RESUMO
BACKGROUND: The profound hemodynamic changes seen in acute liver failure (ALF) resemble the hyperdynamic state found in the later stages of septic shock. Vasopressor support frequently is required after initial volume therapy. Markers of preload dependency have not been studied in this patient group. Dynamic maneuvers such as passive leg raising or end-expiratory hold, which have shown good predictive accuracy in a general intensive care unit population, cannot be considered safe in this cohort because of the concerns of intracranial hypertension. METHODS: Mechanically ventilated patients with ALF admitted to a tertiary specialist intensive care unit in shock and multiorgan failure were enrolled. Markers of fluid responsiveness derived from transpulmonary thermodilution, pulse contour analysis, and echocardiography were compared between responders (cardiac index ≥15%) and nonresponders to a colloid fluid challenge (5 mL/kg predicted body weight). The ability to predict fluid responsiveness of stroke volume variation, pulse pressure variation (PPV), and respiratory change in peak (delta V peak) left ventricular outflow tract velocity for preload dependency were analyzed. RESULTS: Thirty-five patients (mean ± SD age, 38 [14] years, 13 male, 22 female]) were assessed after a single fluid challenge. Ten patients (29%) were fluid responders. Changes in cardiac index and stroke volume index in the cohort of 35 patients were correlated (R = 0.726 [99% confidence interval, 0.401-0.910]; P < .001). PPV predicted fluid responsiveness (area under the receiver operating characteristic curve [AUROC], 0.752 [95% confidence interval, 0.565-0.889]; P = .005; cutoff >9%). The AUROC for stroke volume variation was 0.678 ([95% confidence interval, 0.499-0.825]; P = .084; cutoff >11%). The AUROC for [delta] V peak before fluid bolus was 0.637 (95% confidence interval, 0.413-0.825; P = .322). CONCLUSIONS: PPV based on pulse contour analysis predicted fluid responsiveness in ALF.
Assuntos
Hidratação/métodos , Falência Hepática Aguda/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Débito Cardíaco/fisiologia , Estudos de Coortes , Cuidados Críticos/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/fisiopatologia , Insuficiência de Múltiplos Órgãos/terapia , Valor Preditivo dos Testes , Estudos Prospectivos , Respiração Artificial , Choque/fisiopatologia , Choque/terapia , Volume Sistólico/fisiologia , Termodiluição , Resultado do TratamentoRESUMO
OBJECTIVES: There is a marked propensity for patients with acetaminophen-induced acute liver failure to develop sepsis, which may culminate in multiple organ failure and death. Toll-like receptors sense pathogens and induce inflammatory responses, but whether this is protective or detrimental in acetaminophen-induced acute liver failure remains unknown. DESIGN, SETTING, AND PATIENTS: We assessed Toll-like receptor expression on circulating neutrophils and their function in 24 patients with acetaminophen-induced acute liver failure and compared with 10 healthy controls. INTERVENTIONS: Neutrophil Toll-like receptor 2, -4, and -9 expression and cytokine production and function were studied ex vivo at baseline and following stimulation with lipopolysaccharide, oligodeoxynucleotides, ammonium chloride, and interleukin-8. To examine the influence of acetaminophen-induced acute liver failure plasma and endogenous DNA on Toll-like receptors-9 expression, healthy neutrophils were incubated with acetaminophen-induced acute liver failure plasma with and without deoxyribonuclease-I. MEASUREMENTS AND MAIN RESULTS: Circulating neutrophil Toll-like receptor 9 expression was increased in acetaminophen-induced acute liver failure on day 1 compared with healthy controls (p = 0.0002), whereas Toll-like receptor 4 expression was decreased compared with healthy controls (p < 0.0001). Toll-like receptor 2 expression was unchanged. Neutrophil phagocytic activity was decreased, and spontaneous oxidative burst increased in all patients with acetaminophen-induced acute liver failure compared with healthy controls (p < 0.0001). Neutrophil Toll-like receptor 9 expression correlated with plasma interleukin-8 and peak ammonia concentration (r = 0.6; p < 0.05) and increased with severity of hepatic encephalopathy (grade 0-2 vs 3/4) and systemic inflammatory response syndrome score (0-1 vs 2-4) (p < 0.05). Those patients with advanced hepatic encephalopathy (grade 3/4) or high systemic inflammatory response syndrome score (2-4) on day 1 had higher neutrophil Toll-like receptor 9 expression, arterial ammonia concentration, and plasma interleukin-8 associated with neutrophil exhaustion. Healthy neutrophil Toll-like receptor 9 expression increased upon stimulation with acetaminophen-induced acute liver failure plasma, which was abrogated by preincubation with deoxyribonuclease-I. Intracellular Toll-like receptor 9 was induced by costimulation with interleukin-8 and ammonia. CONCLUSION: These data point to neutrophil Toll-like receptor 9 expression in acetaminophen-induced acute liver failure being mediated both by circulating endogenous DNA as well as ammonia and interleukin-8 in a synergistic manner inducing systemic inflammation, neutrophil exhaustion, and exacerbating hepatic encephalopathy.
