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Yang Y, Luo H, Zhang Y, Zhao Z, Zhang J. Association between ketamine use and mortality in critically ill patients receiving mechanical ventilation: Analysis of the MIMIC-IV database. PLoS One 2025; 20:e0320047. [PMID: 40138307 PMCID: PMC11940653 DOI: 10.1371/journal.pone.0320047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2024] [Accepted: 02/13/2025] [Indexed: 03/29/2025] Open
Abstract
OBJECTIVE Ketamine, as a sedative, has been administered during mechanical ventilation in critically ill patients; however, its impact on survival outcomes in this patient population remains uncertain. METHODS This retrospective cohort study extracted data from the Medical Information Mart for Intensive Care (MIMIC-IV) database, version 3.0. Patients were categorized into the ketamine group and the control group based on whether ketamine was administered during mechanical ventilation. Propensity score matching was performed to adjust for demographic variables and coexisting conditions. The primary outcome was 28-day mortality. Secondary outcomes included 14-day and 90-day mortality rates, as well as hospital and ICU lengths of stay. RESULTS The study included a total of 8569 patients, with 330 in the ketamine group and 8239 in the control group. After propensity score matching, significant differences in mechanical ventilation duration and the proportion of patients with acute respiratory distress syndrome remained between groups. No significant differences were observed in 28-day and 90-day mortality rates between the groups. Subgroup analysis indicated that ketamine was associated with lower 14-day mortality rates among younger patients, those with acute respiratory distress syndrome, and norepinephrine users. Ketamine administration was also found to correlate with increased lengths of stay in both the hospital and ICU. CONCLUSIONS Ketamine was more frequently selected for patients requiring prolonged mechanical ventilation. The administration of ketamine was associated with reduced 14-day but not with 28-day or 90-day mortality rates.
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Affiliation(s)
- Yuecheng Yang
- Department of Anesthesiology, Fudan University Shanghai Cancer Center, Shanghai, China,
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China,
| | - Huanyu Luo
- Department of Anesthesiology, Fudan University Shanghai Cancer Center, Shanghai, China,
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China,
| | - Yunkui Zhang
- Department of Anesthesiology, Fudan University Shanghai Cancer Center, Shanghai, China,
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China,
| | - Zhiyong Zhao
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China,
- Department of Intensive Care Unit, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Jun Zhang
- Department of Anesthesiology, Fudan University Shanghai Cancer Center, Shanghai, China,
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China,
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2
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Schneeweiss-Gleixner M, Krenn K, Petter M, Haselwanter P, Kraft F, Adam L, Semmler G, Hartl L, Halilbasic E, Buchtele N, Krall C, Staudinger T, Zauner C, Trauner M, Stättermayer AF. Presence of cholestasis and its impact on survival in SARS-CoV-2 associated acute respiratory distress syndrome. Sci Rep 2024; 14:23377. [PMID: 39379494 PMCID: PMC11461911 DOI: 10.1038/s41598-024-73948-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Accepted: 09/23/2024] [Indexed: 10/10/2024] Open
Abstract
Data on cholestasis and biliary injury in patients with COVID-19 are scarce. The primary aim of this study was to evaluate the prevalence of cholestasis and factors associated with its development and outcome in critically ill patients with COVID-19 associated acute respiratory distress syndrome (ARDS). In this retrospective exploratory study, COVID-19 patients with ARDS admitted to an intensive care unit (ICU) at the Medical University of Vienna were evaluated for the development of cholestasis defined as an alkaline phosphatase level of 1.67x upper limit of normal for at least three consecutive days. Simple and multiple logistic regression analysis was used to evaluate parameters associated with development of cholestasis and survival. Of 225 included patients 119 (53%) developed cholestasis during ICU stay. Patients with cholestasis had higher peak levels of alkaline phosphatase, gamma-glutamyl transferase, bilirubin and inflammation parameters. Factors independently associated with cholestasis were extracorporeal membrane oxygenation support, ketamine use, high levels of inflammation parameters and disease severity. Presence of cholestasis and peak ALP levels were independently associated with worse ICU and 6-month survival. Development of cholestasis is a common complication in critically ill COVID-19 patients and represents a negative prognostic marker for survival. It is associated with disease severity and specific treatment modalities of intensive care.
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Affiliation(s)
- Mathias Schneeweiss-Gleixner
- Department of Medicine III, Division of Gastroenterology and Hepatology with Intensive Care Unit 13h1, Medical University of Vienna, Vienna, Austria
| | - Katharina Krenn
- Department of Anesthesia, General Intensive Care and Pain Medicine, Medical University of Vienna, Vienna, Austria
| | - Mathias Petter
- Department of Medicine III, Division of Gastroenterology and Hepatology with Intensive Care Unit 13h1, Medical University of Vienna, Vienna, Austria
| | - Patrick Haselwanter
- Department of Medicine III, Division of Gastroenterology and Hepatology with Intensive Care Unit 13h1, Medical University of Vienna, Vienna, Austria
| | - Felix Kraft
- Department of Anesthesia, General Intensive Care and Pain Medicine, Medical University of Vienna, Vienna, Austria
| | - Lukas Adam
- Department of Anesthesia, General Intensive Care and Pain Medicine, Medical University of Vienna, Vienna, Austria
| | - Georg Semmler
- Department of Medicine III, Division of Gastroenterology and Hepatology with Intensive Care Unit 13h1, Medical University of Vienna, Vienna, Austria
| | - Lukas Hartl
- Department of Medicine III, Division of Gastroenterology and Hepatology with Intensive Care Unit 13h1, Medical University of Vienna, Vienna, Austria
| | - Emina Halilbasic
- Department of Medicine III, Division of Gastroenterology and Hepatology with Intensive Care Unit 13h1, Medical University of Vienna, Vienna, Austria
| | - Nina Buchtele
- Department of Medicine I, Intensive Care Unit 13i2, Medical University of Vienna, Vienna, Austria
| | - Christoph Krall
- Department of Medical Statistics, Medical University of Vienna, Vienna, Austria
| | - Thomas Staudinger
- Department of Medicine I, Intensive Care Unit 13i2, Medical University of Vienna, Vienna, Austria
| | - Christian Zauner
- Department of Medicine III, Division of Gastroenterology and Hepatology with Intensive Care Unit 13h1, Medical University of Vienna, Vienna, Austria
| | - Michael Trauner
- Department of Medicine III, Division of Gastroenterology and Hepatology with Intensive Care Unit 13h1, Medical University of Vienna, Vienna, Austria.
| | - Albert Friedrich Stättermayer
- Department of Medicine III, Division of Gastroenterology and Hepatology with Intensive Care Unit 13h1, Medical University of Vienna, Vienna, Austria.
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Amer M, Møller MH, Alshahrani M, Shehabi Y, Arabi YM, Alshamsi F, Sigurðsson MI, Rehn M, Chew MS, Kalliomäki ML, Lewis K, Al-Suwaidan FA, Al-Dorzi HM, Al-Fares A, Alsadoon N, Bell CM, Groth CM, Parke R, Mehta S, Wischmeyer PE, Al-Omari A, Olkkola KT, Alhazzani W. Ketamine analgo-sedation for mechanically ventilated critically ill adults: A rapid practice guideline from the Saudi Critical Care Society and the Scandinavian Society of Anesthesiology and Intensive Care Medicine. Acta Anaesthesiol Scand 2024; 68:1161-1178. [PMID: 39198198 DOI: 10.1111/aas.14470] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Revised: 05/16/2024] [Accepted: 05/29/2024] [Indexed: 09/01/2024]
Abstract
BACKGROUND This Rapid Practice Guideline (RPG) aimed to provide evidence-based recommendations for ketamine analgo-sedation (monotherapy and adjunct) versus non-ketamine sedatives or usual care in adult intensive care unit (ICU) patients on invasive mechanical ventilation (iMV) and to identify knowledge gaps for future research. METHODS The RPG panel comprised 23 multinational multidisciplinary panelists, including a patient representative. An up-to-date systematic review and meta-analysis constituted the evidence base. The Grading Recommendations, Assessment, Development, and Evaluation approach, and the evidence-to-decision framework were used to assess the certainty of evidence and to move from evidence to decision/recommendation. The panel provided input on the balance of the desirable and undesirable effects, certainty of evidence, patients' values and preferences, costs, resources, equity, feasibility, acceptability, and research priorities. RESULTS Data from 17 randomized clinical trials (n = 898) and nine observational studies (n = 1934) were included. There was considerable uncertainty about the desirable and undesirable effects of ketamine monotherapy for analgo-sedation. The evidence was very low certainty and downgraded for risk of bias, indirectness, and inconsistency. Uncertainty or variability in values and preferences were identified. Costs, resources, equity, and acceptability were considered varied. Adjunctive ketamine therapy had no effect on mortality (within 28 days) (relative risk [RR] 0.99; 95% confidence interval [CI] 0.76 to 1.27; low certainty), and may slightly reduce iMV duration (days) (mean difference [MD] -0.05 days; 95% CI -0.07 to -0.03; low certainty), and uncertain effect on the cumulative dose of opioids (mcg/kg/h morphine equivalent) (MD -11.6; 95% CI -20.4 to -2.7; very low certainty). Uncertain desirable effects (cumulative dose of sedatives and vasopressors) and undesirable effects (adverse event rate, delirium, arrhythmia, hepatotoxicity, hypersalivation, use of physical restraints) were also identified. A possibility of important uncertainty or variability in patient-important outcomes led to a balanced effect that favored neither the intervention nor the comparison. Cost, resources, and equity were considered varied. CONCLUSION The RPG panel provided two conditional recommendations and suggested (1) against using ketamine as monotherapy analgo-sedation in critically ill adults on iMV when other analgo-sedatives are available; and (2) using ketamine as an adjunct to non-ketamine usual care sedatives (e.g., opioids, propofol, dexmedetomidine) or continuing with non-ketamine usual care sedatives alone. Large-scale trials should provide additional evidence.
