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Abstract Rationale Recent retrospective evidence suggests the efficacy of early norepinephrine administration during resuscitation; however, prospective data to support this assertion are scarce. Objectives To conduct a phase II trial evaluating the hypothesis that early low-dose norepinephrine in adults with sepsis with hypotension increases shock control by 6 hours compared with standard care. Methods This single-center, randomized, double-blind, placebo-controlled clinical trial was conducted at Siriraj Hospital, Bangkok, Thailand. The study enrolled 310 adults diagnosed with sepsis with hypotension. The patients were randomly divided into two groups: early norepinephrine (n = 155) and standard treatment (n = 155). The primary outcome was shock control rate (defined as achievement of mean arterial blood pressure ≥65 mm Hg, with urine flow ≥0.5 ml/kg/h for 2 consecutive hours, or decreased serum lactate ≥10% from baseline) by 6 hours after diagnosis. Measurements and Main Results The patients in both groups were well matched in background characteristics and disease severity. Median time from emergency room arrival to norepinephrine administration was significantly shorter in the early norepinephrine group (93 vs. 192 min; P < 0.001). Shock control rate by 6 hours was significantly higher in the early norepinephrine group (118/155 [76.1%] vs. 75/155 [48.4%]; P < 0.001). The 28-day mortality was not different between groups: 24/155 (15.5%) in the early norepinephrine group versus 34/155 (21.9%) in the standard treatment group (P = 0.15). The early norepinephrine group was associated with lower incidences of cardiogenic pulmonary edema (22/155 [14.4%] vs. 43/155 [27.7%]; P = 0.004) and new-onset arrhythmia (17/155 [11%] vs. 31/155 [20%]; P = 0.03). Conclusions Early norepinephrine was significantly associated with increased shock control by 6 hours. Further studies are needed before this approach is introduced in clinical resuscitation practice. Clinical trial registered with www.clinicaltrials.gov (NCT01945983) (CENSER trial).

Background Authors of recent meta-analyses have reported that prolonged glucocorticoid treatment is associated with significant improvements in patients with severe pneumonia or acute respiratory distress syndrome (ARDS) of multifactorial etiology. A prospective randomized trial limited to patients with sepsis-associated ARDS is lacking. The objective of our study was to evaluate the efficacy of hydrocortisone treatment in sepsis-associated ARDS. Methods In this double-blind, single-center (Siriraj Hospital, Bangkok), randomized, placebo-controlled trial, we recruited adult patients with severe sepsis within 12 h of their meeting ARDS criteria. Patients were randomly assigned (1:1 ratio) to receive either hydrocortisone 50 mg every 6 h or placebo. The primary endpoint was 28-day all-cause mortality; secondary endpoints included survival without organ support on day 28. Results Over the course of 4 years, 197 patients were randomized to either hydrocortisone ( n  = 98) or placebo ( n  = 99) and were included in this intention-to-treat analysis. The treatment group had significant improvement in the ratio of partial pressure of oxygen in arterial blood to fraction of inspired oxygen and lung injury score ( p  = 0.01), and similar timing to removal of vital organ support (HR 0.74, 95 % CI 0.51–1.07; p  = 0.107). After adjustment for significant covariates, day 28 survival was similar for the whole group (HR 0.80, 95 % CI 0.46–1.41; p  = 0.44) and for the larger subgroup ( n  = 126) with Acute Physiology and Chronic Health Evaluation II score <25 (HR 0.57, 95 % CI 0.24–1.36; p  = 0.20). With the exception of hyperglycemia (80.6 % vs. 67.7 %; p  = 0.04), the rate of adverse events was similar. Hyperglycemia had no impact on outcome. Conclusions In sepsis-associated ARDS, hydrocortisone treatment was associated with a significant improvement in pulmonary physiology, but without a significant survival benefit. Trial registration ClinicalTrials.gov identifier NCT01284452 . Registered on 18 January 2011.

Objective To compare the outcomes of patients with and without a mean serum potassium (K+) level within the recommended range (3.5–4.5 mEq/L). Methods This prospective cohort study involved patients admitted to the medical intensive care unit (ICU) of Siriraj Hospital from May 2012 to February 2013. The patients’ baseline characteristics, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, serum K+ level, and hospital outcomes were recorded. Patients with a mean K+ level of 3.5 to 4.5 mEq/L and with all individual K+ values of 3.0 to 5.0 mEq/L were allocated to the normal K+ group. The remaining patients were allocated to the abnormal K+ group. Results In total, 160 patients were included. Their mean age was 59.3±18.3 years, and their mean APACHE II score was 21.8±14.0. The normal K+ group comprised 74 (46.3%) patients. The abnormal K+ group had a significantly higher mean APACHE II score, proportion of coronary artery disease, and rate of vasopressor treatment. An abnormal serum K+ level was associated with significantly higher ICU mortality and incidence of ventricular fibrillation. Conclusion Critically ill patients with abnormal K+ levels had a higher incidence of ventricular arrhythmia and ICU mortality than patients with normal K+ levels.

