A systematic review and meta-analysis of the clinimetric properties of the core outcome measurement instruments for clinical effectiveness trials of nutritional and metabolic interventions in critical illness (CONCISE).

BACKGROUND: CONCISE is an internationally agreed minimum set of outcomes for use in nutritional and metabolic clinical research in critically ill adults. Clinicians and researchers need to be aware of the clinimetric properties of these instruments and understand any limitations to ensure valid and reliable research. This systematic review and meta-analysis were undertaken to evaluate the clinimetric properties of the measurement instruments identified in CONCISE. METHODS: Four electronic databases were searched from inception to December 2022 (MEDLINE via Ovid, EMBASE via Ovid, CINAHL via Healthcare Databases Advanced Search, CENTRAL via Cochrane). Studies were included if they examined at least one clinimetric property of a CONCISE measurement instrument or recognised variation in adults ≥ 18 years with critical illness or recovering from critical illness in any language. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist for systematic reviews of Patient-Reported Outcome Measures was used. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses were used in line with COSMIN guidance. The COSMIN checklist was used to evaluate the risk of bias and the quality of clinimetric properties. Overall certainty of the evidence was rated using a modified Grading of Recommendations, Assessment, Development and Evaluation approach. Narrative synthesis was performed and where possible, meta-analysis was conducted. RESULTS: A total of 4316 studies were screened. Forty-seven were included in the review, reporting data for 12308 participants. The Short Form-36 Questionnaire (Physical Component Score and Physical Functioning), sit-to-stand test, 6-m walk test and Barthel Index had the strongest clinimetric properties and certainty of evidence. The Short Physical Performance Battery, Katz Index and handgrip strength had less favourable results. There was limited data for Lawson Instrumental Activities of Daily Living and the Global Leadership Initiative on Malnutrition criteria. The risk of bias ranged from inadequate to very good. The certainty of the evidence ranged from very low to high. CONCLUSIONS: Variable evidence exists to support the clinimetric properties of the CONCISE measurement instruments. We suggest using this review alongside CONCISE to guide outcome selection for future trials of nutrition and metabolic interventions in critical illness. TRIAL REGISTRATION: PROSPERO (CRD42023438187). Registered 21/06/2023.

Core outcome measures for clinical effectiveness trials of nutritional and metabolic interventions in critical illness: an international modified Delphi consensus study evaluation (CONCISE).

BACKGROUND: Clinical research on nutritional and metabolic interventions in critically ill patients is heterogenous regarding time points, outcomes and measurement instruments used, impeding intervention development and data syntheses, and ultimately worsening clinical outcomes. We aimed to identify and develop a set of core outcome domains and associated measurement instruments to include in all research in critically ill patients. METHODS: An updated systematic review informed a two-stage modified Delphi consensus process (domains followed by instruments). Measurement instruments for domains considered 'essential' were taken through the second stage of the Delphi and a subsequent consensus meeting. RESULTS: In total, 213 participants (41 patients/caregivers, 50 clinical researchers and 122 healthcare professionals) from 24 countries contributed. Consensus was reached on time points (30 and 90 days post-randomisation). Three domains were considered 'essential' at 30 days (survival, physical function and Infection) and five at 90 days (survival, physical function, activities of daily living, nutritional status and muscle/nerve function). Core 'essential' measurement instruments reached consensus for survival and activities of daily living, and 'recommended' measurement instruments for physical function, nutritional status and muscle/nerve function. No consensus was reached for a measurement instrument for Infection. Four further domains met criteria for 'recommended,' but not 'essential,' to measure at 30 days post-randomisation (organ dysfunction, muscle/nerve function, nutritional status and wound healing) and three at 90 days (frailty, body composition and organ dysfunction). CONCLUSION: The CONCISE core outcome set is an internationally agreed minimum set of outcomes for use at 30 and 90 days post-randomisation, in nutritional and metabolic clinical research in critically ill adults.

Pre-operative nutrition and the elective surgical patient: why, how and what?

Pre-operative nutrition therapy is increasingly recognised as an essential component of surgical care. The present review has been formatted using Simon Sinek's Golden Circle approach to explain 'why' avoiding pre-operative malnutrition and supporting protein anabolism are important goals for the elective surgical patient, 'how' peri-operative malnutrition develops leading in part to a requirement for pre-operative anabolic preparation, and 'what' can be done to avoid pre-operative malnutrition and support anabolism for optimal recovery.

