Early Use of Norepinephrine in Septic Shock Resuscitation (CENSER). A Randomized Trial.

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).

Efficacy of echocardiography during spontaneous breathing trial with low-level pressure support for predicting weaning failure among medical critically ill patients.

BACKGROUND: Echocardiography was reported to be a good predictor of weaning failure when using T-piece method, but information about its efficacy in a pressure support setting is scarce. This study aimed to investigate the efficacy of echocardiography during spontaneous breathing trial with low-level pressure support for predicting weaning failure among medical critically ill patients. METHODS: This prospective cohort study was conducted in adult respiratory failure patients that tolerated low pressure support weaning for 30 minutes. Echocardiogram was performed during pressure support ventilation before extubation. Weaning failure was defined as reintubation within 48 hours. RESULTS: Of the 52 included patients (mean age 65.9 ± 17.8 years), 14 experienced weaning failure. Severe pneumonia, metabolic acidosis, and septic shock were the leading causes of respiratory failure. Univariate analysis identified BMI > 24, peak A wave < 100 cm/s, E/Ea > 14, and inferior vena cava maximum diameter (IVCmax ) > 17 mm as factors associated with reintubation. Multivariate analysis revealed E/Ea > 14 and IVCmax  > 17 mm to be independent predictors of weaning failure. CONCLUSION: Inferior vena cava maximum diameter > 17 and E/Ea ratio ≥ 14 independently predict weaning failure in patients with preserved left ventricular systolic function. This finding confirms that preload status of both ventricles plays a major role in weaning failure.

Hydrocortisone treatment in early sepsis-associated acute respiratory distress syndrome: results of a randomized controlled 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.

High-frequency oscillatory ventilation for patients during exudative phase of severe ARDS.

BACKGROUND: High frequency oscillatory ventilation (HFOV) is theoretically ideal for lung protective strategy ventilation (LPSV) in acute respiratory distress syndrome (ARDS). However, recent studies revealed unsatisfactory outcomes. The authors conducted a study to examine this phenomenon in patients with early phase of moderate to severe ARDS. OBJECTIVE: To evaluate the effectiveness of HFOV in patients with early phase of moderate to severe ARDS. The primary outcome was 30 days all-cause mortality. MATERIAL AND METHOD: The study was a matched-case controlled clinical trial performed in the medical intensive care units, Faculty of Medicine, Siriraj Hospital. The authors compared HFOV with LPSV in adult patients with the early phase of ARDS who received mechanical ventilation less than 72 hours and had moderate to severe hypoxemia (PaO/FiO2 ratio less than or equal 150). RESULTS: Between June 2010 and February 2014, 49 patients with moderate to severe ARDS were included. Fourteen patients who received HFOV were matched with 16 patients who received LPSV. The 30-day mortality in HFOV group was 61.5%; while in control group, 50% (p = 0.53). The authors found use of higher doses of sedative drugs and muscle relaxants in HFOV group. In addition, this group had high-level of mean airway pressure (mPaw). The presence of hemodynamic instability was not different in both groups. CONCLUSION: In adult patients in the early phase of moderate to severe ARDS who received mechanical ventilation for less than 72 hours, HFOV did not decrease the 30-day mortality. Thus, this support should be only a rescue therapy for refractory hypoxemia cases and in highly selected patients.

Transthoracic echocardiogram for the diagnosis of right ventricular dysfunction in critically ill patients.

