Referral for liver transplant following acute variceal bleeding: a multicenter cohort study.

OBJECTIVES: Referral for liver transplant (LT) following acute variceal bleeding (AVB) varies widely. We aimed to characterize and assess its impact on clinical outcomes. METHODS: Observational retrospective cohort including cirrhosis patients with AVB from 3 hospitals in Lisbon, Portugal, from 2018 to 2019. Primary exposure was referral for LT and primary endpoint was all-cause mortality within 2 years of index hospital admission. RESULTS: Among 143 patients, median (IQR) age was 59 (52-72) years and 90 (62.9%) were males. Median (IQR) MELDNa scores on hospital admission and discharge were 15 (11-21) and 13 (10-16), respectively. Overall, 30 (21.0%) patients were assessed for LT, 13 (9.1%) prior to and 17 (11.9%) within 2 years of hospital admission. Overall, 58 (40.6%) patients had at least one potential contra-indication for transplant. LT was performed in 3 (2.1%) patients (among 5 listed). Overall, 34 (23.8%) and 62 (43.4%) patients died at 6 weeks and 2 years post hospital admission, respectively. Following adjustment for confounders, referral for LT was associated with lower 2-year mortality (aHR (95% CI) = 0.20 (0.05-0.85)). CONCLUSION: In a multicenter cohort of cirrhosis patients with AVB, less than a quarter underwent formal LT evaluation. Improved referral for LT following AVB may benefit cirrhosis patients' longer-term mortality.

Continuous renal replacement therapy and survival in acute liver failure: A systematic review and meta-analysis.

OBJECTIVE: Acute liver failure (ALF) is a rare syndrome leading to significant morbidity and mortality. An important cause of mortality is cerebral edema due to hyperammonemia. Different therapies for hyperammonemia have been assessed including continuous renal replacement therapy (CRRT). We conducted a systematic review and meta-analysis to determine the efficacy of CRRT in ALF patients. MATERIALS AND METHODS: We searched MEDLINE, EMBASE, Cochrane Library, and Web of Science. Inclusion criteria included adult patients admitted to an ICU with ALF. Intervention was the use of CRRT for one or more indications with the comparator being standard care without the use of CRRT. Outcomes of interest were overall survival, transplant-free survival (TFS), mortality and changes in serum ammonia levels. RESULTS: In total, 305 patients underwent CRRT while 1137 patients did not receive CRRT. CRRT was associated with improved overall survival [risk ratio (RR) 0.83, 95% confidence interval (CI) 0.70-0.99, p-value 0.04, I2 = 50%] and improved TFS (RR 0.65, 95% CI 0.49-0.85, p-value 0.002, I2 = 25%). There was a trend towards higher mortality with no CRRT (RR 1.24, 95% CI 0.84-1.81, p-value 0.28, I2 = 37%). Ammonia clearance data was unable to be pooled and was not analyzable. CONCLUSION: Use of CRRT in ALF patients is associated with improved overall and transplant-free survival compared to no CRRT.

What every Intensivist should know about ... Ammonia in liver failure.

PURPOSE: Acute liver failure (ALF) or acute-on-chronic liver failure (ACLF) patients have high short-term mortality and morbidity. In the context of liver failure, increased serum ammonia is associated with worse neurological outcomes, including high-grade hepatic encephalopathy (HE), cerebral edema, and intracranial hypertension. Besides its neurotoxicity, hyperammonemia may contribute to immune dysfunction and the risk of infection, a frequent trigger for multi-organ failure in these patients. MATERIAL AND METHODS: We performed a literature-based narrative review. Publications available in PubMed® up to June 2023 were considered. RESULTS: In the ICU management of liver failure patients, serum ammonia may play an important role. Accordingly, in this review, we focus on recent insights about ammonia metabolism, serum ammonia measurement strategies, hyperammonemia prognostic value, and ammonia-targeted therapeutic strategies. CONCLUSIONS: Serum ammonia may have prognostic value in liver failure. Effective ammonia targeted therapeutic strategies are available, such as laxatives, rifaximin, L-ornithine-l-aspartate, and continuous renal replacement therapy.

Alcohol Consumption Post-Liver Transplantation: A Cross-Sectional Study.

