The Growth of Palliative Practice and End of Life Care in an Academic Teaching Intensive Care Unit

Objective Dying in the intensive care unit (ICU) has changed over the last twenty years due to increased utilization of palliative care. We sought to examine how palliative medicine (PM) integration into critical care medicine has changed outcomes in end of life including the utilization of do not resuscitate (no cardiopulmonary resuscitation but continue treatment) and comfort care orders (No resuscitation, only comfort medication). Design: Retrospective observational review of critical care patients who died during admission between two decades, 2008 to 09 and 2018 to 19. Setting: Single urban tertiary care academic medical center in Washington, D.C. Patients: Adult patients who were treated in any ICU during the admission which they died. Interventions and Measurements We sought to measure PM involvement across the two decades and its association with end of life care including do not resuscitate (DNR) and comfort care (CC) orders. Main Results: 571 cases were analyzed. Mean age was 65 ± 15, 46% were female. In univariate analysis significantly more patients received PM in 2018 to 19 (40% vs. 27%, p = .002). DNR status increased significantly over time (74% to 84%, p = .002) and was significantly more common in patients who were receiving PM (96% vs. 72%, p < 0.001). CC also increased over time (56% to 70%, p = <0.001), and was more common in PM patients (87% vs. 53%, p < 0.001). Death in the ICU decreased significantly over time (94% to 86%, p = .002) and was significantly lower in PM patients (76% vs. 96%, p < 0.001). The adjusted odds of getting CC for those receiving versus those not receiving PM were 14.51 (5.49-38.36, p < 0.001) in 2008 to 09 versus 3.89 (2.27-6.68, p < 0.001) in 2018 to 19. Conclusion: PM involvement increased significantly across a decade in our ICU and was significantly associated with incidence of DNR and CC orders as well as the decreased incidence of dying in the ICU. The increase in DNR and CC orders independent of PM over the past decade reflect intensivists delivering PM services.

Kidney and Mortality Outcomes Associated with Ondansetron in Critically Ill Patients

Background: Ondansetron is a preferred anti-emetic in critical care to treat nausea and vomiting, and has historically been considered a largely safe option. A recent pharmacoepidemiology study reported that ondansetron may be associated with an increased risk for acute kidney injury (AKI). Methods: We interrogated the High-Density Intensive Care (HiDenIC-15) database containing intensive care data for 13 hospitals across Western Pennsylvania between Oct 2008-Dec 2014. AKI was defined using the Kidney Disease, Improving Global Outcomes 2012 guidelines. Ondansetron use was considered as receiving any form of ondansetron within 24 h of admission. The subsequent 48 h (hours 25-72 after admission) were analyzed for outcomes. Primary outcome was development of AKI; secondary outcomes included 90-day mortality and time to AKI. Propensity-matched, multivariate logistic regression was applied for both outcomes. Comparator groups were metoclopramide and prochlorperazine using the same exposure criteria. Results:AKI occurred in 965 (5.6%), 12 (3.0%), and 61 (6.5%) patients receiving ondansetron, prochlorperazine, and metoclopramide, respectively. In the adjusted analysis, no anti-emetic was associated with a significant change in the odds of developing AKI. Ondansetron was associated with a 5.48% decrease (CI −6.17–−4.79) in death within 90 days of ICU-admission, which was independent of AKI status; an effect not seen with other anti-emetics. Anti-emetic usage was not associated with a change in the time to first AKI. Conclusion:Anti-emetic usage did not alter AKI risk. Ondansetron was associated with a significant decrease in 90-day mortality that was not seen by other anti-emetics, which requires further exploration.

The Continuing Effect of COVID-19 Pandemic on Physical Well-Being and Mental Health of ICU Healthcare Workers in Turkey: A Single-Centre Cross-Sectional Later-Phase Study

