Search

Abstract Background Surgical placebos are controversial. This in-depth study explored the design, acceptability, and feasibility issues relevant to designing a surgical placebo-controlled trial for the evaluation of the clinical and cost effectiveness of arthroscopic lavage for the management of people with osteoarthritis of the knee in the UK. Methods Two surgeon focus groups at a UK national meeting for orthopaedic surgeons and one regional surgeon focus group (41 surgeons); plenary discussion at a UK national meeting for orthopaedic anaesthetists (130 anaesthetists); three focus groups with anaesthetists (one national, two regional; 58 anaesthetists); two focus groups with members of the patient organisation Arthritis Care (7 participants); telephone interviews with people on consultant waiting lists from two UK regional centres (15 participants); interviews with Chairs of UK ethics committees (6 individuals); postal surveys of members of the British Association of Surgeons of the Knee (382 surgeons) and members of the British Society of Orthopaedic Anaesthetists (398 anaesthetists); two centre pilot (49 patients assessed). Results There was widespread acceptance that evaluation of arthroscopic lavage had to be conducted with a placebo control if scientific rigour was not to be compromised. The choice of placebo surgical procedure (three small incisions) proved easier than the method of anaesthesia (general anaesthesia). General anaesthesia, while an excellent mimic, was more intrusive and raised concerns among some stakeholders and caused extensive discussion with local decision-makers when seeking formal approval for the pilot. Patients were willing to participate in a pilot with a placebo arm; although some patients when allocated to surgery became apprehensive about the possibility of receiving placebo, and withdrew. Placebo surgery was undertaken successfully. Conclusions Our study illustrated the opposing and often strongly held opinions about surgical placebos, the ethical issues underpinning this controversy, and the challenges that exist even when ethics committee approval has been granted. It showed that a placebo-controlled trial could be conducted in principle, albeit with difficulty. It also highlighted that not only does a placebo-controlled trial in surgery have to be ethically and scientifically acceptable but that it also must be a feasible course of action. The place of placebo-controlled surgical trials more generally is likely to be limited and require specific circumstances to be met. Suggested criteria are presented. Trial registration number The trial was assigned ISRCTN02328576 through http://controlled-trials.com/ in June 2006. The first patient was randomised to the pilot in July 2007.

Abstract Background- Hospital acquired infections are a major cause of morbidity and mortality and markedly increased health care costs. Critically ill patients who require management in an Intensive Care Unit are particularly susceptible to these infections which are associated with a very high mortality. Selective decontamination of the digestive tract (SDD) may reduce these infections and improve mortality but it has not been widely adopted into practice. We aim to 1. Clarify reasons why clinicians have avoided implementing SDD into clinical practice despite the current best-evidence 2. Describe barriers to SDD implementation and 3. Identify what further evidence is required before full scale clinical implementation would be considered appropriate and feasible. Methods- We have developed an international 'multi-lens' approach to investigate SDD from several perspectives. In case studies we will identify accounts of implementation of SDD in practice, in terms of the behaviours performed by the full range of individual clinicians, accounts of how SDD was first introduced into the Unit and specific content that may be used to populate the content of behaviour change techniques to be used in an implementation intervention and procedures to consider in order to deliver an implementation trial. In a 4 round Delphi study we will identify the range of stakeholders' beliefs, views and perceived barriers relating to the use of SDD. We will generate hypotheses about key beliefs about SDD and will inform the feasibility of any future randomised controlled trial. In large-scale nationwide postal questionnaire surveys of the state of current practice we will identify the factors predicting acceptability of an effectiveness or implementation trial using, and informed by, the theoretical domains structure. In semi-structured interviews with active international clinical trialists we will assess the feasibility of a randomised controlled trial and identify challenges and barriers to undertaking research in the field of SDD research. Discussion We believe these methods will allow us to determine whether clinical implementation trials or further large effectiveness trials are required before full scale implementation into clinical practice.

