Limitations of life-sustaining therapies in South Africa.

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.

Occurrences of post-traumatic stress disorder, anxiety, depression, and burnout syndrome in ICU staff workers after two-year of the COVID-19 pandemic: the international PSY-CO in ICU study.

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.

Flattening the biological age curve by improving metabolic health: to taurine or not to taurine, that' s the question.

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.

Limiting life-sustaining treatment for very old ICU patients: cultural challenges and diverse practices.

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.

Scoping review on diagnostic criteria and investigative approach in sepsis of unknown origin in critically ill patients.

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.

Plasma and Cerebrospinal Fluid Population Pharmacokinetics of Meropenem in Neurocritical Care Patients: a Prospective Two-Center Study.

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.

Multicenter Population Pharmacokinetic Study of Unbound Ceftriaxone in Critically Ill Patients.

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%.

Global Comparison of Communication of End-of-Life Decisions in the ICU.

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.

Derivation and performance of an end-of-life practice score aimed at interpreting worldwide treatment-limiting decisions in the critically ill.

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.

Effect of the COVID-19 pandemic on cardiac arrest resuscitation practices and outcomes in non-COVID-19 patients.

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.

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.

Early intubation versus late intubation for COVID-19 patients: An in situ simulation identifying factors affecting performance and infection control in airway management.

COVID-19 poses an infectious risk to healthcare workers especially during airway management. We compared the impact of early versus late intubation on infection control and performance in a randomised in situ simulation, using fluorescent powder as a surrogate for contamination. Twenty anaesthetists and intensivists intubated a simulated patient with COVID-19. The primary outcome was the degree of contamination. The secondary outcomes included the use of bag-valve-mask ventilation, the incidence of manikin cough, intubation time, first attempt success and heart rate variability as a measure of stress. The contamination score was significantly increased in the late intubation group, mean (standard deviation, SD) 17.20 (6.17), 95% confidence intervals (CI) 12.80 to 21.62 versus the early intubation group, mean (SD) 9.90 (5.13), 95% CI 6.23 to 13.57, P = 0.005. The contamination score was increased after simulated cough occurrence (mean (SD) 18.0 (5.09) versus 5.50 (2.10) in those without cough; P<0.001), and when first attempt laryngoscopy failed (mean (SD) of 17.1 (6.41) versus 11.6 (6.20) P = 0.038). The incidence of bag-mask ventilation was higher in the late intubation group (80% versus 30%; P=0.035). There was no significant difference in intubation time, incidence of failed first attempt laryngoscopy or heart rate variability between the two groups. Late intubation in patients with COVID-19 may be associated with greater laryngoscopist contamination and potential aerosol-generating events compared with early intubation. There was no difference in performance measured by intubation time and incidence of first attempt success. Late intubation, especially when resources are limited, may be a valid approach. However, strict infection control and appropriate personal protective equipment usage is recommended in such cases.

The Influence of Geography, Religion, Religiosity and Institutional Factors on Worldwide End-of-Life Care for the Critically Ill: The WELPICUS Study.

PURPOSE: To evaluate the association between provider religion and religiosity and consensus about end-of-life care and explore if geographical and institutional factors contribute to variability in practice. MATERIALS AND METHODS: Using a modified Delphi method 22 end-of-life issues consisting of 35 definitions and 46 statements were evaluated in 32 countries in North America, South America, Eastern Europe, Western Europe, Asia, Australia and South Africa. A multidisciplinary, expert group from specialties treating patients at the end-of-life within each participating institution assessed the association between 7 key statements and geography, religion, religiosity and institutional factors likely influencing the development of consensus. RESULTS: Of 3049 participants, 1366 (45%) responded. Mean age of respondents was 45 ± 9 years and 55% were females. Following 2 Delphi rounds, consensus was obtained for 77 (95%) of 81 definitions and statements. There was a significant difference in responses across geographical regions. South African and North American respondents were more likely to encourage patients to write advance directives. Fewer Eastern European and Asian respondents agreed with withdrawing life-sustaining treatments without consent of patients or surrogates. While respondent's religion, years in practice or institution did not affect their agreement, religiosity, physician specialty and responsibility for end-of-life decisions did. CONCLUSIONS: Variability in agreement with key consensus statements about end-of-life care is related primarily to differences among providers, with provider-level variations related to differences in religiosity and specialty. Geography also plays a role in influencing some end-of-life practices. This information may help understanding ethical dilemmas and developing culturally sensitive end-of-life care strategies.

The Effect of Renal Replacement Therapy and Antibiotic Dose on Antibiotic Concentrations in Critically Ill Patients: Data From the Multinational Sampling Antibiotics in Renal Replacement Therapy Study.

