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Chen DF, Farrque M, Karakis I, Gupta N, Rodriguez Ruiz A, Kandiah P. Continuous Electroencephalography in Acute Liver Failure: Findings and Prognostic Value. Neurocrit Care 2025:10.1007/s12028-025-02216-1. [PMID: 39920548 DOI: 10.1007/s12028-025-02216-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Accepted: 01/13/2025] [Indexed: 02/09/2025]
Abstract
BACKGROUND Neurologic complications contribute significantly to morbidity and mortality in acute liver failure (ALF). However, clinical assessment of neurologic function in this population is often challenging. Continuous electroencephalography (cEEG) is a low-risk, noninvasive diagnostic tool that can monitor real-time cerebral function. We aimed to investigate cEEG findings and prognostic significance of specific EEG features in a cohort of strictly defined patients with ALF. METHODS This was a retrospective, single-center study of adult patients with ALF who underwent cEEG monitoring for at least 6 h between 2013 and 2022. Clinical, laboratory, imaging, and treatment characteristics were evaluated. cEEG variables included background continuity, background frequency, the presence of sporadic epileptiform discharges, rhythmic or periodic patterns, and electrographic or electroclinical seizures. The primary outcome was mortality or transition to end-of-life care during the index admission. RESULTS A total of 32 patients with ALF were included. 56.3% of patients had rhythmic or periodic patterns, of which the majority were generalized periodic discharges (37.5%). 12.5% of patients had sporadic epileptiform discharges, and 6.3% of patients demonstrated electrographic or clinical seizures. Eighteen (56.3%) patients died or were transitioned to end-of-life care during the index admission. Worsening background continuity or frequency over the course of the cEEG recording was significantly associated with poor outcome (p = 0.001, p = 0.007, respectively), with a 100% mortality rate in patients demonstrating these EEG trends. A worst recorded continuity of suppression, attenuation, and burst-suppression was also associated with poor outcome (p = 0.012). The presence of rhythmic or periodic patterns, sporadic epileptiform discharges, or seizures was not predictive of outcome. CONCLUSIONS Worsening cEEG background continuity or frequency is associated with poor outcome in adults with ALF. cEEG may contribute useful prognostic information in these patients, in conjunction with other laboratory and clinical markers of disease severity.
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Affiliation(s)
- Denise F Chen
- Department of Neurology, University of Washington School of Medicine, Seattle, WA, USA.
- Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA.
| | - Mirza Farrque
- Department of Neurocritical Care, Emory University School of Medicine, Atlanta, GA, USA
| | - Ioannis Karakis
- Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA
- Department of Neurology, University of Crete School of Medicine, Heraklion, Greece
| | - Navnika Gupta
- Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA
| | | | - Prem Kandiah
- Department of Neurocritical Care, Emory University School of Medicine, Atlanta, GA, USA
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Lal BB, Khanna R, Sood V, Alam S, Nagral A, Ravindranath A, Kumar A, Deep A, Gopan A, Srivastava A, Maria A, Pawaria A, Bavdekar A, Sindwani G, Panda K, Kumar K, Sathiyasekaran M, Dhaliwal M, Samyn M, Peethambaran M, Sarma MS, Desai MS, Mohan N, Dheivamani N, Upadhyay P, Kale P, Maiwall R, Malik R, Koul RL, Pandey S, Ramakrishna SH, Yachha SK, Lal S, Shankar S, Agarwal S, Deswal S, Malhotra S, Borkar V, Gautam V, Sivaramakrishnan VM, Dhawan A, Rela M, Sarin SK. Diagnosis and management of pediatric acute liver failure: consensus recommendations of the Indian Society of Pediatric Gastroenterology, Hepatology, and Nutrition (ISPGHAN). Hepatol Int 2024; 18:1343-1381. [DOI: https:/doi.org/10.1007/s12072-024-10720-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Accepted: 08/08/2024] [Indexed: 04/16/2025]
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Lal BB, Khanna R, Sood V, Alam S, Nagral A, Ravindranath A, Kumar A, Deep A, Gopan A, Srivastava A, Maria A, Pawaria A, Bavdekar A, Sindwani G, Panda K, Kumar K, Sathiyasekaran M, Dhaliwal M, Samyn M, Peethambaran M, Sarma MS, Desai MS, Mohan N, Dheivamani N, Upadhyay P, Kale P, Maiwall R, Malik R, Koul RL, Pandey S, Ramakrishna SH, Yachha SK, Lal S, Shankar S, Agarwal S, Deswal S, Malhotra S, Borkar V, Gautam V, Sivaramakrishnan VM, Dhawan A, Rela M, Sarin SK. Diagnosis and management of pediatric acute liver failure: consensus recommendations of the Indian Society of Pediatric Gastroenterology, Hepatology, and Nutrition (ISPGHAN). Hepatol Int 2024; 18:1343-1381. [PMID: 39212863 DOI: 10.1007/s12072-024-10720-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Accepted: 08/08/2024] [Indexed: 09/04/2024]
Abstract
Timely diagnosis and management of pediatric acute liver failure (PALF) is of paramount importance to improve survival. The Indian Society of Pediatric Gastroenterology, Hepatology, and Nutrition invited national and international experts to identify and review important management and research questions. These covered the definition, age appropriate stepwise workup for the etiology, non-invasive diagnosis and management of cerebral edema, prognostic scores, criteria for listing for liver transplantation (LT) and bridging therapies in PALF. Statements and recommendations based on evidences assessed using the modified Grading of Recommendations Assessment, Development and Evaluation (GRADE) system were developed, deliberated and critically reappraised by circulation. The final consensus recommendations along with relevant published background information are presented here. We expect that these recommendations would be followed by the pediatric and adult medical fraternity to improve the outcomes of PALF patients.
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Affiliation(s)
- Bikrant Bihari Lal
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Rajeev Khanna
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Vikrant Sood
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Seema Alam
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India.
| | - Aabha Nagral
- Department of Gastroenterology, Jaslok Hospital and Research Center, Mumbai, India
- Apollo Hospital, Navi Mumbai, India
| | - Aathira Ravindranath
- Department of Pediatric Gastroenterology, Apollo BGS Hospital, Mysuru, Karnataka, India
| | - Aditi Kumar
- Department of Pediatrics, All India Institute of Medical Sciences, Bhubaneswar, India
| | - Akash Deep
- Department of Pediatric Intensive Care, King's College Hospital, London, UK
| | - Amrit Gopan
- Department of Pediatric Gastroenterology and Hepatology, Sir H.N Reliance Foundation Hospital, Mumbai, India
| | - Anshu Srivastava
- Department of Pediatric Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
| | - Arjun Maria
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Institute of Child Health, Sir Ganga Ram Hospital, New Delhi, India
| | - Arti Pawaria
- Department of Pediatric Hepatology and Gastroenterology, Amrita Institute of Medical Sciences, Faridabad, India
| | - Ashish Bavdekar
- Department of Pediatrics, KEM Hospital and Research Centre, Pune, India
| | - Gaurav Sindwani
- Department of Organ Transplant Anesthesia and Critical Care, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Kalpana Panda
- Department of Pediatrics, Institute of Medical Sciences & SUM Hospital, Bhubaneshwar, India
| | - Karunesh Kumar
- Department of Pediatric Gastroenterology and Liver Transplantation, Indraprastha Apollo Hospitals, New Delhi, India
| | | | - Maninder Dhaliwal
- Department of Pediatric Intensive Care, Amrita Institute of Medical Sciences, Faridabad, India
| | - Marianne Samyn
- Department of Pediatric Hepatology, King's College Hospital, London, UK
| | - Maya Peethambaran
- Department of Pediatric Gastroenterology and Hepatology, VPS Lakeshore Hospital, Kochi, Kerala, India
| | - Moinak Sen Sarma
- Department of Pediatric Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
| | - Moreshwar S Desai
- Department of Paediatric Critical Care and Liver ICU, Baylor College of Medicine &Texas Children's Hospital, Houston, TX, USA
| | - Neelam Mohan
- Department of Pediatric Gastroenterology and Hepatology, Medanta the Medicity Hospital, Gurugram, India
| | - Nirmala Dheivamani
- Department of Paediatric Gastroenterology, Institute of Child Health and Hospital for Children, Egmore, Chennai, India
| | - Piyush Upadhyay
- Department of Pediatrics, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, India
| | - Pratibha Kale
- Department of Microbiology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Rakhi Maiwall
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Rohan Malik
- Department of Pediatric Gastroenterology and Hepatology, All India Institute of Medical Sciences, New Delhi, India
| | - Roshan Lal Koul
- Department of Neurology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Snehavardhan Pandey
- Department of Pediatric Hepatology and Liver Transplantation, Sahyadri Superspeciality Hospital Pvt Ltd Pune, Pune, India
| | | | - Surender Kumar Yachha
- Department of Pediatric Gastroenterology, Hepatology and Liver Transplantation, Sakra World Hospital, Bangalore, India
| | - Sadhna Lal
- Division of Pediatric Gastroenterology and Hepatology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Sahana Shankar
- Division of Pediatric Gastroenterology and Hepatology, Department of Pediatrics, Mazumdar Shaw Medical Centre, Narayana Health City, Bangalore, India
| | - Sajan Agarwal
- Department of Pediatric Gastroenterology and Hepatology, Gujarat Gastro Hospital, Surat, Gujarat, India
| | - Shivani Deswal
- Department of Pediatric Gastroenterology, Hepatology and Liver Transplant, Narayana Health, DLF Phase 3, Gurugram, India
| | - Smita Malhotra
- Department of Pediatric Gastroenterology and Hepatology, Indraprastha Apollo Hospitals, New Delhi, India
| | - Vibhor Borkar
- Department of Paediatric Hepatology and Gastroenterology, Nanavati Max Super Speciality Hospital, Mumbai, Maharashtra, India
| | - Vipul Gautam
- Department of Pediatric Gastroenterology, Hepatology and Liver Transplantation, Max Superspeciality Hospital, New Delhi, India
| | | | - Anil Dhawan
- Department of Pediatric Hepatology, King's College Hospital, London, UK
| | - Mohamed Rela
- Department of Liver Transplantation and HPB (Hepato-Pancreatico-Biliary) Surgery, Dr. Rela Institute & Medical Center, Chennai, India
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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Garrido E, Adeli A, Echeverria-Villalobos M, Fiorda J, Hannawi Y. Prevalence of Electrographic Seizures in Hospitalized Patients With Altered Mental Status With No Significant Seizure Risk Factors Who Underwent Continuous EEG Monitoring: A Retrospective Study. Cureus 2024; 16:e55903. [PMID: 38595868 PMCID: PMC11003702 DOI: 10.7759/cureus.55903] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/01/2024] [Indexed: 04/11/2024] Open
Abstract
OBJECTIVES The objective of this study is to evaluate the prevalence of electrographic seizures in hospitalized patients with altered mental status and no significant risk factors for seizures. METHODS We retrospectively reviewed over a six-year period (2013-2019) the medical records of all adults admitted at Ohio State University Wexner Medical Center (OSUWMC), who underwent continuous electroencephalography (cEEG) monitoring for > 48 hours. Our primary objective was to identify the prevalence of electrographic seizures in patients with altered mental status and no significant acute or remote risk factors for seizures. RESULTS A total of 1966 patients were screened for the study, 1892 were excluded (96.2%) and 74 patients met inclusion criteria. Electrographic seizures were identified in seven of 74 patients (9.45%). We found a significant correlation between electrographic seizures and a history of hepatic cirrhosis, n= 4 (57%), (p=0.035), acute chronic hepatic failure during admission, 71% (n=5), (p=0.027), and hyperammonemia (p =0.009). CONCLUSION In this retrospective study of patients with altered mental status and no significant acute or remote risk factors for seizures who underwent cEEG monitoring for > 48 hours, electrographic seizures were identified in 9.45%. Electrographic seizures were associated with hepatic dysfunction and hyperammonemia. Based on our results, cEEG monitoring should be considered in patients with altered mental status and hepatic dysfunction even in the absence of other seizure risk factors.
