Efficacy and safety of enteral supplementation with high-dose vitamin D in critically ill patients with vitamin D deficiency.

BACKGROUND: Vitamin D deficiency is associated with mortality and morbidity in critically ill patients. This study investigated the safety and effectiveness of enteral high-dose vitamin D supplementation in intensive care unit (ICU) patients in Asia. METHODS: This was a multicenter, prospective, randomized-controlled study. Eligible participants with vitamin D deficiency were randomly assigned to the control or vitamin D supplementation group. In the vitamin D supplementation group, the patients received 569,600 IU vitamin D. The primary outcome was the serum 25(OH)D level on day 7. RESULTS: 41 and 20 patients were included in the vitamin D supplementation and control groups, respectively. On day 7, the serum 25(OH)D level was significantly higher in the vitamin D supplementation group compared to the control group (28.5 [IQR: 20.2-52.6] ng/mL and 13.9 [IQR: 11.6-18.8] ng/mL, p < 0.001). Only 41.5% of the patients achieved serum 25(OH)D levels higher than 30 ng/mL in the supplementation group. This increased level was sustained in the supplementation group on both day 14 and day 28. There were no significant adverse effects noted in the supplementation group. Patients who reached a serum 25(OH)D level of >30 ng/mL on day 7 had a significantly lower 30-day mortality rate than did those who did not (5.9% vs 37.5%, p < 0.05). CONCLUSIONS: In our study, less than half of the patients reached adequate vitamin D levels after the enteral administration of high-dose vitamin D. A reduction in 30-day mortality was noted in the patients who achieved adequate vitamin D levels. TRIAL REGISTRATION CLINICALTRIALS. GOV ID: NCT04292873, Registered, March 1, 2020.

Early prediction of mortality at sepsis diagnosis time in critically ill patients by using interpretable machine learning.

This study applied machine learning for the early prediction of 30-day mortality at sepsis diagnosis time in critically ill patients. Retrospective study using data collected from the Medical Information Mart for Intensive Care IV database. The data of the patient cohort was divided on the basis of the year of hospitalization, into training (2008-2013), validation (2014-2016), and testing (2017-2019) datasets. 24,377 patients with the sepsis diagnosis time < 24 h after intensive care unit (ICU) admission were included. A gradient boosting tree-based algorithm (XGBoost) was used for training the machine learning model to predict 30-day mortality at sepsis diagnosis time in critically ill patients. Model performance was measured in both discrimination and calibration aspects. The model was interpreted using the SHapley Additive exPlanations (SHAP) module. The 30-day mortality rate of the testing dataset was 17.9%, and 39 features were selected for the machine learning model. Model performance on the testing dataset achieved an area under the receiver operating characteristic curve (AUROC) of 0.853 (95% CI 0.837-0.868) and an area under the precision-recall curves of 0.581 (95% CI 0.541-0.619). The calibration plot for the model revealed a slope of 1.03 (95% CI 0.94-1.12) and intercept of 0.14 (95% CI 0.04-0.25). The SHAP revealed the top three most significant features, namely age, increased red blood cell distribution width, and respiratory rate. Our study demonstrated the feasibility of using the interpretable machine learning model to predict mortality at sepsis diagnosis time.

Association between microcirculation in spontaneous breathing trial and extubation success.

PURPOSE: This study assessed the association between changes in sublingual microcirculation after a spontaneous breathing trial (SBT) and successful extubation. MATERIALS AND METHODS: Sublingual microcirculation was assessed using an incident dark-field video microscope before and after each SBT and before extubation. Microcirculatory parameters before the SBT, at the end of the SBT, and before extubation were compared between the successful and failed extubation groups. RESULTS: Forty-seven patients were enrolled and analysed in this study (34 patients in the successful extubation group and 13 patients in the failed extubation group). At the end of the SBT, the weaning parameters did not differ between the two groups. However, the total small vessel density (21.2 [20.4-23.7] versus 24.9 [22.6-26.5] mm/mm2), perfused small vessel density (20.6 [18.5-21.8] versus 23.1 [20.9-25] mm/mm2), proportion of perfused small vessels (91 [87-96] versus 95 [93-98] %), and microvascular flow index (2.8 [2.7-2.9] versus 2.9 [2.9-3]) were significantly lower in the failed extubation group than in the successful extubation group. The weaning and microcirculatory parameters did not differ significantly between the two groups before the SBT. CONCLUSIONS: More patients are required to investigate the difference between baseline microcirculation before a successful SBT and the change in microcirculation at the end of the SBT between the successful and failed extubation groups. Better sublingual microcirculatory parameters at the end of SBT and before extubation are associated with successful extubation.

