Efficacy of additional hemoperfusion in hospitalized patients with severe to critical COVID-19 disease.

The evidence supporting additional hemoperfusion (HP) with cytokine adsorbents for improving clinical outcomes in severe to critical coronavirus disease 2019 (COVID-19) patients remains limited. We compared severe to critical COVID-19 patients who received additional HP with a cytokine adsorbent to matched cases receiving standard medical treatment (SMT). The primary outcome was hospital mortality. In our study, we matched 45 patients who received additional HP 1:1 with the SMT group based on key clinical parameters. The hospital mortality rates did not differ between the groups (33% vs 38%, p = 0.83). The HP group had a significantly shorter ICU stay (22 vs 32 days; p = 0.017) and reduced mechanical ventilation duration (15 vs 35 days; p < 0.001). Additionally, the incidence of pulmonary complications (20% vs 42%; p = 0.04), sepsis (38% vs 64%; p = 0.02), and disseminated intravascular coagulopathy (DIC) (13% vs 33%; p = 0.046) were significantly lower in the HP group. In conclusion, among severe to critical COVID-19 patients, additional HP with a cytokine adsorbent did not improve hospital mortality. However, it reduced ICU length of stay, mechanical ventilator days, and incidences of lung complications, sepsis, and DIC. Trial registration: TCTR20231002006. Registered 02 October 2023 (retrospectively registered).

Factors associated with mortality in acute respiratory failure patients without acute respiratory distress syndrome.

Background: Excess tidal volume and driving pressure were associated with increased mortality in patients with acute respiratory distress syndrome (ARDS). Still, the appropriate mechanical ventilation strategy for patients who do not have ARDS needs to be understood. This study aimed to identify risk factors for mortality in acute respiratory failure patients without ARDS. Methods: We included all mechanically ventilated patients who did not meet the criteria for ARDS and were admitted to the medical intensive care unit (ICU) from October 2017 to September 2018. Patients who had tracheostomy before admission, were intubated for more than 24 hours before transfer to ICU, or underwent extracorporeal membrane oxygenation within 24 hours of ICU admission were excluded. Clinical and physiologic data were recorded and compared between survived and non-survived patients. Results: Of 289 patients with acute respiratory failure, 134 patients without ARDS were included; 69 (51%) died within 28 days. Demographics, principal diagnosis, and lung injury score on the first day of admission were not significantly different between survived and non-survived patients. In multivariate analysis, higher peak inspiratory pressure (PIP) during the first 3 days of admission [odds ratio (OR) 1.11, 95% confidence interval (CI): 1.01-1.22, P=0.04], higher sequential organ failure assessment score (OR 1.15, 95% CI: 1.04-1.28, P=0.008) and underlying cerebrovascular diseases (OR 7.09, 95% CI: 1.78-28.28, P=0.006) were independently associated with mortality in these patients, whereas dynamic lung compliance (Cdyn) and respiratory rate were not associated with mortality in the multivariate model. Conclusions: Mortality was high in mechanically ventilated patients without ARDS. Higher PIP is a potentially modifiable risk factor for mortality in these patients, independent of the baseline Cdyn. Underlying cerebrovascular diseases and increased disease severity are also independent factors associated with 28-day mortality.

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.

Impact of Intensity of Continuous Renal Replacement Therapy on Duration of Ventilation in Critically Ill Patients: A Secondary Analysis of the RENAL Trial.