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Affiliation(s)
- Elena Garrido
- Department of Anesthesiology, The University of Iowa Carver College of Medicine, Iowa City, USA
| | - Amir Adeli
- Department of Neurology, Division of Epilepsy, The Ohio State University Wexner Medical Center, Columbus, USA
| | | | - Juan Fiorda
- Department of Anesthesiology, The Ohio State University Wexner Medical Center, Columbus, USA
| | - Yousef Hannawi
- Department of Neurology, Division of Cerebrovascular Diseases and Neurocritical Care, The Ohio State University Wexner Medical Center, Columbus, USA
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Zorzi S, Ayako Minemura Ordinola A, Cunha De Souza Lima E, Martins Teixeira G, Salvagno M, Sterchele ED, Taccone FS. A glimpse into multimodal neuromonitoring in acute liver failure: a case report. Ann Med Surg (Lond) 2024; 86:539-544. [PMID: 38222739 PMCID: PMC10783349 DOI: 10.1097/ms9.0000000000001519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Accepted: 11/07/2023] [Indexed: 01/16/2024] Open
Abstract
Introduction Acute liver failure (ALF) is a rapidly progressing, life-threatening syndrome characterized by liver-related coagulopathy and hepatic encephalopathy (HE). Given that higher HE grades correlate with poorer outcomes, clinical management of ALF necessitates close neurological monitoring. The primary objective of this case report is to highlight the diagnostic value of utilizing multimodal neuromonitoring (MNM) in a patient suffering from ALF. Case report A 56-year-old male patient with a history of chronic alcoholism, without prior chronic liver disease, and recent acetaminophen use was admitted to the hospital due to fatigue and presenting with a mild flapping tremor. The primary hypothesis was an acute hepatic injury caused by acetaminophen intoxication. In the following hours, the patient's condition deteriorated, accompanied by neurological decline and rising ammonia levels. The patient's neurological status was closely monitored using MNM. Bilaterally altered pupillary light reflex assessed by decreasing in the Neurological Pupil Index values, using automated pupillometry, initially suggested severe brain oedema. However, ultrasound measurements of the optic nerve sheath diameter showed normal values in both eyes, P2/P1 noninvasive intracranial pressure waveform assessment was within normal ranges and the cerebral computed tomography-scan revealed no signs of cerebral swelling. Increased middle cerebral artery velocities measured by Transcranial Doppler and the initiation of electroencephalography monitoring yielded the presence of status epilepticus. Discussion The utilization of MNM facilitated a more comprehensive understanding of the mechanisms underlying the patient's clinical deterioration in the setting of HE. Nonetheless, future studies are needed to show feasibility and to yield valuable insights that can enhance the outcomes for patients with HE using such an approach. Given the absence of specific guidelines in this particular context, it is advisable for physicians to give further consideration to the incorporation of MNM in the management of unconscious patients with ALF.
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Affiliation(s)
- Stefano Zorzi
- Department of Intensive Care, Hôpital Universitaire de Bruxelles (HUB), Université Libre de Bruxelles (ULB), Brussels, Belgium
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Agumava LU, Gulyaev VA, Lutsyk KN, Olisov OD, Akhmetshin RB, Magomedov KM, Kazymov BI, Akhmedov AR, Alekberov KF, Yaremin BI, Novruzbekov MS. Issues of intensive care and liver transplantation tactics in fulminant liver failure. BULLETIN OF THE MEDICAL INSTITUTE "REAVIZ" (REHABILITATION, DOCTOR AND HEALTH) 2023. [DOI: 10.20340/vmi-rvz.2023.1.tx.2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/17/2023]
Abstract
Fulminant liver failure is usually characterized as severe acute liver injury with encephalopathy and synthetic dysfunction (international normalized ratio [INR] ≥1.5) in a patient without cirrhosis or previous liver disease. Management of patients with acute liver failure includes ensuring that the patient is cared for appropriately, monitoring for worsening liver failure, managing complications, and providing nutritional support. Patients with acute liver failure should be treated at a liver transplant center whenever possible. Serial laboratory tests are used to monitor the course of a patient's liver failure and to monitor for complications. It is necessary to monitor the level of aminotransferases and bilirubin in serum daily. More frequent monitoring (three to four times a day) of blood coagulation parameters, complete blood count, metabolic panels, and arterial blood gases should be performed. For some causes of acute liver failure, such as acetaminophen intoxication, treatment directed at the underlying cause may prevent the need for liver transplantation and reduce mortality. Lactulose has not been shown to improve overall outcomes, and it can lead to intestinal distention, which can lead to technical difficulties during liver transplantation. Early in acute liver failure, signs and symptoms of cerebral edema may be absent or difficult to detect. Complications of cerebral edema include increased intracranial pressure and herniation of the brain stem. General measures to prevent increased intracranial pressure include minimizing stimulation, maintaining an appropriate fluid balance, and elevating the head of the patient's bed. For patients at high risk of developing cerebral edema, we also offer hypertonic saline prophylaxis (3%) with a target serum sodium level of 145 to 155 mEq/L (level 2C). High-risk patients include patients with grade IV encephalopathy, high ammonia levels (>150 µmol/L), or acute renal failure, and patients requiring vasopressor support. Approximately 40 % of patients with acute liver failure recover spontaneously with supportive care. Predictive models have been developed to help identify patients who are unlikely to recover spontaneously, as the decision to undergo liver transplant depends in part on the likelihood of spontaneous recovery of the liver. However, among those who receive a transplant, the one-year survival rate exceeds 80 %, making this treatment the treatment of choice in this difficult patient population.
