Hypophosphatemia after Start of Medical Nutrition Therapy Indicates Early Refeeding Syndrome and Increased Electrolyte Requirements in Critically Ill Patients but Has No Impact on Short-Term Survival.

Refeeding syndrome (RFS) is a potentially life-threatening complication in malnourished (critically ill) patients. The presence of various accepted RFS definitions and the inclusion of heterogeneous patient populations in the literature has led to discrepancies in reported incidence rates in patients requiring treatment at an intensive care unit (ICU). We conducted a prospective observational study from 2010 to 2013 to assess the RFS incidence and clinical characteristics among medical ICU patients at a large tertiary center. RFS was defined as a decrease of more than 0.16 mmol/L serum phosphate to values below 0.65 mmol/L within seven days after the start of medical nutrition therapy or pre-existing serum phosphate levels below 0.65 mmol/L. Overall, 195 medical patients admitted to the ICU were included. RFS was recorded in 92 patients (47.18%). The presence of RFS indicated significantly altered phosphate and potassium levels and was accompanied by significantly more electrolyte substitutions (phosphate, potassium, and magnesium). No differences in fluid balance, energy delivery, and insulin requirements were detected. The presence of RFS had no impact on ICU length of stay and ICU mortality. Screening for RFS using simple diagnostic criteria based on serum phosphate levels identified critically ill patients with an increased demand for electrolyte substitutions. Therefore, stringent monitoring of electrolyte levels is indicated to prevent life-threatening complications.

[Treatment of acute diabetic metabolic crises in adults (Update 2023) : Hyperglycemic hyperosmolar state and ketoacidotic metabolic disorder]. / Therapie der akuten diabetischen Stoffwechselentgleisungen bei Erwachsenen (Update 2023) : Hyperglykämisch-hyperosmolare und ketoazidotische Stoffwechselentgleisung.

Diabetic ketoacidosis (DKA) and the hyperglycemic hyperosmolar state (HHS) represent potentially life-threatening situations in adults. Therefore, rapid comprehensive diagnostic and therapeutic measures with close monitoring of vital and laboratory parameters are required. The treatment of DKA and HHS is essentially the same and replacement of the mostly substantial fluid deficit with several liters of a physiological crystalloid solution is the first and most important step. Serum potassium concentrations need to be carefully monitored to guide its substitution. Regular insulin or rapid acting insulin analogues can be initially administered as an i.v. bolus followed by continuous infusion. Insulin should be switched to subcutaneous injections only after correction of the acidosis and stable glucose concentrations within an acceptable range.

Age-dependent differences in energy metabolism in the acute phase of critical illness.

OBJECTIVES: Resting energy expenditure (REE) declines with age in healthy individuals, independent of the age-related decrease in lean body mass. The aim of this study was to evaluate whether this holds true in critically ill medical patients. Moreover, we assessed how measured REE compares with energy requirements calculated by prediction equations in different age groups. METHODS: In this retrospective cohort study, 200 critically ill medical patients with need for mechanical ventilation underwent indirect calorimetry within 72 h of admission after an overnight fast to determine REE. REE was adjusted for body weight (REEaBW). Patients were divided into age quartiles (I: 18-35, n = 21; II: 36-52, n = 43; III 53-69, n = 93; IV = 70-86 y, n = 43). Sex, Simplified Acute Physiology Score II, temperature at time of measurement, height, weight, and body mass index were assessed. We calculated energy requirements by Harris-Benedict and Mifflin-St. Jeor equations. Kruskal-Wallis test was used for group comparisons. Parameters that were significant in univariate regression entered the multivariate regression model. RESULTS: REE (P = 0.009) and REEaBW (P < 0.001) declined with age in our study population. Multivariate regression reveals age (R = -8.49 (95% CI -8.30- -1.83), P = 0.003), P = 0.004) and body temperature (R = 92.52 (95% CI 40.08-135.97, P < 0.001) as independent predictors for REE. CONCLUSION: REE and REEaBW decrease with age in critically ill medical patients. Age and body temperature are independent predictors of both REE and REEaBW. Prediction equations underestimate energy requirements in critically ill medical patients.

Impact of age on the cumulative risk of transformation in patients with chronic myelomonocytic leukaemia.

