Use of selective gut decontamination in critically ill children: PICnIC a pilot RCT and mixed-methods study.

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.

Each year, around 20,000 critically ill children are admitted to paediatric intensive care units in the UK. These children are at a higher risk of healthcare-associated infections, one of the main sources of which is the large number of bacteria in the digestive tract. Spread of bacteria from the digestive tract into other organs, such as the lung (causing ventilator-associated pneumonia) or bloodstream (causing sepsis), can be life-threatening. The risk is highest in those children whose illness is so severe that they require prolonged mechanical ventilation. Stopping the growth of bacteria in the digestive tract (called selective decontamination of the digestive tract) has been shown in adults to reduce the number of hospital-acquired infections. However, there have been no trials in children. We wanted to assess how practical and acceptable such a trial would be comparing standard infection control to selective decontamination of the digestive tract-enhanced infection control and monitoring how each intervention affected antimicrobial resistance. We undertook a pilot study to examine whether clinicians could identify eligible children, enrol them in the study and follow study procedures during the course of paediatric intensive care unit admission. Alongside this, we interviewed parents and clinicians to get their views on the proposed trial. Six hospitals recruited 559 patients over a period of roughly 7 months. Hospitals were randomly allocated to continue with the standard infection control procedure or to give selective decontamination of the digestive tract. Overall, recruitment was higher than expected. Alongside this, we examined the views of patients, caregivers and healthcare professionals to assess their views on whether a trial should be carried out to see if selective decontamination of the digestive tract should become part of the infection control regime for children most at risk of hospital-acquired infection in the paediatric intensive care unit. Overall results suggest that a larger PICnIC trial incorporating patient stakeholder and clinical staff feedback on design and outcomes is feasible and that it is appropriate to conduct a trial into the effectiveness of selective decontamination of the digestive tract administration to minimise hospital-acquired infections.

Inhaled Volatiles for Status Asthmaticus, Epilepsy, and Difficult Sedation in Adult ICU and PICU: A Systematic Review.

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.

Postoperative troponin surveillance to detect myocardial infarction: an observational cohort modelling study.

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.

Cystatin C or creatinine for pre-operative assessment of kidney function and risk of post-operative acute kidney injury: a secondary analysis of the METS cohort study.

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.

Health-related quality of life trajectories in critical illness: Protocol for a Monte Carlo simulation study.

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.

Selective digestive tract decontamination to prevent healthcare associated infections in critically ill children: the PICNIC multicentre randomised pilot clinical trial.

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.

Sex-related differences in functional capacity and its implications in risk stratification before major non-cardiac surgery: a post hoc analysis of the international METS study.

Background: Poor functional capacity has been identified as an important modifiable risk factor for postoperative complications. Cardiopulmonary exercise testing (CPET) provides objective parameters of functional capacity (e.g., oxygen consumption at peak exercise, peak VO2), with significant prognostication for postoperative complications. However, sex-specific thresholds for functional capacity to predict surgical risk are yet to be established. Therefore, we performed a post hoc analysis of the international, multicentre, prospective observational METS (Measurement of Exercise Tolerance before Surgery) study to evaluate if sex-specific thresholds of peak VO2 improve risk prediction of postoperative complications. Methods: We undertook a post hoc analysis (HREC/71824/PMCC) of the METS study, which was performed between March 2013 and March 2016. We investigated whether sex-specific differences exist for CPET-derived parameters and associated thresholds for predicting postoperative complications in this large cohort of patients that had major non-cardiac surgery (n = 1266). Logistic regression models were analyzed for the association of low peak VO2 with moderate-to-severe in-hospital postoperative complications. Optimal sex-specific peak VO2 thresholds were obtained by maximizing the Youden index of receiver operating characteristic (ROC) curves. Finally, multivariable logistic regression models tested the resulting sex-specific thresholds against the established non-sex-specific peak VO2 threshold (14 mL kg-1 min-1) adjusted for clinically relevant features such as comorbidities and surgical complexity. Models were evaluated by bootstrapping optimism-corrected area under the ROC curve and the net reclassification improvement index (NRI). Findings: Female patients (n = 480) had a lower mean (SD) peak VO2 than males (16.7 (4.9) mL kg-1 min-1 versus 21.2 (6.5) mL kg-1 min-1, p < 0.001) and a lower postoperative complication rate (10.4% versus 15.3%; p = 0.018) than males (n = 786). The optimal peak VO2 threshold for predicting postoperative complications was 12.4 mL kg-1 min-1 for females and 22.3 mL kg-1 min-1 for males, respectively. In the multivariable regression model, low non-sex-specific peak VO2 did not independently predict postoperative complications. In contrast, low sex-specific peak VO2 was an independent predictor of postoperative complications (OR 2.29; 95% CI: 1.60, 3.30; p < 0.001). The optimism-corrected AUC-ROC of the sex-specific model was higher compared with the non-sex-specific model (0.73 versus 0.7; DeLong's test: p = 0.021). The sex-specific model classified 39% of the patients more correctly than the baseline model (NRI = 0.39; 95% CI: 0.24, 0.55). In contrast, the non-sex-specific model only classified 9% of the patients more correctly when compared against the baseline model (NRI = 0.09; 95% CI: -0.04, 0.22). Interpretation: Our data report sex-specific differences in preoperative CPET-derived functional capacity parameters. Sex-specific peak VO2 thresholds identify patients at increased risk for postoperative complications with a higher discriminatory ability than a sex-unspecific threshold. As such, sex-specific threshold values should be considered in preoperative CPET to potentially improve risk stratification and to guide surgical decision-making, including eligibility for surgery, preoperative optimization strategies (prehabilitation) or seeking non-surgical options. Funding: There was no funding for the present study. The original METS study was funded by Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Ontario Ministry of Health and Long-Term Care, Ontario Ministry of Research, Innovation and Science, UK National Institute of Academic Anaesthesia, UK Clinical Research Collaboration, Australian and New Zealand College of Anaesthetists, and Monash University.

