ammonium hydroxide and Intracranial Hypertension studies

Intracranial Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including HYDROCEPHALUS; BRAIN EDEMA; intracranial masses; severe systemic HYPERTENSION; PSEUDOTUMOR CEREBRI; and other disorders.

Research Excerpts

Excerpt	Relevance	Reference
"L-Ornithine and phenylacetate act synergistically to successfully attenuate increases in arterial ammonia, which is accompanied by a significant decrease in extracellular brain ammonia and prevention of intracranial hypertension in pigs with ALF."	7.75	L-ornithine phenylacetate attenuates increased arterial and extracellular brain ammonia and prevents intracranial hypertension in pigs with acute liver failure. ( Cobos, MJ; Fuskevåg, OM; Jalan, R; Kalstad, T; Kristiansen, RG; Maehre, H; Revhaug, A; Rose, CF; Ytrebø, LM, 2009)
"L-Ornithine and phenylacetate act synergistically to successfully attenuate increases in arterial ammonia, which is accompanied by a significant decrease in extracellular brain ammonia and prevention of intracranial hypertension in pigs with ALF."	3.75	L-ornithine phenylacetate attenuates increased arterial and extracellular brain ammonia and prevents intracranial hypertension in pigs with acute liver failure. ( Cobos, MJ; Fuskevåg, OM; Jalan, R; Kalstad, T; Kristiansen, RG; Maehre, H; Revhaug, A; Rose, CF; Ytrebø, LM, 2009)
"About 20% of patients with acute liver failure (ALF) die from increased intracranial pressure (ICP) while awaiting transplantation."	2.71	Moderate hypothermia in patients with acute liver failure and uncontrolled intracranial hypertension. ( Deutz, NE; Hayes, PC; Jalan, R; Lee, A; Olde Damink, SW, 2004)
"Hepatic encephalopathy is a syndrome whose pathophysiology is poorly understood, for which we lack high-quality diagnostic tests and markers, and whose treatment has improved only slightly over the last several decades."	2.46	Hepatic encephalopathy: current management strategies and treatment, including management and monitoring of cerebral edema and intracranial hypertension in fulminant hepatic failure. ( O'connor, M; Zafirova, Z, 2010)
"Acute liver failure is a severe condition with a very unfavourable prognosis."	2.46	[Intracranial hypertension in acute liver failure and microdialysis]. ( Lásziková, E; Prazák, J; Ryska, M; Ryska, O, 2010)
"Brain edema with intracranial hypertension is a major complication in patients with acute liver failure."	2.43	Mild hypothermia for acute liver failure: a review of mechanisms of action. ( Blei, AT; Vaquero, J, 2005)