Background: Listing patients with alcohol-associated liver disease (ALD) for liver transplant (LT) remains challenging especially due to the risk of alcohol resumption post-LT. We aimed to evaluate post-LT alcohol consumption at a Portuguese transplant center. Methods: We conducted a cross-sectional study including LT recipients from 2019 at Curry Cabral Hospital, Lisbon, Portugal. A pretested survey and a validated Portuguese translation of the Alcohol Use Disorder Identification Test (AUDIT) were applied via a telephone call. Alcohol consumption was defined by patients' self-reports or a positive AUDIT. Results: In 2019, 122 patients underwent LT, and 99 patients answered the survey (June 2021). The mean (SD) age was 57 (10) years, 70 patients (70.7%) were males, and 49 (49.5%) underwent ALD-related LT. During a median (IQR) follow-up of 24 (20-26) months post-index LT, 22 (22.2%) recipients consumed any amount of alcohol: 14 had a drink monthly or less and 8 drank 2-4 times/month. On drinking days, 18 patients usually consumed 1-2 drinks and the remainder no more than 3-4 drinks. One patient reported having drunk ≥6 drinks on one occasion. All post-LT drinking recipients were considered low risk (score <8) as per the AUDIT score (median [IQR] of 1 [1-2]). No patient reported alcohol-related problems, whether self-inflicted or toward others. Drinking recipients were younger (53 vs. 59 years, p = 0.020), had more non-ALD-related LT (72.7 vs. 44.2%, p = 0.018) and active smoking (31.8 vs. 10.4%, p = 0.037) than abstinent ones. Conclusion: In our cohort, about a quarter of LT recipients consumed alcohol early posttransplant, all with a low-risk pattern according to the AUDIT score.

Introdução: Incluir doentes com doença hepática associada ao álcool (DHA) em lista ativa de transplante hepático (TH) é desafiante, especialmente pelo risco de recidiva de consumo de álcool pós-TH. O objetivo foi avaliar o consumo de álcool pós-TH num centro de transplantação português. Métodos: Realizamos um estudo transversal incluindo doentes submetidos a TH em 2019 no Hospital Curry Cabral, Lisboa, Portugal. Foi realizado um questionário previamente testado e uma tradução validada para o português do Alcohol Use Disorder Identification Test (AUDIT), através de uma chamada telefónica. O consumo de álcool foi definido pelo autorrelato do doente ou por um AUDIT positivo. Resultados: Durante 2019, 122 doentes foram submetidos a TH e 99 responderam ao questionário (junho de 2021). A idade média (SD) foi de 57 (10) anos, 70 doentes (70,7%) eram do sexo masculino e 49 (49,5%) foram submetidos a TH relacionado com DHA. Com uma mediana (IQR) de follow-up de 24 (20­26) meses após o TH-índex, 22 (22,2%) doentes admitiram algum consumo de álcool: 14 beberam mensalmente ou menos e oito beberam 2­4 vezes/mês. Nos dias em que bebiam, 18 consumiam normalmente 1­2 bebidas e os restantes não mais do que 3­4 bebidas. Um doente reportou o consumo de ≥6 bebidas em uma ocasião. Todos os doentes transplantados com consumo alcoólico pós-TH foram considerados de baixo risco (pontuação >8) de acordo com o AUDIT (mediana [IQR] de 1 [1­2]). Nenhum doente reportou problemas relacionados com o álcool, tanto autoinfligido como a terceiros. Os indivíduos transplantados com consumo alcoólico eram mais jovens (53 vs. 59 anos, p = 0,020), o motivo de TH era mais frequentemente não relacionado com DHA (72,7 vs. 44,2%, p = 0,018) e apresentavam mais tabagismo ativo (31,8 vs. 10,4%, p = 0,037) quando comparado com os abstinentes. Conclusão: Na nossa coorte, cerca de um quarto dos doentes transplantados hepáticos consumiram álcool no período pós-transplante precoce, todos com um padrão de baixo risco, de acordo com o AUDIT.

The Impact of Donor Risk Index, Recipients' and Operative Characteristics on Post Liver Transplant One-Year Graft Failure: A Cohort Analysis.

