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Sedative overdoses pose a risk of delirium among patients in the ICU, with potential mitigation through the use of a processed EEG monitor (the bispectral index [BIS]) to guide depth of sedation. Can BIS-guided deep sedation (Richmond Agitation Sedation Scale [RASS] score, –4 or –5) reduce sedative dosage and increase delirium-free and coma-free (DFCF) days? A randomized controlled trial was conducted in a tertiary mixed ICU, enrolling patients requiring deep sedation for > 8 h. Patients were assigned randomly to either the clinical assessment (CA) or BIS groups (BIS range, 40-60). Both groups used a BIS sensor, whereas the CA group's screen remained covered. After deep sedation, BIS sensors were removed, and delirium was assessed twice daily by researchers masked to the randomization. The primary outcome was the number of DFCF days within 14 days after deep sedation. Additionally, we compared doses of sedative drugs and BIS values during deep sedation. Ninety-nine patients were included in the study. We found no significant difference in DFCF days (P =.1) between CA and BIS arms, but propofol doses were significantly lower in the BIS group (CA group, 1.77 mg/kg/h [95% CI, 1.60-1.93] vs BIS group, 1.44 mg/kg/h [95% CI, 1.04-1.83]; P =.03). During deep sedation, the CA group spent 46% of the total hours (95% CI, 35%-57%) with BIS values of < 40, whereas the BIS group spent 32% (95% CI, 25%-40%; P =.03). Subgroup analysis focusing on patients sedated for > 24 h revealed an increase in DFCF days in the BIS group (CA group: median, 1 day [interquartile range, 0-9 days] vs BIS group: median, 8 days [interquartile range, 0-13 days]; P =.04). In this study, BIS-guided deep sedation did not improve DFCF days, but did reduce sedative drug use. In patients requiring sedation for > 24 h, it showed an improvement in DFCF days. ClinicalTrials.gov; No.: NCT03840577 ; URL: www.clinicaltrials.gov [Display omitted] [ABSTRACT FROM AUTHOR]

Use of venovenous extracorporeal membrane oxygenation (ECMO) is increasing, but candidacy selection processes are variable and subject to bias. What are the reasons behind venovenous ECMO candidacy decisions, and are decisions made consistently across patients? Prospective observational study of all patients, admitted or outside hospital referrals, considered for venovenous ECMO at a tertiary referral center. Relevant clinical data and reasons for candidacy determination were cross-referenced with other noncandidates and candidates and were assessed qualitatively. Eighty-one consultations resulted in 44 noncandidates (54%), 29 candidates (36%; nine of whom subsequently underwent cannulation), and eight deferred decisions (10%). Fifteen unique contraindications were identified, variably present across all patients. Five contraindications were invoked as the sole reason to deny ECMO to a patient. In patients with three or more contraindications, additional contraindications were cited even if the severity was relatively minor. All but four contraindications invoked to deny ECMO to a patient were nonprohibitive for at least one other candidate. Contraindications documented in noncandidates were present but not mentioned in 21 other noncandidates (47%). Twenty-six candidates (90%) had at least one contraindication that was prohibitive in a noncandidate, including a contraindication that was the sole reason to deny ECMO. Contraindications were proposed as informing three prognostic domains, through which patterns of inconsistency could be understood better: (1) irreversible underlying pulmonary process, (2) unsurvivable critical illness, and (3) clinical condition too compromised for meaningful recovery. ECMO candidacy decisions are inconsistent. We identified four patterns of inconsistency in our center and propose a three-domain model for understanding and categorizing contraindications, yielding five lessons that may improve candidacy decision processes until further research can guide practice more definitively. [Display omitted] [ABSTRACT FROM AUTHOR]

Enrollment into critical care clinical trials is often hampered by the need to rely on surrogate decision-makers. To identify potential interventions facilitating enrollment into critical care clinical trials, a better understanding of surrogate decision-making for critical care clinical trial enrollment is needed. What are the barriers and facilitators of critical care trial enrollment? What are surrogate decision-makers' perspectives on proposed interventions to facilitate trial enrollment? We conducted semistructured interviews with 20 surrogate decision-makers of critically ill patients receiving mechanical ventilation. The interviews were recorded and transcribed verbatim, and analyzed for themes using an inductive approach. Thematic analysis confirmed previous research showing that trust in the system, assessing the risks and benefits of trial participation, the desire to help others, and building medical knowledge as important motivating factors for trial enrollment. Two previously undescribed concerns among surrogate decision-makers of critically ill patients were identified, including the potential to interfere with clinical treatment decisions and negative sentiment about placebos. Surrogates viewed public recognition and charitable donations for participation as favorable potential interventions to encourage trial enrollment. However, participants viewed direct financial incentives and prioritizing research participants during medical rounds negatively. This study confirms and extends previous findings that health system trust, study risks and benefits, altruism, knowledge generation, interference with clinical care, and placebos are key concerns and barriers for surrogate decision-makers to enroll patients in critical care trials. Future studies are needed to evaluate if charitable giving on the patient's behalf and public recognition are effective strategies to promote enrollment into critical care trials. [Display omitted] [ABSTRACT FROM AUTHOR]

Physicians, patients, and families alike perceive a need to improve how goals of care (GOC) decisions occur in chronic critical illness (CCI), but little is currently known about this decision-making process. How do intensivists from various health systems facilitate decision-making about GOC for patients with CCI? What are barriers to, and facilitators of, this decision-making process? We conducted semistructured interviews with a purposeful sample of intensivists from the United States and Canada using a mental models approach adapted from decision science. We analyzed transcripts inductively using qualitative description. We interviewed 29 intensivists from six institutions. Participants across all sites described GOC decision-making in CCI as a complex, longitudinal, and iterative process that involved substantial preparatory work, numerous stakeholders, and multiple family meetings. Intensivists required considerable time to collect information on prior events and conversations, and to arrive at a prognostic consensus with other involved physicians prior to meeting with families. Many intensivists stressed the importance of scheduling multiple family meetings to build trust and relationships prior to explicitly discussing GOC. Physician-identified barriers to GOC decision-making included 1-week staffing models, limited time and cognitive bandwidth, difficulty eliciting patient values, and interpersonal challenges with care team members or families. Potential facilitators included scheduled family meetings at regular intervals, greater interprofessional involvement in decisions, and consistent messaging from care team members. Intensivists described a complex time- and labor-intensive group process to achieve GOC decision-making in CCI. System-level interventions that improve how information is shared between physicians and decrease logistical and relational barriers to timely and consistent communication are key to improving GOC decision-making in CCI. [ABSTRACT FROM AUTHOR]

Death is common in the ICU and often occurs after a decision to withhold or withdraw life-sustaining therapies. Care of the dying is a core skill for ICU clinicians, requiring expert communication, primarily with family of critically ill patients. Limited high-quality evidence supports specific practices related to the care of dying patients in the ICU; thus, many of the recommendations that exist are based on expert opinion. Value exists in sharing a practical approach to caring for patients during the dying process, including topics to be addressed with family members, rationales for recommended care, and strategies for implementing comfort measures only. Through dedicated preparation and planning, clinicians can help family members navigate this intense experience. After a decision had been made to discontinue life-sustaining therapies, family members need to be given a clear description of comfort measures only and provided with additional detail about what it entails, including therapies or interventions to be discontinued, monitoring during the dying process, and common features of the dying process. Order sets can be a valuable resource for ensuring that adequate analgesia and sedation are available and the care plan is enacted properly. To achieve a good death for patients, a collaborative effort among members of the care team is essential. [ABSTRACT FROM AUTHOR]

Preexisting malnutrition in critically ill patients is associated with adverse clinical outcomes. Malnutrition can be diagnosed with the Global Leadership Initiative on Malnutrition using parameters such as weight loss, muscle wasting, and BMI. International critical care nutrition guidelines recommend high protein treatment to improve clinical outcomes in critically ill patients diagnosed with preexisting malnutrition. However, this recommendation is based on expert opinion. In critically ill patients, what is the association between preexisting malnutrition and time to discharge alive (TTDA), and does high protein treatment modify this association? This multicenter randomized controlled trial involving 16 countries was designed to investigate the effects of high vs usual protein treatment in 1,301 critically ill patients. The primary outcome was TTDA. Multivariable regression was used to identify if preexisting malnutrition was associated with TTDA and if protein delivery modified their association. The prevalence of preexisting malnutrition was 43.8%, and the cumulative incidence of live hospital discharge by day 60 was 41.2% vs 52.9% in the groups with and without preexisting malnutrition, respectively. The average protein delivery in the high vs usual treatment groups was 1.6 g/kg per day vs 0.9 g/kg per day. Preexisting malnutrition was independently associated with slower TTDA (adjusted hazard ratio, 0.81; 95% CI, 0.67-0.98). However, high protein treatment in patients with and without preexisting malnutrition was not associated with TTDA (adjusted hazard ratios of 0.84 [95% CI, 0.63-1.11] and 0.97 [95% CI, 0.77-1.21]). Furthermore, no effect modification was observed (ratio of adjusted hazard ratio, 0.84; 95% CI, 0.58-1.20). Malnutrition was associated with slower TTDA, but high protein treatment did not modify the association. These findings challenge current international critical care nutrition guidelines. ClinicalTrials.gov ; No.: NCT03160547 ; URL: www.clinicaltrials.gov [Display omitted] [ABSTRACT FROM AUTHOR]

