56 the Prophylactive Effect of Mild Hypothermia to Prevent Brain Edema in Patients With Acute Liver Failure: Results of a Multicenter Randomized, Controlled Trial

Larsen, Fin Stolze; Murphy, N.; Bernal, William; Bjerring, Peter Nissen; Hauerberg, John; Wendon, J.

doi:10.1016/s0168-8278(11)60058-5

Cited by 27 publications

(11 citation statements)

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“…If all RCTs that aim to reduce ICP are combined then there are 5 [109][110][111][112][113] trials involving 410 ALF patients with no statistically significant effect of active therapy in reducing mortality (RR mortality, 0.94; 95% CI, 0.75-1.18; P ¼ .61) ( Supplementary Figure 4). Harms of any intervention to reduce ICP were poorly characterized but are likely to occur.…”

Section: Should Therapies Designed To Reduce Intracranial Pressure Bementioning

confidence: 99%

American Gastroenterological Association Institute Technical Review on Initial Testing and Management of Acute Liver Disease

et al. 2017

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Section: Should Therapies Designed To Reduce Intracranial Pressure Bementioning

confidence: 99%

American Gastroenterological Association Institute Technical Review on Initial Testing and Management of Acute Liver Disease

et al. 2017

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“…As the authors state in their discussion, “the data presented largely suggest no benefit of TH, but also no harm.” It is difficult to disagree with this statement, especially because a recent randomized controlled trial published in abstract form has drawn similar conclusions . It is interesting to speculate why the current study and that reported by Larsen et al failed to demonstrate a significant benefit of TH when uncontrolled data and experimental models are so convincing. First, TH may be effective only in hyperacute presentations of ALF such as acetaminophen‐induced ALF.…”

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confidence: 60%

Therapeutic hypothermia in acute liver failure: Not that hot?

O'Beirne

2014

Liver Transpl

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Acute liver failure (ALF) is a rare and devastating clinical syndrome comprising the sudden loss of hepatic function and the development of complications such as coagulopathy, vasoparesis, renal failure, and hepatic encephalopathy. 1 As the syndrome progresses, cerebral edema may occur and lead to intracranial hypertension (ICH), which can progress to brain death from cerebral herniation. During the last 30 years, significant progress has been made in the management of patients with ALF, and survival rates greater than 70% are now reported; this represents a dramatic improvement from early series in which survival rates as low as 16.7% were observed. 2 Undoubtedly, the most significant factor in this improvement is the use of liver transplantation (LT), which results in excellent survival rates for patients who fulfill poor prognostic criteria. 3 Factors that may also be associated with improved outcomes are earlier referral to transplant centers, more frequent use of renal replacement therapy, prophylactic antimicrobials/antifungals, and specific therapies for addressing ICH such as osmotherapy with mannitol and/or hypertonic saline. Despite the advent of LT as the definitive therapy for patients predicted to have the worst outcome, this is not a therapy that can be applied to all. Patients may have contraindications to LT, and approximately 20% of patients who are listed will ultimately not receive a transplant because of the lack of an available graft. In these patients, mortality is almost universal and is usually due to sepsis-induced multiorgan failure, but a significant proportion will die because of cerebral herniation secondary to ICH. 4 The treatment and prevention of ICH, therefore, represent an important target for therapy in patients with ALF.The prevention and management of ICH in patients with ALF are based on therapies that reflect our current understanding of its pathophysiology. Management is, therefore, focused on the control of arterial ammonia levels by the use of continuous renal replacement therapy, the reduction of brain edema by the use of osmotherapy (mannitol and hypertonic saline), the control of cerebral blood flow (monitoring of CO 2 and sedation), and the prevention of systemic inflammation (broad-spectrum antibiotics and antifungals). Despite these measures, 20% of patients still develop ICH in the course of their illness, which may prove refractory to treatment and be associated with significant mortality and morbidity. 2 Therapeutic hypothermia (TH) has been proposed as a rational treatment for ICH in patients with ALF. Early work in animal models characterized by hyperammonemia has shown convincingly that hypothermia protects rodents from a lethal dose of ammonia and attenuates the development of brain edema. 5 TH potentially affects multiple pathways in ALF-related ICH by reducing brain energy demands, stabilizing the blood-brain barrier, decreasing the release of excitatory neurotransmitters, and reducing cerebral blood flow. 6 Jalan et al. 7 reported the first clinical appli...

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“…This result is consistent with a recently completed European study. 3 For younger APAP patients (n = 101), there was a beneficial effect, and this has physiological plausibility. For the small subset of older patients (n = 13), there may have been a harmful effect from hypothermia, but the pool of subjects was so small that it would be unwise to attribute causality to TH.…”

Section: To the Editormentioning

confidence: 98%