Background This study aimed to evaluate the effect of COVID-19 pandemic on physical well-being and mental health of ICU healthcare workers (HCWs). Methods A total of 51 ICU HCWs working at a tertiary care hospital were included in this cross-sectional study conducted before (January 2019-January 2020) and during (January 2021-April 2021) COVID-19 pandemic. Data on sociodemographic and work-related characteristics, COVID 19 history and current mental health issues via Hospital Anxiety-Depression Scale (HADS), Pittsburgh Sleep Quality Index (PSQI), Eating Attitudes Test (EAT-40), Suicidal Ideation Scale (SIS) and Maslach Burnout Inventory (MBI) were recorded. Results Overall, 62.7% of participants were nurses, heavy workload (working ≥200 h/month) was reported by 76.5% of participants and previous history of COVID-19 was confirmed by 62.7%. Current mental health issues involved poor sleep quality in majority (96.1%) of participants, anxiety (51.0%), depression (51.0%) in at least half of them and a moderate degree of emotional exhaustion Heavy workload was associated with more remarkable decrease in sleep duration (median change: −0.5 vs. −1.0 h/day, P = .020), Vit B12 (median change: 60[−48-293] vs. −65[−371-262] pg/mL, P < .001) and Vit D (median change: −1.6[−13.1-20] vs. −9.7[−39.7-21.8] ng/mL, P = .004) during pandemic, while working hours per month were also significantly higher in those with versus without anxiety (264[150-390] vs. 240[150-264] h, P = .003) and with versus without depression (264[150-390] vs. 240[150-264] h, P = .037). Conclusion Our findings indicate high prevalence of mental health issues including anxiety and depression as well as poor sleep quality and emotional burnout among ICU HCWs, particularly those with heavy workload.

Assessment of Safety of Remdesivir in Covid −19 Patients with Estimated Glomerular Filtration Rate (eGFR) < 30 ml/min per 1.73 m^2

Purpose Safety of remdesivir in patients with renal impairment is unknown. Incidence of liver injury secondary to remdesivir is also unknown. The objective of this study is to assess the incidence of acute kidney injury (AKI) and to trend the liver enzymes during remdesivir treatment and change in eGFR from baseline to end of treatment as well as 48 h post completion of remdesivir therapy. Methods This is a retrospective chart review study including adult patients admitted with COVID-19 receiving remdesivir with a baseline eGFR < 30 ml/min per 1.73 m^2 from December 2020 to May 2021. The primary outcome was to assess the incidence of AKI and hepatic injury. The secondary outcome was to assess the efficacy of remdesivir defined by change in oxygen requirement. Results Seventy-one patients were included in the study. Patients experienced an improvement in eGFR from baseline (T0) to end of remdesivir treatment (T1), as well as 48 h after the end of the treatment (T2) ( + 30.3% and + 30.6% respectively, P < .0001). Creatinine reduced from baseline (T0) to T1 and T2 (-20.9% and −20.5% respectively, P < .0001). Creatinine clearance improved from baseline to T1 and T2 ( + 26.6% and + 26.2% respectively, p < .0001). Elevation of aminotransferase (AST) was observed at T1 ( + 2.5%, P = .727), however, AST reduction was seen at T2 (-15.8%, P = .021). Elevation in alanine transaminase (ALT) was observed at T1 and T2 ( + 25% and + 12%, P = .004 and P = .137 respectively). Both direct and total bilirubin remained stable and were not significantly changed from baseline. Conclusion Our study showed that remdesivir use in renally-impaired patients with eGFR < 30 ml/min is safe. Remdesivir may be considered as a therapeutic option in this population with COVID-19 infection.

Recent Advances in Bedside Device-Based Early Detection of Sepsis

Early detection of sepsis is challenging to achieve with current diagnostic methods, leading to expenditures of $27 billion annually in the United States with significant associated mortality. Various scoring systems have been proposed such as the sequential organ failure assessment (SOFA) and systemic inflammatory response syndrome (SIRS) criteria for identification of sepsis, but their sensitivities range from 60% to 70% when used in the emergency department triage. Other methods for the recognition of sepsis may rely on laboratory work, in addition to vitals monitoring, and are often outpaced by the development of sepsis. Automated alerts have not shown any reduction in mortality thus far. New technology may fill a critical gap in the early detection of sepsis. The ideal bedside screening device for would demonstrate rapid time to result, high portability, and high sensitivity to not miss cases, but also reasonable specificity to prevent provider fatigue from excessive false alerts. Non-invasive end-organ perfusion devices analyzing lactate and capillary refill time (CRT) tend to perform well in speed and portability, but may be less sensitive. Biomarker devices demonstrate a wider array of performance metrics. Those analyzing a single biomarker tend to be more sensitive but are less specific to the diagnosis of sepsis than technologies that assess multiple biomarkers, which in turn have lower sensitivity. Additionally, biomarker devices are generally invasive requiring blood samples, which may or may not be feasible in all patients especially when serial draws are needed. Sepsis is a complex disease process and most likely will require a combination of improved technology in addition to vital signs and high-risk patient history for better recognition. This review examines recent advances in the device-based early detection of sepsis between 2017 and 2020 with emphasis on bedside diagnostics, divided into markers of perfusion and biomarkers commonly implicated in sepsis.