COVID-19 has caused > 7 million deaths worldwide since its onset in 2019. Although the severity of illness has varied throughout the pandemic, critical illness related to COVID-19 persists. Survivors of COVID-19 critical illness can be left with sequelae of both the SARS-CoV-2 virus and long-term effects of critical illness included within post-intensive care syndrome. Given the complexity and heterogeneity of COVID-19 critical illness, the biopsychosocial-ecological model can aid in evaluation and treatment of survivors, integrating interactions among physical, cognitive, and psychological domains, as well as social systems and environments. Prolonged illness after COVID-19 critical illness generally can be classified into effects on physical, cognitive, and psychosocial function, with much interaction among the various effects, and includes a wide range of symptoms such as ICU-acquired weakness, prolonged respiratory symptoms, cognitive changes, post-traumatic stress disorder post-traumatic stress disorder, anxiety, and depression. Risk factors for COVID-19 critical illness developing are complex and include preexisting factors, disease course, and specifics of hospitalization in addition to psychological comorbidities and socioenvironmental factors. Recovery trajectories are not well defined, and management requires a comprehensive, interdisciplinary, and individualized approach to care. The onset of vaccinations, new therapeutics, and new strains of SARS-CoV-2 virus have decreased COVID-19 mortality; however, the number of survivors of COVID-19 critical illness remains high. A biopsychosocial-ecological approach is recommended to guide care of COVID-19 critical illness survivors. [ABSTRACT FROM AUTHOR]

A newborn girl presented to the hospital on the first day of life because of respiratory failure. She was born at home at 37 weeks' gestation with minimal prenatal care and was found to be small for gestational age. The patient was found to have partial sternal agenesis and sternal cleft, cutis aplasia, left facial hemangioma, micrognathia, wide-spaced nipples, and low-set ears. The mother's and baby's urine toxicology screening were positive for amphetamines. Chest radiographs on admission showed bilateral hazy opacities. CT scan of the chest showed an absent sternum with midline chest wall concavity. The patient was monitored preoperatively in the cardiac ICU for risks of arrythmia, respiratory failure, altered cardiac output, and acute cardiopulmonary decompensation. [ABSTRACT FROM AUTHOR]

Delirium is a potentially severe form of acute encephalopathy. Minocycline has neuroprotective effects in animal models of neurologic diseases; however, data from human studies remain scarce. Does the neuroprotective effect of minocycline prevent delirium occurrence in critically ill patients? This study was a randomized, placebo-controlled, double-anonymized trial conducted in four ICUs. Patients aged 18 years or older were eligible and randomized to receive minocycline (100 mg, twice daily) or placebo. The primary outcome was delirium incidence within 28 days or before ICU discharge. Secondary outcomes included days in delirium during ICU stay, delirium/coma-free days, length of mechanical ventilation, ICU length of stay, ICU mortality, and hospital mortality. The kinetics of various inflammatory (IL-1β, IL-6, IL-10, and C-reactive protein) and brain-related biomarkers (brain-derived neurotrophic factor and S100B) were used as exploratory outcomes. A total of 160 patients were randomized, but one patient in the placebo group died before treatment; thus the data from 159 patients were analyzed (minocycline, n = 84; placebo, n = 75). After the COVID-19 pandemic it was decided to stop patient inclusion early. There was a small but significant decrease in delirium incidence: 17 patients (20%) in the minocycline arm compared with 26 patients (35%) in the placebo arm (P =.043). No other delirium-related outcomes were modified by minocycline treatment. Unexpectedly, there was a significant decrease in hospital mortality (39% vs. 23%; P =.029). Among all analyzed biomarkers, only plasma levels of C-reactive protein decreased significantly after minocycline treatment (F = 0.75, P =.78, within time; F = 4.09, P =.045, group × time). Our findings in this rather small study signal a possible positive effect of minocycline on delirium incidence. Further studies are needed to confirm the benefits of this drug as a preventive measure in critically ill patients. ClinicalTrials.gov ; No.: NCT04219735; URL: www.clinicaltrials.gov [Display omitted] [ABSTRACT FROM AUTHOR]

Machine learning (ML)-derived notifications for impending episodes of hemodynamic instability and respiratory failure events are interesting because they can alert physicians in time to intervene before these complications occur. Do ML alerts, telemedicine system (TS)-generated alerts, or biomedical monitors (BMs) have superior performance for predicting episodes of intubation or administration of vasopressors? An ML algorithm was trained to predict intubation and vasopressor initiation events among critically ill adults. Its performance was compared with BM alarms and TS alerts. ML notifications were substantially more accurate and precise, with 50-fold lower alarm burden than TS alerts for predicting vasopressor initiation and intubation events. ML notifications of internal validation cohorts demonstrated similar performance for independent academic medical center external validation and COVID-19 cohorts. Characteristics were also measured for a control group of recent patients that validated event detection methods and compared TS alert and BM alarm performance. The TS test characteristics were substantially better, with 10-fold less alarm burden than BM alarms. The accuracy of ML alerts (0.87-0.94) was in the range of other clinically actionable tests; the accuracy of TS (0.28-0.53) and BM (0.019-0.028) alerts were not. Overall test performance (F scores) for ML notifications were more than fivefold higher than for TS alerts, which were higher than those of BM alarms. ML-derived notifications for clinically actioned hemodynamic instability and respiratory failure events represent an advance because the magnitude of the differences of accuracy, precision, misclassification rate, and pre-event lead time is large enough to allow more proactive care and has markedly lower frequency and interruption of bedside physician work flows. [Display omitted] [ABSTRACT FROM AUTHOR]

Since the 1990s, time-limited trials have been described as an approach to navigate uncertain benefits and limits of life-sustaining therapies in patients with critical illness. In this review, we aim to synthesize the evidence on time-limited trials in critical care, establish what is known, and highlight important knowledge gaps. We identified 18 empirical studies and 15 ethical analyses about time-limited trials in patients with critical illness. Observational studies suggest time-limited trials are part of current practice in ICUs in the United States, but their use varies according to unit and physician factors. Some ICU physicians are familiar with, endorse, and have participated in time-limited trials, and some older adults appear to favor time-limited trial strategies over indefinite life-sustaining therapy or care immediately focused on comfort. When time-limited trials are used, they are often implemented incompletely and challenged by systematic barriers (eg, continually rotating ICU staff). Predictive modeling studies support prevailing clinical wisdom that prognostic uncertainty decreases over time in the ICU for some patients. One study prospectively comparing usual ICU care with an intervention designed to support time-limited trials yielded promising preliminary results. Ethical analyses describe time-limited trials as a pragmatic approach within the longstanding discussion about withholding and withdrawing life-sustaining therapies. Time-limited trials are endorsed by physicians, align with the priorities of some older adults, and are part of current practice. Substantial efforts are needed to test their impact on patient-centered outcomes, improve their implementation, and maximize their potential benefit. [ABSTRACT FROM AUTHOR]

During the COVID-19 pandemic, ICUs remained under stress and observed elevated mortality rates and high variations of outcomes. A knowledge gap exists regarding whether an ICU performing best during nonpandemic times would still perform better when under high pressure compared with the least performing ICUs. Does prepandemic ICU performance explain the risk-adjusted mortality variability for critically ill patients with COVID-19? This study examined a cohort of adults with real-time polymerase chain reaction-confirmed COVID-19 admitted to 156 ICUs in 35 hospitals from February 16, 2020, through December 31, 2021, in Brazil. We evaluated crude and adjusted in-hospital mortality variability of patients with COVID-19 in the ICU during the pandemic. Association of baseline (prepandemic) ICU performance and in-hospital mortality was examined using a variable life-adjusted display (VLAD) during the pandemic and a multivariable mixed regression model adjusted by clinical characteristics, interaction of performance with the year of admission, and mechanical ventilation at admission. Thirty-five thousand six hundred nineteen patients with confirmed COVID-19 were evaluated. The median age was 52 years, median Simplified Acute Physiology Score 3 was 42, and 18% underwent invasive mechanical ventilation. In-hospital mortality was 13% and 54% for those receiving invasive mechanical ventilation. Adjusted in-hospital mortality ranged from 3.6% to 63.2%. VLAD in the most efficient ICUs was higher than the overall median in 18% of weeks, whereas VLAD was 62% and 84% in the underachieving and least efficient groups, respectively. The least efficient baseline ICU performance group was associated independently with increased mortality (OR, 2.30; 95% CI, 1.45-3.62) after adjusting for patient characteristics, disease severity, and pandemic surge. ICUs caring for patients with COVID-19 presented substantial variation in risk-adjusted mortality. ICUs with better baseline (prepandemic) performance showed reduced mortality and less variability. Our findings suggest that achieving ICU efficiency by targeting improvement in organizational aspects of ICUs may impact outcomes, and therefore should be a part of the preparedness for future pandemics. [ABSTRACT FROM AUTHOR]

