A Pilot Study of the Use of Dexmedetomidine for the Control of Delirium by Reducing the Serum Concentrations of Brain-Derived Neurotrophic Factor, Neuron-Specific Enolase, and S100B in Polytrauma Patients.

BACKGROUND: Delirium is very common among patients with polytrauma, although no suitable means exist to feasibly reduce the incidence and duration of delirium in these patients. Recent reports have suggested that continuous intravenous (IV) infusions of dexmedetomidine, rather than benzodiazepine, be administered for sedation to reduce the duration of delirium in this population. However, serum neuron-specific enolase (NSE), S100 calcium binding protein B (S100B), and brain-derived neurotrophic factor (BDNF) levels have not yet been investigated in polytrauma patients who received sedation with dexmedetomidine rather than other conventional sedatives. The aim of this study was to assess the association of blood BDNF, NSE, and S100B with the occurrence of delirium among polytrauma patients who had been sedated with dexmedetomidine. MATERIALS AND METHODS: Consecutive patients were randomly assigned to 1 of 2 treatment study groups, namely the "dexmedetomidine group" or the "common group." This case-control study included 18 patients with delirium and 34 matched controls in a 63-bed general intensive care unit (ICU). Blood samples were collected from all patients upon ICU admission, on the day when delirium was diagnosed, and on days 3 and 5 following diagnosis. The serum levels of S100B, BDNF, and NSE were determined by enzyme-linked immunosorbent assay. The sedation levels and delirium were assessed using the Richmond Agitation and Sedation Scale and the Confusion Assessment Method for the ICU. RESULTS: The median BDNF, NSE, and S100B concentrations were significantly lower in the dexmedetomidine group than in the common group on the day when delirium was diagnosed and on the third day after delirium was diagnosed. The rate of delirium was significantly lower in the dexmedetomidine group than in the common group. There were clear differences in the BDNF, NSE, and S100B levels between the 2 groups on the fifth day after delirium was diagnosed. CONCLUSIONS: Our randomized controlled study suggests that the sedation of polytrauma patients with dexmedetomidine could help reduce the serum BDNF, S100B, and NSE levels, which appear to be associated with the occurrence of delirium in the dexmedetomidine group.

The ratio of Th17/Treg cells as a risk indicator in early acute respiratory distress syndrome.

INTRODUCTION: Recent studies have revealed that lung inflammation mediated by CD4+ T cells may contribute to the pathogenesis of acute respiratory distress syndrome (ARDS). The imbalance between CD4 + CD25 + Foxp3 + regulatory T (Treg) cells and T helper (Th)17 cells has been found in a number of different inflammation and autoimmune diseases, while the role of the Th17/Treg balance in ARDS remains largely unknown. The aim of this study was to investigate the Th17/Treg pattern and its impact on disease severity and outcomes in patients with ARDS. METHODS: This prospective, observational study enrolled 79 patients who fulfilled the Berlin definition of ARDS and 26 age- and sex-matched healthy controls. Circulation Th17 and Treg cell frequencies were analyzed by flow cytometry, and the expressions of Th17- and Treg-related cytokines in serum were measured by enzyme-linked immunosorbent assay (ELISA). Acute Physiologic and Chronic Health Evaluation (APACHE) II score, Sequential Organ Failure Assessment (SOFA) score, and the Lung Injury Score were also calculated at enrollment. RESULTS: Within 24 hours after the onset of ARDS, the changes of peripheral circulating Th17 and Treg cell frequencies gradually increased from mild to severe ARDS. Th17/Treg ratio was positively correlated with APACHE II score, SOFA score, and Lung Injury Score, while negatively correlated with PaO2/FiO2. The areas under the receiver operating characteristic (AUC) curves of Th17/Treg ratio for predicting 28-day mortality in ARDS patients was higher than that of APACHE II score, SOFA score, Lung injury score, as well as PaO2/FiO2. Using a Th17/Treg ratio cutoff value of >0.79 to determine 28-day mortality, the sensitivity was 87.5% with 68.1% specificity. Multivariate logistic regression showed Th17/Treg ratio >0.79 (odds ratio = 8.68, P = 0.002) was the independent predictor for 28-day mortality in patients with ARDS. Finally, cumulative survival rates at 28-day follow-up also differed significantly between patients with Th17/Treg ratio >0.79 and ≤0.79 (P <0.001). CONCLUSIONS: The Th17/Treg imbalance favoring a Th17 shift represents a potential therapeutic target to alleviate lung injury and a novel risk indicator in patients with early ARDS.

[The effects of real-time continuous glucose monitoring on oxidative stress and mortality in critically ill patients].

