The role of lipid emulsions containing omega-3 fatty acids for medical and surgical critical care patients.

In critical illness the regulation of inflammation and oxidative stress can improve patient outcomes, and thus omega-3 polyunsaturated fatty acids (PUFAs) have been used as part of parenteral nutrition (PN) owing to their potential anti-inflammatory effects. The international lipids in PN Summit, encompassed discussions and the production of consensus guidelines concerning PN intravenous lipid emulsion (ILE) use in critical care. The Lipid Summit participants agreed that the inclusion of fish oil in ILEs is associated with meaningful clinical benefits without signals of harm, based on a strong biological rationale and current clinical evidence. Decisions concerning ILE choice should be made based on current evidence, thus addressing clinical requirements for guidance, particularly as further definitive evidence seems unlikely to occur. In addition, a future of individualized ICU care is envisioned, yielding better clinical outcomes. This approach will require the greater use of intelligent study designs incorporating the use of biomarkers of omega-3 derivatives, inflammatory-resolving processes, and/or muscle protein breakdown.

A secondary atmosphere on the rocky exoplanet 55 Cancri e.

Characterizing rocky exoplanets is a central aim of astronomy, and yet the search for atmospheres on rocky exoplanets has so far resulted in either tight upper limits on the atmospheric mass1-3 or inconclusive results4-6. The 1.95REarth and 8.8MEarth planet 55 Cancri e (abbreviated 55 Cnc e), with a predominantly rocky composition and an equilibrium temperature of around 2,000 K, may have a volatile envelope (containing molecules made from a combination of C, H, O, N, S and P elements) that accounts for up to a few percent of its radius7-13. The planet has been observed extensively with transmission spectroscopy14-22 and its thermal emission has been measured in broad photometric bands23-26. These observations disfavour a primordial H2/He-dominated atmosphere but cannot conclusively determine whether the planet has a secondary atmosphere27,28. Here we report a thermal emission spectrum of the planet obtained by the NIRCam and MIRI instruments aboard the James Webb Space Telescope (JWST) from 4 to 12 µm. The measurements rule out the scenario in which the planet is a lava world shrouded by a tenuous atmosphere made of vaporized rock29-32 and indicate a bona fide volatile atmosphere that is probably rich in CO2 or CO. This atmosphere can be outgassed from and sustained by a magma ocean.

Considerations for medical nutrition therapy management of the critically ill patient with hematological malignancies: A narrative review.

Patients with hematological malignancies (HMs) are more frequently admitted now than in the past to the intensive care unit (ICU) due to more aggressive approaches in primary therapy of HMs and the need for critical care support. Pathophysiological alterations derived from HMs and the different hematological therapies, such as chemotherapy, negatively affect gastrointestinal (GI) function, metabolism, and nutrition status. Further, malnutrition strongly influences outcomes and tolerance of the different hematological therapies. In consequence, these critically ill patients frequently present with malnutrition and pathophysiological alterations that create challenges for the delivery of medical nutrition therapy (MNT) in the ICU. Frequent screening, gauging tolerance, and monitoring nutrition status are mandatory to provide individualized MNT and achieve nutrition objectives. The present review discusses how HM impact GI function and nutrition status, the importance of MNT in patients with HM, and specific considerations for guidance in providing adequate MNT to these patients when admitted to the ICU.

Enteral nutrition in septic shock: a call for a paradigm shift.