INTRODUCTION: More intensive renal replacement therapy (RRT) has been associated with prolonged mechanical ventilation (MV). However, such finding may be dependent on RRT modality. We hypothesized that, when using continuous renal replacement therapy (CRRT), RRT intensity would not be associated with prolonged MV. METHODS: In a secondary analysis of the Randomized Evaluation of Normal versus Augmented Level (RENAL) Replacement trial comparing different CRRT intensities, we applied Fine-Gray competing risk analysis with time to successful extubation within 28 days as primary outcome. RESULTS: We studied 531 patients in the higher intensity and 551 in the lower intensity group. Higher intensity patients had more hypophosphatemia (66.7 vs. 58.1%; p = 0.004) and more days with hypophosphatemia (2.2 ± 2.8 vs. 1.6 ± 2.2; p < 0.001). There was no difference in the number of patients extubated within 28 days (60.1% vs. 62.4%; adjusted subdistribution hazard ratio [SHR], 0.95 [95% CI, 0.86 to 1.06]) or time to extubation (8 [5-16] vs. 8 [5-15] days; adjusted median difference, 0.65 [95% CI, -0.41 to 1.70]). Among patients from the upper tertile of days with hypophosphatemia, higher intensity CRRT was associated with a lower chance of successful extubation within 28 days (SHR, 0.67 [95% CI, 0.55 to 0.82]; p for heterogeneity = 0.013). CONCLUSIONS: In the RENAL trial, higher intensity CRRT was not associated with delayed extubation. However, it was associated with a greater rate of hypophosphatemia and more days with hypophosphatemia was associated with a lower chance of successful extubation.

Mega-dose sodium ascorbate: a pilot, single-dose, physiological effect, double-blind, randomized, controlled trial.

BACKGROUND: Mega-dose sodium ascorbate (NaAscorbate) appears beneficial in experimental sepsis. However, its physiological effects in patients with septic shock are unknown. METHODS: We conducted a pilot, single-dose, double-blind, randomized controlled trial. We enrolled patients with septic shock within 24 h of diagnosis. We randomly assigned them to receive a single mega-dose of NaAscorbate (30 g over 1 h followed by 30 g over 5 h) or placebo (vehicle). The primary outcome was the total 24 h urine output (UO) from the beginning of the study treatment. Secondary outcomes included the time course of the progressive cumulative UO, vasopressor dose, and sequential organ failure assessment (SOFA) score. RESULTS: We enrolled 30 patients (15 patients in each arm). The mean (95% confidence interval) total 24-h UO was 2056 (1520-2593) ml with placebo and 2948 (2181-3715) ml with NaAscorbate (mean difference 891.5, 95% confidence interval [- 2.1 to 1785.2], P = 0.051). Moreover, the progressive cumulative UO was greater over time on linear mixed modelling with NaAscorbate (P < 0.001). Vasopressor dose and SOFA score changes over time showed faster reductions with NaAscorbate (P < 0.001 and P = 0.042). The sodium level, however, increased more over time with NaAscorbate (P < 0.001). There was no statistical difference in other clinical outcomes. CONCLUSION: In patients with septic shock, mega-dose NaAscorbate did not significantly increase cumulative 24-h UO. However, it induced a significantly greater increase in UO and a greater reduction in vasopressor dose and SOFA score over time. One episode of hypernatremia and one of hemolysis were observed in the NaAscorbate group. These findings support further cautious investigation of this novel intervention. Trial registration Australian New Zealand Clinical Trial Registry (ACTRN12620000651987), Date registered June/5/2020.

Changes in SedLine-derived processed electroencephalographic parameters during hypothermia in patients undergoing cardiac surgery with cardiopulmonary bypass.

Objective: Processed electroencephalography (pEEG) is used to monitor depth-of-anesthesia during cardiopulmonary bypass (CPB). The SedLine device has been recently introduced for pEEG monitoring. However, the effect of hypothermia on its parameters during CPB is unknown. Accordingly, we aimed to investigate temperature-induced changes in SedLine-derived pEEG parameters during CPB. Design: Prospective observational study. Setting: Cardiac surgery operating theatre. Participants: 28 patients undergoing elective cardiac surgery with CPB. Interventions: We continuously measured patient state index (PSI), suppression ratio (SR), bilateral spectral edge frequency (SEF) and temperature. We used linear mixed modelling with fixed and random effects to study the interactions between pEEG parameters and core temperature. Measurements and main results: During CPB maintenance, the median temperature was 32.1°C [interquartile range (IQR): 29.8-33.6] at the end of cooling and 32.8°C (IQR: 30.1-34.0) at rewarming initiation. For each degree Celsius change in temperature during cooling and rewarming the PSI either decreased by 0.8 points [95% confidence interval (CI): 0.7-1.0; p < 0.001] or increased by 0.7 points (95% CI: 0.6-0.8; p < 0.001). The SR increased by 2.9 (95% CI: 2.3-3.4); p < 0.001) during cooling and decreased by 2.2 (95% CI: 1.7-2.7; p < 0.001) during rewarming. Changes in the SEF were not related to changes in temperature. Conclusions: During hypothermic CPB, temperature changes led to concordant changes in the PSI. The SR increased during cooling and decreased during rewarming. Clinicians using SedLine for depth-of-anesthesia monitoring should be aware of these effects when interpreting the PSI and SR values.

