Critical care explorations最新文献

Importance: Electrographic seizures (ESz) are seizures without prominent motor activity diagnosed with electroencephalogram and are a common complication in critically ill patients with alterations of consciousness. Previous studies suggested clinical signs, including ocular movement abnormalities, facial/periorbital twitching, or remote seizure risk factors, are sensitive for presence of ESz.

Objectives: To assess the utility of clinical features in identifying ESz in critically ill patients with alterations of consciousness.

Design, setting, and participants: This is a retrospective case-control study of 50 patients admitted to the University of North Carolina (UNC) Medical Center and UNC Rex Hospital. Inpatients older than 18 years old undergoing continuous video electroencephalogram (cEEG) were included. Patients admitted for neurologic diagnoses were excluded. A total of 25 patients with ESz (Sz-EEG) were matched with 25 controls by electroencephalogram duration ± 12 hours (No-Sz-EEG). Elements of patient's history and physical findings previously shown to be sensitive for presence of ESz were collected. Descriptive statistical analyses were used.

Results: Most patients were admitted to medical ICUs (72%; n = 36). There was no difference between groups in clinical findings previously shown to be sensitive for ESz. Positive and negative likelihood ratios for these findings generally fell between 1-2 and 0.5-1, respectively, indicating they are inaccurate predictors for ESz. Patients with ESz had significantly higher mortality (p = 0.012).

Conclusions and relevance: Our matched case-control study showed that in the critically ill patient population hospitalized in tertiary care centers and admitted for non-neurologic primary diagnoses, incidence of ocular movement abnormalities, facial/periorbital twitching, and presence of remote risk factors for seizures had low predictive accuracy for ESz. However, these findings are not generalizable to patients with neurologic diseases or to other practice settings with different levels of access to cEEG. We concluded that in this exploratory analysis of hospitalized critically ill patients with non-neurologic diagnoses, these clinical signs did not reliably stratify risk for ESz on cEEG. However, further prospective studies are needed to better evaluate these conclusions.

Objectives: Extracorporeal membrane oxygenation (ECMO) is often withheld in patients with significant neurologic injury or recent neurosurgical intervention due to perceived futility. Studies of neurosurgical interventions before or during ECMO are limited to case reports or single-center series, limiting generalizability, and outcomes in this population are unknown. We therefore sought to report the outcomes of ECMO patients with acute neurosurgical interventions at four high-volume ECMO and comprehensive stroke centers.

Design: Retrospective case series.

Setting: Four academic tertiary referral hospitals in the United States.

Patients: Adults (n = 24) having undergone neurosurgical procedures before or during ECMO.

Interventions: None.

Measurements and main results: We retrospectively reviewed adults at four institutions who had undergone neurosurgical procedures immediately before or during ECMO from 2015 to 2023. The primary outcome was survival to hospital discharge. Secondary outcomes included favorable neurologic outcome (Cerebral Performance Category 1 or 2) and neurosurgical complications. Twenty-four of 2957 ECMO patients (0.8%) were included. Primary indications for neurosurgical intervention included traumatic brain (n = 8) or spinal (n = 3) injury, spontaneous intracranial hemorrhage (n = 6), and acute ischemic stroke (n = 5). Procedures included extraventricular drain (EVD) and/or intracranial pressure monitor placement (n = 10), craniectomy/craniotomy (n = 5), endovascular thrombectomy (n = 4), and spinal surgery (n = 3). Fifteen patients (63%) survived to hospital discharge, of whom 12 (80%) were discharged with favorable neurologic outcomes. Survival to discharge was similar for venoarterial and venovenous ECMO patients (8/12 vs. 7/12; p = 0.67) and those who had neurosurgery before vs. during ECMO (8/13 vs. 7/11; p = 0.92). One patient (4%) experienced a neurosurgical complication, a nonlethal tract hemorrhage from EVD placement. Survival to discharge was similar for neurosurgical and nonneurosurgical ECMO patients at participating institutions (63% vs. 57%; p = 0.58).

Conclusions: Patients with acute neurologic injury can feasibly undergo neurosurgery during ECMO or can undergo ECMO after recent neurosurgery. Larger studies are needed to fully understand risks for bleeding and other procedure-related complications.

Objectives: To evaluate the effect of procalcitonin-guided management on the duration of antibiotic therapy in critically ill cancer patients with sepsis.

Design: Randomized, controlled, single-blinded trial.

Setting: A comprehensive multidisciplinary cancer hospital in Jordan.

