Variations in end-of-life practices in intensive care units worldwide (Ethicus-2): a prospective observational study.

BACKGROUND: End-of-life practices vary among intensive care units (ICUs) worldwide. Differences can result in variable use of disproportionate or non-beneficial life-sustaining interventions across diverse world regions. This study investigated global disparities in end-of-life practices. METHODS: In this prospective, multinational, observational study, consecutive adult ICU patients who died or had a limitation of life-sustaining treatment (withholding or withdrawing life-sustaining therapy and active shortening of the dying process) during a 6-month period between Sept 1, 2015, and Sept 30, 2016, were recruited from 199 ICUs in 36 countries. The primary outcome was the end-of-life practice as defined by the end-of-life categories: withholding or withdrawing life-sustaining therapy, active shortening of the dying process, or failed cardiopulmonary resuscitation (CPR). Patients with brain death were included in a separate predefined end-of-life category. Data collection included patient characteristics, diagnoses, end-of-life decisions and their timing related to admission and discharge, or death, with comparisons across different regions. Patients were studied until death or 2 months from the first limitation decision. FINDINGS: Of 87 951 patients admitted to ICU, 12 850 (14·6%) were included in the study population. The number of patients categorised into each of the different end-of-life categories were significantly different for each region (p<0·001). Limitation of life-sustaining treatment occurred in 10 401 patients (11·8% of 87 951 ICU admissions and 80·9% of 12 850 in the study population). The most common limitation was withholding life-sustaining treatment (5661 [44·1%]), followed by withdrawing life-sustaining treatment (4680 [36·4%]). More treatment withdrawing was observed in Northern Europe (1217 [52·8%] of 2305) and Australia/New Zealand (247 [45·7%] of 541) than in Latin America (33 [5·8%] of 571) and Africa (21 [13·0%] of 162). Shortening of the dying process was uncommon across all regions (60 [0·5%]). One in five patients with treatment limitations survived hospitalisation. Death due to failed CPR occurred in 1799 (14%) of the study population, and brain death occurred in 650 (5·1%). Failure of CPR occurred less frequently in Northern Europe (85 [3·7%] of 2305), Australia/New Zealand (23 [4·3%] of 541), and North America (78 [8·5%] of 918) than in Africa (106 [65·4%] of 162), Latin America (160 [28·0%] of 571), and Southern Europe (590 [22·5%] of 2622). Factors associated with treatment limitations were region, age, and diagnoses (acute and chronic), and country end-of-life legislation. INTERPRETATION: Limitation of life-sustaining therapies is common worldwide with regional variability. Withholding treatment is more common than withdrawing treatment. Variations in type, frequency, and timing of end-of-life decisions were observed. Recognising regional differences and the reasons behind these differences might help improve end-of-life care worldwide. FUNDING: None.

Mechanical methods of venous thromboembolism prevention: from guidelines to clinical practice.

The paper discusses guidelines for the prevention of venous thromboembolism (VTE), with particular emphasis on the use of mechanical methods. Mechanical prophylaxis of VTE does not involve the risk of bleeding, which may be life­threatening. Mechanical methods are particularly recommended in patients at high risk of bleeding while on pharmacological thromboprophylaxis. Although antithrombotic prophylaxis is safe and cost­effective, there is evidence that the majority of preventive measures are applied too rarely in clinical practice, and that only a small proportion of patients receive complete and appropriate prophylaxis in the real­world clinical setting.

Surveillance of Antibiotic Prescribing in Intensive Care Units in Poland.

Antibiotic use and microbial resistance in health care-associated infections are increasing globally and causing health care problems. Intensive Care Units (ICUs) represent the heaviest antibiotic burden within hospitals, and sepsis is the second noncardiac cause of mortality in ICUs. Optimizing appropriate antibiotic treatment in the management of the critically ill in ICUs became a major challenge for intensivists. We performed a surveillance study on the antibiotic consumption in 108 Polish ICUs. We determined which classes of antibiotics were most commonly consumed and whether they affected the length of ICU stay and the size and category of the hospital. A total of 292.389 defined daily doses (DDD) and 192.167 patient-days (pd) were identified. Antibiotic consumption ranged from 620 to 3960 DDD/1000 pd. The main antibiotic classes accounted for 59.6% of the total antibiotic consumption and included carbapenems (17.8%), quinolones (14%), cephalosporins (13.7%), penicillins (11.9%), and macrolides (2.2%), respectively, whereas the other antibiotic classes accounted for the remainder (40.4%) and included antifungals (34%), imidazoles (20%), aminoglycosides (18%), glycopeptides (15%), and polymyxins (6%). The most consumed antibiotic classes in Polish ICUs were carbapenems, quinolones, and cephalosporins, respectively. There was no correlation between antibiotic consumption in DDD/1000 patient-days, mean length of ICU stay, size of the hospital, size of the ICU, or the total amount of patient-days. It is crucial that surveillance systems are in place to guide empiric antibiotic treatment and to estimate the burden of resistance. Appropriate use of antibiotics in the ICU should be an important public health care issue.

Longrange PCR-based next-generation sequencing in pharmacokinetics and pharmacodynamics study of propofol among patients under general anaesthesia.