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.

The effect of the AN69 ST100 versus oXiris® membrane on filter life during CRRT for non-anticoagulated liver failure patients.

BACKGROUNDS: In patients with liver failure, continuous renal replacement therapy (CRRT) without anticoagulation may be necessary. A new heparin coated membrane (oXiris®) may prolong circuit life in this setting. OBJECTIVES: In liver failure patients not receiving anticoagulation, to compare CRRT circuit life with the oXiris® versus the AN69 ST100 (usual care) membrane. METHODS: Randomized single cross-over trial. RESULTS: We studied 20 patients and 39 circuits. Twenty-five treatments used femoral and 14 internal jugular access catheters. Median circuit life was 21 h (IQR: 8.25-35.5) with the AN69 versus 16.0 h (14-25) with the oXiris® membrane (p = 0.36). Median first circuit duration was 14 (11.25-23) h for the AN69 ST100 versus 16 (8 -26) for the oXiris® membrane. There was also no difference between the AN69 ST100 or oXiris® membrane circuits using femoral access at 13 (8 -22.5) versus 15.5 (12.5-21.5) h (p = 0.57) or internal jugular access at 28 (13-47) versus 23 (21-29) h (p = 0.79), respectively. CONCLUSIONS: The oXiris® heparin-grafted membrane does not appear to prolong circuit life in liver failure patients receiving CRRT without anticoagulation.

Customized Citrate Anticoagulation versus No Anticoagulant in Continuous Venovenous Hemofiltration in Critically Ill Patients with Acute Kidney Injury: A Prospective Randomized Controlled Trial.

INTRODUCTION: The use of anticoagulants during continuous renal replacement therapy (CRRT) is essential. Regional citrate anticoagulation (RCA) is recommended rather than systemic heparinization to prolong the filter's lifespan in patients at high risk of bleeding. However, commercial citrate is expensive and may not be available in resource-limited areas. The objective of this study is comparing filter life between our locally made customized RCA and no anticoagulation. The primary outcomes were the first circuit life in hours and the number of filters used within the first 72 h of therapy. METHODS: We conducted a single-center prospective randomized controlled trial in critically ill patients requiring CRRT. The participants were randomized to receive continuous venovenous hemofiltration (CVVH) with either customized RCA or no anticoagulant. RESULTS: Of 76 patients, 38 were randomized to receive customized RCA and 38 to receive CVVH without anticoagulant. There was no significant difference in baseline characteristics between the two groups. Compared to anticoagulant-free group, the median circuit life of customized RCA group was significantly longer [44.9 (20.0, 72.0) vs. 14.3 (7.0, 22.0) hours; p < 0.001]. The number of filters used within 72 h was significant lower [2.0 (1.0, 2.0) vs. 2.5 (1.0, 3.0); p < 0.015]. RCA was prematurely discontinued in 5 patients due to citrate accumulation (2 cases) and severe metabolic acidosis requiring higher dose of CVVH (3 cases). No differences in bleeding complications were observed (p = 0.99). CONCLUSION: Customized citrate-based replacement solution improved filter survival in CVVH compared to anticoagulant-free strategy. This regimen is safe, feasible, and suitable for low- to middle-income countries.

Renal outcomes according to renal replacement therapy modality and treatment protocol in the ATN and RENAL trials.

