Pervitin Intoxication with Two-peak Massive Myoglobinemia, Acute Kidney Injury and Marked Procalcitonin Increase Not Associated with Sepsis.

Patients intoxicated with methamphetamine-like substances may present with myoglobinuria but rarely require admission. An 18-year-old female was admitted due to intoxication with pervitin, a methamphetamine derivative. She presented with an altered mental status, fever, and increased heart and respiratory rates. Biomarkers showed leukocytosis and markedly increased procalcitonin levels, suggestive of sepsis. However, blood cultures and infectious disease workup were unrevealing. Clinical course was heralded by rhabdomyolysis and myoglobinuria resulting in multi-organ failure including respiratory failure necessitating mechanical ventilation, hemodynamic compromise with need for inotropic support, and an acute renal failure requiring renal replacement therapy. Surprisingly, after a transient improvement, an unexpected second peak of myoglobin was observed on hospital day 5, controlled by intensifying the elimination methods, and administration of dantrolene. Acute kidney injury resolved by hospital day 15, and the patient could be discharged on day 22. While most patients with intoxications are discharged within 24 hours from emergency departments without being admitted, our case report highlights that the organ injury may evolve beyond the usual observation period, traditional renal-replacement therapies may not be sufficient to mitigate myoglobinemia with resulting acute kidney injury, and that procalcitonin may not be a reliable biomarker of infection in the setting of drug-induced rhabdomyolysis.

Diagnostic and prognostic value of presepsin vs. established biomarkers in critically ill patients with sepsis or systemic inflammatory response syndrome.

BACKGROUND: Inflammatory biomarkers may aid to distinguish between systemic inflammatory response syndrome (SIRS) vs. sepsis. We tested the hypotheses that (1) presepsin, a novel biomarker, can distinguish between SIRS and sepsis, and (2) higher presepsin levels will be associated with increased severity of illness and (3) with 28-day mortality, outperforming traditional biomarkers. METHODS: Procalcitonin (PCT), C-reactive protein (CRP), presepsin, and lactate were analyzed in 60 consecutive patients (sepsis and SIRS, n=30 per group) on day 1 (D1) to D3 (onset sepsis, or after cardiac surgery). The systemic organ failure assessment (SOFA) score was determined daily. RESULTS: There was no difference in mortality in sepsis vs. SIRS (12/30 vs. 8/30). Patients with sepsis had higher SOFA score vs. patients with SIRS (11±4 vs. 8±5; p=0.023), higher presepsin (AUC=0.674; p<0.021), PCT (AUC=0.791; p<0.001), CRP (AUC=0.903; p<0.0001), but not lactate (AUC=0.506; p=0.941). Unlike other biomarkers, presepsin did not correlate with SOFA on D1. All biomarkers were associated with mortality on D1: presepsin (AUC=0.734; p=0.0006; best cutoff=1843 pg/mL), PCT (AUC=0.844; p<0.0001), CRP (AUC=0.701; p=0.0048), and lactate (AUC=0.778; p<0.0001). Multiple regression analyses showed independent associations of CRP with diagnosis of sepsis, and CRP and lactate with mortality. Increased neutrophils (p=0.002) and decreased lymphocytes (p=0.007) and monocytes (p=0.046) were also associated with mortality. CONCLUSIONS: Presepsin did not outperform traditional sepsis biomarkers in diagnosing sepsis from SIRS and in prognostication of mortality in critically ill patients. Presepsin may have a limited adjunct value for both diagnosis and an early risk stratification, performing independently of clinical illness severity.

Ionized Magnesium and Regional Citrate Anticoagulation for Continuous Renal Replacement Therapy.