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Affiliation(s)
- Marwa Amer
- Medical/Critical Pharmacy Division, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
- College of Medicine and Pharmacy, Alfaisal University, Riyadh, Saudi Arabia
| | - Morten Hylander Møller
- Department of Intensive Care, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
- Guidelines in Intensive Care Medicine, Development and Evaluation (GUIDE) Group, The Research Institute of St. Joe's, Hamilton, Canada
| | - Mohammed Alshahrani
- Department of Emergency and Critical Care, King Fahd Hospital of the University, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Yahya Shehabi
- School of Clinical Sciences, Monash University, Clayton, Victoria, Australia
- Clinical School of Medicine, University of New South Wales, Randwick Campus, New South Wales, Australia
| | - Yaseen M Arabi
- Intensive Care Department, Ministry of National Guard Health Affairs, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Fayez Alshamsi
- Department of Internal Medicine, College of Medicine and Health Sciences, United Arab Emirates University, Alain, United Arab Emirates
| | - Martin Ingi Sigurðsson
- Faculty of Medicine, University of Iceland, Reykjavík, Iceland
- Division of Anaesthesia and Intensive Care Medicine, Landspitali-The National University Hospital of Iceland, Reykjavík, Iceland
| | - Marius Rehn
- Division of Prehospital Services, Air Ambulance Department, Oslo University Hospital, Oslo, Norway
- The Norwegian Air Ambulance Foundation, Oslo, Norway
- Faculty of Health Sciences, University of Stavanger, Stavanger, Norway
| | - Michelle S Chew
- Department of Anaesthesia and Intensive Care, Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
| | | | - Kimberley Lewis
- Division of Critical Care, Department of Medicine, McMaster University, Hamilton, Canada
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Canada
| | - Faisal A Al-Suwaidan
- Division of Neurology, Department of Medicine, Security Forces Hospital, Riyadh, Saudi Arabia
- Neurology Clinical Lead, Ministry of Health, Riyadh, Saudi Arabia
- College of Medicine, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia
- College of Medicine, Dar Al-Uloom University, Riyadh, Saudi Arabia
| | - Hasan M Al-Dorzi
- Intensive Care Department, Ministry of National Guard Health Affairs, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Abdulrahman Al-Fares
- Department of Anesthesia, Critical Care Medicine and Pain Medicine, Al-Amiri Hospital, Minister of Health, Kuwait City, Kuwait
- Kuwait Extracorporeal Life Support Program, Al-Amiri Center for Advance Respiratory and Cardiac Failure, Ministry of Health, Kuwait City, Kuwait
| | - Naif Alsadoon
- Alshaya International Trading Company, Riyadh, Saudi Arabia
| | - Carolyn M Bell
- Medical University of South Carolina Hospital Authority, Charleston, South Carolina, USA
- Medical University of South Carolina College of Pharmacy, Charleston, South Carolina, USA
| | | | - Rachael Parke
- School of Nursing University of Auckland, Auckland, New Zealand
- Cardiothoracic and Vascular Intensive Care Unit, Auckland City Hospital, Auckland, New Zealand
| | - Sangeeta Mehta
- Department of Medicine, Mount Sinai Hospital; Interdepartmental Division of Intensive Care Medicine, Toronto, Canada
| | - Paul E Wischmeyer
- Deptartments of Anesthesiology and Surgery, Duke University School of Medicine, Durham, North Carolina, USA
| | - Awad Al-Omari
- Critical Care Department, Dr Sulaiman Al-Habib Medical Group, Riyadh, Saudi Arabia
| | - Klaus T Olkkola
- Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Waleed Alhazzani
- Guidelines in Intensive Care Medicine, Development and Evaluation (GUIDE) Group, The Research Institute of St. Joe's, Hamilton, Canada
- Division of Critical Care, Department of Medicine, McMaster University, Hamilton, Canada
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Canada
- Department of Critical Care, College of Medicine, King Saud University, Riyadh, Saudi Arabia
- Scientific Research Center, Directorate General of Armed Forces Medical Services, Riyadh, Saudi Arabia
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4
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Amer M, Hylander Møller M, Alshahrani M, Shehabi Y, Arabi YM, Alshamsi F, Ingi Sigurðsson M, Rehn M, Chew MS, Kalliomäki ML, Lewis K, Al-Suwaidan FA, Al-Dorzi HM, Al-Fares A, Alsadoon N, Bell CM, Groth CM, Parke R, Mehta S, Wischmeyer PE, Al-Omari A, Olkkola KT, Alhazzani W. Ketamine Analgo-sedation for Mechanically Ventilated Critically Ill Adults: A Rapid Practice Guideline from the Saudi Critical Care Society and the Scandinavian Society of Anesthesiology and Intensive Care Medicine. Anesth Analg 2024:00000539-990000000-00925. [PMID: 39207913 DOI: 10.1213/ane.0000000000007173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/04/2024]
Abstract
BACKGROUND This Rapid Practice Guideline (RPG) aimed to provide evidence‑based recommendations for ketamine analgo-sedation (monotherapy and adjunct) versus non-ketamine sedatives or usual care in adult intensive care unit (ICU) patients on invasive mechanical ventilation (iMV) and to identify knowledge gaps for future research. METHODS The RPG panel comprised 23 multinational multidisciplinary panelists, including a patient representative. An up-to-date systematic review and meta-analysis constituted the evidence base. The Grading Recommendations, Assessment, Development, and Evaluation approach, and the evidence-to-decision framework were used to assess the certainty of evidence and to move from evidence to decision/recommendation. The panel provided input on the balance of the desirable and undesirable effects, certainty of evidence, patients' values and preferences, costs, resources, equity, feasibility, acceptability, and research priorities. RESULTS Data from 17 randomized clinical trials (n=898) and 9 observational studies (n=1934) were included. There was considerable uncertainty about the desirable and undesirable effects of ketamine monotherapy for analgo-sedation. The evidence was very low certainty and downgraded for risk of bias, indirectness, and inconsistency. Uncertainty or variability in values and preferences were identified. Costs, resources, equity, and acceptability were considered varied. Adjunctive ketamine therapy had no effect on mortality (within 28 days) (relative risk [RR] 0.99; 95% confidence interval [CI] 0.76 to 1.27; low certainty), and may slightly reduce iMV duration (days) (mean difference [MD] -0.05 days; 95% CI -0.07 to -0.03; low certainty), and uncertain effect on the cumulative dose of opioids (mcg/kg/h morphine equivalent) (MD -11.6; 95% CI -20.4 to -2.7; very low certainty). Uncertain desirable effects (cumulative dose of sedatives and vasopressors) and undesirable effects (adverse event rate, delirium, arrhythmia, hepatotoxicity, hypersalivation, use of physical restraints) were also identified. A possibility of important uncertainty or variability in patient-important outcomes led to a balanced effect that favored neither the intervention nor the comparison. Cost, resources, and equity were considered varied. CONCLUSION The RPG panel provided two conditional recommendations and suggested (1) against using ketamine as monotherapy analgo-sedation in critically ill adults on iMV when other analgo-sedatives are available; and (2) using ketamine as an adjunct to non-ketamine usual care sedatives (e.g., opioids, propofol, dexmedetomidine) or continuing with non-ketamine usual care sedatives alone. Large-scale trials should provide additional evidence.