Background and Aims: The donor risk index (DRI) quantifies donor-related characteristics potentially associated with increased risk of early graft failure. We aimed to assess the impact of the DRI, recipient and perioperative factors on post liver transplant (LT) outcomes. Methods: This was a single-center retrospective cohort study including all adult (≥18 years) patients who underwent LT from 01/2019 to 12/2019 at Curry Cabral Hospital, Lisbon, Portugal. Primary endpoint was 1-year graft failure post LT. Associations were studied with logistic regression. Results: A total of 131 cadaveric donor LT procedures were performed in 116 recipients. Recipients' median (IQR) age was 57 (47-64) years and 101/131 (77.1%) were males. Cirrhosis was the underlying etiology in 95/131 (81.2%) transplants. Based on 8 predefined donors' characteristics, median (IQR) DRI was 1.96 (1.67-2.16). Following adjustment for MELDNa score pre LT and SOFA score (adjusted odds ratio [aOR], 95% confidence interval [CI] = 0.91 [0.56-1.47]) or lactate (aOR [95% CI] = 2.76 [0.71-10.7]) upon intensive care unit (ICU) admission post LT, DRI was not associated with 1-year graft failure. However, higher SOFA score (aOR [95% CI] = 1.20 [1.05-1.37]) or lactate (aOR [95% CI] = 1.27 [1.10-1.46]) upon ICU admission post LT were independently associated with higher odds of 1-year graft failure. Conclusions: In a recent cohort of patients who underwent LT, DRI, despite being high, was not associated with 1-year graft failure, but SOFA score or lactate upon ICU admission post LT were.

Introdução: O índice de risco do dador (DRI) quantifica as características relacionadas com o dador potencialmente associadas com risco acrescido de falência precoce do enxerto. Procurou-se avaliar o impacto do DRI e factores relacionados com os receptores e cirurgia nos resultados clínicos após transplante hepático (LT). Materiais e Métodos: Estudo coorte retrospectivo de centro único incluindo todos os doentes adultos (≥18 anos) que receberam LT entre 01/2019 e 12/2019 no Hospital Curry Cabral, Lisboa, Portugal. O endpoint primário foi a falência do enxerto após um ano do LT. As associações foram estudadas com regressão logística. Resultados: Um total de 131 transplantes de dadores cadavéricos foram realizados em 116 receptores. A idade mediana (IQR) destes foi 57 (47­64) anos e 101/131 (77.1%) eram homens. A cirrose foi a etiologia subjacente em 95/131 (81.2%) transplantes. Com base nas 8 características dos dadores predefinidas, o DRI mediano (IQR) foi 1.96 (1.67­2.16). Após ajuste para o score MELDNa pre LT e o score SOFA (odds ratio ajustado [aOR], intervalo de confiança 95% [CI] = 0.91 [0.56­1.47]) ou o lactato (aOR [95% CI] = 2.76 [0.71­10.7]) após admissão na unidade de cuidados intensivos (ICU) pós LT, o DRI não se associou com a falência do enxerto um ano depois do LT. Contudo, um maior score SOFA (aOR [95% CI] = 1.20 [1.05­1.37]) ou lactato (aOR [95% CI] = 1.27 [1.10­1.46]) após admissão na ICU depois do LT associaram-se independentemente com a falência do enxerto um ano depois do LT. Conclusões: Num coorte recente de doentes submetidos a LT, o DRI, apesar de alto, não se associou com a falência precoce do enxerto precoce. Contudo, o score SOFA ou lactato após admissão na ICU depois do LT associaram-se com a falência precoce do enxerto.

Early serum ammonia variation in critically ill patients with cirrhosis: A multicentre cohort study.