The individual response of patients to propofol results from the influence of genetic factors. However, the state of knowledge in this matter still remains insufficient. The aim of our study was to determine genetic predictors of variable pharmacokinetics and pharmacodynamics of propofol within selected 9 genes coding for propofol biotransformation enzymes, receptors and transporters. Our studies are the first extensive pharmaocgenetics research of propofol using high throughput sequencing technology. After the design and optimization of long range PCR-based next-generation sequencing experiment, we screened promoter and coding sequences of all genes analyzed among 87 Polish patients undergoing general anaesthesia with propofol. Initially we found that two variants, c.516 G > T in the CYP2B6 gene and c.2677 T > G in the ABCB1 gene, significantly correlate with propofol's metabolic profile, however after Bonferroni correction the P-values were not statistically significant. Our results suggest, that variants within the CYP2B6 and ABCB1 genes correlate stronger with propofol's metabolic profile compared to other 7 genes. CYP2B6 and ABCB1 variants can play a potentially important role in response to this anaesthetic and they are promising object for further studies.

The effect of UGT1A9, CYP2B6 and CYP2C9 genes polymorphism on individual differences in propofol pharmacokinetics among Polish patients undergoing general anaesthesia.

Propofol (2,6-diisopropylphenol) is one of the safest and most commonly used anaesthetic agents for intravenous general anaesthesia. However, in clinical practice, a large inter-individual variability in response to propofol is observed. To limit the risk of adverse effects, pharmacogenetic investigations are recommended. The aim of our study was to verify the impact of genetic changes c.516G>T in the CYP2B6, c.98T>C in the UGT1A9 and c.1075A>C in the CYP2C9 genes on the individual propofol pharmacokinetic profile in the Polish patients undergoing general anaesthesia. Eighty-five patients from the Department of Anaesthesiology and Intensive Therapy, Regional Hospital in Poznan, Poland, anaesthetised with propofol for surgery, were enrolled in the study. We have genotyped CYP2B6, UGT1A9 and CYP2C9 polymorphisms with the use of pyrosequencing. HPLC measurements of propofol plasma concentration were applied for a pharmacokinetic analysis of the anaesthetic. We identified poor (20), intermediate (42) and rapid (23) metabolisers of propofol, which constituted 24%, 49% and 27% of the group, respectively. Homozygotes c.516 T/T in the CYP2B6 gene were statistically more often found in the rapid metabolisers group (p < 0.05). However, polymorphisms c.98T>C in the UGT1A9 and c.1075A>C in the CYP2C9 genes did not affect the pharmacokinetic profile of propofol. The mean propofol retention time (MRT) correlated with the patient's body mass index (BMI) (p < 0.05). From all the analysed changes, only polymorphism c.516G>T in the CYP2B6 gene and BMI affect the metabolism rate of propofol and may play an important role in the optimisation of propofol anaesthesia.

Impact of CYP2E1, GSTA1 and GSTP1 gene variants on serum alpha glutathione S-transferase level in patients undergoing anaesthesia.

BACKGROUND: The serum glutathione S-transferase alpha (α-GST) concentration has been used as a marker of hepatic condition. After sevoflurane anaesthesia a mild impairment of hepatocellular integrity was observed. Genetic polymorphisms in CYP2E1, GSTA1 and GSTP1 genes, affecting enzymes activity, may possibly influence the hepatotoxic effect of sevoflurane. The aim of this study was to assess the influence of genetic polymorphism of CYP2E1, GSTA1 and GSTP1 genes on serum α-GST level in 86 unrelated patients representing ASA physical status I-II, undergoing laryngological surgery under general anaesthesia with sevoflurane. METHODS: The serum samples from three perioperative time points were analyzed using ELISA. Genetic variants were detected by pyrosequencing and sequencing. Finally, the statistical associations between serum α-GST concentration and analyzed alleles of CYP2E1, GSTP1 and GSTA1 genes were estimated. RESULTS: The allele GSTA1*B (-567G, -69T, -52A) frequency was 0.43, whereas the alleles c.313G and c.341T of GSTP1 were identified with frequencies of 0.28 and 0.1 respectively. The -1053T allele of the CYP2E1 gene was observed with 0.01 frequency. We found serum α-GST concentrations in homozygous changes c.313A>G and c.341C>T of the GSTP1 gene significantly higher at the end of anaesthesia as compared with the levels at pre-anaesthetic and 24 h post-anaesthetic time points. Moreover, GSTA1 wild type genotype was associated with increased α-GST concentration at 24 h after the end of anaesthesia. CONCLUSIONS: GSTP1 gene polymorphism has an impact on the perioperative serum α-GST concentration in patients undergoing sevoflurane anaesthesia. A similar association, although not statistically significant exists between GSTA1 gene variants and perioperative serum α-GST level.

Characteristics and risk factors for 28-day mortality of hospital acquired fungemias in ICUs: data from the EUROBACT study.