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Affiliation(s)
- L. U. Agumava
- Research Institute of Ambulance them. N.V. Sklifosovsky, liver transplant center
| | - V. A. Gulyaev
- Research Institute of Ambulance them. N.V. Sklifosovsky, liver transplant center
| | - K. N. Lutsyk
- Research Institute of Ambulance them. N.V. Sklifosovsky, liver transplant center
| | - O. D. Olisov
- Research Institute of Ambulance them. N.V. Sklifosovsky, liver transplant center; Pirogov Russian National Research Medical University, Department of Transplantology and Artificial Organs
| | - R. B. Akhmetshin
- Research Institute of Ambulance them. N.V. Sklifosovsky, liver transplant center
| | - K. M. Magomedov
- Research Institute of Ambulance them. N.V. Sklifosovsky, liver transplant center
| | - B. I. Kazymov
- Research Institute of Ambulance them. N.V. Sklifosovsky, liver transplant center
| | - A. R. Akhmedov
- Research Institute of Ambulance them. N.V. Sklifosovsky, liver transplant center
| | - K. F. Alekberov
- Research Institute of Ambulance them. N.V. Sklifosovsky, liver transplant center
| | - B. I. Yaremin
- Research Institute of Ambulance them. N.V. Sklifosovsky, liver transplant center; Pirogov Russian National Research Medical University, Department of Transplantology and Artificial Organs
| | - M. S. Novruzbekov
- Research Institute of Ambulance them. N.V. Sklifosovsky, liver transplant center; Pirogov Russian National Research Medical University, Department of Transplantology and Artificial Organs
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Mehtani R, Garg S, Kajal K, Soni SL, Premkumar M. Neurological monitoring and sedation protocols in the Liver Intensive Care Unit. Metab Brain Dis 2022; 37:1291-1307. [PMID: 35460476 DOI: 10.1007/s11011-022-00986-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Accepted: 04/10/2022] [Indexed: 11/25/2022]
Abstract
Patients with liver disease often have alteration of neurological status which requires admission to an intensive care unit. Patients with acute liver failure (ALF), acute-on-chronic liver failure (ACLF) and rarely cirrhosis are at risk of cerebral edema. These patients require prompt assessment of neurological status including assessment of intra-cranial pressure (ICP) and monitoring metabolic parameters like arterial/venous ammonia levels, serum creatinine and serum electrolytes so that timely specific therapy for raised ICP can be instituted to prevent permanent neurological dysfunction. The overall aims of neuromonitoring and sedation protocols in a liver intensive care unit are to identify the level of multifactorial metabolic encephalopathy, individualize sedation and analgesia requirements for patients on mechanical ventilation, institute specific therapy to correct the neurological insult in ALF and ACLF, provide clear physiological data for guided therapy of drugs like muscle relaxants, antiepileptics, and cerebral edema reducing agents, and assist with overall prognostication. In this review article we will outline the clinical scenarios related to liver disease requiring intensive care and neuromonitoring, current techniques of neurological assessment, sedation protocols and point of care tests which enable the treating physician and intensivist guide therapy for raised ICP.
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Affiliation(s)
- Rohit Mehtani
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Shankey Garg
- Department of Anesthesiology and Intensive Care, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Kamal Kajal
- Department of Anesthesiology and Intensive Care, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Shiv Lal Soni
- Department of Anesthesiology and Intensive Care, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Madhumita Premkumar
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India.
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Jagadisan B, Dhawan A. Emergencies in paediatric hepatology. J Hepatol 2022; 76:1199-1214. [PMID: 34990749 DOI: 10.1016/j.jhep.2021.12.027] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Revised: 12/17/2021] [Accepted: 12/21/2021] [Indexed: 12/12/2022]
Abstract
The aetiology of several liver diseases in children is age specific and many of these conditions have significant and potentially long-term clinical repercussions if not diagnosed early and managed in a timely fashion. We address 5 clinical scenarios that cover most of the diagnostic and therapeutic emergencies in children: infants with liver disease; acute liver failure; management of bleeding varices; liver-based metabolic disorders; and liver tumours and trauma. A wide spectrum of conditions that cause liver disease in infants may present as conjugated jaundice, which could be the only symptom of time-sensitive disorders - such as biliary atresia, metabolic disorders, infections, and haematological/alloimmune disorders - wherein algorithmic multistage testing is required for accurate diagnosis. In infantile cholestasis, algorithmic multistage tests are necessary for an accurate early diagnosis, while vitamin K, specific milk formulae and disease-specific medications are essential to avoid mortality and long-term morbidity. Management of paediatric acute liver failure requires co-ordination with a liver transplant centre, safe transport and detailed age-specific aetiological work-up - clinical stabilisation with appropriate supportive care is central to survival if transplantation is indicated. Gastrointestinal bleeding may present as the initial manifestation or during follow-up in patients with portal vein thrombosis or chronic liver disease and can be managed pharmacologically, or with endoscopic/radiological interventions. Liver-based inborn errors of metabolism may present as encephalopathy that needs to be recognised and treated early to avoid further neurological sequelae and death. Liver tumours and liver trauma are both rare occurrences in children and are best managed by a multidisciplinary team in a specialist centre.
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Affiliation(s)
- Barath Jagadisan
- Pediatric Liver GI and Nutrition Centre and MowatLabs, King's College Hospital, London, UK
| | - Anil Dhawan
- Pediatric Liver GI and Nutrition Centre and MowatLabs, King's College Hospital, London, UK.
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Abstract
Uremic encephalopathy encompasses a wide range of central nervous system abnormalities associated with poor kidney function occurring with either progressive chronic kidney disease or acute kidney injury. The syndrome is likely caused by retention of uremic solutes, alterations in hormonal metabolism, changes in electrolyte and acid-base homeostasis, as well as changes in vascular reactivity, blood-brain barrier transport, and inflammation. There are no defining clinical, laboratory, or imaging findings, and the diagnosis is often made retrospectively when symptoms improve after dialysis or transplantation. The diagnosis is also made difficult because of the many confounding and overlapping conditions seen in patients with chronic kidney disease and acute kidney injury. Thus, institution of kidney replacement therapy should be considered as a trial to improve symptoms in the right clinical context. Neurological symptoms that do not improve after improvement in clearance should prompt a search for other explanations. Further knowledge linking possible uremic retention solutes with neurological symptoms is needed to better understand this syndrome as well as to develop more tailored treatments that aim to improve cognitive function.
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10
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Bernal W, Williams R. Acute Liver Failure. Clin Liver Dis (Hoboken) 2020; 16:45-55. [PMID: 33042526 PMCID: PMC7538923 DOI: 10.1002/cld.957] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2020] [Accepted: 03/23/2020] [Indexed: 02/04/2023] Open
Affiliation(s)
- William Bernal
- Liver Intensive Therapy UnitInstitute of Liver StudiesKing’s College HospitalLondonUnited Kingdom
| | - Roger Williams
- Institute of Hepatology LondonFoundation for Liver ResearchLondonUnited Kingdom,Faculty of Life Sciences & MedicineKing’s College LondonLondonUnited Kingdom
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Hunt A, Tasker RC, Deep A. Neurocritical care monitoring of encephalopathic children with acute liver failure: A systematic review. Pediatr Transplant 2019; 23:e13556. [PMID: 31407855 DOI: 10.1111/petr.13556] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Revised: 06/14/2019] [Accepted: 07/04/2019] [Indexed: 12/15/2022]
Abstract
Research on non-invasive neuromonitoring specific to PALF is limited. This systematic review identifies and synthesis the existing literature on non-invasive approaches to monitoring for neurological sequelae in patients with PALF. A series of literature searches were performed to identify all publications pertaining to five different non-invasive neuromonitoring modalities, in line with PRISMA guidelines. Each modality was selected on the basis of its potential for direct or indirect measurement of cerebral perfusion; studies on electroencephalographic monitoring were therefore not sought. Data were recorded on study design, patient population, comparator groups, and outcomes. A preponderance of observational studies was observed, most with a small sample size. Few incorporated direct comparisons of different modalities; in particular, comparison to invasive intracranial pressure monitoring was largely lacking. The integration of current evidence is considered in the context of the clinically significant distinctions between pediatric and adult ALF, as well as the implications for planning of future investigations to best support the evidence-based clinical care of these patients.
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Affiliation(s)
- Adam Hunt
- University College Hospital, London, UK
| | - Robert C Tasker
- Harvard Medical School, Chair in Neurocritical Care, Boston Children's Hospital, Boston, MA
| | - Akash Deep
- Paediatric Intensive Care, King's College Hospital, London, UK
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Newey CR, George P, Sarwal A, So N, Hantus S. Electro-Radiological Observations of Grade III/IV Hepatic Encephalopathy Patients with Seizures. Neurocrit Care 2019; 28:97-103. [PMID: 28791561 DOI: 10.1007/s12028-017-0435-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Neurological complications in liver failure are common. Often under-recognized neurological complications are seizures and status epilepticus. These may go unrecognized without continuous electroencephalography (CEEG). We highlight the observed electro-radiological changes in patients with grade III/IV hepatic encephalopathy (HE) found to have seizures and/or status epilepticus on CEEG and the associated neuroimaging. METHODS This study was a retrospective review of patients with West Haven grade III/IV HE and seizures/status epilepticus on CEEG. RESULTS Eleven patients were included. Alcohol was the most common cause of HE (54.5%). All patients were either stuporous/comatose. The most common CEEG pattern was diffuse slowing (100%) followed by generalized periodic discharges (GPDs; 36.4%) and lateralized periodic discharges (LPDs, 36.4%). The subtype of GPDs with triphasic morphology was only seen in 27.3%. All seizures and/or status epilepticus were without clinical signs. Magnetic resonance imaging (MRI) was available in six patients. Cortical hyperintensities on diffusion weighted imaging sequence were seen in all six patients. One patient had CEEG seizure concomitantly with the MRI. Seven patients died prior to discharge. CONCLUSION Seizures or status epilepticus in the setting of HE were without clinical findings and could go unrecognized without CEEG. The finding of cortical hyperintensity on MRI should lead to further evaluation for unrecognized seizure or status epilepticus.