Influenza-associated pulmonary aspergillosis (IAPA) increasingly is being reported in critically ill patients. We conducted this systematic review and meta-analysis to examine the prevalence, risk factors, clinical features, and outcomes of IAPA. What are the prevalence, risk factors, clinical features, and outcomes of IAPA in critically ill patients? Studies reporting IAPA were searched in the following databases: PubMed MEDLINE, CINAHL, Cochrane Library, Embase, Scopus, Cochrane Trials, and ClinicalTrials.gov. We performed one-group meta-analysis on risk factors, clinical features, morbidity, and mortality using random effects models. We included 10 observational studies with 1,720 critically ill patients with influenza, resulting in an IAPA prevalence of 19.2% (331 of 1,720). Patients who had undergone organ transplantation (OR, 4.8; 95% CI, 1.7-13.8; I 2 = 45%), harbored a hematogenous malignancy (OR, 2.5; 95% CI, 1.5-4.1; I 2 = 0%), were immunocompromised (OR, 2.2; 95% CI, 1.6-3.1; I 2 = 0%), and underwent prolonged corticosteroid use before admission (OR, 2.4; 95% CI, 1.4-4.3; I 2 = 51%) were found to be at a higher risk of IAPA developing. Commonly reported clinical and imaging features were not particularly associated with IAPA. However, IAPA was associated with more severe disease progression, a higher complication rate, and longer ICU stays and required more organ supports. Overall, IAPA was associated with a significantly elevated ICU mortality rate (OR, 2.6; 95% CI, 1.8-3.8; I 2 = 0%). IAPA is a common complication of severe influenza and is associated with increased mortality. Early diagnosis of IAPA and initiation of antifungal treatment are essential, and future research should focus on developing a clinical algorithm. International Prospective Register of Systematic Reviews; No.: CRD42022284536; URL: https://www.crd.york.ac.uk/prospero/ [ABSTRACT FROM AUTHOR]

Critical care clinicians are likely to see an increasing number of patients admitted to the ICU who are receiving US Food and Drug Administration-approved medications for opioid use disorder (MOUDs) given the well-documented benefits of these agents. Oral methadone, multiple formulations of buprenorphine, and extended-release naltrexone are the three types of MOUD most likely to be encountered by ICU clinicians; however, these drugs vary with respect to formulations, pharmacokinetics, and adverse effects. No published clinical practice guidelines or consensus statements are available to guide decision-making in patients admitted to the ICU setting who are receiving MOUDs before admission. Additionally, no randomized trials and limited observational studies have evaluated issues related to MOUD use in the ICU. Therefore, ICU clinicians caring for patients admitted who are taking MOUDs must base their decision-making on data extrapolation from pharmacokinetic, pharmacologic, and clinical studies performed in non-ICU settings. Despite the challenges in administering MOUDs in critically ill patients, extrapolation of data from other hospital settings suggests that the benefits of continuing MOUD therapy outweigh the risks in patients able to continue therapy. This article provides guidance for critical care clinicians caring for patients admitted to the ICU already receiving methadone, buprenorphine, or extended-release naltrexone. The guidance includes algorithms to aid clinicians in the clinical decision-making process, recognizing the inherent limitations of the existing evidence on which the algorithms are based and the need to account for patient-specific considerations. [ABSTRACT FROM AUTHOR]

With recent prioritization of equity in pediatric health outcomes, a shift to examine neighborhood-level health care disparities within pediatric populations has occurred, specifically in the context of critical illness. Does an association exist between individual indicators of neighborhood-level disadvantage and incidence of PICU admission? Pediatric patients younger than 18 years admitted to a PICU in a large urban tertiary pediatric hospital from January 1, 2016, through December 31, 2019, with a residential address in the city of Baltimore or Baltimore County on the day of admission were included in this ecological study. Demographic and clinical characteristics of children admitted to the PICU were summarized, with the primary outcome being PICU admission. Unadjusted negative binomial regression was used to examine the association between census tract-level PICU admissions and the previously described census tract-level indicators of neighborhood socioeconomic position. Regression models included an offset term for the population younger than 18 years for each census tract; results of models are reported as incidence rate ratios (IRRs) with corresponding 95% CIs. We identified 2,476 PICU admissions: 1,351 patients from the city of Baltimore (10.25 per 1,000 children) and 1,125 patients from Baltimore County (6.31 per 1,000 children). Most PICU admissions (n = 906 [68%]) for the city of Baltimore represented an area deprivation index (ADI) of > 60, whereas most Baltimore County PICU admissions (n = 919 [82.3%]) represented an ADI of < 60. At the neighborhood level, the percentage of families living below the poverty line was associated with greater incidence of PICU admission in the city of Baltimore (IRR, 1.09; 95% CI, 1.00-1.18) and Baltimore County (IRR, 1.19; 95% CI, 1.05-1.36). For every $10,000 increase in median household income, PICU admission rates dropped by 9% for the city of Baltimore (IRR, 0.91; 95% CI, 0.86-0.95) and Baltimore County (IRR, 0.91; 95% CI, 0.88-0.94). Neighborhoods with vacant housing units also were associated with a higher incidence of PICU admission in the city of Baltimore (IRR, 1.10; 95% CI, 1.01-1.21) and Baltimore County (IRR, 1.46; 95% CI, 1.21-1.77), as was a 10% increase in occupied homes without vehicles (city of Baltimore: IRR, 1.14; 95% CI, 1.07-1.21; Baltimore County: IRR, 1.23; 95% CI, 1.11-1.37). Health outcomes of pediatric critical illness should be examined in the context of structural determinants of health, including neighborhood-level and environmental characteristics. [Display omitted] [ABSTRACT FROM AUTHOR]

Whether intubation should be initiated early in the clinical course of critically ill patients remains a matter of debate. Results from prior observational studies are difficult to interpret because of avoidable flaws including immortal time bias, inappropriate eligibility criteria, and unrealistic treatment strategies. Do treatment strategies that intubate patients early in the critical care admission improve 30-day survival compared with strategies that delay intubation? We estimated the effect of strategies that require early intubation of critically ill patients compared with those that delay intubation. With data extracted from the Medical Information Mart for Intensive Care-IV database, we emulated three target trials, varying the flexibility of the treatment strategies and the baseline eligibility criteria. Under unrealistically strict treatment strategies with broad eligibility criteria, the 30-day mortality risk was 7.1 percentage points higher for intubating early compared with delaying intubation (95% CI, 6.2-7.9). Risk differences were 0.4 (95% CI, –0.1 to 0.9) and –0.9 (95% CI, –2.5 to 0.7) percentage points in subsequent target trial emulations that included more realistic treatment strategies and eligibility criteria. When realistic treatment strategies and eligibility criteria are used, strategies that delay intubation result in similar 30-day mortality risks compared with those that intubate early. Delaying intubation ultimately avoids intubation in most patients. [Display omitted] [ABSTRACT FROM AUTHOR]

Evidence regarding acute kidney injury associated with concomitant administration of vancomycin and piperacillin-tazobactam is conflicting, particularly in patients in the ICU. Does a difference exist in the association between commonly prescribed empiric antibiotics on ICU admission (vancomycin and piperacillin-tazobactam, vancomycin and cefepime, and vancomycin and meropenem) and acute kidney injury? This was a retrospective cohort study using data from the eICU Research Institute, which contains records for ICU stays between 2010 and 2015 across 335 hospitals. Patients were enrolled if they received vancomycin and piperacillin-tazobactam, vancomycin and cefepime, or vancomycin and meropenem exclusively. Patients initially admitted to the ED were included. Patients with hospital stay duration of < 1 h, receiving dialysis, or with missing data were excluded. Acute kidney injury was defined as Kidney Disease: Improving Global Outcomes stage 2 or 3 based on serum creatinine component. Propensity score matching was used to match patients in the control (vancomycin and meropenem or vancomycin and cefepime) and treatment (vancomycin and piperacillin-tazobactam) groups, and ORs were calculated. Sensitivity analyses were performed to study the effect of longer courses of combination therapy and patients with renal insufficiency on admission. Thirty-five thousand six hundred fifty-four patients met inclusion criteria (vancomycin and piperacillin-tazobactam, n = 27,459; vancomycin and cefepime, n = 6,371; vancomycin and meropenem, n = 1,824). Vancomycin and piperacillin-tazobactam was associated with a higher risk of acute kidney injury and initiation of dialysis when compared with that of both vancomycin and cefepime (Acute kidney injury: OR, 1.37 [95% CI, 1.25-1.49]; dialysis: OR, 1.28 [95% CI, 1.14-1.45]) and vancomycin and meropenem (Acute kidney injury: OR, 1.27 [95%, 1.06-1.52]; dialysis: OR, 1.56 [95% CI, 1.23-2.00]). The odds of acute kidney injury developing was especially pronounced in patients without renal insufficiency receiving a longer duration of vancomycin and piperacillin-tazobactam therapy compared with vancomycin and meropenem therapy. VPT is associated with a higher risk of acute kidney injury than both vancomycin and cefepime and vancomycin and meropenem in patients in the ICU, especially for patients with normal initial kidney function requiring longer durations of therapy. Clinicians should consider vancomycin and meropenem or vancomycin and cefepime to reduce the risk of nephrotoxicity for patients in the ICU. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] [ABSTRACT FROM AUTHOR]