OBJECTIVE: To change the culture of healthcare organisations and improve patient safety, new professionals need to be taught about adverse events and how to trap and mitigate against errors. A literature review did not reveal any patient safety courses in the core undergraduate medical curriculum. Therefore a new module was designed and piloted. DESIGN: A 5-h evidence-based module on understanding error in healthcare was designed with a preliminary evaluation using self-report questionnaires. SETTING: A UK medical school. PARTICIPANTS: 110 final year students. MEASUREMENTS AND MAIN RESULTS: Participants completed two questionnaires: the first questionnaire was designed to measure students' self-ratings of knowledge, attitudes and behaviour in relation to patient safety and medical error, and was administered before and approximately 1 year after the module; the second formative questionnaire on the teaching process and how it could be improved was administered after completion of the module. CONCLUSIONS: Before attending the module, the students reported they had little understanding of patient safety matters. One year later, only knowledge and the perceived personal control over safety had improved. The students rated the teaching process highly and found the module valuable. Longitudinal follow-up is required to provide more information on the lasting impact of the module. [ABSTRACT FROM AUTHOR]

Objective: Early warning scoring systems are widely used in clinical practice to allow early recognition of the deteriorating patient, but they lack validation. We aimed to test the ability of physiologic variables, either alone or in existing early scoring systems, to predict major deterioration in a patient's condition and attempt to derive functions with superior accuracy.Design: A comparative cohort study.Setting: A teaching hospital in Scotland.Patients: Two cohorts of general surgical high-dependency patients. The cohorts are a group of surgical high-dependency care patients who did not require intensive care admission and another group of patients who did require admission.Interventions: None.Measurements and Main Results: Prospective physiologic data on consecutive surgical high-dependency unit patients were collected and compared with physiologic data on patients admitted to the intensive care unit from the same surgical high-dependency units. Data were quality checked and summarized, and discriminant analysis and receiver operator curves were used to discriminate between the groups. There were significant physiologic differences between groups with regard to heart rate (p<.001, area under the receiver operating characteristic curve [AUC] 0.7), respiratory rate (p<.001, AUC 0.71), and oxygen saturation (p<.001, AUC 0.78) across time points. This was not present for systolic blood pressure or temperature. Existing early warning scoring systems had good discriminatory power (AUC 0.83-0.86). We derived discriminant functions, which have a high predictive ability to determine differences between groups (p<.0001, AUC 0.86-0.90). We found that heart rate and respiratory rate could detect differences between groups at 6 and 8 hrs before ICU admission, but oxygen saturation and the discriminant function 2 could detect differences 48 hrs before ICU admission.Conclusions: Some commonly used physiologic variables have reasonable power in determining the difference between patients requiring intensive care unit admission, but others are poor. Existing early warning scores have comparatively good discriminatory power. We have derived functions with excellent predictive power in this derivation cohort. [ABSTRACT FROM AUTHOR]

Objective: To determine whether preoperative plasma levels of B-type natriuretic peptide would allow for the prediction of perioperative and early postoperative cardiovascular support requirements and hospital bed usage after coronary artery surgery.Design: A prospective observational cohort study.Setting: A tertiary referral cardiothoracic unit in Scotland.Patients: Forty-six consecutive patients undergoing coronary artery surgery.Interventions: None.Measurements and Main Results: Demographics, clinical details, preoperative and postoperative B-type natriuretic peptide levels, type of surgery, postoperative complications, postoperative cardiac troponin I levels, and duration of stay were collected. Preoperative plasma levels of B-type natriuretic peptide are significantly higher in patients who require perioperative inotropic or mechanical cardiovascular support, compared with those who do not. They are also higher in those who require postoperative inotropic or mechanical cardiovascular support, compared with those who do not. B-type natriuretic peptide levels are higher in those who require increased intensive care unit stay but not a prolonged hospital stay.Conclusions: Preoperative plasma levels of B-type natriuretic peptide levels may be useful in predicting the need for increased peri and postoperative cardiovascular support and a more prolonged stays in intensive care following coronary artery surgery. [ABSTRACT FROM AUTHOR]