[Utilization of Hospice Resources in Adult Intensive Care Units: A Comparison Between Users and Non-Users].

BACKGROUND: The application of palliative care is limited and challenging in intensive care units (ICUs) because of complex factors such as time constraints and unpredictable disease progression. Although research results and international consensus stress the early use of palliative care, utilization remains low, resulting in increased risks of ineffective medical care and poor quality of death. Improving this situation requires a comprehensive understanding of the palliative condition in ICUs. PURPOSE: This study was designed to investigate the utilization of hospice resources in adult ICUs and to compare this utilization between users and non-users. METHODS: This retrospective correlation study recruited cases from the adult ICU database of a medical center in northern Taiwan between June and July 2022. Descriptive statistics, independent t-test and chi-square were used to analyze the data. RESULTS: A total of 1,181 records were analyzed, including 458 (38.8%) females and 723 (61.2%) males. Two hundred and seventeen cases (18.4%) used hospice resources. Although 124 (10.4%) of the 1181 cases were identified as "in urgent need of hospice resources" (i.e., died within 30 days of ICU admission), 25 (20.2%) did not use these resources. Significant differences between the urgent-need cases who did and did not use hospice resources were found in terms of age, disease type, degree of frailty, cardiac arrest, infection, state of consciousness, intubation and tracheostomy status, inotropic and vasopressor medication, renal replacement, ECMO placement, delirium, and Acute Physiology and Chronic Health Evaluation III and Sequential Organ Failure Assessment Scores. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: The roughly 20% of ICU patients in urgent needs of palliative care who did not utilize palliative care resources highlight the needs for continued discussion to better assist patients on palliative care decision-making. The findings show multifaceted differences between those who did and did not access palliative care. Future studies should design and test strategies to facilitate the identification of palliative care needs and ensure the effective allocation of palliative care resources in ICUs.

Score-based prediction model for severe vitamin D deficiency in patients with critical illness: development and validation.

BACKGROUND: Severe vitamin D deficiency (SVDD) dramatically increases the risks of mortality, infections, and many other diseases. Studies have reported higher prevalence of vitamin D deficiency in patients with critical illness than general population. This multicenter retrospective cohort study develops and validates a score-based model for predicting SVDD in patients with critical illness. METHODS: A total of 662 patients with critical illness were enrolled between October 2017 and July 2020. SVDD was defined as a serum 25(OH)D level of < 12 ng/mL (or 30 nmol/L). The data were divided into a derivation cohort and a validation cohort on the basis of date of enrollment. Multivariable logistic regression (MLR) was performed on the derivation cohort to generate a predictive model for SVDD. Additionally, a score-based calculator (the SVDD score) was designed on the basis of the MLR model. The model's performance and calibration were tested using the validation cohort. RESULTS: The prevalence of SVDD was 16.3% and 21.7% in the derivation and validation cohorts, respectively. The MLR model consisted of eight predictors that were then included in the SVDD score. The SVDD score had an area under the receiver operating characteristic curve of 0.848 [95% confidence interval (CI) 0.781-0.914] and an area under the precision recall curve of 0.619 (95% CI 0.577-0.669) in the validation cohort. CONCLUSIONS: This study developed a simple score-based model for predicting SVDD in patients with critical illness. TRIAL REGISTRATION: ClinicalTrials.gov protocol registration ID: NCT03639584. Date of registration: May 12, 2022.

Incidence and management of metabolic acidosis with sodium bicarbonate in the ICU: An international observational study.

BACKGROUND: Metabolic acidosis is a major complication of critical illness. However, its current epidemiology and its treatment with sodium bicarbonate given to correct metabolic acidosis in the ICU are poorly understood. METHOD: This was an international retrospective observational study in 18 ICUs in Australia, Japan, and Taiwan. Adult patients were consecutively screened, and those with early metabolic acidosis (pH < 7.3 and a Base Excess < -4 mEq/L, within 24-h of ICU admission) were included. Screening continued until 10 patients who received and 10 patients who did not receive sodium bicarbonate in the first 24 h (early bicarbonate therapy) were included at each site. The primary outcome was ICU mortality, and the association between sodium bicarbonate and the clinical outcomes were assessed using regression analysis with generalized linear mixed model. RESULTS: We screened 9437 patients. Of these, 1292 had early metabolic acidosis (14.0%). Early sodium bicarbonate was given to 18.0% (233/1292) of these patients. Dosing, physiological, and clinical outcome data were assessed in 360 patients. The median dose of sodium bicarbonate in the first 24 h was 110 mmol, which was not correlated with bodyweight or the severity of metabolic acidosis. Patients who received early sodium bicarbonate had higher APACHE III scores, lower pH, lower base excess, lower PaCO2, and a higher lactate and received higher doses of vasopressors. After adjusting for confounders, the early administration of sodium bicarbonate was associated with an adjusted odds ratio (aOR) of 0.85 (95% CI, 0.44 to 1.62) for ICU mortality. In patients with vasopressor dependency, early sodium bicarbonate was associated with higher mean arterial pressure at 6 h and an aOR of 0.52 (95% CI, 0.22 to 1.19) for ICU mortality. CONCLUSIONS: Early metabolic acidosis is common in critically ill patients. Early sodium bicarbonate is administered by clinicians to more severely ill patients but without correction for weight or acidosis severity. Bicarbonate therapy in acidotic vasopressor-dependent patients may be beneficial and warrants further investigation.