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Affiliation(s)
- Marwa Amer
- Medical/Critical Pharmacy Division, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
- College of Medicine and Pharmacy, Alfaisal University, Riyadh, Saudi Arabia
| | - Morten Hylander Møller
- Department of Intensive Care, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
- Guidelines in Intensive Care Medicine, Development and Evaluation (GUIDE) Group, The Research Institute of St. Joe's, Hamilton, Canada
| | - Mohammed Alshahrani
- Department of Emergency and Critical Care, King Fahd Hospital of the University, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Yahya Shehabi
- School of Clinical Sciences, Monash University, Clayton Campus, Victoria
- Clinical School of Medicine, University of New South Wales, Randwick Campus, New South Wales, Australia
| | - Yaseen M Arabi
- Intensive Care Department, Ministry of National Guard Health Affairs, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Fayez Alshamsi
- Department of Internal Medicine, College of Medicine and Health Sciences, United Arab Emirates University, Alain, United Arab Emirates
| | - Martin Ingi Sigurðsson
- Faculty of Medicine, University of Iceland, Iceland
- Division of Anaesthesia and Intensive Care Medicine, Landspitali-The National University Hospital of Iceland, Iceland
| | - Marius Rehn
- Division of Prehospital Services, Air Ambulance Department, Oslo University Hospital, Oslo, Norway
- The Norwegian Air Ambulance Foundation, Oslo, Norway
- Faculty of Health Sciences, University of Stavanger, Stavanger, Norway
| | - Michelle S Chew
- Department of Anaesthesia and Intensive Care, Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
| | | | - Kimberley Lewis
- Division of Critical Care, Department of Medicine, McMaster University, Hamilton, Canada
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Canada
| | - Faisal A Al-Suwaidan
- Division of Neurology, Department of Medicine, Security Forces Hospital, Riyadh, Saudi Arabia
- Neurology Clinical Lead, Ministry of Health, Saudi Arabia
- College of Medicine, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia
- College of Medicine, Dar Al-Uloom University, Riyadh, Saudi Arabia
| | - Hasan M Al-Dorzi
- Intensive Care Department, Ministry of National Guard Health Affairs, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Abdulrahman Al-Fares
- Department of Anesthesia, Critical Care Medicine and Pain Medicine, Al-Amiri Hospital, Minister of Health, Kuwait City, Kuwait
- Kuwait Extracorporeal Life Support Program, Al-Amiri Center for Advance Respiratory and Cardiac Failure, Ministry of Health, Kuwait City, Kuwait
| | - Naif Alsadoon
- Alshaya International Trading Company, Riyadh, Saudi Arabia
| | - Carolyn M Bell
- Medical University of South Carolina Hospital Authority, Charleston, SC
- Medical University of South Carolina College of Pharmacy, Charleston, SC
| | | | - Rachael Parke
- School of Nursing University of Auckland, New Zealand
- Cardiothoracic and Vascular Intensive Care Unit, Auckland City Hospital, Auckland, New Zealand
| | - Sangeeta Mehta
- Dept. of Medicine, Mount Sinai Hospital; Interdepartmental Division of Intensive Care Medicine, Toronto, Canada
| | - Paul E Wischmeyer
- Deptartments of Anesthesiology and Surgery, Duke University School of Medicine, Durham, NC
| | - Awad Al-Omari
- Dr Sulaiman Al-Habib Medical Group, Critical Care Department, Riyadh, Saudi Arabia
| | - Klaus T Olkkola
- Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Waleed Alhazzani
- Guidelines in Intensive Care Medicine, Development and Evaluation (GUIDE) Group, The Research Institute of St. Joe's, Hamilton, Canada
- Division of Critical Care, Department of Medicine, McMaster University, Hamilton, Canada
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Canada
- Department of Critical Care, College of Medicine, King Saud University, Riyadh, Saudi Arabia
- Scientific Research Center, Directorate General of Armed Forces Medical Services, Riyadh, Saudi Arabia
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Royce-Nagel G, Jarzebowski M, Wongsripuemtet P, Krishnamoorthy V, Fuller M, Ohnuma T, Treggiari M, Yaport M, Cobert J, Garrigan E, Bartz R, Raghunathan K. Use of Early Ketamine Sedation and Association With Clinical and Cost Outcomes Among Mechanically Ventilated Patients With COVID-19: A Retrospective Cohort Study. Crit Care Explor 2024; 6:e1105. [PMID: 38904975 PMCID: PMC11196078 DOI: 10.1097/cce.0000000000001105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/22/2024] Open
Abstract
OBJECTIVES To describe the utilization of early ketamine use among patients mechanically ventilated for COVID-19, and examine associations with in-hospital mortality and other clinical outcomes. DESIGN Retrospective cohort study. SETTING Six hundred ten hospitals contributing data to the Premier Healthcare Database between April 2020 and June 2021. PATIENTS Adults with COVID-19 and greater than or equal to 2 consecutive days of mechanical ventilation within 5 days of hospitalization. INTERVENTION The exposures were early ketamine use initiated within 2 days of intubation and continued for greater than 1 day. MEASUREMENTS Primary was hospital mortality. Secondary outcomes included length of stay (LOS) in the hospital and ICUs, ventilator days, vasopressor days, renal replacement therapy (RRT), and total hospital cost. The propensity score matching analysis was used to adjust for confounders. MAIN RESULTS Among 42,954 patients, 1,423 (3.3%) were exposed to early ketamine use. After propensity score matching including 1,390 patients in each group, recipients of ketamine infusions were associated with higher hospital mortality (52.5% vs. 45.9%, risk ratio: 1.14, [1.06-1.23]), longer median ICU stay (13 vs. 12 d, mean ratio [MR]: 1.15 [1.08-1.23]), and longer ventilator days (12 vs. 11 d, MR: 1.19 [1.12-1.27]). There were no associations for hospital LOS (17 [10-27] vs. 17 [9-28], MR: 1.05 [0.99-1.12]), vasopressor days (4 vs. 4, MR: 1.04 [0.95-1.14]), and RRT (22.9% vs. 21.7%, RR: 1.05 [0.92-1.21]). Total hospital cost was higher (median $72,481 vs. $65,584, MR: 1.11 [1.05-1.19]). CONCLUSIONS In a diverse sample of U.S. hospitals, about one in 30 patients mechanically ventilated with COVID-19 received ketamine infusions. Early ketamine may have an association with higher hospital mortality, increased total cost, ICU stay, and ventilator days, but no associations for hospital LOS, vasopressor days, and RRT. However, confounding by the severity of illness might occur due to higher extracorporeal membrane oxygenation and RRT use in the ketamine group. Further randomized trials are needed to better understand the role of ketamine infusions in the management of critically ill patients.
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Affiliation(s)
- Galen Royce-Nagel
- Critical Care and Perioperative Population Health Research (CAPER) Unit, Department of Anesthesiology, Duke University, Durham, NC
- Department of Anesthesiology, Duke University School of Medicine, Durham, NC
| | - Mary Jarzebowski
- Department of Anesthesiology, University of Michigan, Ann Arbor, MI
| | - Pattrapun Wongsripuemtet
- Critical Care and Perioperative Population Health Research (CAPER) Unit, Department of Anesthesiology, Duke University, Durham, NC
- Department of Anesthesiology, Faculty of Medicine, Siriraj Hospital, Bangkok, Thailand
| | - Vijay Krishnamoorthy
- Critical Care and Perioperative Population Health Research (CAPER) Unit, Department of Anesthesiology, Duke University, Durham, NC
- Department of Anesthesiology, Duke University School of Medicine, Durham, NC
| | - Matthew Fuller
- Critical Care and Perioperative Population Health Research (CAPER) Unit, Department of Anesthesiology, Duke University, Durham, NC
- Department of Anesthesiology, Duke University School of Medicine, Durham, NC
| | - Tetsu Ohnuma
- Critical Care and Perioperative Population Health Research (CAPER) Unit, Department of Anesthesiology, Duke University, Durham, NC
- Department of Anesthesiology, Duke University School of Medicine, Durham, NC
| | - Miriam Treggiari
- Critical Care and Perioperative Population Health Research (CAPER) Unit, Department of Anesthesiology, Duke University, Durham, NC
- Department of Anesthesiology, Duke University School of Medicine, Durham, NC
| | - Miguel Yaport
- Critical Care and Perioperative Population Health Research (CAPER) Unit, Department of Anesthesiology, Duke University, Durham, NC
- Department of Anesthesiology, Duke University School of Medicine, Durham, NC
| | - Julien Cobert
- Department of Anesthesiology, University of California, San Francisco, CA
| | - Ethan Garrigan
- Critical Care and Perioperative Population Health Research (CAPER) Unit, Department of Anesthesiology, Duke University, Durham, NC
- Department of Anesthesiology, Duke University School of Medicine, Durham, NC
| | - Raquel Bartz
- Department of Anesthesiology, Brigham and Women’s Hospital, Boston, MA
| | - Karthik Raghunathan
- Critical Care and Perioperative Population Health Research (CAPER) Unit, Department of Anesthesiology, Duke University, Durham, NC
- Department of Anesthesiology, Duke University School of Medicine, Durham, NC
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6
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Wendel-Garcia PD, Andermatt R, Bode C, David S, Stahl K. "Dosis sola facit venenum"-Evidence for causality in the association between ketamine and cholestatic liver injury. Hepatol Int 2024; 18:1056-1057. [PMID: 38472608 PMCID: PMC11126426 DOI: 10.1007/s12072-024-10646-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Accepted: 01/12/2024] [Indexed: 03/14/2024]
Affiliation(s)
| | - Rea Andermatt
- Institute of Intensive Care Medicine, University Hospital Zurich, Zurich, Switzerland
| | - Christian Bode
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany
| | - Sascha David
- Institute of Intensive Care Medicine, University Hospital Zurich, Zurich, Switzerland
- Department of Nephrology, Hannover Medical School, Hannover, Germany
| | - Klaus Stahl
- Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Carl-Neuberg Straße 1, 30163, Hannover, Germany.
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7
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Phan B, Agyemang A, Klein W, Thapamagar SB. Continuous Infusion of Ketamine in Mechanically Ventilated Patients with SARS-CoV-2. Crit Care Res Pract 2024; 2024:7765932. [PMID: 38766546 PMCID: PMC11101250 DOI: 10.1155/2024/7765932] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2023] [Revised: 04/22/2024] [Accepted: 04/27/2024] [Indexed: 05/22/2024] Open
Abstract
Background Widespread drug shortages led to higher utilization of ketamine in our intensive care unit, especially among patients with SARS-CoV-2. Objectives To evaluate the impact of continuous infusion of ketamine on vasopressor requirements in patients with SARS-CoV-2. Method This was a single-center, retrospective, cohort study comparing mechanically ventilated (MV), adult patients with SARS-CoV-2 receiving either propofol or ketamine for at least 72 hours. Results 84 patients (mean age of 61-year-old, 68% male) were analyzed. 31 patients received ketamine, and 53 patients received propofol. Mean vasopressor doses were not significantly different between ketamine and propofol groups at prespecified timepoints. However, mean arterial pressures (MAP) were higher in the ketamine group at 24 h, 48 h, and 96 h postsedative initiation. The median opioid infusion requirements were 3 vs. 12.5 mg/hr (p < 0.0001) for ketamine and propofol groups, respectively. Comparing to propofol, C-reactive protein (CRP) values were significantly lower in the ketamine group at 24 h (7.53 vs. 15.9 mg/dL, p=0.03), 48 h (5.23 vs. 14.1 mg/dL, p=0.0083), and 72 h (6.4 vs. 12.1 mg/dL, p=0.0085). Conclusion In patients with SARS-CoV-2 on MV, there was no difference in the vasopressor requirement in patients receiving ketamine compared to propofol. Nevertheless, the use of ketamine was associated with higher MAP, reductions in CRP in select timepoints, and overall lower opioid requirements.
