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

IntroductionRespiratory syncytial virus (RSV) infection is an emerging infectious disease. However, the impacts of RSV infection among patients with respiratory failure have not been identified.ObjectiveThis study investigated the 28-day mortality and clinical outcomes of RSV infection in patients with respiratory failure.MethodsThis 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.ResultsRespiratory 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.ConclusionAmong 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

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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13054-022-04151-5

Stability of bicarbonate in normal saline: a technical report

BACKGROUND: The benefit of intravenous sodium bicarbonate administration in patients with severe metabolic acidosis remains controversial, partly due to lack of double-blind trials. From a practical viewpoint, such blinding requires testing of the stability of sodium bicarbonate in polyolefin bags. METHODS: We examined seven samples of 100 mL 8.4% sodium bicarbonate diluted in 150 mL normal saline within a 250 mL polyolefin bag at time 0, 24 and 48 hours after preparation. We measured pH, Pco2, and bicarbonate concentration. RESULTS: Over a period of 48 hours, both pH and Pco2 decreased significantly (hourly rate of change, -0.001 [P = 0.043) and -0.098 [P < 0.001] respectively). However, the concentration of bicarbonate did not decrease, with an hourly rate of change of only -0.009 (P = 0.42). CONCLUSION: When 100 mL of 8.4% sodium bicarbonate are diluted in 150 mL of normal saline within a 250 mL polyolefin bag, changes in pH and Pco2 over a 48-hour period are small and bicarbonate concentration remains stable

Sodium bicarbonate in 5% dextrose: can clinicians tell the difference?

BACKGROUND: Due to the lack of double-blind randomised controlled trials, the true effect of intravenous sodium bicarbonate therapy in ICU patients with metabolic acidosis remains unclear. METHODS: We diluted 100 mL 8.4% sodium bicarbonate in 150 mL 5% dextrose (D5W) within a 250 mL polyolefin bag after removing 100 mL. We asked ICU clinicians to inspect a 250 mL bag containing sodium bicarbonate or a 250 mL bag where 100 mL of D5W had been removed and then returned. The bags were attached to intravenous giving sets. We asked participants to identify the contents of the bags. RESULTS: Among 60 participants (39 nursing staff [65%], 20 medical staff [33.3%] and one pharmacist), 36 (60%) answered correctly. The Cohen κ for agreement between test bag content and participants' answers was 0.20 (95% CI, -0.05 to 0.45; P = 0.12), implying the answers were correct by chance. In the group of 28 participants who indicated they used a clue to help them decide their answer, 15 (53.6%) answered correctly, whereas in the remainder (n = 32), 21 (65.6%) answered correctly (P = 0.49). CONCLUSION: When 100 mL of 8.4% sodium bicarbonate were diluted in 150 mL of D5W within a 250 mL polyolefin bag, clinicians were unable to correctly identify the contents of the bags. Our findings imply that sodium bicarbonate therapy can be successfully blinded

Heterogeneity of Effect of Net Ultrafiltration Rate among Critically Ill Adults Receiving Continuous Renal Replacement Therapy

Introduction: In continuous renal replacement therapy (CRRT)-Treated patients, a net ultrafiltration (NUF) rate >1.75 mL/kg/h has been associated with increased mortality. However, there may be heterogeneity of effect of NUF rate on mortality, according to patient characteristics. Methods: To investigate the presence and impact of heterogeneity of effect, we performed a secondary analysis of the "Randomized Evaluation of Normal versus Augmented Level of Renal Replacement Therapy"(RENAL) trial. Exposure was NUF rate (weight-Adjusted fluid volume removed per hour) stratified into tertiles (1.75 mL/kg/h). Primary outcome was 90-day mortality. Patients were clustered according to baseline characteristics. Heterogeneity of effect was assessed according to clusters and baseline edema and related to the additional impact of baseline cardiovascular Sequential Organ Failure Assessment (SOFA) score. We excluded patients with missing values for baseline weight and/or treatment duration. Results: We identified 2 clusters. The largest (cluster 1; n = 941) included more severely ill patients, with more sepsis, more edema, and more vasopressor therapy (all p < 0.001). Compared to the middle tertile, the probability of harm was greater with the high tertile of NUF rate in patients in cluster 1 and in patients with baseline edema (probability of harm, cluster 1: 99.9%; edema: 99.1%). Moreover, higher baseline cardiovascular SOFA score also increased mortality risk with both high and low compared to middle NUF rates in cluster 1 patients and in patients with edema. Conclusions: In CRRT patients, both high and low NUF rates may be harmful, especially in those with edema, sepsis, and greater illness severity. Cardiovascular SOFA scores modulate this association. Additional studies are needed to test these hypotheses, and targeted trials of NUF rates based on risk stratification appear justified. Trial Registration: ClinicalTrials.gov identifier: NCT00221013