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Affiliation(s)
- Christopher R Newey
- Department of Neurology, University of Missouri, 1 Hospital Drive, Columbia, MO, 65211, USA. .,Neurological Institute, Cerebrovascular Center, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195-5245, USA.
| | - Pravin George
- Neurological Institute, Cerebrovascular Center, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195-5245, USA
| | - Aarti Sarwal
- Neurology and Critical Care (Anesthesia), Wake Forest University School of Medicine, Reynolds M, Medical Center Blvd, Winston Salem, NC, 27157, USA
| | - Norman So
- Neurological Institute, Epilepsy Center, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195-5245, USA
| | - Stephen Hantus
- Neurological Institute, Cerebrovascular Center, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195-5245, USA.,Neurological Institute, Epilepsy Center, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195-5245, USA
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13
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Management of Hepatic Encephalopathy in the Neurocritical Care Unit. Neurocrit Care 2019. [DOI: 10.1017/9781107587908.030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
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14
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Increase in P-glycoprotein levels in the blood-brain barrier of partial portal vein ligation /chronic hyperammonemia rats is medicated by ammonia/reactive oxygen species/ERK1/2 activation: In vitro and in vivo studies. Eur J Pharmacol 2019; 846:119-127. [PMID: 30639310 DOI: 10.1016/j.ejphar.2019.01.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2018] [Revised: 12/19/2018] [Accepted: 01/08/2019] [Indexed: 12/15/2022]
Abstract
Liver failure altered P-glycoprotein (P-gp) function and expression at blood-brain barrier (BBB), partly owing to hyperammonemia. We aimed to examine the effects of partial portal vein ligation (PVL) plus chronic hyperammonemia (CHA) on P-gp function and expression at rat BBB. Experimental rats included sham-operation (SH), PVL, CHA and PVL+CHA. The PVL+CHA rats were developed by ammonia-containing diet for 2 weeks after operation. The brain-to-plasma concentration ratios (Kp) and apparent unidirectional influx constants (Kin) of rhodamine123 and sodium fluorescein were measured to assess function of P-gp and BBB integrity, respectively. Human cerebral microvascular endothelial cells (HCMEC/D3) were used to assess effects of ammonia on P-gp expression and function. It was found that PVL+CHA significantly decreased Kp and Kin of rhodamine123 without affecting brain distribution of fluorescein. The P-gp expressions in membrane protein in cortex and hippocampus were significantly increased in CHA and PVL +CHA rats, especially in PVL + CHA rats, while remarkably increased phosphorylated ERK1/2 was only found in PVL +CHA rats. Expressions of tight junction proteins claudin-5 and occluding in rat brain remained unchanged. In vitro data showed that NH4Cl increased reactive oxygen species, membrane expression and function of P-gp as well as phosphorylated ERK1/2 levels in HCMEC/D3. The NH4Cl-induced alterations were reversed by reactive oxygen species scavenger N-acetylcysteine and ERK1/2 inhibitor U0126. In conclusion, PVL+CHA increased function and membrane translocation of P-gp at rat BBB partly via ammonia. Reactive oxygen species/ERK1/2 pathway activation may be one of the reasons that ammonia upregulated P-gp expression and function at BBB.
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15
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Sheikh MF, Unni N, Agarwal B. Neurological Monitoring in Acute Liver Failure. J Clin Exp Hepatol 2018; 8:441-447. [PMID: 30568346 PMCID: PMC6286879 DOI: 10.1016/j.jceh.2018.04.013] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2018] [Accepted: 04/25/2018] [Indexed: 12/12/2022] Open
Abstract
Cerebral oedema and Intracranial Hypertension (ICH) are serious complications of acute liver failure affecting approximately 30% of patients, resulting in neurological injury or death. Multiple pathogenetic mechanisms contribute to the pathogenesis of HE including circulating neurotoxins such as ammonia, systemic and neuro-inflammation, infection and cerebral hyperaemia due to loss of cerebral vascular autoregulation. Early recognition and diagnosis is often difficult as clinical signs of elevated Intracranial Pressure (ICP) are not uniformly present and maybe masked by other organ support. ICP monitoring provides early diagnosis and monitoring of ICH, allowing targeted therapeutic interventions for prevention and treatment. ICP monitoring is the subject of much debate and there exists significant heterogeneity of clinical practice regarding its use. The procedure is associated with risks of haemorrhage but may be considered in highly selected patients such as those with highest risk for ICH awaiting transplant to allow for patient selection and optimisation. There is limited evidence that ICP monitoring confers a survival benefit which may explain why in the context of risk benefit analysis there is reduced utilisation in clinical practice. Less or non-invasive techniques of neurological monitoring such as measurement of jugular venous oxygen saturation to assess cerebral oxygen utilisation, and transcranial Doppler CNS to measure cerebral blood flow can provide important clinical information. They should be considered in combination as part of a multi-modal platform utilising specific roles of each system and incorporated within locally agreed algorithms. Other tools such as near-infrared spectrophotometry, optic nerve ultrasound and serum biomarkers of brain injury are being evaluated but are not used routinely in current practice.
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Affiliation(s)
- Mohammed F. Sheikh
- Liver Failure Group, UCL Institute for Liver and Digestive Health, Division of Medicine, UCL Medical School, Royal Free Hospital, Rowland Hill Street, NW3 2PF London, UK
| | - Nazri Unni
- Intensive Care Unit, Royal Free Hospital, Rowland Hill Street, NW3 2PF London, UK
| | - Banwari Agarwal
- Liver Failure Group, UCL Institute for Liver and Digestive Health, Division of Medicine, UCL Medical School, Royal Free Hospital, Rowland Hill Street, NW3 2PF London, UK
- Intensive Care Unit, Royal Free Hospital, Rowland Hill Street, NW3 2PF London, UK
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16
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Fan Y, Liu X. Alterations in Expression and Function of ABC Family Transporters at Blood-Brain Barrier under Liver Failure and Their Clinical Significances. Pharmaceutics 2018; 10:pharmaceutics10030102. [PMID: 30041501 PMCID: PMC6161250 DOI: 10.3390/pharmaceutics10030102] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2018] [Revised: 07/20/2018] [Accepted: 07/21/2018] [Indexed: 02/07/2023] Open
Abstract
Liver failure is often associated with hepatic encephalopathy, due to dyshomeostasis of the central nervous system (CNS). Under physiological conditions, the CNS homeostasis is precisely regulated by the blood-brain barrier (BBB). The BBB consists of brain microvessel endothelial cells connected with a junctional complex by the adherens junctions and tight junctions. Its main function is to maintain brain homoeostasis via limiting the entry of drugs/toxins to brain. The brain microvessel endothelial cells are characterized by minimal pinocytotic activity, absent fenestrations, and highly expressions of ATP-binding cassette (ABC) family transporters (such as P-glycoprotein, breast cancer resistance protein and multidrug resistance-associated proteins). These ABC transporters prevent brain from toxin accumulation by pumping toxins out of brain. Accumulating evidences demonstrates that liver failure diseases altered the expression and function of ABC transporters at The BBB, indicating that the alterations subsequently affect drugs’ brain distribution and CNS activity/neurotoxicity. ABC transporters also mediate the transport of endogenous substrates across the BBB, inferring that ABC transporters are also implicated in some physiological processes and the development of hepatic encephalopathy. This paper focuses on the alteration in the BBB permeability, the expression and function of ABC transporters at the BBB under liver failure status and their clinical significances.
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Affiliation(s)
- Yilin Fan
- Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.
| | - Xiaodong Liu
- Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.
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17
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Mastropietro CW, Valentine KM. Medical Management of Acute Liver Failure. PEDIATRIC CRITICAL CARE 2018. [PMCID: PMC7121299 DOI: 10.1007/978-3-319-96499-7_9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
Pediatric acute liver failure is a rapidly progressive, life-threatening, and devastating illness in children without preexisting liver disease. Due to the rarity and heterogeneity of this syndrome, there is a significant lack of data to guide evaluation and management of this disease. Most of our practice is extrapolated from adult literature and guidelines. This leads to significant controversies in medical management of acute liver failure in children. With advances in critical care, there has been a tremendous improvement in outcomes with decreased morbidity and mortality; however, there is a dire need for more research in this field. This chapter discusses challenges as well as controversies in diagnostic evaluation and management of this rare but potentially fatal disease. Latest developments in supportive care of liver failure, including advances in the area of liver support systems, are also discussed.
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Affiliation(s)
- Christopher W. Mastropietro
- grid.257413.60000 0001 2287 3919Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN USA
| | - Kevin M. Valentine
- grid.257413.60000 0001 2287 3919Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN USA
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18
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Abstract
Purpose of Review Pediatric acute liver failure is a rare, complex, rapidly progressing, and life-threatening illness. Majority of pediatric acute liver failures have unknown etiology. This review intends to discuss the current literature on the challenging aspects of management of acute liver failure. Recent Findings Collaborative multidisciplinary approach for management of patients with pediatric acute liver failure with upfront involvement of transplant hepatologist and critical care specialists can improve outcomes of this fatal disease. Extensive but systematic diagnostic evaluation can help to identify etiology and guide management. Early referral to a transplant center with prompt liver transplant, if indicated, can lead to improved survival in these patients. Summary Prompt identification and aggressive management of pediatric acute liver failure and related comorbidities can lead to increased transplant-free survival and improved post-transplant outcomes, thus decreasing mortality and morbidity associated with this potential fatal condition.
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Affiliation(s)
- Heli Bhatt
- Section of Pediatric Gastroenterology, Hepatology and Nutrition, Riley Hospital for Children, Indiana University School of Medicine, Indiana University, 705 Riley Hospital Drive, ROC 4210, Indianapolis, IN 46202 USA
| | - Girish S. Rao
- Section of Pediatric Gastroenterology, Hepatology and Nutrition, Riley Hospital for Children, Indiana University School of Medicine, Indiana University, 705 Riley Hospital Drive, ROC 4210, Indianapolis, IN 46202 USA
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Abstract
Acute liver failure (ALF) is a rare life-threatening condition characterized by rapid progression and death. Causes vary according to geographic region, with acetaminophen and drug-induced ALF being the most common causes in the United States. Determining the cause aids in predicting the prognosis and the presentation of manifestations and guides providers to perform cause-specific management. At initial presentation, nonspecific symptoms are present but may progress to complications, including cerebral edema, infection, coagulopathy, renal failure, cardiopulmonary failure, and acid-base and/or metabolic disturbances. Although some cases of ALF resolve with conservative measures, liver transplantation is the ultimate treatment in many cases.