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Affiliation(s)
- Brian Phan
- Department of Pharmacy, Riverside University Health System, Moreno Valley, California, USA
- Department of Internal Medicine, University of California, Riverside School of Medicine, Riverside, California, USA
| | - Afua Agyemang
- Department of Pharmacy, Allegheny General Hospital, Pittsburg, Pennsylvania, USA
| | - Walter Klein
- Department of Internal Medicine, University of California, Riverside School of Medicine, Riverside, California, USA
- Department of Medicine, Riverside University Health System, Moreno Valley, California, USA
- Department of Medicine, Loma Linda University School of Medicine, Loma Linda, California, USA
| | - Suman B. Thapamagar
- Department of Medicine, Riverside University Health System, Moreno Valley, California, USA
- Department of Medicine, Loma Linda University School of Medicine, Loma Linda, California, USA
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8
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Yoo N, Thomas S, Bender M, Cheng XJC. A Case of Hepatotoxicity Induced by Therapeutic Ketamine Use for Sedation. Case Rep Crit Care 2024; 2024:8366034. [PMID: 38505599 PMCID: PMC10950395 DOI: 10.1155/2024/8366034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Revised: 01/23/2024] [Accepted: 02/19/2024] [Indexed: 03/21/2024] Open
Abstract
Ketamine, initially developed as an anesthetic, has shown versatility in medical applications, including pain management, treatment-resistant depression, and sedation in the intensive care unit (ICU). While generally well-tolerated, long-term use at high doses raises concerns about potential toxicities, particularly in the liver. We present a case of a 27-year-old female with a complex medical history who received ketamine infusion for ICU sedation and experienced a sudden rise in liver function tests (LFTs), indicating possible ketamine-induced liver injury (KILI). The patient's liver function normalized after ketamine discontinuation. KILI is infrequent with short-term ketamine use, but emerging case reports suggest it may be associated with chronic or intermittent exposure. The underlying mechanisms for KILI are not fully understood but may involve the accumulation of ketamine metabolites, causing direct toxic effects on the liver. As ketamine's use expands, especially in critical care settings, clinicians should be vigilant for the potential development of KILI. Further research is needed to better understand its risk factors and mechanisms, as early detection and management of KILI are crucial to ensuring patient safety and optimizing ketamine's therapeutic benefits.
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Affiliation(s)
- Noah Yoo
- NYU Langone Health Long Island, Mineola, NY, USA
| | - Sarun Thomas
- NYU Langone Health Long Island, Mineola, NY, USA
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9
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Vikash F, Vikash S, Ho S, Kotler D, Patel S. Intensive Care Unit-Related Cholangiopathy-Induced Biliary Cast Syndrome Without Liver Transplantation: A Rare Entity. ACG Case Rep J 2024; 11:e01269. [PMID: 38374925 PMCID: PMC10876252 DOI: 10.14309/crj.0000000000001269] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Accepted: 12/22/2023] [Indexed: 02/21/2024] Open
Abstract
The development of biliary cast syndrome (BCS) is very rare, mostly documented in patients with liver transplantation. The etiology of BCS is unknown; however, risk factors include post-liver transplant bile duct injury, ischemia, infection, fasting, parenteral feeding, and increased bile viscosity and gallbladder dysmotility. We present the case of a 41-year-old man who developed BCS secondary to a prolonged intensive care unit course without a liver transplant. This case highlights the importance of monitoring patients with protracted intensive care unit course and abnormal aminotransferases to recognize and timely manage cholangiopathy and BCS-related complications.
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Affiliation(s)
- Fnu Vikash
- Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY
| | - Sindhu Vikash
- Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY
| | - Sammy Ho
- Division of Gastroenterology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY
| | - Donald Kotler
- Division of Gastroenterology, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY
| | - Sunny Patel
- Division of Gastroenterology, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY
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10
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De Tymowski C, Dépret F, Dudoignon E, Moreno N, Zagdanski AM, Hodjat K, Deniau B, Mebazaa A, Legrand M, Mallet V, for the Keta-Cov research group. Ketamine restriction correlates with reduced cholestatic liver injury and improved outcomes in critically ill patients with burn injury. JHEP Rep 2024; 6:100950. [PMID: 38304235 PMCID: PMC10832380 DOI: 10.1016/j.jhepr.2023.100950] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2023] [Accepted: 09/29/2023] [Indexed: 02/03/2024] Open
Abstract
Background & Aims Ketamine-associated cholestatic liver injury is reported in patients with severe burn injury, but its association with patient outcome is unclear. We investigated the relationship between ketamine exposure, cholestatic liver injury, and outcome of critically ill patients with burn injury. Methods In a retrospective study, patients with severe burn injury were analysed across two periods: unrestricted ketamine prescription (ketamine-liberal) and capped ketamine dosage (ketamine-restricted). The primary endpoint was cholestatic liver injury, and the secondary endpoint was 3-month mortality. Binary logistic regression models and the revised electronic causality assessment method were used to measure the strength of associations and causality assessment, respectively. Results Of 279 patients (median age 51 [IQR 31-67] years; 63.1% men; burned surface area 28.5%, IQR 20-45%), 155 (56%) were in the ketamine-liberal group, and 124 (44%) were in the ketamine-restricted group, with comparable clinical characteristics, except for ketamine exposure (median doses 265.0 [IQR 0-8,021] mg and 20 [IQR 0-105] mg, respectively; p <0.001). A dose- and time-dependent relationship was observed between ketamine exposure and cholestatic liver injury. Ketamine restriction was associated with a reduced risk of cholestatic liver injury (adjusted odds ratio 0.16, 95% CI 0.04-0.50; p = 0.003) and with a higher probability of 3-month survival (p = 0.035). The revised electronic causality assessment method indicated that ketamine was probably and possibly the cause of cholestatic liver injury for 14 and 10 patients, respectively. Cholangitis was not observed in the ketamine-restricted group. In propensity-matched patients, the risk of 3-month mortality was higher (adjusted odds ratio 9.92, 95% CI 2.76-39.05; p = 0.001) in patients with cholestatic liver injury and ketamine exposure ≥10,000 mg. Other sedative drugs were not associated with liver and patient outcome. Conclusions In this cohort, ketamine restriction was associated with less cholestatic liver injury and reduced 3-month mortality. Impact and implications In a cohort of 279 critically ill patients with burn injury, ketamine was associated with a risk of liver bile duct toxicity. The risk was found to be dependent on both the dosage and duration of ketamine use. A restriction policy of ketamine prescription was associated with a risk reduction of liver injury and 3-month mortality. These findings have implications for the analgesia and sedation of critically ill patients with ketamine, with higher doses raising safety concerns.
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Affiliation(s)
- Christian De Tymowski
- Université Paris Cité, Paris, France
- Department of Anaesthesiology and Surgical Intensive Care Unit, Groupe Hospitalier Bichat Claude Bernard, DMU PARABOL, Assistance Publique–Hôpitaux de Paris, Paris, France
- Department of Anaesthesiology, Hôpital Louis Mourier, DMU PARABOL, Assistance Publique–Hôpitaux de Paris, Paris, France
- AP-HP.Nord, Groupe Hospitalier Saint Louis Lariboisière, DMU PARABOL, Département d’anesthésie réanimation et centre de traitement des brûlés, Paris, France
- Université Paris Cité, Centre de Recherche sur l’Inflammation, INSERM UMR 1149, CNRS ERL8252, Paris, France
| | - François Dépret
- Université Paris Cité, Paris, France
- AP-HP.Nord, Groupe Hospitalier Saint Louis Lariboisière, DMU PARABOL, Département d’anesthésie réanimation et centre de traitement des brûlés, Paris, France
- Institut National de la Santé et de la Recherche Médicale (INSERM), INSERM UMR-S 942 Mascot, Lariboisière Hospital, Paris, France
- INI-CRCT Network, Nancy, France
- FHU PROMICE, Paris, France
| | - Emmanuel Dudoignon
- Université Paris Cité, Paris, France
- AP-HP.Nord, Groupe Hospitalier Saint Louis Lariboisière, DMU PARABOL, Département d’anesthésie réanimation et centre de traitement des brûlés, Paris, France
- FHU PROMICE, Paris, France
| | - Nabila Moreno
- AP-HP.Nord, Groupe Hospitalier Saint Louis Lariboisière, Laboratoire de Biochimie, Paris, France
| | - Anne-Marie Zagdanski
- AP-HP.Nord, Groupe Hospitalier Saint Louis Lariboisière, Département de radiologie, Paris, France
| | - Kyann Hodjat
- AP-HP.Nord, Groupe Hospitalier Saint Louis Lariboisière, DMU PARABOL, Département d’anesthésie réanimation et centre de traitement des brûlés, Paris, France
| | - Benjamin Deniau
- Université Paris Cité, Paris, France
- AP-HP.Nord, Groupe Hospitalier Saint Louis Lariboisière, DMU PARABOL, Département d’anesthésie réanimation et centre de traitement des brûlés, Paris, France
- Institut National de la Santé et de la Recherche Médicale (INSERM), INSERM UMR-S 942 Mascot, Lariboisière Hospital, Paris, France
- FHU PROMICE, Paris, France
| | - Alexandre Mebazaa
- Université Paris Cité, Paris, France
- AP-HP.Nord, Groupe Hospitalier Saint Louis Lariboisière, DMU PARABOL, Département d’anesthésie réanimation et centre de traitement des brûlés, Paris, France
- Institut National de la Santé et de la Recherche Médicale (INSERM), INSERM UMR-S 942 Mascot, Lariboisière Hospital, Paris, France
- FHU PROMICE, Paris, France
| | - Matthieu Legrand
- INI-CRCT Network, Nancy, France