Neuroprotective effects of intraoperative dexmedetomidine versus saline infusion combined with goal-directed haemodynamic therapy for patients undergoing cranial surgery: A randomised controlled trial.

BACKGROUND: By inhibiting neuroinflammation dexmedetomidine may be neuroprotective in patients undergoing cranial surgery, but it reduces cardiac output and cerebral blood flow. OBJECTIVE: To investigate whether intra-operative dexmedetomidine combined with goal-directed haemodynamic therapy (GDHT) has neuroprotective effects in cranial surgery. DESIGN: A double-blind, single-institution, randomised controlled trial. SETTING: A single university hospital, from April 2017 to April 2020. PATIENTS: A total of 160 adults undergoing elective cranial surgery. INTERVENTION: Infusion of dexmedetomidine (0.5 µg kg-1 h-1) or saline combined with GDHT to optimise stroke volume during surgery. MAIN OUTCOME MEASURES: The proportion who developed postoperative neurological complications was compared. Postoperative disability was assessed using the Barthel Index at time points between admission and discharge, and also the 30-day modified Rankin Scale (mRS). Postoperative delirium was assessed. The concentration of a peri-operative serum neuroinflammatory mediator, high-mobility group box 1 protein (HMGB1), was compared. RESULTS: Fewer patients in the dexmedetomidine group developed new postoperative neurological complications (26.3% vs. 43.8%; P = 0.031), but the number of patients developing severe neurological complications was comparable between the two groups (11.3% vs. 20.0%; P = 0.191). In the dexmedetomidine group the Barthel Index reduction [0 (-10 to 0)] was less than that in the control group [-5 (-15 to 0)]; P = 0.023, and there was a more favourable 30-day mRS (P = 0.013) with more patients without postoperative delirium (84.6% vs. 64.2%; P = 0.012). Furthermore, dexmedetomidine induced a significant reduction in peri-operative serum HMGB1 level from the baseline (222.5 ±â€Š408.3 pg ml-1) to the first postoperative day (152.2 ±â€Š280.0 pg ml-1) P = 0.0033. There was no significant change in the control group. The dexmedetomidine group had a lower cardiac index than did the control group (3.0 ±â€Š0.8 vs. 3.4 ±â€Š1.8 l min-1 m-2; P = 0.0482) without lactate accumulation. CONCLUSIONS: Dexmedetomidine infusion combined with GDHT may mitigate neuroinflammation without undesirable haemodynamic effects during cranial surgery and therefore be neuroprotective. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT02878707.

Hypoxia-induced intestinal barrier changes in balloon-assisted enteroscopy.