Background Approximately 13-31% of medical critical care patients develop deep vein thrombosis (DVT). However, there are very few reports regarding the incidence of DVT among Asian patients without routine prophylaxis. The objectives of this study were to assess the prevalence and incidence proportion of proximal DVT in Thai medical critical care patients not receiving thrombosis prophylaxis. Methods We conducted a prospective cohort study in medical critical care patients admitted to Siriraj Hospital, Thailand between November 2008 and November 2009. Patients were screened for proximal DVT by duplex ultrasonography performed 48 h, 7, 14 and 28 days after admission. Primary outcomes were prevalence and incidence proportion of DVT. Factors associated with the development of proximal DVT were evaluated by multivariate analysis. Results Of the 158 patients enrolled in the study, 25 had proximal DVT (15.8%). Nine patients (5.7%) had DVT on the first test at 48 h, while 10 (6.3%), 2 (1.3%) and 4 (2.5%) patients had developed DVT on days 7, 14, and 28, respectively. Thus, the prevalence at the beginning of the study was 5.7% (95%CI 2.6-10.5) and the incidence proportion was 10.1% (95%CI 5.9-15.9). The multivariate analysis showed that age (odds ratio [OR] per 1-year increase was 1.04, 95% confidence interval [CI] 1.01-1.07), female gender (OR 4.05, 95%CI 1.51-12.03), femoral venous catheter (OR 11.18, 95%CI 3.19-44.83), and the absence of platelet transfusion (OR 0.07, 95%CI 0.003-0.43) were associated with the development of proximal DVT. Patients with proximal DVT had a longer hospital length of stay (22 days [IQR 11-60] vs. 14 days [7-23], p = 0.03) and spent more time on mechanical ventilation (10 days (3.3-57) vs. 6 days (3-12), p = 0.053) than patients without DVT. Patient mortality was not affected by the presence of DVT (52% vs. 38.3%, p = 0.29). Conclusions Routine thromboprophylaxis is not used in our institution and the prevalence and incidence proportion of proximal DVT in Asian medical critical care patients were both substantial. Patients with older age, female gender, an intravenous femoral catheter, and the absence of platelet transfusion all had a higher chance of developing proximal DVT.

Background: Ventilator-induced lung injury (VILI) presents a grave risk to acute respiratory failure patients undergoing mechanical ventilation. Low tidal volume (LTV) ventilation has been advocated as a protective strategy against VILI. However, the effectiveness of limited driving pressure (plateau pressure minus positive end-expiratory pressure) remains unclear. Objectives: This study evaluated the efficacy of LTV against limited driving pressure in preventing VILI in adults with respiratory failure. Design: A single-centre, prospective, open-labelled, randomized controlled trial. Methods: This study was executed in medical intensive care units at Siriraj Hospital, Mahidol University, Bangkok, Thailand. We enrolled acute respiratory failure patients undergoing intubation and mechanical ventilation. They were randomized in a 1:1 allocation to limited driving pressure (LDP; ⩽15 cmH2O) or LTV (⩽8 mL/kg of predicted body weight). The primary outcome was the acute lung injury (ALI) score 7 days post-enrolment. Results: From July 2019 to December 2020, 126 patients participated, with 63 each in the LDP and LTV groups. The cohorts had the mean (standard deviation) ages of 60.5 (17.6) and 60.9 (17.9) years, respectively, and they exhibited comparable baseline characteristics. The primary reasons for intubation were acute hypoxic respiratory failure (LDP 49.2%, LTV 63.5%) and shock-related respiratory failure (LDP 39.7%, LTV 30.2%). No significant difference emerged in the primary outcome: the median (interquartile range) ALI scores for LDP and LTV were 1.75 (1.00–2.67) and 1.75 (1.25–2.25), respectively (p = 0.713). Twenty-eight-day mortality rates were comparable: LDP 34.9% (22/63), LTV 31.7% (20/63), relative risk (RR) 1.08, 95% confidence interval (CI) 0.74–1.57, p = 0.705. Incidences of newly developed acute respiratory distress syndrome also aligned: LDP 14.3% (9/63), LTV 20.6% (13/63), RR 0.81, 95% CI 0.55–1.22, p = 0.348. Conclusions: In adults with acute respiratory failure, the efficacy of LDP and LTV in averting lung injury 7 days post-mechanical ventilation was indistinguishable. Clinical trial registration: The study was registered with the ClinicalTrials.gov database (identification number NCT04035915). Plain language summary Limited breathing pressure or low amount of air given to the lung; which one is better for adults who need breathing help by ventilator machine We conducted this research at Siriraj Hospital in Bangkok, Thailand, aiming to compare two ways of helping patients with breathing problems. We studied 126 patients who were randomly put into two groups. One group received a method where the pressure during breathing was limited (limited driving pressure: LDP), and the other group got a method where the amount of air given to the lungs was kept low (low tidal volume: LTV). We checked how bad the lung injury was at seven days later. The results showed that there was no difference between the two methods. Both ways of helping patients breathe had similar outcomes, and neither was significantly better than the other in preventing lung problems. The study suggests that both approaches work about the same for patients who need help with breathing using a machine.