In older patients with chronic myelomonocytic leukaemia (CMML) and limited life expectancy due to age and or comorbidities, it is particularly important to consider the risk of transformation for individualised treatment decisions. There is limited information on potential differences between younger and older CMML patients regarding the cumulative risk of transformation as well as haematological, molecular and biologic characteristics. We analysed data from the Austrian Biodatabase for CMML (ABCMML) to compare these parameters in 518 CMML patients. Categorisation of patients into 3 age-related groups: <60 years, 60-79 years and ≥80 years, showed a significantly lower risk of transformation at higher age by competing risk analysis, with a 4-year risk of 39%, 23% and 13%, respectively (P < .0001). The lower probability of transformation was associated with a lower percentage of blast cells in the peripheral blood (PB) of older patients. Furthermore, we provide a simple score based on age, PB blasts and platelet counts that allowed us to define subgroups of CMML patients with a different cumulative transformation risk, including a low-risk group with a transformation risk of only 5%. Our findings may facilitate reasonable treatment decisions in elderly patients with CMML.

Correlation of RAS-Pathway Mutations and Spontaneous Myeloid Colony Growth with Progression and Transformation in Chronic Myelomonocytic Leukemia-A Retrospective Analysis in 337 Patients.

Although the RAS-pathway has been implicated as an important driver in the pathogenesis of chronic myelomonocytic leukemia (CMML) a comprehensive study including molecular and functional analyses in patients with progression and transformation has not been performed. A close correlation between RASopathy gene mutations and spontaneous in vitro myeloid colony (CFU-GM) growth in CMML has been described. Molecular and/or functional analyses were performed in three cohorts of 337 CMML patients: in patients without (A, n = 236) and with (B, n = 61) progression/transformation during follow-up, and in patients already transformed at the time of sampling (C, n = 40 + 26 who were before in B). The frequencies of RAS-pathway mutations (variant allele frequency ≥ 20%) in cohorts A, B, and C were 30%, 47%, and 71% (p < 0.0001), and of high colony growth (≥20/105 peripheral blood mononuclear cells) 31%, 44%, and 80% (p < 0.0001), respectively. Increases in allele burden of RAS-pathway mutations and in numbers of spontaneously formed CFU-GM before and after transformation could be shown in individual patients. Finally, the presence of mutations in RASopathy genes as well as the presence of high colony growth prior to transformation was significantly associated with an increased risk of acute myeloid leukemia (AML) development. Together, RAS-pathway mutations in CMML correlate with an augmented autonomous expansion of neoplastic precursor cells and indicate an increased risk of AML development which may be relevant for targeted treatment strategies.

The Austrian biodatabase for chronic myelomonocytic leukemia (ABCMML) : A representative and useful real-life data source for further biomedical research.

In the Austrian biodatabase for chronic myelomonocytic leukemia (ABCMML) clinicolaboratory real-life data have been captured from 606 CMML patients from 14 different hospitals over the last 30 years. It is the only large biodatabase worldwide in which functional methods such as semisolid in vitro cultures complement modern molecular methods such as next generation sequencing. This provides the possibility to comprehensively study the biology of CMML. The aim of this study was to compare patient characteristics with published CMML cohorts and to validate established prognostic parameters in order to examine if this real-life database can serve as a representative and useful data source for further research. After exclusion of patients in transformation characteristics of 531 patients were compared with published CMML cohorts. Median values for age, leukocytes, hemoglobin, platelets, lactate dehydrogenase (LDH) and circulating blasts were within the ranges of reported CMML series. Established prognostic parameters including leukocytes, hemoglobin, blasts and adverse cytogenetics were able to discriminate patients with different outcome. Myeloproliferative (MP) as compared to myelodysplastic (MD)-CMML patients had higher values for circulating blasts, LDH, RAS-pathway mutations and for spontaneous myelomonocytic colony growth in vitro as well as more often splenomegaly. This study demonstrates that the patient cohort of the ABCMML shares clinicolaboratory characteristics with reported CMML cohorts from other countries and confirms phenotypic and genotypic differences between MP-CMML and MD-CMML. Therefore, results obtained from molecular and biological analyses using material from the national cohort will also be applicable to other CMML series and thus may have a more general significance.

[Treatment of acute diabetic metabolic crises in adults (Update 2019) : Hyperglycemic hyperosmolar state and ketoacidotic metabolic disorders]. / Therapie der akuten diabetischen Stoffwechselentgleisungen bei Erwachsenen (Update 2019) : Hyperglykämisch-hyperosmolare und ketoazidotische Stoffwechselentgleisung.

