PURPOSE: The aim of this study was to examine the effects of intravenous (IV) fluid restriction on time to resolution of hyperlactatemia in septic shock. Hyperlactatemia in sepsis is associated with worse outcome. Sepsis guidelines suggest targeting lactate clearance to guide fluid therapy despite the complexity of hyperlactatemia and the potential harm of fluid overload. METHODS: We conducted a post hoc analysis of serial plasma lactate concentrations in a sub-cohort of 777 patients from the international multicenter clinical CLASSIC trial (restriction of intravenous fluids in intensive care unit (ICU) patients with septic shock). Adult ICU patients with septic shock had been randomized to restrictive (n = 385) or standard (n = 392) intravenous fluid therapy. The primary outcome, time to resolution of hyperlactatemia, was analyzed with a competing-risks regression model. Death and discharge were competing outcomes, and administrative censoring was imposed 72 h after randomization if hyperlactatemia persisted. The regression analysis was adjusted for the same stratification variables and covariates as in the original CLASSIC trial analysis. RESULTS: The hazard ratios (HRs) for the cumulative probability of resolution of hyperlactatemia, in the restrictive vs the standard group, in the unadjusted analysis, with time split, were 0.94 (confidence interval (CI) 0.78-1.14) at day 1 and 1.21 (0.89-1.65) at day 2-3. The adjusted analyses were consistent with the unadjusted results. CONCLUSION: In this post hoc retrospective analysis of a multicenter randomized controlled trial (RCT), a restrictive intravenous fluid strategy did not seem to affect the time to resolution of hyperlactatemia in adult ICU patients with septic shock.

• Klíčová slova
• Fluid therapy, Hyperlactatemia, Lactate, Sepsis, Septic shock,
• MeSH
• časové faktory MeSH
• hyperlaktatemie * etiologie   MeSH
• jednotky intenzivní péče * statistika a číselné údaje   MeSH
• kyselina mléčná krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• septický šok * terapie   komplikace   krev   mortalita   MeSH
• tekutinová terapie * metody   normy   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• kyselina mléčná MeSH

BACKGROUND: Hydroxyethyl starch (HES) solutions are used for volume therapy to treat hypovolemia due to acute blood loss and to maintain hemodynamic stability. This study was requested by the European Medicines Agency (EMA) to provide more evidence on the long-term safety and efficacy of HES solutions in the perioperative setting. METHODS: PHOENICS is a randomized, controlled, double-blind, multi-center, multinational phase IV (IIIb) study with two parallel groups to investigate non-inferiority regarding the safety of a 6% HES 130 solution (Volulyte 6%, Fresenius Kabi, Germany) compared with a crystalloid solution (Ionolyte, Fresenius Kabi, Germany) for infusion in patients with acute blood loss during elective abdominal surgery. A total of 2280 eligible patients (male and female patients willing to participate, with expected blood loss ≥ 500 ml, aged > 40 and ≤ 85 years, and ASA Physical status II-III) are randomly assigned to receive either HES or crystalloid solution for the treatment of hypovolemia due to surgery-induced acute blood loss in hospitals in up to 11 European countries. The dosing of investigational products (IP) is individualized to patients' volume needs and guided by a volume algorithm. Patients are treated with IP for maximally 24 h or until the maximum daily dose of 30 ml/kg body weight is reached. The primary endpoint is the treatment group mean difference in the change from the pre-operative baseline value in cystatin-C-based estimated glomerular filtration rate (eGFR), to the eGFR value calculated from the highest cystatin-C level measured during post-operative days 1-3. Further safety and efficacy parameters include, e.g., combined mortality/major post-operative complications until day 90, renal function, coagulation, inflammation, hemodynamic variables, hospital length of stay, major post-operative complications, and 28-day, 90-day, and 1-year mortality. DISCUSSION: The study will provide important information on the long-term safety and efficacy of HES 130/0.4 when administered according to the approved European product information. The results will be relevant for volume therapy of surgical patients. TRIAL REGISTRATION: EudraCT 2016-002162-30 . ClinicalTrials.gov NCT03278548.

• Klíčová slova
• Blood loss, Colloids, Double-blinded, HES, Hydroxyethyl starch, Multi-center, Multinational, Non-inferiority trial, Randomized controlled trial, Safety, Surgery, Volume therapy,
• MeSH
• břicho * chirurgie   MeSH
• deriváty hydroxyethylového škrobu * škodlivé účinky   chemie   MeSH
• dvojitá slepá metoda MeSH
• elektrolyty MeSH
• lidé MeSH
• multicentrické studie jako téma MeSH
• náhražky plazmy škodlivé účinky   MeSH
• prospektivní studie MeSH
• randomizované kontrolované studie jako téma MeSH
• senioři nad 80 let MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• protokol klinické studie MeSH
• Názvy látek
• deriváty hydroxyethylového škrobu * MeSH
• elektrolyty MeSH
• náhražky plazmy MeSH

In patients with acute circulatory failure, fluid administration represents a first-line therapeutic intervention for improving cardiac output. However, only approximately 50% of patients respond to fluid infusion with a significant increase in cardiac output, defined as fluid responsiveness. Additionally, excessive volume expansion and associated hyperhydration have been shown to increase morbidity and mortality in critically ill patients. Thus, except for cases of obvious hypovolaemia, fluid responsiveness should be routinely tested prior to fluid administration. Static markers of cardiac preload, such as central venous pressure or pulmonary artery wedge pressure, have been shown to be poor predictors of fluid responsiveness despite their widespread use to guide fluid therapy. Dynamic tests including parameters of aortic blood flow or respiratory variability of inferior vena cava diameter provide much higher diagnostic accuracy. Nevertheless, they are also burdened with several significant limitations, reducing the reliability, or even precluding their use in many clinical scenarios. This non-systematic narrative review aims to provide an update on the novel, less employed dynamic tests of fluid responsiveness evaluation in critically ill patients.

• Klíčová slova
• circulatory shock, fluid responsiveness, fluid therapy, hypovolemia, preload, tissue perfusion, volume expansion,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Fluid therapy is still the mainstay of acute care in patients with shock or cardiovascular compromise. However, our understanding of the critically ill pathophysiology has evolved significantly in recent years. The revelation of the glycocalyx layer and subsequent research has redefined the basics of fluids behavior in the circulation. Using less invasive hemodynamic monitoring tools enables us to assess the cardiovascular function in a dynamic perspective. This allows pinpointing even distinct changes induced by treatment, by postural changes, or by interorgan interactions in real time and enables individualized patient management. Regarding fluids as drugs of any other kind led to the need for precise indication, way of administration, and also assessment of side effects. We possess now the evidence that patient centered outcomes may be altered when incorrect time, dose, or type of fluids are administered. In this review, three major features of fluid therapy are discussed: the prediction of fluid responsiveness, potential harms induced by overzealous fluid administration, and finally the problem of protocol-led treatments and their timing.

• MeSH
• hemodynamika * MeSH
• kardiovaskulární nemoci * patofyziologie   terapie   MeSH
• lidé MeSH
• monitorování fyziologických funkcí * MeSH
• péče o pacienty v kritickém stavu metody   MeSH
• šok * patofyziologie   terapie   MeSH
• tekutinová terapie * škodlivé účinky   metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH