Resistin Associated With Cytokines and Endothelial Cell Adhesion Molecules Is Related to Worse Outcome in COVID-19.

Introduction: Resistin is reported to form a cytokine network and cause endothelial damage. The pathogenesis of coronavirus disease 2019 (COVID-19) remains unknown, but the association between cytokine storm and endothelial damage is crucial. This study aimed to evaluate resistin in COVID-19 pathogenesis compared with sepsis. Materials and Methods: First, we evaluated the association of plasma resistin levels and disease severity and clinical outcome in two large cohorts: a publicly available cohort including 306 COVID-19 patients in the United States (MGH cohort) and our original cohort including only intubated 113 patients in Japan (Osaka cohort 1). Second, to understand pathogenesis, we evaluate resistin, cytokines and endothelial cell adhesion molecules in COVID-19 compared with sepsis. Blood samples were collected from 62 ICU-treated COVID-19 patients and 38 sepsis patients on day 1 (day of ICU admission), days 2-3, days 6-8, and from 18 healthy controls (Osaka cohort 2). The plasma resistin, inflammatory cytokines (IL-6, IL-8, MCP-1 and IL-10) and endothelial cell adhesion molecules (ICAM-1 and VCAM-1) were compared between patients and control. Correlations among resistin, inflammatory cytokines and endothelial cell adhesion molecules were evaluated in COVID-19 and sepsis. Results: In the MGH cohort, the day 1 resistin levels were associated with disease severity score. The non-survivors showed significantly greater resistin levels than survivors on days 1, 4 and 8. In the Osaka cohort 1, 28-day non-survivors showed significantly higher resistin levels than 28-day survivors on days 6-8. Patients with late recovery (defined as the day of weaning off mechanical ventilation >12 or death) had significantly higher resistin levels than those with early recovery on day 1 and days 6-8. In the Osaka cohort 2, plasma resistin levels were elevated in COVID-19 and sepsis patients compared to controls at all measurement points and were associated with inflammatory cytokines and endothelial cell adhesion molecules. Conclusion: Resistin was elevated in COVID-19 patients and was associated with cytokines and endothelial cell adhesion molecules. Higher resistin levels were related to worse outcome.

A continuous intravenous insulin infusion protocol to manage high-dose methylprednisolone-induced hyperglycemia in patients with severe COVID-19.

BACKGROUND: Many patients with severe COVID-19 have impaired glucose tolerance, and steroid therapy is a standard treatment. Thus, good glycemic control is important and correlates with better patient outcomes. We began using a continuous intravenous insulin infusion protocol for glycemic control whose infusion rate changes based on the currently measured value and previous value. This study aimed to evaluate this protocol for COVID-19 patients requiring mechanical ventilation. METHODS: This single-center, retrospective, case control study was conducted on all adult patients who required mechanical ventilation for severe COVID-19 pneumonia admitted to our critical care center from April 1, 2020 through June 20, 2021. Blood glucose levels were measured in all patients every 4 h after admission. We started using the insulin infusion protocol from August 1, 2020. Patients before starting the protocol comprised the non-protocol group and those after starting the protocol comprised the protocol group. Blood glucose levels and hypo- or hyperglycemia events were compared between groups. We also surveyed ICU nurses about their experience using the protocol. RESULTS: During the study period, 173 patients with COVID-19 were admitted. After 15 patients were excluded for several reasons, the study included 158 patients: non-protocol group (n = 14) and protocol group (n = 144). In the initial phase (days 1-2), blood glucose levels of the protocol group were higher compared with the non-protocol group, and as the number of measurements increased, blood glucose levels were gradually brought under control within the target range in the protocol group. Almost no hypoglycemic events (blood glucose < 80 mg/dL) were detected in either group. The rate of hyperglycemia (blood glucose > 300 mg/dL) was about 5-10% in the initial phase in the protocol group and about 10-15% in the early phase (days 3-4) in the non-protocol group. The questionnaire survey revealed that 80% of ICU nurses responded favorably. CONCLUSIONS: This insulin protocol gradually brought the blood glucose level within target levels in severe COVID-19 patients treated with high-dose steroid. Some hyperglycemia events were detected despite patients being under the protocol in the initial phase, and thus, minor modifications of the protocol might be required in the initial phase.

Comparison between midazolam and propofol in acute phase for ventilated patients with sepsis: a post-hoc analysis of the DESIRE trial.

Aim: There are few assessments of sedatives during the acute phase under sedation protocols for patients with sepsis. We aimed to compare the influence of different sedation strategies using midazolam and propofol under light sedation on clinical outcomes of ventilated patients with sepsis. Methods: This study was a post-hoc analysis of data from the dexmedetomidine for sepsis in the ICU Randomized Evaluation (DESIRE) trial. Patients were divided into propofol and midazolam groups based on continuously used drug, and sedation control between groups compared on day three. We assessed the incidence of delirium, length of ICU stay, number of ventilator-free days within the first 28 days, and mortality after 28 days. Results: The midazolam and propofol groups consisted of 51 and 66 patients, respectively. Both groups had similar characteristics, except for age and emergency surgery. The number of well-controlled sedation patients in the propofol group on day three was significantly higher than that in the midazolam group (odds ratio [OR] 3.9, 95% CI [1.30, 11.7]). The incidence of daily coma and delirium within the initial week was different between groups and increased with midazolam administration (P = 0.0138). The number of Confusion Assessment Method for ICU-positive patients was significantly higher in the midazolam group than in the propofol group (OR 5.71, 95% CI [2.30, 14.2]). Conclusion: In patients with sepsis required mechanical ventilation, sedation with midazolam based on a light sedation protocol may be associated with inappropriate sedation during the acute phase, with increased coma and delirium as compared to propofol.

Radiation Emergency Medical Preparedness in Japan: A Survey of Nuclear Emergency Core Hospitals.

OBJECTIVE: Based on experiences following the Great East Japan Earthquake and nuclear power plant accident in 2011, Nuclear Emergency Core Hospitals (NECHs) were designated as centers for radiation disaster management in Japan. This study aimed to investigate their current status and identify areas for improvement. METHODS: This cross-sectional study was conducted in October 2018. Demographic data were collected by a questionnaire with free text responses about attitudes toward NECHs. Considerations regarding risk communications during a radiation disaster were analyzed using qualitative text mining analysis. RESULTS: A total of 36 hospitals participated in this study. Only 31% of NECHs anticipated a radiation disaster. The importance of business continuity plans and risk communications was shown. Text analysis identified 7 important categories for health care workers during a radiation disaster, including media response, communications to hospital staff, risk communications, radiation effects on children, planning for a radiation disaster in the region, rumors, and the role in the region. CONCLUSION: The radiation disaster medical system and NECHs in Japan were surveyed. The importance of risk communications, planning for a radiation disaster in each region, and the role in the region are identified as issues that need to be addressed.

Simple prognostic factors and change of inflammatory markers in patients with severe coronavirus disease 2019: a single-center observational study.

AIM: The aim of this study was to investigate the prognostic factors and evaluate the change in inflammatory markers of patients with coronavirus disease 2019 (COVID-19) requiring mechanical ventilation. METHODS: This retrospective observational study conducted from April 1, 2020, to February 18, 2021, included 97 adult patients who required mechanical ventilation for severe COVID-19 pneumonia and excluded nonintubated patients with a positive COVID-19 polymerase chain reaction test and those who had any obvious bacterial infection on admission. All patients were followed up to discharge or death. We obtained clinical information and laboratory data including levels of presepsin, interleukin-6, procalcitonin, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody every day. Poor outcome was defined as death or receiving a tracheostomy during hospitalization, and favorable outcome was defined as discharge after extubation. RESULTS: Differences (median [interquartile range]) were detected in age (76 [70-82] versus 66 [55-74] years), day from the onset of first symptoms to admission for mechanical ventilation (5 [3-7] versus 10 [8-12] days), and P/F ratio (i.e., ratio of arterial oxygen concentration to the fraction of inspired oxygen) after intubation (186 [149-251] versus 236 [180-296]) in patients with poor outcome versus those with favorable outcome on admission. Serum SARS-CoV-2 antibody levels had already increased on admission in patients with favorable outcome. We determined the day from the onset of first symptoms to admission for mechanical ventilation to be one of the independent prognostic factors of patients with COVID-19 (adjusted odds ratio 0.69, confidence interval 0.56-0.85). CONCLUSION: These results may contribute to understanding the mechanism of progression in severe COVID-19 and may be helpful in devising an effective therapeutic strategy.