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Affiliation(s)
- Sarah Zahra Maher
- Internal Medicine, Penn State Health Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033, USA.
| | - Ian Roy Schreibman
- Division of Gastroenterology and Hepatology, Penn State Health Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033, USA
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20
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Brain and the Liver: Cerebral Edema, Hepatic Encephalopathy and Beyond. HEPATIC CRITICAL CARE 2018. [PMCID: PMC7122599 DOI: 10.1007/978-3-319-66432-3_8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Occurrence of brain dysfunction is common in both chronic liver disease as well as acute liver failure. While brain dysfunction most commonly manifests as hepatic encephalopathy is chronic liver disease; devastating complications of cerebral edema and brain herniation syndromes may occur with acute liver failure. Ammonia seems to play a central role in the pathogenesis of brain dysfunction in both chronic liver disease and acute liver failure. In this chapter we outline the pathophysiology and clinical management of brain dysfunction in the critically ill patients with liver disease.
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21
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Abstract
Acute liver failure (ALF) is a life-threatening condition of heterogeneous etiology. Outcomes are better with early recognition and prompt initiation of etiology-specific therapy, intensive care protocols, and liver transplantation (LT). Prognostic scoring systems include the King's College Criteria and Model for End-stage Liver Disease score. Cerebral edema and intracranial hypertension are reasons for high morbidity and mortality; hypertonic saline is suggested for patients with a high risk for developing intracranial hypertension, and when it does, mannitol is recommended as first-line therapy. Extracorporeal liver support system may serve as a bridge to LT and may increase LT-free survival in select cases.
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Affiliation(s)
- Chalermrat Bunchorntavakul
- Division of Gastroenterology and Hepatology, Department of Medicine, Rajavithi Hospital, College of Medicine, Rangsit University, Rajavithi Road, Ratchathewi, Bangkok 10400, Thailand; Division of Gastroenterology and Hepatology, Department of Medicine, Hospital of the University of Pennsylvania, University of Pennsylvania, 2 Dulles, 3400 Spruce Street, Philadelphia, PA 19104, USA
| | - K Rajender Reddy
- Division of Gastroenterology and Hepatology, Department of Medicine, Hospital of the University of Pennsylvania, University of Pennsylvania, 2 Dulles, 3400 Spruce Street, Philadelphia, PA 19104, USA.
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22
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Abstract
Hepatic encephalopathy occurs ubiquitously in all causes of advanced liver failure, however, its implications on mortality diverge and vary depending upon acuity and severity of liver failure. This associated mortality has decreased in subsets of liver failure over the last 20 years. Aside from liver transplantation, this improvement is not attributable to a single intervention but likely to a combination of practical advances in critical care management. Misconceptions surrounding many facets of hepatic encephalopathy exists due to heterogeneity in presentation, pathophysiology and outcome. This review is intended to highlight the important concepts, rationales and strategies for managing hepatic encephalopathy.
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Affiliation(s)
- Prem A Kandiah
- Division of Neuro Critical Care, Department of Neurosurgery, Co-appointment in Surgical Critical Care, Emory University Hospital, 1364 Clifton Road Northeast, 2nd Floor, 2D ICU-D264, Atlanta, GA 30322, USA.
| | - Gagan Kumar
- Department of Critical Care, Phoebe Putney Memorial Hospital, 417 Third Avenue, Albany, GA 31701, USA
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23
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Abstract
Pediatric acute liver failure is rare but life-threatening illness that occurs in children without preexisting liver disease. The rarity of the disease, along with its severity and heterogeneity, presents unique clinical challenges to the physicians providing care for pediatric patients with acute liver failure. In this review, practical clinical approaches to the care of critically ill children with acute liver failure are discussed with an organ system-specific approach. The underlying pathophysiological processes, major areas of uncertainty, and approaches to the critical care management of pediatric acute liver failure are also reviewed.
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24
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The role of postictal laboratory blood analyses in the diagnosis and prognosis of seizures. Seizure 2017; 47:51-65. [DOI: 10.1016/j.seizure.2017.02.013] [Citation(s) in RCA: 62] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2016] [Revised: 02/23/2017] [Accepted: 02/24/2017] [Indexed: 12/18/2022] Open
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Abstract
PURPOSE OF REVIEW The objective of this article is to review the latest developments related to the treatment of patients with acute liver failure (ALF). RECENT FINDINGS As the treatment of ALF has evolved, there is an increasing recognition regarding the risk of intracranial hypertension related to advanced hepatic encephalopathy. Therefore, there is an enhanced emphasis on neuromonitoring and therapies targeting intracranial hypertension. Also, new evidence implicates systemic proinflammatory cytokines as an etiology for the development of multiorgan system dysfunction in ALF; the recent finding of a survival benefit in ALF with high-volume plasmapheresis further supports this theory. SUMMARY Advances in the critical care management of ALF have translated to a substantial decrease in mortality related to this disease process. The extrapolation of therapies from general neurocritical care to the treatment of ALF-induced intracranial hypertension has resulted in improved neurologic outcomes. In addition, recognition of the systemic inflammatory response and multiorgan dysfunction in ALF has guided current treatment recommendations, and will provide avenues for future research endeavors. With respect to extracorporeal liver support systems, further randomized studies are required to assess their efficacy in ALF, with attention to nonsurvival end points such as bridging to liver transplantation.
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Nowacki TA, Jirsch JD. Evaluation of the first seizure patient: Key points in the history and physical examination. Seizure 2016; 49:54-63. [PMID: 28190753 DOI: 10.1016/j.seizure.2016.12.002] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2016] [Revised: 10/31/2016] [Accepted: 12/01/2016] [Indexed: 12/16/2022] Open
Abstract
PURPOSE This review will present the history and physical examination as the launching point of the first seizure evaluation, from the initial characterization of the event, to the exclusion of alternative diagnoses, and then to the determination of specific acute or remote causes. Clinical features that may distinguish seizures from alternative diagnoses are discussed in detail, followed by a discussion of acute and remote first seizure etiologies. METHODS This review article is based on a discretionary selection of English language articles retrieved by a literature search in the PubMed database, and the authors' clinical experience. RESULTS The first seizure is a dramatic event with often profound implications for patients and family members. The initial clinical evaluation focuses on an accurate description of the spell to confirm the diagnosis, along with careful scrutiny for previously unrecognized seizures that would change the diagnosis more definitively to one of epilepsy. The first seizure evaluation rests primarily on the clinical history, and to a lesser extent, the physical examination. CONCLUSIONS Even in the era of digital EEG recording and neuroimaging, the initial clinical evaluation remains essential for the diagnosis, treatment, and prognostication of the first seizure.
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Affiliation(s)
- Tomasz A Nowacki
- Division of Neurology, Department of Medicine, University of Alberta, 7th Floor Clinical Sciences Building, 11350 83 Avenue NW, Edmonton, Alberta T6G 2G3, Canada.
| | - Jeffrey D Jirsch
- Division of Neurology, Department of Medicine, University of Alberta, 7th Floor Clinical Sciences Building, 11350 83 Avenue NW, Edmonton, Alberta T6G 2G3, Canada
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Paschoal Jr FM, Nogueira RC, Ronconi KDAL, de Lima Oliveira M, Teixeira MJ, Bor-Seng-Shu E. Multimodal brain monitoring in fulminant hepatic failure. World J Hepatol 2016; 8:915-923. [PMID: 27574545 PMCID: PMC4976210 DOI: 10.4254/wjh.v8.i22.915] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2016] [Revised: 04/22/2016] [Accepted: 06/16/2016] [Indexed: 02/06/2023] Open
Abstract
Acute liver failure, also known as fulminant hepatic failure (FHF), embraces a spectrum of clinical entities characterized by acute liver injury, severe hepatocellular dysfunction, and hepatic encephalopathy. Cerebral edema and intracranial hypertension are common causes of mortality in patients with FHF. The management of patients who present acute liver failure starts with determining the cause and an initial evaluation of prognosis. Regardless of whether or not patients are listed for liver transplantation, they should still be monitored for recovery, death, or transplantation. In the past, neuromonitoring was restricted to serial clinical neurologic examination and, in some cases, intracranial pressure monitoring. Over the years, this monitoring has proven insufficient, as brain abnormalities were detected at late and irreversible stages. The need for real-time monitoring of brain functions to favor prompt treatment and avert irreversible brain injuries led to the concepts of multimodal monitoring and neurophysiological decision support. New monitoring techniques, such as brain tissue oxygen tension, continuous electroencephalogram, transcranial Doppler, and cerebral microdialysis, have been developed. These techniques enable early diagnosis of brain hemodynamic, electrical, and biochemical changes, allow brain anatomical and physiological monitoring-guided therapy, and have improved patient survival rates. The purpose of this review is to discuss the multimodality methods available for monitoring patients with FHF in the neurocritical care setting.
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Abstract
Acute liver failure is life threatening liver injury with coagulopathy and hepatic encephalopathy within 26 weeks and generally, in the absence of preexisting liver disease. Fulminant liver failure occurs when hepatic encephalopathy occurs within 8 weeks of jaundice. The majority of patients with ALF are women with the median age of 38 years. In the United States, drug induced liver injury including acetaminophen causes the majority of ALF cases. The etiology of ALF should be determined, if possible, because many causes have a specific treatment. The mainstay for ALF is supportive care and liver transplantation, if necessary. There are multiple prognostic criteria available. Prognosis can be poor and patients should be referred to a liver transplantation center as soon as possible.
