Critical care explorations最新文献

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.

Objectives: To investigate which independent factor(s) have an impact on the pharmacokinetics of vancomycin in critically ill children, develop an equation to predict the 24-hour area under the concentration-time curve from a trough concentration, and evaluate dosing regimens likely to achieve a 24-hour area under the concentration-time curve to minimum inhibitory concentration ratio (AUC24/MIC) greater than or equal to 400.

Design: Prospective population pharmacokinetic study of vancomycin.

Setting: Critically ill patients in quaternary care PICUs.

Patients: Children 90 days old or older to younger than 18 years who received IV vancomycin treatment, irrespective of the indication for use, in the ICUs at the University of Maryland Children's Hospital and Texas Children's Hospital were enrolled.

Interventions: Vancomycin was prescribed at doses and intervals chosen by the treating clinicians.

Measurements and main results: A median of four serum levels of vancomycin per patient were collected along with other variables for up to 7 days following the first administration. These data were used to characterize vancomycin pharmacokinetics and evaluate the factors affecting the variability in achieving AUC24/MIC ratio greater than or equal to 400 in PICU patients who are not on extracorporeal therapy. A total of 302 children with a median age of 6.0 years were enrolled. A two-compartment model described the pharmacokinetics of vancomycin with the clearance of 2.76 L/hr for a typical patient weighing 20 kg. The glomerular filtration rate estimated using either the bedside Schwartz equation or the chronic kidney disease in children equation was the only statistically significant predictor of clearance among the variables evaluated, exhibiting equal predictive performance. The trough levels achieving AUC24/MIC = 400 were 5.6-10.0 μg/mL when MIC = 1 μg/mL. The target of AUC24/MIC greater than or equal to 400 was achieved in 60.4% and 36.5% with the typical dosing regimens of 15 mg/kg every 6 and 8 hours (q6h and q8h), respectively.

Conclusions: The pharmacokinetics of vancomycin in critically ill children were dependent on the estimated glomerular filtration rate only. Trough concentrations accurately predict AUC24. Typical pediatric vancomycin dosing regimens of 15 mg/kg q6h and q8h will often lead to AUC24/MIC under 400.

Objectives: Continuous, therapeutic anticoagulation is the standard of care for patients on extracorporeal membrane oxygenation (ECMO). The risks of hemorrhage exacerbated by anticoagulation must be weighed with the thrombotic risks associated with ECMO. We hypothesized increased thrombotic events in patients who had interrupted (vs. continuous) anticoagulation during venovenous ECMO.

Design: This is a retrospective, observational study.

Setting: Enrollment of individuals took place at three adult ECMO centers in Minnesota from 2013 to 2022.

Patients: This study consists of 346 patients supported with venovenous ECMO.

Interventions: Anticoagulation administration was collected from electronic health records, including frequency and duration of anticoagulation interruptions (IAs) and timing and type of thrombotic events, and data were analyzed using descriptive statistics.

Measurements and main results: A total of 156 patients had IA during their ECMO run and 190 had continuous anticoagulation. Risk adjusted logistic regression demonstrated that individuals in the IA group were not statistically more likely to experience a thrombotic complication (odds ratio [OR], 0.69; 95% CI, 0.27-1.70) or require ECMO circuit change (OR, 1.36; 95% CI, 0.52-3.49). Subgroup analysis demonstrated greater frequency of overall thrombotic events with increasing frequency and duration of anticoagulation being interrupted (p = 0.001).

Conclusions: Our multicenter analysis found a similar frequency of thrombotic events in patients on ECMO when anticoagulation was interrupted vs. administered continuously. Further investigation into the impact of the frequency and duration of these interruptions is warranted.

Objectives: We sought to evaluate the effectiveness of any antiseizure medication on the incidence of early post-traumatic seizures among adult patients with traumatic brain injury.

Data sources: MEDLINE, Embase, PubMed, Cochrane Central Register of Controlled Trials, and LILACS were searched from inception to October 2023.

Study selection: We included randomized trials of adult patients with traumatic brain injury evaluating any antiseizure medication compared with either placebo or another agent.

Data extraction: Two reviewers independently extracted individual study data and evaluated studies for risk of bias using the Cochrane Risk of Bias tool. Our main outcome of interest was the occurrence of early seizures (i.e., within 7 d); secondary outcomes included late-seizures and all-cause mortality.

Data synthesis: Bayesian network meta-analyses were used to derive risk ratios (RRs) alongside 95% credible intervals (CrIs). We used Grading of Recommendations Assessment, Development, and Evaluation methodology to rate the certainty in our findings. Overall, ten individual randomized controlled trials (1851 participants) were included. Compared with placebo, phenytoin (RR, 0.28; 95% CrI, 0.13-0.57; moderate certainty) and levetiracetam (RR, 0.20; 95% CrI, 0.07-0.60; moderate certainty) were associated with a reduction in the risk of early seizures. Carbamazepine may be associated with a reduced risk of early seizures, but the evidence is very uncertain (RR, 0.41; 95% CrI, 0.12-1.27; very low certainty). Valproic acid may result in little to no difference in the risk of early seizures, but the evidence is very uncertain (RR, 0.97; 95% CrI, 0.16-9.00; very low certainty). The evidence is very uncertain about the impact of any antiseizure medication on the risk of late seizures or all-cause mortality at longest reported follow-up time.

Conclusions: Phenytoin or levetiracetam reduce the risk of early seizures among adult patients with traumatic brain injury. Further research is needed to evaluate required duration of therapy and long-term safety profiles.