Collecting blood cultures from indwelling arterial catheters is an attractive option in critically ill adult patients when peripheral venipuncture is difficult. However, whether the contamination proportion of blood cultures from arterial catheters is acceptable compared with that from venipuncture is inconclusive. Is contamination of blood cultures from arterial catheters noninferior to that from venipuncture in critically ill adult patients with suspected bloodstream infection? In this multicenter prospective diagnostic study conducted at five hospitals, we enrolled episodes of paired blood culture collection, each set consisting of blood drawn from an arterial catheter and another by venipuncture, were obtained from critically ill adult patients with cilinical indication. The primary measure was the proportion of contamination, defined as the number of false-positive results relative to the total number of procedures done. The reference standard for true bloodstream infection was blinded assessment by infectious disease specialists. We examined the noninferiority hypothesis that the contamination proportion of blood cultures from arterial catheters did not exceed that from venipuncture by 2.0%. Of 1,655 episodes of blood culture from December 2018 to July 2021, 590 paired blood culture episodes were enrolled, and 41 of the 590 episodes (6.9%) produced a true bloodstream infection. In blood cultures from arterial catheters, 33 of 590 (6.0%) were positive, and two of 590 (0.3%) were contaminated; in venipuncture, 36 of 590 (6.1%) were positive, and four of 590 (0.7%) were contaminated. The estimated difference in contamination proportion (arterial catheter – venipuncture) was –0.3% (upper limit of one-sided 95% CI, +0.3%). The upper limit of the 95% CI did not exceed the predefined margin of +2.0%, establishing noninferiority (P for noninferiority <.001). Obtaining blood cultures from arterial catheters is an acceptable alternative to venipuncture in critically ill patients. University Hospital Medical Information Network Center (UMIN-CTR); No.: UMIN000035392; URL: https://center6.umin.ac.jp/ [Display omitted] [ABSTRACT FROM AUTHOR]

ICU survivors often have complex care needs and can experience insufficient medication reconciliation and polypharmacy. It is unknown which ICU survivors are at risk of new sedative use posthospitalization. For sedative-naive, older adult ICU survivors, how common is receipt of new and persistent sedative prescriptions, and what factors are associated with receipt? This population-based cohort study included ICU survivors aged ≥ 66 years who had not filled sedative prescriptions within ≤ 6 months before hospitalization (sedative-naive) in Ontario, Canada (2003-2019). Using multilevel logistic regression, demographic, clinical, and hospital characteristics and their association with new sedative prescription within ≤ 7 days of discharge are described. Variation between hospitals was quantified by using the adjusted median OR. Factors associated with persistent prescriptions (≤ 6 months) were examined with a multivariable proportional hazards model. A total of 250,428 patients were included (mean age, 76 years; 61% male). A total of 15,277 (6.1%) filled a new sedative prescription, with variation noted across hospitals (2% [95% CI, 1-3] to 44% [95% CI, 3-57]); 8,458 (3.4%) filled persistent sedative prescriptions. Adjusted factors associated with a new sedative included: discharge to long-term care facility (adjusted OR [aOR], 4.00; 95% CI, 3.72-4.31), receipt of inpatient geriatric (aOR, 1.95; 95% CI, 1.80-2.10) or psychiatry (aOR, 2.76; 95% CI, 2.62-2.91) consultation, invasive ventilation (aOR, 1.59; 95% CI, 1.53-1.66), and ICU length of stay ≥ 7 days (aOR, 1.50; 95% CI, 1.42-1.58). The residual heterogeneity between hospitals (adjusted median OR, 1.43; 95% CI, 1.35-1.49) had a stronger association with new sedative prescriptions than the Charlson Comorbidity Index score or sepsis. Factors associated with persistent sedative use were similar with the addition of female subjects (subdistribution hazard ratio, 1.07; 95% CI, 1.02-1.13) and pre-existing polypharmacy (subdistribution hazard ratio, 0.88; 95% CI, 0.80-0.93). One in 15 sedative-naive, older adult ICU survivors filled a new sedative within ≤ 7 days of discharge; more than one-half of these survivors filled persistent prescriptions. New prescriptions at discharge varied widely across hospitals and represent the potential value of modifying prescription practices, including medication review and reconciliation. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Beyond the question of short-term survival, days spent at home could be considered a patient-centered outcome in critical care trials.Research Question: What are the days spent at home and health care trajectories during the year after surviving critical illness?Study Design and Methods: Data were extracted on adult survivors spending at least 2 nights in a French ICU during 2018 who were treated with invasive mechanical ventilation or vasopressors or inotropes. Trauma, burn, organ transplant, stroke, and neurosurgical patients were excluded. Stays at home, death, and hospitalizations were reported before and after ICU stay, using state sequence analysis. An unsupervised clustering method was performed to identify cohorts based on post-ICU trajectories.Results: Of 77,132 ICU survivors, 89% returned home. In the year after discharge, these patients spent a median of 330 (interquartile range [IQR], 283-349) days at home. At 1 year, 77% of patients were still at home and 17% had died. Fifty-one percent had been re-hospitalized, and 10% required a further ICU admission. Forty-eight percent used rehabilitation facilities, and 5.7%, hospital at home. Three clusters of patients with distinct post-ICU trajectories were identified. Patients in cluster 1 (68% of total) survived and spent most of the year at home (338 [323-354] days). Patients in cluster 2 (18%) had more complex trajectories, but most could return home (91%), spending 242 (174-277) days at home. Patients in cluster 3 (14%) died, with only 37% returning home for 45 (15-90) days.Interpretation: Many patients had complex health care trajectories after surviving critical illness. Wide variations in the ability to return home after ICU discharge were observed between clusters, which represents an important patient-centered outcome. [ABSTRACT FROM AUTHOR]

Background: Research confirms the heterogeneous nature of patient challenges during recovery from the ICU and supports the need for modifying care experiences, but few data are available to guide clinicians seeking to support patients' individual recovery trajectories.Research Question: What is the content of patient-provider dialogues in a telemedicine multidisciplinary ICU recovery clinic (ICU-RC)?Study Design and Methods: We conducted a qualitative descriptive study in a telemedicine multidisciplinary ICU-RC at a tertiary academic medical center in the southeastern United States. The sample included 19 patients and 13 caregivers (≥ 18 years of age) attending a telemedicine ICU-RC visit after critical illness resulting from septic shock or ARDS. Patients and caregivers met with an ICU pharmacist, ICU physician, and a psychologist via a secure web-conferencing platform for 33 ICU-RC visits within 12 weeks of hospital discharge. Telemedicine ICU-RC visits were audio-recorded and transcribed verbatim for analysis. A coding system was developed using iterative inductive and deductive approaches.Results: Two themes were identified from the patient-provider dialogue: (1) problem identification and (2) problem-solving strategies. We identified five subthemes that capture the types of problems identified: health status, mental health and cognition, medication management, health-care access and navigation, and quality of life. Problem-solving subthemes included facilitating care coordination and transitions, providing education, and giving constructive feedback and guidance.Interpretation: Patients surviving a critical illness experience a complexity of problems that may be addressed best by a multidisciplinary ICU-RC. Through analysis of our telemedicine ICU-RC dialogues, we were able to identify problems and solutions to address challenges during a critical transitional phase of ICU recovery.Trial Registry: ClinicalTrials.gov; No.: NCT03926533; URL: www.Clinicaltrials: gov. [ABSTRACT FROM AUTHOR]