Serial computed tomography findings of Coronavirus disease 2019 (COVID-19) pneumonia treated with favipiravir and steroid therapy: report of 11 cases.

BACKGROUND: This study evaluated the time course of computed tomography (CT) findings of patients with COVID-19 pneumonia who required mechanical ventilation and were treated with favipiravir and steroid therapy. RESULTS: Eleven patients with severe COVID-19 pneumonia were included. CT findings assessed at the three time points showed that all patients had ground-glass opacities (GGO) and consolidation and mixed pattern at intubation. Consolidation and mixed pattern disappeared in most of the patients whereas GGO persisted in all patients at 1-month follow-up. In addition to GGO, a subpleural line and bronchus distortion and bronchial dilatation were frequent findings. The degree of resolution of GGO varied depending on each patient. The GGO score correlated significantly with the time from symptoms onset to initiation of steroid therapy (ρ = 0.707, p = 0.015). CONCLUSIONS: At 1-month follow-up after discharge, non-GGO lesions were absorbed almost completely, and GGO were a predominant CT manifestation. Starting steroid therapy earlier after onset of symptoms in severe COVID-19 pneumonia may reduce the extent of GGO at 1-month follow-up.

Effect of age on dexmedetomidine treatment for ventilated patients with sepsis: a post-hoc analysis of the DESIRE trial.

AIM: There are no definitive data to determine whether age influences the effects of dexmedetomidine (DEX) treatment. Thus, we investigated whether older age was associated with more favorable sedative action by DEX in sepsis patients who required mechanical ventilation. METHODS: This study involved a post-hoc analysis of data from the Dexmedetomidine for Sepsis in the ICU Randomized Evaluation (DESIRE) trial. The patients were categorized based on median age into elderly and younger groups. The two groups were then compared during the first 7 days after ventilation based on proportion of patients with well-controlled sedation (Richmond Agitation-Sedation Scale score between -3 and +1), days free from delirium (based on the Confusion Assessment Method for ICU), and days free from coma (Richmond Agitation-Sedation Scale score between -4 and -5). RESULTS: One hundred and one patients were assigned to the elderly group and 100 patients were assigned to the younger group. In the elderly group, 50 patients received DEX treatment and 51 patients received non-DEX treatment, with the DEX arm having significantly better-controlled sedation (range, 14-52% versus 16-27%; P = 0.01). In the younger group, 50 patients received DEX treatment and 50 patients received non-DEX treatment, with no significant difference in the proportions of well-controlled sedation (range, 20-64% versus 24-60%; P = 0.73). There were no significant differences in the numbers of days free from delirium or coma between the groups. CONCLUSION: In elderly sepsis patients who require ventilation, dexmedetomidine could be more effective than other sedative agents for achieving proper sedation.

Cytokine Elevation in Severe COVID-19 From Longitudinal Proteomics Analysis: Comparison With Sepsis.

Introduction: Coronavirus disease 2019 (COVID-19) is a new viral disease. Uncontrolled inflammation called "cytokine storm" is reported to contribute to disease pathogenesis as well as sepsis. We aimed to identify cytokines related to the pathogenesis of COVID-19 through a proteomics analysis of 1463 plasma proteins, validate these cytokines, and compare them with sepsis. Materials and Methods: In a derivation cohort of 306 patients with COVID-19, 1463 unique plasma proteins were measured on days 1, 4, and 8. Cytokines associated with disease severity and prognosis were derived. In a validation cohort of 62 COVID-19 patients and 38 sepsis patients treated in the intensive care unit [ICU], these derived cytokines were measured on days 1 (day of ICU admission), 2-3, and 6-8 (maximum: 3 time points/patient). Derived cytokines were compared with healthy controls and between COVID-19 and sepsis patients, and the associations with prognosis were evaluated. The time to wean off mechanical ventilation (MV) was evaluated only for COVID-19. Results: IL-6, amphiregulin, and growth differentiation factor (GDF)-15 were associated with disease severity and prognosis in the derivation cohort. In the validation cohort, IL-6 and GDF-15 were elevated in COVID-19 and sepsis on day 1, and the levels of these cytokines were higher in sepsis than in COVID-19. IL-6 and GDF-15 were associated with prognosis in sepsis. Cox proportional hazards model with time as a dependent covariate showed a significant relationship between plasma GDF-15 level and time to wean off MV (hazard ratio, 0.549 [95% confidence level, 0.382-0.789]). The GDF-15 level at ICU admission predicted late recovery. Conclusion: GDF-15 and IL-6 derived from proteomics analysis were related with disease severity of COVID-19. Their values were higher in sepsis than in COVID-19 and were associated with prognosis in sepsis. In COVID-19 patients treated in the ICU, GDF-15 was associated with the time to wean off MV and better predicted late recovery.

