halothane and Hepatic Encephalopathy studies

Hepatic Encephalopathy: A syndrome characterized by central nervous system dysfunction in association with LIVER FAILURE, including portal-systemic shunts. Clinical features include lethargy and CONFUSION (frequently progressing to COMA); ASTERIXIS; NYSTAGMUS, PATHOLOGIC; brisk oculovestibular reflexes; decorticate and decerebrate posturing; MUSCLE SPASTICITY; and bilateral extensor plantar reflexes (see REFLEX, BABINSKI). ELECTROENCEPHALOGRAPHY may demonstrate triphasic waves. (From Adams et al., Principles of Neurology, 6th ed, pp1117-20; Plum & Posner, Diagnosis of Stupor and Coma, 3rd ed, p222-5)

Research Excerpts

Excerpt	Relevance	Reference
" We present a case report wherein a person who sustained avulsion injury to his left hand in an industrial accident, died due to, fulminant hepatitis, hepatic encephalopathy and acute renal failure, having undergone six operations under general anesthesia with halothane during his stay in the hospital."	3.73	Fulminant hepatic failure following halothane anaesthesia. ( Bhat, VJ; Kumar, GP; Sowdi, V, 2005)
"Halothane antibodies were detected in 12 of the 16 (75%) patients with hepatic encephalopathy and 16 of the 23 (70%) who did not develop encephalopathy, demonstrating that halothane antibodies are detectable in a wider spectrum of halothane-associated liver damage than previously appreciated."	1.27	Specific antibodies to halothane-induced liver antigens in halothane-associated hepatitis. ( Kenna, JG; Neuberger, J; Williams, R, 1987)
"3."	1.25	Exchange transfusion in hepatic coma: factors affecting results, with long-term follow-up data. ( Darin, JC; Hussey, CV; Lewis, JD; Varma, RR, 1975)

Research

Studies (41)

Authors

Clinical Trials (1)

Trial Overview

Trial Outcomes

Change in Ammonia

Timeframe	Studies, this research(%)	All Research%
pre-1990	32 (78.05)	18.7374
1990's	7 (17.07)	18.2507
2000's	2 (4.88)	29.6817
2010's	0 (0.00)	24.3611
2020's	0 (0.00)	2.80

Authors	Studies
Kumar, GP	1
Bhat, VJ	1
Sowdi, V	1
Burnell, JM	2
Dawborn, JK	1
Epstein, RB	1
Gutman, RA	1
Leinbach, GE	1
Thomas, ED	2
Volwiler, W	2
Sasaki, H	1
Inoue, K	1
Canalese, J	1
Wyke, RJ	1
Vergani, D	1
Eddleston, AL	1
Williams, R	6
Sielaff, TD	1
Hu, MY	1
Rollins, MD	1
Bloomer, JR	1
Amiot, B	1
Hu, WS	1
Cerra, FB	1
Weber, P	1
Scheurlen, M	1
Irkin, I	1
Viebahn, R	1
Schareck, W	1
Becker, W	1
de Groot, H	1
Lauchart, W	1
Puri, AS	1
Sikora, SS	1
Aggarwal, R	1
Naik, SR	1
Elliott, RH	1
Strunin, L	1
Tsubota, A	1
Kumada, H	1
Kharasch, ED	1
Hankins, D	1
Mautz, D	1
Thummel, KE	1
Rodés, J	1
Bruguera, M	1
Schmidt-Wilcke, HA	1
Wolfert, W	1
Grundmann, E	1
Di Nino, GF	1
Faenza, S	1
Martinelli, G	1
Sparta, S	1
Norton, L	1
Moore, G	1
Eiseman, B	1
Lewis, JD	1
Hussey, CV	1
Varma, RR	1
Darin, JC	1
McIntyre, N	1
Patial, RK	1
Sarin, R	1
Patial, SB	1
O'Grady, JG	1
Gimson, AE	1
O'Brien, CJ	1
Pucknell, A	1
Hughes, RD	1
Fossati, C	1
Kenna, JG	1
Neuberger, J	1
Gazzard, BG	1
Weston, MJ	1
Murray-Lyon, IM	1
Flax, H	1
Record, CO	1
Portmann, B	1
Langley, PG	1
Dunlop, EH	1
Mellon, PJ	1
Ward, MB	1
Jones, EA	1
Clain, D	1
Clink, HM	1
MacGillivray, M	1
Sherlock, S	1
Versieck, J	1
Van Waes, L	1
Barbier, F	1
Demeulenaere, L	1
Vermeire, P	1
Naccarato, R	1
Gritti, G	1
Giunta, F	1
Chiaramonte, M	1
Valenti, F	1
Lepore, MJ	1
Goertz, J	1
Runge, C	1
Saunders, FC	1
Hussey, HH	1
Knell, AJ	1
Davidson, AR	1
Kantamaneni, BD	1
Curzon, G	1
Dalsgaard, M	1
Andreasen, PB	1
Ranek, L	1
Trey, C	1
Davidson, CS	1
Hargrove, MD	1
Rogers, AI	1
Winch, J	1
Caravati, CM	1
Hooker, TH	1
Lempinen, M	1
Collan, Y	1
Sivula, A	1
Merikallio, E	1
Salmenkivi, K	1
Paloheimo, M	1
Turunen, MT	1
Jokinen, EJ	1
Ahlqvist, J	1
Peters, RL	1
Edmondson, HA	1
Reynolds, TB	1
Meister, JC	1
Curpey, TJ	1
Condon, RE	1
Bombeck, CT	1
Steigmann, F	1
McKechnie, JC	1
Hersh, T	1
Mihalecz, K	1
Császár, J	1
Thompson, EN	1
Cawdery, J	1
Martin, J	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
A Phase 2a Study to Evaluate the Safety and Tolerability of OCR-002 (Ornithine Phenylacetate) in the Treatment of Patients With Acute Liver Failure/Severe Acute Liver Injury[NCT01548690]	Phase 2	47 participants (Actual)	Interventional	2012-06-30	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