Patients: Adults with cancer treated in the ICU who were started on antibiotics for suspected infection, met the SEPSIS-3 criteria, and were expected to stay in the ICU greater than or equal to 48 hours.

Interventions: Patients were randomized to the procalcitonin-guided or standard care (SC) arms. All patients had procalcitonin measured daily, up to 5 days or until ICU discharge or death. For the procalcitonin arm, a procalcitonin-guided algorithm was provided to guide antibiotic management, but clinicians were allowed to override the algorithm, if clinically indicated. In the SC arm, ICU clinicians were blinded to the procalcitonin levels.

Measurements and main results: Primary outcome was time to antibiotic cessation. We also evaluated the number of antibiotic-free days at 28 days, hospital discharge, or death, whichever came first, and antibiotic defined daily doses (DDDs). We enrolled 77 patients in the procalcitonin arm and 76 in the SC arm. Mean age was 58 ± 14 (sd) years, 67% were males, 74% had solid tumors, and 13% were neutropenic. Median (interquartile range [IQR]) Sequential Organ Failure Assessment scores were 7 (6-10) and 7 (5-9) and procalcitonin concentrations (ng/mL) at baseline were 3.4 (0.8-16) and 3.4 (0.5-26), in the procalcitonin and SC arms, respectively. There was no difference in the median (IQR) time to antibiotic cessation in the procalcitonin and SC arms, 8 (4-11) and 8 (5-13), respectively (p = 0.463). Median (IQR) number of antibiotic-free days were 20 (17-24) and 20 (16-23), (p = 0.484) and total DDDs were 1541.4 and 2050.4 in the procalcitonin and SC arms, respectively.

Conclusions: In critically ill cancer patients with sepsis, procalcitonin-guided management did not reduce the duration of antibiotic treatment.

Context: Conventional MRI is incompatible with extracorporeal membrane oxygenation (ECMO) cannulas and pumps. Ultra-low-field portable MRI (ULF-pMRI) with 0.064 Tesla may provide a solution, but its safety and compatibility is unknown.

Hypothesis: ULF-pMRI does not cause significant displacement and heating of ECMO cannulas and does not affect ECMO pump function.

Methods and models: ECMO cannulas in various sizes were tested ex vivo using phantom models to assess displacement force and heating according to the American Society for Testing and Materials criteria. ECMO pump function was assessed by pump flow and power consumption. In vivo studies involved five female domestic pigs (20-42 kg) undergoing different ECMO configurations (peripheral and central cannulation) and types of cannulas with an imaging protocol consisting of T2-weighted, T1-weighted, FLuid-Attenuated Inversion Recovery, and diffusion-weighted imaging sequences.

Results: Phantom models demonstrated that ECMO cannulas, both single lumen with various sizes (15-24-Fr) and double lumen cannula, had average displacement force less than gravitational force within 5 gauss safety line of ULF-pMRI and temperature changes less than 1°C over 15 minutes of scanning and ECMO pump maintained stable flow and power consumption immediately outside of the 5 gauss line. All pig models showed no visible motion due to displacement force or heating of the cannulas. ECMO flow and the animals' hemodynamic status maintained stability, with no changes greater than 10%, respectively.

Interpretation and conclusions: ULF-pMRI is safe and feasible for use with standard ECMO configurations, supporting its clinical application as a neuroimaging modality in ECMO patients.

Objectives: Persistent skeletal muscle dysfunction in survivors of critical illness due to acute respiratory failure is common, but biological data elucidating underlying mechanisms are limited. The objective of this study was to elucidate the prevalence of skeletal muscle weakness and fatigue in survivors of critical illness due to COVID-19 and determine if cellular changes associate with persistent skeletal muscle dysfunction.

Design: A prospective observational study in two phases: 1) survivors of critical COVID-19 participating in physical outcome measures while attending an ICU Recovery Clinic at short-term follow-up and 2) a nested cohort of patients performed comprehensive muscle and physical function assessments with a muscle biopsy; data were compared with non-COVID controls.

Setting: ICU Recovery Clinic and clinical laboratory.

Patients/subjects: Survivors of critical COVID-19 and non-COVID controls.

Interventions: None.