Background Providing care via telemedicine was suggested worldwide during the COVID-19 pandemic. A new care model and service flow using telephone-based telemedicine (2T SAVE-COVID project) was established to provide care for patients at the Department of Medicine during the pandemic. This study aimed to investigate the clinical outcomes of patients after receiving care through telemedicine in the project. Methods A retrospective cohort study was conducted to compare the clinical outcomes of patients receiving telemedicine compared to routine care at the outpatient clinics of the Medicine department from April 2020 to November 2021, including an original cohort (routine care: n = 54,032; telemedicine: n = 16,388) and a propensity score-matched cohort (n = 16,246 per group). Baseline and clinical characteristics, rates of unplanned visits and mortality outcomes were analyzed. Time prior to unplanned visits was calculated, and multivariate analysis was performed to identify predictors of unplanned visits. Findings In the original cohort, the telemedicine group demonstrated a significantly higher incidence of unplanned outpatient visits (19.7% vs. 18.5%, p < 0.001). Conversely, in the matched cohort, the telemedicine group showed a lower rate of unplanned outpatient visits (19.4% vs. 59.3%, p < 0.001). Multivariate analysis confirmed that telemedicine was independently associated with a reduced risk of unplanned visits (adjusted HR: 0.69, 95% CI: 0.65 – 0.74, p < 0.001). However, other predictors with an increased incidence of unplanned visits included female patients, patients with chronic kidney disease stage 3 to 5, cancer and serum albumin levels below 4 g/dL. Additionally, telemedicine is associated with significantly lower mortality rates compared to routine care. Interpretation Telephone-based telemedicine can be a viable alternative to routine care, offering comparable or improved outcomes in terms of a reduced rate of unplanned visits and lower mortality rates, particularly when combined with appropriate patient selection and monitoring strategies.

Vancomycin is the best-choice medication for methicillin-resistant staphylococcal and enterococcal infections, which are major problems in intensive care units (ICUs). Intermittent infusion is standard for vancomycin, although delayed therapeutic target achievement and supra- and subtherapeutic levels are concerns. A recently proposed alternative with superior therapeutic target achievement is continuous infusion. To compare the benefits of continuous (CVI) and intermittent (IVI) vancomycin infusion. This quasi-experimental study used propensity score-matched historical controls and adult patients in medical and surgical ICUs for whom vancomycin was indicated. The experimental group received CVI for ≥ 48 hours. Data on patients receiving IVI between January 2018 and October 2020 were reviewed. Capability to achieve serum vancomycin therapeutic targets (48 and 96 hours), episodes of supra- and subtherapeutic levels, treatment success, mortality, and incidence of acute kidney injury (AKI) were analyzed before and after one-to-two propensity score matching. The CVI group had 31 patients, while the unmatched IVI group had 125. More CVI patients achieved the therapeutic target within 48 hours (54.8% vs 25.6%; =0.002). CVI patients had a higher median number of supratherapeutic episodes (2 vs 1; =0.007) but a lower median for subtherapeutic episodes (0 vs 1; =0.003). Other outcomes demonstrated no differences. After propensity score matching, target achievement within 48 hours (54.8% vs 22.6%; =0.002) and fewer subtherapeutic episodes (0 vs 1; =0.014) remained significant. CVI's rapid therapeutic target achievement and fewer subtherapeutic episodes make it superior to IVI. No differences in treatment success, mortality, or AKI are evident.

