The effects of higher versus lower protein delivery in critically ill patients: an updated systematic review and meta-analysis of randomized controlled trials with trial sequential analysis.

BACKGROUND: A recent large multicentre trial found no difference in clinical outcomes but identified a possibility of increased mortality rates in patients with acute kidney injury (AKI) receiving higher protein. These alarming findings highlighted the urgent need to conduct an updated systematic review and meta-analysis to inform clinical practice. METHODS: From personal files, citation searching, and three databases searched up to 29-5-2023, we included randomized controlled trials (RCTs) of adult critically ill patients that compared higher vs lower protein delivery with similar energy delivery between groups and reported clinical and/or patient-centred outcomes. We conducted random-effect meta-analyses and subsequently trial sequential analyses (TSA) to control for type-1 and type-2 errors. The main subgroup analysis investigated studies with and without combined early physical rehabilitation intervention. A subgroup analysis of AKI vs no/not known AKI was also conducted. RESULTS: Twenty-three RCTs (n = 3303) with protein delivery of 1.49 ± 0.48 vs 0.92 ± 0.30 g/kg/d were included. Higher protein delivery was not associated with overall mortality (risk ratio [RR]: 0.99, 95% confidence interval [CI] 0.88-1.11; I2 = 0%; 21 studies; low certainty) and other clinical outcomes. In 2 small studies, higher protein combined with early physical rehabilitation showed a trend towards improved self-reported quality-of-life physical function measurements at day-90 (standardized mean difference 0.40, 95% CI - 0.04 to 0.84; I2 = 30%). In the AKI subgroup, higher protein delivery significantly increased mortality (RR 1.42, 95% CI 1.11-1.82; I2 = 0%; 3 studies; confirmed by TSA with high certainty, and the number needed to harm is 7). Higher protein delivery also significantly increased serum urea (mean difference 2.31 mmol/L, 95% CI 1.64-2.97; I2 = 0%; 7 studies). CONCLUSION: Higher, compared with lower protein delivery, does not appear to affect clinical outcomes in general critically ill patients but may increase mortality rates in patients with AKI. Further investigation of the combined early physical rehabilitation intervention in non-AKI patients is warranted. PROSPERO ID: CRD42023441059.

Early experience of using regional citrate anticoagulation for continuous renal replacement therapy in critically ill patients in a resource-limited setting.

AIM: Despite the superiority of regional citrate anticoagulation (RCA) in continuous renal replacement therapy (CRRT), its application is limited in resource-limited settings. We aim to explore the cost and safety of RCA for CRRT in critically ill patients, compared to usual care. METHODS: This prospective observational study included patients requiring CRRT in a tertiary intensive care unit (ICU) from February 2022 to January 2023. They were classified to either the RCA or usual care groups based on the anticoagulation technique chosen by the treating physician, considering contraindications. The CRRT prescription follows the institutional protocol. All relevant data were obtained from the ICU CRRT-RCA charts and electronic medical records. A cost analysis was performed. RESULTS: A total of 54 patients (27 per group) were included, with no demographic differences. Sequential Organ Failure Assessment score and lactate levels were significantly higher in the usual care group. The number of filters used were comparable (p = .108). The median filter duration in the RCA group was numerically longer (35.00 [15.50-56.00] vs. 23.00 [17.00-29.00] h), but not statistically significant (p = .253). The duration of mechanical ventilation, vasopressor requirement, and mortality were similar, but the RCA group had a significantly longer ICU stay. The rate of adverse events was similar, with four severe metabolic alkalosis cases in the RCA group. The RCA group had higher total cost per patient per day (USD 611 vs. 408; p = .013). CONCLUSION: In this resource-limited setting, RCA for CRRT appeared safe and had clinically longer filter lifespan compared with usual care, albeit the increased cost.

Prolonged vs Intermittent Infusions of ß-Lactam Antibiotics in Adults With Sepsis or Septic Shock: A Systematic Review and Meta-Analysis.