Assuntos
Acetaminofen/efeitos adversos , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/imunologia , Neutrófilos/imunologia , Síndrome de Resposta Inflamatória Sistêmica/induzido quimicamente , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Receptor Toll-Like 9/biossíntese , Adulto , Estudos de Coortes , Feminino , Humanos , Falência Hepática Aguda/sangue , Masculino , Pessoa de Meia-Idade , Síndrome de Resposta Inflamatória Sistêmica/sangue , Adulto JovemRESUMO
OBJECTIVE: Prognostic stratification of patients with cirrhosis is common clinical practice. This study compares the prognostic accuracy (28-day and 90-day transplant-free mortality) of the acute-on-chronic liver failure (ACLF) classification (no ACLF, ACLF grades 1, 2 and 3) with that of acute kidney injury (AKI) classification (no AKI, AKI stages 1, 2 and 3). DESIGN: The study was performed in 510 patients with an acute decompensation of cirrhosis previously included in the European Association for the Study of the Liver-Chronic Liver Failure consortium CANONIC study. ACLF was evaluated at enrollment and 48 h after enrollment, and AKI was evaluated at 48 h according to Acute Kidney Injury Network criteria. RESULTS: 240 patients (47.1%) met the criteria of ACLF at enrollment, while 98 patients (19.2%) developed AKI. The presence of ACLF and AKI was strongly associated with mortality. 28-day transplant-free mortality and 90-day transplant-free mortality of patients with ACLF (32% and 49.8%, respectively) were significantly higher with respect to those of patients without ACLF (6.2% and 16.4%, respectively; both p<0.001). Corresponding values in patients with and without AKI were 46% and 59%, and 12% and 25.6%, respectively (p<0.0001 for both). ACLF classification was more accurate than AKI classification in predicting 90-day mortality (area under the receiving operating characteristic curve=0.72 vs 0.62; p<0.0001) in the whole series of patients. Moreover, assessment of ACLF classification at 48 h had significantly better prognostic accuracy compared with that of both AKI classification and ACLF classification at enrollment. CONCLUSIONS: ACLF stratification is more accurate than AKI stratification in the prediction of short-term mortality in patients with acute decompensation of cirrhosis.
Assuntos
Injúria Renal Aguda/classificação , Insuficiência Hepática Crônica Agudizada/classificação , Cirrose Hepática/complicações , Falência Hepática Aguda/classificação , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Insuficiência Hepática Crônica Agudizada/complicações , Insuficiência Hepática Crônica Agudizada/epidemiologia , Causas de Morte/tendências , Europa (Continente)/epidemiologia , Feminino , Humanos , Cirrose Hepática/diagnóstico , Falência Hepática Aguda/etiologia , Masculino , Pessoa de Meia-Idade , Morbidade/tendências , Prognóstico , Curva ROC , Taxa de Sobrevida/tendênciasRESUMO
OBJECTIVE: Hypoxemia is a feared complication of acute liver failure, and high oxygen requirements will frequently lead to removal of patients from the transplant list. As data regarding the prevalence and outcome of acute respiratory distress syndrome in acute liver failure are scant and hypoxemia being a commonly encountered systemic complication, we analyzed radiological, gas exchange, and ventilator data in consecutive patients admitted with acute liver failure. PATIENTS: Acute liver failure patients receiving mechanical ventilation admitted between January 2007 and February 2011 were included. INTERVENTIONS: Patients were categorized according to the Berlin definition as: no acute respiratory distress syndrome, acute respiratory distress syndrome (PaO2/FIO2 < 300 mm Hg), and subdivisions of mild, moderate, and severe acute respiratory distress syndrome (200-300 mm Hg, 100-200 mm Hg, and < 100 mm Hg, respectively). Chest radiographs were independently assessed by two observers for the presence or absence of acute respiratory distress syndrome. Absence of left atrial pressure elevation was based on