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Affiliation(s)
- Carmi S Punzalan
- 1 Department of Medicine, Division of Gastroenterology, University of Massachusetts Memorial Medical Center, Worcester, MA, USA
| | - Curtis T Barry
- 1 Department of Medicine, Division of Gastroenterology, University of Massachusetts Memorial Medical Center, Worcester, MA, USA
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Li Y, Zhang J, Xu P, Sun B, Zhong Z, Liu C, Ling Z, Chen Y, Shu N, Zhao K, Liu L, Liu X. Acute liver failure impairs function and expression of breast cancer-resistant protein (BCRP) at rat blood-brain barrier partly via ammonia-ROS-ERK1/2 activation. J Neurochem 2016; 138:282-94. [DOI: 10.1111/jnc.13666] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2015] [Revised: 05/04/2016] [Accepted: 05/07/2016] [Indexed: 12/26/2022]
Affiliation(s)
- Ying Li
- Center of Drug Metabolism and Pharmacokinetics; China Pharmaceutical University; Nanjing China
| | - Ji Zhang
- Center of Drug Metabolism and Pharmacokinetics; China Pharmaceutical University; Nanjing China
| | - Ping Xu
- Center of Drug Metabolism and Pharmacokinetics; China Pharmaceutical University; Nanjing China
| | - Binbin Sun
- Center of Drug Metabolism and Pharmacokinetics; China Pharmaceutical University; Nanjing China
| | - Zeyu Zhong
- Center of Drug Metabolism and Pharmacokinetics; China Pharmaceutical University; Nanjing China
| | - Can Liu
- Center of Drug Metabolism and Pharmacokinetics; China Pharmaceutical University; Nanjing China
| | - Zhaoli Ling
- Center of Drug Metabolism and Pharmacokinetics; China Pharmaceutical University; Nanjing China
| | - Yang Chen
- Center of Drug Metabolism and Pharmacokinetics; China Pharmaceutical University; Nanjing China
| | - Nan Shu
- Center of Drug Metabolism and Pharmacokinetics; China Pharmaceutical University; Nanjing China
| | - Kaijing Zhao
- Center of Drug Metabolism and Pharmacokinetics; China Pharmaceutical University; Nanjing China
| | - Li Liu
- Center of Drug Metabolism and Pharmacokinetics; China Pharmaceutical University; Nanjing China
| | - Xiaodong Liu
- Center of Drug Metabolism and Pharmacokinetics; China Pharmaceutical University; Nanjing China
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Hepatic Failure. PRINCIPLES OF ADULT SURGICAL CRITICAL CARE 2016. [PMCID: PMC7123541 DOI: 10.1007/978-3-319-33341-0_18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The progression of liver disease can cause several physiologic derangements that may precipitate hepatic failure and require admission to an intensive care unit. The underlying pathology may be acute, acute-on chronic, or chronic in nature. Liver failure may manifest with a variety of clinical signs and symptoms that need prompt attention. The compromised synthetic and metabolic activity of the failing liver affects all organ systems, from neurologic to integumentary. Supportive care and specific therapies should be instituted in order to improve outcome and minimize time of recovery. In this chapter we will discuss the definition, clinical manifestations, workup, and management of acute and chronic liver failure and the general principles of treatment of these patients. Management of liver failure secondary to certain common etiologies will also be presented. Finally, liver transplantation and alternative therapies will also be discussed.
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Abstract
PURPOSE OF REVIEW This article summarizes the most common neurologic sequelae of acute and chronic liver failure, liver transplantation, and other treatments for liver disease, and outlines the pathogenesis, neurologic manifestations, and treatment of Wilson disease. RECENT FINDINGS The neurologic manifestations of liver disease are caused by the liver's failure to detoxify active compounds that have deleterious effects on the central and peripheral nervous systems. In addition, treatments for liver disease such as liver transplantation, transjugular intrahepatic portosystemic shunt, and antiviral medications can also be neurotoxic. Wilson disease affects the liver and nervous system simultaneously and may often initially be diagnosed by a neurologist; treatment options have evolved over recent years. SUMMARY Acute and chronic liver diseases are encountered commonly in the general population. Neurologic dysfunction will eventually affect a significant number of these individuals, especially if the disease progresses to liver failure. Early recognition of these neurologic manifestations can lead to more effective management of these patients.
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Abstract
OPINION STATEMENT Hepatic encephalopathy management varies depending on the acuity of liver failure. However, in patients with either acute or chronic liver failure five basic steps in management are critical: stabilization, addressing modifiable precipitating factors, lowering blood ammonia, managing elevated intracranial pressure (ICP) (if present), and managing complications of liver failure that can contribute to encephalopathy, particularly hyponatremia. Because liver failure patients are prone to a variety of other medical problems that can lead to encephalopathy (such as coagulopathy associated intracranial hemorrhage, electrolyte disarray, renal failure, hypotension, hypoglycemia, and infection), a thorough history, physical and neurologic examination is mandated in all encephalopathic liver failure patients. There should be a low threshold for brain imaging in patients with focal neurological deficits given the propensity for spontaneous intracranial hemorrhage. In patients with acute liver failure and high grade encephalopathy, identification of the etiology of acute liver failure is essential to guide treatment and antidote administration, particularly in the case of acetaminophen poisoning. Equally critical is management of elevated ICP in acute liver failure. Intracranial hypertension can be treated with hypertonic saline and/or adjustment of the dialysis bath. Placement of an intracranial monitor to guide ICP therapy is risky because of concomitant coagulopathy and remains controversial. Continuous renal replacement therapy may help lower serum ammonia, treat coexisting uremia, and improve symptoms. Liver transplantation is the definitive treatment for patients with acute liver failure and hepatic encephalopathy. In patients with chronic hepatic encephalopathy, lactulose and rifaxamin remain a mainstay of therapy. In these patients, it is essential to identify reversible causes of hepatic encephalopathy such as increased ammonia production and/or decreased clearance (eg, infection, GI bleed, constipation, hypokalemia, dehydration). Chronic hyponatremia should be managed by gradual sodium correction of no more than 8‒12 meq/L per day to avoid central myelinolysis syndrome. Free water restriction and increased dietary sodium are reasonable, cost effective treatment options. Many emerging therapies, both pharmacologic and interventional, are currently being studied to improve management of hepatic encephalopathy.
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EEG abnormalities are associated with increased risk of transplant or poor outcome in children with acute liver failure. J Pediatr Gastroenterol Nutr 2014; 58:449-56. [PMID: 24345828 DOI: 10.1097/mpg.0000000000000271] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
OBJECTIVES There are limited data on the incidence of seizures and utility of brain imaging and electroencephalogram (EEG) to predict outcome of children with acute liver failure (ALF). We investigated the association between hepatic encephalopathy (HE) scores, abnormal EEG or neuroimaging, and short-term outcome. METHODS Single-center retrospective observational study of infants and children with ALF who underwent continuous EEG monitoring and brain imaging within 24 hours of admission to the intensive care unit (ICU). RESULTS A total of 19 patients with ALF with a mean age of 6.8 ± 1.5 years were evaluated. The majority of cases (74%) were indeterminate. Of the total, 10 patients (53%) survived to discharge without liver transplant (LT), 5 (26%) received LT, and 4 (21%) died without LT. Seizures occurred in only 2 cases (19%). Patients who had an abnormal EEG on admission (n = 7) were significantly more likely to die or require LT (P < 0.05, Fisher exact test). Patients with either an admission HE score ≤ 2, or liver injury unit score <222, combined with a normal or mildly abnormal EEG were more likely to survive without LT. Neuroimaging was normal in the majority of cases (87%) and was not associated with outcome. CONCLUSIONS Children with a moderate or severe abnormality of EEG background on admission were significantly more likely to require LT or to die. Children with an HE score ≤ 2, and a normal or only mildly abnormal EEG, were significantly more likely to survive without needing LT. These findings are an initial step toward distinguishing patients with ALF who may recover spontaneously from those who will require LT.
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Abstract
Fulminant hepatic failure presents with a hepatic encephalopathy and may progress to coma and often brain death from cerebral edema. This natural progression in severe cases contributes to early mortality, but outcome can be good if liver transplantation is appropriately timed and increased intracranial pressure (ICP) is managed. Neurologists and neurosurgeons have become more involved in these very challenging patients and are often asked to rapidly identify patients who are at risk of cerebral edema, to carefully select the patient population who will benefit from invasive ICP monitoring, to judge the correct time to start monitoring, to participate in treatment of cerebral edema, and to manage complications such as intracranial hemorrhage or seizures. This chapter summarizes the current multidisciplinary approach to fulminant hepatic failure and how to best bridge patients to emergency liver transplantation.
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Pruitt AA, Graus F, Rosenfeld MR. Neurological complications of solid organ transplantation. Neurohospitalist 2013; 3:152-66. [PMID: 24167649 DOI: 10.1177/1941874412466090] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Solid organ transplantation (SOT) is the preferred treatment for an expanding range of conditions whose successful therapy has produced a growing population of chronically immunosuppressed patients with potential neurological problems. While the spectrum of neurological complications varies with the type of organ transplanted, the indication for the procedure, and the intensity of long-term required immunosuppression, major neurological complications occur with all SOT types. The second part of this 2-part article on transplantation neurology reviews central and peripheral nervous system problems associated with SOT with clinical and neuroimaging examples from the authors' institutional experience. Particular emphasis is given to conditions acquired from the donated organ or tissue, problems specific to types of organs transplanted and drug therapy-related complications likely to be encountered by hospitalists. Neurologically important syndromes such as immune reconstitution inflammatory syndrome (IRIS), posterior reversible encephalopathy syndrome (PRES), and posttransplantation lymphoproliferative disorder (PTLD) are readdressed in the context of SOT.