Objective To compare the treatment outcome of venovenous extracorporeal membrane oxygenation (VV-ECMO) versus mechanical ventilation in hypoxemic patients with acute respiratory distress syndrome (ARDS) at a referral center that started offering VV-EMCO support in 2010. Methods This retrospective cohort study enrolled adults with severe ARDS (PaO2/FiO2 ratio of <100 with FiO2 of ≥90 or Murray score of ≥3) who were admitted to the intensive care unit of Siriraj Hospital (Bangkok, Thailand) from January 2010 to December 2018. All patients were treated using a low tidal volume (TV) and optimal positive end-expiratory pressure. The primary outcome was hospital mortality. Results Sixty-four patients (ECMO, n = 30; mechanical ventilation, n = 34) were recruited. There was no significant difference in the baseline PaO2/FiO2 ratio (67.2 ± 25.7 vs. 76.6 ± 16.0), FiO2 (97 ± 9 vs. 94 ± 8), or Murray score (3.4 ± 0.5 vs. 3.3 ± 0.5) between the ECMO and mechanical ventilation groups. The hospital mortality rate was also not significantly different between the two groups (ECMO, 20/30 [66.7%] vs. mechanical ventilation, 24/34 [70.6%]). Patients who underwent ECMO were ventilated with a significantly lower TV than patients who underwent mechanical ventilation (3.8 ± 1.8 vs. 6.6 ± 1.4 mL, respectively). Conclusion Although VV-ECMO promoted lower-TV ventilation, it did not improve the in-hospital mortality rate. Trial registration: www.clinicaltrials.gov (NCT 04031794).

The purpose was to compare glucose variability (GV) obtained via continuous glucose monitoring between nondiabetic sepsis patients and healthy subjects and to seek associations between GV and sepsis severity in nondiabetic sepsis patients. Nondiabetic sepsis inpatients and healthy controls received a 72-hour continuous glucose monitoring (iPro2, Medtronic) postadmission and post–oral glucose tolerance test, respectively. The mean glucose level (MGL) along with GV represented by standard deviation (SD) and the mean amplitude of glycemic excursion (MAGE) were calculated at 24 and 72 hours. Sepsis severity was evaluated with the Sepsis-related Organ Failure Assessment Score (SOFA). MGL and GV in patients with SOFA ≥9 and <9 were compared. Thirty nondiabetic sepsis and 10 healthy subjects were recruited. No differences were found between groups except for higher patient age in sepsis patients. The MGL and MAGE72h of sepsis patients were significantly higher than those of healthy subjects. MGL and GV24h were higher in patients with SOFA ≥9 than in patients with SOFA <9 (MGL24h 195±17 vs 139±27, P<.001; SD24h 32 [28, 36] vs 19 [5, 58], P=.02; and MAGE24h 94 [58, 153] vs 54 [16, 179], P=.01). Nondiabetic sepsis patients had higher MGL and GV values than healthy subjects. MGL and GV24h were associated with sepsis severity. •To evaluate glucose variability from continuous glucose monitoring in sepsis without diabetes mellitus.•The nondiabetic sepsis patients had higher glucose variability than the control group.•Glucose variability during first 24 hours was associated with severity of sepsis.

Data on the characteristics and outcomes of patients hospitalized for Coronavirus Disease 2019 (COVID-19) in Thailand are limited. To determine characteristics and outcomes and identify risk factors for hospital mortality for hospitalized patients with COVID-19. We retrospectively reviewed the medical records of patients who had COVID-19 infection and were admitted to the cohort ward or ICUs at Siriraj Hospital between January 2020 and December 2021. Of the 2,430 patients included in this study, 229 (9.4%) died; the mean age was 54 years, 40% were men, 81% had at least one comorbidity, and 13% required intensive care unit (ICU). Favipiravir (86%) was the main antiviral treatment. Corticosteroids and rescue anti-inflammatory therapy were used in 74 and 6%, respectively. Admission to the ICU was the only factor associated with reduced mortality [odds ratio (OR) 0.01, 95% confidence interval (CI) 0.01-0.05, < 0.001], whereas older age (OR 14.3, 95%CI 5.76-35.54, < 0.001), high flow nasal cannula (HFNC; OR 9.2, 95% CI 3.9-21.6, < 0.001), mechanical ventilation (OR 269.39, 95%CI 3.6-2173.63, < 0.001), septic shock (OR 7.79, 95%CI, 2.01-30.18, = 0.003), and hydrocortisone treatment (OR 27.01, 95%CI 5.29-138.31, < 0.001) were factors associated with in-hospital mortality. The overall mortality of hospitalized patients with COVID-19 was 9%. The only factor associated with reduced mortality was admission to the ICU. Therefore, appropriate selection of patients for admission to the ICU, strategies to limit disease progression and prevent intubation, and early detection and prompt treatment of nosocomial infection can improve survival in these patients.