Survivors of ICU hospitalizations often experience severe and debilitating symptoms long after critical illness has resolved. Many patients experience notable psychiatric sequelae such as depression, anxiety, and posttraumatic stress disorder (PTSD) that may persist for months to years after discharge. The COVID-19 pandemic has produced large numbers of critical illness survivors, warranting deeper understanding of psychological morbidity after COVID-19 critical illness. Many patients with critical illness caused by COVID-19 experience substantial post-ICU psychological sequelae mediated by specific pathophysiologic, iatrogenic, and situational risk factors. Existing and novel interventions focused on minimizing psychiatric morbidity need to be further investigated to improve critical care survivorship after COVID-19 illness. This review proposes a framework to conceptualize three domains of risk factors (pathophysiologic, iatrogenic, and situational) associated with psychological morbidity caused by COVID-19 critical illness: (1) direct and indirect effects of the COVID-19 virus in the brain; (2) iatrogenic complications of ICU care that may disproportionately affect patients with COVID-19; and (3) social isolation that may worsen psychological morbidity. In addition, we review current interventions to minimize psychological complications after critical illness. [ABSTRACT FROM AUTHOR]

Background: Broad-scale adoption of spontaneous awakening trials (SATs) and spontaneous breathing trials (SBTs) into everyday practice has been slow, and uncertainty exists regarding what factors facilitate or impede their routine delivery.Research Question: What patient, practice, and pharmacologic factors are associated with SAT and SBT performance and to what extent do they predict overall SAT/SBT performance?Study Design and Methods: This secondary analysis used data collected from a national quality improvement collaborative composed of 68 diverse ICUs. Adults with critical illness adults who received mechanical ventilation and/or continuously infused sedative medications were included. We performed mixed-effects logistic regression modeling, created receiver operating characteristic curves, and calculated the area under the curve (AUC).Results: Included in the SAT and SBT analysis were 4,847 and 4,938 patients, respectively. In multivariable models controlling for admitting patient characteristics, factors independently associated with higher odds of a next-day SAT and SBT included physical restraint use (adjusted odds ratio [AOR], 1.63; 95% CI, 1.42-1.87; AOR, 1.83; 95% CI, 1.60-2.09), documented target sedation level (AOR, 1.68; 95% CI, 1.41-2.01; AOR, 1.46; 95% CI, 1.24-1.72), more frequent level of arousal assessments (AOR, 1.22; 95% CI, 1.03-1.43; AOR, 1.32; 95% CI, 1.13-1.54), and dexmedetomidine administration (AOR, 1.23; 95% CI, 1.05-1.45; AOR, 1.52; 95% CI, 1.27-1.80). Factors independently associated with lower odds of a next-day SAT and SBT included deep sedation/coma (AOR, 0.69; 95% CI, 0.60-0.80; AOR, 0.33; 95% CI, 0.28-0.37) and benzodiazepine (AOR, 0.83; 95% CI, 0.72-0.95; AOR, 0.67; 95% CI, 0.59-0.77) or ketamine (AOR, 0.34; 95% CI, 0.16-0.71; AOR, 0.40; 95% CI, 0.18-0.88) administration. Models incorporating admitting, daily, and unit variations displayed moderate discriminant accuracy in predicting next-day SAT (AUC, 0.73) and SBT (AUC, 0.72) performance.Interpretation: There are a number of modifiable factors associated with SAT/SBT performance that are amenable to the development and testing of implementation interventions. [ABSTRACT FROM AUTHOR]

Background: Blood products frequently are administered to critically ill patients. Considering recent trials and practice variability, a comprehensive review of current evidence was deemed essential to offer pertinent guidance to critical care practitioners. This American College of Chest Physicians (CHEST) guidelines panel examined the literature on RBC transfusions among critically ill patients overall and specific subgroups, including patients with gastrointestinal bleeding, acute coronary syndrome (ACS), cardiac surgery, isolated troponin elevation, and septic shock, to provide evidence-based recommendations., Study Design and Methods: A panel of experts developed 6 Population, Intervention, Comparator, and Outcome questions addressing RBC transfusions in critically ill patients and performed a comprehensive evidence review. The panel applied the Grading of Recommendations, Assessment, Development, and Evaluations approach to assess the certainty of evidence and to formulate and grade recommendations. A modified Delphi technique was used to reach consensus on the recommendations., Results: The initial search identified a total of 3,082 studies, and after the initial screening, 38 articles were reviewed. Among them, 23 studies met inclusion criteria, comprising 22 randomized controlled trials and 1 cohort study. Based on the analysis of these studies, the panel formulated 2 strong and 4 conditional recommendations. The overall quality of evidence for recommendations ranged from very low to moderate., Conclusions: In most critically ill patients, a restrictive strategy was preferable to a permissive approach because it does not increase the risk of death or complications, but does decrease RBC use significantly. Data from critically ill subpopulations also supported a restrictive approach, except in patients with ACS, for whom favoring a restrictive approach could increase adverse outcomes., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Patients hospitalized with COVID-19 often exhibit markers of a hypercoagulable state and have an increased incidence of VTE. In response, CHEST issued rapid clinical guidance regarding prevention of VTE. Over the past 18 months the quality of the evidence has improved. We thus sought to incorporate this evidence and update our recommendations as necessary.Study Design and Methods: This update focuses on the optimal approach to thromboprophylaxis in hospitalized patients. The original questions were used to guide the search, using MEDLINE via PubMed. Eight randomized controlled trials and one observational study were included. Meta-analysis, using a random effects model, was performed. The panel created summaries using the GRADE Evidence-to-Decision framework. Updated guidance statements were drafted, and a modified Delphi approach was used to obtain consensus.Results: We provide separate guidance statements for VTE prevention for hospitalized patients with acute (moderate) illness and critically ill patients in the ICU. However, we divided each original question and resulting recommendation into two questions: standard prophylaxis vs therapeutic (or escalated dose) prophylaxis and standard prophylaxis vs intermediate dose prophylaxis. This led to a change in one recommendation, and an upgrading of three additional recommendations based upon higher quality evidence.Conclusions: Advances in care for patients with COVID-19 have improved overall outcomes. Despite this, rates of VTE in these patients remain elevated. Critically ill patients should receive standard thromboprophylaxis for VTE, and moderately ill patients with a low bleeding risk might benefit from therapeutic heparin. We see no role for intermediate dose thromboprophylaxis in either setting. [ABSTRACT FROM AUTHOR]

As outcomes have improved across the hematologic malignancy population, candidacy for ICU admission has increased. This complex population may develop a variety of complications related to their treatment or underlying disease that can result in critical illness necessitating ICU support. This review highlights common causes of critical illness associated with hematologic malignancies, including the following: (1) neutropenic sepsis; (2) hyperleukocytosis and leukostasis across patients with acute myeloid leukemia; (3) complications of acute promyelocytic leukemia; (4) tumor lysis syndrome; and (5) critical care complications that can arise following hematopoietic stem cell transplantation. [ABSTRACT FROM AUTHOR]

In critically ill patients receiving mechanical ventilation, expiratory muscles are recruited with high respiratory loading and/or low inspiratory muscle capacity. In this case report, we describe a previously unrecognized patient-ventilator dyssynchrony characterized by ventilator triggering by expiratory muscle relaxation, an observation that we termed expiratory muscle relaxation-induced ventilator triggering (ERIT). ERIT can be recognized with in-depth respiratory muscle monitoring as (1) an increase in gastric pressure (Pga) during expiration, resulting from expiratory muscle recruitment; (2) a drop in Pga (and hence, esophageal pressure) at the time of ventilator triggering; and (3) diaphragm electrical activity onset occurring after ventilator triggering. Future studies should focus on the incidence of ERIT and the impact in the patient receiving mechanical ventilation. [ABSTRACT FROM AUTHOR]

Hematologic conditions (malignant or benign) may progress to acute critical illness requiring prompt recognition and intensive management. This review outlines diagnostic considerations and approaches to management for intensivists of common benign hematologic emergencies, including the following: thrombotic thrombocytopenic purpura, atypical hemolytic uremic syndrome, disseminated intravascular coagulopathy, catastrophic antiphospholipid antibody syndrome, hemophagocytic lymphohistiocytosis, acute chest syndrome associated with sickle cell disease, and hyperhemolysis syndrome. [ABSTRACT FROM AUTHOR]

Background: Current guidelines recommend empirical antifungal therapy in patients with sepsis with high risk of invasive Candida infection. However, many different risk factors have been derived from multiple studies. These risk factors lack specificity, and broad application would render most ICU patients eligible for empirical antifungal therapy.Research Question: What risk factors for invasive Candida infection can be identified by a systematic review and meta-analysis?Study Design and Methods: We searched PubMed, Web of Science, ScienceDirect, Biomed Central, and Cochrane and extracted the raw and adjusted OR for each risk factor associated with invasive Candida infection. We calculated pooled ORs for risk factors present in more than one study.Results: We included 34 studies in our meta-analysis resulting in the assessment of 29 possible risk factors. Risk factors for invasive Candida infection included demographic factors, comorbid conditions, and medical interventions. Although demographic factors do not play a role for the development of invasive Candida infection, comorbid conditions (eg, HIV, Candida colonization) and medical interventions have a significant impact. The risk factors associated with the highest risk for invasive Candida infection were broad-spectrum antibiotics (OR, 5.6; 95% CI, 3.6-8.8), blood transfusion (OR, 4.9; 95% CI, 1.5-16.3), Candida colonization (OR, 4.7; 95% CI, 1.6-14.3), central venous catheter (OR, 4.7; 95% CI, 2.7-8.1), and total parenteral nutrition (OR, 4.6; 95% CI, 3.3-6.3). However, dependence between the various risk factors is probably high.Interpretation: Our systematic review and meta-analysis identified patient- and treatment-related factors that were associated with the risk for the development of invasive Candida infection in the ICU. Most of the factors identified were either related to medical interventions during intensive care or to comorbid conditions. [ABSTRACT FROM AUTHOR]