BACKGROUND: The regional citrate anticoagulation (RCA) induces changes in total (Catot) and ionized (Ca2+) calcium. As of now, we do not have much information about parallel changes of total (Mgtot) and ionized (Mg2+) magnesium. METHODS: The authors compared changes of Mg2+ and Mgtot with changes of Ca2+ and Catot in 32 critically ill patients on 4% trisodium citrate (4% TSC) with calcium-free fluids. RESULTS: The median continuous venovenous hemodiafiltration balance of Mgtot was -0.91 (-1.18 to -0.53) mmol/h compared to the median balance of Catot 0.86 (0.08-1.55) mmol/h. Postfilter Mg2+ decreased by 68.3% (70.8-65.6) in parallel (r = 0.41, p = 0.03) to decrease of postfilter Ca2+ (by 70.2% (73.0-66.1)) and was significantly related to the postfilter Ca2+ (r = 0.50, p < 0.001). The decrease of prefilter to postfilter Ca2+ correlated to a dosage of 4% TSC per blood flow (r = 0.37, p = 0.04). CONCLUSIONS: The loss of Mgtot during RCA is not covered by magnesium concentration in ordinary dialysis/substitution fluid and may lead to the depletion of total body magnesium. The postfilter Mg2+ is significantly related to the postfilter Ca2+. Video Journal Club "Cappuccino with Claudio Ronco" at http://www.karger.com/?doi = 440972.

[Refeeding syndrome]. / Realimentacní syndrom.

Despite being known more than 60 years, refeeding syndrome (RS) still bears many uncertainties. For example, its definition is not clear and definite, and the attitude to it varies from the complete neglect to over-prevention.The term "refeeding syndrome" refers to electrolyte and metabolic changes occurring in malnourished patients after the readministration of nutrition. These changes concern especially to phosphates and ions. Potassium, magnesium, naturism and fluids balance are involved. The changes lead to cell energetic metabolism and electric potential disturbances, with related clinical symptoms.Fully developed refeeding syndrome is quite rare; nevertheless it can be fatal for the patient. However, even its development can lead to many complications increasing the patient's morbidity and the length of stay in the hospital. Yet the refeeding syndrome is more or less predictable and if kept in mind also preventable.The aim of this article is to get the reader to know more about this metabolic phenomenon and possible attitudes towards it.

Pitfalls in the laboratory assessment of serum prealbumin levels in hemato-oncological patients.

BACKGROUND: To highlight specific aspects of serum prealbumin measurements in hemato-oncological patients. METHODS: Retrospective analysis of 4911 serum prealbumin measurements with special attention to values from hemato-oncological Intensive Care Units (ICU) patients. RESULTS: Prealbumin serum levels in hemato-oncological ICU patients (n = 530) were significantly higher when compared to other ICU cohorts (p < 0.0001). Their prealbuminemia did not correlate with serum albumin (p = 0.104) and was not affected by serum cholesterol or triglycerides (p = 0.076 and p = 0.430, respectively). Surprisingly, serum prealbumin has shown a positive correlation with cyclosporine in whole blood levels (r = 0.269, p = 0.010). CONCLUSIONS: A supposed explanation for our findings probably lies in a combination of several factors, including interference with the analysis itself and contamination or possible interference with the medication, e.g., cyclosporine. The prealbumin values do not reflect the actual nutritional state and cannot be regarded as a useful marker of malnutrition in these patients.

The effects of a novel calcium-free lactate buffered dialysis and substitution fluid for regional citrate anticoagulation--prospective feasibility study.

BACKGROUND: Testing metabolic effects of a novel calcium-free, magnesium, phosphate and lactate containing solution (Lactocitrate) in combination with citrate anticoagulation. METHODS: Patients on CRRT (2,000 ml/h, blood flow (Qb) 100 ml/min, trisodium citrate (4% TSC)) with arterial lactate <3 mmol/l were included. At start, bicarbonate-buffered fluid was changed to Lactocitrate and the substitution of magnesium and phosphorus ceased. At 9 h the Qb was increased to 150 ml/min. At 18 h the CRRT dosage was increased to 3,000 ml/h. RESULTS: In 22 CVVHDF patients and another 23 on CVVH the pH, aHCO3 and Na (all p > 0.05) showed no significant changes regardless of the increased dosage of 4% TSC at 9 h (p < 0.001). Mgtot and phosphorus stabilised within normal range. Arterial lactate increased to 1.9 (1.6-2.6) mmol/l at 3,000 ml/h, p < 0.001). Citrate- and lactate-related energetic gains were up to 74 (61-86) kJ/h. CONCLUSIONS: The fluid performed well within ordinary CRRT dosage and Qb up to 150 ml/min. Lactate levels mildly increased and no magnesium and phosphorus replenishments were necessary.

Increasing Rate of Fatal Streptococcus pyogenes Bacteriemia-A Challenge for Prompt Diagnosis and Appropriate Therapy in Real Praxis.