BACKGROUND: In critically ill patients with acute kidney injury, renal replacement therapy (RRT) modality and treatment protocols may affect kidney recovery. This study explored whether RRT modality and treatment protocol affected RRT dependence in the 'Randomized Evaluation of Normal versus Augmented Level of RRT' and the 'Acute Renal Failure Trial Network' (ATN) trials. METHODS: Primary outcome was 28-day RRT dependence. Secondary outcomes included RRT dependence among survivors and in different SOFA-based treatment protocol groups. We used the Fine-Gray competing-risk model sub-distribution hazard ratio (SHR) to assess the primary outcome. Analyses were adjusted for confounders. RESULTS: Of 2542 patients, 2175 (85.5%) received continuous RRT (CRRT) and 367 (14.4%) received intermittent hemodialysis (IHD) as first RRT modality. CRRT-first patients had greater illness severity. After adjustment, there was no between-group difference in 28-day RRT dependence (SHR, 0.96 [95% CI 0.84-1.10]; p = 0.570) or hospital mortality (odds ratio [OR], 1.14 [95% CI 0.86-1.52]; p = 0.361) However, among survivors, CRRT-first was associated with decreased 28-day RRT dependence (OR, 0.54 [95% CI 0.37-0.80]; p = 0.002) and more RRT-free days (common OR: 1.38 [95% CI 1.11-1.71]). Moreover, among CRRT-first patient, the ATN treatment protocol was associated with fewer RRT-free days, greater mortality, and a fourfold increase in RRT dependence at day 28. CONCLUSIONS: There was no difference in RRT dependence at day 28 between IHD and CRRT. However, among survivors and after adjustment, both IHD-first and the ATN treatment protocol were strongly associated with greater risk of RRT dependence at 28 days after randomization. Trial registration NCT00221013 registered September 22, 2005, and NCT00076219 registered January 19, 2004.

The relationship between Nephrocheck® test values, outcomes, and urinary output in critically ill patients at risk of acute kidney injury.

BACKGROUND: Nephrocheck® was approved for acute kidney injury (AKI) risk assessment in critically illness. However, new studies suggest that urinary concentration affects Nephrocheck® and previous studies did not provide data on urinary output (UO) at the time of measurement. METHODS: We performed a prospective cohort study of the Nephrocheck® in intensive care unit patients fulfilling standard inclusion criteria. The primary outcome was Stage 2 or 3 AKI defined by both UO and creatinine Kidney Disease Improving Global Outcomes (KDIGO) criteria in the subsequent 12 h. The secondary outcome was the relationship of UO with Nephrocheck® measurement. RESULTS: Among 98 patients, the primary outcome occurred in 53 (54.1%) overall, but in 23 (23.5%) by creatinine criteria alone. The median (interquartile range) Nephrocheck® in patients with subsequent Stage 2 or 3 AKI was greater than in Stage 1 or no-AKI patients (0.97 [0.48-1.99] vs. 0.46 [0.22-1.17]; p = .005). However, its area under the receiver characteristic curve was 0.66 (95% confidence interval [CI], 0.56-0.77). Moreover, Nephrocheck® was significantly and inversely correlated with UO (ρ = -.46, p < .001) at the time of measurement and, on a multivariable logistic regression, Nephrocheck® was not associated with subsequent Stage 2 or 3 AKI (OR 1.06 [95% CI, 0.74-1.53], p = .73). In contrast, the UO had an OR of 0.98 for each ml/h increase (95% CI, 0.97-1.00, p = .007). CONCLUSION: Nephrocheck®'s predictive performance was limited and its value was inversely correlated with UO. Nephrocheck® had no independent relationship with outcome once UO at measurement was considered.

Ammonia Clearance with Different Continuous Renal Replacement Therapy Techniques in Patients with Liver Failure.