KEY POINTS: Balloon-assisted enteroscopy (BAE) is an emerging standard procedure by utilizing distensible balloons to facilitate deep endoscopy in the small and large intestine. Sporadic cases of bacteraemia were found after BAE. Balloon distension by BAE caused gut tissue hypoxia. The impact of balloon distension-induced hypoxia on intestinal barriers remains unclear. Murine models of BAE by colonic balloon distension showed that short- and long-term hypoxia evoked opposite effects on epithelial tight junctions (TJs). Short-term hypoxia fortified TJ integrity, whereas long-term hypoxia caused damage to barrier function. Our data showed for the first time the molecular mechanisms and signalling pathways of epithelial barrier fortification and TJ reorganization by short-term hypoxia for the maintenance of gut homeostasis. The findings suggest avoiding prolonged balloon distension during BAE to reduce the risk of hypoxia-induced gut barrier dysfunction. ABSTRACT: Balloon-assisted enteroscopy (BAE) is an emerging standard procedure that uses distensible balloons to facilitate deep endoscopy. Intestines are known to harbour an abundant microflora. Whether balloon distension causes perturbation of blood flow and gut barrier dysfunction, and elicits risk of bacterial translocation remains unknown. Our aims were to (1) conduct a prospective study to gather microbiological and molecular evidence of bacterial translocation by BAE in patients, (2) establish a murine model of colonic balloon distension to investigate tissue hypoxia and intestinal barrier, and (3) assess the effect of short- and long-term hypoxia on epithelial permeability using cell lines. Thirteen patients were enrolled for BAE procedures, and blood samples were obtained before and after BAE for paired comparison. Four of the 13 patients (30.8%) had positive bacterial DNA in blood after BAE. Post-BAE endotoxaemia was higher than the pre-BAE level. Nevertheless, no clinical symptom of sepsis or fever was reported. To mimic clinical BAE, mice were subjected to colonic balloon distension. Local tissue hypoxia was observed during balloon inflation, and reoxygenation after deflation. A trend of increased gut permeability was seen after long-term distension, whereas a significant reduction of permeability was observed by short-term distension in the proximal colon. Human colonic epithelial Caco-2 cells exposed to hypoxia for 5-20 min exhibited increased tight junctional assembly, while those exposed to longer hypoxia displayed barrier disruption. In conclusion, sporadic cases of bacteraemia were found after BAE, without septic symptoms. Short-term hypoxia by balloon distension yielded a protective effect whereas long-term hypoxia caused damage to the gut barrier.

Comparison of dexmedetomidine versus propofol on hemodynamics in surgical critically ill patients.

BACKGROUND: Sedation with dexmedetomidine and propofol may cause hypotension or bradycardia. This study aimed to compare the effects of dexmedetomidine and propofol on hemodynamics and clinical outcomes in surgical intensive care unit (ICU) patients after major abdominal surgery. MATERIALS AND METHODS: Enrolled patients were randomly allocated to the dexmedetomidine or propofol group. Cardiac index was measured using a continuous noninvasive cardiac output monitor on the basis of chest bioreactance. Heart rate, blood pressure, opioid requirement, urine output, delirium incidence, ICU length of stay, and total hospital length of stay were compared between the two groups. The incidences of bradycardia, hypotension, and severe low cardiac index were compared. RESULTS: We enrolled 60 patients. Heart rate and mean arterial pressure were significantly lower in the dexmedetomidine group than in the propofol group. Cardiac index did not differ significantly between the two groups (dexmedetomidine group 3.1 L/min/m2, [95% confidence interval {95% CI} 2.8-3.3] versus propofol group 3.2 L/min/m2 [95% CI 2.9-3.5], P = 0.578). The incidences of bradycardia, hypotension, and severe low cardiac index did not differ significantly between the two groups. CONCLUSIONS: Cardiac index did not differ significantly between the dexmedetomidine and propofol groups in surgical ICU patients after major abdominal surgery.

Investigation of microcirculation in patients with venoarterial extracorporeal membrane oxygenation life support.

BACKGROUND: Microcirculatory dysfunction develops in both septic and cardiogenic shock patients, and it is associated with poor prognosis in patients with septic shock. Information on the association between microcirculatory dysfunction and prognosis in cardiogenic shock patients with venoarterial extracorporeal membrane oxygenation (VA-ECMO) support is limited. METHODS: Sublingual microcirculation images were recorded using an incident dark-field video microscope at the following time points: within 12 h (T1), 24 h (T2), 48 h (T3), 72 h (T4), and 96 h (T5) after VA-ECMO placement. If a patient could be weaned off VA-ECMO, sublingual microcirculation images were recorded before and after VA-ECMO removal. Microcirculatory parameters were compared between 28-day nonsurvivors and survivors with VA-ECMO support. In addition, the microcirculation and clinical parameters were assessed as prognostic tests of 28-day mortality, and patients were divided into three subgroups according to microcirculation parameters for survival analysis. RESULTS: Forty-eight patients were enrolled in this study. At T1, the observed heart rate, mean arterial pressure, inotropic score and lactate level of 28-day nonsurvivors and survivors did not differ significantly, but the perfused small vessel density (PSVD) and proportion of perfused vessels (PPV) were lower in the 28-day nonsurvivors than in the survivors. The PSVD and PPV were slightly superior to lactate levels in predicting 28-day mortality (area under curve of 0.68, 0.70, and 0.62, respectively). The subgroup with the lowest PSVD (< 15 mm/mm2) and PPV (< 64%) values exhibited less favorable survival compared with the other two subgroups. CONCLUSIONS: Early microcirculatory parameters could be used to predict the survival of cardiogenic shock patients with VA-ECMO support. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02393274 . Registered on 19 March 2015.