"Cerebral edema is a well-recognized and potentially fatal complication of acute liver failure (ALF)."	1.39	Cerebral microdialysis reflects the neuroprotective effect of fractionated plasma separation and adsorption in acute liver failure better and earlier than intracranial pressure: a controlled study in pigs. ( Koblihova, E; Laszikova, E; Pantoflicek, T; Prazak, J; Ryska, M; Ryska, O, 2013)
"Patients with acute liver failure (ALF) often die of intracranial pressure (IP) and cerebral herniation."	1.37	Brain region-selective mechanisms contribute to the progression of cerebral alterations in acute liver failure in rats. ( Agusti, A; Boix, J; Cauli, O; Cerdán, S; Felipo, V; López-Larrubia, P; Nieto-Charques, L; Rodrigo, R, 2011)
" The study consisted of three experiments: The first was a dose-finding study of four different dosing regimens of magnesium sulfate (MgSO4) in healthy rats."	1.37	Hypermagnesemia does not prevent intracranial hypertension and aggravates cerebral hyperperfusion in a rat model of acute hyperammonemia. ( Bernal, W; Bjerring, PN; Eefsen, M; Larsen, FS; Wendon, J, 2011)
"In 87 patients with acute liver failure admitted to the intensive care unit, we simultaneously evaluated arterial ammonia, pNH(3), clinical grade of hepatic encephalopathy, the sequential organ failure assessment score (SOFA score), and evidence of intracranial hypertension."	1.35	Severity of organ failure is an independent predictor of intracranial hypertension in acute liver failure. ( Ferenci, P; Funk, GC; Holzinger, U; Kaider, A; Kitzberger, R; Kramer, L; Madl, C; Miehsler, W, 2009)
"Patients with acute liver failure (ALF) display impairment of cerebral blood flow (CBF) autoregulation, which may contribute to the development of fatal intracranial hypertension, but the pathophysiological mechanism remains unclear."	1.35	Cerebral blood flow autoregulation in experimental liver failure. ( Dethloff, TJ; Knudsen, GM; Larsen, FS, 2008)
"The initial development of cerebral edema and increased ICP occurs independently of CBF changes in this noninflammatory model of ALF."	1.33	Effect of albumin dialysis on intracranial pressure increase in pigs with acute liver failure: a randomized study. ( Butterworth, RF; Davies, NA; Deutz, NE; Drevland, SS; Hodges, SJ; Jalan, R; Kjønnø, M; Nedredal, GI; Prinzen, FW; Revhaug, A; Rose, C; Sen, S; Williams, R; Ytrebø, LM, 2006)
"Mild hypothermia could be tested for treatment of intracranial hypertension in fulminant hepatic failure."	1.30	Mild hypothermia modifies ammonia-induced brain edema in rats after portacaval anastomosis. ( Blei, AT; Córdoba, J; Crespin, J; Gottstein, J, 1999)