Diabetic ketoacidosis (DKA) and the hyperglycemic hyperosmolar state (HHS) represent potentially life-threatening situations in adults. Therefore, rapid comprehensive diagnostic and therapeutic measures with close monitoring of vital and laboratory parameters are required. The treatment of DKA and HHS is essentially the same and replacement of the mostly substantial fluid deficit with several liters of a physiological crystalloid solution is the first and most important step. Serum potassium concentrations need to be carefully monitored to guide its substitution. Regular insulin or rapid acting insulin analogues can be initially administered as an i.v. bolus followed by continuous infusion. Insulin should be switched to subcutaneous injections only after correction of the acidosis and stable glucose concentrations within an acceptable range.

Correction: Different enteral nutrition formulas have no effect on glucose homeostasis but on diet-induced thermogenesis in critically ill medical patients: a randomized controlled trial.

After publication, the author noticed that Table 2 was incorrectly formatted for the final PDF despite being correct in earlier proofs. The table was correct in the HTML version of the article. The EJCN apologizes for the inadvertent error in the formatting of Table 2. The corrected version is uploaded and should be read in conjunction with the original paper. Any inconvenience to the author and readership is regretted.

Acid-base status and its clinical implications in critically ill patients with cirrhosis, acute-on-chronic liver failure and without liver disease.

BACKGROUND: Acid-base disturbances are frequently observed in critically ill patients at the intensive care unit. To our knowledge, the acid-base profile of patients with acute-on-chronic liver failure (ACLF) has not been evaluated and compared to critically ill patients without acute or chronic liver disease. RESULTS: One hundred and seventy-eight critically ill patients with liver cirrhosis were compared to 178 matched controls in this post hoc analysis of prospectively collected data. Patients with and without liver cirrhosis showed hyperchloremic acidosis and coexisting hypoalbuminemic alkalosis. Cirrhotic patients, especially those with ACLF, showed a marked net metabolic acidosis owing to increased lactate and unmeasured anions. This metabolic acidosis was partly antagonized by associated respiratory alkalosis, yet with progression to ACLF resulted in acidemia, which was present in 62% of patients with ACLF grade III compared to 19% in cirrhosis patients without ACLF. Acidemia and metabolic acidosis were associated with 28-day mortality in cirrhosis. Patients with pH values < 7.1 showed a 100% mortality rate. Acidosis attributable to lactate and unmeasured anions was independently associated with mortality in liver cirrhosis. CONCLUSIONS: Cirrhosis and especially ACLF are associated with metabolic acidosis and acidemia owing to lactate and unmeasured anions. Acidosis and acidemia, respectively, are associated with increased 28-day mortality in liver cirrhosis. Lactate and unmeasured anions are main contributors to metabolic imbalance in cirrhosis and ACLF.

Different enteral nutrition formulas have no effect on glucose homeostasis but on diet-induced thermogenesis in critically ill medical patients: a randomized controlled trial.

BACKGROUND/OBJECTIVES: Hyperglycemia is common in critically ill patients and associated with increased mortality. It has been suggested that different nutrition formulas may beneficially influence glucose levels in surgical intensive care patients. In this prospective randomized clinical cohort study we investigated glucose homeostasis in response to different enteral nutrition formulas in medical critically ill patients. SUBJECTS/METHODS: 60 medical critically ill patients were randomized to receive continuous fat-based (group A, n = 30) or glucose-based enteral nutrition (group B, n = 30) for seven days. Indirect calorimetry was performed to determine energy demand at baseline and on days 3 and 7. Glucose levels and area under the curve (AUC), insulin demand, glucose variability, and calorie and substrate intake per 24 h were assessed for 7 days. RESULTS: Over the course of 7 days patients had similar average daily glucose (p = 0.655), glucose AUC (A: 758 (641-829) mg/dl/day vs B: 780 (733-845) mg/dl/day, p = 0.283), similar overall insulin demand (A: 153.5 (45.3-281.5) IE vs B: 167.9 (82.3-283.8) IE, p = 0.525), and received similar amounts of enteral nutrition per 24 h. Resting energy expenditure was similar at baseline (A: 1556 (1227-1808) kcal/day vs B: 1563 (1306-1789) kcal/day, p = 0.882) but energy expenditure increased substantially over time in group A (p < 0.0001), but not in group B (p = 0.097). CONCLUSION: Fat-based and glucose-based EN influence glucose homeostasis and insulin demand similarly, yet diet-induced thermogenesis was substantially higher in critically ill patients receiving fat-based enteral nutrition.

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.