Utility of a prediction model for delirium in intensive care unit patients (PRE-DELIRIC) in mechanically ventilated patients with sepsis.

AIM: Delirium frequently develops in patients with sepsis during their intensive care unit (ICU) stay, which is associated with increased morbidity and mortality. A prediction model for delirium in patients in ICU, PRE-DELIRIC, has been utilized in overall ICU patients, but its utility is uncertain among patients with sepsis. This study aims to examine the utility of PRE-DELIRIC to predict delirium in mechanically ventilated patients with sepsis. METHODS: This is a post hoc analysis of a randomized clinical trial in eight Japanese ICUs, which aimed to evaluate the sedative strategy with/without dexmedetomidine in adult mechanically ventilated patients with sepsis. The Confusion Assessment Method for the ICU was used every day to assess for delirium throughout their ICU stay. We excluded patients who were delirious on the first day of ICU, those who were under sustained coma throughout their ICU stay, and those who stayed in the ICU less than 24 h. The discriminative ability of PRE-DELIRIC was evaluated by measuring the area under the receiver operating characteristic curve (AUROC). RESULTS: Of the 201 patients enrolled in the trial, we analyzed 158 patients. The mean age was 69.4 ± 14.0 years, and 99 patients (63%) were men. Delirium occurred at least once during the ICU stay of 63 patients (40%). The AUROC of PRE-DELIRIC was 0.60 (95% confidence interval, 0.50-0.69). Subgroup analyses indicated that PRE-DELIRIC was useful in those with Sequential Organ Failure Assessment score >8 with AUROC of 0.65 (95% confidence interval, 0.51-0.77). CONCLUSIONS: The PRE-DELIRIC model could not predict delirium in mechanically ventilated patients with sepsis.

Effect of dexmedetomidine on inflammation in patients with sepsis requiring mechanical ventilation: a sub-analysis of a multicenter randomized clinical trial.

BACKGROUND: Administration of dexmedetomidine has been reported to improve inflammatory response in animals. We explored the effects of administering dexmedetomidine on the levels of C-reactive protein (CRP) and procalcitonin, and thus on inflammation, in patients with sepsis enrolled in a randomized clinical trial. METHODS: The DESIRE trial was a multicenter randomized clinical trial in which adult patients with sepsis were sedated with (DEX group) or without (non-DEX group) dexmedetomidine while on mechanical ventilators. As a prespecified sub-analysis, we compared CRP and procalcitonin levels during the first 14 days of treatment between the two groups. The 14-day mortality rate, albumin level, and the number of patients with disseminated intravascular coagulation (DIC) were also assessed. We used generalized linear models to estimate the differences in these outcomes between groups. We also used the Kaplan-Meier method to estimate the 14-day mortality rate and the log-rank test to assess between-group differences. RESULTS: Our study comprised 201 patients: 100 in the DEX group and 101 in the non-DEX group. CRP and procalcitonin levels were lower in the DEX vs. non-DEX group during the 14-day treatment period [CRP-range, 5.6-20.3 vs. 8.3-21.1 mg/dL (P = 0.03); procalcitonin-range, 1.2-37.4 vs. 1.7-52.9 ng/mL (P = 0.04)]. Albumin levels were higher in the DEX group (range, 2.3-2.6 g/dL) than in the non-DEX group (range, 2.1-2.7 g/dL; P = 0.01). The percentage of patients with DIC did not significantly differ between the groups (range, 21-59% and 17-56% for the DEX and non-DEX groups, respectively; P = 0.49). The 14-day mortality rates in the DEX and non-DEX groups were 13 and 21%, respectively (P = 0.16). CONCLUSION: Sedation using dexmedetomidine reduced inflammation in patients with sepsis requiring mechanical ventilation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01760967 . Registered on 4 January 2013.