To evaluate the effect of OCR-002 on ammonia levels in patients with acute liver failure/severe acute liver injury (NCT01548690)
Timeframe: Baseline and 72 Hours

Measurement of OCR-002 Plasma Concentration

Intervention	Percent Change (Mean)
Maximum Dose Level 3.33 g/24h	41.2
Maximum Dose Level 6.65 g/24h	16.6
Maximum Dose Level 10 g/24h	41.8
Maximum Dose Level 20g/24h	38.4

To evaluate the steady state pharmacokinetic and pharmacodynamic profile of OCR-002 in patients with impaired and intact renal function using urinary phenylacetylglutamine (PAGN) as a surrogate marker (NCT01548690)
Timeframe: 24 Hours after last infusion

Neurological Function Measured by the Orientation Log (O-log)

Intervention	micrograms per millileter (Mean)
Maximum Dose Level 3.33 g/24h	65.6
Maximum Dose Level 6.65 g/24h	32.2
Maximum Dose Level 10 g/24h	33.4
Maximum Dose Level 20g/24h	104.9

The orientation log focuses on orientation to place, time, and circumstance. There are 10 items on the orientation log, which are scored 0-3. A spontaneous correct response is awarded 3 points. A spontaneous response that is lacking or incorrect, but a correct response is provided following a logical cue is awarded 2 points. A score of 1 is given if spontaneous and cued responses are lacking or incorrect, but a correct response is provided in a recognition format. A score of 0 is given if the spontaneous, cued, or recognition format does not generate a correct answer. Scores from the 10 items are summed and the final score ranges from 0 to 30. (NCT01548690)
Timeframe: 30 Days

Neurological Function Measured by the West Haven Criteria (WHC) for Hepatic Encephalopathy

Intervention	units on a scale (Mean)
Maximum Dose Level 3.33 g/24h	23.8
Maximum Dose Level 6.65 g/24h	24.0
Maximum Dose Level 10 g/24h	24.0
Maximum Dose Level 20g/24h	24.0

The West Haven Criteria (WHC) for Hepatic Encephalopathy measures the severity of encephalopathy and patient's level of consciousness. The scale ranges from 0 to 4; a minimum score of 0 represents a better outcome, and a maximum total score of 4 represents a worse outcome. A score of 0 corresponds to normal consciousness and behavior and normal neurological examination. A score of 1 corresponds to mild lack of awareness, shortened attention span, and impaired addition or subtraction; mild asterixis or tremor. A score of 2 corresponds to lethargy, disorientated or inappropriate behavior, obvious asterixis; slurred speech. A score of 3 corresponds to somnolent but arousable, gross disorientation or bizarre behavior, muscle rigidity and clonus; hyperreflexia. A score of 4 corresponds to coma and decerebrate posturing. (NCT01548690)
Timeframe: 120 hours from start of infusion