Importance: There is uncertainty about whether prolonged infusions of ß-lactam antibiotics improve clinically important outcomes in critically ill adults with sepsis or septic shock. Objective: To determine whether prolonged ß-lactam antibiotic infusions are associated with a reduced risk of death in critically ill adults with sepsis or septic shock compared with intermittent infusions. Data Sources: The primary search was conducted with MEDLINE (via PubMed), CINAHL, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov from inception to May 2, 2024. Study Selection: Randomized clinical trials comparing prolonged (continuous or extended) and intermittent infusions of ß-lactam antibiotics in critically ill adults with sepsis or septic shock. Data Extraction and Synthesis: Data extraction and risk of bias were assessed independently by 2 reviewers. Certainty of evidence was evaluated with the Grading of Recommendations Assessment, Development and Evaluation approach. A bayesian framework was used as the primary analysis approach and a frequentist framework as the secondary approach. Main Outcomes and Measures: The primary outcome was all-cause 90-day mortality. Secondary outcomes included intensive care unit (ICU) mortality and clinical cure. Results: From 18 eligible randomized clinical trials that included 9108 critically ill adults with sepsis or septic shock (median age, 54 years; IQR, 48-57; 5961 men [65%]), 17 trials (9014 participants) contributed data to the primary outcome. The pooled estimated risk ratio for all-cause 90-day mortality for prolonged infusions of ß-lactam antibiotics compared with intermittent infusions was 0.86 (95% credible interval, 0.72-0.98; I2 = 21.5%; high certainty), with a 99.1% posterior probability that prolonged infusions were associated with lower 90-day mortality. Prolonged infusion of ß-lactam antibiotics was associated with a reduced risk of intensive care unit mortality (risk ratio, 0.84; 95% credible interval, 0.70-0.97; high certainty) and an increase in clinical cure (risk ratio, 1.16; 95% credible interval, 1.07-1.31; moderate certainty). Conclusions and Relevance: Among adults in the intensive care unit who had sepsis or septic shock, the use of prolonged ß-lactam antibiotic infusions was associated with a reduced risk of 90-day mortality compared with intermittent infusions. The current evidence presents a high degree of certainty for clinicians to consider prolonged infusions as a standard of care in the management of sepsis and septic shock. Trial Registration: PROSPERO Identifier: CRD42023399434.

The impact of higher protein dosing on outcomes in critically ill patients with acute kidney injury: a post hoc analysis of the EFFORT protein trial.

BACKGROUND: Based on low-quality evidence, current nutrition guidelines recommend the delivery of high-dose protein in critically ill patients. The EFFORT Protein trial showed that higher protein dose is not associated with improved outcomes, whereas the effects in critically ill patients who developed acute kidney injury (AKI) need further evaluation. The overall aim is to evaluate the effects of high-dose protein in critically ill patients who developed different stages of AKI. METHODS: In this post hoc analysis of the EFFORT Protein trial, we investigated the effect of high versus usual protein dose (≥ 2.2 vs. ≤ 1.2 g/kg body weight/day) on time-to-discharge alive from the hospital (TTDA) and 60-day mortality and in different subgroups in critically ill patients with AKI as defined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria within 7 days of ICU admission. The associations of protein dose with incidence and duration of kidney replacement therapy (KRT) were also investigated. RESULTS: Of the 1329 randomized patients, 312 developed AKI and were included in this analysis (163 in the high and 149 in the usual protein dose group). High protein was associated with a slower time-to-discharge alive from the hospital (TTDA) (hazard ratio 0.5, 95% CI 0.4-0.8) and higher 60-day mortality (relative risk 1.4 (95% CI 1.1-1.8). Effect modification was not statistically significant for any subgroup, and no subgroups suggested a beneficial effect of higher protein, although the harmful effect of higher protein target appeared to disappear in patients who received kidney replacement therapy (KRT). Protein dose was not significantly associated with the incidence of AKI and KRT or duration of KRT. CONCLUSIONS: In critically ill patients with AKI, high protein may be associated with worse outcomes in all AKI stages. Recommendation of higher protein dosing in AKI patients should be carefully re-evaluated to avoid potential harmful effects especially in patients who were not treated with KRT. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov (NCT03160547) on May 17th 2017.

The diuretic effect of adding aminophylline or theophylline to furosemide in pediatric populations: a systematic review.