PURPOSE OF REVIEW: The purpose of this review is to identify contemporary evidence evaluating enteral nutrition in patients with septic shock, outline risk factors for enteral feeding intolerance (EFI), describe the conundrum of initiating enteral nutrition in patients with septic shock, appraise current EFI definitions, and identify bedside monitors for guiding enteral nutrition therapy. RECENT FINDINGS: The NUTRIREA-2 and NUTRIREA-3 trial results have better informed the dose of enteral nutrition in critically ill patients with circulatory shock. In both trials, patients with predominant septic shock randomized to receive early standard-dose nutrition had more gastrointestinal complications. Compared to other contemporary RCTs that included patients with circulatory shock, patients in the NUTRIREA-2 and NUTRIREA-3 trials had higher bowel ischemia rates, were sicker, and received full-dose enteral nutrition while receiving high baseline dose of vasopressor. These findings suggest severity of illness, vasopressor dose, and enteral nutrition dose impact outcomes. SUMMARY: The provision of early enteral nutrition preserves gut barrier functions; however, these benefits are counterbalanced by potential complications of introducing luminal nutrients into a hypo-perfused gut, including bowel ischemia. Findings from the NUTRIREA2 and NUTRIREA-3 trials substantiate a 'less is more' enteral nutrition dose strategy during the early acute phase of critical illness. In the absence of bedside tools to guide the initiation and advancement of enteral nutrition in patients with septic shock, the benefit of introducing enteral nutrition on preserving gut barrier function must be weighed against the risk of harm by considering dose of vasopressor, dose of enteral nutrition, and severity of illness.

Why Wonder Why?

This essay describes how a physician's encounter with a patient with repeated intensive care unit admissions illuminated the value of wonder in clinical care and medical education.

Recent Advances in Management of Neuropathic, Nociceptive, and Chronic Pain: A Narrative Review with Focus on Nanomedicine, Gene Therapy, Stem Cell Therapy, and Newer Therapeutic Options.

PURPOSE OF REVIEW: This manuscript summarizes novel clinical and interventional approaches in the management of chronic, nociceptive, and neuropathic pain. RECENT FINDINGS: Pain can be defined as a feeling of physical or emotional distress caused by an external stimulus. Pain can be grouped into distinct types according to characteristics including neuropathic pain, which is a pain caused by disease or lesion in the sensory nervous system; nociceptive pain, which is pain that can be sharp, aching, or throbbing and is caused by injury to bodily tissues; and chronic pain, which is long lasting or persisting beyond 6 months. With improved understanding of different signaling systems for pain in recent years, there has been an upscale of methods of analgesia to counteract these pathological processes. Novel treatment methods such as use of cannabinoids, stem cells, gene therapy, nanoparticles, monoclonal antibodies, and platelet-rich plasma have played a significant role in improved strategies for therapeutic interventions. Although many management options appear to be promising, extensive additional clinical research is warranted to determine best practice strategies in the future for clinicians.

Factors influencing diagnostic accuracy among intensive care unit clinicians - an observational study.

OBJECTIVES: Diagnostic errors are a source of morbidity and mortality in intensive care unit (ICU) patients. However, contextual factors influencing clinicians' diagnostic performance have not been studied in authentic ICU settings. We sought to determine the accuracy of ICU clinicians' diagnostic impressions and to characterize how various contextual factors, including self-reported stress levels and perceptions about the patient's prognosis and complexity, impact diagnostic accuracy. We also explored diagnostic calibration, i.e. the balance of accuracy and confidence, among ICU clinicians. METHODS: We conducted an observational cohort study in an academic medical ICU. Between June and August 2019, we interviewed ICU clinicians during routine care about their patients' diagnoses, their confidence, and other contextual factors. Subsequently, using adjudicated final diagnoses as the reference standard, two investigators independently rated clinicians' diagnostic accuracy and on each patient on a given day ("patient-day") using 5-point Likert scales. We conducted analyses using both restrictive and conservative definitions of clinicians' accuracy based on the two reviewers' ratings of accuracy. RESULTS: We reviewed clinicians' responses for 464 unique patient-days, which included 255 total patients. Attending physicians had the greatest diagnostic accuracy (77-90 %, rated as three or higher on 5-point Likert scale) followed by the team's primary fellow (73-88 %). Attending physician and fellows were also least affected by contextual factors. Diagnostic calibration was greatest among ICU fellows. CONCLUSIONS: Additional studies are needed to better understand how contextual factors influence different clinicians' diagnostic reasoning in the ICU.

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.

Nutrition dose in the early acute phase of critical illness: Finding the sweet spot and heeding the lessons from the NUTRIREA trials.