combined hemodynamic and echocardiographic assessment. MEASUREMENTS AND MAIN RESULTS: Two hundred acute liver failure patients were admitted during the study period of whom 148, median age 39 years (16-74 yr), were included. Thirty-one (21%) had acute respiratory distress syndrome (17 mild acute respiratory distress syndrome [12%], 9 moderate acute respiratory distress syndrome [12%], and 5 severe acute respiratory distress syndrome) within the first 72 hours following admission. Acute respiratory distress syndrome patients required higher positive end-expiratory pressure (7 vs 6 vs 10 vs 15 cm H2O for no, mild, moderate, or severe acute respiratory distress syndrome, p = 0.014), had reduced respiratory system compliance (34 vs 29 vs 30 vs 23 L/cm H2O, p = 0.028), and an increased number of ventilator days (no acute respiratory distress syndrome, 10 d; mild acute respiratory distress syndrome acute lung injury, 12 d; moderate acute respiratory distress syndrome, 23 d; severe acute respiratory distress syndrome, 22 d; p = 0.097). Duration of liver intensive therapy unit stay (p = 0.175), survival (p = 0.877), inotrope requirements (p = 0.495), need for extracorporeal renal support (p = 0.565), and severity of organ failure scores were not affected. Extravascular lung water index had a moderate sensitivity of 65% and specificity of 77% for the prediction of acute respiratory distress syndrome. CONCLUSION: The prevalence of lung injury is relatively low in acute liver failure, where 21% fulfilled acute respiratory distress syndrome criteria. Overall presence of acute respiratory distress syndrome appeared to have a limited impact on outcome.
Assuntos
Lesão Pulmonar Aguda/epidemiologia , Causas de Morte , Mortalidade Hospitalar/tendências , Unidades de Terapia Intensiva , Falência Hepática Aguda/epidemiologia , Síndrome do Desconforto Respiratório/epidemiologia , APACHE , Lesão Pulmonar Aguda/diagnóstico por imagem , Lesão Pulmonar Aguda/terapia , Adolescente , Adulto , Idoso , Gasometria , Estudos de Coortes , Comorbidade , Estado Terminal/mortalidade , Estado Terminal/terapia , Feminino , Humanos , Falência Hepática Aguda/diagnóstico , Falência Hepática Aguda/terapia , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio/fisiologia , Prevalência , Prognóstico , Radiografia Torácica , Respiração Artificial/métodos , Síndrome do Desconforto Respiratório/diagnóstico por imagem , Síndrome do Desconforto Respiratório/terapia , Estudos Retrospectivos , Medição de Risco , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) has a rapidly progressive disease course associated with significant mortality. The prevalence of clinically significant cerebral oedema in ACLF is unknown. METHODS: We aimed to describe the prevalence of cerebral oedema in a cohort of ACLF adult (>18 years). We identified patients admitted to a single, specialist intensive care unit between January 2005 and January 2011 with high-grade hepatic encephalopathy (≥3) and a clinical picture of either ACLF or chronic liver disease (CLD). Patients who had undergone cranial CT imaging were identified and their imaging reviewed. The ACLF and CLD groups were compared. RESULTS: One thousand and eight patients with CLD were admitted. One hundred and seventy-three patients (110 male) underwent neuroimaging. Eighty-one (48 male) fulfilled criteria for ACLF. Variceal bleeding (30%) and sepsis (31%) were the most frequent precipitants of ACLF. Of those with neuroimaging from the total cohort, 30% of CT scans were normal, 30% demonstrated increased cerebral atrophy for age, 17% small vessel disease and 16% intracranial haemorrhage (ICH). Cerebral oedema was seen in three patients with ACLF only. An increased prevalence of ICH was observed in the ACLF group (23% vs. 9%, P = 0.008). CONCLUSION: The prevalence of clinically relevant cerebral oedema was low (4%) but fatal. Death was attributable to tonsillar herniation. An increased prevalence of ICH was seen in ACLF patients and remains an important differential.