Research

Studies (27)

Authors

Clinical Trials (1)

Trial Overview

Trial Outcomes

Change in Ammonia

Timeframe	Studies, this research(%)	All Research%
pre-1990	0 (0.00)	18.7374
1990's	3 (11.11)	18.2507
2000's	17 (62.96)	29.6817
2010's	7 (25.93)	24.3611
2020's	0 (0.00)	2.80

Authors	Studies
Prazak, J	3
Laszikova, E	3
Pantoflicek, T	2
Ryska, O	3
Koblihova, E	2
Ryska, M	3
Rama Rao, KV	1
Jayakumar, AR	1
Norenberg, MD	1
Bjerring, PN	2
Eefsen, M	2
Hansen, BA	1
Larsen, FS	3
Kitzberger, R	1
Funk, GC	1
Holzinger, U	1
Miehsler, W	1
Kramer, L	1
Kaider, A	1
Ferenci, P	1
Madl, C	1
Ytrebø, LM	2
Kristiansen, RG	1
Maehre, H	1
Fuskevåg, OM	1
Kalstad, T	1
Revhaug, A	2
Cobos, MJ	1
Jalan, R	7
Rose, CF	1
Zafirova, Z	1
O'connor, M	1
Cauli, O	1
López-Larrubia, P	1
Rodrigo, R	1
Agusti, A	1
Boix, J	1
Nieto-Charques, L	1
Cerdán, S	1
Felipo, V	1
Bernal, W	2
Wendon, J	2
Olde Damink, SW	3
Hayes, PC	2
Deutz, NE	3
Lee, A	2
Vaquero, J	1
Blei, AT	4
Kundra, A	1
Jain, A	1
Banga, A	1
Bajaj, G	1
Kar, P	1
Sen, S	1
Rose, C	1
Davies, NA	1
Nedredal, GI	1
Drevland, SS	1
Kjønnø, M	1
Prinzen, FW	1
Hodges, SJ	1
Williams, R	1
Butterworth, RF	1
Raghavan, M	1
Marik, PE	1
Hall, C	1
Karvellas, CJ	1
Auzinger, G	1
Sizer, E	1
Wright, G	1
Shawcross, D	1
Dethloff, TJ	1
Knudsen, GM	1
Córdoba, J	1
Crespin, J	1
Gottstein, J	1
Conn, HO	2
Hwang, YJ	1
Kim, YI	1
Lee, JG	1
Lee, JW	1
Kim, JW	1
Chung, JM	1
Venkatasubramanian, PN	1
Tom, B	1
Wyrwicz, AM	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
Brain edema in acute liver failure: mechanisms and concepts. Metabolic brain disease, 2014, Volume: 29, Issue:4 Topics: Acute Disease; Ammonia; Animals; Astrocytes; Body Water; Brain Edema; Cell Size; Confounding Factors	2014
The brain in acute liver failure. A tortuous path from hyperammonemia to cerebral edema. Metabolic brain disease, 2009, Volume: 24, Issue:1 Topics: Ammonia; Animals; Brain; Brain Edema; Hepatic Encephalopathy; Humans; Hyperammonemia; Intracranial H	2009
Hepatic encephalopathy: current management strategies and treatment, including management and monitoring of cerebral edema and intracranial hypertension in fulminant hepatic failure. Current opinion in anaesthesiology, 2010, Volume: 23, Issue:2 Topics: Ammonia; Brain Edema; Hepatic Encephalopathy; Humans; Intracranial Hypertension; Liver Failure, Acut	2010
[Intracranial hypertension in acute liver failure and microdialysis]. Rozhledy v chirurgii : mesicnik Ceskoslovenske chirurgicke spolecnosti, 2010, Volume: 89, Issue:10 Topics: Ammonia; Brain Edema; Glutamine; Humans; Intracranial Hypertension; Liver Failure, Acute; Microdialy	2010
Intracranial hypertension in acute liver failure: pathophysiological basis of rational management. Seminars in liver disease, 2003, Volume: 23, Issue:3 Topics: Ammonia; Animals; Brain Edema; Cerebrovascular Circulation; Environmental Monitoring; Humans; Intrac	2003
Mild hypothermia for acute liver failure: a review of mechanisms of action. Journal of clinical gastroenterology, 2005, Volume: 39, Issue:4 Suppl 2 Topics: Ammonia; Brain; Brain Edema; Cerebrovascular Circulation; Glucose; Hemodynamics; Humans; Hypothermia	2005
Pathophysiological basis of therapy of raised intracranial pressure in acute liver failure. Neurochemistry international, 2005, Volume: 47, Issue:1-2 Topics: Ammonia; Animals; Brain Edema; Cerebrovascular Circulation; Encephalitis; Hepatic Encephalopathy; Hu	2005
Therapy of intracranial hypertension in patients with fulminant hepatic failure. Neurocritical care, 2006, Volume: 4, Issue:2 Topics: Ammonia; Anesthetics, Intravenous; Brain; Cardiovascular Agents; Cerebrovascular Circulation; Electr	2006
Brain edema and intracranial hypertension: a focus for the use of liver support systems. Artificial organs, 1997, Volume: 21, Issue:11 Topics: Ammonia; Animals; Bioreactors; Brain Edema; Cerebral Cortex; Glutamine; Intracranial Hypertension; I	1997