Effects of Polymyxin B Hemoperfusion on Mortality in Patients With Severe Sepsis and Septic Shock: A Systemic Review, Meta-Analysis Update, and Disease Severity Subgroup Meta-Analysis.

OBJECTIVE: Several studies have reported a survival benefit for polymyxin B hemoperfusion treatment in patients with severe sepsis and septic shock. However, recently, a propensity-matched analysis and a randomized controlled trial reported no survival benefit for polymyxin B hemoperfusion treatment. We performed an up-to-date meta-analysis to determine the effect of polymyxin B hemoperfusion treatment on mortality in patients with severe sepsis and septic shock. DATA SOURCES: PubMed, Embase, and Cochrane Library were searched from inception to May 2016. STUDY SELECTION: Studies investigating the effect of polymyxin B hemoperfusion on mortality were considered eligible. We searched for terms related to severe sepsis and septic shock and terms related to polymyxin B hemoperfusion. DATA EXTRACTION: The following data were extracted from the original articles: the name of the first author and publication year, subjects and setting, inclusion and exclusion criteria, mean age and size of the study population, male percentage, mortality, blood pressure, Sequential Organ Failure Assessment score, pulmonary oxygenation, and levels of endotoxin and humoral cytokines. DATA SYNTHESIS: A total of 17 trials were included. The pooled risk ratio for overall mortality was 0.81 (95% CI, 0.70-0.95), favoring polymyxin B hemoperfusion (p = 0.007). Disease severity subgroup meta-analysis revealed a significant reduction of mortality in the intermediate- and high-risk groups (risk ratio, 0.84; 95% CI, 0.77-0.92 and risk ratio, 0.64; 95% CI, 0.52-0.78, respectively), but not in the low-risk group (risk ratio, 1.278; 95% CI, 0.888-1.839). The nonlinear meta-regression with restricted cubic spline showed an almost linear inverse association between the baseline mortality rate and reduction in the risk of mortality. CONCLUSION: The present study demonstrated that polymyxin B hemoperfusion treatment may reduce mortality in patients with severe sepsis and septic shock in specific disease severity subgroups.

An observational study of microcirculation in dialysis patients and kidney transplant recipients.

BACKGROUND: Microcirculatory dysfunction contributes to acute and chronic kidney diseases. To the best of our knowledge, no study has compared differences in microcirculation among healthy volunteers, dialysis patients and kidney transplant recipients. MATERIALS AND METHODS: Sublingual microcirculation was examined using sidestream dark field imaging and was compared among 90 healthy volunteers, 40 dialysis patients and 40 kidney transplant recipients. The gender effect on microcirculation and the correlations among the microcirculation parameters, age, body mass index, heart rate and blood pressure were analysed. RESULTS: Total small vessel density, perfused small vessel density and the proportion of perfused small vessels were lower in the dialysis patients than in the healthy volunteers and kidney transplant recipients [total small vessel density; healthy volunteers vs. dialysis patients vs. kidney transplant recipients, 25·2 (2·3) vs. 22·8 (2·6) vs. 24·2 (2·9) mm/mm2 , P < 0·001]. Systolic blood pressure showed a weak negative correlation with the microvascular flow index scores in the healthy volunteers. By contrast, systolic blood pressure, diastolic blood pressure and mean arterial pressure showed weak positive correlations with proportion of perfused small vessels and the microvascular flow index scores in the dialysis patients. CONCLUSIONS: Microcirculatory dysfunction is noted in dialysis patients, and this alteration is ameliorated in KT recipients. The positive correlation between blood pressure and microcirculation in dialysis patients suggests that additional studies should investigate the optimal goal of blood pressure management for dialysis patients.

Effects of endotoxin absorber hemoperfusion on microcirculation in septic pigs.