- Department of Anesthesia and Peri-operative Care, Division of Critical Care Medicine, University of California, San Francisco, CA, USA
| | - Vincent Mallet
- Université Paris Cité, Paris, France
- AP-HP.Nord, Groupe Hospitalier Saint Louis Lariboisière, DMU PARABOL, Département d’anesthésie réanimation et centre de traitement des brûlés, Paris, France
- Assistance Publique–Hôpitaux de Paris (AP-HP), Groupe Hospitalier Cochin Port Royal, DMU Cancérologie et spécialités médico-chirurgicales, Service de Maladie du Foie, Paris, France
| | - for the Keta-Cov research group
- Université Paris Cité, Paris, France
- Department of Anaesthesiology and Surgical Intensive Care Unit, Groupe Hospitalier Bichat Claude Bernard, DMU PARABOL, Assistance Publique–Hôpitaux de Paris, Paris, France
- Department of Anaesthesiology, Hôpital Louis Mourier, DMU PARABOL, Assistance Publique–Hôpitaux de Paris, Paris, France
- AP-HP.Nord, Groupe Hospitalier Saint Louis Lariboisière, DMU PARABOL, Département d’anesthésie réanimation et centre de traitement des brûlés, Paris, France
- Université Paris Cité, Centre de Recherche sur l’Inflammation, INSERM UMR 1149, CNRS ERL8252, Paris, France
- Institut National de la Santé et de la Recherche Médicale (INSERM), INSERM UMR-S 942 Mascot, Lariboisière Hospital, Paris, France
- INI-CRCT Network, Nancy, France
- FHU PROMICE, Paris, France
- AP-HP.Nord, Groupe Hospitalier Saint Louis Lariboisière, Laboratoire de Biochimie, Paris, France
- AP-HP.Nord, Groupe Hospitalier Saint Louis Lariboisière, Département de radiologie, Paris, France
- Department of Anesthesia and Peri-operative Care, Division of Critical Care Medicine, University of California, San Francisco, CA, USA
- Assistance Publique–Hôpitaux de Paris (AP-HP), Groupe Hospitalier Cochin Port Royal, DMU Cancérologie et spécialités médico-chirurgicales, Service de Maladie du Foie, Paris, France
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11
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Rasheed MA, Ballotin VR, Bigarella LG, Soldera J. Post-COVID-19 cholangiopathy: Systematic review. World J Methodol 2023; 13:296-322. [PMID: 37771872 PMCID: PMC10523251 DOI: 10.5662/wjm.v13.i4.296] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2023] [Revised: 06/07/2023] [Accepted: 08/23/2023] [Indexed: 09/20/2023] Open
Abstract
BACKGROUND The coronavirus disease 2019 (COVID-19) pandemic has had a profound impact on global health, primarily characterized by severe respiratory illness. However, emerging evidence suggests that COVID-19 can also lead to secondary sclerosing cholangitis (SC), referred to as post-COVID-19 cholangiopathy. AIM To synthesize currently reported cases to assess the current state of knowledge on post-COVID-19 cholangiopathy. METHODS Medical Subject Headings and Health Sciences Descriptors were used to retrieve relevant studies, which were combined using Boolean operators. Searches were conducted on electronic databases including Scopus, Web of Science, and MEDLINE (PubMed). Studies published in English, Spanish, or Portuguese were included, with no restrictions on the publication date. Additionally, the reference lists of retrieved studies were manually searched. Simple descriptive analyses were used to summarize the results. Then the data were extracted and assessed based on Reference Citation Analysis (https://www.referencecitationanalysis.com/). RESULTS The initial search yielded a total of 192 articles. After screening, 85 articles were excluded due to duplication, leaving 107 articles for further review. Of these, 63 full-length articles met the inclusion criteria and were included in the analyses. Most of the patients were male and exhibited elevated liver function tests (93.8%). Magnetic resonance imaging revealed duct thickening with contrast enhancement (47.7%), as well as beading of the intrahepatic ducts (45.7%) with peribiliary contrast enhancement on diffusion (28.7%). Liver biopsy results confirmed SC in most cases (74.4%). Sixteen patients underwent liver transplantation, with three experiencing successful outcomes. CONCLUSION Post-COVID-19 cholangiopathy is a serious condition that is expected to become increasingly concerning in the coming years, particularly considering long COVID syndromes. Although liver transplantation has been proposed as a potential treatment option, more research is necessary to establish its efficacy and explore other potential treatments.
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Affiliation(s)
| | | | | | - Jonathan Soldera
- Acute Medicine, University of South Wales, Cardiff CF37 1DL, United Kingdom
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12
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Bartoli A, Cursaro C, Seferi H, Andreone P. Secondary Sclerosing Cholangitis After SARS-CoV2: ICU Ketamine Use or Virus-Specific Biliary Tropism and Injury in the Context of Biliary Ischemia in Critically Ill Patients? Hepat Med 2023; 15:93-112. [PMID: 37547355 PMCID: PMC10404108 DOI: 10.2147/hmer.s384220] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Accepted: 07/12/2023] [Indexed: 08/08/2023] Open
Abstract
Purpose From the beginning of the Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV2) pandemic, different cases of a cholangiopathy with features of secondary sclerosing cholangitis in critically ill patients (SSC-CIP) have been reported. Patients developing it are generally recovering from severe Coronavirus disease 19 (COVID-19) and required intensive care unit (ICU) admission and mechanical ventilation. Many of them have been administered with ketamine during their ICU stay. The pathogenesis of this novel disease is still debated, and, since prognosis is poor, efforts are needed in order to better understand it. Patients and Methods In this review, we focused our attention on COVID-19 SSC clinical, imaging, and histology findings in order to clarify the different pathogenetic options, particularly in regard of the ischemic-direct viral damage and ketamine-related theories, beginning with a recapitulation of SSC-CIP and ketamine-induced cholangiopathy in abusers. The research has been conducted using PubMed and Google Scholar databases. Key-words were "Secondary Sclerosing Cholangiopathy", "SSC-CIP", "Secondary Sclerosing Cholangiopathy in critically ill patients", "Ketamine and cholangiopathy", "Ketamine abusers and liver disease", "Ketamine-related cholangiopathy", "SARS-CoV2 infection and liver disease", "post Covid-19 secondary sclerosing cholangitis", "Covid-19 cholangiopathy". Results Many authors, based on the clinical, histological, imaging, and prognostic features of the disease, have pointed out the similarities between post COVID-19 SSC and SSC-CIP; however, peculiar features in the former were not previously observed. Therefore, a direct viral cytopathic action and SARS-CoV2-related coagulopathy are considered the most likely causes. On the other hand, ketamine, with the available data, cannot be surely linked as the main determinant cause of cholangiopathy. Moreover, ketamine-induced cholangitis (KIC) presentation is different from post COVID-19 SSC. Its role as a cofactor precipitating the disease cannot be ruled out. Conclusion Post COVID-19 SSC is a rare clinical entity following severe COVID-19 disease. The most accepted theory is that a sum of different insults determines the disease: biliary ischemia, direct viral damage, toxic bile, possibly worsened by ketamine and hyperinflammation due to the cytokine storm. Given the severe prognosis of the disease, with persistent cholangiopathy, organ failure, and orthotopic liver transplantation (OLT), further study on this novel clinical entity is needed.
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Affiliation(s)
- Alessandra Bartoli
- Division of Internal Medicine and Metabolism, Department of Internal Medicine, Ospedale Civile di Baggiovara, University of Modena and Reggio Emilia, Modena, Italy
- Post Graduate School of Allergy and Clinical Immunology, Department of Internal Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | - Carmela Cursaro
- Division of Internal Medicine and Metabolism, Department of Internal Medicine, Ospedale Civile di Baggiovara, University of Modena and Reggio Emilia, Modena, Italy
| | - Hajrie Seferi
- Division of Internal Medicine and Metabolism, Department of Internal Medicine, Ospedale Civile di Baggiovara, University of Modena and Reggio Emilia, Modena, Italy
| | - Pietro Andreone
- Chief of Division of Internal Medicine and metabolism, Department of Internal Medicine, University Hospital of Modena, Modena, Italy
- Chief of Post Graduate School of Allergy and Clinical Immunology, Department of Internal Medicine, University of Modena and Reggio Emilia, Modena, Italy
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13
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Zippi M, Fiorino S, Hong W, de Biase D, Gallo CG, Grottesi A, Centorame A, Crispino P. Post-COVID-19 cholangiopathy: A systematic review. World J Meta-Anal 2023; 11:229-237. [DOI: 10.13105/wjma.v11.i5.229] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/28/2023] Open
Abstract
BACKGROUND The recent and still ongoing pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entailed various long-term complications, including post-infectious cholangiopathy.
AIM To identify the available studies concerning post-coronavirus disease 2019 (COVID-19) cholangiopathy.
METHODS An extensive bibliographical search was carried out in PubMed and in Cochrane Library to identify the articles (retrospective and prospective studies, cohort studies, case series and case reports) published between January 1, 2020 and August 22, 2022, using both MeSH terms and free-language keywords: cholangiopathy; COVID-19; post-COVID-19 cholangiopathy; SARS-CoV-2.
RESULTS Thirteen studies fulfilled the inclusion criteria, which included 64 patients suffering from this condition. The patients were male in 82.8% of cases. Liver transplant was executed in 6 patients and scheduled in 7 patients, while 2 patients refused the surgical approach. Therefore in 23.4% of the cases, performing this procedure appeared to be necessary.
CONCLUSION This review has revealed that generally the involvement of the liver in the course of SARS-CoV-2 infection is mild and transient, inducing cholestasis of cholangiocytes but can also be severe enough to cause organ failure in some cases.
