a 39 year - old female patient with ovarian cancer ( stage iii ) underwent tah with bso ( total abdominal hysterectomy and bilateral salpingo - oophorectomy ) at another hospital . during chemotherapy with paclitaxel and carboplatin ( day 9 , pod 16 ) , she showed melena followed by hematochezia . she was diagnosed with neutropenic / septic shock due to ascending colon perforation and was transferred to our hospital . emergent total colectomy was successfully conducted , and the patient was moved to the icu . the patient experienced difficulty in weaning from mechanical ventilation due to severe tachypnea and labored breathing . neutropenia did not improve in spite of granulocyte colony - stimulating factor ( g - csf ) injection chemotherapy induced neutropenia and sepsis was suspected , thus g - csf and antibiotics ( piperacillin / tazobactam ) were administered . the patient was extubated but she complained of dyspnea and showed deteriorating levels of consciousness . after reintubation , brain ct and electroencephalography ( eeg ) were performed which showed no abnormal findings ( fig . her neurologic status did not show improvement and on the next day , she suddenly developed partial seizure which progressed to generalized tonic - clonic ( gtc ) seizure . arterial blood gas analysis showed respiratory alkalosis with metabolic alkalosis ( ph : 7.604 , paco2 : 24.2 mmhg , hco3 : 27.4 mmol / l ) , while electrolytes and liver panel were unremarkable . continuous renal replacement therapy ( crrt ) for the treatment of hyperammonemia was not effective ( follow - up ammonia level was 1,356 g / dl ) . the patient showed recurrent episodes of gtc type seizure requiring management of status epilepticus . midazolam and phenytoin fluctuating level of consciousness is common in icu patients and it has been associated with increased mortality . when serious neurological insults such as stroke or seizure affect a patient , it is often too late to attempt for a significant alteration in the outcome of the patient . therefore , it seems best to identify the underlying risk factors and prevent / attenuate such critical conditions . however , given the multi - factorial and unpredictable nature of hyperammonemia , critical events can occur unexpectedly . common symptoms of hyperammonemia include hypotonia , vomiting , lethargy , seizures , coma , ataxia , anorexia , abnormal behavior patterns , dysarthria , weakness , liver enlargement , and dementia . ammonia , along with inflammation , has been consistently shown to play a central role in hepatic encephalopathy . hepatic causes of hyperammonemia are well documented and include hepatotoxins , reye syndrome , or carnitine deficiency . however , hyperammonemia in the context of unremarkable liver function tests is a challenge for physicians - the differential diagnosis becomes more difficult . causes worth considering in patients with non - hepatic hyperammonemia include inborn errors of metabolism ( defects of the urea cycle , fatty acid oxidation , organic acid disorders ) , circulatory shock with or without portosystemic shunt , hematological malignancies , urinary infection with urease - producing bacteria , anticonvulsants or chemotherapeutic drugs , and excessive amino acid load / increased catabolism . laboratory tests pertaining to enzyme deficiencies were not conducted in the present case because it was considered less worthwhile given the rapid clinical deterioration of the patient . hyperammonemia after chemotherapy has also been reported in the literature , mostly with hematological malignancies but also in colorectal cancer patients . it has also been described in patients with multiple myeloma in those receiving chemotherapy with aspraginase , 5-fluorouracil , and in those receiving rituximab . however , there have been no reports on chemotherapy agents ( taxanes and platinum agents ) used in the treatment of ovarian cancer , as the case in our patient . surgical procedures or interventions reported to be associated with hyperammonemia include lung transplantation , bone marrow transplantation , and bariatric surgery . although the most common cause of hyperammonemia seems to be hepatic dysfunction , this is unlikely to be the cause in our patient given the normal liver function test results . we believe that the cause may have been infection , bleeding , chemotherapy or the sum of the factors listed . the goal for the treatment of acute hyperammonemia should be rapid reduction of serum ammonia , regardless of the cause . whenever possible , protein intake should be discontinued and hypercaloric glucose - based solution should be provided to enhance anabolism . supportive treatment and correction of hydration , nutritional status , mineral ( calcium , potassium ) , and electrolyte imbalances should be addressed . benzoate binds glycerine and forms hippurate while phenylacetate binds glutamine to form phenyl - acetylglutamine . when ammonia production exceeds removal , the role of dialysis becomes significant . on the other hand , dialysis may cause rebound increases in ammonia by removing nutrients from plasma and creating a catabolic state . orthotopic liver transplantation may be necessary in patients who display poor response to conservative management with refractory / recurrent hyperammonemia . one report showed that liver transplantation resulted in a 3-year survival of 93% and improved quality of life , including a normal - protein diet . given the high level of ammonia in our patient , crrt and sodium benzoate were administered . some advocate the use of hemodialysis which may have been more beneficial in our patient , but the substantial hemodynamic instability of our patient hindered its use . severe hyperammonemia is associated with high mortality and morbidity . when this is not primarily due to liver failure , prompt and early diagnosis followed by appropriate intervention is pivotal but challenging . with regard to our case , there were several possible causes of non - hepatic hyperammonemia that are unlikely when considered separately , but potentially possible when considered altogether . the possible causes that may have contributed to increased ammonia production include underlying infection , recent history of chemotherapy , gi bleeding , total parenteral nutrition . in hindsight , serial levels of ammonia , including the baseline level , would have been helpful in managing the patient . whether it would have altered the outcome remains uncertain . from the lessons of our case , we recommend that serum levels of ammonia should be included in the initial diagnostic work - up of patients with risk factors for hyperammonemia , especially if they show altered consciousness and convulsion / seizure in the icu .