Streptococcus pyogenes, group A streptococci (GAS) bacteriaemia, is a life-threatening infection with high mortality, requiring fast diagnosis together with the use of appropriate antibiotic therapy as soon as possible. Our study analysed data from 93 patients with GAS bacteraemia at the General University Hospital in Prague between January 2006 and March 2024. In the years 2016-2019 there was an increase in GAS bacteraemia. Mortality in the period 2006-2019 was 21.9%; in the period 2020-2024, the mortality increased to 41.4%, p = 0.08. At the same time, in the post-2020 period, the time from hospital admission to death was reduced from 9.5 days to 3 days. A significant predictor of worse outcome in this period was high levels of procalcitonin, >35.1 µg/L (100% sensitivity and 82.35% specificity), and lactate, >5 mmol/L (90.91% sensitivity and 91.67% specificity). Myoglobin was a significant predictor in both compared periods, the AUC was 0.771, p = 0.044, and the AUC was an even 0.889, p ≤ 0.001, respectively. All isolates of S. pyogenes were susceptible to penicillin, and resistance to clindamycin was 20.3% from 2006-2019 and 10.3% in 2020-2024. Appropriate therapy was initiated in 89.1%. and 96.6%, respectively. We hypothesise that the increase in mortality after 2020 might be due to a decrease in the immune status of the population.

Biomarkers for neuroprognostication after standard versus extracorporeal cardiopulmonary resuscitation - A sub-analysis of Prague-OHCA study.

BACKGROUND: Limited evidence exists for prognostic performance of biomarkers in patients resuscitated from out-of-hospital cardiac arrest (OHCA) with extracorporeal CPR (ECPR). We hypothesized that (1) the time course and (2) prognostic performance of biomarkers might differ between CPR and ECPR in a sub-analysis of Prague-OHCA study. METHODS: Patients received either CPR (n = 164) or ECPR (n = 92). The primary outcome was favorable neurologic survival at 180 days [cerebral performance category (CPC) 1-2]. Secondary outcomes included biomarkers of neurologic injury, inflammation and hemocoagulation. RESULTS: Favorable neurologic outcome was not different between groups: CPR 29.3% vs. ECPR 21.7%; p = 0.191. Biomarkers exhibited similar trajectories in both groups, with better values in patients with CPC 1-2. Procalcitonin (PCT) was higher in ECPR group at 24-72 h (all p < 0.01). Neuron-specific enolase (NSE), C-reactive protein and neutrophil-to-lymphocyte ratio did not differ between groups. Platelets, D-dimers and fibrinogen were lower in ECPR vs. CPR groups at 24-72 h (all p < 0.001). ROC analysis (24-48-72 h) showed the best performance of NSE in both CPR and ECPR groups (AUC 0.89 vs. 0.78; 0.9 vs. 0.9; 0.91 vs. 0.9). PCT showed good performance specifically in ECPR (0.72 vs. 0.84; 0.73 vs. 0.87; 0.73 vs. 0.86). Optimal cutoff points of NSE and PCT were higher in ECPR vs. CPR. CONCLUSIONS: Biomarkers exhibited similar trajectories although absolute values tended to be higher in ECPR. NSE had superior performance in both groups. PCT showed a good performance specifically in ECPR. Additional biomarkers may have modest incremental value. Prognostication algorithms should reflect the resuscitation method.

Substantially elevated C-reactive protein (CRP), together with low levels of procalcitonin (PCT), contributes to diagnosis of fungal infection in immunocompromised patients.