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Affiliation(s)
- Maddalena Zippi
- Unit of Gastroenterology and Digestive Endoscopy, Sandro Pertini Hospital, Rome 00157, Italy
| | - Sirio Fiorino
- Unit of Internal Medicine, Maggiore Hospital, Local Health Unit of Bologna, Bologna 40133, Italy
| | - Wandong Hong
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China
| | - Dario de Biase
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna 40126, Italy
| | | | - Alfonso Grottesi
- Unit of General Surgery, Sandro Pertini Hospital, Rome 00157, Italy
| | | | - Pietro Crispino
- Unit of Emergency Medicine, Santa Maria Goretti Hospital, Latina 04100, Italy
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14
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Schep LJ, Slaughter RJ, Watts M, Mackenzie E, Gee P. The clinical toxicology of ketamine. Clin Toxicol (Phila) 2023:1-14. [PMID: 37267048 DOI: 10.1080/15563650.2023.2212125] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Revised: 05/01/2023] [Accepted: 05/04/2023] [Indexed: 06/04/2023]
Abstract
INTRODUCTION Ketamine is a pharmaceutical drug possessing both analgesic and anaesthetic properties. As an anaesthetic, it induces anaesthesia by producing analgesia with a state of altered consciousness while maintaining airway tone, respiratory drive, and hemodynamic stability. At lower doses, it has psychoactive properties and has gained popularity as a recreational drug. OBJECTIVES To review the epidemiology, mechanisms of toxicity, pharmacokinetics, clinical features, diagnosis and management of ketamine toxicity. METHODS Both OVID MEDLINE (January 1950-April 2023) and Web of Science (1900-April 2023) databases were searched using the term "ketamine" in combination with the keywords "pharmacokinetics", "kinetics", "poisoning", "poison", "toxicity", "ingestion", "adverse effects", "overdose", and "intoxication". Furthermore, bibliographies of identified articles were screened for additional relevant studies. These searches produced 5,268 non-duplicate citations; 185 articles (case reports, case series, pharmacokinetic studies, animal studies pertinent to pharmacology, and reviews) were considered relevant. Those excluded were other animal investigations, therapeutic human clinical investigations, commentaries, editorials, cases with no clinical relevance and post-mortem investigations. EPIDEMIOLOGY Following its introduction into medical practice in the early 1970s, ketamine has become a popular recreational drug. Its use has become associated with the dance culture, electronic and dubstep dance events. MECHANISM OF ACTION Ketamine acts primarily as a non-competitive antagonist on the glutamate N-methyl-D-aspartate receptor, causing the loss of responsiveness that is associated with clinical ketamine dissociative anaesthesia. PHARMACOKINETICS Absorption of ketamine is rapid though the rate of uptake and bioavailability is determined by the route of exposure. Ketamine is metabolized extensively in the liver. Initially, both isomers are metabolized to their major active metabolite, norketamine, by CYP2B6, CYP3A4 and CYP2C9 isoforms. The hydroxylation of the cyclohexan-1-one ring of norketamine to the three positional isomers of hydroxynorketamine occurs by CYP2B6 and CYP2A6. The dehydronorketamine metabolite occurs either by direct dehydrogenation from norketamine via CYP2B6 metabolism or non-enzymatic dehydration of hydroxynorketamine. Norketamine, the dehydronorketamine isomers, and hydroxynorketamine have pharmacological activity. The elimination of ketamine is primarily by the kidneys, though unchanged ketamine accounts for only a small percentage in the urine. The half-life of ketamine in humans is between 1.5 and 5 h. CLINICAL FEATURES Acute adverse effects following recreational use are diverse and can include impaired consciousness, dizziness, irrational behaviour, hallucinations, abdominal pain and vomiting. Chronic use can result in impaired verbal information processing, cystitis and cholangiopathy. DIAGNOSIS The diagnosis of acute ketamine intoxication is typically made on the basis of the patient's history, clinical features, such as vomiting, sialorrhea, or laryngospasm, along with neuropsychiatric features. Chronic effects of ketamine toxicity can result in cholangiopathy and cystitis, which can be confirmed by endoscopic retrograde cholangiopancreatography and cystoscopy, respectively. MANAGEMENT Treatment of acute clinical toxicity is predominantly supportive with empiric management of specific adverse effects. Benzodiazepines are recommended as initial treatment to reduce agitation, excess neuromuscular activity and blood pressure. Management of cystitis is multidisciplinary and multi-tiered, following a stepwise approach of pharmacotherapy and surgery. Management of cholangiopathy may require pain management and, where necessary, biliary stenting to alleviate obstructions. Chronic effects of ketamine toxicity are typically reversible, with management focusing on abstinence. CONCLUSIONS Ketamine is a dissociative drug employed predominantly in emergency medicine; it has also become popular as a recreational drug. Its recreational use can result in acute neuropsychiatric effects, whereas chronic use can result in cystitis and cholangiopathy.
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Affiliation(s)
- Leo J Schep
- Professional Practice Fellow, Department of Biochemistry, University of Otago, Dunedin, New Zealand
| | | | - Martin Watts
- Emergency Department, Southland Hospital, Invercargill, New Zealand
| | - Elliot Mackenzie
- Obstetrics and Gynaecology, Women and Childrens Health. Dunedin Public Hospital, Dunedin, New Zealand
| | - Paul Gee
- National Poisons Centre, University of Otago, Dunedin, New Zealand
- Emergency Department, Christchurch Hospital, Christchurch, New Zealand
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15
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Toxicity patterns associated with chronic ketamine exposure. TOXICOLOGIE ANALYTIQUE ET CLINIQUE 2023. [DOI: 10.1016/j.toxac.2023.02.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/08/2023]
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16
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Henrie J, Gerard L, Declerfayt C, Lejeune A, Baldin P, Robert A, Laterre PF, Hantson P. Profile of liver cholestatic biomarkers following prolonged ketamine administration in patients with COVID-19. BMC Anesthesiol 2023; 23:44. [PMID: 36750971 PMCID: PMC9902832 DOI: 10.1186/s12871-023-02006-2] [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] [Received: 05/17/2022] [Accepted: 02/02/2023] [Indexed: 02/09/2023] Open
Abstract
BACKGROUND To investigate the possible influence of prolonged ketamine (K) or esketamine (ESK) infusion on the profile of liver cholestatic biomarkers in patients with COVID-19 infection. METHODS A retrospective analysis was performed on 135 patients with COVID-19 related ARDS who received prolonged K or ESK infusion. They were compared to 15 COVID-19 ICU patients who did not receive K/ESK while being mechanically ventilated and 108 COVID-19 patients who did not receive mechanical ventilation nor K/ESK. The profile of the liver function tests was analysed in the groups. RESULTS Peak values of ALP, GGT and bilirubin were higher in the K/ESK group, but not for AST and ALT. Peak values of ALP were significantly higher among patients who underwent mechanical ventilation and who received K/ESK, compared with mechanically ventilated patients who did not receive K/ESK. There was a correlation between these peak values and the cumulative dose and duration of K/ESK therapy. CONCLUSIONS Based on the observations of biliary anomalies in chronic ketamine abusers, prolonged exposure to ketamine sedation during mechanical ventilation may also be involved, in addition to viral infection causing secondary sclerosing cholangitis. The safety of prolonged ketamine sedation on the biliary tract requires further investigations.
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Affiliation(s)
- Julie Henrie
- grid.7942.80000 0001 2294 713XDepartment of Intensive Care, Cliniques St-Luc, Université Catholique de Louvain, Avenue Hippocrate, 10, 1200 Brussels, Belgium
| | - Ludovic Gerard
- grid.7942.80000 0001 2294 713XDepartment of Intensive Care, Cliniques St-Luc, Université Catholique de Louvain, Avenue Hippocrate, 10, 1200 Brussels, Belgium
| | - Caroline Declerfayt
- grid.7942.80000 0001 2294 713XDepartment of Intensive Care, Cliniques St-Luc, Université Catholique de Louvain, Avenue Hippocrate, 10, 1200 Brussels, Belgium
| | - Adrienne Lejeune
- grid.7942.80000 0001 2294 713XDepartment of Intensive Care, Cliniques St-Luc, Université Catholique de Louvain, Avenue Hippocrate, 10, 1200 Brussels, Belgium
| | - Pamela Baldin
- grid.7942.80000 0001 2294 713XDepartment of Pathology, Cliniques St-Luc, Université Catholique de Louvain, 1200 Brussels, Belgium
| | - Arnaud Robert
- grid.7942.80000 0001 2294 713XDepartment of Intensive Care, Cliniques St-Luc, Université Catholique de Louvain, Avenue Hippocrate, 10, 1200 Brussels, Belgium
| | - Pierre-François Laterre
- grid.7942.80000 0001 2294 713XDepartment of Intensive Care, Cliniques St-Luc, Université Catholique de Louvain, Avenue Hippocrate, 10, 1200 Brussels, Belgium
| | - Philippe Hantson
- Department of Intensive Care, Cliniques St-Luc, Université Catholique de Louvain, Avenue Hippocrate, 10, 1200, Brussels, Belgium. .,Louvain Centre for Toxicology and Applied Pharmacology (LTAP), Université Catholique de Louvain, 1200, Brussels, Belgium.
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17
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Zippi M, Fiorino S, Hong W, de Biase D, Gallo CG, Grottesi A, Centorame A, Crispino P. Post-COVID-19 cholangiopathy: A systematic review. World J Meta-Anal 2023; 11:29-37. [DOI: 10.13105/wjma.v11.i1.29] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Revised: 10/13/2022] [Accepted: 11/23/2022] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND The recent and still ongoing pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entailed various long-term complications, including post-infectious cholangiopathy.
AIM To identify the available studies concerning post-coronavirus disease 2019 (COVID-19) cholangiopathy.