BACKGROUND: Serum ammonia variation in critically ill patients with cirrhosis has been poorly studied. AIM: To describe and assess the impact of serum ammonia variation in these patients' outcomes. METHODS: We studied patients ≥18 years old admitted to the intensive care units (ICUs) at University of Alberta Hospital (Edmonton, Canada) and Curry Cabral Hospital (Lisbon, Portugal; derivation cohort, n = 492) and Northwestern University Hospital (Chicago, USA; validation cohort, n = 600) between January 2010 and December 2021. Primary exposure was ICU days 1-3 serum ammonia. Primary endpoint was all-cause hospital mortality. RESULTS: In the derivation cohort, 330 (67.1%) patients were male and median (IQR) age was 57 (50-63) years. On ICU day 1, median ammonia was higher in patients with grade 3/4 hepatic encephalopathy (HE) than those with grade 2 HE or grade 0/1 HE (112 vs. 88 vs. 77 µmoL/L, respectively; p < 0.001). Furthermore, medium ammonia was higher in hospital non-survivors than survivors (99 vs. 86 µmol/L; p < 0.030). Following adjustment for significant confounders (age, HE, vasopressor use and renal replacement therapy delivery), higher ICU day 2 ammonia was independently associated with higher hospital mortality (adjusted OR per each 10 µmoL/L increment [95% CI] = 1.11 [1.01-1.21]; p = 0.024). In the validation cohort, this model with serial ammonia (ICU days 1 and 3) predicted hospital mortality with reasonably good discrimination (c-statistic = 0.73) and calibration (R2 = 0.19 and Brier score = 0.17). CONCLUSIONS: Among patients with cirrhosis in the ICU, early serum ammonia variation was independently associated with hospital mortality. In this context, serial serum ammonia may have prognostic value.

Post liver transplantation delirium assessment using the CAM-ICU-7 scale: A cohort analysis.

Background: We applied the Confusion Assessment Method (CAM)-Intensive Care Unit (ICU)-7 delirium scale to patients who underwent liver transplant (LT). Methods: Retrospective cohort including patients who underwent LT for cirrhosis admitted to the ICU from June 2013 to June 2016 at the University of Alberta Hospital, Canada. Delirium was assessed using the CAM-ICU-7 scale (0-7 points) twice daily on days one and 3 post LT, with the highest score being considered. Primary endpoint was hospital mortality. Results: Among all patients, 101/150 (67.3%) were men and mean age was 52.4 (SD 11.8) years. On days 1 and 3 post LT, mean CAM-ICU-7 scores were 1.8 (SD 1.3) and 1.6 (SD 1.8), respectively. Therefore, on days 1 and 3 post LT, 38/150 (25.3%) and 26/95 (27.4%) patients had delirium. While delirium on day 3 post LT was associated with higher hospital mortality (11.5% versus 0%; p = 0.019), it was not associated with length-of-hospital stay (29.2 versus 34.4 days; p = 0.36). Following adjustment for APACHEII score, delirium on day 3 post LT was associated with higher odds of hospital mortality (adjusted odds ratio [aOR] 1.89 [95% CI 1.02-3.50]). Following adjustment for Glasgow Coma Scale and mechanical ventilation, serum creatinine was associated with higher odds of delirium on day 3 post LT (aOR 2.02 [95% CI 1.08-3.77]). Conclusions: Using the CAM-ICU-7 scale, delirium was diagnosed in a fourth of patients who underwent LT. Delirium on day 3 post LT was associated with higher odds of hospital mortality.

Abdominal perfusion pressure in critically ill cirrhotic patients: a prospective observational study.

In critical patients, abdominal perfusion pressure (APP) has been shown to correlate with outcome. However, data from cirrhotic patients is scarce. We aimed to characterize APP in critically ill cirrhotic patients, analyze the prevalence and risk factors of abdominal hypoperfusion (AhP) and outcomes. A prospective cohort study in a general ICU specialized in liver disease at a tertiary hospital center recruited consecutive cirrhotic patients between October 2016 and December 2021. The study included 101 patients, with a mean age of 57.2 (± 10.4) years and a female gender proportion of 23.5%. The most frequent etiology of cirrhosis was alcohol (51.0%), and the precipitant event was infection (37.3%). ACLF grade (1-3) distribution was 8.9%, 26.7% and 52.5%, respectively. A total of 1274 measurements presented a mean APP of 63 (± 15) mmHg. Baseline AhP prevalence was 47%, independently associated with paracentesis (aOR 4.81, CI 95% 1.46-15.8, p = 0.01) and ACLF grade (aOR 2.41, CI 95% 1.20-4.85, p = 0.01). Similarly, AhP during the first week (64%) had baseline ACLF grade (aOR 2.09, CI 95% 1.29-3.39, p = 0.003) as a risk factor. Independent risk factors for 28-day mortality were bilirubin (aOR 1.10, CI 95% 1.04-1.16, p < 0.001) and SAPS II score (aOR 1.07, CI 95% 1.03-1.11, p = 0.001). There was a high prevalence of AhP in critical cirrhotic patients. Abdominal hypoperfusion was independently associated with higher ACLF grade and baseline paracentesis. Risk factors for 28-day mortality included clinical severity and total bilirubin. The prevention and treatment of AhP in the high-risk cirrhotic patient is prudential.