PURPOSE: Serum procalcitonin (PCT) has become a routinely utilized parameter with a high prediction value of the severity of bacterial infectious complications and their immediate outcomes. Whereas the utility of PCT in differentiating between bacterial and viral infection is generally accepted, its significance in fungal infections has yet to be determined. The aim of the study was to determine the role of PCT testing in patients at high risk for invasive fungal infections. METHODS: Immunocompromised hematological patients undergoing cyclic chemotherapy treatment or allogeneic hemopoietic stem cell transplantation with infectious complications in which the infectious agents were identified during the disease course were evaluated. In patients with bacterial infection, positive hemocultures were documented, and in patients with fungal infection, the presence of either proven or probable disease was confirmed according to Ascioglu criteria. C-reactive protein (CRP) and PCT were prospectively assessed from the day following fever onset, for four consecutive days. RESULTS: Overall, 34 patients were evaluated, 21 with bacterial and 13 with fungal infections. Significant elevations of CRP concentrations (i.e., above the upper normal limit) were observed in all patients, with a tendency toward higher levels in bacterial (both gram-positive [Gr+] and Gr-negative [Gr-]) than in fungal infections. PCT levels were significantly elevated in patients with bacterial infections (e.g., predominantly in Gr- compared to Gr+), whereas in patients with fungal infections, we identified minimal or no PCT elevations, p < 0.01. For the fungal infections, according to constructed receiver operating characteristic curves, a combination of PCT <0.5 µg/L and CRP 100-300 mg/L offers the best specificity, sensitivity and positive and negative predictive values (81, 85, 73, and 89 %, respectively). CONCLUSION: Altogether, our data suggest that the finding of substantially elevated CRP combined with low PCT in immunocompromised patients may indicate systemic fungal infection. The use of this combination might simplify the diagnostic process, which otherwise can often be lengthy and arduous.

Soluble receptor for advanced glycation end products predicts 28-day mortality in critically ill patients with sepsis.

OBJECTIVE: Multiple biomarkers are used to assess sepsis severity and prognosis. Increased levels of the soluble receptor for advanced glycation end products (sRAGE) were previously observed in sepsis but also in end-organ injury without sepsis. We evaluated associations between sRAGE and (i) 28-day mortality, (ii) sepsis severity, and (iii) individual organ failure. Traditional biomarkers procalcitonin (PCT), C-reactive protein (CRP) and lactate served as controls. METHODS: sRAGE, PCT, CRP, and lactate levels were observed on days 1 (D1) and 3 (D3) in 54 septic patients. We also assessed the correlation between the biomarkers and acute respiratory distress syndrome (ARDS), acute kidney injury (AKI) and acute heart failure. RESULTS: There were 38 survivors and 16 non-survivors. On D1, non-survivors had higher sRAGE levels than survivors (p = 0.027). On D3, sRAGE further increased only in non-survivors (p < 0.0001) but remained unchanged in survivors. Unadjusted odds ratio (OR) for 28-day mortality was 8.2 (95% CI: 1.02-60.64) for sRAGE, p = 0.048. Receiver operating characteristic analysis determined strong correlation with outcome on D3 (AUC = 0.906, p < 0.001), superior to other studied biomarkers. sRAGE correlated with sepsis severity (p < 0.00001). sRAGE showed a significant positive correlation with PCT and CRP on D3. In patients without ARDS, sRAGE was significantly higher in non-survivors (p < 0.0001) on D3. CONCLUSION: Increased sRAGE was associated with 28-day mortality in patients with sepsis, and was superior compared to PCT, CRP and lactate. sRAGE correlated with sepsis severity. sRAGE was increased in patients with individual organ failure. sRAGE could be used as an early biomarker in prognostication of outcome in septic patients.

The Role of Micronutrients in Neurological Disorders.

Trace elements and vitamins, collectively known as micronutrients, are essential for basic metabolic reactions in the human body. Their deficiency or, on the contrary, an increased amount can lead to serious disorders. Research in recent years has shown that long-term abnormal levels of micronutrients may be involved in the etiopathogenesis of some neurological diseases. Acute and chronic alterations in micronutrient levels may cause other serious complications in neurological diseases. Our aim was to summarize the knowledge about micronutrients in relation to selected neurological diseases and comment on their importance and the possibilities of therapeutic intervention in clinical practice.

Serum lactate in refractory out-of-hospital cardiac arrest: Post-hoc analysis of the Prague OHCA study.

