Iron deficiency in sepsis patients based on reticulocyte hemoglobin and hepcidin concentration: a prospective cohort study.

Introduction: Iron tests are deranged in sepsis; therefore new biomarkers should be used for diagnosis of iron deficiency (ID)/ID anemia (IDA). Methods: Diagnosis of ID/IDA was based on reticulocyte (Ret) hemoglobin (Hb) equivalent (Ret-He) and Hb concentration, with hepcidin (Hep) determined retrospectively. Results: The prevalence of ID and IDA was 7% and 47%, respectively. The AUROCs for Rets number and Hep in prediction of ID/IDA were 0.69 and 0.62, respectively. Conclusions: Approximately half of sepsis patients are iron-deficient. Number of Rets may be a predictor of ID/IDA when Ret-He is not available. Hepcidin is a poor IDA predictor.

Comparison of Standard and New Iron Status Biomarkers: A Prospective Cohort Study in Sepsis Patients.

Both iron deficiency (ID) and iron overload can have negative effects on the risk and course of infection. Therefore, the ability to accurately assess iron status in these patients is of the utmost importance. Systemic inflammation in sepsis patients affects the results of standard iron biomarkers and makes accurate diagnosis of ID problematic. The aim of our study was to analyze the association between widely available standard iron biomarkers and selected new iron biomarkers in various iron status subgroups among sepsis patients. Consecutive patients diagnosed with sepsis or septic shock and procalcitonin concentration > 0.5 ng/mL were enrolled. The following iron biomarkers were determined: iron, ferritin, transferrin, transferrin saturation, reticulocyte (Ret) number and percentage, Ret hemoglobin equivalent, Ret fluorescence subpopulations, and hepcidin concentration. The study group comprised 90 study subjects. There were 42 (47%) patients with normal iron status, 6 (6%) with ID without anemia, and 42 (47%) with ID anemia. No meaningful correlation exists between standard and new iron biomarkers in various iron status subgroups among sepsis patients. Therefore, standard iron biomarkers cannot be used to diagnose ID in this cohort.

Iron deficiency in sepsis patients managed with divided doses of iron dextran: a prospective cohort study.

Iron deficiency (ID) impairs hemoglobin (Hb) synthesis and immune function, both crucial for sepsis patients. We assessed the impact of iron dextran on reticulocyte (Ret) Hb equivalent (Ret-He) and Ret subpopulations in iron-deficient sepsis patients. In this prospective clinical study we enrolled patients with sepsis or septic shock with procalcitonin concentration > 0.5 ng/mL, diagnosed with ID based on Ret-He. Study subjects received divided doses of iron dextran until normalization of Ret-He. The study population included 35 subjects. The median Ret-He increase after 2 doses of iron dextran was 3.0 (IQR 1.9-6.1) pg (p < 0.01) with median time to normalization 4 (IQR 3-5) days. Although no change in Ret percentage [Me 1.5 (IQR 1.1-2.1) vs. Me 1.4 (IQR 1.1-2.4) %, p = 0.39] and number [Me 0.05 (IQR 0.04-0.07) vs. Me 0.05 (IQR 0.03-0.06) 106/µL, p = 0.88] was noted, Ret subpopulations changed significantly (p for all < 0.01). Divided doses of iron dextran relatively quickly normalize Ret-He in iron-deficient sepsis patients. Changes in Ret subpopulations suggest increased erythropoietic activity. Further research is needed to explore the role of intravenous iron in this clinical setting.

Management Strategies in Septic Coagulopathy: A Review of the Current Literature.

One of the 'organs' that can be affected by sepsis is the coagulation system. Coagulopathy in sepsis may take the form of sepsis-induced coagulopathy (SIC) or sepsis-associated disseminated intravascular coagulation (DIC). It is important to identify SIC early, as at this stage of coagulopathy anticoagulants may be of the greatest benefit. The most recent diagnostic scoring systems for septic coagulopathy come from the International Society on Thrombosis and Hemostasis and the Japanese Association for Acute Medicine. Recommendations regarding the management of septic coagulopathy differ between organizations. Moreover, septic coagulopathy is an area of intense research in recent years. Therefore we searched three databases to review the most recent management strategies in septic coagulopathy. The mainstream management strategies in septic coagulopathy include the causal treatment of sepsis, unfractionated heparin, low-molecular-weight heparin, antithrombin, and recombinant human thrombomodulin. The last two have been associated with the highest survival benefit. Nevertheless, the indiscriminate use of these anticoagulants should be avoided due to the lack of mortality benefit and increased risk of bleeding. The early diagnosis of SIC and monitoring of coagulation status during sepsis is crucial for the timely management and selection of the most suitable treatment at a time. New directions in septic coagulopathy include new diagnostic biomarkers, dynamic diagnostic models, genetic markers for SIC management, and new therapeutic agents. These new research avenues may potentially result in timelier SIC diagnosis and improved management of all stages of septic coagulopathy by making it more effective, safe, and personalized.