Association of Surge Conditions with Mortality Among Critically Ill Patients with COVID-19

Objective To determine whether surge conditions were associated with increased mortality. Design Multicenter cohort study. Setting U.S. ICUs participating in STOP-COVID. Patients Consecutive adults with COVID-19 admitted to participating ICUs between March 4 and July 1, 2020. Interventions None Measurements and Main Results The main outcome was 28-day in-hospital mortality. To assess the association between admission to an ICU during a surge period and mortality, we used two different strategies: (1) an inverse probability weighted difference-in-differences model limited to appropriately matched surge and non-surge patients and (2) a meta-regression of 50 multivariable difference-in-differences models (each based on sets of randomly matched surge- and non-surge hospitals). In the first analysis, we considered a single surge period for the cohort (March 23 – May 6). In the second, each surge hospital had its own surge period (which was compared to the same time periods in matched non-surge hospitals). Our cohort consisted of 4342 ICU patients (average age 60.8 [sd 14.8], 63.5% men) in 53 U.S. hospitals. Of these, 13 hospitals encountered surge conditions. In analysis 1, the increase in mortality seen during surge was not statistically significant (odds ratio [95% CI]: 1.30 [0.47-3.58], p = .6). In analysis 2, surge was associated with an increased odds of death (odds ratio 1.39 [95% CI, 1.34-1.43], p < .001). Conclusions Admission to an ICU with COVID-19 in a hospital that is experiencing surge conditions may be associated with an increased odds of death. Given the high incidence of COVID-19, such increases would translate into substantial excess mortality.

Intensive Care Unit Sedation Practices at a Large, Tertiary Academic Center

Background Sedatives are frequently administered in an ICU and are often dependent on patient population and ICU type. These differences may affect patient-centered outcomes. Objective Our primary objective was to identify differences in sedation practice among three different ICU types at an academic medical center. Methods This was a retrospective cross-sectional study of adult patients (≥18 years) requiring a continuous sedative for ≥6 h and admitted to a medical ICU, surgical ICU, and medical/surgical ICU at a single academic medical center in Rochester Minnesota from June 1, 2018 to May 31, 2020. We extracted baseline characteristics; sedative type, dose, and duration; concomitant therapies; and patient outcomes. Summary statistics are presented. Results A total of 2154 patients met our study criteria (1010 from medical ICU, 539 from surgical ICU, 605 from medical/surgical ICU). Propofol was the most frequently used sedative in all ICU settings (74.1% in medical ICU, 53.8% in surgical ICU, 68.9% in medical/surgical ICU, and 67.5% in all ICUs). The mortality rate was highest in the medical/surgical ICU (40.2% in medical ICU, 26.0% in surgical ICU, 40.7% in medical/surgical ICU, and 36.8% in all ICUs). 90.7% of all patients required mechanical ventilation (92.9% in medical ICU, 88.5% in surgical ICU, and 89.1% in medical/surgical ICU). Overall, patients spent more time in light sedation than deep sedation, 75% versus 10.3%, during their ICU admission. Patients in the medical ICU spent a greater proportion of time positive for delirium than the other ICU settings (35.7% in medical ICU, 9.8% in surgical ICU, and 20% in medical/surgical ICU). Similar amounts of opioids (morphine milligram equivalents) were used during the continuous sedative infusion between the three settings. Conclusions We observed that patients in the medical ICU spent more time deeply sedated with multiple agents which was associated with a higher proportion of delirium.

Family Outcomes After the Pediatric Intensive Care Unit: A Scoping Review

Background Intensivists are increasingly attuned to the postdischarge outcomes experienced by families because patient recovery and family outcomes are interdependent after childhood critical illness. In this scoping review of international contemporary literature, we describe the evidence of family effects and functioning postpediatric intensive care unit (PICU) as well as outcome measures used to identify strengths and weaknesses in the literature. Methods We reviewed all articles published between 1970 and 2017 in PubMed, Embase, PsycINFO, Cumulative Index of Nursing and Allied Health Literature (CINAHL), or the Cochrane Controlled Trials Registry. Our search used a combination of terms for the concept of “critical care/illness” combined with additional terms for the prespecified domains of social, cognitive, emotional, physical, health-related quality of life (HRQL), and family functioning. Results We identified 71 articles reporting on the postPICU experience of more than 2400 parents and 3600 families of PICU survivors in 8 countries. These articles used 101 different metrics to assess the various aspects of family outcomes; 34 articles also included open-ended interviews. Overall, most families experienced significant disruption in at least five out of six of our family outcomes subdomains, with themes of decline in mental health, physical health, family cohesion, and family finances identified. Almost all articles represented relatively small, single-center, or disease-specific observational studies. There was a disproportionate representation of families of higher socioeconomic status (SES) and Caucasian race, and there was much more data about mothers compared to fathers. There was also very limited information regarding outcomes for siblings and extended family members after a child's PICU stay. Conclusions Significant opportunities remain for research exploring family functioning after PICU discharge. We recommend that future work include more diverse populations with respect to the critically ill child as well as family characteristics, include more intervention studies, and enrich existing knowledge about outcomes for siblings and extended family.