Introduction: Fluid strategies may impact on patient outcomes in major elective surgery. We aimed to study the effectiveness and cost-effectiveness of pre-operative fluid loading in high-risk surgical patients undergoing major elective surgery.Methods: This was a pragmatic, non-blinded, multi-centre, randomised, controlled trial. We sought to recruit 128 consecutive high-risk surgical patients undergoing major abdominal surgery. The patients underwent pre-operative fluid loading with 25 ml/kg of Ringer's solution in the six hours before surgery. The control group had no pre-operative fluid loading. The primary outcome was the number of hospital days after surgery with cost-effectiveness as a secondary outcome.Results: A total of 111 patients were recruited within the study time frame in agreement with the funder. The median pre-operative fluid loading volume was 1,875 ml (IQR 1,375 to 2,025) in the fluid group compared to 0 (IQR 0 to 0) in controls with days in hospital after surgery 12.2 (SD 11.5) days compared to 17.4 (SD 20.0) and an adjusted mean difference of 5.5 days (median 2.2 days; 95% CI -0.44 to 11.44; P = 0.07). There was a reduction in adverse events in the fluid intervention group (P = 0.048) and no increase in fluid based complications. The intervention was less costly and more effective (adjusted average cost saving: £2,047; adjusted average gain in benefit: 0.0431 quality adjusted life year (QALY)) and has a high probability of being cost-effective.Conclusions: Pre-operative intravenous fluid loading leads to a non-significant reduction in hospital length of stay after high-risk major surgery and is likely to be cost-effective. Confirmatory work is required to determine whether these effects are reproducible, and to confirm whether this simple intervention could allow more cost-effective delivery of care.Trial Registration: Prospective Clinical Trials, ISRCTN32188676. [ABSTRACT FROM AUTHOR]

Introduction: Previous cost-effectiveness analyses (CEA) reported that Drotrecogin alfa (DrotAA) is cost-effective based on a Phase III clinical trial (PROWESS). There is little evidence on whether DrotAA is cost-effective in routine clinical practice. We assessed whether DrotAA is cost-effective in routine practice for adult patients with severe sepsis and multiple organ systems failing.Methods: This CEA used data from a prospective cohort study that compared DrotAA versus no DrotAA (control) for severe sepsis patients with multiple organ systems failing admitted to critical care units in England, Wales, and Northern Ireland. The cohort study used case-mix and mortality data from a national audit, linked with a separate audit of DrotAA infusions. Re-admissions to critical care and corresponding mortality were recorded for four years. Patients receiving DrotAA (n = 1,076) were matched to controls (n = 1,650) with a propensity score (Pscore), and Genetic Matching (GenMatch). The CEA projected long-term survival to report lifetime incremental costs per quality-adjusted life year (QALY) overall, and for subgroups with two or three to five organ systems failing at baseline.Results: The incremental costs per QALY for DrotAA were £30,000 overall, and £16,000 for the subgroups with three to five organ systems failing. For patients with two organ systems failing, DrotAA resulted in an average loss of one QALY at an incremental cost of £15,000. When the subgroup with two organ systems was restricted to patients receiving DrotAA within 24 hours, DrotAA led to a gain of 1.2 QALYs at a cost per QALY of £11,000. The results were robust to other assumptions including the approach taken to projecting long-term outcomes.Conclusions: DrotAA is cost-effective in routine practice for severe sepsis patients with three to five organ systems failing. For patients with two organ systems failing, this study could not provide unequivocal evidence on the cost-effectiveness of DrotAA. [ABSTRACT FROM AUTHOR]

Importance: Cyclophosphamide and calcineurin inhibitors are the most used nonsteroid immunosuppressive medications globally for children with various chronic inflammatory conditions. Their comparative effectiveness remains uncertain, leading to worldwide practice variation. Nephrotic syndrome is the most common kidney disease managed by pediatricians globally and suboptimal treatment is associated with high morbidity., Objective: To evaluate the comparative effectiveness of cyclophosphamide vs calcineurin inhibitors (tacrolimus or cyclosporine) for childhood nephrotic syndrome relapse prevention., Design, Setting, and Participants: Using target trial emulation methods, the study team emulated a pragmatic, open-label clinical trial using available data from the Insight Into Nephrotic Syndrome: Investigating Genes, Health, and Therapeutics (INSIGHT) study. INSIGHT is a multicenter, prospective cohort study in the Greater Toronto Area, Canada. Participants included children (1 to 18 years) with steroid-sensitive nephrotic syndrome diagnosed between 1996 and 2019 from the Greater Toronto Area, who initiated cyclophosphamide or a calcineurin inhibitor treatment. Data analysis was performed in 2024., Exposures: Incident cyclophosphamide or calcineurin inhibitor treatment. Randomization was emulated by overlap weighting of propensity scores for treatment assignment., Main Outcomes: The primary outcome was time to relapse, analyzed by weighted Kaplan-Meier and Cox proportional hazards models. Secondary outcomes included relapse rates, subsequent immunosuppression, kidney function, hypertension, adverse events, and quality of life., Results: Of 578 children (median age at diagnosis, 3.7 [IQR, 2.8-6.0] years; 371 male [64%] and 207 female [36%]), 252 initiated cyclophosphamide, 131 initiated calcineurin inhibitors, and 87 sequentially initiated both medications. Baseline characteristics were well balanced after propensity score weighting. During median 5.5-year (quarter 1 to quarter 3, 2.5-9.2) follow-up, there was no significant difference in time to relapse between calcineurin inhibitor vs cyclophosphamide treatment (hazard ratio [HR], 1.25; 95% CI, 0.84-1.87). Relapses were more common after calcineurin inhibitor treatment than cyclophosphamide (85% vs 73%) in the weighted cohorts, but not statistically significant. There were also no significant differences in subsequent relapse rates, nonsteroid immunosuppression use, or kidney function between medications. Calcineurin inhibitor treatment was associated with more hospitalizations (HR, 1.83; 95% CI, 1.14-2.92) and intravenous albumin use (HR, 2.81; 95% CI, 1.65-4.81)., Conclusions and Relevance: In this study, there was no evidence of difference in time to relapse after cyclophosphamide and calcineurin inhibitor treatment in children with nephrotic syndrome. Cyclophosphamide treatment is shorter in duration and more accessible globally than calcineurin inhibitors.