Assuntos
Insuficiência Hepática Crônica Agudizada/mortalidade , Edema Encefálico/diagnóstico , Encefalopatia Hepática/complicações , Adulto , Idoso , Estudos de Coortes , Doença Hepática Terminal , Varizes Esofágicas e Gástricas/complicações , Feminino , Hemorragia Gastrointestinal/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND & AIMS: Ammonia is recognized as a toxin central to complications of liver failure. Hyperammonaemia has important clinical consequences, but optimal means to reduce circulating levels are uncertain. In patients with liver disease, continuous renal replacement therapy (CRRT) with haemofiltration (HF) is often required to treat concurrent kidney injury, but its effects upon ammonia levels are poorly characterized. To evaluate the effect of HF at different treatment intensities on ammonia clearance (AC) and arterial ammonia concentration. METHODS: Prospective study of adult patients with liver failure and arterial ammonia >100 µmol/L requiring CRRT using veno-venous HF. Arterial ammonia concentration and AC measured at 1 and 24 h after initiation of low (35 ml/kg/h) or high (90 ml/kg/h) filtration volume. RESULTS: Twenty-four patients (10 acute liver failure, 10 chronic liver disease and 4 following liver resection) were studied. Clearance of urea and ammonia solutes correlated closely (r = 0.819, P = 0.007). Ammonia clearance correlated closely with ultrafiltration rate (r = 0.86, P < 0.001). At 1 h, AC was 39 (34-54) ml/min (low volume) vs 85 (62-105) ml/min (high volume) CRRT, (P < 0.001) and at 24 h 44 (34-63) vs 105 (82-109) ml/min, (P = 0.01). Overall, a 22% reduction in median arterial ammonia concentration was observed over 24 h of HF from 156 (137-176) to 122 (85-133) µmol/L, (P ≤ 0.0001). CONCLUSION: Clinically significant ammonia clearance can be achieved in adult patients with hyperammonaemia utilizing continuous VVHF. Ammonia clearance is closely correlated with ultrafiltration rate. HF was associated with a fall in arterial ammonia concentration.
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Amônia/sangue , Hemodiafiltração , Hiperamonemia/terapia , Falência Hepática/terapia , Adulto , Feminino , Humanos , Hiperamonemia/sangue , Hiperamonemia/diagnóstico , Falência Hepática/sangue , Falência Hepática/diagnóstico , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento , Ureia/sangueRESUMO
PURPOSE OF REVIEW: Acute liver failure (ALF) is associated with significant mortality. Although specific therapies may be available, the evidence base for these and for many aspects of supportive therapy has been slow to emerge. Liver transplantation continues to be a cornerstone of treatment, and the management of ALF, therefore, remains the domain of the specialist ICU. The purpose of this review is to identify and critically appraise the recent evidence and to inspire those who strive to provide excellent care for a difficult patient cohort. RECENT FINDINGS: Effective vaccination programmes have reduced the incidence of viral hepatitis in Europe and the USA. Spontaneous survival has improved in causes such as acetaminophen toxicity. Early recognition and proactive intensive management have reduced the incidence of early neurological death. The use of artificial liver assist devices and therapeutic plasma exchange is controversial, yet intriguing, with some early evidence of efficacy. SUMMARY: Increasingly sophisticated prognostication tools are evolving, which have the potential to transform clinical decision-making. A review of the indications for transplantation in acetaminophen toxicity is overdue. The use of therapeutic plasma exchange and extracorporeal liver support in ALF requires further investigation.