BACKGROUND: The severity of tissue hypoxia is routinely assessed by serum lactate. We aimed to determine whether early lactate levels predict outcomes in refractory out-of-hospital cardiac arrest (OHCA) treated by conventional and extracorporeal cardiopulmonary resuscitation (ECPR). METHODS: This study is a post-hoc analysis of a randomized Prague OHCA study (NCT01511666) assessing serum lactate levels in refractory OHCA treated by ECPR (the ECPR group) or conventional resuscitation with prehospital achieved return of spontaneous circulation (the ROSC group). Lactate concentrations measured on admission and every 4 hours (h) during the first 24 h were used to determine their relationship with the neurological outcome (the best Cerebral Performance Category score within 180 days post-cardiac arrest). RESULTS: In the ECPR group (92 patients, median age 58.5 years, 83% male) 26% attained a favorable neurological outcome. In the ROSC group (82 patients, median age 55 years, 83% male) 59% achieved a favorable neurological outcome. In ECPR patients lactate concentrations could discriminate favorable outcome patients, but not consistently in the ROSC group. On admission, serum lactate >14.0 mmol/L for ECPR (specificity 87.5%, sensitivity 54.4%) and >10.8 mmol/L for the ROSC group (specificity 83%, sensitivity 41.2%) predicted an unfavorable outcome. CONCLUSION: In refractory OHCA serum lactate concentrations measured anytime during the first 24 h after admission to the hospital were found to correlate with the outcome in patients treated by ECPR but not in patients with prehospital ROSC. A single lactate measurement is not enough for a reliable outcome prediction and cannot be used alone to guide treatment.

Evaluation of presepsin as a diagnostic tool in newborns with risk of early-onset neonatal sepsis.

Objectives: To evaluate the efficacy of presepsin (P-SEP) as a potential biomarker of early-onset neonatal sepsis (EOS) and compare it to other routinely used markers of inflammation. To establish the cut-off values of P-SEP for EOS. Study design: 184 newborns were prospectively recruited between January 2018 to December 2020. Newborns >34th gestational week with suspected infection were included up to 72 h after delivery, and divided into three categories (i.e., unlikely, possible, and probable infection) based on risk factors, clinical symptoms and laboratory results. Values of plasma P-SEP were sequentially analyzed. Results: Median values of P-SEP in newborns with probable infection were significantly higher compared to healthy newborns (p = 0.0000013) and unlikely infection group (p = 0.0000025). The AUC for discriminating the probable infection group from the unlikely infection group was 0.845 (95% Cl: 0.708-0.921). The diagnostic efficacy of P-SEP was highest when used in combination with IL-6 and CRP (0.97; 95% CI: 0.911-0.990). The optimal cut-off value of P-SEP was determined to be 695 ng/L. Conclusion: P-SEP, when combined with IL-6 and CRP, may be utilized as a negative predictive marker of EOS (NPV 97.2%, 95% CI: 93.3-101), especially in newborns at low to medium risk of infection.

Procalcitonin interference in an immunometric calcitonin assay.

BACKGROUND: Procalcitonin (PCT) increases in septic patients, and is not transformed into calcitonin (CT). We found in septic patients, a significant increase of CT, as determined by an immunoassay using polyclonal antibodies. We compare determination using polyclonal and monoclonal AB. METHODS: We included 34 patients: 17 with clinical signs of sepsis, a positive haemoculture (PCT > 0.5 µg/L) and 17 without them (PCT < 0.1 µg/L). CT was determined by two above-mentioned methods. The influence on CT levels was observed after using the high-concentration PCT calibrator addition to a mixed serum sample with a low concentration of CT. The dilution test of the high-concentration calibrator PCT was performed by an IBL calibrator, with a zero calcitonin concentration. RESULTS: In the septic patients we found an interference in calcitonin determination using the polyclonal AB (IRMA); 24.1-718 µg/L, proportional to the PCT levels (r = 0.814, p < 0.0001). When using the monoclonal AB (ELISA), the calcitonin levels < 6.5-46.3 ng/L, and no interference of PCT was observed. In the non-septic group, we did not record any PCT interference using either the polyclonal or the monoclonal AB, and the CT levels were within the reference ranges using the two methods (r = 0.997, p < 0.0001). The recovery and dilution tests confirmed interference by PCT on the calcitonin determination with the polyclonal antibody. CONCLUSIONS: Results show that in septic patients there is visible interference of PCT in the calcitonin determination, principally in the IRMA method (polyclonal AB); while no such relationship was observed in the ELISA method (monoclonal AB).

Comparison of long-term stability of parenteral all-in-one admixtures containing new lipid emulsions prepared under hospital pharmacy conditions.