Preoperative assessment of functional capacity with the six-minute walk test (6MWT) allows for estimation of surgical risk and targeted triage to prehabilitation services. Patient with abdominal and pelvic cancers have worse preoperative function compared with the general population. However, six-minute walk distance (6MWD) reference values from cancer patients are unknown, which limits the interpretation of 6MWT in this population. This study aimed to establish an explanatory reference value model for preoperative 6MWD in patients with abdominal or pelvic cancers undergoing elective surgery. Adult patients undergoing surgery for abdominal or pelvic cancers at major international hospitals were included. The 6MWT was assessed before surgery using a standardised protocol. Anthropometric data including age, sex, height, weight and body mass index (BMI) were collected and included in multiple linear regression analysis to model preoperative 6MWD. A total of 742 patients were included. Age, height and BMI were correlated with 6MWD. Six regression models were estimated, including two from the entire cohort, two from the subset of males and two from the subset of females. A sex-neutral model was the most representative, explaining 15% of the variance in 6MWD (6MWD = 761.00-3.00 * Age (years) -2.86 * BMI (kg/m 2 ) - 48.09 * Sex (M1, F2)). The explored regression models, using anthropometric variables, poorly explained the variance between measured and modelled 6MWD, which suggests that these models have no clinical utility in the cancer population. Consideration of additional, non-anthropometric variables may improve regression modelling of preoperative 6MWD in patients in abdominal and pelvic cancers., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The COVID-19 pandemic challenged both research and clinical teams in critical care to collaborate on research solutions to new clinical problems. Although an effective, nationally coordinated response helped facilitate critical care research, reprioritisation of research efforts towards COVID-19 studies had significant consequences for existing and planned research activity in critical care., Aims: Our aim was to explore the impact of the COVID-19 pandemic research prioritisation policies and practices on critical care research funded prior to the pandemic, the conduct of pandemic research, and implications for ongoing and future critical care research., Methods: We undertook a descriptive qualitative study recruiting research-active clinician researchers and research delivery team members working in critical care. We conducted digitally recorded, semi-structured interviews in 2021-2022. Framework Analysis was used to analyse the data., Results: We interviewed 22 participants comprising principal investigators, senior trial coordinators and research delivery nurses from across the UK. Six themes were identified: Unit, organisational and national factors; Study specific factors; Resources; Individual/clinician factors; Family/patient factors; Contextual factors. These themes explained how a nationally coordinated response during the pandemic affected individuals, studies and wider organisations in managing the research response in critical care, highlighting future implications for critical care research., Conclusion: Harnessing the collective response seen in the COVID-19 pandemic in critical care could better support integration of research activity into routine critical care activities. Future endeavours should focus on workforce preparations, contingency planning, strategies for study prioritisation and integration of research as part of the continuum of clinical care., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (© The Intensive Care Society 2024.)