Article	Year
Cerebral microdialysis reflects the neuroprotective effect of fractionated plasma separation and adsorption in acute liver failure better and earlier than intracranial pressure: a controlled study in pigs. BMC gastroenterology, 2013, Jun-08, Volume: 13 Topics: Ammonia; Animals; Brain Edema; Cerebrum; Extracorporeal Circulation; Glucose; Glutamic Acid; Glutami	2013
Severity of organ failure is an independent predictor of intracranial hypertension in acute liver failure. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, 2009, Volume: 7, Issue:9 Topics: Adult; Ammonia; APACHE; Female; Hepatic Encephalopathy; Humans; Intensive Care Units; Intracranial H	2009
L-ornithine phenylacetate attenuates increased arterial and extracellular brain ammonia and prevents intracranial hypertension in pigs with acute liver failure. Hepatology (Baltimore, Md.), 2009, Volume: 50, Issue:1 Topics: Ammonia; Animals; Arteries; Brain; Drug Combinations; Extracellular Space; Intracranial Hypertension	2009
Brain region-selective mechanisms contribute to the progression of cerebral alterations in acute liver failure in rats. Gastroenterology, 2011, Volume: 140, Issue:2 Topics: Ammonia; Animals; Blood-Brain Barrier; Brain Edema; Capillary Permeability; Cerebellum; Cerebrum; En	2011
Hypermagnesemia does not prevent intracranial hypertension and aggravates cerebral hyperperfusion in a rat model of acute hyperammonemia. Hepatology (Baltimore, Md.), 2011, Volume: 53, Issue:6 Topics: Ammonia; Animals; Aquaporin 4; Blood Pressure; Brain; Cerebrovascular Circulation; Dose-Response Rel	2011
Artificial liver support system reduces intracranial pressure more effectively than bioartificial system: an experimental study. The International journal of artificial organs, 2012, Volume: 35, Issue:7 Topics: Ammonia; Animals; Bilirubin; Biomarkers; Cerebrovascular Circulation; Disease Models, Animal; Equipm	2012
Pathogenesis of intracranial hypertension in acute liver failure: inflammation, ammonia and cerebral blood flow. Journal of hepatology, 2004, Volume: 41, Issue:4 Topics: Adult; Ammonia; Biomarkers; Brain; Cardiovascular System; Cerebrovascular Circulation; Female; Hemod	2004
Evaluation of plasma ammonia levels in patients with acute liver failure and chronic liver disease and its correlation with the severity of hepatic encephalopathy and clinical features of raised intracranial tension. Clinical biochemistry, 2005, Volume: 38, Issue:8 Topics: Adult; Ammonia; Brain Edema; Chronic Disease; Female; Hepatic Encephalopathy; Humans; Intracranial H	2005
Effect of albumin dialysis on intracranial pressure increase in pigs with acute liver failure: a randomized study. Critical care medicine, 2006, Volume: 34, Issue:1 Topics: Albumins; Ammonia; Animals; Brain Edema; Cerebrovascular Circulation; Disease Models, Animal; Female	2006
Arterial ammonia and clinical risk factors for encephalopathy and intracranial hypertension in acute liver failure. Hepatology (Baltimore, Md.), 2007, Volume: 46, Issue:6 Topics: Adult; Aged; Ammonia; Brain Edema; Female; Hepatic Encephalopathy; Humans; Intracranial Hypertension	2007
Brain cytokine flux in acute liver failure and its relationship with intracranial hypertension. Metabolic brain disease, 2007, Volume: 22, Issue:3-4 Topics: Adult; Ammonia; Brain; Cross-Sectional Studies; Cytokines; Hepatic Encephalopathy; Humans; Interleuk	2007
Cerebral blood flow autoregulation in experimental liver failure. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2008, Volume: 28, Issue:5 Topics: Ammonia; Animals; Blood Pressure; Cerebral Cortex; Cerebrovascular Circulation; Disease Models, Anim	2008
Mild hypothermia modifies ammonia-induced brain edema in rats after portacaval anastomosis. Gastroenterology, 1999, Volume: 116, Issue:3 Topics: Acetates; Ammonia; Animals; Body Water; Brain; Brain Edema; Cardiac Output; Cerebrovascular Circulat	1999
Hyperammonia and cerebral herniation: is an abnormality of ammonia metabolism responsible? The American journal of gastroenterology, 1999, Volume: 94, Issue:12 Topics: Ammonia; Brain; Encephalocele; Hepatic Encephalopathy; Humans; Intracranial Hypertension; Liver; Liv	1999
Hyperammonemia and intracranial hypertension: lying in wait for patients with hepatic disorders? The American journal of gastroenterology, 2000, Volume: 95, Issue:3 Topics: Ammonia; Encephalocele; Humans; Intracranial Hypertension; Liver Failure, Acute; Predictive Value of	2000
Development of bioartificial liver system using a fluidized-bed bioreactor. Transplantation proceedings, 2000, Volume: 32, Issue:7 Topics: Ammonia; Ammonium Chloride; Animals; Bioreactors; Cell Separation; Cells, Cultured; Hepatocytes; Int	2000
Monitoring of brain water by chemical shift imaging during ammonia-induced brain swelling in rats after portacaval anastomosis. Artificial organs, 2001, Volume: 25, Issue:7 Topics: Ammonia; Animals; Body Water; Brain Edema; Cerebral Cortex; Intracranial Hypertension; Liver Failure	2001

ammonium hydroxide and Intracranial Hypertension