BACKGROUND: Successful conversion from insulin therapy to glucagon-like peptide 1 receptor agonist (GLP-1RA) with basal insulin in well-controlled patients has already been demonstrated. However, the data concerning individuals with poor glycaemic control are scarce. The aim of this work was to assess the success rate of insulin therapy to liraglutide transition in poorly controlled diabetes in a real-world clinical setting and to define predictors of success. We are the first to present the method of a fasting test as a way to identify the patients at higher risk of failure after treatment de-intensification. METHODS: The retrospective observational study analyzed data of 62 poorly controlled obese diabetic patients on high-dose insulin therapy, who were subjected to a 72 h fasting test during hospitalization and subsequently switched to liraglutide ± basal insulin therapy. During the fasting, all antidiabetic treatment was discontinued. Patients were classified as responders if they remained on GLP-1RA treatment after 12 months. Non-responders restarted the basal-bolus insulin (BBI) regimen. Development of glycated hemoglobin (HbA1c) and body weight in both groups, alongside with parameters associated with the higher risk of return to the BBI regimen, were analyzed. RESULTS: A total of 71% of patients were switched successfully (=responders). Responders had more significant improvement in HbA1c (-6.4 ± 19.7 vs. -3.4 ± 22.9 mmol/mol) and weight loss (-4.6 ± 7.1 vs. -2.5 ± 4.0). Statistically significant difference between groups was found in initial HbA1c (75.6 ± 17.9 vs. 90.5 ± 23.6; p = 0.04), total daily dose of insulin (67.6 ± 36.4 vs. 90.8 ± 32.4; p = 0.02), and mean glycaemia during the fasting test (6.9 ± 1.7 vs. 8.6 ± 2.2 mmol/L; p < 0.01). CONCLUSIONS: This study confirms that therapy de-intensification in poorly controlled patients with a BBI regimen is possible. Higher baseline HbA1c, total daily insulin dose, and mean glucose during fasting test are negative predictive factors of successful therapy de-escalation.
- Publikační typ
- časopisecké články MeSH
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.
- 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
Almost a quarter of a millennium after the discovery of an acidic substance in sour milk by Swedish chemist Carl Wilhelm Scheele and more than 100 years after the demonstration of a tight connection between this lactic acid and tissue hypoxia in shock, we are still surrounded by false beliefs and misunderstandings regarding this fascinating molecule. Common perceptions of lactate, the conjugate base of lactic acid, as a plain waste product of anaerobic metabolism and a marker of cellular distress could not be further from the truth. Lactate is formed and utilized continuously by our cells, even under fully aerobic conditions, in large quantities, and although marked hyperlactatemia is always a red flag in our patients, not all these conditions are life-threatening and vice versa-not all critically ill patients have hyperlactatemia. Lactate also does not promote acidosis by itself; it is not toxic, nor is it a metabolic renegade. On the contrary, it has many beneficial properties, and an interpretation of hyperlactatemia might be trickier than we tend to think. The aim of this article is to debunk some of the deeply rooted myths regarding this fascinating molecule.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Komunitní pneumonie je akutní zánětlivé onemocnění plicního parenchymu vzniklé mimo zdravotnické zařízení nebo do 48 hodin od přijetí do nemocnice. I přes dostupnost kauzální antibiotické léčby se dle dat Světové zdravotnické organizace jedná o celosvětově nejčastější příčinu úmrtí z infekčních příčin. Přestože by se mohlo zdát, že léčba infekčních onemocnění dolních cest dýchacích je uzavřenou kapitolou, opak je pravdou. Diagnostický rámec pneumonie zahrnuje heterogenní skupinu pacientů, kteří svým individuálním fenotypem onemocnění vyžadují specifický terapeutický přístup. Kontroverzní otázkou posledních dvaceti let je především adjuvantní použití kortikosteroidů s cílem modulace imunitně ‐inflamatorního poškození plicního parenchymu u těžké komunitní pneumonie. Výsledky klinických studií a jejich metaanalýz jsou bohužel protichůdné. Poslední konsensus čtyř významných evropských odborných společností doporučuje podání kortikoidů pouze u pacientů se současně přítomným septickým šokem. Stanovisko však bylo vydáno před uveřejněním dosud největší studie (CAPE COD), která svými závěry kontrastuje s uvedeným doporučením a velmi pravděpodobně v dohledné době změní přísné vymezení kortikoidů u pacientů se závažnou komunitní pneumonií. Cílem tohoto sdělení je poskytnout krátký klinicky orientovaný přehled ve stále kontroverzním problému a nabídnout k další odborné diskuzi pohled našeho pracoviště do doby, než budou k dispozici nová data a doporučení relevantních odborných grémií.