The impact of multidrug-resistant microorganisms on critically ill patients with cirrhosis in the intensive care unit: a cohort study.

The impact of multidrug-resistant (MDR) colonization and MDR infection in critically ill cirrhosis patients remains unclear. We assessed the association of MDR colonization and MDR infection with these patients' survival. Observational cohort study including adult cirrhosis patients admitted to 5 intensive care units at Northwestern Memorial Hospital (Chicago, Illinois, USA) on January 1, 2010, to December 31, 2017. Patients admitted for elective liver transplant or with previous liver transplant were excluded. Patients were screened for MDR colonization on intensive care unit admission. Infection diagnoses during the intensive care unit stay were considered. The primary endpoint was hospital transplant-free survival. Among 600 patients included, 362 (60%) were men and median (interquartile range) age was 58.0 (49.0, 64.0) years. Median (interquartile range) Model for End-stage Liver Disease, Sequential Organ Failure Assessment, and Chronic Liver Failure-Acute-on-Chronic Liver Failure scores on intensive care unit day 1 were 28.0 (20.0, 36.0), 9.0 (6.0, 13.0), and 55.0 (48.0, 64.0), respectively. Overall, 76 (13%) patients were transplanted and 443 (74%) survived the hospital stay. Infections were diagnosed in 347 (58%) patients: pneumonia in 197 (33%), urinary tract infection in 119 (20%), peritonitis in 93 (16%), bloodstream infection in 99 (16%), Clostridium difficile colitis in 9 (2%), and catheter tip infection in 7 (1%). MDR colonization and MDR infection were identified in 200 (33%) and 69 (12%) patients, respectively. MDR colonization was associated with MDR infection (p < 0.001). MDR colonization or MDR infection was associated with higher number and duration of antibiotics (p < 0.001). Following adjustment for covariables (age, sex, etiology, portal hypertension, and Sequential Organ Failure Assessment score), MDR colonization [OR (95% CI), 0.64 (0.43, 0.95)] or MDR infection [adjusted OR (95% CI), 0.22 (0.12, 0.40)] were independently associated with lower transplant-free survival. Among critically ill cirrhosis patients, MDR colonization or MDR infection portended a worse prognosis.

Persistent But Not Transient Acute Kidney Injury Was Associated With Lower Transplant-Free Survival in Patients With Acute Liver Failure: A Multicenter Cohort Study.