Measurements and main results: One hundred twenty patients with a median of 56 years old (interquartile range [IQR], 42-65 yr old), 43% female, and 33% individuals of underrepresented race attended follow-up 44 ± 17 days after discharge. Patients had a median Acute Physiology and Chronic Health Evaluation-II score of 24.0 (IQR, 16-29) and 98 patients (82%) required mechanical ventilation with a median duration of 14 days (IQR, 9-21 d). At short-term follow-up significant physical dysfunction was observed with 93% of patients reporting generalized fatigue and performing mean 218 ± 151 meters on 6-minute walk test (45% ± 30% of predicted). Eleven patients from this group agreed to participate in long-term assessment and muscle biopsy occurring a mean 267 ± 98 days after discharge. Muscle tissue from COVID exhibited a greater abundance of M2-like macrophages and satellite cells and lower activity of mitochondrial complex II and complex IV compared with controls.

Conclusions: Our findings suggest that aberrant repair and altered mitochondrial activity in skeletal muscle associates with long-term impairments in patients surviving an ICU admission for COVID-19.

Objectives: To analyze dynamic changes in the renin-angiotensin system (RAS) during septic shock, focusing on angiotensin-converting enzyme (ACE) activity and the balance between angiotensin peptides, using a mass spectrometry method.

Design: Experimental septic shock model induced by peritonitis in swine.

Setting: Experimental Laboratory, Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles.

Subjects: Forty time points from eight mechanically ventilated pigs.

Interventions: Septic shock was induced using intraperitoneal instillation of autologous feces, followed by standardized fluid resuscitation, norepinephrine infusion, antibiotic administration, and peritoneal lavage.

Measurements and main results: The induction of sepsis resulted in a significant increase in plasma renin activity and levels of angiotensin I and II, with a significant decrease in ACE activity observed from 4 hours post-resuscitation and a notable rise in the angiotensin I/angiotensin II ratio at 12 hours. Additionally, a shift toward the angiotensin-(1-7) axis was observed, evidenced by an increased angiotensin-(1-7)/angiotensin II ratio.

Conclusions: The study highlighted dynamic shifts in the RAS during septic shock, characterized by reduced circulating ACE activity, elevated angiotensin I/II ratio, and a shift toward the angiotensin-(1-7) axis. These findings suggest an adaptive response within the RAS, potentially offering new insights into sepsis management and therapeutic targets.

Background: Early diagnostic uncertainty for infection causes delays in antibiotic administration in infected patients and unnecessary antibiotic administration in noninfected patients.

Objective: To develop a machine learning model for the early detection of untreated infection (eDENTIFI), with the presence of infection determined by clinician chart review.

Derivation cohort: Three thousand three hundred fifty-seven adult patients hospitalized between 2006 and 2018 at two health systems in Illinois, United States.

Validation cohort: We validated in 1632 patients in a third Illinois health system using area under the receiver operating characteristic curve (AUC).

Prediction model: Using a longitudinal discrete-time format, we trained a gradient boosted machine model to predict untreated infection in the next 6 hours using routinely available patient demographics, vital signs, and laboratory results.

Results: eDENTIFI had an AUC of 0.80 (95% CI, 0.79-0.81) in the validation cohort and outperformed the systemic inflammatory response syndrome criteria with an AUC of 0.64 (95% CI, 0.64-0.65; p < 0.001). The most important features were body mass index, age, temperature, and heart rate. Using a threshold with a 47.6% sensitivity, eDENTIFI detected infection a median 2.0 hours (interquartile range, 0.9-5.2 hr) before antimicrobial administration, with a negative predictive value of 93.6%. Antibiotic administration guided by eDENTIFI could have decreased unnecessary IV antibiotic administration in noninfected patients by 10.8% absolute or 46.4% relative percentage points compared with clinicians.

Conclusion: eDENTIFI could both decrease the time to antimicrobial administration in infected patients and unnecessary antibiotic administration in noninfected patients. Further prospective validation is needed.

Objectives: Monocytes are plastic cells that assume different polarization states that can either promote inflammation or tissue repair and inflammation resolution. Polarized monocytes are partially defined by their transcriptional profiles that are influenced by environmental stimuli. The airway monocyte response in pediatric acute respiratory distress syndrome (PARDS) is undefined. To identify differentially expressed genes and networks using a novel transcriptomic reporter assay with donor monocytes exposed to the airway fluid of intubated children with and at-risk for PARDS. To determine differences in gene expression at two time points using the donor monocyte assay exposed to airway fluid from intubated children with PARDS obtained 48-96 hours following initial tracheal aspirate sampling.

Design: In vitro pilot study carried out using airway fluid supernatant.

Setting: Academic 40-bed PICU.