The diuretic effect of the combined furosemide and aminophylline/theophylline among pediatric patients remains unclear. The primary aim of this systematic review was to examine the clinical diuretic effects (urine output and fluid balance) of co-administration of furosemide and aminophylline/theophylline as compared to furosemide alone in pediatric population. Ovid MEDLINE, CENTRAL, and EMBASE were searched from its inception until March 2022 for observational studies and randomized controlled trials (RCTs) comparing the administration of furosemide versus furosemide and aminophylline/theophylline in pediatric population. Case reports, case series, commentaries, letters to editors, systematic reviews, and meta-analyses were excluded. Five articles with a total sample population of 187 patients were included in this systematic review. As compared to the furosemide alone, our pooled data demonstrated that co-administration of furosemide and aminophylline/theophylline was associated with higher urine output (mean difference: 2.91 [90% CI 1.54 to 4.27], p < 0.0001, I2 = 90%) and a more negative fluid balance (mean difference - 28.27 [95% CI: - 46.21 to - 10.33], p = 0.002, I2 = 56%) than those who received furosemide alone. CONCLUSION: This is the first paper summarizing the evidence of combined use of furosemide with aminophylline/theophylline in pediatric population. Our systematic review demonstrated that the co-administration of furosemide and aminophylline/theophylline could potentially yield better diuretic effects of urine output and negative fluid balance than furosemide alone in pediatric patients with fluid overload. Given the substantial degree of heterogeneity and low level of evidence, future adequately powered trials are warranted to provide evidence regarding the combined use of aminophylline/theophylline and furosemide as diuretic in the pediatric population. WHAT IS KNOWN: • Fluid overload is associated with poor prognosis for children in the intensive care unit. • The ineffective result of furosemide alone, even at high dose, as diuretic agent for children with diuretic resistant fluid overload in the intensive care unit. WHAT IS NEW: • This is the first systematic review that compares furosemide alone and co-administration of furosemide and aminophylline/theophylline. • This paper showed potential benefit of co-administration of furosemide and aminophylline/theophylline promoting urine output and negative fluid balance compared to furosemide alone.

Association between intraoperative remifentanil use and postoperative hyperalgesia in adolescent idiopathic scoliosis surgery: a retrospective study.

BACKGROUND: The liberal use of remifentanil in spine surgery has been associated with an increased incidence of postoperative hyperalgesia. Nevertheless, controversies remain as the existing evidence is inconclusive to determine the relationship between remifentanil use and the development of opioid-induced hyperalgesia. We hypothesized that intraoperative infusion of higher dose remifentanil during scoliosis surgery is associated with postoperative hyperalgesia, manifesting clinically as greater postoperative morphine consumption and pain scores. METHODS: Ninety-seven patients with adolescent idiopathic scoliosis (AIS) who underwent posterior spinal fusion surgery at a single tertiary institution from March 2019 until June 2020 were enrolled in this retrospective study. Anesthesia was maintained using a target-controlled infusion of remifentanil combined with volatile anesthetic desflurane in 92 patients, while five patients received it as part of total intravenous anesthesia. Intravenous ketamine, paracetamol, and fentanyl were administered as multimodal analgesia. All patients received patient-controlled analgesia (PCA) morphine postoperatively. Pain scores at rest and on movement, assessed using the numerical rating scale, and the cumulative PCA morphine consumption were collected at a six-hourly interval for up to 48 h. According to the median intraoperative remifentanil dose usage of 0.215 µg/kg/min, patients were divided into two groups: low dose and high dose group. RESULTS: There were no significant differences in the pain score and cumulative PCA morphine consumption between the low and high dose remifentanil group. The mean duration of remifentanil infusion was 134.9 ± 22.0 and 123.4 ± 23.7 min, respectively. CONCLUSION: Intraoperative use of remifentanil as an adjuvant in AIS patients undergoing posterior spinal fusion surgery was not associated with postoperative hyperalgesia.

Changing predominant SARS-CoV-2 lineages drives successive COVID-19 waves in Malaysia, February 2020 to March 2021.

Malaysia has experienced three waves of coronavirus disease 2019 (COVID-19) as of March 31, 2021. We studied the associated molecular epidemiology and SARS-CoV-2 seroprevalence during the third wave. We obtained 60 whole-genome SARS-CoV-2 sequences between October 2020 and January 2021 in Kuala Lumpur/Selangor and analyzed 989 available Malaysian sequences. We tested 653 residual serum samples collected between December 2020 to April 2021 for anti-SARS-CoV-2 total antibodies, as a proxy for population immunity. The first wave (January 2020) comprised sporadic imported cases from China of early Pango lineages A and B. The second wave (March-June 2020) was associated with lineage B.6. The ongoing third wave (from September 2020) was propagated by a state election in Sabah. It is due to lineage B.1.524 viruses containing spike mutations D614G and A701V. Lineages B.1.459, B.1.470, and B.1.466.2 were likely imported from the region and confined to Sarawak state. Direct age-standardized seroprevalence in Kuala Lumpur/Selangor was 3.0%. The second and third waves were driven by super-spreading events and different circulating lineages. Malaysia is highly susceptible to further waves, especially as alpha (B.1.1.7) and beta (B.1.351) variants of concern were first detected in December 2020/January 2021. Increased genomic surveillance is critical.