Dexmedetomidine improved renal function in patients with severe sepsis: an exploratory analysis of a randomized controlled trial.

BACKGROUND: Dexmedetomidine has been reported to improve organ dysfunction in critically ill patients. In a recent randomized controlled trial (Dexmedetomidine for Sepsis in Intensive Care Unit (ICU) Randomized Evolution [DESIRE]), we demonstrated that dexmedetomidine was associated with reduced mortality risk among patients with severe sepsis. We performed this exploratory sub-analysis to examine the mechanism underlying improved survival in patients sedated with dexmedetomidine. METHODS: The DESIRE trial compared a sedation strategy with and without dexmedetomidine among 201 mechanically ventilated adult patients with sepsis across eight ICUs in Japan. In the present study, we included 104 patients with Acute Physiology and Chronic Health Evaluation II (APACHE II) scores of ≥ 23 (54 in the dexmedetomidine [DEX] group and 50 in the non-dexmedetomidine [non-DEX] group). Initially, we compared the changes in the sequential organ failure assessment (SOFA) scores from the baseline within 6 days after randomization between groups. Subsequently, we evaluated the variables comprising the organ component of the SOFA score that showed relevant improvement in the initial comparison. RESULTS: The mean patient age was 71.0 ± 14.1 years. There was no difference in the median APACHE II score between the two groups (29 [interquartile range (IQR), 25-31] vs. 30 [IQR, 25-33]; p = 0.35). The median SOFA score at the baseline was lower in the DEX group (9 [IQR, 7-11] vs. 11 [IQR, 9-13]; p = 0.01). While the renal SOFA subscore at the baseline was similar for both groups, it significantly decreased in the DEX group on day 4 (p = 0.02). During the first 6 days, the urinary output was not significantly different (p = 0.09), but serum creatinine levels were significantly lower (p = 0.04) in the DEX group. The 28-day and in-hospital mortality rates were significantly lower in the DEX group (22% vs. 42%; p = 0.03, 28% vs. 52%; p = 0.01, respectively). CONCLUSION: A sedation strategy with dexmedetomidine is associated with improved renal function and decrease mortality rates among patients with severe sepsis. TRIAL REGISTRATION: This trial was registered on ClinicalTrials.gov (NCT01760967) on January 1, 2013.

Incidence, risk factors, and outcomes for sepsis-associated delirium in patients with mechanical ventilation: A sub-analysis of a multicenter randomized controlled trial.

PURPOSE: This study aimed to investigate incidence, risk factors, and outcomes for sepsis-associated delirium (SAD) in mechanically ventilated patients. MATERIALS AND METHODS: We performed a retrospective post-hoc analysis of the DExmedetomidine for Sepsis in Intensive care unit Randomized Evaluation (DESIRE) trial. Outcomes included 28-day mortality, ventilator-free days, length of ICU stay, self-extubation, and re-intubation. Multivariable analysis was performed to identify variables independently associated with SAD. RESULTS: We retrospectively divided the patients into two groups: delirium group (n = 89) and non-delirium group (n = 98). There were no significant differences between the groups in 28-day mortality, self-extubation, and re-intubation. The number of ventilator-free days was significantly less in the delirium vs. non-delirium group (17 vs. 22 days, p = .006), and the length of ICU stay was significantly longer in the delirium group (10 vs. 5 days, p = .04). Multivariable analyses revealed that emergency surgery, more doses of midazolam, and fentanyl were independent predictors for SAD. CONCLUSIONS: SAD was associated with a less number of ventilator-free days and longer length of ICU stay. Emergency surgery, more doses of midazolam, and fentanyl may be independent risk factors for SAD in mechanically ventilated patients with sepsis.

The Development of an Active Learning Program for the Medical Responders in a Nuclear Disaster.