Objectives: A narrative expert review aiming to summarize the clinical epidemiology and management of critically ill patients with malignant hyperthermia (MH)., Data Sources: Medline searches were conducted to identify relevant articles describing the epidemiology, pathophysiology, and management of MH. Guidelines from key MH organizations were also incorporated into this review., Study Selection: Relevant studies regarding MH in both ICU and perioperative settings were reviewed., Data Extraction: Data from relevant studies were summarized and qualitatively assessed., Data Synthesis: MH is a severe reaction triggered by inhalational volatile anesthetics and succinylcholine in genetically susceptible patients. The condition is characterized by an early onset (min to hr) rise in temperature, hypercarbia, and muscular rigidity following exposure to triggering medications with potential complications of coagulopathy, rhabdomyolysis, and acute kidney injury. Acute management necessitates a coordinated multidisciplinary team approach with specific management using dantrolene, active cooling, and hyperventilation. A suspected MH reaction has important implications for future anesthetic exposure for both the patient and their family. All suspected reactions should be followed up at a specialized MH testing center using muscle contracture and genetic testing., Conclusions: Increasing use of inhalational anesthetics in the ICU underscores the need for enhanced education on the diagnosis and management of MH to ensure optimal patient sedation care and safety., Competing Interests: Drs. Riazi, Cuthbertson, and Jerath received support for article research from the University of Toronto; they received the Merit Award from the University of Toronto. Dr. Riazi is a board member of the Malignant Hyperthermia Association of the United States (MHAUS) and chair of the Professional Advisory Council (PAC) on Malignant Hyperthermia (MH). Dr. Pinyavat is the Medical Director of the MHAUS MH Hotline and member of the PAC. Drs. Slessarev, Cuthbertson, and Jerath are conducting research on the use of inhalation anesthetics in ICU settings (NCT04415060); they received funding from the Canadian Institutes of Health Research and the Ontario Government. Dr. Jerath disclosed off-label use of inhalational anesthetics. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Rationale: Whether extubation immediately after a successful spontaneous breathing trial is associated with clinical benefits in adult patients with acute brain injury is unknown., Objectives: We sought to estimate the association between a prompt extubation attempt and ventilator-free days among adult patients with acute brain injury., Methods: We performed an emulation of a previously designed randomized controlled trial using data from the Toronto Intensive Care Observational Registry in 8 intensive care units in Toronto, Ontario. We included mechanically ventilated adult patients with acute brain injury who had a first successful spontaneous breathing trial. Our main exposure was prompt extubation (i.e., on the same calendar day following the first successful spontaneous breathing trial). The primary outcome was ventilator-free days up to 28 days. We used inverse probability of treatment weighting to adjust for confounding and reported treatment effects using incidence rate ratios (IRR) and 95% confidence intervals (CI)., Measurements and Main Results: 1,406 patients between April 2014 through March 2023 met inclusion criteria. The main reasons for admission were traumatic brain injury (40%), stroke (ischemic or hemorrhagic; 20%), seizures (11%), and subarachnoid hemorrhage (9%). Over half (57%) of patients underwent prompt extubation following their first successful spontaneous breathing trial. Prompt extubation was associated with more ventilator-free days (IRR: 1.24; 95% CI: 1.19 - 1.29) when compared to no prompt extubation., Conclusions: Prompt extubation following a first successful spontaneous breathing trial was associated with more ventilator-free days (up to 28 days) among adults with acute brain injury receiving invasive mechanical ventilation.

Introduction: The use of volatile anesthetic agents in the paediatric intensive care unit (PICU) is experiencing increased interest since the availability of the miniature vapourizing device. However, the effectiveness of scavenging systems in the presence of humidifiers in the ventilator circuit is unknown., Approach Methods: We performed a bench study to evaluate the effectiveness of the Deltasorb® scavenging system in the presence of isoflurane and active humidity by simulating both infant and child ventilator test settings. A total of four ventilators were set to ventilate test lungs, all with active humidity and a Deltasorb scavenging canister collecting exhaled ventilation gas. Two ventilators also had isoflurane delivered using the Anesthesia Conserving Device- small (ACD®-S) on the inspiratory limb (also called alternative ventilator configuration). We performed instantaneous measurements of isoflurane and continuous sampling with passive badges to measure average environmental exposure over a test period of 6.5 hours. Scavenging canisters were returned to the company, where desorption analysis showed the volume of water and isoflurane captured in each canister., Findings: Both instantaneous point sampling and diffusive sampling results were below the occupational exposure limit confirming safety. The canisters collected both isoflurane and a portion of the water vapour delivered; the percentage of captured water and isoflurane collected in infants was higher than the child ventilator test settings., Practice Implications Conclusion: The tested scavenging configuration was effective in maintaining a safe working environment with active humidity and inspiratory limb (alternative) ventilator configuration of the the miniature vapourizing device., Competing Interests: Blue Zone Technologies, Canada did perform the desorption procedure and provided analysis of volatile and water vapor capture. All data related to occupational health and safety was undertaken through our office of Occupational Health and Safety, and neither Sedana Medical nor Blue Zone contributed to testing nor were aware of the results.