BACKGROUND: The optimal dosing of antibiotics in critically ill patients receiving renal replacement therapy (RRT) remains unclear. In this study, we describe the variability in RRT techniques and antibiotic dosing in critically ill patients receiving RRT and relate observed trough antibiotic concentrations to optimal targets. METHODS: We performed a prospective, observational, multinational, pharmacokinetic study in 29 intensive care units from 14 countries. We collected demographic, clinical, and RRT data. We measured trough antibiotic concentrations of meropenem, piperacillin-tazobactam, and vancomycin and related them to high- and low-target trough concentrations. RESULTS: We studied 381 patients and obtained 508 trough antibiotic concentrations. There was wide variability (4-8-fold) in antibiotic dosing regimens, RRT prescription, and estimated endogenous renal function. The overall median estimated total renal clearance (eTRCL) was 50 mL/minute (interquartile range [IQR], 35-65) and higher eTRCL was associated with lower trough concentrations for all antibiotics (P < .05). The median (IQR) trough concentration for meropenem was 12.1 mg/L (7.9-18.8), piperacillin was 78.6 mg/L (49.5-127.3), tazobactam was 9.5 mg/L (6.3-14.2), and vancomycin was 14.3 mg/L (11.6-21.8). Trough concentrations failed to meet optimal higher limits in 26%, 36%, and 72% and optimal lower limits in 4%, 4%, and 55% of patients for meropenem, piperacillin, and vancomycin, respectively. CONCLUSIONS: In critically ill patients treated with RRT, antibiotic dosing regimens, RRT prescription, and eTRCL varied markedly and resulted in highly variable antibiotic concentrations that failed to meet therapeutic targets in many patients.

A Systematic Review of Studies Reporting Antibiotic Pharmacokinetic Data in the Cerebrospinal Fluid of Critically Ill Patients with Uninflamed Meninges.

Ventriculostomy-associated infections in critically ill patients remain therapeutically challenging because of drug- and disease-related factors that contribute to suboptimal antibiotic concentrations in cerebrospinal fluid. Optimal antibiotic dosing for the treatment and prevention of such infections should be based on robust and contextually specific pharmacokinetic data. The objects of this study were to describe and critically appraise studies with reported antibiotic concentrations or pharmacokinetic data in cerebrospinal fluid of critically ill patients without meningeal inflammation. We systematically reviewed the literature to identify published reports and studies describing antibiotic concentrations, pharmacokinetics, and pharmacokinetics/pharmacodynamics in cerebrospinal fluid of critically ill patients with uninflamed meninges. Fifty-eight articles met the inclusion criteria. There was significant heterogeneity in methodologies and results. When available, antibiotic pharmacokinetic parameters displayed large intersubject variability. Intraventricular dosing achieved substantially higher antibiotic concentrations in cerebrospinal fluid than did intravenous doses. Few studies conducted a robust pharmacokinetic analysis and described relevant clinical pharmacokinetic/pharmacodynamic indices and exposure targets in cerebrospinal fluid. Robust and clinically relevant antibiotic pharmacokinetic data describing antibiotic disposition in cerebrospinal fluid are necessary. Such studies should use a standardized approach to accurately describe pharmacokinetic variability. These data should ideally be tied to clinical outcomes whereby therapeutic targets in the cerebrospinal fluid can be better defined. Altered dosing strategies, in conjunction with exploring the utility of therapeutic drug monitoring, can then be developed to optimize antibiotic exposure with the goal of improving outcomes in this difficult-to-treat patient group.

Adult ICU Triage During the Coronavirus Disease 2019 Pandemic: Who Will Live and Who Will Die? Recommendations to Improve Survival.

OBJECTIVES: Coronavirus disease 2019 patients are currently overwhelming the world's healthcare systems. This article provides practical guidance to front-line physicians forced to make critical rationing decisions. DATA SOURCES: PubMed and Medline search for scientific literature, reviews, and guidance documents related to epidemic ICU triage including from professional bodies. STUDY SELECTION: Clinical studies, reviews, and guidelines were selected and reviewed by all authors and discussed by internet conference and email. DATA EXTRACTION: References and data were based on relevance and author consensus. DATA SYNTHESIS: We review key challenges of resource-driven triage and data from affected ICUs. We recommend that once available resources are maximally extended, triage is justified utilizing a strategy that provides the greatest good for the greatest number of patients. A triage algorithm based on clinical estimations of the incremental survival benefit (saving the most life-years) provided by ICU care is proposed. "First come, first served" is used to choose between individuals with equal priorities and benefits. The algorithm provides practical guidance, is easy to follow, rapidly implementable and flexible. It has four prioritization categories: performance score, ASA score, number of organ failures, and predicted survival. Individual units can readily adapt the algorithm to meet local requirements for the evolving pandemic. Although the algorithm improves consistency and provides practical and psychologic support to those performing triage, the final decision remains a clinical one. Depending on country and operational circumstances, triage decisions may be made by a triage team or individual doctors. However, an experienced critical care specialist physician should be ultimately responsible for the triage decision. Cautious discharge criteria are proposed acknowledging the difficulties to facilitate the admission of queuing patients. CONCLUSIONS: Individual institutions may use this guidance to develop prospective protocols that assist the implementation of triage decisions to ensure fairness, enhance consistency, and decrease provider moral distress.