Disturbances of coagulation and hemostasis are common in patients with liver cirrhosis. The typical laboratory pattern mimics disseminated intravascular coagulation (DIC). The aim of this study was to assess the impact of routine coagulation parameters in critically ill cirrhosis patients with regard to new onset of major bleeding and outcome. A total of 1,493 critically ill patients were studied prospectively. Routine coagulation parameters were assessed, and the DIC score was calculated based on platelets, fibrinogen, d-dimer, and prothrombin index. New onset of major bleeding during the stay at the intensive care unit and mortality were assessed. Patients were followed for 1 year. Two hundred eleven patients of the cohort had liver cirrhosis. Platelets, fibrinogen, prothrombin index, activated partial thromboplastin time, and d-dimer as well as the DIC score differed significantly between patients with and without cirrhosis (P < 0.001 for all). Moreover, fibrinogen, platelets, and activated partial thromboplastin time (but not prothrombin index) differed significantly between cirrhosis patients with and without major bleeding (P < 0.01 for all). Bleeding on admission, platelet count <30 < 10 9 /L, fibrinogen level <60 mg/dL, and activated partial thromboplastin time values >100 seconds were the strongest independent predictors for new onset of major bleeding in multivariate regression analysis. One-year mortality in cirrhosis patients with and without major bleeding was 89% and 68%, respectively (P < 0.05 between groups). Conclusion: Abnormal coagulation parameters and high DIC scores (primarily due to fibrinogen and platelets) correspond to increased bleeding risk in patients with liver cirrhosis in the intensive care unit, and fibrinogen and platelet count were identified as the best routine coagulation parameters for prediction of new onset of major bleeding; however, further studies are required to evaluate the potential therapeutic implications of these findings. (HEPATOLOGY 2016;64:556-568)

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Ammonia is considered the major pathogenetic factor of cerebral dysfunction in hepatic failure. The correlation between total plasma ammonia and the severity of hepatic encephalopathy (HE), however, is variable. Because ammonia that is present in gaseous form readily enters the brain, the correlation with the grade of HE of the pH-dependent partial pressure of gaseous ammonia (pNH 3 ) could be better than that of total arterial ammonia levels. To test this hypothesis, 56 cirrhotic patients with acute episodes of clinical HE (median age, 54 years; range, 21-75) were studied by clinical examination and by long-latency mediannerve sensory-evoked potentials (SEPs) N70 peak, an objective and sensitive electrophysiological measure of HE. pNH 3 was calculated from arterial blood according to published methods. The clinical grade of HE correlated (P F .001) with both pNH 3 and total ammonia, but correlation was stronger with pNH 3 (r ‫؍‬ .79 vs. .69, P ‫؍‬ .01). A similar correlation was found for N70 peak latency (r ‫؍‬ .71 with pNH 3 vs. .64 with total ammonia, respectively, P ‫؍‬ .08). In summary, arterial pNH 3 correlates more closely than total ammonia with the degree of clinical and electrophysiological abnormalities in HE. These findings support the ammonia hypothesis of HE and suggest that pNH 3 might be superior to total ammonia in the pathophysiological evaluation of HE. (HEPATOLOGY 2000;31:30-34.)Although there is little doubt that ammonia plays a major role in the pathogenesis of hepatic encephalopathy (HE), 1-3 the relation between plasma ammonia and the severity of cerebral dysfunction is variable. 4 Many investigators have described a close correlation between ammonia levels and cerebral function (for review, see Butterworth et al. 3 ), whereas others have questioned either the strength of such a correlation or even any causal relationship between ammonia and HE. 5-7 Some of this discrepancy can be resolved by accounting for the frequent use of venous ammonia levels, which are appreciably lower than arterial ammonia, to which the brain is exposed. 4 A further important reason may be related to ammonia kinetics. In biological fluids, ammonia exists in 2 forms: as ammonium ion and as gaseous, unionized ammonia (NH 3 ). 8 At a physiological pH of 7.4, 98% of total plasma ammonia is ionized and 2% is present as gaseous NH 3 . 8 In intracellular fluid where the pH is about 7.0, an even smaller fraction exists as unionized NH 3 . Because biological membranes are much more permeable to nonionized than to ionized molecules, 8 only the nonionized NH 3 freely diffuses through the blood-brain barrier. 9 Partial pressure of NH 3 (pNH 3 ) can be calculated from total ammonia and pH 10 and increases with pH. Despite an almost universal validity across species, 8 the phenomenon of pH-dependent ammonia toxicity has been largely ignored in the clinical setting. In this study, arterial pNH 3 was compared with total arterial ammonia levels regarding their correlation with the severity of HE. Cerebral dysfunction was assesse...

Alongside the kidneys and lungs, the liver has been recognised as an important regulator of acid-base homeostasis. While respiratory alkalosis is the most common acid-base disorder in chronic liver disease, various complex metabolic acid-base disorders may occur with liver dysfunction. While the standard variables of acid-base equilibrium, such as pH and overall base excess, often fail to unmask the underlying cause of acid-base disorders, the physical-chemical acid-base model provides a more in-depth pathophysiological assessment for clinical judgement of acid-base disorders, in patients with liver diseases. Patients with stable chronic liver disease have several offsetting acidifying and alkalinising metabolic acid-base disorders. Hypoalbuminaemic alkalosis is counteracted by hyperchloraemic and dilutional acidosis, resulting in a normal overall base excess. When patients with liver cirrhosis become critically ill (e.g., because of sepsis or bleeding), this fragile equilibrium often tilts towards metabolic acidosis, which is attributed to lactic acidosis and acidosis due to a rise in unmeasured anions. Interestingly, even though patients with acute liver failure show significantly elevated lactate levels, often, no overt acid-base disorder can be found because of the offsetting hypoalbuminaemic alkalosis. In conclusion, patients with liver diseases may have multiple co-existing metabolic acid-base abnormalities. Thus, knowledge of the pathophysiological and diagnostic concepts of acid-base disturbances in patients with liver disease is critical for therapeutic decision making.

Hypoxic hepatitis (HH) is the most frequent cause of acute liver injury in critically ill patients. No clinical data exist about new onset of jaundice in patients with HH. This study aimed to evaluate the incidence and clinical effect of jaundice in critically ill patients with HH. Two hundred and six consecutive patients with HH were screened for the development of jaundice during the course of HH. Individuals with preexisting jaundice or liver cirrhosis at the time of admission (n = 31) were excluded from analysis. Jaundice was diagnosed in patients with plasma total bilirubin levels >3 mg/dL. One‐year‐survival, infections, and cardiopulmonary, gastrointestinal (GI), renal, and hepatic complications were prospectively documented. New onset of jaundice occurred in 63 of 175 patients with HH (36%). In patients who survived the acute event of HH, median duration of jaundice was 6 days (interquartile range, 3‐8). Patients who developed jaundice (group 1) needed vasopressor treatment (P < 0.05), renal replacement therapy (P < 0.05), and mechanical ventilation (P < 0.05) more often and had a higher maximal administered dose of norepinephrine (P < 0.05), compared to patients without jaundice (group 2). One‐year survival rate was significantly lower in group 1, compared to group 2 (8% versus 25%, respectively; P < 0.05). Occurrence of jaundice was associated with an increased frequency of complications during follow‐up (54% in group 1 versus 35% in group 2; P < 0.05). In particular, infections as well as renal and GI complications occurred more frequently in group 1 during follow‐up. Conclusion: Jaundice is a common finding during the course of HH. It leads to an increased rate of complications and worse outcome in patients with HH. (HEPATOLOGY 2012)