Background: Clinical presentation of postoperative myocardial infarction (POMI) is often silent. Several international guidelines recommend routine troponin surveillance in patients at risk. We compared how these different guidelines select patients for surveillance after noncardiac surgery with our established risk stratification model., Methods: We used outcome data from two prospective studies: Measurement of Exercise Tolerance before Surgery (METS) and Troponin Elevation After Major non-cardiac Surgery (TEAMS). We compared the major American, Canadian, and European guideline recommendations for troponin surveillance with our established risk stratification model. For each guideline and model, we quantified the number of patients requiring monitoring, % POMI detected, sensitivity, specificity, diagnostic odds ratio, and number needed to screen (NNS)., Results: METS and TEAMS contributed 2350 patients, of whom 319 (14%) had myocardial injury, 61 (2.5%) developed POMI, and 14 (0.6%) died. Our risk stratification model selected fewer patients for troponin monitoring (20%), compared with the Canadian (78%) and European (79%) guidelines. The sensitivity to detect POMI was highest with the Canadian and European guidelines (0.85; 95% confidence interval [CI] 0.74-0.92). Specificity was highest using the American guidelines (0.91; 95% CI 0.90-0.92). Our risk stratification model had the best diagnostic odds ratio (2.5; 95% CI 1.4-4.2) and a lower NNS (21 vs 35) compared with the guidelines., Conclusions: Most postoperative myocardial infarctions were detected by the Canadian and European guidelines but at the cost of low specificity and a higher number of patients undergoing screening. Patient selection based on our risk stratification model was optimal., (Copyright © 2023 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Objectives: Inhaled volatile anesthetics support management of status asthmaticus (SA), status epilepticus (SE), and difficult sedation (DS). This study aimed to evaluate the effectiveness, safety, and feasibility of using inhaled anesthetics for SA, SE, and DS in adult ICU and PICU patients., Data Sources: MEDLINE, Cochrane Central Register of Controlled Trials, and Embase., Study Selection: Primary literature search that reported the use of inhaled anesthetics in ventilated patients with SA, SE, and DS from 1970 to 2021., Data Extraction: Study data points were extracted by two authors independently. Quality assessment was performed using the Joanna Briggs Institute appraisal tool for case studies/series, Newcastle criteria for cohort/case-control studies, and risk-of-bias framework for clinical trials., Data Synthesis: Primary outcome was volatile efficacy in improving predefined clinical or physiologic endpoints. Secondary outcomes were adverse events and delivery logistics. From 4281 screened studies, the number of included studies/patients across diagnoses and patient groups were: SA (adult: 38/121, pediatric: 28/142), SE (adult: 18/37, pediatric: 5/10), and DS (adult: 21/355, pediatric: 10/90). Quality of evidence was low, consisting mainly of case reports and series. Clinical and physiologic improvement was seen within 1-2 hours of initiating volatiles, with variable efficacy across diagnoses and patient groups: SA (adult: 89-95%, pediatric: 80-97%), SE (adults: 54-100%, pediatric: 60-100%), and DS (adults: 60-90%, pediatric: 62-90%). Most common adverse events were cardiovascular, that is, hypotension and arrhythmias. Inhaled sedatives were commonly delivered using anesthesia machines for SA/SE and miniature vaporizers for DS. Few (10%) of studies reported required non-ICU personnel, and only 16% had ICU volatile delivery protocol., Conclusions: Volatile anesthetics may provide effective treatment in patients with SA, SE, and DS scenarios but the quality of evidence is low. Higher-quality powered prospective studies of the efficacy and safety of using volatile anesthetics to manage SA, SE, and DS patients are required. Education regarding inhaled anesthetics and the protocolization of their use is needed., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Competing Interests: We declare no competing interests.