BACKGROUND: Acute right ventricular dysfunction (RVD) is one of the hemodynamic alterations in patients with septic shock, pulmonary embolism and ARDS. This condition had previously been diagnosed by pulmonary artery catheters (PAC). This report is on the use of transthoracic echocardiography (TTE) to diagnose RVD in critically ill patients. OBJECTIVE: To evaluate the use of TTE for the diagnosis of RVD. MATERIAL AND METHOD: A single center, cohort study, was performed in a 12-bed medical ICU. All patients who had had PAC insertions during the period from August 2009 to October 2010 were included in this study. TTE was performed by an investigator (WS. or ST) who was not aware of the patients' diagnoses. The hemodynamic parameters were measured within the hour prior to performing a TTE. The RVD was diagnosed according to the following criteria: Right atrial (RA) pressure > or = 12 mmHg, pulmonary artery occlusion pressure (PAOP) < 18 mmHg, mean pulmonary artery pressure (PAP) > 25 mmHg, and pulmonary vascular resistance (PVR) > 250 dyne*sec*cm(-5). RESULTS: The PACs were inserted in 59 patients. Of these, 15 had been diagnosed with RVD. A total of 83 TTE examinations, in comparison with hemodynamic parameters measured from PACs, were studied. The TTE parameters; left ventricular (LV) D-shape (sensitivity 61.1%, specificity 84.6%), loss of right ventricular (RV) apical triangle (sensitivity 44.4%, specificity 80%), RV systolic pressure > 40 mmHg (sensitivity 77.8%, specificity 60%) and right ventricular end systolic areas: left ventricular end systolic areas (RVESA:LVESA) > 0.65 (sensitivity 94.4%, specificity 39.1%) were consistent with RVD. The presence of at least 2 out of 4 echocardiograph findings correlated with RVD, with the area under the ROC curve at 0.79, with a sensitivity of 77.8% and a specificity of 67.7%. CONCLUSION: TTE is an accurate tool for the diagnosis RVD in critically ill patients with acceptable sensitivities and specificities.

Therapeutic goal achievements during severe sepsis and septic shock resuscitation and their association with patients' outcomes.

BACKGROUND: Severe sepsis and septic shock are associated with high mortality. "Early goal-directed therapy" (EGDT) has been shown to improve survival. The authors report here the goal achievements in the protocol and their association with patients' outcomes. MATERIAL AND METHOD: A prospective cohort study of patients with severe sepsis and septic shock who were admitted from the Emergency Department from April 2011 to September 2012. All underwent the resuscitation protocol aimed to achieve hemodynamic goals within 6 hours after diagnosis. These goals included: 1) mean arterial > 65 mmHg, 2) urine output > 0.5 ml/kg/hour and 3) superior vena cava O2 saturation > 70% or serum lactate clearance > 10%. The primary outcome was 28-day mortality RESULTS: Of the 175 enrolled patients, 23 (13.1%) achieved all 3 goals at 6 hour while 75 (42.8%) achieved 2 goals and 52 (29.8%) achieved only 1 goal. The 28-day mortality of these patients was 8.7%, 16% and 35.5%, respectively while 44% of those who did not achieve any goal died. A central venous catheter was placed in 79 patients, 46 of whom had it inserted during the first 6 hours, and 42 of whom had a CVP of 8-12 mmHg. Only 13 patients had their ScvO2 measured. Mean arterial pressure target was achieved in 129 patients, who had lower initial APACHE II score, lower initial lactate level and higher initial blood pressures than those who did not. These patients received less fluid at 6 hours, at 24 hours and at 3 days, respectively; they also received less norepinephrine. This group had lower mortality (28-day mortality 19.4% vs. 34.86%, p = 0.043). Of 119 patients who had achieved the urine output goal, 21 reached this goal alone and their survival was better than those who did not achieve any target goal. Serum lactate was monitored in 51 patients and a clearance of > 10% was noted in 23 of them. These patients were divided into 3 groups.: group 1 consisted of patients with initial lactate < 2; group 2 were patients with initial lactate > 2, which decreased during resuscitation; group 3 consisted of patients with initial lactate > 2, which increased after wards. The mortalities were 7.7%, 14.3% and 43.6%, respectively, p = 0.011. CONCLUSION: The achievement of therapeutic targets at 6 hours after sepsis/septic shock resuscitation was associated with improved survival, especially when more goals were reached. Although the achievement of adequate tissue oxygenation was proved beneficial, only one-third of the patients were monitored.

Prevalence, predictive factors, and outcomes of refeeding syndrome among medically critically ill patients: A retrospective cohort study.

