A multicentre randomized controlled trial of moderate hypothermia to prevent intracranial hypertension in acute liver failure

Bernal, William; Murphy, Nick; Brown, Sarah E.; Whitehouse, Tony; Bjerring, Peter Nissen; Hauerberg, John; Frederiksen, Hans Jørgen; Auzinger, G.; Wendon, Julia; Larsen, Fin Stolze

doi:10.1016/j.jhep.2016.03.003

Cited by 85 publications

(56 citation statements)

References 31 publications

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“…A similar inding was observed in HE patients where reducing their core temperature to 32-33°C was able to decrease levels of circulating TNFα, IL-1β and IL-6 as well as reduce cerebral edema and intracranial pressure [53]. However, a recent report investigating moderate hypothermia (33-34°C) in HE patients from acute liver failure determined that this treatment strategy did litle to reduce increased intracranial pressures or mortality [54]. Therefore, more studies are necessary to determine the clinical potential of therapeutic hypothermia in patients with HE.…”

Section: Pre-clinical Therapies Targeting Inlammationmentioning

confidence: 68%

Neuroinflammatory Signals during Acute and Chronic Liver Diseases

McMillin¹,

DeMorrow²

2017

Mechanisms of Neuroinflammation

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A spectrum of neurological complications can result from acute and chronic liver diseases and is termed hepatic encephalopathy. The precise pathogenic mechanisms by which hepatic encephalopathy occurs is unclear. However, it is commonly accepted that the development of hepatic encephalopathy shares a long-standing relationship with neuroinlammation. This chapter will outline the evidence for a role of neuroinlammation and proinlammatory cytokines in the pathogenesis of hepatic encephalopathy. Furthermore, we will identify the possible circulating factors, released from the liver after damage, that may contribute to the neurological complications of hepatic encephalopathy, including neuroinlammation. Lastly, we discuss the current and experimental treatment options aimed at reducing neuroinlammation for the management of hepatic encephalopathy.

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Section: Pre-clinical Therapies Targeting Inlammationmentioning

confidence: 68%

Neuroinflammatory Signals during Acute and Chronic Liver Diseases

McMillin¹,

DeMorrow²

2017

Mechanisms of Neuroinflammation

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“…Table 6 lists the studies that have described the use of IICPM in ALF [10–14, 16, 21–23, 26–29, 37]. Our study is distinct for several reasons.…”

Section: Discussionmentioning

confidence: 99%

Protocol based invasive intracranial pressure monitoring in acute liver failure: feasibility, safety and impact on management

et al. 2017

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BackgroundAcute liver failure (ALF) may result in elevated intracranial pressure (ICP). While invasive ICP monitoring (IICPM) may have a role in ALF management, these patients are typically coagulopathic and at risk for intracranial hemorrhage (ICH). Contemporary ICP monitoring techniques and coagulopathy reversal strategies may be associated with a lower risk of hemorrhage. Our objective was to evaluate the safety, feasibility, impact on clinical management and outcomes associated with protocol-directed use of IICPM in ALF.MethodsAdult patients admitted between June 2011 and October 2016, with ALF and grade-4 encephalopathy with a reasonable likelihood of survival, were eligible for IICPM. The coagulopathy reversal protocol included administration of recombinant Factor VIIa (rFVIIa) and desmopressin, a goal platelet count >50,000/mm3 and fibrinogen >100 mg/dL. Monitor insertion was performed within an hour of the rFVIIa dose. Only intraparenchymal monitors were used. Computed tomography of the brain was performed prior to and within 24 hours of monitor placement. Outcomes of interest included ICH, sustained intracranial hypertension, therapeutic intensity level (TIL) for ICP management, mortality and functional outcome on the Glasgow Outcome Scale (GOS) at discharge and 6 months.ResultsA total of 24/37 patients (65%) with ALF underwent IICPM. The most common reason for exclusion was encephalopathy grade <4. Four patients underwent liver transplantation. There was one asymptomatic ICH following IICPM, in a patient who had an excellent outcome. Sustained intracranial hypertension occurred in 13/24 monitored patients (54%), 5/24 (21%) required extreme measures (TIL-4) for ICP control, which were successful in 4 patients: 12/24 patients (50%) died but only 4 deaths (17%) were attributed to intracranial hypertension. Six of the 8 survivors with 6-month follow up had good functional outcome (GOS >3).ConclusionsProtocol-directed use of IICPM in ALF is feasible, associated with a low incidence of serious complications and has a significant impact on clinical management.

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“…However, a recent multicenter clinical study investigating the use of therapeutic hypothermia observed no benefit in reducing brain swelling or increasing the survival rate of acute liver failure patients. 8 Therefore, as the study by Lin et al found that lower temperatures were associated with increased prevalence of ACLF, it was likely not due to any direct effect of hyperthermia or hypothermia. 5 While the influence of seasonal meteorological factors on liver diseases is an area that has not been extensively studied, there is some evidence of seasonality towards the viral hepatitis infections of hepatitis A, B, C, and E as they are more prominent in the spring and summer.…”

mentioning

confidence: 88%

Can Weather Influence the Prevalence of Acute-on-chronic Liver Failure?

McMillin

2019

Journal of Clinical and Translational Hepatology

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A multicentre randomized controlled trial of moderate hypothermia to prevent intracranial hypertension in acute liver failure

Cited by 85 publications

References 31 publications

Neuroinflammatory Signals during Acute and Chronic Liver Diseases

Neuroinflammatory Signals during Acute and Chronic Liver Diseases

Protocol based invasive intracranial pressure monitoring in acute liver failure: feasibility, safety and impact on management

Can Weather Influence the Prevalence of Acute-on-chronic Liver Failure?

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