Background: Healthcare-associated infections are a major cause of morbidity and mortality in critically ill children. In adults, data suggest the use of selective decontamination of the digestive tract may reduce the incidence of healthcare-associated infections. Selective decontamination of the digestive tract has not been evaluated in the paediatric intensive care unit population., Objectives: To determine the feasibility of conducting a multicentre, cluster-randomised controlled trial in critically ill children comparing selective decontamination of the digestive tract with standard infection control., Design: Parallel-group pilot cluster-randomised controlled trial with an integrated mixed-methods study., Setting: Six paediatric intensive care units in England., Participants: Children (> 37 weeks corrected gestational age, up to 16 years) requiring mechanical ventilation expected to last for at least 48 hours were eligible for the PICnIC pilot cluster-randomised controlled trial. During the ecology periods, all children admitted to the paediatric intensive care units were eligible. Parents/legal guardians of recruited patients and healthcare professionals working in paediatric intensive care units were eligible for inclusion in the mixed-methods study., Interventions: The interventions in the PICnIC pilot cluster-randomised controlled trial included administration of selective decontamination of the digestive tract as oro-pharyngeal paste and as a suspension given by enteric tube during the period of mechanical ventilation., Main Outcome Measures: The decision as to whether a definitive cluster-randomised controlled trial is feasible is based on multiple outcomes, including (but not limited to): (1) willingness and ability to recruit eligible patients; (2) adherence to the selective decontamination of the digestive tract intervention; (3) acceptability of the definitive cluster-randomised controlled trial; (4) estimation of recruitment rate; and (5) understanding of potential clinical and ecological outcome measures., Results: A total of 368 children (85% of all those who were eligible) were enrolled in the PICnIC pilot cluster-randomised controlled trial across six paediatric intensive care units: 207 in the baseline phase (Period One) and 161 in the intervention period (Period Two). In sites delivering selective decontamination of the digestive tract, the majority (98%) of children received at least one dose of selective decontamination of the digestive tract, and of these, 68% commenced within the first 6 hours. Consent for the collection of additional swabs was low (44%), though data completeness for potential outcomes, including microbiology data from routine clinical swab testing, was excellent. Recruited children were representative of the wider paediatric intensive care unit population. Overall, 3.6 children/site/week were recruited compared with the potential recruitment rate for a definitive cluster-randomised controlled trial of 3 children/site/week, based on data from all UK paediatric intensive care units. The proposed trial, including consent and selective decontamination of the digestive tract, was acceptable to parents and staff with adaptations, including training to improve consent and communication, and adaptations to the administration protocol for the paste and ecology monitoring. Clinical outcomes that were considered important included duration of organ failure and hospital stay, healthcare-acquired infections and survival., Limitations: The delivery of the pilot cluster-randomised controlled trial was disrupted by the COVID-19 pandemic, which led to slow set-up of sites, and a lack of face-to face training., Conclusions: PICnIC's findings indicate that a definitive cluster-randomised controlled trial in selective decontamination of the digestive tract in paediatric intensive care units is feasible with the inclusion modifications, which would need to be included in a definitive cluster-randomised controlled trial to ensure that the efficiency of trial processes is maximised., Future Work: A definitive trial that incorporates the protocol adaptations and outcomes arising from this study is feasible and should be conducted., Trial Registration: This trial is registered as ISRCTN40310490., Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/152/01) and is published in full in Health Technology Assessment ; Vol. 28, No. 8. See the NIHR Funding and Awards website for further award information.

Background: Post-operative acute kidney injury (PO-AKI) is a common surgical complication consistently associated with subsequent morbidity and mortality. Prior kidney dysfunction is a major risk factor for PO-AKI, however it is unclear whether serum creatinine, the conventional kidney function marker, is optimal in this population. Serum cystatin C is a kidney function marker less affected by body composition and might provide better prognostic information in surgical patients., Methods: This was a pre-defined, secondary analysis of a multi-centre prospective cohort study of pre-operative functional capacity. Participants were aged ≥40 years, undergoing non-cardiac surgery. We assessed the association of pre-operative estimated glomerular filtration rate (eGFR) calculated using both serum creatinine and serum cystatin C with PO-AKI within 3 days after surgery, defined by KDIGO creatinine changes. The adjusted analysis accounted for established AKI risk factors., Results: A total of 1347 participants were included (median age 65 years, interquartile range 56-71), of whom 775 (58%) were male. A total of 82/1347 (6%) patients developed PO-AKI. These patients were older, had higher prevalence of cardiovascular disease and related medication, were more likely to have intra-abdominal procedures, had more intraoperative transfusion, and were more likely to be dead at 1 year after surgery 6/82 (7.3%) vs 33/1265 (2.7%) ( P  = .038). Pre-operative eGFR was lower in AKI than non-AKI patients using both creatinine and cystatin C. When both measurements were considered in a single age- and sex-adjusted model, eGFR-Cysc was strongly associated with PO-AKI, with increasing risk of AKI as eGFR-Cysc decreased below 90, while eGFR-Cr was no longer significantly associated., Conclusions: Data from over 1000 prospectively recruited surgical patients confirms