BACKGROUND: Refeeding syndrome (RFS) is a life-threatening metabolic derangement occurring when nutrition is reintroduced after prolonged starvation. Limited data exist regarding RFS prevalence, risk factors, and outcome, particularly in critically ill patients. METHODS: A retrospective cohort study was conducted in a medical intensive care unit from June 2018 to August 2020. RFS diagnostic criteria from the National Institute for Health and Care Excellence (NICE) and the American Society for Parenteral and Enteral Nutrition (ASPEN) were used. The primary outcome was 30-day mortality. RESULTS: Among 216 patients, RFS was diagnosed in 22.7% and 27.3% of patients per the NICE and ASPEN criteria, respectively. There was no significant difference in 30-day mortality between patients with and without RFS (22/59 [37.3%] vs 53/157 [33.8%]; P = 0.627). Independent predictors of RFS were malignancy (odds ratio [OR] = 2.09; 95% CI = 1.06-4.15; P = 0.035), septic shock (OR = 2.26; 95% CI = 1.17-4.39; P = 0.016), and high NICE RFS risk classification (OR = 2.52; 95% CI = 1.20-5.31; P = 0.015). Factors associated with reduced RFS risk were Sequential Organ Failure Assessment (SOFA) scores >12 (OR = 0.45; 95% CI = 0.23-0.88; P = 0.020) and high-dose vasopressor treatment (OR = 0.34; 95% CI = 0.14-0.79; P = 0.012). CONCLUSION: RFS affected one-fourth of the critically ill patients but did not significantly impact 30-day mortality. Malignancy, septic shock, and high NICE RFS risk classification were positively associated with RFS, whereas high SOFA scores and extensive vasopressor use were linked to decreased risk.

Comparison of limited driving pressure ventilation and low tidal volume strategies in adults with acute respiratory failure on mechanical ventilation: a randomized controlled trial.

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).

Limited breathing pressure or low amount of air given to the lung; which one is better for adults who need breathing help by ventilator machineWe 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.

Predicting factors, incidence and prognosis of cardiac arrhythmia in medical, non-acute coronary syndrome, critically ill patients.

BACKGROUND: Cardiac arrhythmia is an important complication of critically ill patients, especially in perioperative period and early after myocardial infarction. However, the information regarding this condition in medical critically ill without active coronary artery disease patients is limited. OBJECTIVE: To identify the predictive factors, incidence, and prognosis of tachyarrhythmia and bradyarrhythmia in non-coronary critically ill medical patients. MATERIAL AND METHOD: A single center prospective cohort study, included medical critically ill patients, age > or = 18 year-old, admitted in a 15-bed medical ICU between September 2010 and August 2011. The patients with active coronary artery disease, end stage organ failure and not expected to survive > or = 48 hours were excluded. The patients' baseline characteristic, APACHE II score, laboratory investigations in the first 24 hours and treatment modalities were recorded. Continuous electrocardiographic monitoring was performed during ICU admission. The arrhythmic event, requiring treatment, was recorded. RESULTS: A total of 247 patients were included, the mean age was 58.5 +/- 20.0 year-old and mean APACHE II score was 20.1 +/- 9.8. Most of them had septic shock (57.1%) and respiratory failure (55.1%). The incidence of arrhythmia was 39.7%. Of 45 patients (18.2%) who had tachyarrhythmia, new onset atrial fibrillation was demonstrated in 34 patients (13.8%), following by ventricular fibrillation (9 patients, 3.6%) and supraventricular tachycardia (2 patients, 0.8%). Bradyarrhythmia was noted in 53 patients (21.5%). Of these, junctional bradycardia was witnessed in 34 patients (13.8%), followed by symptomatic bradycardia (15 patients, 6.1%) and atrioventricular blockage (4 patients, 1.60%). The multivariate by logistic regression analysis revealed the receiving of norepinephrine and APACHE II > or = 25 as an independent predictor for tachyarrhythmia, while the receiving of norepinephrine, arterial pH < 7.3 and HCO3 > or = 18 were associated with bradyarrhythmia. The presence of arrhythmia, especially ventricular fibrillation, symptomatic sinus bradycardia and junctional bradycardia in medical ICU is associated with higher hospital mortality (bradyarrhythmia 88. 7%, tachyarrhythmia 66.70%) than the absent group (18.1%, p < 0.001). CONCLUSION: Arrhythmia is a serious complication of medical critically ill patients and associated with high mortality rate. Appropriate shock management together with proper metabolic support may prevent this condition.