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Affiliation(s)
- Amy A Pruitt
- Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA
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36
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Whitehouse T, Wendon J. Acute liver failure. Best Pract Res Clin Gastroenterol 2013; 27:757-69. [PMID: 24160932 DOI: 10.1016/j.bpg.2013.08.010] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2013] [Revised: 08/01/2013] [Accepted: 08/11/2013] [Indexed: 01/31/2023]
Abstract
Untreated acute liver failure (ALF) has a poor outcome and so rapid diagnosis and management is vital if the patient is to survive. ALF has such profound and widespread physiological consequences that whenever possible, patients with ALF should be managed in an intensive care unit. Management is to support the physiology and treat the underlying cause. Advice should be sought from a centre capable of performing liver transplantation. Should recovery seem unlikely, liver transplantation is a viable treatment option in some cases.
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Affiliation(s)
- Tony Whitehouse
- University Hospital Birmingham, Edgbaston, Birmingham B15 2WB, UK.
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37
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Akamatsu N, Sugawara Y, Kokudo N. Acute liver failure and liver transplantation. Intractable Rare Dis Res 2013; 2:77-87. [PMID: 25343108 PMCID: PMC4204547 DOI: 10.5582/irdr.2013.v2.3.77] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2013] [Accepted: 07/18/2013] [Indexed: 12/19/2022] Open
Abstract
Acute liver failure (ALF) is defined by the presence of coagulopathy (International Normalized Ratio ≥ 1.5) and hepatic encephalopathy due to severe liver damage in patients without pre-existing liver disease. Although the mortality due to ALF without liver transplantation is over 80%, the survival rates of patients have considerably improved with the advent of liver transplantation, up to 60% to 90% in the last two decades. Recent large studies in Western countries reported 1, 5, and 10-year patient survival rates after liver transplantation for ALF of approximately 80%, 70%, and 65%, respectively. Living donor liver transplantation (LDLT), which has mainly evolved in Asian countries where organ availability from deceased donors is extremely scarce, has also improved the survival rate of ALF patients in these regions. According to recent reports, the overall survival rate of adult ALF patients who underwent LDLT ranges from 60% to 90%. Although there is still controversy regarding the graft type, optimal graft volume, and ethical issues, LDLT has become an established treatment option for ALF in areas where the use of deceased donor organs is severely restricted.
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Affiliation(s)
- Nobuhisa Akamatsu
- Department of Hepato-biliary-pancreatic Surgery, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan
| | - Yasuhiko Sugawara
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Norihiro Kokudo
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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38
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Abstract
Acute liver failure (ALF) is a condition wherein the previously healthy liver rapidly deteriorates, resulting in jaundice, encephalopathy, and coagulopathy. There are approximately 2000 cases per year of ALF in the United States. Viral causes (fulminant viral hepatitis [FVH]) are the predominant cause of ALF in developing countries. Given the ease of spread of viral hepatitis and the high morbidity and mortality associated with ALF, a systematic approach to the diagnosis and treatment of FVH is required. In this review, the authors describe the viral causes of ALF and review the intensive care unit management of patients with FVH.
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MESH Headings
- Acetylcysteine/therapeutic use
- Adult
- Brain Edema/etiology
- Brain Edema/virology
- Developing Countries
- Female
- Hepatectomy
- Hepatitis, Viral, Human/complications
- Hepatitis, Viral, Human/drug therapy
- Hepatitis, Viral, Human/prevention & control
- Herpesviridae/pathogenicity
- Humans
- Hypothermia, Induced/adverse effects
- Hypothermia, Induced/standards
- Immunocompromised Host
- Intensive Care Units
- Intubation, Intratracheal
- Liver Failure, Acute/etiology
- Liver Failure, Acute/therapy
- Liver Failure, Acute/virology
- Liver Transplantation
- Pregnancy
- Pregnancy Complications, Infectious/virology
- Prognosis
- Viral Hepatitis Vaccines/administration & dosage
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Affiliation(s)
- Saumya Jayakumar
- Faculty of Medicine and Dentistry, Division of Gastroenterology, University of Calgary, TRW Building, 3280 Hospital Drive NW, Calgary, Alberta T2N 4Z6, Canada
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39
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Ryan JM, Tranah T, Mitry RR, Wendon JA, Shawcross DL. Acute liver failure and the brain: a look through the crystal ball. Metab Brain Dis 2013; 28:7-10. [PMID: 23212480 DOI: 10.1007/s11011-012-9363-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2012] [Accepted: 11/15/2012] [Indexed: 12/19/2022]
Abstract
Over the past 35 years, the outlook for a patient presenting with acute liver failure (ALF) has changed beyond all recognition. A patient presenting in 1984 had an 80 % likelihood of succumbing to intracranial hypertension. Today due to dramatic improvements in intensive care in dedicated liver transplant units, this has been reduced to just 20 %. Prompt fluid resuscitation, empirical treatment for sepsis and standardised management protocols that include early intubation and high flow hemofiltration for ammonia removal, limit the numbers of patients who die from the sequelae of cerebral edema and ALF. With the evolution and development of bedside prognostic markers that will include personalised genomic, metabonomic and immune profiling, rationalisation of grafts to those who are not predicted to survive is likely to further minimise the number of grafts utilised. Furthermore, in those patients with a dismal prognosis, the use of plasmapheresis, immunomodulatory therapies, biological liver support systems and hepatocyte transplantation offer a potential bridge until the injured liver can begin to regenerate avoiding transplantation and life-long immunosuppressant therapy.
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Affiliation(s)
- Jennifer M Ryan
- Institute of Liver Studies, King's College London School of Medicine at King's College Hospital, King's College Hospital, Denmark Hill, London, UK.
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40
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Abstract
PURPOSE OF REVIEW This article summarizes the most common etiologies and approaches to management of metabolic encephalopathy. RECENT FINDINGS Metabolic encephalopathy is a frequent occurrence in the intensive care unit setting. Common etiologies include hepatic failure, renal failure, sepsis, electrolyte disarray, and Wernicke encephalopathy. Current treatment paradigms typically focus on supportive care and management of the underlying etiology. Directed therapies that target neurochemical and neurotransmitter pathways that mediate encephalopathy are not currently available and represent an important area for future research. Although commonly thought of as reversible neurologic insults, delirium and encephalopathy have been associated with increased mortality, prolonged length of stay and hospital complications, and worse long-term cognitive and functional outcomes. SUMMARY Recognition and treatment of encephalopathy is critical to improving outcomes in critically ill patients.
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Affiliation(s)
- Jennifer A Frontera
- Mount Sinai School of Medicine, Department of Neurology, One Gustave Levy Place, Box 1136, New York, NY 10029, USA.
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41
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Vaquero J. Therapeutic hypothermia in the management of acute liver failure. Neurochem Int 2012; 60:723-35. [DOI: 10.1016/j.neuint.2011.09.006] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2011] [Revised: 09/13/2011] [Accepted: 09/13/2011] [Indexed: 02/07/2023]
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Kumar R, Bhatia V. Structured approach to treat patients with acute liver failure: A hepatic emergency. Indian J Crit Care Med 2012; 16:1-7. [PMID: 22557825 PMCID: PMC3338232 DOI: 10.4103/0972-5229.94409] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Acute liver failure (ALF) is a condition of acute hepatic emergency where rapid deterioration of hepatocyte function leads to hepatic encephalopathy, coagulopathy, cerebral edema (CE), infection and multi-organ dysfunction syndrome resulting in a high mortality rate. Urgent liver transplantation is the standard of care for most of these patients in Western countries. However, in India, access to liver transplantation is severely limited and, hence, the management is largely based on intensive medical care. With earlier recognition of disease, better understanding of pathophysiology and improved intensive care, ALF patients have shown a significant improvement in spontaneous survival. An evidence base for practice for supportive care is still lacking; however, intensive organ support as well as control of infection and CE are likely to be key to the successful outcome in this acute and potentially reversible condition without any sequel. A structured approach to decision making about intensive care is important in each case. Unlike in Western countries where acetamenophen is the most common cause of ALF, the role of a specific agent, such as N-acetylcysteine, is limited in India. Ammonia-lowering therapy is still in an evolving phase. The current review highlights the important medical management issues in patients with ALF in general as well as the management of major complications associated with ALF. We performed a MEDLINE search using combinations of the key words such as acute liver failure, intensive treatment of acute liver failure and fulminant hepatic failure. We reviewed the relevant publications with regard to intensive care of patients with ALF.