Community-acquired pneumonia (CAP) is an acute inflammatory disease of the lung parenchyma acquired outside the healthcare facilities or within 48 hours after admission to the hospital. Despite the availability of antibiotics, pneumonia remains the leading cause of death from infectious causes, according to World Health Organization data. Although it might seem that the treatment of lower respiratory tract infections is a closed chapter in a medical textbooks, it is quite the opposite. Our perception of pneumonia as a unifying diagnosis comes with a burden of heterogeneity and we need to approach each patient individually, based on their disease-specific phenotype. The adjuvant use of corticosteroids to modulate and dampen inflammation-induced lung injury in severe community-acquired pneumonia has been a matter of debate for the last twenty years. Up until recently, clinical trials and meta-analyses yielded conflicting results. Therefore, the last consensus of four respected European societies, recommends using corticosteroids in patients with severe community-acquired pneumonia only if septic shock is present. Unfortunately, those guidelines had been released shortly before the largest trial ever conducted on this group of patients (CAPE COD), which indicated different conclusions. This will probably lead to a reevaluation of the current strict recommendations for the use of corticosteroids. The following text aims to provide a brief clinically-oriented review of this controversial topic and present a perspective of our intensive care unit for further discussion until we have new relevant data and subsequent guidelines.
UNLABELLED: The most common cause of vasoplegic shock in critical care is sepsis. However, although rarely and only in specifically sensitised individuals previously bitten by a tick, red meat may provoke a delayed allergic reaction called an alpha-gal syndrome. We present a case of a protracted life-threatening manifestation of alpha-gal syndrome, which, due to an unusual absence of typical features of anaphylaxis can masquerade as septic shock and calls attention to the premature diagnostic closure as a contributor to diagnostic error. Alpha-gal syndrome is a relatively new, but increasingly recognised health issue. We propose that alpha-gal syndrome should be considered in the differential diagnosis of vasoplegic shock of unclear aetiology even in the absence of typical allergic symptomatology and typical allergen exposure since alpha-gal is present in a wide variety of carriers. LEARNING POINTS: Alpha-gal syndrome, otherwise known as "red meat allergy", is a potentially life-threatening allergic syndrome induced by the immunological properties of tick saliva.A typical case of alpha-gal syndrome is a patient bitten by a tick who develops an allergic reaction, anaphylaxis or anaphylactic shock even after an ingestion of a significant amount of alpha-gal, typically present in red mammalian meat or organs.As global warming continues, we may expect tick-borne diseases to spread wider around the globe and due to the possibility of complete absence of typical allergic symptomatology and the delayed onset of symptoms, this syndrome needs to be considered when encountering vasoplegic shock of uncertain origin.
