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BACKGROUND: Sepsis is a life-threatening condition which may arise from infection in any organ system and requires early recognition and management. Healthcare professionals working in any specialty may need to manage patients with sepsis. Educating medical students about this condition may be an effective way to ensure all future doctors have sufficient ability to diagnose and treat septic patients. However, there is currently no consensus on what competencies medical students should achieve regarding sepsis recognition and treatment. This study aims to outline what sepsis-related competencies medical students should achieve by the end of their medical student training in both high or upper-middle incomes countries/regions and in low or lower-middle income countries/regions. METHODS: Two separate panels from high or upper-middle income and low or lower-middle income countries/regions participated in a Delphi method to suggest and rank sepsis competencies for medical students. Each panel consisted of 13-18 key stakeholders of medical education and doctors in specialties where sepsis is a common problem (both specialists and trainees). Panelists came from all continents, except Antarctica. RESULTS: The panels reached consensus on 38 essential sepsis competencies in low or lower-middle income countries/regions and 33 in high or upper-middle incomes countries/regions. These include competencies such as definition of sepsis and septic shock and urgency of antibiotic treatment. In the low or lower-middle income countries/regions group, consensus was also achieved for competencies ranked as very important, and was achieved in 4/5 competencies rated as moderately important. In the high or upper-middle incomes countries/regions group, consensus was achieved in 41/57 competencies rated as very important but only 6/11 competencies rated as moderately important. CONCLUSION: Medical schools should consider developing curricula to address essential competencies, as a minimum, but also consider addressing competencies rated as very or moderately important.
Subject(s)
Clinical Competence , Consensus , Delphi Technique , Sepsis , Students, Medical , Humans , Clinical Competence/standards , Sepsis/diagnosis , Sepsis/therapy , Developing Countries , CurriculumABSTRACT
BACKGROUND: Frailty is common in patients undergoing cardiac surgery and is associated with poorer postoperative outcomes. Ultrasound examination of skeletal muscle morphology may serve as an objective assessment tool as lean muscle mass reduction is a key feature of frailty. METHODS: This study investigated the association of ultrasound-derived muscle thickness, cross-sectional area, and echogenicity of the rectus femoris muscle (RFM) with preoperative frailty and predicted subsequent poor recovery after surgery. Eighty-five patients received preoperative RFM ultrasound examination and frailty-related assessments: Clinical Frailty Scale (CFS) and 5-m gait speed test (GST5m). Association of each ultrasound measurement with frailty assessments was examined. Area under receiver-operating characteristic curve (AUROC) was used to assess the discriminative ability of each ultrasound measurement to predict days at home within 30 days of surgery (DAH30). RESULTS: By CFS and GST5m criteria, 13% and 34% respectively of participants were frail. RFM cross-sectional area alone demonstrated moderate predictive association for frailty by CFS criterion (AUROC: 0.76, 95% CI: 0.66-0.85). Specificity improved to 98.7% (95% CI: 93.6%-100.0%) by utilising RFM cross-sectional area as an 'add-on' test to a positive gait speed test, and thus a combined muscle size and function test demonstrated higher predictive performance (positive likelihood ratio: 40.4, 95% CI: 5.3-304.3) for frailty by CFS criterion than either test alone (p < 0.001). The combined 'add-on' test predictive performance for DAH30 (AUROC: 0.90, 95% CI: 0.81-0.95) may also be superior to either CFS or gait speed test alone. CONCLUSIONS: Preoperative RFM ultrasound examination, especially when integrated with the gait speed test, may be useful to identify patients at high risk of frailty and those with poor outcomes after cardiac surgery. TRIAL REGISTRATION: The study was registered on the Chinese Clinical Trials Registry (ChiCTR2000031098) on 22 March 2020.
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PURPOSE: Limitations of life sustaining therapies (LLST) are frequent in intensive care units (ICUs), but no previous studies have examined end-of-life (EOL) care and LLST in South Africa (SA). MATERIALS AND METHODS: This study evaluated LLST in SA from the data of a prospective, international, multicentre, observational study (Ethicus-2) and compared practices with countries in the rest of the world. RESULTS: LLST was relatively common in SA, and withholding was more frequent than withdrawing therapy. However, withdrawing and withholding therapy were less common, while failed CPR was more common, than in many other countries. No patients had an advance directive. Primary reasons for LLST in SA were poor quality of life, multisystem organ failure and patients' unresponsiveness to maximal therapy. Primary considerations for EOL decision-making were good medical practice and patients' best-interest, with the need for an ICU bed only rarely considered. CONCLUSIONS: Withholding was more common than withdrawing treatment both in SA and worldwide, although both were significantly less frequent in SA compared with the world average.