OBJECTIVES: Acute liver failure (ALF) is an orphan disease often complicated by acute kidney injury (AKI). We assessed the impact of transient versus persistent AKI on survival in patients with ALF. DESIGN: International multicenter retrospective cohort. SETTING: U.S. ALF Study Group prospective registry. PATIENTS: Patients with greater than or equal to 18 years and ALF in the registry from 1998 to 2016 were included. Patients with less than 3 days of follow-up, without kidney function evaluation on day 3, or with cirrhosis were excluded. INTERVENTIONS: AKI was defined by Kidney Disease Improving Global Outcomes guidelines on day 1. Kidney recovery was defined on day 3 as transient AKI, by a return to no-AKI within 48 hours or persistent AKI if no such recovery or renal replacement therapy (RRT) was observed. Primary outcome was transplant-free survival (TFS) at 21 days. MEASUREMENTS AND MAIN RESULTS: Among 1,071 patients with ALF, 339 (31.7%) were males, and median (interquartile range) age was 39 years (29-51 yr). Acetaminophen-related ALF was found in 497 patients (46.4%). On day 1, 485 of 1,071 patients (45.3%) had grade 3-4 hepatic encephalopathy (HE), 500 of 1,070 (46.7%) required invasive mechanical ventilation (IMV), 197 of 1,070 (18.4%) were on vasopressors, and 221 of 1,071 (20.6%) received RRT. On day 1, 673 of 1,071 patients (62.8%) had AKI. On day 3, 72 of 1,071 patients (6.7%) had transient AKI, 601 of 1,071 (56.1%) had persistent AKI, 71 of 1,071 (6.6%) had late onset AKI, and 327 of 1,071 (30.5%) remained without AKI. Following adjustment for confounders (age, sex, race, etiology, HE grade, use of IMV and vasopressors, international normalized ratio, and year), although persistent acute kidney injury (adjusted odds ratio [aOR] [95% CI] 0.62 [0.44-0.88]) or late onset AKI (aOR [95% CI] 0.48 [0.26-0.89]) was associated with lower TFS, transient AKI was not (aOR [95% CI] 1.89 [0.99-3.64]). CONCLUSIONS: In a multicenter cohort of patients with ALF, persistent but not transient AKI was independently associated with lower short-term TFS.

Variation in the Care of Acute Liver Failure: A Survey of Intensive Care Professionals.

INTRODUCTION: Acute liver failure (ALF) is a rare disease with potentially high mortality. We sought to assess the individual approach to ALF by intensive care unit (ICU) professionals. METHODS: Cross-sectional survey of ICU professionals. Web-based survey capturing data on respondents' demographics, characteristics of patients with ALF admitted to ICU, and their management. RESULTS: Among 204 participants from 50 countries, 140 (68.6%) worked in Europe, 146 (71.6%) were intensivists, 142 (69.6%) admitted <25 patients with ALF per year, and 166 (81.8%) reported <25% of patients had paracetamol-related ALF. On patients' outcomes, 126 (75.0%) reported an emergency liver transplantation (ELT) rate <25% and 140 (73.3%) a hospital mortality rate <50%. The approach to ALF in the ICU varied with age, region, level of training, type of hospital, and etiology (prescribing N-acetylcysteine for paracetamol toxicity, triggers for endotracheal intubation, measurement of and strategies for lowering serum ammonia, extracorporeal device deployment, and prophylactic antibiotics). CONCLUSIONS: The management of patients with ALF by ICU professionals differed substantially concerning the relevant clinical measures taken. Further education and high-quality research are warranted.

INTRODUÇÃO: A falência hepatica aguda (ALF) é uma doença rara potencialmente letal. Pretendeu-se avaliar a abordagem individual à ALF por profissionais da Unidade de Cuidados Intensivos (UCI). MÉTODOS: Inquérito transversal de profissionais da UCI. Inquérito online capturando informação da demografia dos respondedores, características dos doentes com ALF admitidos na UCI e sua abordagem. RESULTADOS: Entre 204 participantes de 50 países, 140 (68.6%) trabalhavam na Europa, 146 (71.6%) eram inten-sivistas, 142 (62.9%) admitiam <25 doentes com ALF por ano, e 166 (81.8%) reportaram <25% dos doentes com ALF relacionada com paracetamol. Quanto aos resultados dos doentes, 126 (75.0%) reportaram uma taxa de transplantação hepatica emergente (ELT) <25% e 140 (73.3%) uma taxa de mortalidade hospitalar <50%. A abordagem da ALF variou com a idade, região, nível de treino, tipo de hospital, ou etiologia nos seguintes tópicos: prescrição de N-acetil-cisteína, critérios de intubação orotraqueal, medição e estratégias de control da amoniémia, uso de técnicas extracorporais, e a prescrição de antibióticos profilácticos. CONCLUSÕES: A abordagem de doentes com ALF por profissionais da UCI diferiu substancialmente em aspectos clínicos importantes. Educação e investigação de qualidade adicionais serão necessárias.

Liver trauma in the intensive care unit.

