Antineoplastics
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Reactions 1232 - 13 Dec 2008 ★ S Antineoplastics Hyperammonaemic encephalopathy (first report with mitoxantrone) in an elderly patient: case report A 69-year-old man with relapsed non-Hodgkin’s lymphoma (NHL) developed hyperammonaemic encephalopathy after receiving rituximab-containing chemotherapy and died. Following the diagnosis of NHL in July 2004, the man received 2 cycles of CVP chemotherapy and 6 cycles of rituximab plus CHOP chemotherapy; he achieved a partial response. However, he experienced a relapse in September 2005 and was treated with rituximab, mitoxantrone, cyclophosphamide, etoposide, vincristine and prednisolone [dosages not stated]. Concomitant medications included warfarin, candesartan cilexetil and omeprazole. The first 2 cycles were well tolerated; however, he reported feeling lethargic and generally unwell 3 days after his third cycle. On presentation, he appeared confused with incoherent speech and poor mobility. On examination, his Glasgow Coma Score was 12 and he displayed an expressive and partial receptive dysphasia, left to right disorientation, cortical inattention and acalculia; no other focal neurological deficits were detected. Laboratory test results were within normal limits other than mild normochromocytic anaemia. Primary respiratory alkalosis and secondary metabolic acidosis were evident on arterial blood gas analysis. Brain MRI and CT scan were unremarkable, as were the results of a lumbar puncture. His level of consciousness continued to deteriorate over the following 2 days and he was intubated. He experienced multiple focal motor seizures, prompting treatment with phenytoin and clonazepam. Testing revealed a serum ammonium level of 195 µmol/L (normal 20–80), which increased to 345 µmol/L within 24 hours. A repeat brain CT scan revealed severe cerebral oedema with no grey-white differentiation. Continuous venous-venous haemofiltration was initiated to remove excess ammonia and the man received IV dextrose, lactulose and a continuous insulin infusion. Analysis of plasma amino acid levels by column chromatography showed increased levels of glutamine (1330 µmol/L; < 770), methionine (81 µmol/L; 40–50), tyrosine (96 µmol/L; 20–90) and phenylalanine (88 µmol/L; 40–70), indicative of hepatic dysfunction. There was a marked increase in urinary orotic acid (610 µmol/mmolCr) and smaller increases in urine lactate, uracil and p-hydroxyphenyl lactate. Over the following 48 hours, his serum ammonia levels decreased to within normal limits and haemofiltration was stopped. He received sodium benzoate to scavenge ammonia and low protein feeds were started. He remained on ventilatory support for the next 2 weeks. A repeat brain CT scan showed continuing cerebral oedema along with bilateral internal capsular hypodensities suggestive of cytotoxic cell necrosis. Following neurological assessment, he was extubated and died 1 week later on hospital day 23. Author comment: "Our patient’s acquired hyperammonaemic encephalopathy most probably resulted from overload or bypass of the urea-generating system secondary to combination chemotherapy." Nott L, et al. Hyperammonaemic encephalopathy associated with rituximab- containing chemotherapy. Internal Medicine Journal 38: 800-803, No. 10, Oct 2008 - Australia 801124847 » Editorial comment: A search of AdisBase, Medline, Embase and the WHO Adverse Drug Reactions database did not reveal any previous case reports of hyperammonaemia associated with mitoxantrone. 1 Reactions 13 Dec 2008 No. 1232 0114-9954/10/1232-0001/$14.95 Adis © 2010 Springer International Publishing AG. All rights reserved
Transcript of Antineoplastics
Reactions 1232 - 13 Dec 2008
★ SAntineoplastics
Hyperammonaemic encephalopathy (first reportwith mitoxantrone) in an elderly patient: case report
A 69-year-old man with relapsed non-Hodgkin’s lymphoma(NHL) developed hyperammonaemic encephalopathy afterreceiving rituximab-containing chemotherapy and died.
Following the diagnosis of NHL in July 2004, the manreceived 2 cycles of CVP chemotherapy and 6 cycles ofrituximab plus CHOP chemotherapy; he achieved a partialresponse. However, he experienced a relapse in September2005 and was treated with rituximab, mitoxantrone,cyclophosphamide, etoposide, vincristine and prednisolone[dosages not stated]. Concomitant medications includedwarfarin, candesartan cilexetil and omeprazole. The first2 cycles were well tolerated; however, he reported feelinglethargic and generally unwell 3 days after his third cycle. Onpresentation, he appeared confused with incoherent speechand poor mobility. On examination, his Glasgow Coma Scorewas 12 and he displayed an expressive and partial receptivedysphasia, left to right disorientation, cortical inattention andacalculia; no other focal neurological deficits were detected.Laboratory test results were within normal limits other thanmild normochromocytic anaemia. Primary respiratoryalkalosis and secondary metabolic acidosis were evident onarterial blood gas analysis. Brain MRI and CT scan wereunremarkable, as were the results of a lumbar puncture. Hislevel of consciousness continued to deteriorate over thefollowing 2 days and he was intubated. He experiencedmultiple focal motor seizures, prompting treatment withphenytoin and clonazepam. Testing revealed a serumammonium level of 195 µmol/L (normal 20–80), whichincreased to 345 µmol/L within 24 hours. A repeat brain CTscan revealed severe cerebral oedema with no grey-whitedifferentiation.
Continuous venous-venous haemofiltration was initiated toremove excess ammonia and the man received IV dextrose,lactulose and a continuous insulin infusion. Analysis of plasmaamino acid levels by column chromatography showedincreased levels of glutamine (1330 µmol/L; < 770),methionine (81 µmol/L; 40–50), tyrosine (96 µmol/L; 20–90)and phenylalanine (88 µmol/L; 40–70), indicative of hepaticdysfunction. There was a marked increase in urinary oroticacid (610 µmol/mmolCr) and smaller increases in urine lactate,uracil and p-hydroxyphenyl lactate. Over the following48 hours, his serum ammonia levels decreased to withinnormal limits and haemofiltration was stopped. He receivedsodium benzoate to scavenge ammonia and low protein feedswere started. He remained on ventilatory support for the next2 weeks. A repeat brain CT scan showed continuing cerebraloedema along with bilateral internal capsular hypodensitiessuggestive of cytotoxic cell necrosis. Following neurologicalassessment, he was extubated and died 1 week later onhospital day 23.
Author comment: "Our patient’s acquiredhyperammonaemic encephalopathy most probably resultedfrom overload or bypass of the urea-generating systemsecondary to combination chemotherapy."Nott L, et al. Hyperammonaemic encephalopathy associated with rituximab-containing chemotherapy. Internal Medicine Journal 38: 800-803, No. 10, Oct 2008- Australia 801124847
» Editorial comment: A search of AdisBase, Medline, Embaseand the WHO Adverse Drug Reactions database did not revealany previous case reports of hyperammonaemia associated withmitoxantrone.
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Reactions 13 Dec 2008 No. 12320114-9954/10/1232-0001/$14.95 Adis © 2010 Springer International Publishing AG. All rights reserved