Background: Perceived health is one of the strongest determinants of subjective well-being, but it has received little attention among survivors of ARDS.Research Question: How well do self-reported measures of physical, emotional, and social functioning predict perceived overall health (measured using the EQ-5D visual analog scale [EQ-5D-VAS]) among adult survivors of ARDS? Are demographic features, comorbidity, or severity of illness correlated with perceived health after controlling for self-reported functioning?Study Design and Methods: We analyzed the ARDSNet Long Term Outcomes Study (ALTOS) and Improving Care of Acute Lung Injury Patients (ICAP) Study, two longitudinal cohorts with a total of 823 survivors from 44 US hospitals, which prospectively assessed survivors at 6 and 12 months after ARDS. Perceived health, evaluated using the EQ-5D-VAS, was predicted using ridge regression and self-reported measures of physical, emotional, and social functioning. The difference between observed and predicted perceived health was termed perspective deviation (PD). Correlations between PD and demographics, comorbidities, and severity of illness were explored.Results: The correlation between observed and predicted EQ-5D-VAS scores ranged from 0.68 to 0.73 across the two cohorts and time points. PD ranged from -80 to +34 and was more than the minimum clinically important difference for 52% to 55% of survivors. Neither demographic features, comorbidity, nor severity of illness were correlated strongly with PD, with |r| < 0.25 for all continuous variables in both cohorts and time points. The correlation between PD at 6- and 12-month assessments was weak (ALTOS: r = 0.22, P < .001; ICAP: r = 0.20, P = .02).Interpretation: About half of survivors of ARDS showed clinically important differences in actual perceived health vs predicted perceived health based on self-reported measures of functioning. Survivors of ARDS demographic features, comorbidities, and severity of illness were correlated only weakly with perceived health after controlling for measures of perceived functioning, highlighting the challenge of predicting how individual patients will respond psychologically to new impairments after critical illness. [ABSTRACT FROM AUTHOR]

Background: Critically ill adults are at increased risk of VTE, including DVT, and pulmonary embolism. Various agents exist for venous thromboprophylaxis in this population.Research Question: What is the comparative efficacy and safety of prophylaxis agents for prevention of VTE in critically ill adults?Study Design and Methods: Systematic review and network meta-analysis of randomized clinical trials (RCTs) evaluating efficacy of thromboprophylaxis agents among critically ill patients. We searched six databases (including PubMed, EMBASE, and Medline) from inception through January 2021 for RCTs of patients in the ICU receiving pharmacologic, mechanical, or combination therapy (pharmacologic agents and mechanical devices) for thromboprophylaxis. Two reviewers performed screening, full-text review, and extraction. We used the Grading of Recommendations Assessment, Development, and Evaluation to rate certainty of effect estimates.Results: We included 13 RCTs (9,619 patients). Compared with control treatment (a composite of no prophylaxis, placebo, or compression stockings only), low-molecular-weight heparin (LMWH) reduced the incidence of DVT (OR, 0.59 [95% credible interval [CrI], 0.33-0.90]; high certainty) and unfractionated heparin (UFH) may reduce the incidence of DVT (OR, 0.82 [95% CrI, 0.47-1.37]; low certainty). LMWH probably reduces DVT compared with UFH (OR, 0.72 [95% CrI, 0.46-0.98]; moderate certainty). Compressive devices may reduce risk of DVT compared with control treatments; however, this is based on low-certainty evidence (OR, 0.85 [95% CrI, 0.50-1.50]). Combination therapy showed unclear effect on DVT compared with either therapy alone (very low certainty).Interpretation: Among critically ill adults, compared with control treatment, LMWH reduces incidence of DVT, whereas UFH and mechanical compressive devices may reduce the risk of DVT. LMWH is probably more effective than UFH in reducing incidence of DVT and should be considered the primary pharmacologic agent for thromboprophylaxis. The efficacy and safety of combination pharmacologic therapy and mechanical compressive devices were unclear.Trial Registry: Open Science Framework; URL: https://osf.io/694aj. [ABSTRACT FROM AUTHOR]

Background: The coping styles of the Sickness Insight in Coping Questionnaire (SICQ; positivism, redefinition, toughness, fighting spirit, nonacceptance) may affect the health and recovery of hospitalized critically ill patients.Research Question: Do the SICQ coping styles of hospitalized critically ill patients relate to the patients health-related quality of life (HRQoL) and recovery?Study Design and Methods: A prospective cohort study was conducted in a single university-affiliated Dutch hospital. Participants were critically ill adult patients admitted to a mixed medical-surgical ICU (start: n = 417; pre-ICU: n = 391; hospital discharge: n = 350; 3-month follow-up: n = 318; 6-month follow-up: n = 308; 12-month follow-up: n = 285). Coping was recorded with the SICQ pre-ICU and at discharge. HRQoL was measured with the SF-12 pre-ICU, at discharge, and 3, 6, and 12 months after discharge. Indicators of recovery were ICU and hospital length of stay, discharge disposition, and mortality. Correlation and regression analyses were used for data analysis.Results: Positivism (r = 0.28-0.51), fighting spirit (r = 0.14-0.35), and redefinition (r = 0.12-0.23) associated significantly (P < .05) with mental HRQoL after discharge. Furthermore, positivism associated positively (P < .01) with physical HRQoL (r = 0.17-0.26) after discharge. Increase in positivism (r = 0.13), redefinition (r = 0.13), and toughness (r = 0.13) across the period of hospitalization associated positively (P ≤ .05) with mental HRQoL at discharge. Pre-ICU positivism associated with hospital length of stay (ρ = -.21, P ≤ .05) and hazard for death (HR = 0.57, P < .01) and had a unidirectional effect on mental HRQoL (β = .30, P < .001).Interpretation: SICQ coping is associated with long-term mental HRQoL, hospital length of stay, and hazard for death among hospitalized critically ill patients. [ABSTRACT FROM AUTHOR]

The prevalence of obesity is rising worldwide. Adipose tissue exerts anatomic and physiological effects with significant implications for critical illness. Changes in respiratory mechanics cause expiratory flow limitation, atelectasis, and V̇/Q̇ mismatch with resultant hypoxemia. Altered work of breathing and obesity hypoventilation syndrome may cause hypercapnia. Challenging mask ventilation and peri-intubation hypoxemia may complicate intubation. Patients with obesity are at increased risk of ARDS and should receive lung-protective ventilation based on predicted body weight. Increased positive end expiratory pressure (PEEP), coupled with appropriate patient positioning, may overcome the alveolar decruitment and intrinsic PEEP caused by elevated baseline pleural pressure; however, evidence is insufficient regarding the impact of high PEEP strategies on outcomes. Venovenous extracorporeal membrane oxygenation may be safely performed in patients with obesity. Fluid management should account for increased prevalence of chronic heart and kidney disease, expanded blood volume, and elevated acute kidney injury risk. Medication pharmacodynamics and pharmacokinetics may be altered by hydrophobic drug distribution to adipose depots and comorbid liver or kidney disease. Obesity is associated with increased risk of VTE and infection; appropriate dosing of prophylactic anticoagulation and early removal of indwelling catheters may decrease these risks. Obesity is associated with improved critical illness survival in some studies. It is unclear whether this reflects a protective effect or limitations inherent to observational research. Obesity is associated with increased risk of intubation and death in SARS-CoV-2 infection. Ongoing molecular studies of adipose tissue may deepen our understanding of how obesity impacts critical illness pathophysiology. [ABSTRACT FROM AUTHOR]

