Cerebral edema in a patient following cytoreductive surgery and hyperthermic intraoperative intraperitoneal chemoperfusion
© Nair et al; licensee BioMed Central Ltd. 2006
Received: 30 June 2006
Accepted: 30 November 2006
Published: 30 November 2006
Cytoreductive surgery and intraoperative, intraperitoneal hyperthermic chemoperfusion (HIPEC) is increasingly used to treat peritoneal surface metastases. We describe a fatal case of cerebral edema in a patient with appendiceal carcinoma and an underlying seizure disorder who underwent cytoreductive surgery and HIPEC.
A case of fatal postoperative cerebral edema is presented in a patient with an underlying seizure disorder and recurrent mucinous adenocarcinoma of the appendix. The patient was treated with cytoreductive surgery and intraoperative intraperitoneal hyperthermic chemoperfusion. The details and implications of this complication are discussed.
The recognition of this potential complication is important for physicians performing cytoreductive surgery and HIPEC. Special caution should be taken when patients with seizure disorders are being considered for this treatment.
The treatment of peritoneal metastases remains one of the most challenging problems in clinical oncology. Over the last decade, interest in the use of aggressive cytoreductive surgery combined with hyperthermic intraperitoneal intraoperative chemotherapy (HIPEC) has increased . This interest has been fueled by data from single institutions and collected series demonstrating long-term survival for selected patients with peritoneal surface metastases treated with this combined modality approach . Along with the availability of new cytotoxic and biologic therapies for gastrointestinal cancers, recent data demonstrating improved survival for ovarian cancer patients treated with postoperative intraperitoneal therapy has only served to increase the interest in such treatment for patients with GI malignancies [3–6].
To date, there has been only a single large randomized study, which demonstrated a benefit for patients with colon carcinoma treated with cytoreductive surgery, HIPEC and systemic chemotherapy versus palliative surgery and chemotherapy alone . Not surprisingly, the most successful outcomes for cytoreduction and HIPEC have been achieved in patients with low-grade malignancies of the appendix . These tumors have a propensity to metastasize solely to peritoneal surfaces, and thus are an ideal tumor type to apply aggressive surgery and intraperitoneal therapies. Along with tumor grade, the completeness of cytoreduction appears to most strongly correlate with patient outcome . Current practice for HIPEC involves either an open abdomen or closed abdomen into which the chemotherapeutic agent(s) are heated to approximately 41°C. Mitomycin and cisplatin are the most commonly used chemotherapeutic agents. HIPEC using these agents results in major morbidity in approximately one third of patients and mortality rates range from 0–12% in recent series [9, 10]. Common complications include intraabdominal abscess/fistula, pulmonary embolism and neutropenia. Here we present a case of death secondary to cerebral edema in a patient who underwent cytoreductive surgery + HIPEC for recurrent appendiceal carcinoma with Mitomycin C.
Studies of HIPEC have revealed characterized several alterations in the physiology of patients during this treatment. Core body temperature is seen to increase significantly, but can usually be maintained in acceptable range by pre-cooling and/or through the use of external cooling measures. Heart rate, CVP and PAP also increase, yet MAP, CO, oxygen delivery, and oxygen consumption do not change significantly [11, 12]. Transient hyperglycemia occurs presumably secondary both to the stress response from surgery and hyperthermia, and to the presence of dextrose in the perfusate. In our patient, electrolytes remained within the normal range. The expected transient hyperglycemia responded appropriately to insulin. Core temperature peaked at 38.7°C and subsequently returned to normal. These are not likely to have contributed to the acute cerebral edema that she suffered.
Seizures are temporary abnormal electrophysiologic phenomena of the brain that result in abnormal synchronization of electrical neuronal activity. They can manifest as an alteration in mental state, tonic or clonic movements and various other symptoms.
When seizure activity is continuous it is referred to as status epilepticus. This persistent condition can lead to neuronal injury. Generalized convulsive status epilepticus (GCSE) is the most common form and is associated with a significant risk of mortality. All other forms of status epilepticus are grouped as nonconvulsive status epilepticus. Etiologies may include high fever and infection in children, electrolyte abnormalities, previous CNS insult, and hypoxia .
Acute brain swelling occurs is seen in a variety of clinical settings. Systemic complications of brain swelling include fever, lactic acidosis, hyperglycemia, respiratory difficulties, and cardiovascular changes [14, 15]. In one animal study, persistent seizures resulted in generalized cerebral edema at 2 hours and necrotic edema at 24 hours . Acute cerebral edema has been documented after generalized convulsive status epilepticus. Our patient suffered from complex partial seizures. We were unable to find evidence of cerebral edema occurring in a patient with complex partial epilepticus. In a case report, transient seizure-induced MR enhancement consistent with ictal or postictal hyperemia in patients with complex partial seizures was reported. However, there changes were noted to be transient . Despite the absence of reports, it remains a possibility that in this patient, acute cerebral edema may have occurred secondary to unrecognized partial complex seizures in a patient whose seizure threshold may have been lowered secondary to the stress of surgery and hyperthermia. Patients with documented complex partial seizure may have confusion as the only manifestation of their seizure activity and thus it is possible to miss the only clinical signs. However, the postoperative EEG in our patient showed no evidence of status epilepticus, thus arguing against this explanation. Additionally, there have been no reports of any association between the presence of a vagus nerve stimulator and acute cerebral edema.
Hyperthermia is reported to predispose the brain to hypoxic/anoxic injury. In our patient, systemic hyperthermia never reached critical levels and had resolved post-operatively. There were no instances of hypoxia in this patient. Thus, unfortunately the etiology of the cerebral edema remains unclear. Given the increasing use of HIPEC, we believe the documentation of unusual complications such as this is important in the consideration of operative risk and for informed consent in future patients with peritoneal surface metastases.
As a result of this event, our group has now incorporated preoperative consultation with a neurologist to insure adequacy of preoperative anticonvulsant therapy and to comment on the possible value of intraoperative EEG monitoring prior to considering HIPEC in any patient with a history of seizures.
This article represents the first description of fatal cerebral edema following treatment of appendiceal carcinoma with intraperitoneal hyperthermic chemoperfusion. This complication occurred in a patient with an underlying seizure disorder and raises the question as to whether this may have been a causative factor. The recognition of this potential complication is important for physicians performing cytoreductive surgery and HIPEC. Special caution should be taken when patients with seizure disorders are being considered for this treatment.
Patients consent was obtained for publication of this case report
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