The landmark NUTRIREA-2 and NUTRIREA-3 trials compared the route and dose of nutrition, respectively, in critically ill patients with circulatory shock. The results of both trials support a "less-is-more" paradigm shift in the early acute phase of critical illness. In this review, the authors outline and appraise the results of the NUTRIREA-2 and NUTRIREA-3 trials, introduce the concept of identifying the "sweet spot" for nutrition dose based on severity of illness/nutrition risk and nutrition dose, and identify the unintended consequences of delivering full-dose nutrition in sicker critically ill patients during the early acute phase of critical illness.

A randomised controlled trial of a nutrition and a decision support intervention to enable partnerships with families of critically ill patients.

AIMS AND OBJECTIVES: The aim of the study was to investigate the effect of supporting family members to partner with health professionals on nutrition intakes and decision-making and to evaluate intervention and study feasibility. BACKGROUND: Family partnerships can improve outcomes for critically ill patients and family members. Interventions that support families to engage with health professionals require evaluation. DESIGN: A multi-centre, randomised, parallel group superiority Phase II randomised controlled trial. METHODS: In nine intensive care units (ICUs) across three countries, critically ill patients ≥60 years, or those 55-59 years with advanced chronic diseases and expected ICU length of stay >72 h and their family member were enrolled between 9 May 2017 and 31 March 2020. Participants were randomised (1:1:1) to either a decision support or nutrition optimisation family-centred intervention, or usual care. Primary outcomes included protein and energy intake during ICU and hospital stay (nutrition intervention) and family satisfaction (decision support). Study feasibility was assessed as a composite of consent rate, intervention adherence, contamination and physician awareness of intervention assignment. RESULTS: We randomised 135 patients/family members (consent rate 51.7%). The average rate of randomisation was 0.5 (0.13-1.53) per month. Unavailability (staff/family) was the major contributor to families not being approached for consent. Declined consent was attributed to families feeling overwhelmed (58/126, 46%). Pandemic visitor restrictions contributed to early study cessation. Intervention adherence for the decision support intervention was 76.9%-100.0% and for the nutrition intervention was 44.8%-100.0%. Nutritional adequacy, decisional conflict, satisfaction with decision-making and overall family satisfaction with ICU were similar for all groups. CONCLUSIONS: Active partnerships between family members and health professionals are important but can be challenging to achieve in critical care contexts. We were unable to demonstrate the efficacy of either intervention. Feasibility outcomes suggest further refinement of interventions and study protocol may be warranted. RELEVANCE TO CLINICAL PRACTICE: Interventions to promote family partnerships in critical illness are needed but require a greater understanding of the extent to which families want and are able to engage and the activities in which they have most impact. REPORTING METHOD: This study has been reported following the Consolidated Standards of Reporting Trials (CONSORT) and the Template for Intervention Description and Replication (TIDieR) guidelines. PATIENT OR PUBLIC CONTRIBUTION: Patients and caregivers were engaged in and contributed to the development and subsequent iterations of the two family-centred interventions use in this study. CLINICAL TRIAL REGISTRATION NUMBER: Trial registration. CLINICALTRIALS: gov, ID: NCT02920086. Registered on 30 September 2016. First patient enrolled on 9 May 2017 https://clinicaltrials.gov/ct2/results?cond=&term=NCT02920086&cntry=&state=&city=&dist=.

A Mixed-Methods Feasibility Study: Eliciting ICU Experiences and Measuring Outcomes of Family Caregivers of Patients Who Have Undergone Hematopoietic Stem Cell Transplantation.

The impact of an intensive care unit (ICU) admission on family caregivers of patients who have undergone hematopoietic stem cell transplantation (HSCT) has not been well described. Aims of this study were to determine the feasibility of conducting research with family caregivers of HSCT patients during an ICU admission and generate preliminary data about their experiences and engagement in care. Using a mixed-methods, repeated measures design, we collected data from family caregivers after 48 hr in the ICU (T1) and at 48 hr after transferring out of ICU (T2). Enrolling HSCT caregivers in research while in the ICU was feasible (10/13 consented; 9/10 completed data collection at T1); however, data collection at T2 was not possible for most caregivers. Caregiver distress levels were high, and engagement in care was moderate. The three themes that emerged from interviews (n = 5) highlighted that although HSCT family caregivers faced many challenges and received limited support during their ICU experience, they were able to access their own personal resources and demonstrated resilience.