Background: Subphenotypes have been identified in patients with sepsis and ARDS and are associated with different outcomes and responses to therapies.Research Question: Can unique subphenotypes be identified among critically ill patients with COVID-19?Study Design and Methods: Using data from a multicenter cohort study that enrolled critically ill patients with COVID-19 from 67 hospitals across the United States, we randomly divided centers into discovery and replication cohorts. We used latent class analysis independently in each cohort to identify subphenotypes based on clinical and laboratory variables. We then analyzed the associations of subphenotypes with 28-day mortality.Results: Latent class analysis identified four subphenotypes (SP) with consistent characteristics across the discovery (45 centers; n = 2,188) and replication (22 centers; n = 1,112) cohorts. SP1 was characterized by shock, acidemia, and multiorgan dysfunction, including acute kidney injury treated with renal replacement therapy. SP2 was characterized by high C-reactive protein, early need for mechanical ventilation, and the highest rate of ARDS. SP3 showed the highest burden of chronic diseases, whereas SP4 demonstrated limited chronic disease burden and mild physiologic abnormalities. Twenty-eight-day mortality in the discovery cohort ranged from 20.6% (SP4) to 52.9% (SP1). Mortality across subphenotypes remained different after adjustment for demographics, comorbidities, organ dysfunction and illness severity, regional and hospital factors. Compared with SP4, the relative risks were as follows: SP1, 1.67 (95% CI, 1.36-2.03); SP2, 1.39 (95% CI, 1.17-1.65); and SP3, 1.39 (95% CI, 1.15-1.67). Findings were similar in the replication cohort.Interpretation: We identified four subphenotypes of COVID-19 critical illness with distinct patterns of clinical and laboratory characteristics, comorbidity burden, and mortality. [ABSTRACT FROM AUTHOR]

Background: Long-term cognitive impairment frequently occurs after critical illness; no treatments are known to improve long-term cognition.Research Question: Does a single high-dose (540,000 International Units) enteral treatment of vitamin D3 given shortly after hospital admission in critically ill patients who are vitamin D deficient improve long-term global cognition or executive function?Study Design and Methods: This study evaluated long-term cognitive outcomes among patients enrolled in a multicenter, blinded, randomized clinical trial comparing vitamin D3 treatment vs placebo in critically ill adults with vitamin D deficiency. Global cognition was measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Executive function was measured with a composite score derived from three Delis-Kaplan Executive Function System subscales. Outcomes were assessed at a median of 443 days (interquartile range, 390-482 days) after randomization and were compared using multivariate proportional odds regression. Adjusted ORs of > 1.0 would indicate better outcomes in the vitamin D3 group compared with the placebo group.Results: Ninety-five patients were enrolled, including 47 patients randomized to vitamin D3 treatment and 48 patients randomized to placebo. The adjusted median RBANS score at follow-up was 79.6 (95% CI, 73.0-84.0) in the vitamin D3 group and 82.1 (95% CI, 74.7-84.6) in the placebo group (adjusted OR, 0.83; 95% CI, 0.50-1.38). The adjusted median executive function composite scores were 8.1 (95% CI, 6.8-9.0) and 8.7 (95% CI, 7.4-9.3), respectively (adjusted OR, 0.72; 95% CI, 0.36-1.42).Interpretation: In vitamin D-deficient, critically-ill adults, a large dose of enteral vitamin D3 did not improve long-term global cognition or executive function.Trial Registry: ClinicalTrials.gov; No.: NCT03733418; URL: www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Background: Delirium is a deleterious condition affecting up to 60% of patients in the surgical ICU (SICU). Few SICU-focused delirium interventions have been implemented, including those addressing sleep-wake disruption, a modifiable delirium risk factor common in critically ill patients.Research Question: What is the effect on delirium and sleep quality of a multicomponent nonpharmacologic intervention aimed at improving sleep-wake disruption in patients in the SICU setting?Study Design and Methods: Using a staggered pre-post design, we implemented a quality improvement intervention in two SICUs (general surgery or trauma and cardiovascular) in an academic medical center. After a preintervention (baseline) period, a multicomponent unit-wide nighttime (ie, efforts to minimize unnecessary sound and light, provision of earplugs and eye masks) and daytime (ie, raising blinds, promotion of physical activity) intervention bundle was implemented. A daily checklist was used to prompt staff to complete intervention bundle elements. Delirium was evaluated twice daily using the Confusion Assessment Method for the Intensive Care Unit. Patient sleep quality ratings were evaluated daily using the Richards-Campbell Sleep Questionnaire (RCSQ).Results: Six hundred forty-six SICU admissions (332 baseline, 314 intervention) were analyzed. Median age was 61 years (interquartile range, 49-70 years); 35% of the cohort were women and 83% were White. During the intervention period, patients experienced fewer days of delirium (proportion ± SD of ICU days, 15 ± 27%) as compared with the preintervention period (20 ± 31%; P = .022), with an adjusted pre-post decrease of 4.9% (95% CI, 0.5%-9.2%; P = .03). Overall RCSQ-perceived sleep quality ratings did not change, but the RCSQ noise subscore increased (9.5% [95% CI, 1.1%-17.5%; P = .02).Interpretation: Our multicomponent intervention was associated with a significant reduction in the proportion of days patients experienced delirium, reinforcing the feasibility and effectiveness of a nonpharmacologic sleep-wake bundle to reduce delirium in critically ill patients in the SICU.Trial Registry: ClinicalTrials.gov; No.: NCT03313115; URL: www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Family engagement is a key component of high-quality critical care, with known benefits for patients, care teams, and family members themselves. The COVID-19 pandemic led to rapid enactment of prohibitions or restrictions on visitation that now persist, particularly for patients with COVID-19. Reevaluation of these policies in response to advances in knowledge and resources since the early pandemic is critical because COVID-19 will continue to be a public health threat for months to years, and future pandemics are likely. This article reviews rationales and evidence for restricting or permitting family members' physical presence and provides broad guidance for health care systems to develop and implement policies that maximize benefit and minimize risk of family visitation during COVID-19 and future similar public health crises. [ABSTRACT FROM AUTHOR]

Background: Few small studies have described hospital-acquired infections (HAIs) occurring in patients with COVID-19.Research Question: What characteristics in critically ill patients with COVID-19 are associated with HAIs and how are HAIs associated with outcomes in these patients?Study Design and Methods: Multicenter retrospective analysis of prospectively collected data including adult patients with severe COVID-19 admitted to eight Italian hub hospitals from February 20, 2020, through May 20, 2020. Descriptive statistics and univariate and multivariate Weibull regression models were used to assess incidence, microbial cause, resistance patterns, risk factors (ie, demographics, comorbidities, exposure to medication), and impact on outcomes (ie, ICU discharge, length of ICU and hospital stays, and duration of mechanical ventilation) of microbiologically confirmed HAIs.Results: Of the 774 included patients, 359 patients (46%) demonstrated 759 HAIs (44.7 infections/1,000 ICU patient-days; 35% multidrug-resistant [MDR] bacteria). Ventilator-associated pneumonia (VAP; n = 389 [50%]), bloodstream infections (BSIs; n = 183 [34%]), and catheter-related BSIs (n = 74 [10%]) were the most frequent HAIs, with 26.0 (95% CI, 23.6-28.8) VAPs per 1,000 intubation-days, 11.7 (95% CI, 10.1-13.5) BSIs per 1,000 ICU patient-days, and 4.7 (95% CI, 3.8-5.9) catheter-related BSIs per 1,000 ICU patient-days. Gram-negative bacteria (especially Enterobacterales) and Staphylococcus aureus caused 64% and 28% of cases of VAP, respectively. Variables independently associated with infection were age, positive end expiratory pressure, and treatment with broad-spectrum antibiotics at admission. Two hundred thirty-four patients (30%) died in the ICU (15.3 deaths/1,000 ICU patient-days). Patients with HAIs complicated by septic shock showed an almost doubled mortality rate (52% vs 29%), whereas noncomplicated infections did not affect mortality. HAIs prolonged mechanical ventilation (median, 24 days [interquartile range (IQR), 14-39 days] vs 9 days [IQR, 5-13 days]; P < .001), ICU stay (24 days [IQR, 16-41 days] vs 9 days [IQR, 6-14 days]; P = .003), and hospital stay (42 days [IQR, 25-59 days] vs 23 days [IQR, 13-34 days]; P < .001).Interpretation: Critically ill patients with COVID-19 are at high risk for HAIs, especially VAPs and BSIs resulting from MDR organisms. HAIs prolong mechanical ventilation and hospitalization, and HAIs complicated by septic shock almost double mortality.Trial Registry: ClinicalTrials.gov; No.: NCT04388670; URL: www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic has led to unprecedented demand for ICUs, with the need to triage admissions along with the development of ICU triage criteria. However, how these criteria relate to outcomes in patients already admitted to the ICU is unknown, as is the incremental ICU capacity that triage of these patients might create given existing admission practices.Research Question: What is the short- and long-term survival of low- vs high-priority patients for ICU admission according to current pandemic triage criteria?Study Design and Methods: This study analyzed prospectively collected registry data (2007-2018) in 23 ICUs in Victoria, Australia, with probabilistic linkage with death registries. After excluding elective surgery, admissions were stratified according to existing ICU triage protocol prioritization as low (age ≥ 85 years, or severe chronic illness, or Sequential Organ Failure Assessment [SOFA] score = 0 or ≥ 12), medium (SOFA score = 8-11) or high (SOFA score = 1-7) priority. The primary outcome was long-term survival. Secondary outcomes were in-hospital mortality, ICU length of stay (LOS) and bed-day usage.Results: This study examined 126,687 ICU admissions. After 5 years of follow-up, 1,093 of 3,296 (33%; 95% CI, 32-34) of "low-priority" patients aged ≥ 85 years or with severe chronic illness and 86 of 332 (26%; 95% CI, 24-28) with a SOFA score ≥ 12 were still alive. Sixty-three of 290 (22%; 95% CI, 17-27) of patients in these groups followed up for 10 years were still alive. Together, low-priority patients accounted for 27% of all ICU bed-days and had lower in-hospital mortality (22%) than the high-priority patients (28%). Among nonsurvivors, low-priority admissions had shorter ICU LOS than medium- or high-priority admissions.Interpretation: Current SOFA score or age or severe comorbidity-based ICU pandemic triage protocols exclude patients with a close to 80% hospital survival, a > 30% five-year survival, and 27% of ICU bed-day use. These findings imply the need for stronger evidence-based ICU triage protocols. [ABSTRACT FROM AUTHOR]

