Cortisol Levels During First Admission Day Are Associated With Clinical Outcomes in Surgical Critically Ill Patients.

IMPORTANCE: To explore the correlation between cortisol levels during first admission day and clinical outcomes. OBJECTIVES: Although most patients exhibit a surge in cortisol levels in response to stress, some suffer from critical illness-related corticosteroid insufficiency (CIRCI). Literature remains inconclusive as to which of these patients are at greater risk of poor outcomes. DESIGN: A retrospective study. SETTING: A surgical ICU (SICU) in a tertiary medical center. PARTICIPANTS: Critically ill patients admitted to the SICU who were not treated with steroids. MAIN OUTCOMES AND MEASURES: Levels of cortisol taken within 24 hours of admission (day 1 [D1] cortisol) in 1412 eligible patients were collected and analyzed. Results were categorized into four groups: low (0-10 µg/dL), normal (10-25 µg/dL), high (25-50 µg/dL), and very high (above 50 µg/dL) cortisol levels. Primary endpoint was 90-day mortality. Secondary endpoints were the need for organ support (use of vasopressors and mechanical ventilation [MV]), ICU length of stay (LOS), and duration of MV. RESULTS: The majority of patients (63%) had high or very high D1 cortisol levels, whereas 7.6% had low levels and thus could be diagnosed with CIRCI. There were statistically significant differences in 90-day mortality between the four groups and very high levels were found to be an independent risk factor for mortality, primarily in patients with Sequential Organ Failure Assessment (SOFA) less than or equal to 3 or SOFA greater than or equal to 7. Higher cortisol levels were associated with all secondary endpoints. CIRCI was associated with favorable outcomes. CONCLUSIONS AND RELEVANCE: In critically ill surgical patients D1 cortisol levels above 50 mcg/dL were associated with mortality, need for organ support, longer ICU LOS, and duration of MV, whereas low levels correlated with good clinical outcomes even though untreated. D1 cortisol level greater than 50 mcg/dL can help discriminate nonsurvivors from survivors when SOFA less than or equal to 3 or SOFA greater than or equal to 7.

Kinetics of C-reactive protein during extracorporeal membrane oxygenation.

BACKGROUND: The exposure of blood to the artificial circuit during extracorporeal membrane oxygenation (ECMO) can induce an inflammatory response. C-reactive protein (CRP) is a commonly used biomarker of systemic inflammation. METHODS: In this retrospective observational study, we analyzed results of daily plasma CRP measurements in 110 critically ill patients, treated with ECMO. We compared CRP levels during the first 5 days of ECMO operation, between different groups of patients according to ECMO configurations, Coronavirus disease 2019 (COVID-19) status, and mechanical ventilation parameters. RESULTS: There was a statistically significant decrease in CRP levels during the first 5 days of veno-venous (VV) ECMO (173 ± 111 mg/L, 154 ± 107 mg/L, 127 ± 97 mg/L, 114 ± 100 mg/L and 118 ± 90 mg/L for days 1-5 respectively, p < 0.001). Simultaneously, there was a significant reduction in ventilatory parameters, as represented by the mechanical power (MP) calculation, from 24.02 ± 14.53 J/min to 6.18 ± 4.22 J/min within 3 h of VV ECMO initiation (p < 0.001). There was non-significant trend of increase in CRP level during the first 5 days of veno arterial (VA) ECMO (123 ± 80 mg/L, 179 ± 91 mg/L, 203 ± 90 mg/L, 179 ± 95 mg/L and 198 ± 93 for days 1-5 respectively, p = 0.126) and no significant change in calculated MP (from 14.28 ± 8.56 J/min to 10.81 ± 8.09 J/min within 3 h if ECMO initiation, p = 0.071). CONCLUSIONS: We observed a significant decrease in CRP levels during the first 5 days of VV ECMO support, and suggest that the concomitant reduction in ventilatory MP may have mitigated the degree of alveolar stress and strain that could have contributed to a decrease in the systemic inflammatory process.

Two-hour indirect calorimetry measurement as a predictor of 24-hour energy expenditure in critically ill surgical patients: A longitudinal study.

BACKGROUND: Measuring energy expenditure (EE) by indirect calorimetry (IC) has become the gold standard tool for critically ill patients to define energy targets and tailor nutrition. Debate remains as to the optimal duration of measurements or the optimal time of day in which to perform IC. METHODS: In this retrospective longitudinal study, we analyzed results of daily continuous IC in 270 mechanically ventilated, critically ill patients admitted to the surgical intensive care unit in a tertiary medical center and compared measurements performed at different hours of the day. RESULTS: A total of 51,448 IC hours was recorded, with an average 24-h EE of 1523 ± 443 kcal/day. Night shift (00:00-8:00) was found to have significantly lower EE measurements (mean, 1499 ± 439 kcal/day) than afternoon (16:00-00:00; mean, 1526 ± 435 kcal/day) and morning (8:00-16:00; mean, 1539 ± 462 kcal/day) measurements (P < 0.001 for all). The bi-hourly time frame that most closely resembled the daily mean was 18:00-19:59, with a mean of 1521 ± 433 kcal/day. Daily EE measurements of the continuous IC at days 3-7 of admission showed a trend toward a daily increase in 24-h EE, but the difference was not statistically significant (P = 0.081). CONCLUSIONS: Periodic measurements of EE can differ slightly when performed at various hours of the day, but the error range is small and may not necessarily have a clinical impact. When continuous IC is not available, a 2-h EE measurement between 18:00 and 19:59 can serve as a reasonable alternative.