Number of Participants That do Not Tolerate the Administered Dose and Had Grade 3 or 4 Treatment Emergent Adverse Events as a Measure of Safety and Tolerability

Intervention	units on a scale (Mean)
Maximum Dose Level 3.33 g/24h	2.4
Maximum Dose Level 6.65 g/24h	3.2
Maximum Dose Level 10 g/24h	1.6
Maximum Dose Level 20g/24h	1.8

To evaluate the safety and tolerability of OCR-002 in patients with acute liver failure/severe acute liver injury (NCT01548690)
Timeframe: 30 Days

Article	Year
Hepatotoxicity of volatile anaesthetics. British journal of anaesthesia, 1993, Volume: 70, Issue:3 Topics: Anesthetics; Animals; Antibodies; Chemical and Drug Induced Liver Injury; Enflurane; Halothane; Hepa	1993
[Emergency drug therapy of fulminant hepatitis]. Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine, 1995, Nov-10, Volume: 84, Issue:11 Topics: Alprostadil; Amino Acids, Branched-Chain; Apoptosis; Cytokines; Emergencies; Halothane; Hepatic Ence	1995
Hepatobiliary disease: medical emergencies. Bailliere's clinical gastroenterology, 1991, Volume: 5, Issue:4 Topics: Acetaminophen; Biliary Tract Diseases; Emergencies; Halothane; Hepatic Encephalopathy; Hepatitis, Vi	1991
[Toxicity and hepatotoxicity of halothane]. La Clinica terapeutica, 1986, Mar-31, Volume: 116, Issue:6 Topics: Drug Hypersensitivity; Halothane; Hepatic Encephalopathy; Humans; Liver	1986
The management of fulminant hepatic failure. Progress in liver diseases, 1970, Volume: 3 Topics: Acute Disease; Blood Transfusion; Chemical and Drug Induced Liver Injury; Drug Hypersensitivity; Hal	1970
Therapeutic considerations in selected forms of acute and chronic liver disease. The Medical clinics of North America, 1971, Volume: 55, Issue:2 Topics: Acute Disease; Age Factors; Alcoholism; Azathioprine; Chemical and Drug Induced Liver Injury; Chroni	1971

Article	Year
Identification of the enzyme responsible for oxidative halothane metabolism: implications for prevention of halothane hepatitis. Lancet (London, England), 1996, May-18, Volume: 347, Issue:9012 Topics: Adult; Alanine Transaminase; Cytochrome P-450 CYP2E1; Cytochrome P-450 Enzyme Inhibitors; Cytochrome	1996
Controlled trials of charcoal hemoperfusion and prognostic factors in fulminant hepatic failure. Gastroenterology, 1988, Volume: 94, Issue:5 Pt 1 Topics: Acetaminophen; Adolescent; Adult; Aged; Charcoal; Child; Clinical Trials as Topic; Female; Halothane	1988

