Christian Zauner

Weight-adjusted resting energy expenditure is not constant in critically ill patients

ObjectiveIn critically ill patients, energy requirements are frequently calculated as axa0multiple of total body weight presuming axa0linear relationship between total body weight and resting energy expenditure (REE); however, it is doubtful if this estimation of energy needs should be applied to all patients, particularly to overweight patients, since adipose tissue has axa0low contribution to REE. This study was undertaken to test the hypothesis that REE adjusted for total body weight decreases with increasing body mass index in critically ill patients. Additionally, measured REE was compared with three predictive equations.Design and SettingClinical study in axa0university hospital intensive care unit.PatientsOne hundred critically ill patients admitted to the intensive care unit.Measurements and resultsPatients were included into four groups according to their body mass index (normal weight, pre-obese, obese, and morbidly obese). Measured REE was assessed using indirect calorimetry. Energy needs were calculated using the basal metabolic rate, the Consensus Statement of the American College of Chest Physicians (REEacs), and 25u202fkcal/kg of ideal body weight (REEibw). Adjusted REE was 24.8u202f±u202f5.5u202fkcal/kg in normal weight, 22.0u202f±u202f3.7u202fkcal/kg in pre-obese, 20.4u202f±u202f2.6u202fkcal/kg in obese, and 16.3u202f±u202f2.3u202fkcal/kg in morbidly obese patients (pu202f<u202f0.01). Basal metabolic rate underestimated measured REE in normal weight and pre-obese patients. REEacs and REEibw over- and underestimated measured REE in overweight patients, respectively.ConclusionsPredictive equations were not able to estimate measured REE adequately in all the patients. Adjusted REE decreased with increasing body mass index; thus, axa0body mass index group-specific adaptation for the estimation of energy needs should be applied.

Clinical impact of arterial ammonia levels in ICU patients with different liver diseases

PurposeIncreased arterial ammonia levels are associated with high mortality in patients with acute liver failure (ALF). Data on the prognostic impact of arterial ammonia is lacking in hypoxic hepatitis (HH) and scarce in critically ill patients with cirrhosis.MethodsThe patient cohort comprised 72 patients with HH, 43 patients with ALF, 100 patients with liver cirrhosis and 45 patients without evidence for liver disease. Arterial ammonia concentrations were assessed on a daily basis in all patients and the results were compared among these four patient groups and between 28-day survivors and 28-day non-survivors overall and in each group.ResultsOverall 28-day mortality rates in patients with HH, ALF and cirrhosis and in the control group were 54, 30, 49 and 27xa0%, respectively. Peak arterial ammonia levels differed significantly between transplant-free 28-day survivors and non-survivors in the HH and ALF groups (pxa0<xa00.01 for both). Multivariate regression identified peak arterial ammonia concentrations as an independent predictor of 28-day mortality or liver transplantation in patients with HH and ALF, respectively (pxa0<xa00.01). There was no association between mortality and arterial ammonia in patients with liver cirrhosis and in the control group. Admission arterial ammonia levels were independently linked to hepatic encephalopathy grades 3/4 in patients with HH (pxa0<xa00.01), ALF (pxa0<xa00.05) and cirrhosis (pxa0<xa00.05), respectively.ConclusionsElevated arterial ammonia levels indicate a poor prognosis in acute liver injury and are associated with advanced HE in HH, ALF and cirrhosis. Arterial ammonia levels provide additional information in the risk assessment of critically ill patients with liver disease.

Statin therapy is associated with reduced incidence of hypoxic hepatitis in critically ill patients

