Critical Care Explorations最新文献

Earlier treatment of sepsis leads to decreased mortality. Epic is an electronic medical record providing a predictive alert system for sepsis, the Epic Sepsis Model (ESM) Inpatient Predictive Analytic Tool. External validation of this system is lacking. This study aims to evaluate the ESM as a sepsis screening tool and determine whether an association exists between ESM alert system implementation and subsequent sepsis-related mortality.

Design: Before-and-after study comparing baseline and intervention period.

Setting: Urban 746-bed academic level 1 trauma center.

Patients: Adult acute care inpatients discharged between January 12, 2018, and July 31, 2019.

Interventions: During the before period, ESM was turned on in the background, but nurses and providers were not alerted of results. The system was then activated to alert providers of scores greater than or equal to 5, a set point determined using receiver operating characteristic curve analysis (area under the curve, 0.834; p < 0.001).

Measurements and main results: Primary outcome was mortality during hospitalization; secondary outcomes were sepsis order set utilization, length of stay, and timing of administration of sepsis-appropriate antibiotics. Of the 11,512 inpatient encounters assessed by ESM, 10.2% (1,171) had sepsis based on diagnosis codes. As a screening test, the ESM had sensitivity, specificity, positive predictive value, and negative predictive value rates of 86.0%, 80.8%, 33.8%, and 98.11%, respectively. After ESM implementation, unadjusted mortality rates in patients with ESM score greater than or equal to 5 and who had not yet received sepsis-appropriate antibiotics declined from 24.3% to 15.9%; multivariable analysis yielded an odds ratio of sepsis-related mortality (95% CI) of 0.56 (0.39-0.80).

Conclusions: In this single-center before-and-after study, utilization of the ESM score as a screening test was associated with a 44% reduction in the odds of sepsis-related mortality. Due to wide utilization of Epic, this is a potentially promising tool to improve sepsis mortality in the United States. This study is hypothesis generating, and further work with more rigorous study design is needed.

We sought to identify the primary causes of death of adult patients admitted to the medical ICU with symptomatic COVID-19 who ultimately suffered in-hospital mortality over the span of three major waves of COVID-19: Wild-type, alpha/epsilon, and delta.

Design: Retrospective single-center cohort study from March 2020 to December 2021.

Setting: One medical ICU in a 600-bed Tertiary Care Hospital in Los Angeles, CA.

Patients: Adult (n = 306) ICU patients admitted with symptomatic COVID-19 who suffered in-hospital mortality.

Interventions: None.

Main results: Of the 306 patients with COVID-19 who died in the hospital, 86.3% were Hispanic/Latino. The leading cause of death was respiratory failure, occurring in 57.8% of patients. There was no significant change in the rate of pulmonary deaths across the three waves of COVID-19 in our study period. The mean time from symptom onset to admission was 6.5 days, with an average hospital length of stay of 18 days. This did not differ between pulmonary and other causes of death. Sepsis was the second most common cause of death at 23.9% with a significant decrease from the wild-type wave to the delta wave. Among patients with sepsis as the cause of death, 22% (n = 16) were associated with fungemia. There was no significant association between steroid administration and cause of death. Lastly, the alpha/epsilon wave from December 2020 to May 2021 had the highest mortality rate when compared with wild-type or delta waves.

Conclusions: We found the primary cause of death in ICU patients with COVID-19 was acute respiratory failure, without significant changes over the span of three waves of COVID-19. This finding contrasts with reported causes of death for patients with non-COVID-19 acute respiratory distress syndrome, in which respiratory failure is an uncommon cause of death. In addition, we identified a subset of patients (5%) who died primarily due to fungemia, providing an area for further investigation.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to an infection. Septic shock is when initial fluid resuscitation fails to increase the mean atrial pressure to greater than or equal to 65 mm Hg. The 2021 Surviving Sepsis Campaign guidelines recommend corticosteroids for vasopressor and fluid-refractory septic shock patients. Medication shortages can arise, and their etiologies include natural disasters, quality control issues, and manufacturing discontinuation. The U.S. Food and Drug Administration and the American Society of Health-System Pharmacists announced a shortage of IV hydrocortisone. Methylprednisolone and dexamethasone are considered therapeutic alternatives to hydrocortisone. This commentary aims to guide clinicians on the alternative to hydrocortisone among septic shock patients due to medication shortage.