Dynamics of central venous oxygen saturation and serum lactate during septic shock resuscitation.

BACKGROUND: Septic shock is a serious condition leading to high mortality and morbidity. Many varieties of attempts aiming toward improving outcomes have been implemented. However the appropriate therapeutic endpoint of shock resuscitation is still under investigation. The authors report here the dynamics of commonly used parameters, namely central venous oxygen saturation (ScvO2) and lactate concentration during resuscitation. MATERIAL AND METHOD: Adult patients admitted with severe sepsis and septic shock from October 1, 2009 to January 31, 2009 were enrolled. During hemodynamic resuscitation, the central venous blood was drawn for ScvO2 and lactate measurement right after the CVC was placed (T1) and at the point where the blood pressure goal was achieved (T2). The third and the fourth measurements were obtained at 1 and 2 hours thereafter (T3 and T4). These samples were ice chilled and were sent to central laboratory for blood gas analysis and lactate determination. RESULTS: Twenty patients underwent the study. There was no significant change in ScvO2 from T1 to T4. All but five ScvO2 at T1 were above 70%. Lactate level gradually declined during the course of treatment and the clearance from T1 to T3 was calculated as 15.4%. No correlation between ScvO2 and lactate level was noted at any sampling time. When partitioning venous oxygen saturation in to 4 groups, that is ScvO2 < 65, 65 - < 75, 75-<85 and > 85, respectively, those with ScvO2 > 85% had the highest lactate concentration. CONCLUSION: Central venous oxygen saturation and its changes during treatment were heterogeneous which made this parameter less reliable than others to monitor management. The lactate clearance, although slow, is uniform and may be used alone or in combination with other parameters to monitor resuscitation.

Comparing Outcomes of Critically Ill Patients in Intensive Care Units and General Wards: A Comprehensive Analysis.

Background: The admission of critically ill patients to intensive care unit (ICU) plays a crucial role in reducing mortality. However, the scarcity of available ICU beds presents a significant challenge. In resource-limited settings, the outcomes of critically ill patients, particularly those who are not accepted for ICU admission, have been a topic of ongoing debate and contention. Objective: This study aimed to explore the outcomes and factors associated with ICU admission and mortality among critically ill patients in Thailand. Methods: This prospective cohort study enrolled critically ill adults indicated for medical ICU admission. Patients were followed for 28 days regardless of whether they were admitted to an ICU. Data on mortality, hospital length of stay, duration of organ support, and factors associated with mortality and ICU admission were collected. Results: Of the 180 patients enrolled, 72 were admitted to ICUs, and 108 were cared for in general wards. The ICU group had a higher 28-day mortality rate (44.4% vs 20.4%; P=0.001), but other outcomes of interest were comparable. Multivariate analysis identified alteration of consciousness, norepinephrine use, and epinephrine use as independent predictors of 28-day mortality. Higher body mass index (BMI), higher APACHE II score, and acute kidney injury were predictive factors associated with ICU acceptance. Conclusion: Among patients indicated for ICU admission, those who were admitted had a higher 28-day mortality rate. Higher mortality was associated with alteration of consciousness and vasopressor use. Patients who were sicker and had higher BMI were more likely to be admitted to an ICU.

Predictive factors and outcomes of respiratory syncytial virus infection among patients with respiratory failure.