Administration of vitamin D and its metabolites in critically ill adult patients: an updated systematic review with meta-analysis of randomized controlled trials.

BACKGROUND: The clinical significance of vitamin D administration in critically ill patients remains inconclusive. The purpose of this systematic review with meta-analysis was to investigate the effect of vitamin D and its metabolites on major clinical outcomes in critically ill patients, including a subgroup analysis based on vitamin D status and route of vitamin D administration. METHODS: Major databases were searched through February 9, 2022. Randomized controlled trials of adult critically ill patients with an intervention group receiving vitamin D or its metabolites were included. Random-effect meta-analyses were performed to estimate the pooled risk ratio (dichotomized outcomes) or mean difference (continuous outcomes). Risk of bias assessment included the Cochrane tool for assessing risk of bias in randomized trials. RESULTS: Sixteen randomized clinical trials with 2449 patients were included. Vitamin D administration was associated with lower overall mortality (16 studies: risk ratio 0.78, 95% confidence interval 0.62-0.97, p = 0.03; I2 = 30%), reduced intensive care unit length of stay (12 studies: mean difference - 3.13 days, 95% CI - 5.36 to - 0.89, n = 1250, p = 0.006; I2 = 70%), and shorter duration of mechanical ventilation (9 studies: mean difference - 5.07 days, 95% CI - 7.42 to - 2.73, n = 572, p < 0.0001; I2 = 54%). Parenteral administration was associated with a greater effect on overall mortality than enteral administration (test of subgroup differences, p = 0.04), whereas studies of parenteral subgroups had lower quality. There were no subgroup differences based on baseline vitamin D levels. CONCLUSIONS: Vitamin D supplementation in critically ill patients may reduce mortality. Parenteral administration might be associated with a greater impact on mortality. Heterogeneity and assessed certainty among the studies limits the generalizability of the results. TRIAL REGISTRATION: PROSPERO international prospective database of systematic reviews (CRD42021256939-05 July 2021).

High-Dose versus Low-Dose Corticosteroids in COVID-19 Patients: a Systematic Review and Meta-analysis.

OBJECTIVES: The clinical efficacy of corticosteroids remains unclear. The primary aim of this systematic review and meta-analysis was to evaluate the use of high-dose versus low- dose corticosteroids on the mortality rate of COVID-19 patients. DESIGN: Systematic review and meta-analysis. SETTING: Electronic search for randomized controlled trials and observational studies (MEDLINE, EMBASE, CENTRAL). PARTICIPANTS: Hospitalized adults ≥ 18 years old who were SARS-CoV-2 PCR positive. INTERVENTIONS: High-dose and low-dose corticosteroids. MEASUREMENTS AND MAIN RESULTS: A total of twelve studies (n=2759 patients) were included in this review. The pooled analysis demonstrated no significant difference in mortality rate between the high-dose and low-dose corticosteroids groups (n=2632; OR: 1.07 [95%CI 0.67, 1.72], p=0.77, I2=76%, trial sequential analysis=inconclusive). No significant differences were observed in the incidence of intensive care unit (ICU) admission rate (n=1544; OR: 0.77[95%CI 0.43, 1.37], p=0.37, I2= 72%), duration of hospital stay (n=1615; MD: 0.53[95%CI -1.36, 2.41], p=0.58, I2=87%), respiratory support (n=1694; OR: 1.51[95%CI 0.77, 2.96], p=0.23, I2=84%), duration of mechanical ventilation (n=419; MD: -1.44[95%CI -4.27, 1.40], p=0.32, I2=93%), incidence of hyperglycemia (n=516, OR: 0.91[95%CI 0.58, 1.43], p=0.68, I2=0%) and infection rate (n=1485, OR: 0.86[95%CI 0.64, 1.16], p=0.33, I2=29%). CONCLUSION: The meta-analysis demonstrated high-dose corticosteroids did not reduce mortality rate. However, high-dose corticosteroids did not pose higher risk of hyperglycemia and infection rate for COVID-19 patients. Due to the inconclusive trial sequential analysis, substantial heterogeneity and low level of evidence, future large-scale randomized clinical trials are warranted to improve the certainty of evidence for the use of high-dose compared to low-dose corticosteroids in COVID-19 patients.