Article	Year
Fulminant hepatic failure following halothane anaesthesia. Journal of clinical forensic medicine, 2005, Volume: 12, Issue:5 Topics: Acute Kidney Injury; Adult; Anesthetics, Inhalation; Forensic Pathology; Halothane; Hand Injuries; H	2005
Acute hepatic coma treated by cross-circulation or exchange transfusion. The New England journal of medicine, 1967, Apr-27, Volume: 276, Issue:17 Topics: Adult; Anesthesia, Inhalation; Blood Transfusion; Child; Exchange Transfusion, Whole Blood; Female;	1967
[Factors contributing development of acute hepatitis]. Nihon rinsho. Japanese journal of clinical medicine, 1982, Volume: 40, Issue:4 Topics: Acute Disease; Female; Halothane; Hepatic Encephalopathy; Hepatitis, Viral, Human; Humans; Infant, N	1982
Circulating immune complexes in patients with fulminant hepatic failure. Gut, 1981, Volume: 22, Issue:10 Topics: Acetaminophen; Adolescent; Adult; Aged; Antigen-Antibody Complex; Chemical and Drug Induced Liver In	1981
An anesthetized model of lethal canine galactosamine fulminant hepatic failure. Hepatology (Baltimore, Md.), 1995, Volume: 21, Issue:3 Topics: Anesthesia; Animals; Disease Models, Animal; Dogs; Galactosamine; Halothane; Hepatic Encephalopathy;	1995
[Liver transplantation in halothane-induced liver necrosis]. Zentralblatt fur Chirurgie, 1994, Volume: 119, Issue:5 Topics: Adult; Anesthesia, General; Appendectomy; Appendicitis; Chemical and Drug Induced Liver Injury; Halo	1994
Halothane-induced fulminant hepatic failure. Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology, 1993, Volume: 12, Issue:3 Topics: Halothane; Hepatic Encephalopathy; Humans; Liver Function Tests; Male; Middle Aged; Time Factors	1993
The uses of error: iatrogenic hepatitis. Lancet (London, England), 2001, Mar-10, Volume: 357, Issue:9258 Topics: Aged; Anesthetics, Inhalation; Antitubercular Agents; Chemical and Drug Induced Liver Injury; Female	2001
[Halothane and antituberculous drugs--a hepatotoxic combination? (author's transl)]. Zeitschrift fur Gastroenterologie, 1977, Volume: 15, Issue:8 Topics: Adult; Antitubercular Agents; Chemical and Drug Induced Liver Injury; Ethambutol; Female; Halothane;	1977
[Comparative study of 3 different technics of anesthesia in swine for isolated liver perfusion and for corssed circulation with heterotopic liver in experimental hepatic coma. Experiments on 140 animals]. Minerva anestesiologica, 1976, Volume: 42, Issue:9 Topics: Anesthesia, Inhalation; Animals; Enflurane; Evaluation Studies as Topic; Extracorporeal Circulation;	1976
Liver failure in the postoperative patient: the role of sepsis and immunologic deficiency. Surgery, 1975, Volume: 78, Issue:1 Topics: Anesthetics; Bacterial Infections; Endotoxins; Escherichia coli Infections; Esophageal and Gastric V	1975
Exchange transfusion in hepatic coma: factors affecting results, with long-term follow-up data. American journal of surgery, 1975, Volume: 129, Issue:2 Topics: Adolescent; Adult; Aged; Ammonia; Bilirubin; Biopsy; Chemical and Drug Induced Liver Injury; Child;	1975
Halothane associated hepatitis and phenobarbitone. The Journal of the Association of Physicians of India, 1989, Volume: 37, Issue:7 Topics: Adult; Anesthesia, Obstetrical; Chemical and Drug Induced Liver Injury; Drug Synergism; Female; Halo	1989
Specific antibodies to halothane-induced liver antigens in halothane-associated hepatitis. British journal of anaesthesia, 1987, Volume: 59, Issue:10 Topics: Adolescent; Adult; Aged; Antibodies; Antigens; Chemical and Drug Induced Liver Injury; Child; Child,	1987
Charcoal haemoperfusion in the treatment of fulminant hepatic failure. Lancet (London, England), 1974, Jun-29, Volume: 1, Issue:7870 Topics: Adolescent; Adult; Amino Acids; Autopsy; Biopsy, Needle; Blood; Blood Cell Count; Blood Coagulation;	1974
Hepatic coma due to acute hepatic necrosis treated by exchange blood-transfusion. Lancet (London, England), 1967, Jul-22, Volume: 2, Issue:7508 Topics: Aged; Anesthesia, Inhalation; Anuria; Electroencephalography; Exchange Transfusion, Whole Blood; Fem	1967