BACKGROUND: Endotoxins contribute to systemic inflammatory response and microcirculatory dysfunctions under conditions of sepsis. Polymyxin B hemoperfusion (PMX-HP) is used to remove circulating endotoxins and improve clinical outcomes. This study aims to investigate the effect of PMX-HP on microcirculation in septic pigs. MATERIALS AND METHODS: By using a septic pig model, we tested the hypothesis that PMX-HP can correct intestinal microcirculation, tissue oxygenation saturation, and histopathologic alterations. A total of 18 male pigs were divided into three groups: (1) sham; (2) sepsis (fecal peritonitis); and (3) sepsis + PMX-HP groups. A sidestream dark field video microscope was used to record microcirculation throughout the terminal ileal mucosa, colon mucosa, kidney surface, and sublingual area. A superficial tissue oxygenation monitor employing the light reflectance spectroscopy technique was used to measure the tissue oxygen saturation. Hematoxylin and eosin staining was used for histologic examination. RESULTS: The perfused small vessel density and tissue oxygen saturation of the ileal mucosa at 6 h were higher in the sepsis + PMX-HP group than those in the sepsis group. The fluid amount and norepinephrine infusion rate between the sepsis group and sepsis + PMX-HP groups did not differ significantly. The histologic score for the ileal mucosa was lower in the sepsis + PMX-HP group than that in the sepsis group. Finally, the urine output was higher in the sepsis + PMX-HP group than it was in the sepsis group. CONCLUSIONS: This study demonstrates that PMX-HP attenuates microcirculatory dysfunction, tissue desaturation, and histopathologic alterations in the ileal mucosa in septic pigs.

Effects of Dexmedetomidine on Intestinal Microcirculation and Intestinal Epithelial Barrier in Endotoxemic Rats.

BACKGROUND: Dexmedetomidine reduces cytokine production in septic patients and reduces inflammation and mortality in experimental models of endotoxemia and sepsis. This study investigated whether dexmedetomidine attenuates endothelial dysfunction, intestinal microcirculatory dysfunction, and intestinal epithelial barrier disruption in endotoxemic rats. METHODS: Ninety-two male Wistar rats were randomly assigned to the following four groups: (1) Sham; (2) lipopolysaccharide, received IV lipopolysaccharide 15 and 10 mg/kg at 0 and 120 min; (3) dexmedetomidine, received IV dexmedetomidine for 240 min; and (4) lipopolysaccharide + dexmedetomidine, received both lipopolysaccharide and dexmedetomidine. Sidestream dark-field videomicroscope, tissue oxygen monitor, and full-field laser perfusion image were used to investigate the microcirculation of the terminal ileum. Serum endocan level was measured. The Ussing chamber permeability assay, lumen-to-blood gadodiamide passage by magnetic resonance imaging, and bacterial translocation were conducted to determine epithelial barrier function. Mucosal apoptotic levels and tight junctional integrity were also examined. RESULTS: The density of perfused small vessels in mucosa, serosal muscular layer, and Peyer patch in the lipopolysaccharide + dexmedetomidine group was higher than that of the lipopolysaccharide group. Serum endocan level was lower in the lipopolysaccharide + dexmedetomidine group than in the lipopolysaccharide group. Mucosal ratio of cleaved to full-length occludin and spleen bacterial counts were significantly lower in the lipopolysaccharide + dexmedetomidine group than in the lipopolysaccharide group. CONCLUSION: The study finding suggests that dexmedetomidine protects against intestinal epithelial barrier disruption in endotoxemic rats by attenuating intestinal microcirculatory dysfunction and reducing mucosal cell death and tight junctional damage. (Anesthesiology 2016; 125:355-67).

Laser speckle contrast imaging for assessing microcirculatory changes in multiple splanchnic organs and the gracilis muscle during hemorrhagic shock and fluid resuscitation.

OBJECTIVE: Hemorrhagic shock induces both macrocirculatory and microcirculatory impairment. Persistent microcirculatory dysfunction is associated with the dysfunction of multiple organs, especially in the splanchnic organs. However, few studies have simultaneously investigated microcirculation in multiple organs. In the present study, we used laser speckle contrast imaging to simultaneously investigate microcirculatory changes secondary to hemorrhagic shock and after fluid resuscitation among multiple splanchnic organs and the gracilis muscle. MATERIALS AND METHODS: 72 male Wistar rats were subjected to sham operation, hemorrhagic shock (total blood loss of 30mL/kg) and saline resuscitation. Macrocirculatory parameters, including the mean arterial pressure (MAP) and heart rate, and microcirculatory parameters, including microcirculatory blood flow intensity and tissue oxygen saturation in the liver, kidney, intestine (mucosa, serosal muscular layer, and Peyer's patch), and gracilis muscle were compared in a period of 3h. RESULTS: Hemorrhagic shock induced a significant reduction of microcirculatory blood flow intensity in the kidney and intestine (especially the mucosa). Tissue oxygen saturation reduction secondary to hemorrhagic shock was comparable among the various splanchnic organs but lower than the gracilis muscle. Fluid resuscitation restored the MAP but not the microcirculatory blood flow in the intestine and the tissue oxygen saturation in each splanchnic organ. CONCLUSION: Hemorrhagic shock induced the largest reduction in microcirculatory blood flow intensity in the intestinal mucosa. By comparison, the reduction of tissue oxygen saturation was not significantly different among the various splanchnic organs. Although fluid resuscitation restored the MAP, the intestinal microcirculation remained damaged.