Background: Because of the high risk of thrombotic complications (TCs) during SARS-CoV-2 infection, several scientific societies have proposed to increase the dose of preventive anticoagulation, although arguments in favor of this strategy are inconsistent.Research Question: What is the incidence of TC in critically ill patients with COVID-19 and what is the relationship between the dose of anticoagulant therapy and the incidence of TC?Study Design and Methods: All consecutive patients referred to eight French ICUs for COVID-19 were included in this observational study. Clinical and laboratory data were collected from ICU admission to day 14, including anticoagulation status and thrombotic and hemorrhagic events. The effect of high-dose prophylactic anticoagulation (either at intermediate or equivalent to therapeutic dose), defined using a standardized protocol of classification, was assessed using a time-varying exposure model using inverse probability of treatment weight.Results: Of 538 patients included, 104 patients experienced a total of 122 TCs with an incidence of 22.7% (95% CI, 19.2%-26.3%). Pulmonary embolism accounted for 52% of the recorded TCs. High-dose prophylactic anticoagulation was associated with a significant reduced risk of TC (hazard ratio, 0.81; 95% CI, 0.66-0.99) without increasing the risk of bleeding (HR, 1.11; 95% CI, 0.70-1.75).Interpretation: High-dose prophylactic anticoagulation is associated with a reduction in thrombotic complications in critically ill patients with COVID-19 without an increased risk of hemorrhage. Randomized controlled trials comparing prophylaxis with higher doses of anticoagulants are needed to confirm these results.Trial Registry: ClinicalTrials.gov; No.: NCT04405869; URL: www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Background: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection causes direct lung damage, overwhelming endothelial activation, and inflammatory reaction, leading to acute respiratory failure and multi-organ dysfunction. Ongoing clinical trials are evaluating targeted therapies to hinder this exaggerated inflammatory response. Critically ill coronavirus disease 2019 (COVID-19) patients have shown heterogeneous severity trajectories, suggesting that response to therapies is likely to vary across patients.Research Question: Are critically ill COVID-19 patients biologically and immunologically dissociable based on profiling of currently evaluated therapeutic targets?Study Design and Methods: We did a single-center, prospective study in an ICU department in France. Ninety-six critically ill adult patients admitted with a documented SARS-CoV-2 infection were enrolled. We conducted principal components analysis and hierarchical clustering on a vast array of immunologic variables measured on the day of ICU admission.Results: We found that patients were distributed in three clusters bearing distinct immunologic features and associated with different ICU outcomes. Cluster 1 had a "humoral immunodeficiency" phenotype with predominant B-lymphocyte defect, relative hypogammaglobulinemia, and moderate inflammation. Cluster 2 had a "hyperinflammatory" phenotype, with high cytokine levels (IL-6, IL-1β, IL-8, tumor necrosis factor-alpha [TNF⍺]) associated with CD4+ and CD8+ T-lymphocyte defects. Cluster 3 had a "complement-dependent" phenotype with terminal complement activation markers (elevated C3 and sC5b-9).Interpretation: Patients with severe COVID-19 exhibiting cytokine release marks, complement activation, or B-lymphocyte defects are distinct from each other. Such immunologic variability argues in favor of targeting different mediators in different groups of patients and could serve as a basis for patient identification and clinical trial eligibility. [ABSTRACT FROM AUTHOR]

Background: Corticosteroid therapy is used commonly in patients with COVID-19, although its impact on outcomes and which patients could benefit from corticosteroid therapy are uncertain.Research Question: Are clinical phenotypes of COVID-19 associated with differential response to corticosteroid therapy?Study Design and Methods: Critically ill patients with COVID-19 from Tongji Hospital treated between January and February 2020 were included, and the main exposure of interest was the administration of IV corticosteroids. The primary outcome was 28-day mortality. Marginal structural modeling was used to account for baseline and time-dependent confounders. An unsupervised machine learning approach was carried out to identify phenotypes of COVID-19.Results: A total of 428 patients were included; 280 of 428 patients (65.4%) received corticosteroid therapy. The 28-day mortality was significantly higher in patients who received corticosteroid therapy than in those who did not (53.9% vs 19.6%; P < .0001). After marginal structural modeling, corticosteroid therapy was not associated significantly with 28-day mortality (hazard ratio [HR], 0.80; 95% CI, 0.54-1.18; P = .26). Our analysis identified two phenotypes of COVID-19, and compared with the hypoinflammatory phenotype, the hyperinflammatory phenotype was characterized by elevated levels of proinflammatory cytokines, higher Sequential Organ Failure Assessment scores, and higher rates of complications. Corticosteroid therapy was associated with a reduced 28-day mortality (HR, 0.45; 95% CI, 0.25-0.80; P = .0062) in patients with the hyperinflammatory phenotype.Interpretation: For critically ill patients with COVID-19, corticosteroid therapy was not associated with 28-day mortality, but the use of corticosteroids showed significant survival benefits in patients with the hyperinflammatory phenotype. [ABSTRACT FROM AUTHOR]

Background: Cardiac injury has been reported in up to 30% of coronavirus disease 2019 (COVID-19) patients. However, cardiac injury is defined mainly by troponin elevation without description of associated structural abnormalities and its time course has not been studied.Research Question: What are the ECG and echocardiographic abnormalities as well as their time course in critically ill COVID-19 patients?Study Design and Methods: The cardiac function of 43 consecutive COVID-19 patients admitted to two ICUs was assessed prospectively and repeatedly, combining ECG, cardiac biomarker, and transthoracic echocardiographic analyses from ICU admission to ICU discharge or death or to a maximum follow-up of 14 days. Cardiac injury was defined by troponin elevation and newly diagnosed ECG or echocardiographic abnormalities, or both.Results: At baseline, 49% of patients demonstrated a cardiac injury, and 70% of patients experienced cardiac injury within the first 14 days of ICU stay, with a median time of occurrence of 3 days (range, 0-7 days). The most frequent abnormalities were ECG or echocardiographic signs, or both, of left ventricular (LV) abnormalities (87% of patients with cardiac injury), right ventricular (RV) systolic dysfunction (47%), pericardial effusion (43%), new-onset atrial arrhythmias (33%), LV relaxation impairment (33%), and LV systolic dysfunction (13%). Between baseline and day 14, the incidence of pericardial effusion and of new-onset atrial arrhythmias increased and the incidence of ECG or echocardiographic signs, or both, of LV abnormalities as well as the incidence of LV relaxation impairment remained stable, whereas the incidence of RV and LV systolic dysfunction decreased.Interpretation: Cardiac injury is common and early in critically ill COVID-19 patients. ECG or echocardiographic signs, or both, of LV abnormalities were the most frequent abnormalities, and patients with cardiac injury experienced more RV than LV systolic dysfunction. [ABSTRACT FROM AUTHOR]

To the Editor: The coronavirus disease 2019 (COVID-19)-associated critical illness poses an unprecedented challenge to ICU capacity and resources[1] SP , sp [2] with an estimated mortality rate of 41.6% and a long ICU stay.[3] Initial data have linked multiple patient-level risk factors with worse clinical outcomes[4] SP , sp [5] and include older age, preexisting conditions (diabetes mellitus, hypertension, and obesity), initial illness severity, acute inflammation markers, and coagulation.[4] SP , sp [5] However, few studies reported the impact of hospital-level factors on ICU outcome. We show that ICU outcomes have improved significantly in patients with COVID-19 and were comparable with outcomes in non-COVID-19 ICU-related admissions. Compared with patients without COVID-19, ICU and hospital mortality rates were significantly higher in patients with COVID-19 in March (both P <.001), but not statistically different in June (both P =.16). [Extracted from the article]