Association between Functional Parameters of Coagulation and Conventional Coagulation Tests in the Setting of Fluid Resuscitation with Balanced Crystalloid or Gelatine: A Secondary Analysis of an In Vivo Prospective Randomized Crossover Study.

Functional point-of-care tests (POCTs) have evolved into useful tools for diagnosing disorders of blood coagulation and fibrinolysis. We aimed to describe the in vivo association between standard and functional parameters of coagulation and fibrinolysis in the setting of acute hemodilution induced by an infusion of balanced crystalloid or synthetic gelatine solutions. This prospective randomized crossover in vivo study included healthy male volunteers aged 18-30 years. Enrolled participants were randomly assigned to receive either the Optilyte® or Geloplasma® infusion. Laboratory analysis included conventional coagulation parameters and rotational thromboelastometry (ROTEM) assays. A total of 25 healthy Caucasian males were included. ROTEM viscoelastic assays presented moderate to strong correlations with conventional coagulation tests, regardless of the fluid type utilized. Irrespectively of the extent of hemodilution, significant correlations remained unaffected. The strongest associations were found between the ROTEM clot formation and clot strength and the fibrinogen concentration and platelet count, and between the ROTEM clotting time and the APTT and PT. This in vivo experimental study in healthy male volunteers demonstrated that ROTEM may be used as a credible alternative to standard laboratory tests to assess blood coagulation and fibrinolysis in the setting of fluid resuscitation with both crystalloid and colloid solutions. The study was registered online in the ClinicalTrials.gov database (NCT05148650).

In Vivo Effects of Balanced Crystalloid or Gelatine Infusions on Functional Parameters of Coagulation and Fibrinolysis: A Prospective Randomized Crossover Study.

Prudent administration of fluids helps restore or maintain hemodynamic stability in the setting of perioperative blood loss. However, fluids may arguably exacerbate the existing coagulopathy. We sought to investigate the influence of balanced crystalloid and synthetic gelatine infusions on coagulation and fibrinolysis in healthy volunteers. This prospective randomized crossover study included 25 males aged 18-30 years. Infusions performed included 20 mL/kg of a balanced crystalloid solution (Optilyte®) or 20 mL/kg of gelatine 26.500 Da (Geloplasma®) in a random order over a period of 2 weeks. Laboratory analysis included conventional coagulation parameters and rotational thromboelastometry (ROTEM) assays. We confirmed a decrease in fibrinogen concentration and the number of platelets, and prolongation of PT after infusions. Compared to baseline values, differences in the ROTEM assays' results after infusions signified the decrease in coagulation factors and fibrinogen concentration, causing impaired fibrin polymerization and clot structure. The ROTEM indicator of clot lysis remained unaffected. In the case of both Optilyte® and Geloplasma®, the results suggested relevant dilution. Gelatine disrupted the process of clot formation more than balanced crystalloid. Infusions of both crystalloid and saline-free colloid solutions causing up to 30% blood dilution cause significant dilution of the coagulation factors, platelets, and fibrinogen. However, balanced crystalloid infusion provides less infusion-induced coagulopathy compared to gelatine.

Efficacy and safety of therapeutic plasma exchange in stiff person syndrome.

The stiff person syndrome (SPS) is an extremely rare neurological disorder with primarily immune-mediated etiology. The cardinal symptoms are progressive, fluctuating axial/proximal limb muscle stiffness and spasms. The diagnosis is based on the clinical picture, electromyography examination and detection of antibodies to glutamic acid decarboxylase (anti-GAD). Adverse effects of medications might preclude its use or increase in dosing, therefore symptomatic and/or immunomodulatory medical therapy might be ineffective in acute exacerbation of the disease. We present a case of a 49-year-old female with exacerbation of SPS, in whom some standard pharmacotherapy could not be introduced (clonazepam, baclofen used in the past) and doses of existing standard medications could not be increased (diazepam, gabapentin, and levetiracetam) due to adverse effects. Moreover, a newly introduced medication (methylprednisolone) also led to a serious adverse effect (severe hyperglycemia). The patient underwent therapeutic plasma exchange (TPE) with good effect and no complications. We review the literature regarding the efficacy and safety profile of TPE in exacerbation of SPS unresponsive to medical therapy. The procedure seems to have a good safety profile as an adjunct therapy for exacerbation of SPS not responding to standard medical therapy in this patient population.

What Do We Know about Early Management of Sepsis and Septic Shock in Polish Hospitals? A Questionnaire Study.