BACKGROUND: To characterize and identify prognostic factors for 28-day mortality among patients with hospital-acquired fungemia (HAF) in the Intensive Care Unit (ICU). METHODS: A sub-analysis of a prospective, multicenter non-representative cohort study conducted in 162 ICUs in 24 countries. RESULTS: Of the 1156 patients with hospital-acquired bloodstream infections (HA-BSI) included in the EUROBACT study, 96 patients had a HAF. Median time to its diagnosis was 20 days (IQR 10.5-30.5) and 9 days (IQR 3-15.5) after hospital and ICU admission, respectively. Median time to positivity of blood culture was longer in fungemia than in bacteremia (48.7 h vs. 38.1 h; p = 0.0004). Candida albicans was the most frequent fungus isolated (57.1%), followed by Candida glabrata (15.3%) and Candida parapsilosis (10.2%). No clear source of HAF was detected in 33.3% of the episodes and it was catheter-related in 21.9% of them. Compared to patients with bacteremia, HAF patients had a higher rate of septic shock (39.6% vs. 21.6%; p = 0.0003) and renal dysfunction (25% vs. 12.4%; p = 0.0023) on admission and a higher rate of renal failure (26% vs. 16.2%; p = 0.0273) at diagnosis. Adequate treatment started within 24 h after blood culture collection was less frequent in HAF patients (22.9% vs. 55.3%; p < 0.001). The 28-day all cause fatality was 40.6%. According to multivariate analysis, only liver failure (OR 14.35; 95% CI 1.17-175.6; p = 0.037), need for mechanical ventilation (OR 8.86; 95% CI 1.2-65.24; p = 0.032) and ICU admission for medical reason (OR 3.87; 95% CI 1.25-11.99; p = 0.020) were independent predictors of 28-day mortality in HAF patients. CONCLUSIONS: Fungi are an important cause of hospital-acquired BSI in the ICU. Patients with HAF present more frequently with septic shock and renal dysfunction on ICU admission and have a higher rate of renal failure at diagnosis. HAF are associated with a significant 28-day mortality rate (40%), but delayed adequate antifungal therapy was not an independent risk factor for death. Liver failure, need for mechanical ventilation and ICU admission for medical reason were the only independent predictors of 28-day mortality.

Glutathione S-transferase as a toxicity indicator in general anesthesia: genetics and biochemical function.

General anesthesia may lead in patients to unexpected and adverse reactions including toxicity. Glutathione S-transferases (GSTs) are enzymes responsible for the detoxification process of anesthetic agents. Plasma and urine GST measurements are used in multiple studies as a hepatocellular integrity or renal injury indicator. The importance of GST enzyme measurements in monitoring the hepatotoxic and nephrotoxic effect in anesthetized patients is presented. The biochemical function and specific properties of GST render it a prognostic biomarker. This review demonstrates that GST can be valuable and promising toxicity indicator in patients undergoing general anesthesia.

Genotype and allele frequencies of polymorphic UGT1A9 in the Polish population.

The human UDP-glucuronosyltransferase 1A9 (UGT1A9) plays a central role in the metabolism of different therapeutic drugs, carcinogens and endobiotics. The UGT1A9 gene shows genetic polymorphism with frequencies significantly different in populations and ethnic groups. Many of these genetic variants are directly responsible for polymorphic drug metabolism. Three crucial alleles of UGT1A9, UGT1A9*3 (p.Met33Thr), *4 (p.Tyr242X), *5 (p.Asp256Asn) are associated with decrease or absence of enzyme activity, which intensify the risk of toxic effect during biotransformation. The goal of the present study was to discover frequencies of these genetic variations in 308 healthy individuals representing Polish population. The genotypes were determined by pyrosequencing. We demonstrated that the frequency of the variant UGT1A9*3 was 0.016, which suggests the need for detailed analysis of its effect on important drugs metabolism level in Polish population. Alleles UGT1A9*4 and UGT1A9*5 were not present in any of the subjects. So far, no studies have been conducted in which the distribution of these alleles has been determined in the Polish population.

[Critical care of patients with nicotine addiction]. / Problemy intensywnej terapii pacjentów uzaleznionych od nikotyny.

Tabacco smoking is a major public health problem. The evidence demonstrates that smokers are over-represented among the patients with severe diseases. Smoking in the significant way influence the prognosis related to the outcome of treatment and the length of stay in Intensive Care Units (ICUs). Recent studies confirmed that smoking has an independent dose-related adverse effect on mortality of critically ill patients. This review covers the issues connected with critically ill patients addicted to nicotine emphasizing the problems that could occur during their stay in ICU. Identifying patients at risk of complication at ICU may lead to earlier intervention in routine clinical practice.

[Respiratory complications in patients with nicotine addiction]. / Powiklania oddechowe u pacjentów z uzaleznieniem od nikotyny.

Chronic Obstructive Pulmonary Disease (COPD) is one of major causes of chronic morbidity and mortality both in Poland and throughout the world. Tobacco smoking is one of the best documented risk factors for COPD. In critically ill patients symptoms associated with the withdrawal syndrome are particularly evident during the process of weaning from mechanical ventilation. The present study outlines the case of a patient treated in the anaesthesiology and intensive therapy unit due to respiratory failure secondary to ischaemic stroke, exacerbation of COPD and septic complications, with a documented history of nicotine dependence syndrome.