Participants: Fifty-seven children: 44 children with PARDS and 13 children at-risk for PARDS.

Interventions: None.

Measurements and main results: We performed bulk RNA sequencing using a transcriptomic reporter assay of monocytes exposed to airway fluid from intubated children to discover gene networks differentiating PARDS from at-risk for PARDS and those differentiating mild/moderate from severe PARDS. We also report differences in gene expression in children with PARDS 48-96 hours following initial tracheal aspirate sampling. We found that interleukin (IL)-10, IL-4, and IL-13, cytokine/chemokine signaling, and the senescence-associated secretory phenotype are upregulated in monocytes exposed to airway fluid from intubated children with PARDS compared with those at-risk for PARDS. Signaling by NOTCH, histone deacetylation/acetylation, DNA methylation, chromatin modifications (B-WICH complex), and RNA polymerase I transcription and its associated regulatory apparatus were upregulated in children with PARDS 48-96 hours following initial tracheal aspirate sampling.

Conclusions: We identified gene networks important to the PARDS airway immune response using bulk RNA sequencing from a monocyte reporter assay that exposed monocytes to airway fluid from intubated children with and at-risk for PARDS. Mechanistic investigations are needed to validate our findings.

Objectives: We aimed to summarize the most significant and impactful publications describing the pharmacotherapeutic care of critically ill patients in 2023.

Data sources: PubMed/MEDLINE and the Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update.

Study selection: Randomized controlled trials and prospective studies of adult critically ill patients assessing a pharmacotherapeutic intervention and reporting clinical endpoints published between January 1, 2023, and December 31, 2023, were eligible for inclusion in this article.

Data extraction: Articles from a systematic search and the Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update were included. An a priori defined three-round modified Delphi process was employed to achieve consensus on the most impactful publications based on the following considerations: 1) overall contribution to scientific knowledge and 2) novelty to the literature.

Data synthesis: The systematic search and Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update returned a total of 1202 articles, of which 1164 were excluded. The remaining 38 articles underwent a three-round modified Delphi process. In each round, articles were independently scored based on overall contribution to scientific knowledge and novelty to the literature. Included articles are summarized and their impact discussed. Article topics included hydrocortisone for severe community-acquired pneumonia, inhaled amikacin for prevention of ventilator-associated pneumonia, methylene blue for septic shock, restrictive vs. liberal fluid management for sepsis-induced hypotension, andexanet alfa for major bleeding associated with factor Xa inhibitors, and early administration of four-factor prothrombin complex concentrate in patients with trauma at risk for massive transfusion.

Conclusions: This review provides a summary and perspective on the potential impact of the most relevant articles in 2023 describing advances in the pharmacotherapeutic care of critically ill patients.

Importance: Timely intervention for clinically deteriorating ward patients requires that care teams accurately diagnose and treat their underlying medical conditions. However, the most common diagnoses leading to deterioration and the relevant therapies provided are poorly characterized.

Objectives: We aimed to determine the diagnoses responsible for clinical deterioration, the relevant diagnostic tests ordered, and the treatments administered among high-risk ward patients using manual chart review.

Design, setting, and participants: This was a multicenter retrospective observational study in inpatient medical-surgical wards at four health systems from 2006 to 2020. Randomly selected patients (1000 from each health system) with clinical deterioration, defined by reaching the 95th percentile of a validated early warning score, electronic Cardiac Arrest Risk Triage, were included.

Main outcomes and measures: Clinical deterioration was confirmed by a trained reviewer or marked as a false alarm if no deterioration occurred for each patient. For true deterioration events, the condition causing deterioration, relevant diagnostic tests ordered, and treatments provided were collected.

Results: Of the 4000 included patients, 2484 (62%) had clinical deterioration confirmed by chart review. Sepsis was the most common cause of deterioration (41%; n = 1021), followed by arrhythmia (19%; n = 473), while liver failure had the highest in-hospital mortality (41%). The most common diagnostic tests ordered were complete blood counts (47% of events), followed by chest radiographs (42%) and cultures (40%), while the most common medication orders were antimicrobials (46%), followed by fluid boluses (34%) and antiarrhythmics (19%).

Conclusions and relevance: We found that sepsis was the most common cause of deterioration, while liver failure had the highest mortality. Complete blood counts and chest radiographs were the most common diagnostic tests ordered, and antimicrobials and fluid boluses were the most common medication interventions. These results provide important insights for clinical decision-making at the bedside, training of rapid response teams, and the development of institutional treatment pathways for clinical deterioration.