INTRODUCTION: Continuous renal replacement therapy (CRRT) can be used to treat hyperammonaemia. However, no study has assessed the effect of different CRRT techniques on ammonia clearance. METHODS: We compared 3 different CRRT techniques in adult patients with hyperammonaemia, liver failure, and acute kidney injury. We protocolized CRRT to progressively deliver continuous veno-venous haemofiltration (CVVH), haemodialysis (CVVHD) or haemodiafiltration (CVVHDF). Ammonia was simultaneously sampled from the patient's arterial blood and effluent fluid for each technique. We applied accepted equations to calculate clearance. RESULTS: We studied 12 patients with a median age of 47 years (interquartile range [IQR] 25-79). Acute liver failure was present in 4 (25%) and acute-on-chronic liver failure in 8 (75%). There was no significant difference in median ammonia clearance between CRRT technique; CVVH: 27 (IQR 23-32) mL/min versus CVVHD: 21 (IQR 17-28) mL/min versus CVVHDF: 20 (IQR 14-28) mL/min, p = 0.32. Moreover, for all techniques, ammonia clearance was significantly less than urea and creatinine clearance; urea 50 (47-54) mL/min versus creatinine 42 (IQR 38-46) mL/min versus ammonia 25 (IQR 18-29) mL/min, p = 0.0001. CONCLUSION: We found no significant difference in ammonia clearance according to CRRT technique and demonstrated that ammonia clearance is significantly less than urea or creatinine clearance.

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.

A comparison of the hemodynamic effects of fluid bolus therapy with crystalloids vs. 4% albumin and vs. 20% albumin in patients after cardiac surgery.

BACKGROUND: Crystalloids, 4% albumin and 20% albumin are used for fluid bolus therapy (FBT) in patients after cardiac surgery. However, their detailed early (30 min) hemodynamic effects remain unstudied. METHODS: In a comparative prospective observational trial of 120 ventilated, we studied post cardiac surgery patients who received crystalloid 500 ml FBT, 4% albumin 500 ml FBT or 20% albumin 100 ml FBT (40 per group). We recorded second-by-second hemodynamic parameters and 15-minutely cardiac index (CI) data before and for 30 min after FBT. We compared the crystalloid group (reference) vs. the 4% albumin group, and vs. the 20% albumin group. RESULTS: Immediately after FBT, the mean (standard deviation) CI increase was 0.4 (0.4) L/min/m2 with crystalloids, 0.4 (0.5) L/min/m2 with 4% albumin and 0.3 (0.4) L/min/m2 with 20% albumin, despite the much smaller FBT volume with 20% albumin. Mean arterial pressure (MAP) increase was 11 (10), 12 (9) and 9 (6) mm Hg, respectively. There was no group effect or interaction for changes in CI. However, there were time-group interactions for MAP changes such that crystalloid FBT had faster MAP reduction than 4% (p<0.001) or 20% albumin (p < 0.001). Moreover, patients treated with crystalloid FBT showed a faster decline in central venous pressure, perfusion pressure than the two groups. Finally, 20% albumin attenuated the fall in temperature induced by FBT. CONCLUSION: In postoperative cardiac surgery patients, after a similar initial CI and MAP response, the MAP effect of crystalloid FBT dissipates faster than that of 4% or 20% albumin FBT. These findings can be used to inform clinical practice.

High Mobility Group Box 1 and Interleukin 6 at Intensive Care Unit Admission as Biomarkers in Critically Ill COVID-19 Patients.

Exuberant inflammation manifesting as a "cytokine storm" has been suggested as a central feature in the pathogenesis of severe coronavirus disease 2019 (COVID-19). This study investigated two prognostic biomarkers, the high mobility group box 1 (HMGB1) and interleukin-6 (IL-6), in patients with severe COVID-19 at the time of admission in the intensive care unit (ICU). Of 60 ICU patients with COVID-19 enrolled and analyzed in this prospective cohort study, 48 patients (80%) were alive at ICU discharge. HMGB1 and IL-6 plasma levels at ICU admission were elevated compared with a healthy control, both in ICU nonsurvivors and ICU survivors. HMGB1 and IL-6 plasma levels were higher in patients with a higher Sequential Organ Failure Assessment (SOFA) score (> 10), and the presence of septic shock or acute kidney injury. HMGB1 and IL-6 plasma levels were also higher in patients with a poor oxygenation status (PaO2/FiO2 < 150 mm Hg) and a longer duration of ventilation (> 7 days). Plasma HMGB1 and IL-6 levels at ICU admission also correlated with other prognostic markers, including the maximum neutrophil/lymphocyte ratio, D-dimer levels, and C-reactive protein levels. Plasma HMGB1 and IL-6 levels at ICU admission predicted ICU mortality with comparable accuracy to the SOFA score and the COVID-GRAM risk score. Higher HMGB1 and IL-6 were not independently associated with ICU mortality after adjustment for age, gender, and comorbidities in multivariate analysis models. In conclusion, plasma HMGB1 and IL6 at ICU admission may serve as prognostic biomarkers in critically ill COVID-19 patients.