Subject(s)
Intensive Care Units , Life Support Care , Terminal Care , Withholding Treatment , Humans , South Africa , Prospective Studies , Male , Female , Middle Aged , Quality of Life , Aged , Decision Making , AdultABSTRACT
PURPOSE: The present study aimed at assessing the prevalences of post-traumatic stress disorder (PTSD) (main objective), anxiety, depression, and burnout syndrome (BOS) and their associated factors in intensive care unit (ICU) staff workers in the second year of the COVID-19 pandemic. MATERIALS AND METHODS: An international cross-sectional multicenter ICU-based online survey was carried out among the ICU staff workers in 20 ICUs across 3 continents. ICUs staff workers (both caregivers and non-caregivers) were invited to complete PCL-5, HADS, and MBI questionnaires for assessing PTSD, anxiety, depression, and the different components of BOS, respectively. A personal questionnaire was used to isolate independent associated factors with these disorders. RESULTS: PCL-5, HADS, and MBI questionnaires were completed by 585, 570, and 539 responders, respectively (525 completed all questionnaires). PTSD was diagnosed in 98/585 responders (16.8%). Changing familial environment, being a non-caregiver staff worker, having not being involved in a COVID-19 patient admission, having not been provided with COVID-19-related information were associated with PTSD. Anxiety was reported in 130/570 responders (22.8%). Working in a public hospital, being a woman, being financially impacted, being a non-clinical healthcare staff member, having no theoretical or practical training on individual preventive measures, and fear of managing COVID-19 patients were associated with anxiety. Depression was reported in 50/570 responders (8.8%). Comorbidity at risk of severe COVID-19, working in a public hospital, looking after a child, being a non-caregiver staff member, having no information, and a request for moving from the unit were associated with depression. Having received no information and no adequate training for COVID-19 patient management were associated with all 3 dimensions of BOS. CONCLUSION: The present study confirmed that ICU staff workers, whether they treated COVID-19 patients or not, have a substantial prevalence of psychological disorders.
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The demographic shift, together with financial constraint, justify a re-evaluation of the trajectory of care of very old critically ill patients (VIP), defined as older than 80 years. We must avoid over- as well as under-utilisation of critical care interventions in this patient group and ensure the inclusion of health care professionals, the patient and their caregivers in the decision process. This new integrative approach mobilises expertise at each step of the process beginning prior to intensive care unit (ICU) admission and extending to long-term follow-up. In this review, several international experts have contributed to provide recommendations that can be universally applied. Our aim is to define a minimum core dataset of information to be shared and discussed prior to ICU admission and to facilitate the shared-decision-making process with the patient and their caregivers, throughout the patient journey. Documentation of uncertainty may contribute to a tailored level of care and ultimately to discussions around possible limitations of life sustaining treatments. The goal of ICU care is not only to avoid death, but more importantly to maintain an acceptable quality of life and functional autonomy after hospital discharge. Societal consideration is important to highlight, together with alternatives to ICU admission. We discuss challenges for the future and potential areas of research. In summary, this review provides a state-of-the-art current overview and aims to outline future directions to address the challenges in the treatment of VIP.