BACKGROUND: Sepsis and septic shock are medical emergencies with a high risk of poor prognosis. We investigate the correspondence between Surviving Sepsis Campaign (SSC) guidelines and clinical practice in Poland, with special attention given to differences between ICU and non-ICU environments as well as regional variations within the country. METHODS: A web-based questionnaire study was performed on a random sample of 60 hospitals from the three most populated regions in Poland-Masovia, Silesia, and Greater Poland. A 19-item questionnaire was built based on the most recent edition of SSC guidelines. RESULTS: Sepsis diagnosis was primarily based on clinical evaluation (ICUs: 94%, non-ICUs: 62%; p = 0.02). There were significant differences between ICUs and non-ICUs regarding taking blood cultures for pathogen identification (2-times more frequent in ICUs) and having hospital-based operating procedures to adjust antimicrobial treatment to a clinical scenario (a difference of 17%). Modification of empiric antimicrobial treatment was required post-ICU admission in 70% of cases. ICUs differed from non-ICUs with regard to the methods of fluid responsiveness assessment and the types of catecholamines and fluids used to treat septic shock. The mean fluid load applied before the implementation of catecholamines was 25.8 ± 10.6 mL/kg. Norepinephrine was the first-line agent used to treat shock, and balanced crystalloids were preferred in both ICUs and non-ICUs. CONCLUSION: Compliance with SCC guidelines in Polish hospitals is insufficient, especially outside ICUs. There is a need for education among healthcare professionals to reach at least an acceptable level of knowledge and attitude in this field.

Clinical usefulness of the international renal research institute of vicenza (irriv) score in the intensive care subjects with renal failure: single-centre experience.

OBJECTIVE: The aim: Acute kidney injury (AKI) is a common and clinically important condition that affects both kidney structure and function. International Renal Research Institute of Vicenza (IRRIV) score has been designed to enable early identification of patients who may require renal replacement therapy (RRT). We aimed to assess the usefulness of the IRRIV score in predicting the outcome in the intensive care unit (ICU) patients who may require renal replacement therapy (RRT). PATIENTS AND METHODS: Material and Methods: This retrospective study screened 955 consecutive patients hospitalized in a mixed tertiary ICU between Jan 2015 and Jul 2018. Patients with sCr>3.5 mg/dl on the first 24 hours post-admission constituted the study group 1 (G1, n=54). Subjects who underwent RRT based on indications other than elevated sCr level were a study group 2 (G2, n=31). ICU mortality, a need for RRT and ICU length of stay (LoS) were the outcomes. RESULTS: Results: Median IRRIV score was 5.5 points (IQR 4.5-6.5) in G1 and 3.5 points (IQR 3-5.5) in G2. IRRIV score poorly predicted the need for RRT implementation (AUC=0.652, 95%CI 0.510-0.776, P=0.048). The IRRIV score failed to predict mortality in both groups (G1: AUC=0.610, 95%CI 0.468-0.740, P=0.16; G2: AUC=0.530, 95%CI 0.343-0.710, P=0.79). No correlation was found between the score and ICU LoS (G1: R= -0.13, P=0.36; G2: R= -0.27, P=0.15). CONCLUSION: Conclusions: The retrospective analysis of our regional data did not confirm the expected usefulness of the IRRIV score in predicting the need for RRT nor in the prognostication of the patients admitted to the ICU due to renal failure.

Hyperosmolar Treatment for Patients at Risk for Increased Intracranial Pressure: A Single-Center Cohort Study.

Treatment with osmoactive agents such as mannitol or hypertonic saline (HTS) solutions is widely used to manage or prevent the increase of intracranial pressure (ICP) in central nervous system (CNS) disorders. We sought to evaluate the variability and mean plasma concentrations of the water and electrolyte balance parameters in critically ill patients treated with osmotic therapy and their influence on mortality. This cohort study covered patients hospitalized in an intensive care unit (ICU) from January 2017 to June 2019 with presumed increased ICP or considered to be at risk of it, treated with 15% mannitol (G1, n = 27), a combination of 15% mannitol and 10% hypertonic saline (HTS) (G2, n = 33) or 10% HTS only (G3, n = 13). Coefficients of variation (Cv) and arithmetic means (mean) were calculated for the parameters reflecting the water and electrolyte balance, i.e., sodium (NaCv/NaMean), chloride (ClCv/ClMean) and osmolality (mOsmCv/mOsmMean). In-hospital mortality was also analyzed. The study group comprised 73 individuals (36 men, 49%). Mortality was 67% (n = 49). Median NaCv (G1: p = 0.002, G3: p = 0.03), ClCv (G1: p = 0.02, G3: p = 0.04) and mOsmCv (G1: p = 0.001, G3: p = 0.02) were higher in deceased patients. NaMean (p = 0.004), ClMean (p = 0.04), mOsmMean (p = 0.003) were higher in deceased patients in G3. In G1: NaCv (AUC = 0.929, p < 0.0001), ClCv (AUC = 0.817, p = 0.0005), mOsmCv (AUC = 0.937, p < 0.0001) and in G3: NaMean (AUC = 0.976, p < 0.001), mOsmCv (AUC = 0.881, p = 0.002), mOsmMean (AUC = 1.00, p < 0.001) were the best predictors of mortality. The overall mortality prediction for combined G1+G2+G3 was very good, with AUC = 0.886 (p = 0.0002). The mortality of critically ill patients treated with osmotic agents is high. Electrolyte disequilibrium is the independent predictor of mortality regardless of the treatment method used. Variations of plasma sodium, chloride and osmolality are the most deleterious factors regardless of the absolute values of these parameters.