While opioids are part of usual care for analgesia in the ICU, there are concerns regarding excess use. This is a systematic review of nonsteroidal anti-inflammatory drugs (NSAIDs) use in postoperative critical care adult patients.

Data sources: We searched Medical Literature Analysis and Retrieval System Online, Excerpta Medica database, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, trial registries, Google Scholar, and relevant systematic reviews through March 2023.

Study selection: Titles, abstracts, and full texts were reviewed independently and induplicate by two investigators to identify eligible studies. We included randomized control trials (RCTs) that compared NSAIDs alone or as an adjunct to opioids for systemic analgesia. The primary outcome was opioid utilization.

Data extraction: In duplicate, investigators independently extracted study characteristics, patient demographics, intervention details, and outcomes of interest using predefined abstraction forms. Statistical analyses were conducted using Review Manager software Version 5.4. (The Cochrane Collaboration, Copenhagen, Denmark).

Data synthesis: We included 15 RCTs (n = 1,621 patients) for admission to the ICU for postoperative management after elective procedures. Adjunctive NSAID therapy to opioids reduced 24-hour oral morphine equivalent consumption by 21.4 mg (95% CI, 11.8-31.0 mg reduction; high certainty) and probably reduced pain scores (measured by Visual Analog Scale) by 6.1 mm (95% CI, 12.2 decrease to 0.1 increase; moderate certainty). Adjunctive NSAID therapy probably had no impact on the duration of mechanical ventilation (1.6 hr reduction; 95% CI, 0.4 hr to 2.7 reduction; moderate certainty) and may have no impact on ICU length of stay (2.1 hr reduction; 95% CI, 6.1 hr reduction to 2.0 hr increase; low certainty). Variability in reporting adverse outcomes (e.g., gastrointestinal bleeding, acute kidney injury) precluded their meta-analysis.

Conclusions: In postoperative critical care adult patients, systemic NSAIDs reduced opioid use and probably reduced pain scores. However, the evidence is uncertain for the duration of mechanical ventilation or ICU length of stay. Further research is required to characterize the prevalence of NSAID-related adverse outcomes.

CD4⁺ T cells contribute to lung inflammation in acute respiratory distress syndrome. The CD4⁺ T-cell response in pediatric acute respiratory distress syndrome (PARDS) is unknown.

Objectives: To identify differentially expressed genes and networks using a novel transcriptomic reporter assay with donor CD4⁺ T cells exposed to the airway fluid of intubated children with mild versus severe PARDS.

Design: In vitro pilot study.

Setting: Laboratory-based study using human airway fluid samples admitted to a 36-bed university-affiliated pediatric intensive care unit.

Patients/subjects: Seven children with severe PARDS, nine children with mild PARDS, and four intubated children without lung injury as controls.

Interventions: None.

Measurements and main results: We performed bulk RNA sequencing using a transcriptomic reporter assay of CD4⁺ T cells exposed to airway fluid from intubated children to discover gene networks differentiating severe from mild PARDS. We found that innate immunity pathways, type I (α and β), and type II (γ) interferon response and cytokine/chemokine signaling are downregulated in CD4⁺ T cells exposed to airway fluid from intubated children with severe PARDS compared with those with mild PARDS.

Conclusions: We identified gene networks important to the PARDS airway immune response using bulk RNA sequencing from a novel CD4⁺ T-cell reporter assay that exposed CD4⁺ T cells to airway fluid from intubated children with severe and mild PARDS. These pathways will help drive mechanistic investigations into PARDS. Validation of our findings using this transcriptomic reporter assay strategy is needed.

Temporal trends and factors associated with the withdrawal of life-sustaining therapy (WLST) after acute stroke are not well determined.

Design: Observational study (2008-2021).

Setting: Florida Stroke Registry (152 hospitals).

Patients: Acute ischemic stroke (AIS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH) patients.

Interventions: None.