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Critical Illness , Quality of Life , Humans , Critical Illness/therapy , Critical Care , Health Personnel , HospitalizationABSTRACT
BACKGROUND: Good nutritional screening tests can triage malnourished patients for further assessment and management by dietitians before surgery to reduce the risk of postoperative complications. The authors assessed the diagnostic test accuracy of common nutritional screening tools for preoperative malnutrition in adults undergoing surgery and determined which test had the highest accuracy. METHODS: MEDLINE, EMBASE, CINAHL, and Web of Science were searched for relevant titles with no language restriction from inception till 1 January 2023. Studies reporting on the diagnostic test accuracy of preoperative malnutrition in adults using one or more of the following index nutritional screening tools were included: Malnutrition Screening Tool (MST), Malnutrition Universal Screening Tool (MUST), Mini Nutritional Assessment (MNA), short-form Mini Nutritional Assessment (MNA-SF), Nutritional Risk Index (NRI), Nutrition Risk Screening Tool 2002 (NRS-2002), and Preoperative Nutrition Screening (PONS). The reference standard was the Subjective Global Assessment (SGA) before surgery. Random-effects bivariate binomial model meta-analyses, meta-regressions, and a network meta-analysis were used to estimate the pooled and relative sensitivities and specificities. RESULTS: Of the 16 included studies (5695 participants with an 11 957 index and 11 957 SGA tests), all were conducted after hospital admission before surgery. Eleven studies ( n =3896) were at high risk of bias using the Quality Assessment of Diagnostic Accuracy Studies tool due to a lack of blinded assessments. MUST had the highest overall test accuracy performance (sensitivity 86%, 95% CI: 75-93%; specificity 89%, 95% CI: 83-93%). Network meta-analysis showed NRI had similar relative sensitivity (0.93, 95% CI: 0.77-1.13) but lower relative specificity (0.75, 95% CI: 0.61-0.92) than MUST. CONCLUSIONS: Of all easy-to-use tests applicable at the bedside, MUST had the highest test accuracy performance for screening preoperative malnutrition. However, its predictive accuracy is likely insufficient to justify the application of nutritional optimization interventions without additional assessments.
Subject(s)
Malnutrition , Nutritional Status , Adult , Humans , Nutrition Assessment , Network Meta-Analysis , Malnutrition/diagnosis , Mass Screening , Diagnostic Tests, RoutineABSTRACT
The aging population is an important issue around the world especially in developed countries. Although medical advances have substantially extended life span, the same cannot be said for the duration of health span. We are seeing increasing numbers of elderly people who are frail and/or have multiple chronic conditions; all of these can affect the quality of life of the elderly population as well as increase the burden on the healthcare system. Aging is mechanistically related to common medical conditions such as diabetes mellitus, ischemic heart disease, cognitive decline, and frailty. A recently accepted concept termed 'Accelerated Biological Aging' can be diagnosed when a person's biological age-as measured by biomarkers of DNA methylation-is older than their corresponding chronological age. Taurine, a conditionally essential amino acid, has received much attention in the past few years. A substantial number of animal studies have provided a strong scientific foundation suggesting that this amino acid can improve cellular and metabolic health, including blood glucose control, so much that it has been labelled one of the 'longevity amino acids'. In this review article, we propose the rationale that an adequately powered randomized-controlled-trial (RCT) is needed to confirm whether taurine can meaningfully improve metabolic and microbiome health, and biological age. This trial should incorporate certain elements in order to provide the much-needed evidence to guide doctors, and also the community at large, to determine whether this promising and inexpensive amino acid is useful in improving human metabolic health.
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BACKGROUND: Decisions about life-sustaining therapy (LST) in the intensive care unit (ICU) depend on predictions of survival as well as the expected functional capacity and self-perceived quality of life after discharge, especially in very old patients. However, prognostication for individual patients in this cohort is hampered by substantial uncertainty which can lead to a large variability of opinions and, eventually, decisions about LST. Moreover, decision-making processes are often embedded in a framework of ethical and legal recommendations which may vary between countries resulting in divergent management strategies. METHODS: Based on a vignette scenario of a multi-morbid 87-year-old patient, this article illustrates the spectrum of opinions about LST among intensivsts with a special interest in very old patients, from ten countries/regions, representing diverse cultures and healthcare systems. RESULTS: This survey of expert opinions and national recommendations demonstrates shared principles in the management of very old ICU patients. Some guidelines also acknowledge cultural differences between population groups. Although consensus with families should be sought, shared decision-making is not formally required or practised in all countries. CONCLUSIONS: This article shows similarities and differences in the decision-making for LST in very old ICU patients and recommends strategies to deal with prognostic uncertainty. Conflicts should be anticipated in situations where stakeholders have different cultural beliefs. There is a need for more collaborative research and training in this field.