UNLABELLED: All-in-one (AIO) admixtures for parenteral nutrition are common in hospital pharmacy practices. They are extemporaneously prepared and should be stable during preparation, storage, and administration. Lipid emulsion is a clinically important and very susceptible component of instability. The objective of study was to evaluate the long-term stability of AIO admixtures containing modern lipid emulsions. MATERIAL AND METHODS: AIO admixtures with two different emulsions (SMOFlipid and Lipoplus) containing the same amount of glucose and complex amino acid solution, and variable amounts of ions were prepared. Samples were evaluated at 2, 5, 8 and 30 days after preparation. The main indicator of AIO system stability was the amount of lipid globules greater than 5 µm in diameter, which is limited by pharmacopoeia. Optical microscopy was used for particle size measurement. RESULTS: All prepared AIO admixtures remained stable during observation. The counts of overlimit lipid particles were within pharmacopeial limit nevertheless tended to increase in time. After 30-day storage, their value was influenced mainly by concentration of calcium ions, which at lower concentrations had a greater impact on SMOFlipid-based admixtures, whereas at the highest concentration on Lipoplus-based admixtures. The concentration of ions and osmolarity remained without changes; pH of admixtures slightly decreased. CONCLUSIONS: Both lipid emulsions were found to be suitable for preparation AIO admixtures with different concentrations of electrolytes. The formulations were stable even if contained high concentrations of divalent ions. The comparison of emulsions revealed the superiority of Lipoplus - electrolyte concentrations and duration of storage had a greater impact on admixtures with SMOFlipid.

Plasma calprotectin in chronically dialyzed end-stage renal disease patients.

OBJECTIVE: The current study aimed to evaluate plasma calprotectin levels and clearance end-stage renal disease (ESRD) patients with and without acute infection undergoing chronic hemodialysis (HD). MATERIALS AND METHODS: Blood samples from 54 HD patients were obtained before and after the HD and 42 healthy blood donors were examined as controls. The blood levels of calprotectin, procalcitonin, C-reactive protein (CRP), and intracellular production of interleukins 10 and 12 in monocytes were determined in both groups. RESULTS: The concentrations of plasma calprotectin in ESRD patients were significantly higher than in healthy controls (p < 0.05). No differences between pre- and post-HD calprotectin plasma levels were observed (p = 0.07 for two-tailed test). Plasma calprotectin levels were not significantly influenced by the presence of acute infection (p = 0.19) or diabetes (p = 0.42). A significant positive correlation of plasma calprotectin to plasma beta-2 microglobulin was proven (p < 0.05). Procalcitonin (PCT), CRP, IL-10, and IL-12 were not correlated with plasma calprotectin before or after HD. The elevation of plasma calprotectin was correlated strongly to the hemodialysis vintage (r = 0.55, p < 0.01). CONCLUSIONS: Significantly elevated levels of plasma calprotectin in ESRD patients occur without an acute infectious cause and are not affected by the presence of diabetes. By analogy to plasma beta-2 microglobulin, a close relation of plasma calprotectin to HD vintage was shown.

Marked increase of procalcitonin after the administration of anti-thymocyte globulin in patients before hematopoietic stem cell transplantation does not indicate sepsis: a prospective study.

INTRODUCTION: Procalcitonin (PCT) and C-reactive protein (CRP) are established markers of infection in the general population. In contrast, several studies reported falsely increased PCT levels in patients receiving T-cell antibodies. We evaluated the validity of these markers in patients scheduled for hemopoietic stem cell transplantation receiving anti-thymocyte globulin (ATG) during conditioning. We also assessed renal and liver functions and their relationship to PCT and CRP changes. METHODS: Twenty-six patients without clinical signs of infection were prospectively studied. ATG was administered in up to three doses over the course of 5 days. PCT, CRP, white blood cell (WBC) count, urea, creatinine, glomerular filtration rate, bilirubin, alanin amino-transferase (ALT), and gamma-glutamyl transferase (GGT) were assessed daily during ATG administration. Pharyngeal, nose, and rectal swabs and urine samples were cultured twice weekly. Blood cultures were obtained if clinical symptoms of infection were present. RESULTS: Baseline (BL) levels of both PCT and CRP before ATG administration were normal. WBC count decreased after ATG administration (P = 0.005). One day after ATG administration, both PCT and CRP levels increased significantly, returning to BL levels on day 4. Microbiological results were clinically unremarkable. There was no interrelationship between PCT levels and BL markers of renal or liver functions (P > 0.05 for all comparisons). Bilirubin and GGT were increased on days 2 to 5 and ALT was increased on day 3 (P < 0.05 versus BL). No difference in renal functions was observed. Three patients developed bacterial infection on days 7 to 11 with different dynamics of PCT and CRP. There was no association between the number of ATG doses and PCT levels or between the risk of developing infection and previous PCT levels. CONCLUSIONS: ATG triggered a marked early surge in PCT and CRP followed by a steady decrease over the course of 3 days. The dynamics of both PCT and CRP were similar and were not associated with infection. PCT levels were independent of renal and liver functions and were not predictive of further infectious complications. A direct effect of ATG on T lymphocytes could be the underlying mechanism. Hepatotoxic effect could be a contributing factor. Neither PCT nor CRP is a useful marker that can identify infection in patients receiving ATG.