OBJECTIVE: To evaluate the effects of real-time continuous glucose monitoring (RT-CGM) system on oxidative stress and mortality in critically ill patients and to explore the correlation between glucose index, oxidative stress and mortality. METHODS: Selected 123 cases of critically ill patients were enrolled in this prospective randomized controlled study. They were randomly divided into the RT-CGM group (n = 61) and blood glucose meter group (GM group, n = 62). The following parameters were compared between the two groups: mean amplitude of glucose excursions (MAGE), hypoglycemia incidence, low blood glucose index (LBGI), high blood glucose index (HBGI), 28-day mortality and plasma level of 8-iso-PGF2α (8-iso) at 48 hours (R2), 72 hours (R3) and 96 hours (R4) after admission to ICU. The correlation between glucose index and plasma level of 8-iso-PGF2α were analyzed. The correlation between glucose index, plasma 8-iso level and 28-day death were analyzed. RESULTS: The parameters of MAGE, hypoglycemia incidence, LBGI and HBGI in the RT-CGM group and the GM group were (3.73 ± 1.09) mmol/L and (4.19 ± 1.11) mmol/L (P = 0.02), 3.28% and 14.52% (P = 0.03), 0.0011 and 0.0119 (P < 0.01) and 0.2258 and 0.3697 (P < 0.01), respectively. The plasma levels of 8-iso at R2, R3, R4 in the RT-CGM group and the GM group were (111.44 ± 16.99) ng/L and (114.03 ± 14.64) ng/L (P = 0.37), (94.53 ± 14.92) ng/L and (110.31 ± 13.42) ng/L (P < 0.01) and (57.84 ± 12.22) ng/L and (84.41 ± 14.16) ng/L (P < 0.01), respectively. The r values between MAGE, LBGI, HBGI and the plasma level of 8-iso were 0.69, 0.71 and 0.67, respectively (all P values < 0.01). Multivariate stepwise regression analysis showed MAGE, LBGI, HBGI entered final models (corrected R2 = 0.61, P < 0.01) with ß values of 0.64, 0.65 and 0.6 respectively (all P values < 0.01). The 28-day mortality in the RT-CGM group and the GM group was 9.84% and 30.65% (P < 0.01). The OR values of MAGE, hypoglycemia incidence, LBGI, HBGI and the plasma level of 8-iso for 28-day death were 2.14 (0.98 - 4.35), 3.43 (1.12 - 5.82), 2.67 (1.01 - 5.14), 1.32 (0.24 - 2.96) and 1.89 (0.67 - 3.44), respectively. CONCLUSION: RT-CGM can optimize the care in critically ill patients by improving hypoglycemia, hyperglycemia, glucose variability and oxidative stress and bring more detailed concern in the process, and to reduce the mortality.

Value of serum procalcitonin in evaluating the prognosis of sepsis in elderly patients with colorectal cancer undergoing emergency colorectal surgery.

Serum procalcitonin (PCT) levels may have predictive value in the prognosis of postoperative sepsis in elderly patients who have undergone colorectal surgery for colorectal cancer in intensive care units (ICUs). A prospective study involving 90 critically ill patients who underwent colorectal surgery for colorectal cancer in ICUs was performed. Twenty-eight patients were diagnosed with sepsis, in accordance with the American College of Chest Physicians/Society of Critical Care Medicine consensus criteria, and these patients were included in the sepsis group. Sixty-two patients, who were without evidence of sepsis, were enrolled in the control group. We measured the serum PCT concentrations preoperatively (immediately before induction of anesthesia), upon arrival in the ICU (ICU day 0), on the morning of the first postoperative day (postoperative day 1), and on the morning of the third postoperative day (postoperative day 3). The C-reactive protein (CRP) index, acute physiology and chronic health evaluation II (APACHE II) score, mechanical duration of ventilation, mortality rate, incidence of multiple organ failure, and usage of continuous renal replacement therapy were evaluated. The area under the curve for the receiver operating characteristic curve (AUC-ROCC) was measured to explore the association between the serum PCT and the prognosis. In the sepsis group, 12/28 patients died (mortality rate 43 %). In the control group, 6/62 patients died (mortality rate 9.7 %). On the first postoperative day, the serum PCT level was dramatically higher in the sepsis group than in the control group (2.71 ± 1.13 vs. 1.37 ± 0.57, P ≤ 0.05). The PCT level on the first postoperative day was distinctly higher than that measured upon arrival in the ICU (2.71 ± 1.13 vs. 1.31 ± 0.58, P ≤ 0.05). In the two groups, the CRP concentrations were both markedly higher on the first postoperative day than upon arrival in the ICU (138.89 ± 45.12 vs. 70.43 ± 23.54 in the sepsis group, and 133.13 ± 44.91 vs. 69.65 ± 24.98 in the control group, P ≤ 0.05). Linear regression analysis was performed. The results suggest that the PCT and APACHE-II scores were not significantly associated. On the first and third postoperative days, the PCT levels were associated with increased odds of sepsis (AUC-ROCC, 95 % confidence interval 0.817-0.973, P = 0.000, and 0.755-0.944, P = 0.000, respectively). The outcomes of patients in the sepsis group were worse than those in the control group. PCT levels appear to be early markers of postoperative sepsis in elderly patients undergoing colorectal surgery for colorectal cancer during the ICU course. These findings could allow for early identification of postoperative septic complications and be used for prognostic evaluation of these patients.

[Effect of continuous renal replacement therapy started at different time on patients with multiple organ dysfunction syndrome].