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INTRODUCTION: Protein malnutrition is associated with higher risks of postoperative complications, mortality, prolonged postoperative stays in hospital, slower physical and mental recovery after surgery and lower subsequent health-related quality of life. To reduce the risk of postoperative morbidity and mortality, nutritional prehabilitation programmes have been developed recently to build up patient's nutritional reserve to withstand the stress of surgery. The intervention involves nutritional screening and counselling, and increasing dietary protein intake in protein-malnourished patients in the several weeks before surgery. However, there are few well-conducted preoperative studies to examine the effect of increasing dietary protein intake on the quality of recovery of malnourished patients after elective cardiac surgery. METHOD AND ANALYSIS: This randomised controlled trial of malnourished patients undergoing major elective cardiac surgery will compare the quality of postoperative recovery in patients with or without nutritional prehabilitation. One hundred and thirty-two patients will be randomised to receive nutritional prehabilitation (target-adjusted whey protein powder supplementation and an individualised 1 hour session/week counselling by a dietician 1 month before operation date) or standard care (no nutritional prehabilitation). Primary outcomes will be the quality of recovery after surgery (15-item Quality of Recovery) on the third postoperative day. Secondary outcomes will include days (alive and) at home within 30 days, changes in the WHO Disability Assessment Schedule 2.0, changes in health-related quality of life (EQ-5D) and Cardiac Postoperative Morbidity Survey. An outcomes assessor will be blinded to the treatment allocation. Appropriate univariate analyses, generalised estimating equations and multiple regressions will be performed for intention-to-treat and per-protocol analyses. ETHICS AND DISSEMINATION: The Joint CUHK-NTEC Clinical Research Ethics Committee approved the study protocol (CREC Ref. No.: 2021.703 T). The findings will be presented at scientific meetings, peer-reviewed journals and to study participants. TRIAL REGISTRATION NUMBER: ChiCTR2200057463.
Subject(s)
Cardiac Surgical Procedures , Preoperative Exercise , Humans , Quality of Life , Dietary Proteins , Nutrition Assessment , Preoperative Care/methods , Nutritional Status , Cardiac Surgical Procedures/adverse effects , Postoperative Complications/prevention & control , Postoperative Complications/etiology , Randomized Controlled Trials as TopicABSTRACT
OBJECTIVES: Direct comparisons between COVID-19 and influenza A in the critical care setting are limited. The objective of this study was to compare their outcomes and identify risk factors for hospital mortality. DESIGN AND SETTING: This was a territory-wide, retrospective study on all adult (≥18 years old) patients admitted to public hospital intensive care units in Hong Kong. We compared COVID-19 patients admitted between 27 January 2020 and 26 January 2021 with a propensity-matched historical cohort of influenza A patients admitted between 27 January 2015 and 26 January 2020. We reported outcomes of hospital mortality and time to death or discharge. Multivariate analysis using Poisson regression and relative risk (RR) was used to identify risk factors for hospital mortality. RESULTS: After propensity matching, 373 COVID-19 and 373 influenza A patients were evenly matched for baseline characteristics. COVID-19 patients had higher unadjusted hospital mortality than influenza A patients (17.5% vs 7.5%, p<0.001). The Acute Physiology and Chronic Health Evaluation IV (APACHE IV) adjusted standardised mortality ratio was also higher for COVID-19 than influenza A patients ((0.79 (95% CI 0.61 to 1.00) vs 0.42 (95% CI 0.28 to 0.60)), p<0.001). Adjusting for age, PaO2/FiO2, Charlson Comorbidity Index and APACHE IV, COVID-19 (adjusted RR 2.26 (95% CI 1.52 to 3.36)) and early bacterial-viral coinfection (adjusted RR 1.66 (95% CI 1.17 to 2.37)) were directly associated with hospital mortality. CONCLUSIONS: Critically ill patients with COVID-19 had substantially higher hospital mortality when compared with propensity-matched patients with influenza A.