Biomarkers Facilitate the Assessment of Prognosis in Critically Ill Patients with Primary Brain Injury: A Cohort Study.

Primary injuries to the brain are common causes of hospitalization of patients in intensive care units (ICU). The Acute Physiology and Chronic Health Evaluation (APACHE) II scoring system is widely used for prognostication among critically ill subjects. Biomarkers help to monitor the severity of neurological status. This study aimed to identify the best biomarker, along with APACHE II score, in mortality prediction among patients admitted to the ICU with the primary brain injury. This cohort study covered 58 patients. APACHE II scores were assessed 24 h post ICU admission. The concentrations of six biomarkers were determined, including the C-reactive protein (CRP), the S100 calcium-binding protein B (S100B), neuron-specific enolase (NSE), neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase 9 (MMP-9), and tissue inhibitor of metalloproteinase 1 (TIMP-1), using commercially available ELISA kits. The biomarkers were specifically chosen for this study due to their established connection to the pathophysiology of brain injury. In-hospital mortality was the outcome. Median APACHE II was 18 (IQR 13-22). Mortality reached 40%. Median concentrations of the CRP, NGAL, S100B, and NSE were significantly higher in deceased patients. S100B (AUC = 0.854), NGAL (AUC = 0.833), NSE (AUC = 0.777), and APACHE II (AUC = 0.766) were the best independent predictors of mortality. Combination of APACHE II with S100B, NSE, NGAL, and CRP increased the diagnostic accuracy of mortality prediction. MMP and TIMP-1 were impractical in prognostication, even after adjustment for APACHE II score. S100B protein and NSE seem to be the best predictors of compromised outcome among critically ill patients with primary brain injuries and should be assessed along with the APACHE II calculation after ICU admission.

Intraoperative Blood Pressure Variability Predicts Postoperative Mortality in Non-Cardiac Surgery-A Prospective Observational Cohort Study.

Little is known about the clinical importance of blood pressure variability (BPV) during anesthesia in non-cardiac surgery. We sought to investigate the impact of intraoperative BPV on postoperative mortality in non-cardiac surgery subjects, taking into account patient- and procedure-related variables. This prospective observational study covered 835 randomly selected patients who underwent gastrointestinal (n = 221), gynecological (n = 368) and neurosurgical (n = 246) procedures. Patient's and procedure's risks were assessed according to the validated tools and guidelines. Blood pressure (systolic, SBP, and diastolic, DBP) was recorded in five-minute intervals during anesthesia. Mean arterial pressure (MAP) was assessed. Individual coefficients of variation (Cv) were calculated. Postoperative 30-day mortality was considered the outcome. Median SBP_Cv was 11.2% (IQR 8.4-14.6), DBP_Cv was 12.7% (IQR 9.8-16.3) and MAP_Cv was 10.96% (IQR 8.26-13.86). Mortality was 2%. High SBP_Cv (i.e., ≥11.9%) was associated with increased mortality by 4.5 times (OR = 4.55; 95% CI 1.48-13.93; p = 0.008). High DBP_Cv (i.e., ≥22.4%) was associated with increased mortality by nearly 10 times (OR = 9.73; 95% CI 3.26-28.99; p < 0.001). High MAP_Cv (i.e., ≥13.6%) was associated with increased mortality by 3.5 times (OR = 3.44; 95% CI 1.34-8.83; p = 0.01). In logistic regression, it was confirmed that the outcome was dependent on both SBPV and DBPV, after adjustment for perioperative variables, with AUCSBP_Cv = 0.884 (95% CI 0.859-0.906; p < 0.001) and AUCDBP_Cv = 0.897 (95% CI 0.873-0.918; p < 0.001). Therefore, intraoperative BPV may be considered a prognostic factor for the postoperative mortality in non-cardiac surgery, and DBPV seems more accurate in outcome prediction than SBPV.