METHODS An extensive bibliographical search was carried out in PubMed and in Cochrane Library to identify the articles (retrospective and prospective studies, cohort studies, case series and case reports) published between January 1, 2020 and August 22, 2022, using both MeSH terms and free-language keywords: cholangiopathy; COVID-19; post-COVID-19 cholangiopathy; SARS-CoV-2.
RESULTS Thirteen studies fulfilled the inclusion criteria, which included 64 patients suffering from this condition. The patients were male in 82.8% of cases. Liver transplant was executed in 6 patients and scheduled in 7 patients, while 2 patients refused the surgical approach. Therefore in 23.4% of the cases, performing this procedure appeared to be necessary.
CONCLUSION This review has revealed that generally the involvement of the liver in the course of SARS-CoV-2 infection is mild and transient, inducing cholestasis of cholangiocytes but can also be severe enough to cause organ failure in some cases.
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Affiliation(s)
- Maddalena Zippi
- Unit of Gastroenterology and Digestive Endoscopy, Sandro Pertini Hospital, Rome 00157, Italy
| | - Sirio Fiorino
- Unit of Internal Medicine, Maggiore Hospital, Local Health Unit of Bologna, Bologna 40133, Italy
| | - Wandong Hong
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China
| | - Dario de Biase
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna 40126, Italy
| | | | - Alfonso Grottesi
- Unit of General Surgery, Sandro Pertini Hospital, Rome 00157, Italy
| | | | - Pietro Crispino
- Unit of Emergency Medicine, Santa Maria Goretti Hospital, Latina 04100, Italy
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18
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Sarkis Y, Saleem N, Vuppalanchi R, Gromski M. COVID-Associated Cast-Forming Cholangiopathy: A Commentary on Disease Mechanism, Treatment, and Prognosis. Hepat Med 2023; 15:27-32. [PMID: 37013139 PMCID: PMC10066716 DOI: 10.2147/hmer.s384176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2022] [Accepted: 03/23/2023] [Indexed: 04/05/2023] Open
Abstract
The complete impact of COVID-19 infection continues to develop since the onset of the COVID-19 pandemic. COVID-19 cholangiopathy has been recently described in a subset of patients who recovered from severe COVID-19 infection. The most common phenotype of patients suffering from COVID-19 cholangiopathy had severe infection requiring a stay in the intensive care unit, mechanical ventilation and vasopressor medications. Patients with COVID-cholangiopathy present with severe and prolonged cholestatic liver injury. In cases where biliary cast formation is identified, we defined the entity as "COVID-19 cast-forming cholangiopathy". This subset of COVID-19 cholangiopathy is not well understood and there are no standardized diagnosis or management to this date. The reported clinical outcomes are variable, from resolution of symptoms and liver test abnormalities to liver transplant and death. In this commentary, we discuss the proposed pathophysiology, diagnosis, management, and prognosis of this disease.
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Affiliation(s)
- Yara Sarkis
- Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Nasir Saleem
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Raj Vuppalanchi
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Mark Gromski
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
- Correspondence: Mark Gromski, Gastroenterology and Hepatology Department, Indiana University Hospital, 550 N. University Blvd, Suite 1634, Indianapolis, IN, 46202, USA, Tel +317-944-0925, Fax +317-968-1265, Email
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19
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Schmid S, Kandulski A, Müller-Schilling M. COVID-19 und Lebererkrankungen. DIE GASTROENTEROLOGIE 2023; 18:107-114. [PMCID: PMC9993380 DOI: 10.1007/s11377-023-00680-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 02/02/2023] [Indexed: 01/03/2025]
Abstract
Bis zu 53 % der PatientInnen mit Coronavirus Disease 2019 (COVID-19) weisen eine hepatische Beteiligung auf. Durch die Expression der Hauptzielstruktur für „severe acute respiratory syndrome coronavirus type 2“ (SARS-CoV-2), des Angiotensin-converting-Enzym-2(ACE2)-Rezeptors, auch auf Cholangiozyten, sinusoidalen Endothelzellen und Hepatozyten kann es zu einer direkten Schädigung der Leber kommen. Ferner spielt eine indirekte (nicht durch Rezeptoren vermittelte) Schädigung der Leber im Rahmen von COVID-19 durch eine schwere systemische Inflammation mit Zytokinsturm, hepatischen Thrombosen und einer systemischen Hypoxie eine wichtige Rolle. Bei COVID-19 gelten Leberwerte als wichtige Prädiktoren für die Prognose der PatientInnen. Wichtig ist es hierbei Differenzialdiagnosen für die Leberwerterhöhung, wie andere Virusinfektionen, medikamentös-toxisch induzierte Leberschädigung sowie autoimmune, metabolische und andere Lebererkrankungen, abzuklären. Von hoher klinischer Relevanz für die Behandlung kritisch kranker PatientInnen auf der Intensivstation ist das Krankheitsbild der „secondary sclerosing cholangitis in critically ill patients“ (SSC-CIP). Hierfür sind unter anderem hochdosierte Katecholamine, eine Beatmung mit hohem positivem endexspiratorischem Druck (PEEP) und die extrakorporale Membranoxygenierung (ECMO) Risikofaktoren. Eine frühe Diagnose dieser Erkrankung und Behandlung mittels interventioneller endoskopischer retrograder Cholangiographie (ERC) ist hierbei von entscheidender Bedeutung. Auch sollte eine Lebertransplantation evaluiert werden. Bei einer COVID-19-Erkrankung treten Fälle mit SSC, sog. COVID-SSC, auf. Die COVID-SSC und die SSC-CIP sind im klinischen Phänotyp, Risikofaktoren, Prognose und transplantatfreien Überleben vergleichbar. PatientInnen mit vorbestehender Lebererkrankung haben kein erhöhtes Risiko für eine Infektion mit SARS-CoV‑2, erkranken jedoch schwerer an COVID-19 als PatientInnen ohne Lebervorerkrankungen. Bei PatientInnen mit einer vorbestehenden Leberzirrhose kann eine SARS-CoV-2-Infektion ein akut-auf-chronisches Leberversagen (ACLF) induzieren. Hierbei handelt es sich um ein Krankheitsbild mit einer sehr hohen Mortalität, das im Rahmen einer intensivmedizinischen Behandlung therapiert werden muss.
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Affiliation(s)
- Stephan Schmid
- Klinik und Poliklinik für Innere Medizin 1, Gastroenterologie, Endokrinologie, Infektiologie und Rheumatologie, Universitätsklinikum Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Deutschland
| | - Arne Kandulski
- Klinik und Poliklinik für Innere Medizin 1, Gastroenterologie, Endokrinologie, Infektiologie und Rheumatologie, Universitätsklinikum Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Deutschland
| | - Martina Müller-Schilling
- Klinik und Poliklinik für Innere Medizin 1, Gastroenterologie, Endokrinologie, Infektiologie und Rheumatologie, Universitätsklinikum Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Deutschland
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20
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Polyzogopoulou E, Amoiridou P, Abraham TP, Ventoulis I. Acute liver injury in COVID-19 patients hospitalized in the intensive care unit: Narrative review. World J Gastroenterol 2022; 28:6662-6688. [PMID: 36620339 PMCID: PMC9813941 DOI: 10.3748/wjg.v28.i47.6662] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Revised: 11/14/2022] [Accepted: 12/05/2022] [Indexed: 12/19/2022] Open
Abstract
In recent years, humanity has been confronted with a global pandemic due to coronavirus disease 2019 (COVID-19), which has caused an unprecedented health and economic crisis worldwide. Apart from the respiratory symptoms, which are considered the principal manifestations of COVID-19, it has been recognized that COVID-19 constitutes a systemic inflammatory process affecting multiple organ systems. Across the spectrum of organ involvement in COVID-19, acute liver injury (ALI) has been gradually gaining increasing attention by the international scientific community. COVID-19 associated liver impairment can affect a considerable proportion of COVID-19 patients and seems to correlate with the severity of the disease course. Indeed, COVID-19 patients hospitalized in the intensive care unit (ICU) run a greater risk of developing ALI due to the severity of their clinical condition and in the context of multi-organ failure. The putative pathophysiological mechanisms of COVID-19 induced ALI in ICU patients remain poorly understood and appear to be multifactorial in nature. Several theories have been proposed to explain the occurrence of ALI in the ICU setting, such as hypoperfusion and ischemia due to hemodynamic instability, passive liver congestion as a result of congestive heart failure, ischemia-reperfusion injury, hypoxia due to respiratory failure, mechanical ventilation itself, sepsis and septic shock, cytokine storm, endotheliitis with concomitant coagulopathy, drug-induced liver injury, parenteral nutrition and direct cytopathic viral effect. It should be noted that no specific therapy for COVID-19 induced ALI exists. Therefore, the therapeutic approach lies in preventive measures and is exclusively supportive once ALI ensues. The aim of the current review is to scrutinize the existing evidence on COVID-19 associated ALI in ICU patients, explore its clinical implications, shed light on the underlying pathophysiological mechanisms and propose potential therapeutic approaches. Ongoing research on the particular scientific field will further elucidate the pathophysiology behind ALI and address unresolved issues, in the hope of mitigating the tremendous health consequences imposed by COVID-19 on ICU patients.