Subject(s)
COVID-19 , Influenza, Human , Adult , Humans , Adolescent , Retrospective Studies , Influenza, Human/epidemiology , Length of Stay , Intensive Care Units , Hospitals, PublicABSTRACT
INTRODUCTION: The importance of antibiotic treatment for sepsis in critically ill septic patients is well established. Consistently achieving the dose of antibiotics required to optimally kill bacteria, minimize the development of resistance, and avoid toxicity is challenging. The increasing understanding of the pharmacokinetic and pharmacodynamic (PK/PD) characteristics of antibiotics, and the effects of critical illness on key PK/PD parameters, is gradually re-shaping how antibiotics are dosed in critically ill patients. AREAS COVERED: The PK/PD characteristics of commonly used carbapenem antibiotics, the principles of the application of therapeutic drug monitoring (TDM), and current as well as future methods of utilizing TDM to optimally devise dosing regimens will be reviewed. The limitations and evidence-base supporting the use of carbapenem TDM to improve outcomes in critically ill patients will be examined. EXPERT OPINION: It is important to understand the principles of TDM in order to correctly inform dosing regimens. Although the concept of TDM is attractive, and the ability to utilize PK software to optimize dosing in the near future is expected to rapidly increase clinicians' ability to meet pre-defined PK/PD targets more accurately, current evidence provides only limited support for the use of TDM to guide carbapenem dosing in critically ill patients.
Subject(s)
Carbapenems , Sepsis , Humans , Carbapenems/adverse effects , Critical Illness/therapy , Drug Monitoring , Anti-Bacterial Agents , Sepsis/drug therapyABSTRACT
BACKGROUND: Tuberculosis (TB) is a preventable and curable disease, but mortality remains high among those who develop sepsis and critical illness from TB. METHODS: This was a population-based, multicentre retrospective cohort study of patients admitted to all 15 publicly funded Hong Kong adult intensive care units (ICUs) between 1 April 2008 and 31 March 2019. 940 adult critically ill patients with at least one positive Mycobacterium tuberculosis (MTB) culture were identified out of 133 858 ICU admissions. Generalised linear modelling was used to determine the impact of delay in TB treatment on hospital mortality. Trend of annual Acute Physiology and Chronic Health Evaluation (APACHE) IV-adjusted standardised mortality ratio (SMR) over the 11-year period was analysed by Mann-Kendall's trend test. RESULTS: ICU and hospital mortality were 24.7% (232/940) and 41.1% (386/940), respectively. Of those who died in the ICU, 22.8% (53/232) never received antituberculosis drugs. SMR for ICU patients with TB remained unchanged over the study period (Kendall's τb=0.37, p=0.876). After adjustment for age, Charlson comorbidity index, APACHE IV, albumin, vasopressors, mechanical ventilation and renal replacement therapy, delayed TB treatment was directly associated with hospital mortality. In 302/940 (32.1%) of patients, TB could only be established from MTB cultures alone as Ziehl-Neelsen staining or PCR was either not performed or negative. Among this group, only 31.1% (94/302) had concurrent MTB PCR performed. CONCLUSIONS: Survival of ICU patients with TB has not improved over the last decade and mortality remains high. Delay in TB treatment was associated with higher hospital mortality. Use of MTB PCR may improve diagnostic yield and facilitate early treatment.
Subject(s)
Critical Illness , Tuberculosis , Adult , Humans , Critical Illness/therapy , Retrospective Studies , Intensive Care Units , Hospital Mortality , Treatment OutcomeABSTRACT
BACKGROUND: Up to 11% of critically ill patients with sepsis have an unknown source, where the pathogen and site of infection are unclear. The aim of this scoping review is to document currently reported diagnostic criteria of sepsis of unknown origin (SUO) and identify the types and breadth of existing evidence supporting diagnostic processes to identify the infection source in critically ill patients with suspected SUO. METHODS: A literature search of Embase, MEDLINE and PubMed for published studies from 1910 to August 19, 2021 addressing the topic of SUO was performed. Study type, country of origin according to World Bank classification, diagnostic criteria of sepsis of unknown origin, and investigative approaches were extracted from the studies. RESULTS: From an initial 722 studies, 89 unique publications fulfilled the inclusion and exclusion criteria and were included for full text review. The most common publication type was case report/series 45/89 (51%). Only 10/89 (11%) of studies provided a diagnostic criteria of SUO, but a universally accepted diagnostic criterion was not identified. The included studies discussed 30/89 (34%) history, 23/89 (26%) examination, 57/89 (64%) imaging, microbiology 39/89 (44%), and special tests 32/89 (36%) as part of the diagnostic processes in patients with SUO. CONCLUSIONS: Universally accepted diagnostic criteria for SUO was not found. Prospective studies on investigative processes in critically ill patients managed as SUO across different healthcare settings are needed to understand the epidemiology and inform the diagnostic criteria required to diagnose SUO.