Time to Initiation of Renal Replacement Therapy Among Critically Ill Patients With Acute Kidney Injury: A Current Systematic Review and Meta-Analysis.

OBJECTIVES: The optimal time to initiate renal replacement therapy in critically ill patients with acute kidney injury is controversial. We investigated the effect of such earlier versus later initiation of renal replacement therapy on the primary outcome of 28-day mortality and other patient-centered secondary outcomes. DESIGN: We searched MEDLINE (via PubMed), EMBASE, and Cochrane databases to July 17, 2020, and included randomized controlled trials comparing earlier versus later renal replacement therapy. SETTING: Multiple centers involved in eight trials. PATIENTS: Total of 4,588 trial participants. INTERVENTION: Two independents investigators screened and extracted data using a predefined form. We selected randomized controlled trials in critically ill adult patients with acute kidney injury and compared of earlier versus later initiation of renal replacement therapy regardless of modality. MEASUREMENTS AND MAIN RESULTS: Overall, 28-day mortality was similar between earlier and later renal replacement therapy initiation (38.43% vs 38.06%, respectively; risk ratio, 1.01; [95% CI, 0.94-1.09]; I2 = 0%). Earlier renal replacement therapy, however, shortened hospital length of stay (mean difference, -2.14 d; [95% CI, -4.13 to -0.14]) and ICU length of stay (mean difference, -1.18 d; [95% CI, -1.95 to -0.42]). In contrast, later renal replacement therapy decreased the use of renal replacement therapy (relative risk, 0.69; [95% CI, 0.58-0.82]) and lowered the risk of catheter-related blood stream infection (risk ratio, 0.50, [95% CI, 0.29-0.86). Among survivors, renal replacement therapy dependence at day 28 was similar between earlier and later renal replacement therapy initiation (risk ratio, 0.98; [95% CI, 0.66-1.40]). CONCLUSIONS: Earlier or later initiation of renal replacement therapy did not affect mortality. However, earlier renal replacement therapy was associated with significantly shorter ICU and hospital length of stay, whereas later renal replacement therapy was associated with decreased use of renal replacement therapy and decreased risk of catheter-related blood stream infection. These findings can be used to guide the management of critically ill patients with acute kidney injury.

The Effect of Early Sedation With Dexmedetomidine on Body Temperature in Critically Ill Patients.

OBJECTIVES: Previous case series reported an association between dexmedetomidine use and hyperthermia. Temperature data have not been systematically reported in previous randomized controlled trials evaluating dexmedetomidine. A causal link between dexmedetomidine administration and elevated temperature has not been demonstrated. DESIGN: Post hoc analysis. SETTING: Four ICUs in Australia and New Zealand. PATIENTS: About 703 mechanically ventilated ICU patients. INTERVENTIONS: Early sedation with dexmedetomidine versus usual care. MEASUREMENTS AND MAIN RESULTS: The primary outcome was mean daily body temperature. Secondary outcomes included the proportions of patients with body temperatures greater than or equal to 38.3°C and greater than or equal to 39°C, respectively. Outcomes were recorded for 5 days postrandomization in the ICU. The mean daily temperature was not different between the dexmedetomidine (n = 351) and usual care (n = 352) groups (36.84°C ± sd vs 36.78°C ± sd; p = 0.16). Over the first 5 ICU days, more dexmedetomidine group (vs usual care) patients had a temperature greater than or equal to 38.3°C (43.3% vs 32.7%, p = 0.004; absolute difference 10.6 percentage points) and greater than or equal to 39.0°C (19.4% vs 12.5%, p = 0.013; absolute difference 6.9 percentage points). Results were similar after adjusting for diagnosis, admitting temperature, age, weight, study site, sepsis occurrence, and the time from dexmedetomidine initiation to first hyperthermia recorded. There was a significant dose response relationship with temperature increasing by 0.30°C ±0.08 for every additional 1 µg/kg/hr of dexmedetomidine received p < 0.0002. CONCLUSIONS: Our study suggests potentially important elevations in body temperature are associated with early dexmedetomidine sedation, in adults who are mechanically ventilated in the ICU.