- Publikační typ
- časopisecké články MeSH
PURPOSE: To assess long-term outcomes of restrictive versus standard intravenous (IV) fluid therapy in adult intensive care unit (ICU) patients with septic shock included in the European Conservative versus Liberal Approach to Fluid Therapy in Septic Shock in Intensive Care (CLASSIC) trial. METHODS: We conducted the pre-planned analyses of mortality, health-related quality of life (HRQoL) using EuroQol (EQ)-5D-5L index values and EQ visual analogue scale (VAS), and cognitive function using Mini Montreal Cognitive Assessment (Mini MoCA) test at 1 year. Deceased patients were assigned numerical zero for HRQoL as a state equal to death and zero for cognitive function outcomes as worst possible score, and we used multiple imputation for missing data on HRQoL and cognitive function. RESULTS: Among 1554 randomized patients, we obtained 1-year data on mortality in 97.9% of patients, HRQoL in 91.3%, and cognitive function in 86.3%. One-year mortality was 385/746 (51.3%) in the restrictive-fluid group versus 383/767 (49.9%) in the standard-fluid group, absolute risk difference 1.5%-points [99% confidence interval (CI) - 4.8 to 7.8]. Mean differences were 0.00 (99% CI - 0.06 to 0.05) for EQ-5D-5L index values, - 0.65 for EQ VAS (- 5.40 to 4.08), and - 0.14 for Mini MoCA (- 1.59 to 1.14) for the restrictive-fluid group versus the standard-fluid group. The results for survivors only were similar in both groups. CONCLUSIONS: Among adult ICU patients with septic shock, restrictive versus standard IV fluid therapy resulted in similar survival, HRQoL, and cognitive function at 1 year, but clinically important differences could not be ruled out.
- MeSH
- dospělí MeSH
- jednotky intenzivní péče MeSH
- kvalita života MeSH
- lidé MeSH
- péče o pacienty v kritickém stavu MeSH
- přežívající MeSH
- septický šok * terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- komentáře MeSH
BACKGROUND/AIM: Patients with unresectable liver colorectal cancer metastases are treated with neoadjuvant chemotherapy often accompanied by biological therapy aimed at reducing the mass of metastases and thus increasing the chances of resectability. Bevacizumab comprises an anti-VEGF (vascular endothelial growth factor) humanized IgG monoclonal antibody that is used for biological therapy purposes. It acts to inhibit angiogenesis, thereby slowing down the growth of metastases. Due to its being administered systematically, bevacizumab also exerts an effect on the surrounding healthy liver parenchyma and potentially limits the process of neovascularization and thus regeneration of the liver. Since the remnant liver volume forms an important factor in postoperative morbidity and mortality following a major hepatectomy, we decided to study the effect of bevacizumab on vascular and biliary microarchitecture in healthy liver parenchyma and its ability to regenerate following major hepatectomy. MATERIALS AND METHODS: We performed an experiment employing a large animal model where a total of 16 piglets were divided into two groups (8 piglets in the control group and 8 piglets in the experimental group with bevacizumab). All the animals were subjected to major hepatectomy and the experimental group was given bevacizumab prior to hepatectomy. All the animals were sacrificed after 4 weeks. We performed biochemical analyses at regular time intervals during the follow-up period. Histological examination of the liver tissue was performed following sacrifice of the animals. RESULTS: No statistical difference was shown between groups in terms of the biochemical and immunohistochemical parameters. The histological examination of the regenerating liver tissue revealed the higher length density of sinusoids in the experimental group. CONCLUSION: Bevacizumab does not act to impair liver regeneration following hepatectomy.