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Morbidity and mortality related to ventriculitis in neurocritical care patients remain high. Antibiotic dose optimization may improve therapeutic outcomes. In this study, a population pharmacokinetic model of meropenem in infected critically ill patients was developed. We applied the final model to determine optimal meropenem dosing regimens required to achieve targeted cerebrospinal fluid exposures. Neurocritical care patients receiving meropenem and with a diagnosis of ventriculitis or extracranial infection were recruited from two centers to this study. Serial plasma and cerebrospinal fluid samples were collected and assayed. Population pharmacokinetic modeling and Monte Carlo dosing simulations were performed using Pmetrics. We sought to determine optimized dosing regimens that achieved meropenem cerebrospinal fluid concentrations above pathogen MICs for 40% of the dosing interval, or a higher target ratio of meropenem cerebrospinal fluid trough concentrations to pathogen MIC of ≥1. In total, 53 plasma and 34 cerebrospinal fluid samples were obtained from eight patients. Meropenem pharmacokinetics were appropriately described using a three-compartment model with linear plasma clearance scaled for creatinine clearance and cerebrospinal fluid penetration scaled for patient age. Considerable interindividual pharmacokinetic variability was apparent, particularly in the cerebrospinal fluid. Percent coefficients of variation for meropenem clearance from plasma and cerebrospinal fluid were 41.7% and 89.6%, respectively; for meropenem, the volume of distribution in plasma and cerebrospinal fluid values were 63.4% and 58.3%, respectively. High doses (up to 8 to 10 g/day) improved attainment of meropenem cerebrospinal fluid target exposures, particularly for less susceptible organisms (MICs, ≥0.25 mg/L). Standard meropenem doses of 2 g every 8 h may not achieve effective concentrations in cerebrospinal fluid in all critically ill patients. Higher doses, or alternative dosing methods (e.g., loading dose followed by continuous infusion) may be required to optimize cerebrospinal fluid exposures. Doses of up to 8 to 10 g/day either as intermittent boluses or continuous infusion would be suitable for patients with augmented renal clearance; lower doses may be considered for patients with impaired renal function as empirical suggestions. Ongoing dosing should be tailored to the individual patient circumstances. Notably, the study population was small and dosing recommendations may not be generalizable to all critically ill patients.
Subject(s)
Cerebral Ventriculitis , Renal Insufficiency , Anti-Bacterial Agents , Critical Illness , Humans , Meropenem/pharmacokinetics , Prospective Studies , ThienamycinsABSTRACT
The objective of this study was to describe the total and unbound population pharmacokinetics of ceftriaxone in critically ill adult patients and to define optimized dosing regimens. Total and unbound ceftriaxone concentrations were obtained from two pharmacokinetic studies and from a therapeutic drug monitoring (TDM) program at a tertiary hospital intensive care unit. Population pharmacokinetic analysis and Monte Carlo simulations were used to assess the probability of achieving a free trough concentration/MIC ratio of ≥1 using Pmetrics for R. A total of 474 samples (267 total and 207 unbound) were available from 36 patients. A two-compartment model describing ceftriaxone-albumin binding with both nonrenal and renal elimination incorporating creatinine clearance to explain the between-patient variability best described the data. An albumin concentration of ≤20 g/L decreased the probability of target attainment (PTA) by up to 20% across different dosing regimens and simulated creatinine clearances. A ceftriaxone dose of 1 g twice daily is likely therapeutic in patients with creatinine clearance of <100 mL/min infected with susceptible isolates (PTA, ~90%). Higher doses administered as a continuous infusion (4 g/day) are needed in patients with augmented renal clearance (creatinine clearance, >130 mL/min) who are infected by pathogens with a MIC of ≥0.5 mg/L. The ceftriaxone dose should be based on the patient's renal function and albumin concentration, as well as the isolate MIC. Hypoalbuminemia decreases the PTA in patients receiving intermittent dosing by up to 20%.