Resting energy expenditure and substrate oxidation rates correlate to temperature and outcome after cardiac arrest - a prospective observational cohort study.

INTRODUCTION: Targeted temperature management improves outcome after cardiopulmonary resuscitation. Reduction of resting energy expenditure might be one mode of action. The aim of this study was to correlate resting energy expenditure and substrate oxidation rates with targeted temperature management at 33°C and outcome in patients after cardiac arrest. METHODS: This prospective, observational cohort study was performed at the department of emergency medicine and a medical intensive care unit of a university hospital. Patients after successful cardiopulmonary resuscitation undergoing targeted temperature management at 33°C for 24 hours with subsequent rewarming to 36°C and standardized sedation, analgesic and paralytic medication were included. Indirect calorimetry was performed five times within 48 h after cardiac arrest. Measurements were correlated to outcome with repeated measures ANOVA, linear and logistic regression analysis. RESULTS: In 25 patients resting energy expenditure decreased 20 (18 to 27) % at 33°C compared to 36°C without differences between outcome groups (favourable vs. unfavourable: 25 (21 to 26) vs. 21 (16 to 26); P = 0.5). In contrast to protein oxidation rate (favourable vs. unfavourable: 35 (11 to 68) g/day vs. 39 (7 to 75) g/day, P = 0.8) patients with favourable outcome had a significantly higher fat oxidation rate (139 (104 to 171) g/day vs. 117 (70 to 139) g/day, P <0.05) and a significantly lower glucose oxidation rate (30 (-34 to 88) g/day vs. 77 (19 to 138) g/day; P < 0.05) as compared to patients with unfavourable neurological outcome. CONCLUSIONS: Targeted temperature management at 33°C after cardiac arrest reduces resting energy expenditure by 20% compared to 36°C. Glucose and fat oxidation rates differ significantly between patients with favourable and unfavourable neurological outcome. TRIAL REGISTRATION: Clinicaltrials.gov NCT00500825. Registered 11 July 2007.

Renal tubular acidosis is highly prevalent in critically ill patients.

INTRODUCTION: Hyperchloremic 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. METHODS: This 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 ≥24 h, 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 7 days 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. RESULTS: During 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 ≤150 mosmol/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. CONCLUSIONS: RTA 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 REGISTRATION: Clinicaltrials.gov NCT02392091. Registered 17 March 2015.

Evaporation of free water causes concentrational alkalosis in vitro.

BACKGROUND: The development of metabolic alkalosis was described recently in patients with hypernatremia. However, the causes for this remain unknown. The current study serves to clarify whether metabolic alkalosis develops in vitro after removal of free water from plasma and whether this can be predicted by a mathematical model. MATERIALS AND METHODS: Ten serum samples of healthy humans were dehydrated by 29 % by vacuum centrifugation corresponding to an increase of the contained concentrations by 41 %. Constant partial pressure of carbon dioxide at 40 mmHg was simulated by mathematical correction of pH [pH(40)]. Metabolic acid-base state was assessed by Gilfix' base excess subsets. Changes of acid-base state were predicted by the physical-chemical model according to Watson. RESULTS: Evaporation increased serum sodium from 141 (140-142) to 200 (197-203) mmol/L, i.e., severe hypernatremia developed. Acid-base analyses before and after serum concentration showed metabolic alkalosis with alkalemia: pH(40): 7.43 (7.41 to 7.45) vs 7.53 (7.51 to 7.55), p = 0.0051; base excess: 1.9 (0.7 to 3.6) vs 10.0 (8.2 to 11.8), p = 0.0051; base excess of free water: 0.0 (- 0.2 to 0.3) vs 17.7 (16.8 to 18.6), p = 0.0051. The acidifying effects of evaporation, including hyperalbuminemic acidosis, were beneath the alkalinizing ones. Measured and predicted acid-base changes due to serum evaporation agreed well. CONCLUSIONS: Evaporation of water from serum causes concentrational alkalosis in vitro, with good agreement between measured and predicted acid-base values. At least part of the metabolic alkalosis accompanying hypernatremia is independent of renal function.

A critique of Stewart's approach: the chemical mechanism of dilutional acidosis.