Efficacy and Safety of Parenteral High-Dose Vitamin C Therapy in Pediatric Patients: A Scoping Review.

OBJECTIVES: Recently, several adult trials have investigated the potential benefit of high-dose vitamin C therapy in critically ill patients. In pediatric patients, little is known on the efficacy, safety, and risk of high-dose vitamin C therapy. We aimed to review the efficacy and potential harm associated with high-dose vitamin C treatment. DATA SOURCES: We searched MEDLINE, EMBASE, Cochrane Library, and National Institute of Health Clinical Trials Register. STUDY SELECTION: We included studies in neonatal and pediatric patients who received IV or intra-arterial high-dose vitamin C (ascorbic acid) defined as greater than or equal to 75 mg/kg/d. DATA EXTRACTION: Two independent investigators screened articles and extracted data. DATA SYNTHESIS: We found 1,364 articles, assessed 193 full texts for eligibility, and identified 12 eligible studies. These studies included 855 patients, with 194 receiving high-dose vitamin C. The age of patients who received high-dose vitamin C ranged from 2 hours after delivery to 8.4 years (median 2.4 yr), and the vitamin C dose ranged from 100 to 1,500 mg/kg/d (median 260.5 mg/kg/d). Four studies were double-blind randomized controlled trials, and no clinical efficacy outcome was reported in favor of or against vitamin C. Furthermore, no adverse event or signal of harm was reported with high-dose vitamin C. CONCLUSIONS: In 12 studies with 194 children treated with parenteral high-dose vitamin C, there was no evidence of clinical efficacy or inferior clinical outcomes in double-blind randomized controlled trials, and no reported harmful effects. These findings justify further investigations of this treatment in children.

Comparison of the Hemodynamic and Temperature Effects of a 500-mL Bolus of 4% Albumin at Room Versus Body Temperature in Cardiac Surgery Patients.

OBJECTIVE: To compare the hemodynamic effect of room temperature (cold) 4% albumin fluid bolus therapy (FBT) with body temperature (warm) albumin FBT. DESIGN: Prospective, before-after trial. SETTING: A tertiary intensive care unit (ICU). PARTICIPANTS: Sixty ventilated, post-cardiac surgery patients prescribed with 4% albumin FBT. INTERVENTION: Cold or warm 4% albumin 500 ml FBT. MEASUREMENTS AND MAIN RESULTS: We recorded hemodynamic parameters before and for 30 minutes after FBT. Cardiac index (CI) and mean arterial pressure (MAP) responses were defined by a CI increase >15% and a MAP increase >10%, respectively. Immediately after FBT, median [interquartile range] core temperature changed by -0.3 [-0.4; -0.3] °C with cold albumin vs. 0.0 [0.0; 0.1]°C with warm albumin (P<0.001). The median CI increase was 0.3 [0.0; 0.5] L/min/m2 with 14 CI-responders (47%) in both groups (P>0.99). The median immediate MAP increase was 9 [3; 15] mmHg with cold albumin vs. 11 [5; 13] mmHg with warm albumin (P=0.79), with a MAP-response in 16 vs. 17 patients (P=0.99). There was an interaction between group and time for MAP (P=0.002), mean pulmonary artery pressure (PAP) (P=0.002) and core temperature (P<0.001). In the cold albumin group, after the initial response, MAP and mean PAP decreased more slowly than with warm albumin and, after the initial fall, core temperature increased toward baseline. CONCLUSION: In postoperative cardiac surgery patients, warm albumin FBT prevents the decrease in core temperature and, after an initial similar increase, is associated with a faster return of MAP and mean PAP toward baseline.