Subject(s)
Ceftriaxone , Critical Illness , Adult , Albumins , Anti-Bacterial Agents/pharmacokinetics , Ceftriaxone/pharmacokinetics , Creatinine , Humans , Microbial Sensitivity Tests , Monte Carlo MethodABSTRACT
BACKGROUND: Prolonging life in the ICU increasingly is possible, so decisions to limit life-sustaining therapies frequently are made and communicated to patients and families or surrogates. Little is known about worldwide communication practices and influencing factors. RESEARCH QUESTION: Are there regional differences in end-of-life communication practices in ICUs worldwide? STUDY DESIGN AND METHODS: This analysis of data from a prospective, international study specifically addressed end-of-life communications in consecutive patients who died or had limitation of life-sustaining therapy over 6 months in 199 ICUs in 36 countries, grouped regionally. End-of-life decisions were recorded for each patient and ethical practice was assessed retrospectively for each ICU using a 12-point questionnaire developed previously. RESULTS: Of 87,951 patients admitted, 12,850 died or experienced a limitation of therapy (14.6%). Of these, 1,199 patients (9.3%) were known to have an advance directive, and wishes were elicited from 6,456 patients (50.2%). Limitations of life-sustaining therapy were implemented for 10,401 patients (80.9%), 1,970 (19.1%) of whom had mental capacity at the time, and were discussed with 1,507 patients (14.5%) and 8,461 families (81.3%). Where no discussions with patients occurred (n = 8,710), this primarily was because of a lack of mental capacity in 8,114 patients (93.2%), and where none occurred with families (n = 1,622), this primarily was because of unavailability (n = 720 [44.4%]). Regional variation was noted for all end points. In generalized estimating equation (GEE) analyses, the odds for discussions with the patient or family increased by 30% (OR, 1.30; 95% CI, 1.18-1.44; P < .001) for every one-point increase in the Ethical Practice Score and by 92% (OR, 1.92; 95% CI, 1.28-2.89; P = .002) in the presence of an advance directive. INTERPRETATION: End-of-life communication with patients and families or surrogates varies markedly in different global regions. GEE analysis supports the hypothesis that communication may increase with ethical practice and an advance directive. Greater effort is needed to align treatment with patients' wishes.
Subject(s)
Decision Making , Terminal Care , Humans , Prospective Studies , Retrospective Studies , Intensive Care Units , Communication , DeathABSTRACT
Multidrug resistant organisms (MDRO) are commonly isolated in respiratory specimens taken from mechanically ventilated patients. The purpose of this narrative review is to discuss the approach to antimicrobial prescription in ventilated patients who have grown a new MDRO isolate in their respiratory specimen. A MEDLINE and PubMed literature search using keywords "multidrug resistant organisms", "ventilator-associated pneumonia" and "decision making", "treatment" or "strategy" was used to identify 329 references as background for this review. Lack of universally accepted diagnostic criteria for ventilator-associated pneumonia, or ventilator-associated tracheobronchitis complicates treatment decisions. Consideration of the clinical context including signs of respiratory infection or deterioration in respiratory or other organ function is essential. The higher the quality of respiratory specimens or the presence of bacteremia would suggest the MDRO is a true pathogen, rather than colonization, and warrants antimicrobial therapy. A patient with higher severity of illness has lower safety margins and may require initiation of antimicrobial therapy until an alternative diagnosis is established. A structured approach to the decision to treat with antimicrobial therapy is proposed.