A survey of inhalational anaesthetic abuse in anaesthesia training programmes.

This study aims to assess the prevalence and outcomes of inhalational anaesthetic abuse among anaesthesia training programmes. Online surveys were completed by chairpersons of academic anaesthesia training programmes in the United States. The response rate was 84% (106/126 programmes). Twenty-two percent of the departments had had at least one incident of inhalational anaesthetic abuse. Forty-eight percent (15/31) of the persons abusing inhalational anaesthetics were sent for rehabilitation. Only 22% (7/31) of those found to be abusing inhalational anaesthetics were ultimately able to return successfully to anaesthesia practice with sustained recovery. The mortality rate among individuals found abusing inhalational anaesthetics was 26% (8/31). The majority of the anaesthesia departments (97/104, 93%) did not have any pharmacy accounting of inhalational anaesthetics. This is the first published survey of inhalational anaesthesia abuse. Inhalational anaesthetic abuse should be considered in at-risk individuals or those with a history of substance abuse. The concern about substance abuse is not unique to American anaesthetists. Countries around the world deal with similar substance abuse issues.

Distance of cecum ligated influences mortality, tumor necrosis factor-alpha and interleukin-6 expression following cecal ligation and puncture in the rat.

BACKGROUND/AIM: A mainstay of laboratory research into new therapies for sepsis has been the cecal ligation and puncture (CLP) model in rodents. Previous data indicate that the number of punctures made in the cecum and needle size utilized are primary determinants of mortality. Despite this, variability exists in mortality from this model, even when needle size is held constant. The aim of the present study was to evaluate the influence of the length of cecum ligated, independent of needle size, as a determinant of mortality. MATERIALS AND METHODS: We evaluated this by ligating various cecal lengths in male Sprague-Dawley rats. A double puncture was then made with a 20-gauge needle, and mortality was analyzed. Plasma TNF-alpha and IL-6 expression was assessed at 6 h. Animals received no antibiotics, were not fasted, and fluid resuscitation was administered. RESULTS: We determined that mortality does not begin to occur until a distance of >5% of cecal length is ligated. Further, our findings indicate that in this model, 90-100% mortality occurs 4 days following CLP when a distance of >30% is ligated. TNF-alpha and IL-6 expression is markedly increased with increasing length of cecum ligated. CONCLUSIONS: Our data demonstrate that the length of cecum ligated is a major determinant of mortality in the CLP model of sepsis. These findings indicate that investigators must rigorously control the distance of the cecum ligated in order to generate consistent mortality and inflammation data when utilizing the CLP model in rats. Further, the mortality from this model can be adjusted to fit the individual needs of a particular experiment.

Glutamine reduces cytokine release, organ damage, and mortality in a rat model of endotoxemia.

Clinical trials have demonstrated that glutamine (GLN) supplementation can decrease infectious morbidity and improve survival in a number of settings of critical illness. The mechanism of this protection remains unclear. The objective of this study was to evaluate the effect of GLN on cytokine release, organ injury, and survival from endotoxin-induced septic shock. Endotoxemia was induced in Male Sprague-Dawley rats by intravenous administration of 5 mg/kg Escherichia coli lipopolysaccharide (LPS). Concomitantly, animals were fluid resuscitated with a lactated ringers (LR) solution and given GLN (0.75 g/kg i.v.) or LR alone. Blood samples were obtained at multiple time points post-LPS injury for cytokine analysis. Survival rates were monitored for 72 h. Organ injury was evaluated in a separate set of animals via pathologic exam of tissues harvested 6 h post-LPS injury. A single dose of GLN significantly attenuated the release of TNF-alpha at 2 h (P < 0.005) and IL-1 beta at 4 h (P < 0.0001). This attenuation of cytokine release was associated with a significant decrease in mortality (P < 0.003). Pathologic exam demonstrated significant protection of both lung and small bowel tissue by GLN. Blood gas values 6-h post-LPS injury showed increased PaO2 and bicarbonate concentration in GLN treated animals. These data indicate that GLN can significantly attenuate pro-inflammatory cytokine release, protect against end-organ damage, and decrease mortality from endotoxemia. GLN confers protection even when administered at the onset of endotoxemia, rather then as pre-treatment. Thus, one explanation for the clinical benefits observed from GLN-supplementation may be related to the attenuation of pro-inflammatory cytokines.