PURPOSE OF REVIEW: To review the surgical and critical care management of liver trauma; one of the most common abdominal injuries sustained due to its size and location. RECENT FINDINGS: Hepatic injuries range from negligible to life threatening: in the acute phase, the most common cause of morbidity and mortality is hemorrhage; however, severe traumatic hepatic injuries can also lead to biochemical abnormalities, altered coagulation, and ultimately liver failure. This brief review will review the classification of traumatic liver injuries by mechanism, grade, and severity. Most Grades I-III injuries can be managed nonoperatively, whereas the majority of Grades IV-VI injuries require operative management. Therapeutic strategies for traumatic liver injury including nonoperative, operative, radiologic will be described. The primary goal of liver trauma management in the acute setting is hemorrhage control, then the management of secondary factors such as bile leaks. The rapid restoration of homeostasis may prevent further damage to the liver and allow for deferred nonoperative management, which has been shown to be associated with good clinical outcomes. SUMMARY: A multidisciplinary approach to the care of these patients at an experienced liver surgery center is warranted.

Optic Nerve Sheath Diameter in Acute Liver Failure: A Prospective Cohort Study.

INTRODUCTION: Acute liver failure (ALF) is a rare disease that may lead to cerebral edema and death. An increased optic nerve sheath diameter (ONSD) may reflect an early increase in intracranial pressure. We assessed the feasibility and safety of the ONSD measurement and its association with outcomes in patients with ALF. METHODS: This was an open-label prospective cohort study including adult patients with ALF admitted to a liver-specialized intensive care unit (ICU) in an academic center between October 2018 and February 2020 (among 24): 20 as intention-to-treat and 17 as per-protocol analyses. The ONSD measurement (primary exposure) used an ultrasound transducer (3 determinations on each eye per patient). The primary outcome was hospital mortality. RESULTS: Among the 20 patients, 11 (55.0%) were females and the mean age was 45 ± 16 years. On the day of ONSD measurement (median 32.4 h post-ICU admission; IQR 19.8-59.8): 8 patients (40.0%) were in a coma, the mean international normalized ratio (INR) was 3.3 ± 1.4, median bilirubin was 12.3 mg/dL (IQR 4.7-24.5), mean ammonia was 163 ± 101 µmol/L, and mean SOFA score was 11 ± 5. The mean bilateral ONSD was 5.6 ± 0.7 mm, with a very good correlation between right and left eyes (Pearson's r = 0.90). Ten (50.0%) patients were transplanted and 13 (65.0%) patients survived the hospital stay (all with a 2-month extended Glasgow Outcome Scale of 8). The mean ONSD was significantly higher for hospital non-survivors than survivors both in the intention-to-treat (6.2 vs. 5.3 mm; p = 0.004) and per-protocol (6.2 vs. 5.2 mm; p = 0.004) analyses. No adverse effects from ONSD measurements were reported. CONCLUSIONS: In patients with ALF, a higher ONSD was associated with higher hospital mortality. ONSD measurement is feasible and safe and may have prognostic value.

INTRODUÇÃO: A falência hepatica aguda (ALF) é uma doença rara que pode complicar com edema cerebral e morte. O aumento do diâmetro da bainha do nervo óptico (ONSD) pode reflectir um aumento precose da pressão intracraniana. Avaliámos a viabilidade e segurança da medição do ONSD e a sua associação com os resultados de doentes com ALF. MÉTODOS: Coorte prospectivo aberto incluindo doentes adultos com ALF admitidos numa unidade de cuidados intensivos (ICU) especializada em fígado entre 10/2018 e 02/2020 (em 24): 20 como análise intenção-de-tratar e 17 como análise por-protocolo. A medição do ONSD (exposição primária) foi realizada com um transdutor ultra-sónico (3 medições em cada olho por doente). O resultado primário foi a mortalidade hospitalar. RESULTADOS: Entre 20 doentes, 11 (55.0%) eram mulheres e a idade média (SD) foi 45 (16) anos. No dia da medição do ONSD (mediana (IQR) de 32.4 (19.8­59.8) horas pós admissão na ICU): coma em 8 (40.0%) doentes, INR médio (SD) de 3.3 (1.4), bilirrubina mediana (IQR) de 12.3 (4.7­24.5) mg/dL, amónia média (SD) de 163 (101) µmol/L, e SOFA médio (SD) de 11 (5). O ONSD bilateral médio (SD) foi de 5.6 (0.7) mm, com boa correlação entre os olhos (Pearson r = 0.90). Dez (50.0%) doentes foram transplantados e 13 (65.0%) sobreviveram à hospitalização (todos com escala de Glasgow Outcome aos 2 meses de 8). O ONSD médio foi significativamente maior nos não-sobreviventes do que nos sobreviventes quer na análise intenção-de-tratar (6.2 mm vs. 5.3 mm; p = 0.004) quer na análise por-protocolo (6.2 mm vs. 5.2 mm; p = 0.004). Não se registaram efeitos adversos. CONCLUSÕES: Em doentes com ALF, maior ONSD esteve associado com maior mortalidade hospitalar. A medição do ONSD é viável, segura, e poderá ter valor prognóstico.