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Affiliation(s)
- Ramesh Kumar
- From: Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Vikram Bhatia
- From: Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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43
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Mpabanzi L, Jalan R. Neurological complications of acute liver failure: pathophysiological basis of current management and emerging therapies. Neurochem Int 2011; 60:736-42. [PMID: 22100567 DOI: 10.1016/j.neuint.2011.10.014] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2011] [Revised: 10/17/2011] [Accepted: 10/26/2011] [Indexed: 12/11/2022]
Abstract
One of the major causes of mortality in patients with acute liver failure (ALF) is the development of hepatic encephalopathy (HE) which is associated with increased intracranial pressure (ICP). High ammonia levels, increased cerebral blood flow and increased inflammatory response have been identified as major contributors to the development of HE and the related brain swelling. The general principles of the management of patients with ALF are straightforward. They include identifying the insult causing hepatic injury, providing organ systems support to optimize the patient's physical condition, anticipation and prevention of development of complications. Increasing insights into the pathophysiological mechanisms of ALF are contributing to better therapies. For instance, the evident role of cerebral hyperemia in the pathogenesis of increased ICP has led to a re-evaluation of established therapies such as hyperventilation, N-acetylcysteine, thiopentone sodium and propofol. The role of systemic inflammatory response in the pathogenesis of increased ICP has also gained importance supporting the concept that antibiotics given prophylactically reduce the risk of developing sepsis during the course of illness. Moderate hypothermia has also been established as a therapy able to reduce ICP in patients with uncontrolled intracranial hypertension and to prevent increases in ICP during orthopic liver transplantation. Ornithine phenylacetate, a new drug in the treatment of liver failure, and liver replacement therapies are still being investigated both experimentally and clinically. Despite many advances in the understanding of the pathophysiological basis and the management of intracranial hypertension in ALF, more clinical trials should be conducted to determine the best therapeutic management for this difficult clinical event.
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Affiliation(s)
- Liliane Mpabanzi
- Department of Surgery, Maastricht University Medical Centre, and NUTRIM School of Nutrition, Toxicology and Metabolism, Maastricht University, PO Box 5800, Maastricht, The Netherlands
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44
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Shawcross DL, Wendon JA. The neurological manifestations of acute liver failure. Neurochem Int 2011; 60:662-71. [PMID: 22067133 DOI: 10.1016/j.neuint.2011.10.006] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2011] [Revised: 10/12/2011] [Accepted: 10/14/2011] [Indexed: 12/12/2022]
Abstract
Acute liver failure is a disorder which impacts on multiple organ systems and results from hepatocellular necrosis in a patient with no previous history of chronic liver disease. It typically culminates in the development of liver dysfunction, coagulopathy and encephalopathy, and is associated with high mortality in poor prognostic groups. In acute liver failure, some patients may develop cerebral edema and increased intracranial pressure although recent data suggest that intracranial hypertension is less frequent than previously described, complicating 29% of acute cases who have proceeded to grade 3/4 coma. Neurological manifestations are primarily underpinned by the development of brain edema. The onset of encephalopathy can be rapid and dramatic with the development of asterixis, delirium, hyperreflexia, clonus, seizures, extensor posturing and coma. Ammonia plays a definitive role in the development of cytotoxic brain edema. Patients with acute liver failure have a marked propensity to develop renal insufficiency and hence impaired ammonia excretion. The incidence of both bacterial and fungal infection occurs in approximately one third of patients. The relationship between inflammation, as opposed to infection, and progression of encephalopathy is similar to that observed in chronic liver disease. Intracranial pressure monitoring is valuable in identifying surges in intracranial hypertension requiring intervention. Insertion of an intracranial bolt should be considered only in the subgroup of patients who have progressed to grade 4 coma. Risk factors for developing intracranial hypertension are those with hyperacute and acute etiologies, progression to grade 3/4 hepatic encephalopathy, those who develop pupillary abnormalities (dilated pupils, sluggishly responsive to light) or seizures, have systemic inflammation, an arterial ammonia >150 μmol/L, hyponatremia, and those in receipt of vasopressor support. Strategies employed in patients with established encephalopathy (grade 3/4) aim to maintain freedom from infection/inflammatory milieu, provide adequate sedation, and correct hypo-osmolality.
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Affiliation(s)
- Debbie L Shawcross
- Institute of Liver Studies, King's College London School of Medicine at King's College Hospital, King's College Hospital, Denmark Hill, London SE5 9RS, United Kingdom.
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45
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Abstract
Intracranial hemorrhage is a life-threatening condition, the outcome of which can be improved by intensive care. Intracranial hemorrhage may be spontaneous, precipitated by an underlying vascular malformation, induced by trauma, or related to therapeutic anticoagulation. The goals of critical care are to assess the proximate cause, minimize the risks of hemorrhage expansion through blood pressure control and correction of coagulopathy, and obliterate vascular lesions with a high risk of acute rebleeding. Simple bedside scales and interpretation of computed tomography scans assess the severity of neurological injury. Myocardial stunning and pulmonary edema related to neurological injury should be anticipated, and can usually be managed. Fever (often not from infection) is common and can be effectively treated, although therapeutic cooling has not been shown to improve outcomes after intracranial hemorrhage. Most functional and cognitive recovery takes place weeks to months after discharge; expected levels of functional independence (no disability, disability but independence with a device, dependence) may guide conversations with patient representatives. Goals of care impact mortality, with do-not-resuscitate status increasing the predicted mortality for any level of severity of intraparenchymal hemorrhage. Future directions include refining the use of bedside neuro-monitoring (electroencephalogram, invasive monitors), novel approaches to reduce intracranial hemorrhage expansion, minimizing vasospasm, and refining the assessment of quality of life to guide rehabilitation and therapy.
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Affiliation(s)
- Andrew M Naidech
- Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
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46
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Wright G, Chattree A, Jalan R. Management of hepatic encephalopathy. Int J Hepatol 2011; 2011:841407. [PMID: 21994873 PMCID: PMC3177461 DOI: 10.4061/2011/841407] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2011] [Accepted: 06/08/2011] [Indexed: 12/11/2022] Open
Abstract
Hepatic encephalopathy (HE), the neuropsychiatric presentation of liver disease, is associated with high morbidity and mortality. Reduction of plasma ammonia remains the central therapeutic strategy, but there is a need for newer novel therapies. We discuss current evidence supporting the use of interventions for both the general management of chronic HE and that necessary for more acute and advanced disease.
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Affiliation(s)
- G. Wright
- University College London Institute of Hepatology, The Royal Free Hospital, Pond Street, London NW3 2PF, UK
| | - A. Chattree
- Department of Gastroenterology, King Georges Hospital, Barley Lane, Goodmayes, Ilford, Essex IG3 8YB, UK
| | - R. Jalan
- University College London Institute of Hepatology, The Royal Free Hospital, Pond Street, London NW3 2PF, UK
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47
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Sundaram V, Shaikh OS. Acute liver failure: current practice and recent advances. Gastroenterol Clin North Am 2011; 40:523-39. [PMID: 21893272 DOI: 10.1016/j.gtc.2011.06.009] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
ALF is an important cause of liver-related morbidity and mortality. Advances in the management of ICH and SIRS, and cardiorespiratory, metabolic, and renal support have improved the outlook of such patients. Early transfer to a liver transplant center is essential. Routine use of NAC is recommended for patients with early hepatic encephalopathy, irrespective of the etiology. The role of hypothermia remains to be determined. Liver transplantation plays a critical role, particularly for those with advanced encephalopathy. Several detoxification and BAL support systems have been developed to serve as a bridge to transplantation or to spontaneous recovery. However, such systems lack sufficient reliability and efficacy to be applied routinely in clinical practice. Hepatocyte and stem cell transplantation may provide valuable adjunctive therapy in the future.
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Affiliation(s)
- Vinay Sundaram
- Department of Medicine, Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA
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48
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Abstract
Acute liver failure (ALF) is uncommon in the United States, but presents acutely and catastrophically, often with deadly consequences. Hepatic encephalopathy, cerebral edema, elevated intracranial pressure, and intracranial hemorrhage due to coagulopathy are common occurrences in patients with ALF. Appropriate management of multi-system organ failure and neurological complications are essential in bridging patients to transplant and ensuring satisfactory outcomes.
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Affiliation(s)
- Jennifer A Frontera
- Neuroscience Intensive Care Unit, Department of Neurosurgery, Mount Sinai School of Medicine, One Gustave Levy Place, P.O. Box 1136, New York, NY 10029, USA.
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49
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50
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Abstract
OPINION STATEMENT Cerebral edema is very common in patients with acute liver failure and encephalopathy. In severe cases, it produces brain tissue shift and potentially fatal herniation. Brain swelling in acute liver failure is produced by a combination of cytotoxic (cellular) and vasogenic edema. Accumulation of ammonia and glutamine leads to disturbances in the regulation of cerebral osmolytes, increased free radical production and calcium-mediated mitochondrial injury, and alterations in glucose metabolism (inducing high levels of brain lactate), resulting in astrocyte swelling. Activation of inflammatory cytokines can cause increased blood-brain barrier permeability leading to vasogenic edema, although the relative contribution of vasogenic edema is probably minor compared with cellular swelling. Cerebral blood flow is disturbed and generally increased in patients with acute liver failure; persistent vasodilatation and loss of autoregulation may generate hyperemia, and the consequent augmentation in cerebral blood volume may exacerbate brain edema.Adequate management of intracranial hypertension demands continuous monitoring of intracranial pressure and cerebral perfusion pressure. Coagulation status should be assessed and bleeding diathesis should be treated prior to insertion of the intracranial pressure monitor. Standard treatment measures such as hyperventilation and osmotic agents (e.g., mannitol, hypertonic saline) remain useful first-line interventions. Although hypertonic saline may be preferred in patients with coexistent hyponatremia, the rate of correction of hyponatremia must be gradual to avoid the risk of osmotic demyelination. Barbiturate coma and intravenous indomethacin are available options in refractory cases. The most promising novel therapeutic alternative is the induction of moderate hypothermia (aiming for a core temperature of 32-34°C). However, the safety and efficacy of therapeutic hypothermia for brain swelling caused by liver failure still needs to be proven in randomized, controlled clinical trials. Management of intracranial pressure in patients with acute liver failure should be guided by well-defined treatment protocols.
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Affiliation(s)
- Alejandro A Rabinstein
- Department of Neurology, W8B, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA,
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