothorac Surg. 2014; 9: 125. doi:10.1186/1749-8090-9-125
2. Unigarro-Londoño F, Navarro-Ripoll R, Sánchez-Lorente D, et al. Perioperative anaesthetic management of patients undergoing thoracic cytoreductive surgery and hyperthermic intrathoracic chemotherapy. Ann Transl Med. 2021; 9(11): 956. doi:10.21037/atm-20-6221
3. Markowiak T, Larisch C, Hofmann HS. Hyperthermic intrathoracic chemotherapy (HITHOC): narrative review of the current literature, recommendations and future studies. Ann Transl Med. 2021; 9(11): 955. doi:10.21037/atm-20-5444
4. Zhou H, Wu W, Tang X, et al. Effect of hyperthermic intrathoracic chemotherapy on malignant pleural effusion: a systematic review and meta-analysis. Medicine (Baltimore). 2017; 96(1): e5532. doi:10.1097/MD.0000000000005532
5. Oliveira RENN, Peres CAP, Oliveira AC, et al. Efficacy of cytoreductive surgery and hyperthermic intrathoracic chemotherapy (HITHOC) in thymic neoplasia: a systematic review and single-arm meta-analysis. Ann Surg Oncol. 2025; 32(3): 1670-1678. doi:10.1245/s10434-024-16547-4
6. Danuzzo F, Sibilia MC, Vaquer S, et al. The role of hyperthermic intrathoracic chemotherapy (HITHOC) in thoracic tumors. Cancers (Basel). 2024; 16(14): 2513. doi:10.3390/cancers16142513