Measurements and main results: Importance plots were performed to generate the most predictive factors of WLST. Area under the curve (AUC) for the receiver operating curve were generated for the performance of logistic regression (LR) and random forest (RF) models. Regression analysis was applied to evaluate temporal trends. Among 309,393 AIS patients, 47,485 ICH patients, and 16,694 SAH patients; 9%, 28%, and 19% subsequently had WLST. Patients who had WLST were older (77 vs 70 yr), more women (57% vs 49%), White (76% vs 67%), with greater stroke severity on the National Institutes of Health Stroke Scale greater than or equal to 5 (29% vs 19%), more likely hospitalized in comprehensive stroke centers (52% vs 44%), had Medicare insurance (53% vs 44%), and more likely to have impaired level of consciousness (38% vs 12%). Most predictors associated with the decision to WLST in AIS were age, stroke severity, region, insurance status, center type, race, and level of consciousness (RF AUC of 0.93 and LR AUC of 0.85). Predictors in ICH included age, impaired level of consciousness, region, race, insurance status, center type, and prestroke ambulation status (RF AUC of 0.76 and LR AUC of 0.71). Factors in SAH included age, impaired level of consciousness, region, insurance status, race, and stroke center type (RF AUC of 0.82 and LR AUC of 0.72). Despite a decrease in the rates of early WLST (< 2 d) and mortality, the overall rates of WLST remained stable.

Conclusions: In acute hospitalized stroke patients in Florida, factors other than brain injury alone contribute to the decision to WLST. Potential predictors not measured in this study include education, culture, faith and beliefs, and patient/family and physician preferences. The overall rates of WLST have not changed in the last 2 decades.

To analyze the temporal trend in enrollment rates in a COVID-19 platform trial during the first three waves of the pandemic in the United States.

Design: Secondary analysis of data from the I-SPY COVID randomized controlled trial (RCT).

Setting: Thirty-one hospitals throughout the United States.

Patients: Patients who were approached, either directly or via a legally authorized representative, for consent and enrollment into the I-SPY COVID RCT.

Interventions: None.

Measurements and main results: Among 1,338 patients approached for the I-SPY COVID trial from July 30, 2020, to February 17, 2022, the number of patients who enrolled (n = 1,063) versus declined participation (n = 275) was used to calculate monthly enrollment rates. Overall, demographic and baseline clinical characteristics were similar between those who enrolled versus declined. Enrollment rates fluctuated over the course of the COVID-19 pandemic, but there were no significant trends over time (Mann-Kendall test, p = 0.21). Enrollment rates were also comparable between vaccinated and unvaccinated patients. In multivariable logistic regression analysis, age, sex, region of residence, COVID-19 severity of illness, and vaccination status were not significantly associated with the decision to decline consent.

Conclusions: In this secondary analysis of the I-SPY COVID clinical trial, there was no significant association between the enrollment rate and time period or vaccination status among all eligible patients approached for clinical trial participation. Additional studies are needed to better understand whether the COVID-19 pandemic has altered clinical trial participation and to develop strategies for encouraging participation in future COVID-19 and critical care clinical trials.

This is a study of lipid metabolic gene expression patterns to discover precision medicine for sepsis.

Objectives: Sepsis patients experience poor outcomes including chronic critical illness (CCI) or early death (within 14 d). We investigated lipid metabolic gene expression differences by outcome to discover therapeutic targets.

Design setting and particitpants: Secondary analysis of samples from prospectively enrolled sepsis patients (first 24 hr) and a zebrafish endotoxemia model for drug discovery. Patients were enrolled from the emergency department or ICU at an urban teaching hospital. Enrollment samples from sepsis patients were analyzed. Clinical data and cholesterol levels were recorded. Leukocytes were processed for RNA sequencing and reverse transcriptase polymerase chain reaction. A lipopolysaccharide zebrafish endotoxemia model was used for confirmation of human transcriptomic findings and drug discovery.

Main outcomes and measures: The derivation cohort included 96 patients and controls (12 early death, 13 CCI, 51 rapid recovery, and 20 controls) and the validation cohort had 52 patients (6 early death, 8 CCI, and 38 rapid recovery).

Results: The cholesterol metabolism gene 7-dehydrocholesterol reductase (DHCR7) was significantly up-regulated in both derivation and validation cohorts in poor outcome sepsis compared with rapid recovery patients and in 90-day nonsurvivors (validation only) and validated using RT-qPCR analysis. Our zebrafish sepsis model showed up-regulation of dhcr7 and several of the same lipid genes up-regulated in poor outcome human sepsis (dhcr24, sqlea, cyp51, msmo1, and ldlra) compared with controls. We then tested six lipid-based drugs in the zebrafish endotoxemia model. Of these, only the Dhcr7 inhibitor AY9944 completely rescued zebrafish from lipopolysaccharide death in a model with 100% lethality.