The effect of higher versus lower protein delivery in critically ill patients: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The optimal protein dose in critical illness is unknown. We aim to conduct a systematic review of randomized controlled trials (RCTs) to compare the effect of higher versus lower protein delivery (with similar energy delivery between groups) on clinical and patient-centered outcomes in critically ill patients. METHODS: We searched MEDLINE, EMBASE, CENTRAL and CINAHL from database inception through April 1, 2021.We included RCTs of (1) adult (age ≥ 18) critically ill patients that (2) compared higher vs lower protein with (3) similar energy intake between groups, and (4) reported clinical and/or patient-centered outcomes. We excluded studies on immunonutrition. Two authors screened and conducted quality assessment independently and in duplicate. Random-effect meta-analyses were conducted to estimate the pooled risk ratio (dichotomized outcomes) or mean difference (continuous outcomes). RESULTS: Nineteen RCTs were included (n = 1731). Sixteen studies used primarily the enteral route to deliver protein. Intervention was started within 72 h of ICU admission in sixteen studies. The intervention lasted between 3 and 28 days. In 11 studies that reported weight-based nutrition delivery, the pooled mean protein and energy received in higher and lower protein groups were 1.31 ± 0.48 vs 0.90 ± 0.30 g/kg and 19.9 ± 6.9 versus 20.1 ± 7.1 kcal/kg, respectively. Higher vs lower protein did not significantly affect overall mortality [risk ratio 0.91, 95% confidence interval (CI) 0.75-1.10, p = 0.34] or other clinical or patient-centered outcomes. In 5 small studies, higher protein significantly attenuated muscle loss (MD -3.44% per week, 95% CI -4.99 to -1.90; p < 0.0001). CONCLUSION: In critically ill patients, a higher daily protein delivery was not associated with any improvement in clinical or patient-centered outcomes. Larger, and more definitive RCTs are needed to confirm the effect of muscle loss attenuation associated with higher protein delivery. PROSPERO registration number: CRD42021237530.

A Single-Center Prospective Observational Study Comparing Resting Energy Expenditure in Different Phases of Critical Illness: Indirect Calorimetry Versus Predictive Equations.

OBJECTIVES: Several predictive equations have been developed for estimation of resting energy expenditure, but no study has been done to compare predictive equations against indirect calorimetry among critically ill patients at different phases of critical illness. This study aimed to determine the degree of agreement and accuracy of predictive equations among ICU patients during acute phase (≤ 5 d), late phase (6-10 d), and chronic phase (≥ 11 d). DESIGN: This was a single-center prospective observational study that compared resting energy expenditure estimated by 15 commonly used predictive equations against resting energy expenditure measured by indirect calorimetry at different phases. Degree of agreement between resting energy expenditure calculated by predictive equations and resting energy expenditure measured by indirect calorimetry was analyzed using intraclass correlation coefficient and Bland-Altman analyses. Resting energy expenditure values calculated from predictive equations differing by ± 10% from resting energy expenditure measured by indirect calorimetry was used to assess accuracy. A score ranking method was developed to determine the best predictive equations. SETTING: General Intensive Care Unit, University of Malaya Medical Centre. PATIENTS: Mechanically ventilated critically ill patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Indirect calorimetry was measured thrice during acute, late, and chronic phases among 305, 180, and 91 ICU patients, respectively. There were significant differences (F= 3.447; p = 0.034) in mean resting energy expenditure measured by indirect calorimetry among the three phases. Pairwise comparison showed mean resting energy expenditure measured by indirect calorimetry in late phase (1,878 ± 517 kcal) was significantly higher than during acute phase (1,765 ± 456 kcal) (p = 0.037). The predictive equations with the best agreement and accuracy for acute phase was Swinamer (1990), for late phase was Brandi (1999) and Swinamer (1990), and for chronic phase was Swinamer (1990). None of the resting energy expenditure calculated from predictive equations showed very good agreement or accuracy. CONCLUSIONS: Predictive equations tend to either over- or underestimate resting energy expenditure at different phases. Predictive equations with "dynamic" variables and respiratory data had better agreement with resting energy expenditure measured by indirect calorimetry compared with predictive equations developed for healthy adults or predictive equations based on "static" variables. Although none of the resting energy expenditure calculated from predictive equations had very good agreement, Swinamer (1990) appears to provide relatively good agreement across three phases and could be used to predict resting energy expenditure when indirect calorimetry is not available.

Posterior parasagittal in-plane ultrasound-guided infraclavicular brachial plexus block-a case series.