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Affiliation(s)
- Effie Polyzogopoulou
- Department of Emergency Medicine, Attikon University Hospital, National and Kapodistrian University of Athens Medical School, Athens 12462, Greece
| | - Pinelopi Amoiridou
- Department of Intensive Care, AHEPA University Hospital, Thessaloniki 54621, Greece
| | - Theodore P Abraham
- Hypertrophic Cardiomyopathy Center of Excellence, University of California, San Francisco, CA 94117, United States
| | - Ioannis Ventoulis
- Department of Occupational Therapy, University of Western Macedonia, Ptolemaida 50200, Greece
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21
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Heucke N, Keitel V. COVID-19-associated cholangiopathy: What is left after the virus has gone? Hepatology 2022; 76:1560-1562. [PMID: 35822670 PMCID: PMC9350171 DOI: 10.1002/hep.32668] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Accepted: 07/01/2022] [Indexed: 12/08/2022]
Affiliation(s)
- Niklas Heucke
- Department of Gastroenterology, Hepatology and Infectious DiseasesUniversity Hospital Magdeburg, Medical Faculty of Otto von Guericke UniversityMagdeburgGermany
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22
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Li P, Liu Y, Cheng Z, Yu X, Li Y. COVID-19-associated liver injury: Clinical characteristics, pathophysiological mechanisms and treatment management. Biomed Pharmacother 2022; 154:113568. [PMID: 36029543 PMCID: PMC9381432 DOI: 10.1016/j.biopha.2022.113568] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Revised: 08/14/2022] [Accepted: 08/15/2022] [Indexed: 02/06/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become a global epidemic and poses a major threat to public health. In addition to COVID-19 manifesting as a respiratory disease, patients with severe disease also have complications in extrapulmonary organs, including liver damage. Abnormal liver function is relatively common in COVID-19 patients; its clinical manifestations can range from an asymptomatic elevation of liver enzymes to decompensated hepatic function, and liver injury is more prevalent in severe and critical patients. Liver injury in COVID-19 patients is a comprehensive effect mediated by multiple factors, including liver damage directly caused by SARS-CoV-2, drug-induced liver damage, hypoxia reperfusion dysfunction, immune stress and inflammatory factor storms. Patients with chronic liver disease (especially alcohol-related liver disease, nonalcoholic fatty liver disease, cirrhosis and hepatocellular carcinoma) are at increased risk of severe disease and death after infection with SARS-CoV-2, and COVID-19 aggravates liver damage in patients with chronic liver disease. This article reviews the latest SARS-CoV-2 reports, focusing on the liver damage caused by COVID-19 and the underlying mechanism, and expounds on the risk, treatment and vaccine safety of SARS-CoV-2 in patients with chronic liver disease and liver transplantation.
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Affiliation(s)
- Penghui Li
- Center for Health Research, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; University of Chinese Academy of Sciences, Beijing, China; Key Laboratory of Stem Cell and Regenerative Medicine, CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China
| | - Ying Liu
- Center for Health Research, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; University of Chinese Academy of Sciences, Beijing, China; Key Laboratory of Stem Cell and Regenerative Medicine, CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China
| | - Ziqi Cheng
- Center for Health Research, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; University of Chinese Academy of Sciences, Beijing, China; Key Laboratory of Stem Cell and Regenerative Medicine, CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China
| | - Xiaorui Yu
- Center for Health Research, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; University of Chinese Academy of Sciences, Beijing, China; Key Laboratory of Stem Cell and Regenerative Medicine, CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China
| | - Yinxiong Li
- Center for Health Research, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; University of Chinese Academy of Sciences, Beijing, China; Key Laboratory of Stem Cell and Regenerative Medicine, CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; State Key Laboratory of Respiratory Disease, Guangzhou, China; China-New Zealand Joint Laboratory on Biomedicine and Health, Guangzhou, China.
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23
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Tanaka S, De Tymowski C, Stern J, Bouzid D, Zappella N, Snauwaert A, Robert T, Lortat-jacob B, Tran-dinh A, Augustin P, Boutten A, Tashk P, Peoc’h K, Meilhac O, Montravers P. Relationship between liver dysfunction, lipoprotein concentration and mortality during sepsis. PLoS One 2022; 17:e0272352. [PMID: 35994439 PMCID: PMC9394828 DOI: 10.1371/journal.pone.0272352] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Accepted: 07/19/2022] [Indexed: 11/18/2022] Open
Abstract
Background
High-density lipoproteins (HDLs) are synthesized by the liver and display endothelioprotective properties, including anti-inflammatory, antiapoptotic, antithrombotic and antioxidant effects. In both septic and chronic liver failure patients, a low HDL cholesterol (HDL-C) concentration is associated with overmortality. Whereas sepsis-associated liver dysfunction is poorly defined, the aim of this study was to characterize the relationship between liver dysfunction, lipoprotein concentrations and mortality in septic patients in the intensive care unit (ICU).
Methods
A prospective observational study was conducted in a university hospital ICU. All consecutive patients admitted for septic shock or sepsis were included. Total cholesterol, HDL-C, low-density lipoprotein-cholesterol (LDL-C), and triglyceride levels were assessed at admission. Sepsis-associated liver dysfunction was defined as a serum bilirubin≥ 2N or aspartate aminotransferase/alanine aminotransferase concentrations ≥ 2N. Short-term and one-year prognostic outcomes were prospectively assessed.
Results
A total of 219 septic patients were included, and 15% of them presented with sepsis-associated liver dysfunction at admission. Low concentrations of lipoproteins were associated with mortality at Day 28 in the overall population. Sepsis-associated liver dysfunction at admission was associated with overmortality. In this subgroup, patients had a lower HDL-C concentration than patients without hepatic dysfunction (HDL-C = 0.31 [0.25, 0.55] mmol/L vs. 0.48 [0.29, 0.73] mmol/L, p = 0.0079) but there was no relationship with the outcome. Interestingly, no correlation was observed between lipoprotein concentrations and liver dysfunction markers.
Conclusion
Sepsis-associated liver dysfunction at ICU admission is strongly associated with overmortality and is associated with a lower HDL-C concentration. However, in this subgroup of patients, HDL-C concentration had no relationship with mortality. Further exploratory studies are needed to better understand the interaction between lipoproteins and liver dysfunction during sepsis.
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Affiliation(s)
- Sébastien Tanaka
- Assistance Publique—Hôpitaux de Paris (AP-HP), Department of Anesthesiology and Critical Care Medicine, Bichat-Claude Bernard Hospital, Paris, France
- Réunion Island University, French Institute of Health and Medical Research (INSERM), Diabetes atherothrombosis Réunion Indian Ocean (DéTROI), CYROI Plateform, Saint-Denis de La Réunion, Saint Denis, France
- * E-mail:
| | - Christian De Tymowski
- Assistance Publique—Hôpitaux de Paris (AP-HP), Department of Anesthesiology and Critical Care Medicine, Bichat-Claude Bernard Hospital, Paris, France
- French Institute of Health and Medical Research (INSERM), Center for Research on Inflammation, Paris, France
- Université de Paris, UFR Paris Nord, Paris, France
| | - Jules Stern
- Assistance Publique—Hôpitaux de Paris (AP-HP), Department of Anesthesiology and Critical Care Medicine, Bichat-Claude Bernard Hospital, Paris, France
| | - Donia Bouzid
- Université de Paris, UFR Paris Nord, Paris, France
- Assistance Publique—Hôpitaux de Paris (AP-HP), Emergency Department, Bichat-Claude Bernard Hospital, Paris, France
- French Institute of Health and Medical Research (INSERM), Infection, Antimicrobials, Modelling, Evolution, Paris, France
| | - Nathalie Zappella
- Assistance Publique—Hôpitaux de Paris (AP-HP), Department of Anesthesiology and Critical Care Medicine, Bichat-Claude Bernard Hospital, Paris, France
| | - Aurélie Snauwaert
- Assistance Publique—Hôpitaux de Paris (AP-HP), Department of Anesthesiology and Critical Care Medicine, Bichat-Claude Bernard Hospital, Paris, France
| | - Tiphaine Robert
- Assistance Publique—Hôpitaux de Paris (AP-HP), Biochemistry Department, Bichat-Claude Bernard Hospital, Paris, France
| | - Brice Lortat-jacob
- Assistance Publique—Hôpitaux de Paris (AP-HP), Department of Anesthesiology and Critical Care Medicine, Bichat-Claude Bernard Hospital, Paris, France
| | - Alexy Tran-dinh
- Assistance Publique—Hôpitaux de Paris (AP-HP), Department of Anesthesiology and Critical Care Medicine, Bichat-Claude Bernard Hospital, Paris, France
- Université de Paris, UFR Paris Nord, Paris, France
- French Institute of Health and Medical Research (INSERM), Laboratory for Vascular Translational Science, Paris France
| | - Pascal Augustin
- Assistance Publique—Hôpitaux de Paris (AP-HP), Department of Anesthesiology and Critical Care Medicine, Bichat-Claude Bernard Hospital, Paris, France
| | - Anne Boutten
- Assistance Publique—Hôpitaux de Paris (AP-HP), Biochemistry Department, Bichat-Claude Bernard Hospital, Paris, France
| | - Parvine Tashk
- Assistance Publique—Hôpitaux de Paris (AP-HP), Department of Anesthesiology and Critical Care Medicine, Bichat-Claude Bernard Hospital, Paris, France
| | - Katell Peoc’h
- French Institute of Health and Medical Research (INSERM), Center for Research on Inflammation, Paris, France
- Université de Paris, UFR Paris Nord, Paris, France
- Assistance Publique—Hôpitaux de Paris (AP-HP), Biochemistry Department, Bichat-Claude Bernard Hospital, Paris, France
| | - Olivier Meilhac
- Réunion Island University, French Institute of Health and Medical Research (INSERM), Diabetes atherothrombosis Réunion Indian Ocean (DéTROI), CYROI Plateform, Saint-Denis de La Réunion, Saint Denis, France
- Réunion Island University-affiliated Hospital, Saint Denis, France
| | - Philippe Montravers
- Assistance Publique—Hôpitaux de Paris (AP-HP), Department of Anesthesiology and Critical Care Medicine, Bichat-Claude Bernard Hospital, Paris, France
- Université de Paris, UFR Paris Nord, Paris, France
- French Institute of Health and Medical Research (INSERM), Physiopathology and Epidemiology of respiratory diseases, Paris, France
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