OBJECTIVE: While Stewart's acid-base approach is increasingly used in clinical practice, it has also led to new controversies. Acid-base disorders can be seen from different viewpoints: on the diagnostic/clinical, quantitative/mathematical, or the mechanistic level. In recent years, confusion in the interpretation and terminology of Stewart's approach has arisen from mixing these different levels. This will be demonstrated on the basis of a detailed analysis of the mechanism of "dilutional acidosis." In the classical dilution concept, metabolic acidosis after resuscitation with large volumes is attributed to the dilution of serum bicarbonate. However, Stewart's approach rejects this explanation and offers an alternative one that is based on a decrease in a "strong ion difference." This mechanistic explanation is questionable for principal chemical reasons. The objective of this study is to clarify the chemical mechanism of dilutional acidosis. METHODS: Experimental data and simulations of various dilution experiments, as well as theoretical and chemical considerations were used. RESULTS: 1. The key to understanding the mechanism of dilutional acidosis lies in the open CO2/HCO3 (-)-buffer system where the buffer base (HCO3(-)) is diluted whereas the buffer acid is not diluted (constant pCO2). 2. The categorization in independent and dependent variables depends on the system regarded. 3. Neither the principle of electroneutrality, nor a change in [SID], nor increased H2O dissociation plays a mechanistic role. CONCLUSION: Stewart's approach is valid at the mathematical level but does not provide any mechanistic insights. However, the quantification and categorization of acid-base disorders, using Stewart approach, may be helpful in clinical practice. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00134-009-1528-y) contains supplementary material, which is available to authorized users.

The strong ion gap and outcome after cardiac arrest in patients treated with therapeutic hypothermia: a retrospective study.

OBJECTIVE: This study investigates whether the strong ion gap (SIG) is associated with long-term outcome after cardiac arrest in patients treated with therapeutic hypothermia. The hypothesis of the study was that an elevated SIG was associated with unfavourable outcome after cardiac arrest. DESIGN: Retrospective review of records from 1995 to 2007 of patients who received cardiopulmonary resuscitation. SETTING: Emergency department of a university hospital. PATIENTS: Patients who were successfully resuscitated after cardiac arrest (n = 288) and treated with mild therapeutic hypothermia. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Acid-base variables were calculated according to Stewart's approach, as modified by Figge and Fencl, and were determined immediately on admission and 12 h after the return of spontaneous circulation. Acid-base variables were determined at 37 degrees C and are reported without correction for patient temperature. Differences in SIG were compared between patients with favourable (survival 6 months with cerebral performance category 1 or 2) and unfavourable outcomes. SIG on admission and 12 h after return of spontaneous circulation was higher in patients with unfavourable outcome (n = 151; 52%). SIG 12 h after return of spontaneous circulation was identified as an independent predictor of outcome. A SIG > 8.9 mmol/L was associated with an increased cumulative hazard of death. CONCLUSIONS: An elevated SIG 12 h after return of spontaneous circulation may be associated with unfavourable outcome in patients after cardiac arrest treated with mild therapeutic hypothermia. The unmeasured anions hidden behind an elevated SIG may represent markers of tissue damage.

Hypernatremia in the critically ill is an independent risk factor for mortality.

BACKGROUND: Hypernatremia is common in the intensive care unit (ICU). We assessed the prevalence of hypernatremia and its impact on mortality and ICU length of stay (LOS). STUDY DESIGN: Retrospective analysis. SETTING & PARTICIPANTS: All patients admitted to a medical ICU of a university hospital during a 35-month observation period. PREDICTOR: Hypernatremia (serum sodium > 149 mmol/L) after admission to the ICU. OUTCOMES & MEASUREMENTS: Main outcomes were 28-day hospital mortality and ICU LOS. Demographic factors, main diagnosis, and severity of illness. Cox proportional hazards regression models were used for data analysis. RESULTS: Of 981 patients, 90 (9%) had hypernatremia, on admission to the ICU in 21 (2%) and developed during the ICU stay in 69 patients (7%). Of these 981 patients, 235 (24%) died; LOS was 8 +/- 9 (SD) days. Mortality rates were 39% and 43% in patients with hypernatremia on admission or that developed after admission compared with 24% in patients without hypernatremia (P < 0.01). LOS was 20 +/- 16 days in patients with hypernatremia compared with 8 +/- 10 days in patients without hypernatremia (P < 0.001). In multivariable analysis, hypernatremia was an independent risk factor for mortality (relative risk, 2.1; 95% confidence interval, 1.4 to 3.3). LIMITATIONS: Retrospective design, absence of data for long-term mortality. CONCLUSIONS: Most cases of hypernatremia in the ICU developed after admission, suggesting an iatrogenic component in its evolution. Hypernatremia is associated with increased mortality. Strategies for preventing hypernatremia in the ICU should be encouraged.