Peritoneoscopy during hepatic coma. Acta gastro-enterologica Belgica, 1973, Volume: 36, Issue:12 Topics: Adolescent; Adult; Aged; Biopsy; Chemical and Drug Induced Liver Injury; Cholestasis; Female; Haloth	1973
[Exchange transfusion in the treatment of acute hepatic insufficiency]. Minerva chirurgica, 1974, Sep-30, Volume: 29, Issue:18 Topics: Acute Disease; Adolescent; Adult; Child; Child, Preschool; Exchange Transfusion, Whole Blood; Fatty	1974
Fulminant hepatic failure. Postgraduate medicine, 1973, Volume: 53, Issue:1 Topics: Adolescent; Adult; Age Factors; Aged; Enzymes; Exchange Transfusion, Whole Blood; Halothane; Hepatic	1973
Histological appearances in fulminant hepatic failure with reference to aetiology, time of survival and role of immunological processes. Digestion, 1973, Volume: 8, Issue:1 Topics: Acetaminophen; Adolescent; Adult; Aged; Cell Nucleus; Chemical and Drug Induced Liver Injury; Haloth	1973
Acute hepatic failure treated by cross circulation. Archives of internal medicine, 1973, Volume: 132, Issue:4 Topics: Acute Disease; Adult; Anesthesia; Aspartate Aminotransferases; Bilirubin; Blood Donors; Blood Platel	1973
Editorial: Fulminant hepatic failure. JAMA, 1973, Dec-03, Volume: 226, Issue:10 Topics: Age Factors; Aged; Anesthesia; Calcium; Chemical and Drug Induced Liver Injury; Exchange Transfusion	1973
Dopamine and serotonin metabolism in hepatic encephalopathy. British medical journal, 1974, Mar-23, Volume: 1, Issue:5907 Topics: Acetaminophen; Acute Disease; Adult; Aged; Brain; Dopamine; Fatty Acids, Nonesterified; Female; Halo	1974
[Halothane hepatitis. 11 cases of hepatitis after repeated halothane anesthesia]. Ugeskrift for laeger, 1974, Jan-14, Volume: 136, Issue:3 Topics: Adult; Anesthesia; Chemical and Drug Induced Liver Injury; Child; Female; Halothane; Hepatic Encepha	1974
Chronic active hepatitis: possible adverse effect of exploratory laparotomy. Surgery, 1970, Volume: 68, Issue:5 Topics: Adolescent; Anesthesia, Inhalation; Chronic Disease; Escherichia coli; Female; Halothane; Hepatic En	1970
A model which can be used to improve the treatment of acute hepatic failure. The British journal of surgery, 1972, Volume: 59, Issue:10 Topics: Albumins; Anesthesia, General; Animals; Biotransformation; Blood Coagulation; Blood Pressure; Fibrin	1972
Acute massive hepatic necrosis with fatal liver failure. The American journal of digestive diseases, 1971, Volume: 16, Issue:9 Topics: Acute Disease; Adolescent; Adult; Aged; Anticonvulsants; Antitubercular Agents; Azathioprine; Blood	1971
Pig-liver perfusion. Extracorporeal pig-liver perfusion in a patient with acute hepatic failure. Scandinavian journal of gastroenterology, 1971, Volume: 6, Issue:5 Topics: Adult; Ammonia; Anesthesia, Inhalation; Animals; Autopsy; Bilirubin; Biopsy; Embolism; Female; Halot	1971
Hepatic necrosis associated with halothane anesthesia. The American journal of medicine, 1969, Volume: 47, Issue:5 Topics: Anesthesia; Autopsy; Biopsy; Chemical and Drug Induced Liver Injury; Cholestasis; Collagen; Connecti	1969
Heterologous bovine liver perfusion therapy of acute hepatic failure. American journal of surgery, 1970, Volume: 119, Issue:2 Topics: Adenosine Triphosphate; Adolescent; Adult; Animals; Cattle; Consciousness; Drug Hypersensitivity; Fe	1970
Exchange transfusion in hepatic coma. A review of 19 cases. The American journal of gastroenterology, 1971, Volume: 56, Issue:1 Topics: Adolescent; Adult; Alanine Transaminase; Ammonia; Anesthesia, Inhalation; Autopsy; Bilirubin; Blood	1971
[Liver necrosis in consequence of fluothane anesthesia]. Zentralblatt fur Chirurgie, 1967, Sep-23, Volume: 92, Issue:38 Topics: Chemical and Drug Induced Liver Injury; Fatty Liver; Halothane; Hepatic Encephalopathy; Humans; Live	1967
Hepatic coma with renal failure, treated by repeated exchange transfusion. Archives of disease in childhood, 1968, Volume: 43, Issue:229 Topics: Acute Kidney Injury; Adult; Aphasia; Arthrogryposis; Bilirubin; Calcium; Chemical and Drug Induced L	1968

halothane and Hepatic Encephalopathy