Project description:Hyperglycemia is associated with increased morbidity and mortality in critically ill patients and strict glycemic control has become standard care for adults. Recent studies have questioned the optimal targets for such management and reported increased rates of iatrogenic hypoglycemia in both critically ill children and adults. The ability to provide accurate, real-time continuous glucose monitoring would improve the efficacy and safety of this practice in critically ill patients. The aim of our study is to determine if a continuous, interstitial glucose monitor will correlate with blood glucose values in critically ill children.We evaluated 50 critically ill children age 6 weeks to 16 years old with a commercially available continuous glucose monitor (CGM; Medtronic Guardian®). CGM values and standard blood glucose (BG) values were compared. During the study, no changes in patient management were made based on CGM readings alone.Forty-seven patients had analyzable CGM data. A total of 1,555 CGM and routine BG measurements were compared using Clarke error grid and Bland-Altman analysis. For all readings, 97.9% were within clinically acceptable agreement. The mean absolute relative difference between CGM and BG readings was 15.3%. For the 1,555 paired CGM and BG measurements, there is a statistically significant linear relationship between CGM values and BG (P < .0001). A high degree of clinical agreement existed in three subpopulation analyses based on age, illness severity, and support measures. This included some of our smallest patients (that is, < 12 months old), those who required vasopressors, and those who were treated for critical illness hyperglycemia.In one of the largest studies to date, in a highly vulnerable ICU population, CGM values have a clinically acceptable correlation with the BG values now used diagnostically and therapeutically. Our data contest the theoretical concerns posed by some regarding CGM use in the ICU. The existing medical evidence may now support a role for CGM devices in the identification and management of hyperglycemia in diverse ICU settings.
Project description:BackgroundFluid responsiveness prediction with continuously available monitoring is an unsettled matter for the vast majority of critically ill patients, and development of new and reliable methods is desired. We hypothesized that the post-ectopic beat, which is associated with increased preload, could be analyzed in relation to preceding sinus beats and that the change in cardiac performance (e.g., systolic blood pressure) at the post-ectopic beat could predict fluid responsiveness.MethodsCritically ill patients were observed when scheduled for a 500-ml volume expansion. The 30-min ECG prior to volume expansion was analyzed for the occurrence of extrasystoles. Classification variables were defined as the change in a variable (e.g., systolic blood pressure or pre-ejection period) from the median of ten preceding sinus beats to extrasystolic post-ectopic beat. A stroke volume increase > 10% following volume expansion defined fluid responsiveness.ResultsTwenty-six patients were included. The change in systolic blood pressure predicted fluid responsiveness with receiver operating characteristic (ROC) area 0.79 (CI [0.52:1.00]), specificity 100%, sensitivity 67%, positive predictive value 100%, and negative predictive value 91% (threshold: 5%). The change in pre-ejection period predicted fluid responsiveness with ROC area 0.74 (CI [0.53:0.94]), specificity 78%, sensitivity 67%, positive predictive value 50%, and negative predictive value 88% (threshold 7.5 ms).ConclusionsBased on standard critical care monitoring, analysis of the extrasystolic post-ectopic beat predicts fluid responsiveness in critical care patients with good accuracy. The presented results are considered preliminary proof-of-concept results, and further validation is needed to confirm these preliminary findings.
Project description:PurposePosaconazole is an antifungal drug currently being used for prophylaxis and treatment of invasive fungal infections such as aspergillosis. To date, therapeutic drug monitoring (TDM) of posaconazole is recommended with the use of oral suspension, but the potential need of TDM with the use of IV formulations is rising. Therefore, we aimed to investigate the pharmacokinetics of IV posaconazole in critically ill patients.MethodsIn a prospective study, we analysed 168 consecutivelly collected posaconazole levels from 10 critically ill patients drawn during a 7 day curse. Posaconazole concentrations were measured using a chromatographic method. Demographic and laboratory data were collected, and the data was analysed using descriptive statistics.ResultsWe included 168 posaconazole levels, resulting in a median trough of 0.62 [0.29-1.05] mg/L with 58% not reaching the suggested target of 0.5 mg/L for fungal prophylaxis. Moreover, 74% of the trough levels were under the target of 1 mg/L which is proposed for the treatment of aspergillosis.ConclusionPosaconazole exposure is highly variable in critically ill patients resulting in potentially insufficient drug concentrations in many cases. TDM is highly recommended to identify and avoid underexposure.Trial registration numberNCT05275179, March 11, 2022.