OBJECTIVE: To explore the effects of continuous renal replacement therapy (CRRT) on serum cytokines and prognosis in multiple organ dysfunction syndrome (MODS) patients based on different therapeutic opportunities. METHODS: A total of 34 MODS patients in the treatment of CRRT after admission to ICU of our hospital between July 2008 and October 2010 were recruited. Based on the time interval from the onset of MODS to the initiation of CRRT, the patients were stratified into early group (0 - 3 days, n = 16) and late group (4 - 10 days, n = 18). Both groups of MODS patients received conventional treatment in addition to 72 hours of high-volume hemofiltration (HVHF). The serum levels of such inflammatory mediators as interleukin (IL)-1ß, interleukin-1 receptor antagonist (IL-1Ra), IL-6, tumor necrosis factor (TNF)-α, soluble tumor necrosis factor receptor1 (sTNFR1) and IL-10 were detected by enzyme linked immunosorbent assay (ELISA) before CRRT (0 h) and 6, 12, 18, 24, 48 and 72 h during the treatment of CRRT. Dynamic APACHEII scores were also evaluated. RESULTS: (1) The early group had lower serum levels of IL-1ß, IL-6, IL-10 and higher IL-1Ra, L-1Ra/IL-1ß ratio at 72 h than those of 0 h (P < 0.05). And the late group had a declining serum level of IL-1ß, IL-6, TNF-α and IL-10 and a rising ratio of IL-1Ra and IL-1Ra/IL-1ß during the first 24 h (P < 0.05). As compared with the late group, the early group had a lower level of IL-10 [(25 ± 12) vs (51 ± 33) ng/L] and higher ratios of IL-1Ra and IL-1Ra/IL-1ß at 72 h [(1382 ± 899 vs (683 ± 188) ng/L, (54 ± 10) vs (23 ± 6)] (both P < 0.05). (2) The early group had a lower APACHEIIscore than the late group at 0 h (P < 0.05). APACHEII score at 72 h was significantly lower than 0 h in the early group. And there was no obvious change in the late group. There was no statistical difference in the numbers of MODS patients with dysfunctional organs number ≥ 4 at 0 h in both groups. The number of MODS patients with dysfunctional organs number ≥ 4 at 72 h was lower than 0 h in the early group (P < 0.05). And there was no statistical difference in the late group. CONCLUSION: Regulating the ratio of anti-inflammatory/pro-inflammatory mediators is critical in the immunomodulation of CRRT. And CRRT may provide more clinical benefits in the early phase (0 - 3 days) of MODS.

[Application of continuous veno-venous hemofiltration in patients with acute respiratory distress syndrome].

OBJECTIVE: To investigate the changes of interleukin (IL)-6 serum level in patients with acute respiratory distress syndrome (ARDS) and the effects of continuous renal replacement therapy (CRRT) on IL-6 level and its clinical significance. METHODS: Forty ARDS patients were randomly divided into 2 equal groups: Group A undergoing conventional treatment and Group B receiving conventional treatment plus CRRT at onset of ARDS. Serum IL-6 level was measured by enzyme linked immunosorbent assay (ELISA) at the onset (0 h) and 12, 24, 48, and 72 hours later. Dynamic APACHEII score was also evaluated at the time points of 0, 24, 48, and 72 h. The incidence of ventilator-associated pneumonia (VAP), intensive care unit (ICU) mortality rate, duration of total mechanical ventilation, and ICU stay were assessed. Twenty-five healthy examinees were used as controls. RESULTS: The serum IL-6 level of the whole ARDS patients was significantly higher then that of the normal controls (P < 0.01), and the serum IL-6 level of the ARDS patients who died was significantly higher than that of the ARDS patients who survived (P < 0.01). The IL-6 serum level was correlated well with the APACHEIIscore either in the survival subgroup or the non-survival subgroup (for the former: r = 0.560 P = 0.008, and for the latter: r = 0.518 P = 0.023). Group B, contrary to Group A, had persistently decreased serum IL-6 levels and APACHEII scores at the onset and during the progression of ARDS (all P < 0.05). The incidence of VAP in Group B was 45%, significantly lower than that in Group A (80%, P = 0.022) while the ICU mortality rate didn't differ between the two groups (40% vs 55%, P = 0.342). The duration of total mechanical ventilation and ICU stay of the Group B patients who underwent early CRRT were (12 +/- 5) days and (16 +/- 5) days respectively, both significantly shorter than those of Group A patients [(16 +/- 5) days, P = 0.027 and (19 +/- 5) days, P = 0.030]. CONCLUSION: The elevated serum IL-6 level in ARDS patients seems to be correlated well with the severity of lung injury, and appears to be a good marker to judge the prognosis of the disease combined with APACHEII score. In the early phase of ARDS, CRRT can decrease the high serum level of IL-6, shorten the duration of total mechanical ventilation and ICU stay, and decrease the incidence of VAP. Removal of the circulating proinflammatory cytokines by CRRT may be one of the most vital mechanisms to treat ARDS.