Glutamine administration reduces Gram-negative bacteremia in severely burned patients: a prospective, randomized, double-blind trial versus isonitrogenous control.

OBJECTIVE: To determine the effect of intravenous glutamine supplementation vs. an isonitrogenous control on infectious morbidity in severely burned patients. Previous clinical studies in seriously ill patients suggest a beneficial effect of glutamine on infectious morbidity, but no trials have examined possible clinical benefits in severely burned patients. DESIGN: Prospective, double-blind, randomized trial. SETTING: Burn intensive care unit of a university hospital. PATIENTS: Twenty-six severe burn patients with total burn surface area of 25% to 90% and presence of full-thickness burns. Patients were evaluated for occurrence of bacteremia and antibiotic use during the first 30 days of their burn unit admission. Nutritional status and overall inflammation were also measured. INTERVENTION: Either intravenous glutamine or an isonitrogenous control amino acid solution was administered as a continuous infusion during burn intensive care unit stay. MEASUREMENTS AND MAIN RESULTS: The incidence of Gram-negative bacteremia was significantly reduced in the glutamine-supplemented group (8%) vs. control (43%; p <.04). No difference was seen in the incidence of Gram-positive bacteremia or fungemia. Average number of positive blood cultures, antibiotic usage, and mortality rates also were reduced but did not reach statistical significance. Significant improvements in serum transferrin and prealbumin were observed in glutamine-supplemented patients at 14 days after burn injury (p <.01 and.04, respectively). C-reactive protein was also significantly reduced at 14 days after burn injury in the glutamine group (p <.01). CONCLUSIONS: Significantly fewer bacteremic episodes with Gram-negative organisms occurred in the glutamine-supplemented patients. Glutamine supplementation improved measures of nutrition and decreased measures of overall inflammation. In addition, a trend toward lower mortality rate, decreased overall bacteremia incidence, and antibiotic usage in the glutamine group was observed. Glutamine's beneficial effects may be a result of improved gut integrity or immune function, but the precise mechanism of glutamine's protection is unknown.

Glutamine induces heat shock protein and protects against endotoxin shock in the rat.

Enhanced expression of heat shock protein (HSP) has been shown to be protective against laboratory models of septic shock. Induction of HSPs to improve outcome in human disease has not been exploited because laboratory induction agents are themselves toxic and not clinically relevant. In this study, we demonstrate that a single dose of intravenous glutamine causes a rapid and significant increase in HSP25 and HSP72 expression in multiple organs of the unstressed Sprague-Dawley rat. With the utilization of a fluid-resuscitated rat model of endotoxemia, mortality was dramatically reduced by glutamine administration concomitant with the endotoxin injury. Endotoxin-treated animals given glutamine exhibited dramatic increases in tissue HSP expression and marked reduction of end-organ damage. These data suggest glutamine may protect against mortality and attenuate end-organ injury in endotoxemic shock via enhanced HSP expression. Furthermore, glutamine confers protection when administered at the initiation of sepsis, rather than as pretreatment. Thus glutamine appears to be a clinically viable enhancer of HSP expression and may prove beneficial in the therapy of sepsis and sepsis-induced organ injury.

Glutamine protects intestinal epithelial cells: role of inducible HSP70.

Glutamine (Gln) protects gut mucosa against injury and promotes mucosal healing. Because the induction of heat shock proteins (HSP) protects cells under conditions of stress, we determined whether Gln conferred protection against stress in an intestinal epithelial cell line through HSP induction. Gln added to IEC-18 cells induces an increase in HSP70, a concentration-dependent effect also seen with mRNA. Two forms of injury, lethal heat (49 degrees C) and oxidant, were used, and viability was determined by 51Cr release. Gln-treated cells were significantly more resistant to injury. Treatment with 6-diazo-5-oxo-L-norleucine (DON), a nonmetabolizable analog of Gln, induced HSP70 and protected cells from injury, but less than Gln. These findings suggest that the effects of Gln on HSP70 induction and cellular protection are mediated by metabolic and nonmetabolic mechanisms. To determine whether HSP induction was central to the action of Gln and DON, quercetin, which blocks HSP induction, was used. Quercetin blocked HSP70 induction and the protective effect of Gln and DON. We conclude that the protective effects of Gln in intestinal epithelial cells are in part mediated by HSP70 induction.