Effects of different types of fluid resuscitation for hemorrhagic shock on splanchnic organ microcirculation and renal reactive oxygen species formation.

INTRODUCTION: Fluid resuscitation is an indispensable procedure in the acute management of hemorrhagic shock for restoring tissue perfusion, particularly microcirculation in splanchnic organs. Resuscitation fluids include crystalloids, hypertonic saline (HTS), and synthetic colloids, and their selection affects the recovery of microcirculatory blood flow and reactive oxygen species (ROS) formation, which is often evident in the kidney, following reperfusion. In this study, the effects of acute resuscitation with 0.9% saline (NS), 3% HTS, 4% succinylated gelatin (GEL), and 6% hydroxyethyl starch (HES) 130/0.4 were compared in a hemorrhagic shock rat model to analyze restoration of microcirculation among various splanchnic organs and the gracilis muscle and reperfusion-induced renal ROS formation. METHODS: A total of 96 male Wistar rats were subjected to sham operation (sham group), hemorrhagic shock (control group), and resuscitation with NS, HTS, GEL and HES. Two hours after resuscitation, changes in the mean arterial pressure (MAP), serum lactate level and the microcirculatory blood flow among various splanchnic organs, namely the liver, kidney, and intestine (mucosa, serosal muscular layer, and Peyer's patch), and the gracilis muscle, were compared using laser speckle contrast imaging. Renal ROS formation after reperfusion was investigated using an enhanced in vivo chemiluminescence (CL) method. RESULTS: Microcirculatory blood flow was less severely affected by hemorrhaging in the liver and gracilis muscle. Impairment of microcirculation in the kidney was restored in all resuscitation groups. Resuscitation in the NS group failed to restore intestinal microcirculation. Resuscitation in the HTS, GEL, and HES groups restored intestinal microcirculatory blood flow. By comparison, fluid resuscitation restored hemorrhagic shock-induced hypotension and decreased lactatemia in all resuscitation groups. Reperfusion-induced in vivo renal ROS formation was significantly higher in the GEL and HES groups than in the other groups. CONCLUSION: Although fluid resuscitation with NS restored the MAP and decreased lactatemia following hemorrhagic shock, intestinal microcirculation was restored only by other volume expanders, namely 3% HTS, GEL, and HES. However, reperfusion-induced renal ROS formation was significantly higher when synthetic colloids were used.

Evaluation of tracheal intubation: A retrospective study of skill acquisition by medical students in the operating theater.

BACKGROUND/PURPOSE: Tracheal intubation is a critical life-saving invasive procedure. Medical students generally obtain the skill of performing tracheal intubation in the operating theater during their anesthesiology rotation. In this study, we sought to characterize medical students' skill acquisition of tracheal intubation. METHODS: We retrospectively reviewed the logbooks of 94 medical students who had completed a 3-4 week rotation in our department between January 2011 and June 2012. RESULTS: Ninety-four students performed 934 tracheal intubations. The success rate of intubation was 76.7%. After adjustment for age, body mass index, Mallampati class and grade, American Society of Anesthesiology (ASA) scores, and surgical category, the odds ratio of successful tracheal intubation improved with cumulative practice [odds ratio (OR) = 1.05 for each additional intubation performed; 95% confidence interval (CI) 1.00-1.09]. By contrast, the success rate decreased significantly with increasing scores of Mallampati class (OR = 0.32 for each increase in class; 95% CI 0.23-0.24) and grade (OR = 0.57 for each increase in grade; 95% CI 0.39-0.84). The main reason for intubation failure (57%) was poor visualization of vocal cords, due to suboptimal placement of the position of the laryngoscope. The satisfaction and confidence of students regarding the ability of performing tracheal intubation increased with each additional procedure, but decreased significantly after multiple unsuccessful attempts and the occurrence of any complication. CONCLUSION: Medical students acquired the ability of tracheal intubation and overcame major challenges through cumulative clinical practice of the procedure.

Changes in endotracheal tube cuff pressure during laparoscopic surgery in head-up or head-down position.