Plasma sRAGE is independently associated with increased mortality in ARDS: a meta-analysis of individual patient data.

PURPOSE: The soluble receptor for advanced glycation end-products (sRAGE) is a marker of lung epithelial injury and alveolar fluid clearance (AFC), with promising values for assessing prognosis and lung injury severity in acute respiratory distress syndrome (ARDS). Because AFC is impaired in most patients with ARDS and is associated with higher mortality, we hypothesized that baseline plasma sRAGE would predict mortality, independently of two key mediators of ventilator-induced lung injury. METHODS: We conducted a meta-analysis of individual data from 746 patients enrolled in eight prospective randomized and observational studies in which plasma sRAGE was measured in ARDS articles published through March 2016. The primary outcome was 90-day mortality. Using multivariate and mediation analyses, we tested the association between baseline plasma sRAGE and mortality, independently of driving pressure and tidal volume. RESULTS: Higher baseline plasma sRAGE [odds ratio (OR) for each one-log increment, 1.18; 95% confidence interval (CI) 1.01-1.38; P = 0.04], driving pressure (OR for each one-point increment, 1.04; 95% CI 1.02-1.07; P = 0.002), and tidal volume (OR for each one-log increment, 1.98; 95% CI 1.07-3.64; P = 0.03) were independently associated with higher 90-day mortality in multivariate analysis. Baseline plasma sRAGE mediated a small fraction of the effect of higher ΔP on mortality but not that of higher VT. CONCLUSIONS: Higher baseline plasma sRAGE was associated with higher 90-day mortality in patients with ARDS, independently of driving pressure and tidal volume, thus reinforcing the likely contribution of alveolar epithelial injury as an important prognostic factor in ARDS. Registration: PROSPERO (ID: CRD42018100241).

The Effects of High Level Magnesium Dialysis/Substitution Fluid on Magnesium Homeostasis under Regional Citrate Anticoagulation in Critically Ill.

BACKGROUND: The requirements for magnesium (Mg) supplementation increase under regional citrate anticoagulation (RCA) because citrate acts by chelation of bivalent cations within the blood circuit. The level of magnesium in commercially available fluids for continuous renal replacement therapy (CRRT) may not be sufficient to prevent hypomagnesemia. METHODS: Patients (n = 45) on CRRT (2,000 ml/h, blood flow (Qb) 100 ml/min) with RCA modality (4% trisodium citrate) using calcium free fluid with 0.75 mmol/l of Mg with additional magnesium substitution were observed after switch to the calcium-free fluid with magnesium concentration of 1.50 mmol/l (n = 42) and no extra magnesium replenishment. All patients had renal indications for CRRT, were treated with the same devices, filters and the same postfilter ionized calcium endpoint (<0.4 mmol/l) of prefilter citrate dosage. Under the high level Mg fluid the Qb, dosages of citrate and CRRT were consequently escalated in 9h steps to test various settings. RESULTS: Median balance of Mg was -0.91 (-1.18 to -0.53) mmol/h with Mg 0.75 mmol/l and 0.2 (0.06-0.35) mmol/h when fluid with Mg 1.50 mmol/l was used. It was close to zero (0.02 (-0.12-0.18) mmol/h) with higher blood flow and dosage of citrate, increased again to 0.15 (-0.11-0.25) mmol/h with 3,000 ml/h of high magnesium containing fluid (p<0.001). The arterial levels of Mg were mildly increased after the change for high level magnesium containing fluid (p<0.01). CONCLUSIONS: Compared to ordinary dialysis fluid the mildly hypermagnesemic fluid provided even balances and adequate levels within ordinary configurations of CRRT with RCA and without a need for extra magnesium replenishment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01361581.