Hourly fluid balance in patients receiving continuous renal replacement therapy

Little is known about early (first 48 h) hourly and cumulative fluid balance (FB) during continuous renal replacement therapy (CRRT). To study the characteristics and outcome associations of early hourly and cumulative FB. Methods: We studied FB in CRRT patients (2016-2018). Results: Among 350 patients, mean hourly FB became negative after 20 CRRT hours, but within 6 CRRT hours in patients with baseline fluid overload. A negative early FB was never achieved in patients receiving vasopressor therapy (p < 0.001). Mortality was 31%. The percentage of hourly negative FB was independently associated with decreased ICU mortality. A time-weighted hourly FB between 18.5 and -33 mL/h was also significantly and independently associated with decreased mortality. Conclusions: In CRRT patients, an early FB conservative approach is possible, modulated by patient characteristics, and associated with a low mortality. Moreover, avoidance of an early positive FB is associated with decreased mortality

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

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

Mediators of the impact of hourly net ultrafiltration rate on mortality in critically ill patients receiving continuous renal replacement therapy

Objectives: During continuous renal replacement therapy, a high net ultrafiltration rate has been associated with increased mortality. However, it is unknown what might mediate its putative effect on mortality. In this study, we investigated whether the relationship between early (first 48 hr) net ultrafiltration and mortality is mediated by fluid balance, hemodynamic instability, or low potassium or phosphate blood levels using mediation analysis and the primary outcome was hospital mortality. Design: Retrospective, observational study. Setting: Mixed medical and surgical ICUs at Austin hospital, Melbourne, Australia. Patients: Critically ill patients treated with continuous renal replacement therapy within 14 days of ICU admission who survived greater than 48 hours. Interventions: None. Measurements and Main Results: We studied 347 patients (median [interquartile range] age: 64 yr [53-71 yr] and Acute Physiology and Chronic Health Evaluation III score: 73 (54-90)]. After adjustment for confounders, compared with a net ultrafiltration less than 1.01 mL/kg/hr, a net ultrafiltration rate greater than 1.75 mL/kg/hr was associated with significantly greater mortality (adjusted odds ratio, 1.15; 95% CI, 1.03-1.29; p = 0.011). Adjusted univariable mediation analysis found no suggestion of a causal mediation pathway for this effect by blood pressure, vasopressor therapy, or potassium levels, but identified a possible mediation effect for fluid balance (average causal mediation effect, 0.95; 95% CI, 0.89-1.00; p = 0.060) and percentage of phosphate measurements with hypophosphatemia (average causal mediation effect, 0.96; 95% CI, 0.92-1.00; p = 0.055). However, on multiple mediator analyses, these two variables showed no significant effect. In contrast, a high net ultrafiltration rate had an average direct effect of 1.24 (95% CI, 1.11-1.40; p < 0.001). Conclusions: An early net ultrafiltration greater than 1.75 mL/kg/hr was independently associated with increased hospital mortality. Its putative effect on mortality was direct and not mediated by a causal pathway that included fluid balance, low blood pressure, vasopressor use, hypokalemia, or hypophosphatemia