BACKGROUND: The abdominal insufflation and surgical positioning in the laparoscopic surgery have been reported to result in an increase of airway pressure. However, associated effects on changes of endotracheal tube cuff pressure are not well established. METHODS: 70 patients undergoing elective laparoscopic colorectal tumor resection (head-down position, n = 38) and laparoscopic cholecystecomy (head-up position, n = 32) were enrolled and were compared to 15 patients undergoing elective open abdominal surgery. Changes of cuff and airway pressures before and after abdominal insufflation in supine position and after head-down or head-up positioning were analysed and compared. RESULTS: There was no significant cuff and airway pressure changes during the first fifteen minutes in open abdominal surgery. After insufflation, the cuff pressure increased from 26 ± 3 to 32 ± 6 and 27 ± 3 to 33 ± 5 cmH2O in patients receiving laparoscopic cholecystecomy and laparoscopic colorectal tumor resection respectively (both p < 0.001). The head-down tilt further increased cuff pressure from 33 ± 5 to 35 ± 5 cmH2O (p < 0.001). There six patients undergoing colorectal tumor resection (18.8%) and eight patients undergoing cholecystecomy (21.1%) had a total increase of cuff pressure more than 10 cm H2O (18.8%). There was no significant correlation between increase of cuff pressure and either the patient's body mass index or the common range of intra-abdominal pressure (10-15 mmHg) used in laparoscopic surgery. CONCLUSIONS: An increase of endotracheal tube cuff pressure may occur during laparoscopic surgery especially in the head-down position.

Comparison of dexmedetomidine versus propofol sedation on microcirculation and organ injuries in critically ill surgical patients: A randomized controlled pilot study.

BACKGROUND: Recent studies have shown that dexmedetomidine may improve microcirculation and prevent organ failure. However, most evidence was obtained from experimental animals and patients receiving cardiac surgery with cardiopulmonary bypass. This study aimed to investigate the effect of dexmedetomidine on microcirculation and organ injuries in critically ill general surgical patients. METHODS: In this prospective randomized trial, patients admitted to the surgical intensive care unit after general surgery were enrolled and randomly allocated to the dexmedetomidine or propofol groups. Patients received continuous dexmedetomidine or propofol infusions to meet their requirement of sedation according to their grouping. At each time point, sublingual microcirculation images were obtained using the incident dark field video microscope. RESULTS: Overall, 60 patients finished the trial and were analyzed. Microcirculation parameters did not differ significantly between two groups. Heart rate at 4 h after ICU admission and mean arterial pressures at 12 h and 24 h after ICU admission were lower in the dexmedetomidine group than in the propofol group. At 24 h, serum aspartate aminotransferase (41 (25-118) vs 86 (34-129) U/L, p = 0.035) and alanine aminotransferase (50 (26-160) vs 68 (35-172) U/L, p = 0.019) levels were significantly lower in the dexmedetomidine group than in the propofol group. CONCLUSION: Microcirculation parameters did not differ significantly between the dexmedetomidine and propofol groups. At 24 h after ICU admission, serum liver enzyme levels were lower in patients receiving dexmedetomidine as compared to propofol.

Immunometabolic features of natural killer cells are associated with infection outcomes in critical illness.

Immunosuppression increases the risk of nosocomial infection in patients with chronic critical illness. This exploratory study aimed to determine the immunometabolic signature associated with nosocomial infection during chronic critical illness. We prospectively recruited patients who were admitted to the respiratory care center and who had received mechanical ventilator support for more than 10 days in the intensive care unit. The study subjects were followed for the occurrence of nosocomial infection until 6 weeks after admission, hospital discharge, or death. The cytokine levels in the plasma samples were measured. Single-cell immunometabolic regulome profiling by mass cytometry, which analyzed 16 metabolic regulators in 21 immune subsets, was performed to identify immunometabolic features associated with the risk of nosocomial infection. During the study period, 37 patients were enrolled, and 16 patients (43.2%) developed nosocomial infection. Unsupervised immunologic clustering using multidimensional scaling and logistic regression analyses revealed that expression of nuclear respiratory factor 1 (NRF1) and carnitine palmitoyltransferase 1a (CPT1a), key regulators of mitochondrial biogenesis and fatty acid transport, respectively, in natural killer (NK) cells was significantly associated with nosocomial infection. Downregulated NRF1 and upregulated CPT1a were found in all subsets of NK cells from patients who developed a nosocomial infection. The risk of nosocomial infection is significantly correlated with the predictive score developed by selecting NK cell-specific features using an elastic net algorithm. Findings were further examined in an independent cohort of COVID-19-infected patients, and the results confirm that COVID-19-related mortality is significantly associated with mitochondria biogenesis and fatty acid oxidation pathways in NK cells. In conclusion, this study uncovers that NK cell-specific immunometabolic features are significantly associated with the occurrence and fatal outcomes of infection in critically ill population, and provides mechanistic insights into NK cell-specific immunity against microbial invasion in critical illness.