- MeSH
- bevacizumab farmakologie terapeutické užití MeSH
- hepatektomie MeSH
- humanizované monoklonální protilátky farmakologie terapeutické užití MeSH
- kolorektální nádory * farmakoterapie patologie chirurgie MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- nádory jater * farmakoterapie sekundární chirurgie MeSH
- patologická angiogeneze farmakoterapie MeSH
- prasata MeSH
- regenerace jater MeSH
- vaskulární endoteliální růstový faktor A MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Intravenous fluids are recommended for the treatment of patients who are in septic shock, but higher fluid volumes have been associated with harm in patients who are in the intensive care unit (ICU). METHODS: In this international, randomized trial, we assigned patients with septic shock in the ICU who had received at least 1 liter of intravenous fluid to receive restricted intravenous fluid or standard intravenous fluid therapy; patients were included if the onset of shock had been within 12 hours before screening. The primary outcome was death from any cause within 90 days after randomization. RESULTS: We enrolled 1554 patients; 770 were assigned to the restrictive-fluid group and 784 to the standard-fluid group. Primary outcome data were available for 1545 patients (99.4%). In the ICU, the restrictive-fluid group received a median of 1798 ml of intravenous fluid (interquartile range, 500 to 4366); the standard-fluid group received a median of 3811 ml (interquartile range, 1861 to 6762). At 90 days, death had occurred in 323 of 764 patients (42.3%) in the restrictive-fluid group, as compared with 329 of 781 patients (42.1%) in the standard-fluid group (adjusted absolute difference, 0.1 percentage points; 95% confidence interval [CI], -4.7 to 4.9; P = 0.96). In the ICU, serious adverse events occurred at least once in 221 of 751 patients (29.4%) in the restrictive-fluid group and in 238 of 772 patients (30.8%) in the standard-fluid group (adjusted absolute difference, -1.7 percentage points; 99% CI, -7.7 to 4.3). At 90 days after randomization, the numbers of days alive without life support and days alive and out of the hospital were similar in the two groups. CONCLUSIONS: Among adult patients with septic shock in the ICU, intravenous fluid restriction did not result in fewer deaths at 90 days than standard intravenous fluid therapy. (Funded by the Novo Nordisk Foundation and others; CLASSIC ClinicalTrials.gov number, NCT03668236.).
- MeSH
- dospělí MeSH
- intravenózní podání MeSH
- jednotky intenzivní péče MeSH
- lidé MeSH
- péče o pacienty v kritickém stavu metody MeSH
- septický šok * mortalita terapie MeSH
- tekutinová terapie * škodlivé účinky metody MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
- srovnávací studie MeSH
Management intravenózní tekutinové terapie je již více než 180 let součástí klinické praxe. Za tu dobu procházel vývoj složení tekutinových přípravků, postupů při jejich aplikaci a chápání příslušné fyziologie mnohými milníky. Přesto v dnešní době nelze stále říci, že je tato evoluce u konce. Cílem dalších bádání je proto doplnit chybějící znalosti v této problematice, ověřit dosavadní zjištění a pokusit se optimalizovat přístup v terapii specificky nemocných pacientů. Zásadní při tom bude nalezení optimálního složení, dávky a načasování tekutinové terapie u pacientů v intenzivní péči. V tomto přehledovém článku se zaměřujeme na klíčové předěly historie tekutinové léčby, abychom čtenářům přiblížili vývoj preskripce tekutinové léčby a vliv přibývajících poznatků na změny v uvažování o přístupu k terapii tekutinami v rámci péče o kriticky nemocné.
Management of intravenous fluid therapy has been part of clinical practice for more than 180 years. During that time, the development of fluid composition, the procedures for their application and the understanding of the respective physiology went through many milestones. Even nowadays, the evolution is not over. Further research should aim to fill in the gaps of knowledge on this issue, to verify current findings and to optimize prescription in the treatment of specific groups of critically ill patients. It will be crucial, to find credible evidence for optimal composition, dose, and timing of fluid therapy in intensive care. In this review article, we focus on the key lessons in the history of fluid therapy to enlighten the readers with the development of fluid therapy, prescribing practices, and the impact of recent findings on the conceptual changes in the management of fluid therapy in the critically ill.
- Klíčová slova
- infuzní roztoky,
- MeSH
- dějiny 19. století MeSH
- dějiny 20. století MeSH
- dějiny 21. století MeSH
- intravenózní infuze dějiny MeSH
- koloidy dějiny MeSH
- krystaloidní roztoky dějiny MeSH
- lidé MeSH
- tekutinová terapie * dějiny MeSH
- Check Tag
- dějiny 19. století MeSH
- dějiny 20. století MeSH
- dějiny 21. století MeSH
- lidé MeSH
- Publikační typ
- historické články MeSH