Introduction: Respiratory syncytial virus (RSV) infection is an emerging infectious disease. However, the impacts of RSV infection among patients with respiratory failure have not been identified. Objective: This study investigated the 28-day mortality and clinical outcomes of RSV infection in patients with respiratory failure. Methods: This retrospective study enrolled patients admitted with respiratory failure and requiring mechanical ventilator support for more than 24 h at Siriraj Hospital, Bangkok, Thailand, between January 2014 and July 2019. Respiratory samples of the patients were examined to identify RSV infections. The primary outcome was 28-day mortality. Results: Respiratory syncytial virus infection was identified in 67 of the 335 patients with respiratory failure enrolled in this study. There were no significant differences in the following baseline characteristics of the patients with and without RSV infection: mean age (72.7 ± 12.7 years vs. 71 ± 14.8 years), sex (male: 46.3% vs. 47.4%), comorbidities, and initial Murray lung injury scores (1.1 ± 0.8 vs. 1.1 ± 0.9). The 28-day mortality was 38.8% (26/67) for the RSV group and 37.1% (99/268) for the non-RSV group (p = 0.79). However, the RSV group had significantly higher proportions of bronchospasm (98.5% vs. 60.8%; p < 0.001), ventilator-associated pneumonia (52.2% vs. 33.8%; p = 0.005), and lung atelectasis (10.4% vs. 3.0%; p = 0.009) than the non-RSV group. Conclusion: Among the patients with respiratory failure, the 28-day mortality of patients with and without RSV infection did not differ. However, patients with RSV infection had an increased risk of complications, such as bronchospasm, ventilation-associated pneumonia, and lung atelectasis.

Anti-SARS-CoV-2 antibody among SARS-CoV-2 vaccinated vs post-infected blood donors in a tertiary hospital, Bangkok, Thailand.

SARS-CoV-2 virus infection has imposed a significant healthcare burden globally. To contain its spread and decrease infection-related mortality, several vaccines have been deployed worldwide in the past 3 years. We conducted a cross-sectional seroprevalence study to assess the immune response against the virus among blood donors at a tertiary care hospital, Bangkok, Thailand. From December 2021 to March 2022, total of 1,520 participants were enrolled, and their past history of SARS-CoV-2 infection and vaccination was recorded. Two serology test, namely, quantitative IgG spike protein (IgGSP) and qualitative IgG nucleocapsid antibody (IgGNC) were performed. The median age of study participants was 40 years (IQR 30-48) and 833 (54.8%) were men. Vaccine uptake was reported in 1,500 donors (98.7%) and 84 (5.5%) reported the past infection history. IgGNC was detected in 46/84 donors with the past infection history (54.8%) and in 36 out of the rest 1,436 (2.5%) with no past history. IgGSP positivity was observed in 1484 donors (97.6%). When compared to unvaccinated donors (n = 20), IgGSP level was higher in the donors who had received one vaccine dose (p< 0.001) and these antibody levels increased significantly among those with 3rd and 4th vaccine doses. Factors associated with low IgGSP (lowest quartile) by multivariate analysis included: no past infection history, homologous vaccination, < 3 vaccine doses, and > 90 days duration since last vaccination. In conclusion, vaccine uptake among our study donors was high (98.7%) and IgGSP antibody was observed in nearly all the vaccinated donors (97.6%). Previous SARS-CoV-2 infection, use of heterologous vaccination, vaccines ≥ 3 doses, and duration of the last vaccination >90 days affected IgGSP levels. Use of serological assays were found beneficial in the evaluation and differentiation of immune response to vaccination, and natural infection including the identification of previous asymptomatic infections.

Patient-Level Meta-Analysis of Low-Dose Hydrocortisone in Adults with Septic Shock.