BACKGROUND: The brachial plexus at the infraclavicular level runs deeper compared to its course proximally, giving rise to impaired needle visualisation due to the steep angle of needle insertion with the current ultrasound-guided approach. A new posterior parasagittal in-plane ultrasound-guided infraclavicular approach was introduced to improve needle visibility. However no further follow up study was done. METHODS: We performed a case series and a cadaveric dissection to assess its feasibility in a single centre, University of Malaya Medical Centre, Kuala Lumpur, Malaysia from November 2012 to October 2013. After obtaining approval from the Medical Ethics Committee, University Malaya Medical Centre, 18 patients undergoing upper limb surgery were prospectively recruited. A cadaveric dissection was also performed. The endpoints of this study were the success rate, performance time, total anaesthesia-related time, quality of anaesthesia and any incidence of complications. RESULTS: All patients had 100 % success rate. The imaging time, needling time and performance time were comparable with previously published study. There were no adverse events encountered in this study. The cadaveric dissection revealed a complete spread of methylene blue dye over the brachial plexus. CONCLUSION: This study demonstrated that the posterior parasagittal in-plane approach is a feasible and reliable technique with high success rate. Future studies shall compare this technique with the conventional lateral parasagittal in-plane approach. TRIAL REGISTRATION: ClinicalTrials.gov NCT02312453 . Registered on 8 December 2014.

Dexmedetomidine and ketamine sedation for dental extraction in children with cyanotic heart disease.

Treating children with cyanotic congenital heart disease poses many challenges to anesthesiologists because of the multiple problems associated with the condition. The anesthetic technique and drugs used perioperatively can affect a patient's physiologic status during surgery. The adherence to certain hemodynamic objectives and the avoidance of factors that could worsen the abnormal cardiopulmonary physiology cannot be overemphasized. In the present case series, we describe the use of a dexmedetomidine-ketamine combination for dental extraction in spontaneously breathing children with cyanotic congenital heart disease. The anesthetic concerns regarding airway management, the pharmacologic effects of drugs, and maintenance of adequate hemodynamic, blood gases, and acid-base status are discussed.

Outcomes of extracorporeal blood purification with oXiris® membrane in critically ill patients: A systematic review and meta-analysis.

PURPOSE: To evaluate the efficacy of the novel oXiris® membrane in critically ill adult patients. METHODS: We systematically searched MEDLINE, EMBASE, and CENTRAL from inception to 01/06/2023 for relevant randomised controlled trials (RCTs) and non-randomised studies of intervention (NRSI). The primary outcome was overall mortality. Random effect meta-analyses were conducted in RevMan 5.4.1. Study quality was evaluated using Cochrane's risk of bias tool. (PROSPERO: CRD42023389198). RESULTS: Ten studies (2 RCTs and 8 NRSIs) with 481 patients were included. None had low risk of bias. Treatment using oXiris® was associated with reduced overall mortality (RR 0.78, 95%CI 0.62-0.98; p = 0.03; 6 NRSI). One RCT reported 28-day mortality, finding no significant difference between groups. Besides, pooled NRSIs results showed significant reductions in SOFA scores, norepinephrine dosage, and several inflammatory biomarkers (C-reactive protein [CRP], lactate, and interleukin-6 [IL-6]) post oXiris® treatment. However, other clinical outcomes (ICU and hospital length of stay, mechanical ventilation duration) were similar between groups. CONCLUSION: In critically ill patients, the use of oXiris® membrane was associated with reduced overall mortality, norepinephrine dosage, CRP, IL-6, lactate levels, along with improved organ function. However, the certainty of evidence was very low, necessitating high-quality RCTs to further evaluate its efficacy in this population.

Early protein delivery in critically ill patients with acute kidney injury: post hoc analysis of a multicenter cluster-randomized controlled trial.