The Efficacy of Glutamine Supplementation in Severe Adult Burn Patients: A Systematic Review With Trial Sequential Meta-Analysis.

OBJECTIVES: Evidence supporting glutamine supplementation in severe adult burn patients has created a state of uncertainty due to the variability in the treatment effect reported across small and large randomized controlled trials (RCTs). We aimed to systematically review the effect of glutamine supplementation on mortality in severe adult burn patients. DATA SOURCES: MEDLINE, Embase, CINAHL, and Cochrane Central were searched from inception to February 10, 2023. STUDY SELECTION: RCTs evaluating the effect of enteral or IV glutamine supplementation alone in severe adult burn patients were included. DATA EXTRACTION: Two reviewers independently extracted data on study characteristics, burn injury characteristics, description of the intervention between groups, adverse events, and clinical outcomes. DATA SYNTHESIS: Random effects meta-analyses were performed to estimate the pooled risk ratio (RR). Trial sequential analyses (TSA) for mortality and infectious complications were performed. Ten RCTs (1,577 patients) were included. We observed no significant effect of glutamine supplementation on overall mortality (RR, 0.65, 95% CI, 0.33-1.28; p = 0.21), infectious complications (RR, 0.83; 95% CI, 0.63-1.09; p = 0.18), or other secondary outcomes. In subgroup analyses, we observed no significant effects based on administration route or burn severity. We did observe a significant subgroup effect between single and multicenter RCTs in which glutamine significantly reduced mortality and infectious complications in singe-center RCTs but not in multicenter RCTs. However, TSA showed that the pooled results of single-center RCTs were type 1 errors and further trials would be futile. CONCLUSIONS: Glutamine supplementation, regardless of administration, does not appear to improve clinical outcomes in severely adult burned patients.

Current practices in nutrition therapy in cardiac surgery patients: An international multicenter observational study.

BACKGROUND: Cardiac surgery patients with a prolonged stay in the intensive care unit (ICU) are at high risk for acquired malnutrition. Medical nutrition therapy practices for cardiac surgery patients are unknown. The objective of this study is to describe the current nutrition practices in critically ill cardiac surgery patients worldwide. METHODS: We conducted a prospective observational study in 13 international ICUs involving mechanically ventilated cardiac surgery patients with an ICU stay of at least 72 h. Collected data included the energy and protein prescription, type of and time to the initiation of nutrition, and actual quantity of energy and protein delivered (maximum: 12 days). RESULTS: Among 237 enrolled patients, enteral nutrition (EN) was started, on average, 45 h after ICU admission (range, 0-277 h; site average, 53 [range, 10-79 h]). EN was prescribed for 187 (79%) patients and combined EN and parenteral nutrition in 33 (14%). Overall, patients received 44.2% (0.0%-117.2%) of the prescribed energy and 39.7% (0.0%-122.8%) of the prescribed protein. At a site level, the average nutrition adequacy was 47.5% (30.5%-78.6%) for energy and 43.6% (21.7%-76.6%) for protein received from all nutrition sources. CONCLUSION: Critically ill cardiac surgery patients with prolonged ICU stay experience significant delays in starting EN and receive low levels of energy and protein. There exists tremendous variability in site performance, whereas achieving optimal nutrition performance is doable.

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.

Benefits and harm of probiotics and synbiotics in adult critically ill patients. A systematic review and meta-analysis of randomized controlled trials with trial sequential analysis.