BACKGROUND: Trials and study-level meta-analyses have failed to resolve the role of corticosteroids in the management of patients with septic shock. Patient-level meta-analyses may provide more precise estimates of treatment effects, particularly subgroup effects. METHODS: We pooled individual patient data from septic shock trials investigating the adjunctive use of intravenous hydrocortisone. The primary outcome was 90-day all-cause mortality, and it was also analyzed across predefined subgroups. Secondary outcomes included mortality at intensive care unit and hospital discharge, at 28 and 180 days, and vasopressor-, ventilator-, and organ failure­free days. Adverse events included superinfection, muscle weakness, hyperglycemia, hypernatremia, and gastroduodenal bleeding. RESULTS: Of 24 eligible trials (n=8528), 17 (n=7882) provided individual patient data, and 7 (n=5929) provided 90-day mortality. The marginal relative risk (RR) for 90-day mortality of hydrocortisone versus placebo was 0.93 (95% confidence interval [CI], 0.82 to 1.04; P=0.22; moderate certainty). It was 0.86 (95% CI, 0.79 to 0.92) for hydrocortisone with fludrocortisone and 0.96 (95% CI, 0.82 to 1.12) without fludrocortisone. There was no significant differential treatment effect across subgroups. Hydrocortisone was associated with little to no difference in any of the secondary outcomes except vasopressor-free days (mean difference, 1.24 days; 95% CI, 0.74 to 1.73; high certainty). Hydrocortisone may not be associated with an increase in the risk of superinfection (RR, 1.04; 95% CI, 0.95 to 1.15; low certainty), hyperglycemia (RR, 1.05; 95% CI, 0.98 to 1.12; low certainty), or gastroduodenal bleeding (RR, 1.11; 95% CI, 0.83 to 1.48; low certainty). Hydrocortisone may be associated with an increase in the risk of hypernatremia (RR, 2.01; 95% CI, 1.56 to 2.60; low certainty) and muscle weakness (n=2647; RR, 1.73; 95% CI, 1.49 to 1.99; low certainty). CONCLUSIONS: In this patient-level meta-analysis, hydrocortisone compared with placebo was not associated with reduced mortality for patients with septic shock. (Funded by "Programme d'Investissements d'Avenir," a research Professorship from the National Institute of Health and Care Research, Leadership Fellowships from the National Health and Medical Research Council of Australia, and Emerging Leaders Fellowship from the National Health and Medical Research Council of Australia; PROSPERO registration number, CRD42017062198.)

Serum lactate levels in cirrhosis and non-cirrhosis patients with septic shock.

BACKGROUND: In septic shock patients with cirrhosis, impaired liver function might decrease lactate elimination and produce a higher lactate level. This study investigated differences in initial lactate, lactate clearance, and lactate utility between cirrhotic and non-cirrhotic septic shock patients. METHODS: This is a retrospective cohort study conducted at a referral, university-affiliated medical center. We enrolled adults admitted during 2012-2018 who satisfied the septic shock diagnostic criteria of the Surviving Sepsis Campaign: 2012. Patients previously diagnosed with cirrhosis by an imaging modality were classified into the cirrhosis group. The initial lactate levels and levels 6 hours after resuscitation were measured and used to calculate lactate clearance. We compared initial lactate, lactate at 6 hours, and lactate clearance between the cirrhosis and non-cirrhosis groups. The primary outcome was in-hospital mortality. RESULTS: Overall 777 patients were enrolled, of whom 91 had previously been diagnosed with cirrhosis. Initial lactate and lactate at 6 hours were both significantly higher in cirrhosis patients, but there was no difference between the groups in lactate clearance. A receiver operating characteristic curve analysis for predictors of in-hospital mortality revealed cut-off values for initial lactate, lactate at 6 hours, and lactate clearance of >4 mmol/L, >2 mmol/L, and <10%, respectively, among non-cirrhosis patients. Among patients with cirrhosis, the cut-off values predicting in-hospital mortality were >5 mmol/L, >5 mmol/L, and <20%, respectively. Neither lactate level nor lactate clearance was an independent risk factor for in-hospital mortality among cirrhotic and non-cirrhotic septic shock patients. CONCLUSIONS: The initial lactate level and lactate at 6 hours were significantly higher in cirrhosis patients than in non-cirrhosis patients.

Continuous Vancomycin Infusion versus Intermittent Infusion in Critically Ill Patients.

Background: 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. Objective: To compare the benefits of continuous (CVI) and intermittent (IVI) vancomycin infusion. Methods: 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. Results: 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%; P=0.002). CVI patients had a higher median number of supratherapeutic episodes (2 vs 1; P=0.007) but a lower median for subtherapeutic episodes (0 vs 1; P=0.003). Other outcomes demonstrated no differences. After propensity score matching, target achievement within 48 hours (54.8% vs 22.6%; P=0.002) and fewer subtherapeutic episodes (0 vs 1; P=0.014) remained significant. Conclusion: 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.

Extracorporeal membrane oxygenation (ECMO) support for acute hypoxemic respiratory failure patients: outcomes and predictive factors.