Background: There is controversy over the optimal early protein delivery in critically ill patients with acute kidney injury (AKI). This study aims to evaluate whether the association between early protein delivery and 28-day mortality was impacted by the presence of AKI in critically ill patients. Methods: This is a post hoc analysis of data from a multicenter cluster-randomised controlled trial enrolling newly admitted critically ill patients (n = 2772). Participants without chronic kidney disease and with complete data concerning baseline renal function were included in this study. The primary outcome was 28-day mortality. Cox proportional hazards models were used to analyze the association between early protein delivery, reflected by mean protein delivery from day 3-5 after enrollment, 28-day mortality and whether baseline AKI stages interacted with this association. Results: Overall, 2552 patients were included, among whom 567 (22.2%) had AKI at enrollment (111 stage I, 87 stage II, 369 stage III). Mean early protein delivery was 0.60 ± 0.38 g/kg/day among the study patients. In the overall study cohort, each 0.1 g/kg/day increase in protein delivery was associated with a 5% reduction in 28-day mortality[hazard ratio (HR) = 0.95; 95% confidence interval (CI) 0.92-0.98, p < 0.001]. The association between early protein delivery and 28-day mortality significantly interacted with baseline AKI stages (adjusted interaction p = 0.028). Each 0.1 g/kg/day increase in early protein delivery was associated with a 4% reduction in 28-day mortality (HR = 0.96; 95%CI 0.92-0.99, p = 0.011) among patients without AKI and 9% (HR = 0.91; 95%CI 0.84-0.99, p = 0.021) among those with AKI stage III. However, such associations cannot be observed among patients with AKI stages I and II. Conclusions: Increased early protein delivery (up to close to the guideline recommendation) was associated with reduced 28-day mortality in critically ill patients without AKI and with AKI stage III, but not in those with AKI stage I or II.

Intravenous vitamin C monotherapy in critically ill patients: a systematic review and meta-analysis of randomized controlled trials with trial sequential analysis.

BACKGROUND: A recent landmark randomized controlled trial (RCT) in septic patients demonstrated an increased risk of death and persistent organ dysfunction with intravenous Vitamin C (IVVC) monotherapy, which represents a disparate result from previous systematic reviews and meta-analyses (SRMA). We performed an updated SRMA of IVVC monotherapy to summarize and explore heterogeneity across current trials and conduct trial sequential analysis (TSA) to guard against type-I or type-II statistical errors. METHODS: RCTs evaluating IVVC in adult critically ill patients were included. Four databases were searched from inception to 22 June 2022 without language restrictions. The primary outcome was overall mortality. Random effect meta-analysis was performed to estimate the pooled risk ratio. TSA for mortality was performed using the DerSimonian-Laird random effect model, alpha 5%, beta 10%, and relative risk reduction (RRR) of 30%, 25%, and 20%. RESULTS: We included 16 RCTs (n = 2130). IVVC monotherapy is associated with significant reduction in overall mortality [risk ratio (RR) 0.73, 95% confidence interval (CI) 0.60-0.89; p = 0.002; I2 = 42%]. This finding is supported by TSA using RRR of 30% and 25%, and sensitivity analysis using fixed-effect meta-analysis. However, the certainty of our mortality finding was rated low using GRADE due to the serious risk of bias and inconsistency. In a priori subgroup analyses, we found no differences between single vs multicenter, higher (≥ 10,000 mg/day) vs lower dose and sepsis vs non-sepsis trials. Post-hoc, we found no differences in subgroup analysis of earlier (< 24 h) vs delayed treatment, longer (> 4 days) vs shorter treatment duration, and low vs other risk of bias studies. IVVC may have the greatest benefit in trials that enrolled patients above (i.e., > 37.5%; RR 0.65, 95% CI 0.54-0.79) vs below (i.e., ≤ 37.5%; RR 0.89, 95% CI 0.68-1.16) median control group mortality (test for subgroup differences: p = 0.06), and TSA supported this. CONCLUSIONS: IVVC monotherapy may be associated with mortality benefits in critically ill patients, particularly in patients with a high risk of dying. Given the low certainty of evidence, this potentially life-saving therapy warrants further studies to identify the optimal timing, dosage, treatment duration, and patient population that will benefit most from IVVC monotherapy. PROSPERO Registration ID: CRD42022323880. Registered 7th May 2022.

Nutrition therapy in the older critically ill patients: A scoping review.

INTRODUCTION: There is a lack of guidelines or formal systematic synthesis of evidence for nutrition therapy in older critically ill patients. This study is a scoping review to explore the state of evidence in this population. METHOD: MEDLINE and Embase were searched from inception until 9 February 2022 for studies that enrolled critically ill patients aged ≥60 years and investigated any area of nutrition therapy. No language or study design restrictions were applied. RESULTS: Thirty-two studies (5 randomised controlled trials) with 6 topics were identified: (1) nutrition screening and assessments, (2) muscle mass assessment, (3) route or timing of nutrition therapy, (4) determination of energy and protein requirements, (5) energy and protein intake, and (6) pharmaconutrition. Topics (1), (3) and (6) had similar findings among general adult intensive care unit (ICU) patients. Skeletal muscle mass at ICU admission was significantly lower in older versus young patients. Among older ICU patients, low muscularity at ICU admission increased the risk of adverse outcomes. Predicted energy requirements using weight-based equations significantly deviated from indirect calorimetry measurements in older vs younger patients. Older ICU patients required higher protein intake (>1.5g/kg/day) than younger patients to achieve nitrogen balance. However, at similar protein intake, older patients had a higher risk of azotaemia. CONCLUSION: Based on limited evidence, assessment of muscle mass, indirect calorimetry and careful monitoring of urea level may be important to guide nutrition therapy in older ICU patients. Other nutrition recommendations for general ICU patients may be used for older patients with sound clinical discretion.