BACKGROUND & AIMS: Several systematic reviews and meta-analyses of randomized controlled trials concluded that probiotics administration in critically ill patients was safe and associated with reduced rates of ventilator-associated pneumonia and diarrhea. However, a recent large multicenter trial found probiotics administration, compared to placebo, was not efficacious and increased adverse events. An updated meta-analysis that controls for type-1 and -2 errors using trial sequential analysis, with a detailed account of adverse events associated with probiotic administration, is warranted to confirm the safety and efficacy of probiotic use in critically ill patients. METHODS: RCTs that compared probiotics or synbiotics to usual care or placebo and reported clinical and diarrheal outcomes were searched in 4 electronic databases from inception to March 8, 2022 without language restriction. Four reviewers independently extracted data and assessed the study qualities using the Critical Care Nutrition (CCN) Methodological Quality Scoring System. Random-effect meta-analysis and trial sequential analysis (TSA) were used to synthesize the results. The primary outcome was ventilator-associated pneumonia (VAP). The main subgroup analysis compared the effects of higher versus lower quality studies (based on median CCN score). RESULTS: Seventy-five studies with 71 unique trials (n = 8551) were included. In the overall analysis, probiotics significantly reduced VAP incidence (risk ratio [RR] 0.70, 95% confidence interval [CI] 0.56-0.88; I2 = 65%; 16 studies). However, such benefits were demonstrated only in lower (RR 0.47, 95% CI 0.32, 0.69; I2 = 44%; 7 studies) but not higher quality studies (RR 0.89, 95% CI 0.73, 1.08; I2 = 43%; 9 studies), with significant test for subgroup differences (p = 0.004). Additionally, TSA showed that the VAP benefits of probiotics in the overall and subgroup analyses were type-1 errors. In higher quality trials, TSA found that future trials are unlikely to demonstrate any benefits of probiotics on infectious complications and diarrhea. Probiotics had higher adverse events than control (pooled risk difference: 0.01, 95% CI 0.01, 0.02; I2 = 0%; 22 studies). CONCLUSION: High-quality RCTs did not support a beneficial effect of probiotics on clinical or diarrheal outcomes in critically ill patients. Given the lack of benefits and the increased incidence of adverse events, probiotics should not be routinely administered to critically ill patients. PROSPERO REGISTRATION: CRD42022302278.

The effect of higher protein dosing in critically ill patients with high nutritional risk (EFFORT Protein): an international, multicentre, pragmatic, registry-based randomised trial.

BACKGROUND: On the basis of low-quality evidence, international critical care nutrition guidelines recommend a wide range of protein doses. The effect of delivering high-dose protein during critical illness is unknown. We aimed to test the hypothesis that a higher dose of protein provided to critically ill patients would improve their clinical outcomes. METHODS: This international, investigator-initiated, pragmatic, registry-based, single-blinded, randomised trial was undertaken in 85 intensive care units (ICUs) across 16 countries. We enrolled nutritionally high-risk adults (≥18 years) undergoing mechanical ventilation to compare prescribing high-dose protein (≥2·2 g/kg per day) with usual dose protein (≤1·2 g/kg per day) started within 96 h of ICU admission and continued for up to 28 days or death or transition to oral feeding. Participants were randomly allocated (1:1) to high-dose protein or usual dose protein, stratified by site. As site personnel were involved in both prescribing and delivering protein dose, it was not possible to blind clinicians, but patients were not made aware of the treatment assignment. The primary efficacy outcome was time-to-discharge-alive from hospital up to 60 days after ICU admission and the secondary outcome was 60-day morality. Patients were analysed in the group to which they were randomly assigned regardless of study compliance, although patients who dropped out of the study before receiving the study intervention were excluded. This study is registered with ClinicalTrials.gov, NCT03160547. FINDINGS: Between Jan 17, 2018, and Dec 3, 2021, 1329 patients were randomised and 1301 (97·9%) were included in the analysis (645 in the high-dose protein group and 656 in usual dose group). By 60 days after randomisation, the cumulative incidence of alive hospital discharge was 46·1% (95 CI 42·0%-50·1%) in the high-dose compared with 50·2% (46·0%-54·3%) in the usual dose protein group (hazard ratio 0·91, 95% CI 0·77-1·07; p=0·27). The 60-day mortality rate was 34·6% (222 of 642) in the high dose protein group compared with 32·1% (208 of 648) in the usual dose protein group (relative risk 1·08, 95% CI 0·92-1·26). There appeared to be a subgroup effect with higher protein provision being particularly harmful in patients with acute kidney injury and higher organ failure scores at baseline. INTERPRETATION: Delivery of higher doses of protein to mechanically ventilated critically ill patients did not improve the time-to-discharge-alive from hospital and might have worsened outcomes for patients with acute kidney injury and high organ failure scores. FUNDING: None.