pre-operative kidney function as major risk factor for PO-AKI. Of the kidney function markers available, compared with creatinine, cystatin C had greater strength of association with PO-AKI and merits further assessment in pre-operative assessment of surgical risk., Competing Interests: J.R.P. has received honoraria from Paion Ltd, Baxter Inc., Biomerieux SA and Nikkiso Europe GmbH; he is a scientific advisor for Mission Therapeutics Ltd, Jafron Biomedical Co. Ltd and Nephrolyx GmbH, and serves on a Data Monitoring and Safety Board for Novartis Inc.; he is a specialty editor for the Clinical Kidney Journal and Blood Purification. B.H.C. and D.N.W. are supported in part by Merit Awards from the Department of Anesthesiology and Pain Medicine at the University of Toronto. D.N.W. is supported in part by the Endowed Chair in Translational Anesthesiology Research at St Michael's Hospital and the University of Toronto. D.N.W. has received honoraria from Edwards Lifesciences within the last 5 years and is a member of the Scientific Advisory Board for Surgical Safety Technologies Inc. T.E.F.A. is an NIHR Clinical Lecturer, an editor of the British Journal of Anaesthesia, has received research funding from the Medical Research Council, the National Institute of Academic Anaesthesia and Barts Charity, and has received consultancy fees from MSD and Edwards Life Sciences unrelated to this work. All other authors report no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years, and no other relationships or activities that could appear to have influenced the submitted work., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: Health-related quality of life (HRQoL) is a patient-centred outcome increasingly used as a secondary outcome in critical care research. It may cover several important dimensions of clinical status in intensive care unit (ICU) patients that arguably elude other more easily quantified outcomes such as mortality. Poor associations with harder outcomes, conflicting data on HRQoL in critically ill compared to the background population, and paradoxical effects on HRQoL and mortality complicate the current operationalisation in critical care trials. This protocol outlines a simulation study that will gauge if the areas under the HRQoL trajectories could be a viable alternative., Methods: We will gauge the behaviour of the proposed HRQoL operationalisation through Monte Carlo simulations, under clinical scenarios that reflect a broad critical care population eligible for inclusion in a large pragmatic trial. We will simulate 15,360 clinical scenarios based on a full factorial design with the following seven simulation parameters: number of patients per arm, relative mortality reduction in the interventional arm, acceleration of HRQoL improvement in the interventional arm, the relative improvement in final HRQoL in the interventional arm, dampening effect of mortality on HRQoL values at discharge from the ICU, proportion of so-called mortality benefiters in the interventional arm and mortality trajectory shape. For each clinical scenario, we will simulate 100,000 two-arm trials with 1:1 randomisation. HRQoL will be sampled fortnightly after ICU discharge. Outcomes will include HRQoL in survivors and all patients at the end of follow-up; mean areas under the HRQoL trajectories in both arms; and mean difference between areas under the HRQoL trajectories and single-sampled HRQoLs at the end of follow-up., Discussion: In the outlined simulation study, we aim to assess whether the area under the HRQoL trajectory curve could be a candidate for reconciling the seemingly paradoxical effects on improved mortality and reduced HRQoL while remaining sensitive to early or accelerated improvement in patient outcomes. The resultant insights will inform subsequent methodological work on prudent collection and statistical analysis of such data from real critically ill patients., (© 2023 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Healthcare-associated infections (HCAIs) are a major cause of morbidity and mortality in critically ill children. Data from adult studies suggest Selective Decontamination of the Digestive tract (SDD) may reduce the incidence of HCAIs and improve survival. There are no data from randomised clinical trials in the paediatric setting. An open label, parallel group pilot cRCT and mixed-methods perspectives study was conducted in six paediatric intensive care units (PICUs) in England. Participants were children (> 37 weeks corrected gestational age, up to 16 years) requiring mechanical ventilation expected to last for at least 48 h. Sites undertook standard care for a period of 9 weeks and were randomised into 3 sites which continued standard care and 3 where SDD was incorporated into infection control practice for eligible children. Interviews and focus groups were conducted for parents and staff working in PICU. 434 children fulfilled eligibility criteria, of whom 368 (85%) were enrolled. This included 207 in the baseline phase (Period One) and 161 in the intervention period (Period Two). In sites delivering SDD, the majority (98%) of children received at least one dose of SDD and of these, 68% commenced within the first 6 h. Whilst admission swabs were collected in 91% of enrolled children, consent for the collection of additional swabs was low (44%). Recruited children were representative of the wider PICU population. Overall, 3.6 children/site/week were recruited compared with the potential recruitment rate for a definitive cRCT of 3 children/site/week, based on data from all UK PICUs. Parents (n = 65) and staff (n = 44) were supportive of the aims of the study, suggesting adaptations for a larger definitive trial including formulation and administration of SDD paste, approaches to consent and ecology monitoring. Stakeholders identified preferred clinical outcomes, focusing on complications of critical illness and quality-of-life. A definitive cRCT in SDD to prevent HCAIs in critically ill children is feasible but should include adaptations to ecology monitoring along with the dosing schedule and packaging into a paediatric specific format. A definitive study is supported by the findings with adaptations to ecology monitoring and SDD administration.Trial Registration: ISRCTN40310490 Registered 30/10/2020., (© 2023. The Author(s).)