Conclusions: DHCR7, an important cholesterol metabolism gene, was up-regulated in poor outcome sepsis patients warranting external validation. This pathway may serve as a potential therapeutic target to improve sepsis outcomes.

Standardized clinical measurements of edema do not exist.

Objectives: To describe a 19-point clinical edema score (CES), investigate its interobserver agreement, and compare changes between such CES and body weight.

Design setting and participants: Prospective observational study in a tertiary PICU of mechanically ventilated children with congenital heart disease.

Main outcomes and measures: Differences in the median CES between observer groups.

Results: We studied 61 children, with a median age of 8.0 days (interquartile range, 1.0-14.0 d). A total of 539 CES were performed by three observer groups (medical 1 [reference], medical 2, and bedside nurse) at 0, 24, and 48 hours from enrollment. Overall, there was close agreement between observer groups in mean, median, and upper quartile of CES scores, with least agreement observed in the lower quartile of scores. Across all quartiles of CES, after adjusting for baseline weight, cardiac surgical risk, duration of cardiopulmonary bypass, or peritoneal dialysis during the study, observer groups returned similar mean scores (medical 2: 25th centile +0.1 [95% CI, -0.2 to 0.5], median +0.6 [95% CI, -0.4 to 1.5], 75th centile +0.1 [95% CI, -1.1 to 1.4] and nurse: 25th centile +0.5 [95% CI, 0.0-0.9], median +0.7 [95% CI, 0.0-1.5], 75th centile -0.2 [95% CI, -1.3 to 1.0]) Within a multivariable mixed-effects linear regression model, including adjustment for baseline CES, each 1 point increase in CES was associated with a 12.1 grams (95% CI, 3.2-21 grams) increase in body weight.

Conclusions and relevance: In mechanically ventilated children with congenital heart disease, three groups of observers tended to agree when assessing overall edema using an ordinal clinical score assessed in six body regions, with agreement least at low edema scores. An increase in CES was associated with an increase in body weight, suggesting some validity for quantifying edema. Further exploration of the CES as a rapid clinical tool is indicated.

Sepsis survivors are at increased risk for morbidity and functional impairment. There are recommended practices to support recovery after sepsis, but it is unclear how often they are implemented. We sought to assess the current use of recovery-based practices across hospitals.

Design: Electronic survey assessing the use of best practices for recovery from COVID-related and non-COVID-related sepsis. Questions included four-point Likert responses of "never" to "always/nearly always."

Setting: Twenty-six veterans affairs hospitals with the highest (n = 13) and lowest (n = 13) risk-adjusted 90-day sepsis survival.

Subjects: Inpatient and outpatient clinician leaders.

Interventions: None.

Measurements and main results: For each domain, we calculated the proportion of "always/nearly always" responses and mean Likert scores. We assessed for differences by hospital survival, COVID versus non-COVID sepsis, and sepsis case volume. Across eight domains of care, the proportion "always/nearly always" responses ranged from: 80.7% (social support) and 69.8% (medication management) to 22.5% (physical recovery and adaptation) and 0.0% (emotional support). Higher-survival hospitals more often performed screening for new symptoms/limitations (49.2% vs 35.1% "always/nearly always," p = 0.02) compared with lower-survival hospitals. There was no difference in "always/nearly always" responses for COVID-related versus non-COVID-related sepsis, but small differences in mean Likert score in four domains: care coordination (3.34 vs 3.48, p = 0.01), medication management (3.59 vs 3.65, p = 0.04), screening for new symptoms/limitations (3.13 vs 3.20, p = 0.02), and anticipatory guidance and education (2.97 vs 2.84, p < 0.001). Lower case volume hospitals more often performed care coordination (72.7% vs 43.8% "always/nearly always," p = 0.02), screening for new symptoms/limitations (60.6% vs 35.8%, p < 0.001), and social support (100% vs 74.2%, p = 0.01).

Conclusions: Our findings show variable adoption of practices for sepsis recovery. Future work is needed to understand why some practice domains are employed more frequently than others, and how to facilitate practice implementation, particularly within rarely adopted domains such as emotional support.