Rhinovirus/enterovirus was the most common respiratory virus detected in adults with severe acute respiratory infections pre-COVID-19 in Kuala Lumpur, Malaysia.

BACKGROUND: Severe acute respiratory infections (SARI) pose a great global burden. The contribution of respiratory viruses to adult SARI is relatively understudied in Asia. We aimed to determine viral aetiology of adult SARI patients in Kuala Lumpur, Malaysia. METHODS: The prevalence of 20 common (mainly viral) respiratory pathogens, and MERS-CoV, SARS-CoV and 5 bacterial select agents was investigated from May 2017 to October 2019 in 489 SARI adult patients in Kuala Lumpur, Malaysia, using molecular assays (Luminex NxTAG-RPP kit and qPCR assays). Viral metagenomics analysis was performed on 105 negative samples. RESULTS: Viral respiratory pathogens were detected by PCR in 279 cases (57.1%), including 10 (2.0%) additional detections by metagenomics analysis. The most detected viruses were rhinovirus/enterovirus (RV/EV) (49.1%) and influenza virus (7.4%). Three melioidosis cases were detected but no SARS-CoV, MERS-CoV or other bacterial select agents. Bacterial/viral co-detections and viral co-detections were found in 44 (9.0%) and 27 (5.5%) cases respectively, mostly involving RV/EV. Independent predictors of critical disease were male gender, chronic lung disease, lack of runny nose and positive blood culture with a significant bacterial pathogen. Asthma and sore throat were associated with increased risk of RV/EV detection, while among RV/EV cases, males and those with neurological disease were at increased risk of critical disease. CONCLUSIONS: Prior to the COVID-19 pandemic, the high prevalence of respiratory viruses in adults with SARI was mainly attributed to RV/EV. Continued surveillance of respiratory virus trends contributes to effective diagnostic, prevention, and treatment strategies.

Initial development and validation of a novel nutrition risk, sarcopenia, and frailty assessment tool in mechanically ventilated critically ill patients: The NUTRIC-SF score.

BACKGROUND: Nutrition risk, sarcopenia, and frailty are interrelated. They may be due to suboptimal or prevented by optimal nutrition intake. The combination of nutrition risk (modified nutrition risk in the critically ill [mNUTRIC]), sarcopenia (SARC-F combined with calf circumference [SARC-CALF]), and frailty (clinical frailty scale [CFS]) in a single score may better predict adverse outcomes and prioritize resources for optimal nutrition in the intensive care unit (ICU) METHODS: This is a retrospective analysis of a single-center prospective observational study that enrolled mechanically ventilated adults with expected ≥96 h of ICU stay. SARC-F and CFS questionnaires were administered to patient's next-of-kin and mNUTRIC were calculated. Right calf circumference was measured. Nutrition data were collected from nursing record. The high-risk scores (mNUTRIC ≥ 5, SARC-CALF > 10, or CFS ≥ 4) of these variables were combined to become the nutrition risk, sarcopenia, and frailty (NUTRIC-SF) score (range: 0-3). RESULTS: Eighty-eight patients were analyzed. Increasing mNUTRIC was independently associated with 60-day mortality, whereas increasing SARC-CALF and CFS showed a strong trend towards a higher 60-day mortality. Discriminative ability of NUTRIC-SF for 60-day mortality is better than its component (C-statistics, 0.722; 95% confidence interval [CI], 0.677-0.868). Every increment of 300 kcal/day and 30 g/day is associated with a trend towards higher rate of discharge alive for high (≥2; adjusted hazard ratio, 1.453 [95% CI, 0.991-2.130] for energy; 1.503 [0.936-2.413] for protein) but not low (<2) NUTRIC-SF score. CONCLUSION: NUTRIC-SF may be a clinically relevant risk stratification tool in the ICU.