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Doença Hepática Induzida por Substâncias e Drogas/terapia , Cuidados Críticos/métodos , Hepatite Viral Humana/complicações , Falência Hepática Aguda/terapia , Transplante de Fígado/métodos , Troca Plasmática , Acetaminofen/efeitos adversos , Antivirais/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Feminino , Humanos , Falência Hepática Aguda/etiologia , Falência Hepática Aguda/mortalidade , Falência Hepática Aguda/virologia , Fígado Artificial/tendências , Masculino , Seleção de Pacientes , Troca Plasmática/métodos , Prevalência , Resultado do TratamentoRESUMO
INTRODUCTION: Acute liver failure (ALF) is a life-threatening multisystem illness complicated by multiple organ failure (MOF) and haemodynamic disturbances. Morbidity and mortality remains high and various prognostic and scoring models are in use to predict outcome. A recent observation in a large cohort of ALF patients suggested a prognostic value of troponin I (cTnI) and its role as a marker of subclinical myocardial injury and outcome. METHODS: Data from consecutive ALF patients over a four-year period from January 2007 to March 2011 were included. The aim of this study was to correlate any relationship that may exist between cTnI, mortality, severity of illness and non-hepatic organ failure. RESULTS: A total of 218 subjects (age 36 (16 to 90) years, M:F 103:115) were studied, of which 136 had an elevated cTnI > 0.05 µg/L. Higher organ failure scores were found with positive cTnI: APACHE II (19.5 (3 to 51) vs 14 (2 to 51), P = 0.001), APACHE III (81 (15 to 148) vs 59 (8 to 172), P = < 0.001) SOFA (15 (4 to 20) vs 13 (2 to 21), P = 0.027) and SAPS (48 (12 to 96) vs 34 (12 to 97), P = 0.001). Patients with positive cTnI had higher serum creatinine (192 µmol/l (38 to 550) vs 117 µmol/l (46 to 929), P < 0.001), arterial lactate (0.25, P < 0.001) and a lower pH (-0.21, P = 0.002). Also a higher proportion required renal replacement therapy (78% vs 60%, P = 0.006). Patients with elevated cTnI more frequently required vasopressors-norepinephrine (73% vs 50%, P = 0.008). Elevated cTnI did not predict outcome as effectively as other models (AUROC 0.61 (95% CI 0.52 to 0.68)). CONCLUSIONS: More than 60% of ALF patients in this study demonstrated elevated cTnI. Despite a close correlation with organ failure severity, cTnI was a poor independent predictor of outcome. cTnI may not represent true myocardial injury and may be better viewed as a marker of metabolic stress.
Assuntos
Falência Hepática Aguda/diagnóstico , Troponina I/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ecocardiografia , Eletrocardiografia , Feminino , Coração/fisiopatologia , Humanos , Falência Hepática Aguda/sangue , Falência Hepática Aguda/mortalidade , Falência Hepática Aguda/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Índice de Gravidade de Doença , Adulto JovemRESUMO
PURPOSE OF REVIEW: The incidence of cirrhosis is growing steadily and this cohort of patients will present in ever-greater numbers to critical care with acute decompensation, usually secondary to an inter-current event or following elective surgery. This review examines the evidence for treatment options and outcomes. RECENT FINDINGS: Outcome of cirrhotics presenting with end-organ dysfunction is steadily improving and their outcomes are not as poor as sometimes suggested. Treatment options for variceal bleeding and renal dysfunction are evolving and outcomes improving. SUMMARY: Critical care support should be offered to patients with cirrhosis and in high-risk variceal bleed patients transhepatic portosystemic shunt should be considered.
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Cuidados Críticos , Cirrose Hepática/terapia , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/etiologia , Derivação Portossistêmica Cirúrgica , Resultado do TratamentoRESUMO
Despite considerable advances in maternity care, maternal death rates remain unacceptably high. Even with optimal care, unexpected complications can result in catastrophic consequences. Hemorrhage, cardiovascular and coronary conditions, and cardiomyopathy make up the three most common causes of pregnancy-associated deaths, followed by sepsis and thromboembolic disease. Although a number of deaths may be deemed to be potentially avoidable with appropriate education and infrastructure, others such as refractory hypoxia and peripartum cardiomyopathy are not. All possible interventions should be explored, including the use of more novel and aggressive life support technologies, such as extracorporeal membrane oxygenation. We report the successful use of extracorporeal membrane oxygenation in three cases of severe peripartum morbidity. The first case describes spontaneous coronary artery dissection supported with veno-arterial extracorporeal membrane oxygenation for refractory cardiogenic shock after out-of-hospital cardiac arrest. The second is a case of severe pregnancy-related liver disease bridged to emergency liver transplantation with veno-venous extracorporeal membrane oxygenation. Finally, we report the use of extracorporeal cardiopulmonary resuscitation for refractory cardiac arrest in a postpartum patient. Peripartum extracorporeal membrane oxygenation is feasible in carefully selected patients, and should be considered early when conventional therapy is failing, or as a salvage rescue therapy when it has failed.