Long-Term Follow up of Renal and Other Acute Organ Failure in Survivors of Critical Illness Due to Covid-19

Background Little is known about the long-term health sequelae and outcomes of various organ failures in ICU survivors of Covid-19. The aim of our research was to study the characteristics of 120-day ICU survivors of the initial pandemic surge and report their long term (>6 months) outcomes. Methods We conducted a telephone questionnaire-based follow up study of 120- day survivors of Covid-19 admitted to ICUs at Montefiore Medical Center, Bronx, NY from 3/10/2020 to 4/11/2020. The study period was 2 months (11/1/2020-12/31/2020). Results 126 out of 300 (42%) survived to 120-days post-hospital discharge. The median age of survivors was 54 (47-61) years. Seventy-eight (62%) patients developed acute kidney injury (AKI); thirty-five (44.9%) of them required renal replacement therapy (RRT). One hundred-five (83.3%) required invasive mechanical ventilation; ten of them required tracheotomy. 103 (81.7%) completed the telephone questionnaire-based study, at a median (IQR) of 216.5 (200-234.5) days after hospital discharge. 29 (28.2%) patients reported persistent shortness of breath, 24, (23.3%) complained of persistent cough, and persistent anosmia in 9 (8.8%). AKI resolved completely in 58 (74.4%) patients. Of 35 AKI patients who required initiation of RRT during hospitalization, 27 (77%) were liberated from RRT and 20 (57%) had resolution of AKI. Of 20 patients without AKI resolution, 12 developed chronic kidney disease, whereas 8 still require RRT. Thirty-three (32.4%) patients developed post-traumatic stress disorder (PTSD) and 10 (11.8%) reported major depression. Many of the patients (68%) regained baseline functional status. Readmissions occurred in 22.3% patients within first 6 months after discharge. Conclusion Persistent symptoms of long Covid have been reported in ICU survivors of Covid-19 for extended durations. Outcomes of Covid-19 associated acute kidney injury are excellent. There is a high incidence of PTSD and depression in COVID-19 ICU survivors. Functional outcomes are good, but these patients remain at increased risk of hospital readmission.

External Validation of the Cardiac Surgery Score in a Quaternary Hospital in the United States of America

Background The Cardiac Surgery Score (CASUS) was developed to assist in predicting post-cardiac surgery mortality using parameters measured in the intensive care unit. It is calculated by assigning points to ten physiologic variables and adding them to obtain a score (additive CASUS), or by logistic regression to weight the variables and estimate the probability of mortality (logistic CASUS). Both additive and logistic CASUS have been externally validated elsewhere, but not yet in the United States of America (USA). This study aims to validate CASUS in a quaternary hospital in the USA and compare the predictive performance of additive to logistic CASUS in this setting. Methods Additive and logistic CASUS (postoperative days 1-5) were calculated for 7098 patients at Cleveland Clinic from January 2015 to February 2017. 30-day mortality data were abstracted from institutional records and the Death Registries for Ohio State and the Centers for Disease Control. Given a low event rate, model discrimination was assessed by area under the curve (AUROC), partial AUROC (pAUC), and average precision (AP). Calibration was assessed by curves and quantified using Harrell's Emax, and Integrated Calibration Index (ICI). Results 30-day mortality rate was 1.37%. For additive CASUS, odds ratio for mortality was 1.41 (1.35-1.46, P <0.001). Additive and logistic CASUS had comparable pAUC and AUROC (all >0.83). However, additive CASUS had greater AP, especially on postoperative day 1 (0.22 vs. 0.11). Additive CASUS had better calibration curves, and lower Emax, and ICI on all days. Conclusions Additive and logistic CASUS discriminated well for postoperative 30-day mortality in our quaternary center in the USA, however logistic CASUS under-predicted mortality in our cohort. Given its ease of calculation, and better predictive accuracy, additive CASUS may be the preferred model for postoperative use. Validation in more typical cardiac surgery centers in the USA is recommended.