OBJECTIVE: In Japan, with the revision of the Nuclear Emergency Response Guidelines in 2015, nuclear emergency medical assistance teams responsible for the medical treatment in the acute phase of nuclear disaster have been developed nationwide. The purpose of this research is to develop active learning materials for the education of medical staff, to confirm the educational effect of the materials, and to identify the gaps in nuclear disaster risk reduction in Japan. METHODS: We established a working group and created active learning materials. We trained members of the nuclear emergency medical assistance team using the developed active learning materials and then conducted a questionnaire survey for trainees who participated in the training. RESULTS: Regarding the developed teaching materials, out of 33 trainees, 33 (100%) answered "easy to understand" or "a little understandable" to the item dealing with how to use the radiation detectors and attaching/detaching personal protective equipment. Regarding the simulation about practicing hospital support and medical provision, 3 (8%) answered "a little confusing." CONCLUSION: The study demonstrated that the developed materials have an educational effect. Additionally, the results of the trainee questionnaire showed the necessity for improvement in the triage system and new protocols to help both the patients and responders.

Treatment strategy for a penetrating stab wound to the vertebral artery: a case report.

CASE: Vertebral artery injury is a low-frequency but high-mortality injury. The surgical approach to a bleeding vertebral artery injury is one of the most difficult procedures in trauma surgery.A 64-year-old woman was transported to our emergency department after being stabbed in the middle side of the right neck with a large kitchen knife. Her initial hospital examination indicated a shock state, and computed tomography images revealed a right vertebral artery injury. We undertook angiography and transcatheter arterial embolization before the surgical operation. OUTCOME: The patient suffered right upper extremity paralysis due to brachial plexus injury and was transferred to another hospital for rehabilitation on the 24th hospital day. CONCLUSION: Computed tomography angiography for diagnosis and interventional radiology treatment are useful for the management of penetrating neck trauma. Transcatheter arterial embolization for vertebral artery injury is safe and allows for easy control of bleeding compared to a surgical procedure.

Necrotizing fasciitis of the thigh due to penetrated descending colon cancer: a case report.

BACKGROUND: Necrotizing fasciitis (NF) caused by colorectal cancer is rare, and very few cases associated with colon cancer have been reported. We describe the case of a patient with NF in the left thigh due to penetration of descending colon cancer who was treated with one-stage surgical resection without creating a stoma. CASE PRESENTATION: An 80-year-old woman was brought to our hospital complaining of fever and difficulty with body movement. A physical examination showed subcutaneous emphysema from the left lower abdomen to the left femoral region. CT showed abscess formation with emphysema around the descending colon, and the wall of the descending colon was thickened, which led to suspicion of colon cancer. The patient was subsequently diagnosed with NF due to penetration of descending colon cancer. Left hemicolectomy and open drainage of the left femoral region was performed. The histopathological findings were well-differentiated adenocarcinoma, with the tumor grown through the serosa (T4a) and with no metastasis to lymph nodes (N0). After surgery, the patient received intensive care for septic shock and lavage of the open drainage site, and sepsis was controlled progressively. After closure of the drainage site, the patient was transferred to a different hospital at 26 days after surgery, and she has had 6-month relapse-free survival. CONCLUSIONS: In NF caused by colon cancer, early one-stage resection may improve the oncological outcome. Physical status should be assessed carefully, and one-stage resection should be considered if the patient has the capacity to undergo this procedure.

Mortality Effects of Prolonged Hemoperfusion Therapy Using a Polymyxin B-Immobilized Fiber Column for Patients with Septic Shock: A Sub-Analysis of the DESIRE Trial.

BACKGROUND/AIMS: The optimal duration of hemoperfusion therapy with a polymyxin B-immobilized fiber column has not yet been verified. METHODS: This analysis examined whether hemoperfusion therapy with a polymyxin B-immobilized fiber column lasting longer than 2 h (prolonged polymyxin) improved outcomes for patients with septic shock compared to 2-h polymyxin therapy (sub-analysis of data from the DESIRE trial). RESULTS: The 2-h and prolonged polymyxin groups contained 22 and 14 patients, respectively. Both groups had similar characteristics. The polymyxin duration per session in the prolonged polymyxin group was significantly longer (median, 5.5 h) than in the 2-h polymyxin group (p < 0.01). The 28-day mortality rate was significantly higher in the 2-h polymyxin group (7, 31.8%) than in the prolonged polymyxin group (0, 0%; p = 0.019). CONCLUSION: Prolonged polymyxin therapy might be associated with better clinical outcomes than 2-h polymyxin therapy in patients with septic shock. Video Journal Club "Cappuccino with Claudio Ronco" at http://www.karger.com/?doi=491744.