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BACKGROUND: Limitations of life-sustaining interventions in intensive care units (ICUs) exhibit substantial changes over time, and large, contemporary variation across world regions. We sought to determine whether a weighted end-of-life practice score can explain a large, contemporary, worldwide variation in limitation decisions. METHODS: The 2015-2016 (Ethicus-2) vs. 1999-2000 (Ethicus-1) comparison study was a two-period, prospective observational study assessing the frequency of limitation decisions in 4952 patients from 22 European ICUs. The worldwide Ethicus-2 study was a single-period prospective observational study assessing the frequency of limitation decisions in 12,200 patients from 199 ICUs situated in 8 world regions. Binary end-of-life practice variable data (1 = presence; 0 = absence) were collected post hoc (comparison study, 22/22 ICUs, n = 4592; worldwide study, 186/199 ICUs, n = 11,574) for family meetings, daily deliberation for appropriate level of care, end-of-life discussions during weekly meetings, written triggers for limitations, written ICU end-of-life guidelines and protocols, palliative care and ethics consultations, ICU-staff taking communication or bioethics courses, and national end-of-life guidelines and legislation. Regarding the comparison study, generalized estimating equations (GEE) analysis was used to determine associations between the 12 end-of-life practice variables and treatment limitations. The weighted end-of-life practice score was then calculated using GEE-derived coefficients of the end-of-life practice variables. Subsequently, the weighted end-of-life practice score was validated in GEE analysis using the worldwide study dataset. RESULTS: In comparison study GEE analyses, end-of-life discussions during weekly meetings [odds ratio (OR) 0.55, 95% confidence interval (CI) 0.30-0.99], end-of-life guidelines [OR 0.52, (0.31-0.87)] and protocols [OR 15.08, (3.88-58.59)], palliative care consultations [OR 2.63, (1.23-5.60)] and end-of-life legislation [OR 3.24, 1.60-6.55)] were significantly associated with limitation decisions (all P < 0.05). In worldwide GEE analyses, the weighted end-of-life practice score was significantly associated with limitation decisions [OR 1.12 (1.03-1.22); P = 0.008]. CONCLUSIONS: Comparison study-derived, weighted end-of-life practice score partly explained the worldwide study's variation in treatment limitations. The most important components of the weighted end-of-life practice score were ICU end-of-life protocols, palliative care consultations, and country end-of-life legislation.
Subject(s)
Critical Illness , Terminal Care , Critical Illness/therapy , Death , Humans , Intensive Care Units , Palliative Care , Terminal Care/methodsABSTRACT
A recent mutation analysis suggested that Non-Structural Protein 6 (NSP6) of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a key determinant of the viral pathogenicity. Here, by transcriptome analysis, we demonstrated that the inflammasome-related NOD-like receptor signaling was activated in SARS-CoV-2-infected lung epithelial cells and Coronavirus Disease 2019 (COVID-19) patients' lung tissues. The induction of inflammasomes/pyroptosis in patients with severe COVID-19 was confirmed by serological markers. Overexpression of NSP6 triggered NLRP3/ASC-dependent caspase-1 activation, interleukin-1ß/18 maturation, and pyroptosis of lung epithelial cells. Upstream, NSP6 impaired lysosome acidification to inhibit autophagic flux, whose restoration by 1α,25-dihydroxyvitamin D3, metformin or polydatin abrogated NSP6-induced pyroptosis. NSP6 directly interacted with ATP6AP1, a vacuolar ATPase proton pump component, and inhibited its cleavage-mediated activation. L37F NSP6 variant, which was associated with asymptomatic COVID-19, exhibited reduced binding to ATP6AP1 and weakened ability to impair lysosome acidification to induce pyroptosis. Consistently, infection of cultured lung epithelial cells with live SARS-CoV-2 resulted in autophagic flux stagnation, inflammasome activation, and pyroptosis. Overall, this work supports that NSP6 of SARS-CoV-2 could induce inflammatory cell death in lung epithelial cells, through which pharmacological rectification of autophagic flux might be therapeutically exploited.
Subject(s)
COVID-19 , Coronavirus Nucleocapsid Proteins , NLR Family, Pyrin Domain-Containing 3 Protein , SARS-CoV-2 , Vacuolar Proton-Translocating ATPases , COVID-19/metabolism , COVID-19/virology , Coronavirus Nucleocapsid Proteins/genetics , Coronavirus Nucleocapsid Proteins/metabolism , Humans , Inflammasomes/metabolism , Interleukin-1beta/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Pyroptosis , SARS-CoV-2/genetics , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Vacuolar Proton-Translocating ATPases/metabolismABSTRACT
The effect of changes to cardiopulmonary resuscitation (CPR) procedures in response to Coronavirus disease 2019 (COVID-19) on in-hospital cardiac arrest (IHCA) management and outcomes are unreported. In this multicenter retrospective study, we showed that median time to arrival of resuscitation team has increased and proportion of patients receiving first-responder CPR has lowered during this pandemic. IHCA during the pandemic was independently associated with lower return of spontaneous circulation OR 0.63 (95% CI 0.43-0.91), despite adjustment for lowered patient comorbidity and increased time to resuscitation team arrival. Changes to resuscitation practice in this pandemic had effects on IHCA outcomes, even in patients without COVID-19.