Size and lipid modification determine liposomal Indocyanine green performance for tumor imaging in a model of rectal cancer.

Localization of rectal tumors is a challenge in minimally invasive surgery due to the lack of tactile sensation. We had developed liposomal indocyanine green (Lip-ICG) for localization of rectal tumor. In this study we evaluated the effects of liposome size and lipid PEGylation on imaging. We used an endoscopically-guided orthotopic experimental rectal cancer model in which tumor fluorescence was determined at different time points after intravenous (i.v.) administration of Lip-ICG and PEGylated liposomes (PEG-Lip-ICG). Signal intensity was measured by tumor-to-background ratio (TBR), or normalized TBR (compared to TBR of free ICG). Fluorescence microscopy of tumor tissue was performed to determine fluorescence localization within the tissue and blood vessels. Liposomes of 60 nm showed an increased TBR compared with free ICG at 12 hours after i.v. injection: normalized TBR (nTBR) = 3.11 vs. 1, respectively (p = 0.006). Larger liposomes (100 nm and 140 nm) had comparable signal to free ICG (nTBR = 0.98 ± 0.02 and 0.78 ± 0.08, respectively), even when additional time points were examined (0.5, 3 and 24 hours). PEG-Lip- ICG were more efficient than Lip-ICG (TBR = 4.2 ± 0.18 vs. 2.5 ± 0.12, p < 0.01) presumably because of reduced uptake by the reticulo-endothelial system. ICG was found outside the capillaries in tumor margins. We conclude that size and lipid modification impact imaging intensity.

Optimization of liposomal indocyanine green for imaging of the urinary pathways and a proof of concept in a pig model.

BACKGROUND: Iatrogenic ureteral injury is an increasing concern in the laparoscopic era, affecting both patient morbidity and costs. Current techniques enabling intraoperative ureteral identification require invasive procedures or radiations. Our aim was to develop a real-time, non-invasive, radiation-free method to visualize ureters, based on near-infrared (NIR) imaging. For this purpose, we interfered with the biliary excretion pathway of the indocyanine green (ICG) fluorophore by loading it into liposomes, enabling renal excretion. In this work, we studied various parameters influencing ureteral imaging. METHODS: Fluorescence intensity (FI) of various liposomal ICG sizes and doses were characterized in vitro and subsequently tested in vivo in mice and pigs. Quantification was performed by measuring FI in multiple points and applying the ureteral/retroperitoneum ratio (U/R). RESULTS: The optimal liposomal ICG loading dose was 20%, for the different liposomes' sizes tested (30, 60, 100 nm). Higher concentration of ICG decreased FI. In vivo, the optimal liposome size for ureteral imaging was 60 nm, which yielded a U/R of 5.2 ± 1.7 (p < 0.001 vs. free ICG). The optimal ICG dose was 8 mg/kg (U/R = 2.1 ± 0.4, p < 0.05 vs. 4 mg/kg). Only urine after liposomal ICG injection had a measurable FI, and not after free ICG injection. Using a NIR-optimized laparoscopic camera, ureters could be effectively imaged in pigs, from 10 min after injection and persisting for at least 90 min. Ureteral peristaltic waves could be clearly identified only after liposomal ICG injection. CONCLUSIONS: Optimization of liposomal ICG allowed to visualize enhanced ureters in animal models and seems a promising fluorophore engineering, which calls for further developments.

Clinical benefits of diffusion tensor imaging in hydrocephalus.

OBJECT The object of this study was to use diffusion tensor imaging (DTI) to evaluate and characterize white matter changes in hydrocephalus. METHODS The authors performed a retrospective analysis of DTI in a cohort of patients with hydrocephalus (n = 35), 19 of whom had both pre- and postsurgical imaging studies. These patient's DTI values were compared with values extracted from age-dependent trend lines computed from a healthy subject group (n = 70, age span 14 months-14 years). Several DTI parameters in different regions of interest (ROIs) were evaluated to find the most sensitive parameters for clinical decision making in hydrocephalus. RESULTS Compared with healthy controls, patients with active hydrocephalus had a statistically significant change in all DTI parameters. The most sensitive and specific DTI parameter for predicting hydrocephalus was axial diffusivity (λ1) measured at the level of the corona radiata. Diffusion tensor imaging parameters correlated with several conventional radiological parameters in the assessment of hydrocephalus but were not superior to them. There was no convincing correlation between clinical disease severity and DTI parameters. When examining the pre- and postsurgical effect, it was found that DTI may be a sensitive tool for estimating tissue improvement. CONCLUSIONS This large-cohort study with a multidisciplinary approach combining clinical, neurological, radiological, and multiple DTI parameters revealed the most sensitive DTI parameters for identifying hydrocephalus and suggested that they may serve as an important tool for the disorder's quantitative radiological assessment.