Effect of norepinephrine dosage on mortality in patients with septic shock.

BACKGROUND: Use of high-dose norepinephrine is thought to have an immunosuppressive action that increases mortality. This study aimed to evaluate the correlation between norepinephrine dosage and prognosis of patients with septic shock. METHODS: This study was a nested cohort of the DExmedetomidine for Sepsis in Intensive Care Unit Randomized Evaluation (DESIRE) trial. We evaluated 112 patients with septic shock and an initial Sequential Organ Failure Assessment Cardiovascular (SOFA-C) category score > 2 and initial lactate level > 2 mmol/L. We divided the patients into two groups according to the norepinephrine dosage administered over the initial 7 days: high dose (≥ 416 µg/kg/week) (H group, n = 56) and low dose (< 416 µg/kg/week) (L group, n = 56). The primary outcome of interest was 28-day mortality. Secondary outcomes were ventilator-free days, initial 24-h infusion volume, initial 24- to 48-h infusion volume, and the need for renal replacement therapy. For comparisons between the H group and L group, we used the chi-square test or Fisher's exact test for categorical variables and the t test or Wilcoxon rank sum test for continuous variables. For time-to-event outcomes, Cox proportional hazards models were used. Kaplan-Meier survival curves were created for graphical representation. RESULTS: Patient characteristics appeared to be similar between the two groups except for the SOFA-C score and fibrinogen degradation product level. The cumulative incidence of death at 28 days was 29.9% (16 patients) in the L group and 29.7% (15 patients) in the H group (p = 0.99). The median number of 28-day ventilator-free days was 20 (0, 25) in the L group and 16 (0, 22) in the H group (p < 0.05). Initial infusion volume at 0-24 h in the H group was significantly higher than that in the L group (p = 0.004). Infusion volume at 24-48 h in the H group was also significantly higher than that in the L group (p = 0.03). CONCLUSIONS: No statistically significant difference was observed in 28-day mortality between patients with septic shock treated with high-dose norepinephrine compared with those treated with low-dose norepinephrine. However, the number of ventilator-free days in the L group was higher than that in the H group. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01760967 Date of trial registration: January 4, 2013.

Effect of Dexmedetomidine on Lactate Clearance in Patients With Septic Shock: A Subanalysis of a Multicenter Randomized Controlled Trial.

Lactate clearance is useful to guide initial resuscitation of patients with septic shock. We conducted this study to evaluate whether dexmedetomidine increases lactate clearance in patients with septic shock. This was a randomized controlled trial that involved a post hoc subgroup analysis. Adult patients with septic shock under ventilation were randomized to receive sedation strategy with or without dexmedetomidine (60 in the dexmedetomidine and 51 in the nondexmedetomidine groups). The primary outcome was the lactate clearance at 6 h, defined as the percent decrease in lactate from randomization to 6 h after. The median Acute Physiology and Chronic Health Evaluation II score was 25 (interquartile range 19-31). The median serum lactate value at randomization was lower in the dexmedetomidine group than in the nondexmedetomidine group (4.0 mmol/L vs. 4.8 mmol/L; P = 0.053). The lactate clearance at 6 h was higher in the dexmedetomidine group, although this was not statistically significant (23.3 ±â€Š29.8 vs. 11.1 ±â€Š54.4, mean difference 12.2, 95% confidence interval (CI), -4.4 to 28.8). After adjusting for the lactate level at randomization, lactate clearance at 6 h was significantly higher in the dexmedetomidine group (adjusted mean difference 18.5, 95% CI, 2.2-34.9). There was no statistically significant difference in the 28-day mortality between the dexmedetomidine and the nondexmedetomidine groups (13 [22%] vs. 18 [35%] patients, P = 0.11). In conclusion, among mechanically ventilated patients with septic shock, sedation with dexmedetomidine resulted in increased lactate clearance compared with sedation without dexmedetomidine.