Project description:Cessation of enteral nutrition prior to an operation/procedure is the most common reason for feeding interruption in critically ill trauma patients and contributes to substantial calorie deficits. This study reports on a strategy to increase calorie intake by continuing feeds until transfer for operations/procedures.Nutrition guidelines were modified in 2006 to allow continuation of feeding in intubated patients up until transfer to the operating room. Prior to 2006, enteral feeding was stopped at least 6 hours prior to surgery. A retrospective cohort design from 2003 to 2010 compared clinical outcomes in groups of adult trauma subjects before and after guideline changes and in subjects at other centers without guideline changes.During the first week, subjects in the preimplementation cohort (n = 245) received a median of 3,787 kcal per person per week, while subjects in the postimplementation cohort (n = 368) received a median of 6,662 kcal per person per week (p < 0.001). There was no change in calorie intake for subjects at other centers (n = 1,002). The risks of acute respiratory distress syndrome, pneumonia, and mortality were decreased after implementation relative to the preimplementation cohort (acute respiratory distress syndrome: relative risk ratio [RR], 0.69; 95% confidence interval [CI], 0.59-0.81; pneumonia: RR, 0.82; 95% CI, 0.65-1.00; mortality: RR, 0.67; 95% CI, 0.46-0.99). Ventilator-free days increased by 1.4 days (95% CI, 0.1-2.7), while intensive care unit stay and hospital length of stay were unchanged. These outcomes showed similar trends over time at other participating centers.Allowing intubated trauma patients to continue enteral nutrition until transfer for operations or procedures was associated with increased caloric intake without evidence of increased pulmonary complications. This represents an important strategy to reduce calorie deficits in the trauma intensive care unit.Therapeutic study/care management, level III.
Project description:ObjectiveSexual dimorphism (variation in outcome related to sex) after trauma-hemorrhage and sepsis is well documented in animals, with the pro-estrus state being proinflammatory and associated with a survival advantage. Although some observational studies confirm this pattern in humans, others demonstrate no difference in mortality. Estrogens are important modulators of the inflammatory response and insulin resistance in humans and have been linked to increased mortality during sepsis. Our objective was to determine whether sex hormone levels were associated with outcomes in critically ill surgical patients.DesignProspective cohort.PatientsA total of 301 adult critically ill or injured surgical patients remaining in the intensive care unit for > or = 48 hrs at two academic medical centers.InterventionsNone.MeasurementsBlood was collected 48 hrs after intensive care unit admission and assayed for sex hormones (estradiol, testosterone, prolactin, and progesterone) and cytokines (tumor necrosis factor-alpha and interleukin-1, -2, -4, -6, -8, and -10). Demographic and outcome data were also collected.Main resultsEstradiol was significantly higher in nonsurvivors (p < .001). Analysis by quartiles of estradiol demonstrated greater than a three-fold increase in the mortality rate for the highest vs. the lowest estradiol quartiles (29% vs. 8%, p < .001). Estradiol was also higher in nonsurvivors. An estradiol level of 100 pg/mL was associated with an odds ratio for death of 4.60 (95% confidence interval, 1.56-13.0) compared with a reference estradiol level of 45 pg/mL.ConclusionsWe conclude that serum estradiol correlates with mortality in critically ill and injured surgical patients and discuss potential mechanisms for this observation.
Project description:Objective: Identify genes that are differentially expressed between critically ill trauma patients who go on to develop ventilator-associated pneumonia (VAP) compared to similar patients who do not develop VAP Using gene expression differences, develop a model that predicts which patients are at greater risk of developing VAP. Prospective observational study, analysis of gene expression in 20 patient samples, 10 that developed ventilator-associated pneumonia, 10 that did not
Project description:BackgroundSedation of intensive care patients is needed for patient safety, but deep sedation is associated with adverse outcomes. Frontal electromyogram-based Responsiveness Index (RI) aims to quantify the level of sedation and is scaled 0-100 (low index indicates deep sedation). We compared RI-based sedation to Richmond Agitation-Sedation Scale- (RASS-) based sedation. Our hypothesis was that RI-controlled sedation would be associated with increased total time alive without mechanical ventilation at 30 days without an increased number of adverse events.Methods32 critically ill adult patients with mechanical ventilation and administration of sedation were randomized to either RI- or RASS-guided sedation. Patients received propofol and oxycodone, if possible. The following standardized sedation protocol was utilized in both groups to achieve the predetermined target sedation level: either RI 40-80 (RI group) or RASS -3 to 0 (RASS group). RI measurement was blinded in the RASS group, and the RI group was blinded to RASS assessments. State Entropy (SE) values were registered in both groups.ResultsRI and RASS groups did not differ in total time alive in 30 days without mechanical ventilation (p=0.72). The incidence of at least one sedation-related adverse event did not differ between the groups. Hypertension was more common in the RI group (p=0.01). RI group patients were in the target RI level 22% of the time and RASS group patients had 57% of scores within the target RASS level. The RI group spent significantly more time in their target sedation level than the RASS group spent in the corresponding RI level (p=0.03). No difference was observed between the groups (p=0.13) in the corresponding analysis for RASS. Propofol and oxycodone were administered at higher RI and SE values and lower RASS values in the RI group than in the RASS group.ConclusionFurther studies with a larger sample size are warranted to scrutinize the optimal RI level during different phases of critical illness.