BACKGROUND & AIMSnHypoxic hepatitis (HH) is a frequent and life-threatening complication associated with states of oxygen depletion in critically ill patients. Ischemia and reperfusion contribute to liver injury in HH. Experimental data suggest beneficial effects of statins in hepatic ischemia/reperfusion injury. This study was conducted to investigate whether statin treatment prior to intensive care unit (ICU) admission affects incidence rates and severity of HH.nnnMETHODSnEight hundred fifty-one patients admitted consecutively to three medical ICUs between December 2008 and December 2009 were prospectively screened for new occurrence of HH within 48 h following ICU admission. Statin treatment prior to ICU admission was assessed. 28-day-, 90-day-, and 1-year-survival as well as new-onset of complications in HH patients were prospectively documented.nnnRESULTSnEighty-seven patients (10%) developed HH. Statin treatment prior to ICU admission was significantly associated with decreased incidence of HH within 48 h after ICU admission in the multivariate analysis (adjusted OR=0.42 (95% CI 0.19-0.95); p<0.05). Cardiogenic shock (p<0.001), septic shock (p<0.001) and active alcohol consumption (p<0.01) were identified as independent risk factors for development of HH. 28-day-, 90-day-, and 1-year-mortality rates in HH were 58%, 67%, and 74%, respectively. Statins were associated with improved 28-day-survival in the total study cohort (p<0.05), but did not affect 90-day- and 1-year-mortality, respectively.nnnCONCLUSIONSnCardiogenic shock, septic shock, and active alcohol consumption were independent factors predisposing patients to new onset of HH. Statin treatment prior to ICU admission was the only protective factor regarding the new occurrence of HH in critically ill patients.

Renal replacement therapy in critically ill liver cirrhotic patients – Outcome and Clinical Implications

Current guidelines discourage renal replacement therapy (RRT) in critically ill cirrhotics in the lack of liver transplant (LT) options. This study aimed to identify patients who benefit from RRT in the short and long‐term.

Outcome and features of acute kidney injury complicating hypoxic hepatitis at the medical intensive care unit

BackgroundHypoxic hepatitis (HH) is a frequent and potentially life-threatening event typically occurring in critically ill patients as a consequence of hemodynamic impairment. While acute kidney injury (AKI) has been well described in patients with acute liver failure, incidence and outcome of AKI accompanying HH are unclear. The aim of this study was to assess incidence, clinical implications and outcome of AKI and renal replacement therapy (RRT) in critically ill patients with HH.MethodsA total of 1948 consecutive critically ill admissions were studied at the Medical University of Vienna. Laboratory and clinical parameters as well as the presence of HH and AKI were assessed on a daily basis. Outcome, renal recovery and length of stay were assessed and documented, and patients were followed for 1xa0year.ResultsA total of 295 admissions (15xa0%) developed HH. Main precipitators were cardiogenic (44xa0%) and septic shock (36xa0%). Occurrence of HH was significantly associated with AKI [OR 4.50 (95xa0% CI 3.30–6.12)] and necessity of renal replacement therapy [RRT; OR 3.36 (95xa0% CI 2.58–4.37)], pxa0<xa00.001 for both. Two hundred forty admissions with HH (81xa0%) developed AKI, 159 of whom (66xa0%) had AKI stage 3. Both HH and AKI were significantly linked to mortality. AKI stage 3, international normalized ratio (INR, during HH) and the presence of septic shock were identified as independent predictors of 28-day mortality in admissions with HH, whereas RRT was identified as an independent protective factor. There was a synergistic effect of HH and AKI on length of stay at the ICU. Of all HH survivors treated with RRT, 71xa0% showed renal recovery during follow-up.ConclusionHH is frequently complicated by occurrence of AKI. Severity of HH, AKI stage and the presence of septic shock seem to contribute to poor outcome in these patients. Initiation of RRT in HH with AKI may enable renal recovery and should not be withheld in medical ICU patients.

Mixed‐lineage eosinophil/basophil crisis in MDS: a rare form of progression

Backgroundu2002 Basophilic crisis and eosinophilia are well recognized features of advanced chronic myeloid leukaemia. In other myeloid neoplasms, however, transformation with marked basophilia and eosinophilia is considered unusual.

Acid-base disorders in liver disease

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.

Gender-specific differences in energy metabolism during the initial phase of critical illness.