Background: Extracorporeal membrane oxygenation (ECMO) is an important rescue therapy for patients with refractory respiratory or circulatory failure. High cost and associated complications warrant careful case selection. The aim of this study was to investigate the outcomes and factors associated with mortality in acute hypoxemic respiratory failure patients who received ECMO support, and to externally validate preexisting ECMO survival prediction scoring systems. Methods: This retrospective study enrolled acute hypoxemic respiratory failure patients who received veno-venous (VV) or veno-arterial (VA) ECMO support at Siriraj Hospital (Bangkok, Thailand) from 2010 to 2020. All relevant baseline patient characteristics including ECMO survival prediction scores were recorded. The primary outcome was in-hospital mortality. Multivariate logistic regression analysis was employed to identify independent predictors of in-hospital mortality. Results: Of a total of 65 patients, 34 (52%) were male, the median (IQR) age was 61 years (49-70 years), the median body mass index (BMI) was 22.6 kg/m2 (20.6-28 kg/m2), and the median Sequential Organ Failure Assessment (SOFA) score was 13 [11-16]. Forty-three patients (66%) received VV-ECMO, and 22 (34%) received VA-ECMO support. In-hospital mortality was 69%. Multivariate analysis identified a SOFA score >14, hospitalized >72 hours before ECMO initiation, PaO2/FiO2 ratio <60, and pH <7.2 as independent predictors of in-hospital mortality. These four parameters were combined to create the SHOP (S: SOFA >14, H: hospitalize >72 hours, O: PF ratio <60, and P: pH <7.2) score. Compared with three different preexisting ECMO survival prediction scoring systems, the SHOP score had the highest area under the curve (AUC) for predicting in-hospital mortality (overall: 0.873, VV-EMCO: 0.866, and VA-EMCO: 0.891). Conclusions: In-hospital mortality among ECMO-supported patients was high at 69%. SOFA score >14, hospitalized >72 hours, PaO2/FiO2 ratio <60, and pH <7.2 were found to be independent predictors of in-hospital mortality. A SHOP score of 2 or higher significantly predicts in-hospital mortality in EMCO-supported patients. Trial Registration: www.clinicaltrials.gov (reg. No. NCT04031794).

Characteristics, outcomes, and risk factors for in-hospital mortality of COVID-19 patients: A retrospective study in Thailand.

Introduction: Data on the characteristics and outcomes of patients hospitalized for Coronavirus Disease 2019 (COVID-19) in Thailand are limited. Objective: To determine characteristics and outcomes and identify risk factors for hospital mortality for hospitalized patients with COVID-19. Methods: 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. Results: 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, P < 0.001], whereas older age (OR 14.3, 95%CI 5.76-35.54, P < 0.001), high flow nasal cannula (HFNC; OR 9.2, 95% CI 3.9-21.6, P < 0.001), mechanical ventilation (OR 269.39, 95%CI 3.6-2173.63, P < 0.001), septic shock (OR 7.79, 95%CI, 2.01-30.18, P = 0.003), and hydrocortisone treatment (OR 27.01, 95%CI 5.29-138.31, P < 0.001) were factors associated with in-hospital mortality. Conclusion: 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.

Correlation of arterial, central venous and capillary lactate levels in septic shock patients.

BACKGROUND: Blood lactate level increases in response to tissue hypoxia and this level is currently used to monitor shock management. To obtain the arterial lactate value in clinical practice is a time consuming process. Our previous study demonstrated good correlation between the capillary lactate determined by a portable lactate analyzer and the standard arterial lactate in critically ill patients. This study was aimed to examine the uses of this capillary lactate in septic shock. MATERIAL AND METHOD: A prospective comparison of arterial, venous and capillary lactate level from septic shock patients admitted in the general wards and the Medical ICU, Department of Medicine, Siriraj hospital was performed during October 2009 to February 2010. RESULTS: Thirty patients were included in the study. The mean age was 66 (24-86) years and 16 (53%) were female. The correlation between arterial and central venous was 0.992 and the correlation between arterial and capillary lactate level was 0.945 (p = 0.01 in both comparisons). In addition, there was certain agreement between the arterial and the capillary lactate especially when arterial lactate was below 10 mmol/L. CONCLUSION: The capillary lactate level determined by the portable lactate analyzer (Accutrend Plus) correlated well with arterial lactate level. This method, when used cautiously, may be used to monitor septic shock treatment as an alternative to the standard arterial lactate determination.