Project description:Intensive care unit-acquired weakness (ICUAW) occurs secondary to patients treated for life-threatening conditions in the ICU being diagnosed based on the Medical Research Council sum score (MRC-SS). However, patients often complain of fatigability and poor endurance, which are not evaluated by muscle strength. In this study, we explored the feasibility of assessing muscle quality and endurance in trauma ICU patients. The modified Functional Index-2 (FI2) testing was applied to evaluate muscle endurance. The maximal voluntary contraction (MVC) was measured when evaluating the MRC-SS using surface electromyography (sEMG), and the fatigue index (FI) was also recorded at the time of endurance testing. The ultrasonic muscle echogenicity by gray-scale analysis of rectus femoris (RF) and tibialis anterior (TA) muscles was evaluated at the initial (<72 h) and end of ICU care. A total of 14 patients were enrolled in this study. Fatigue was induced in eight patients (fatigue group), and six (non-fatigue group) completed endurance testing. All patients except one had an MRC-SS exceeding 48 points. There was no difference in US echogenicity, MRC-SS, and FI between groups. In sEMG, the root mean square (RMS) values of MVC in RF and TA muscles showed a significant difference (p < 0.05). To evaluate and predict the functional activity of ICU patients, measuring muscle strength alone is insufficient, and it is necessary to evaluate muscle endurance. In this respect, the modified FI2 test and sEMG monitoring are considered to be promising procedures for evaluating the muscle condition of critically ill patients even in complex situations in the ICU.
Project description:Background: Systemic inflammation is a whole body reaction that can have an infection-positive (i.e. sepsis) or infection-negative origin. It is important to distinguish between septic and non-septic presentations early and reliably, because this has significant therapeutic implications for critically ill patients. We hypothesized that a molecular classifier based on a small number of RNAs expressed in peripheral blood could be discovered that would: 1) determine which patients with systemic inflammation had sepsis; 2) be robust across independent patient cohorts; 3) be insensitive to disease severity; and 4) provide diagnostic utility. The overall goal of this study was to identify and validate such a molecular classifier. Methods and Findings: We conducted an observational, non-interventional study of adult patients recruited from tertiary intensive care units (ICU). Biomarker discovery was conducted with an Australian cohort (n = 105) consisting of sepsis patients and post -surgical patients with infection-negative systemic inflammation. Using this cohort, a four-gene classifier consisting of a combination of CEACAM4, LAMP1, PLA2G7 and PLAC8 RNA biomarkers was identified. This classifier, designated SeptiCyte® Lab, was externally validated using RT-qPCR and receiver operating characteristic (ROC) curve analysis in five cohorts (n = 345) from the Netherlands. Cohort 1 (n=59) consisted of unambiguous septic cases and infection-negative systemic inflammation controls; SeptiCyte® Lab gave an area under curve (AUC) of 0.96 (95% CI: 0.91-1.00). ROC analysis of a more heterogeneous group of patients (Cohorts 2-5; 249 patients after excluding 37 patients with infection likelihood possible) gave an AUC of 0.89 (95% CI: 0.85-0.93). Disease severity, as measured by Sequential Organ Failure Assessment (SOFA) score or the Acute Physiology and Chronic Health Evaluation (APACHE) IV score, was not a significant confounding variable. The diagnostic utility o f SeptiCyte® Lab was evaluated by comparison to various clinical and laboratory parameters that would be available to a clinician within 24 hours of ICU admission. SeptiCyte® Lab was significantly better at differentiating sepsis from infection-negative systemic inflammation than all tested parameters, both singly and in various logistic combinations. SeptiCyte® Lab more than halved the diagnostic error rate compared to PCT in all tested cohorts or cohort combinations. Conclusions: SeptiCyte® Lab is a rapid molecular assay that may be clinically useful in the management of ICU patients with systemic inflammation. SIRS and Sepsis ICU patients, admission samples Retrospective, mutli-site sutdy using retrospective physician adjudication as a comparator