Background/objectives:Women and men differ in substrate and energy metabolism. Such differences may affect energy requirements during the acute phase of critical illness.Subjects/methods:Data of 155 critically ill medical patients were reviewed for this study. Indirect calorimetry in each patient was performed within the first 72u2009h following admission to the medical intensive care unit after an overnight fast.Results:In overweight (body mass index (BMI)⩾25u2009kg/m2) but not in normal-weight patients, resting energy expenditure (REE) adjusted for body weight (REEaBW) differed significantly between women and men (17.2 (interquartile range (IQR) 15.2–20.7) vs 20.9 (IQR 17.9–23.4) kcal/kg/day, P<0.01). Similarly, REE adjusted for ideal body weight (REEaIBW) was significantly lower in women compared with men (25.5 (IQR 22.6–28.1) vs 28.0 (IQR 25.2–30.0) kcal/kg/day, P<0.05). In overweight patients, gender was identified as an independent predictor of REEaBW in the multivariate regression model (r=−2.57 (95% CI −4.57 to −0.57); P<0.05), even after adjustment for age, simplified acute physiology score (SAPS II), body temperature, body weight and height.Conclusions:REEaBW decreases with increasing body mass in both sexes. This relationship differs between women and men. Overweight critically ill women show significantly lower REEaBW and REEaIBW, respectively, compared with men. These findings could affect the current practice of nutritional support during the early phase of critical illness.

Renal tubular acidosis is highly prevalent in critically ill patients.

IntroductionHyperchloremic acidosis is frequent in critically ill patients. Renal tubular acidosis (RTA) may contribute to acidemia in the state of hyperchloremic acidosis, but the prevalence of RTA has never been studied in critically ill patients. Therefore, we aimed to investigate the prevalence, type, and possible risk factors of RTA in critically ill patients using a physical-chemical approach.MethodsThis prospective, observational trial was conducted in a medical ICU of a university hospital. One hundred consecutive critically ill patients at the age ≥18, expected to stay in the ICU for ≥24xa0h, with the clinical necessity for a urinary catheter and the absence of anuria were included.Base excess (BE) subset calculation based on a physical-chemical approach on the first 7xa0days after ICU admission was used to compare the effects of free water, chloride, albumin, and unmeasured anions on the standard base excess. Calculation of the urine osmolal gap (UOG) - as an approximate measure of the unmeasured urine cation NH4+ - served as determinate between renal and extrarenal bicarbonate loss in the state of hyperchloremic acidosis.ResultsDuring the first week of ICU stay 43 of the patients presented with hyperchloremic acidosis on one or more days represented as pronounced negative BEChloride. In 31 patients hyperchloremic acidosis was associated with RTA characterized by a UOG ≤150xa0mosmol/kg in combination with preserved renal function. However, in 26 of the 31 patients with RTA metabolic acidosis was neutralized by other acid-base disturbances leading to a normal arterial pH.ConclusionsRTA is highly prevalent in critically ill patients with hyperchloremic acidosis, whereas it is often neutralized by the simultaneous occurrence of other acid-base disturbances.Trial registrationClinicaltrials.gov NCT02392091. Registered 17 March 2015

Pharmacokinetics of Ganciclovir during Continuous Venovenous Hemodiafiltration in Critically Ill Patients

ABSTRACT Ganciclovir is an antiviral agent that is frequently used in critically ill patients with cytomegalovirus (CMV) infections. Continuous venovenous hemodiafiltration (CVVHDF) is a common extracorporeal renal replacement therapy in intensive care unit patients. The aim of this study was to investigate the pharmacokinetics of ganciclovir in anuric patients undergoing CVVHDF. Population pharmacokinetic analysis was performed for nine critically ill patients with proven or suspected CMV infection who were undergoing CVVHDF. All patients received a single dose of ganciclovir at 5 mg/kg of body weight intravenously. Serum and ultradiafiltrate concentrations were assessed by high-performance liquid chromatography, and these data were used for pharmacokinetic analysis. Mean peak and trough prefilter ganciclovir concentrations were 11.8 ± 3.5 mg/liter and 2.4 ± 0.7 mg/liter, respectively. The pharmacokinetic parameters elimination half-life (24.2 ± 7.6 h), volume of distribution (81.2 ± 38.3 liters), sieving coefficient (0.76 ± 0.1), total clearance (2.7 ± 1.2 liters/h), and clearance of CVVHDF (1.5 ± 0.2 liters/h) were determined. Based on population pharmacokinetic simulations with respect to a target area under the curve (AUC) of 50 mg · h/liter and a trough level of 2 mg/liter, a ganciclovir dose of 2.5 mg/kg once daily seems to be adequate for anuric critically ill patients during CVVHDF.