Positive fluid balance was associated with mortality in patients with acute-on-chronic liver failure: A cohort study.

PURPOSE: We aimed to study the effect of FB in the outcomes of critically-ill patients with cirrhosis. MATERIALS: Retrospective analysis of all adult consecutive admissions of patients with cirrhosis and organ failures to the Intensive Care Unit (ICU) at Curry Cabral Hospital (Lisbon, Portugal) and University of Alberta Hospital (Edmonton, Canada) on 08/2013-08/2017. Primary exposure was FB at 3 and 7 days post ICU admission. Primary endpoint was hospital mortality. RESULTS: Amongst 333 patients, median age was 56 years and 67.6% were men. Median MELD, APACHEII, CLIF-SOFA, and CLIF-C-ACLF scores on ICU admission were 27, 28, 14, and 54, respectively. ICU and hospital mortality rates were 33.0% and 49.2%, respectively. While median FB at 3 days post ICU admission (+5.46 l vs. +6.62 l; P = 0.74) was not associated with hospital mortality, higher median FB at 7 days post ICU admission (+13.50 l vs. +6.90 l; P = 0.036) was associated with higher hospital mortality. This association remained significant (OR 95%CI = 1.04 [1.01;1.07] per each l) after adjustment for confounders (age, ascites, infection, lactate, and number of organ failures). CONCLUSIONS: FB may be a therapeutic target that helps to improve the outcomes of patients with acute-on-chronic liver failure. This data may inform future clinical trials.

Significant lung injury and its prognostic significance in acute liver failure: A cohort analysis.

BACKGROUND AND AIMS: Respiratory failure complicating acute liver failure (ALF) may preclude liver transplantation (LT). We evaluated the association between significant lung injury (SLI) and important clinical outcomes. METHODS: Retrospective cohort study of 947 ALF patients with chest radiograph (CXR) and arterial blood gas (ABG) data enrolled in the US Acute Liver Failure Study Group (US-ALFSG) from January 1998 to December 2016. SLI was defined by moderate hypoxaemia (Berlin classification; PaO2 /FiO2  < 200 mm Hg) and abnormalities on CXR. Primary outcomes were 21-day transplant-free survival (TFS) and overall survival. RESULTS: Of 947 ALF patients, 370 (39%) had evidence of SLI. ALF patients with SLI (ALF-SLI) had significantly worse oxygenation than controls on admission (median PF ratio 120 vs 300 mm Hg, P < .0001) and higher lactate (6.1 vs 4.6 mmol/l, P = .0008). ALF-SLI patients had higher rates of tracheal (19% vs 14%) and bloodstream (17% vs 11%, P < .005 for both) infections and were more likely to receive transfusions (red cells 55% vs 43%; FFP 74% vs 66%; P < .009 for both). ALF-SLI patients were less likely to receive LT (18% vs 25%, P = .02) and had significantly decreased 21-day TFS (34% vs 42%) and overall survival (49% vs 64%, P < .007 for both). After adjusting for significant covariates (INR, bilirubin, acetaminophen aetiology), the development of SLI was independently associated with decreased 21-day TFS (OR 0.71, P = .03) in ALF patients (C-index 0.78). The incorporation of SLI improved discriminatory ability of the King's College Criteria (P = .0061) but not the ALFSG prognostic index (P = .34). CONCLUSION: Significant lung injury is a common complication in ALF patients that adversely affects patient outcomes.