Association between preoperative cardiac risk assessment and health care costs in major noncardiac surgery: a multicentre health economic analysis.

PURPOSE: Patients with impaired functional capacity who undergo major surgery are at increased risk of postoperative morbidity including complications and increased length of stay. These outcomes have been associated with increased hospital and health system costs. We aimed to assess whether common preoperative risk indices are associated with postoperative cost. METHODS: We conducted a health economic analysis focused on the subset of Measurement of Exercise Tolerance before Surgery (METS) study participants in Ontario, Canada. Participants were scheduled for major elective noncardiac surgery and underwent several preoperative assessments of cardiac risk, including physicians' subjective assessment, Duke Activity Status Index (DASI) questionnaire, peak oxygen consumption, and N-terminal pro-B-type natriuretic peptide concentration. Using linked health administrative data, postoperative costs were calculated for both one year and in-hospital. Using multiple regression models, we tested for association between the preoperative measures of cardiac risk and postoperative costs. RESULTS: Our study included 487 patients (mean [standard deviation] age 68 [11] yr and 47.0% female) who underwent noncardiac surgery between 13 June 2013 and 8 March 2016. Overall, the median [interquartile range] cost incurred within one year postoperatively was CAD 27,587 [13,902-32,590], of which CAD 12,928 [10,253-12,810] were incurred in-hospital and CAD 14,497 [10,917-15,017] were incurred by 30 days. None of the four preoperative measures of cardiac risk assessment were associated with costs incurred in hospital or at one year postoperatively. This lack of strong association persisted in sensitivity analyses considering type of surgical procedure, burden of preoperative cost, and when costs were categorized as quantiles. CONCLUSION: In patients undergoing major noncardiac surgery, common measures of functional capacity are not consistently associated with total postoperative cost. Until further data exist that differ from this analysis, clinicians and health care funders should not assume that preoperative measures of cardiac risk are associated with annual health care or hospital costs for such surgeries.

RéSUMé: OBJECTIF: La patientèle présentant une capacité fonctionnelle dégradée qui bénéficie d'une intervention chirurgicale majeure court un risque accru de morbidité postopératoire, y compris de complications et de prolongation de la durée de séjour. Ces issues ont été associées à une augmentation des coûts hospitaliers et du système de santé. Notre objectif était d'évaluer si des indices de risque préopératoires communs étaient associés aux coûts postopératoires. MéTHODE: Nous avons effectué une analyse de l'économie de la santé axée sur le sous-ensemble des participant·es à l'étude METS (Measurement of Exercise Tolerance before Surgery) en Ontario, au Canada. Les participant·es devaient bénéficier d'une chirurgie non cardiaque et non urgente majeure et ont complété plusieurs évaluations préopératoires du risque cardiaque, notamment l'évaluation subjective des médecins, le questionnaire DASI (Duke Activity Status Index), la consommation maximale d'oxygène et la concentration de prohormone N-terminale du peptide natriurétique de type B (cérébral) (NT-proBNP). À l'aide de données administratives couplées de santé, les coûts postopératoires ont été calculés à la fois pour une année et à l'hôpital. À l'aide de modèles de régression multiples, nous avons testé l'association entre les mesures préopératoires du risque cardiaque et les coûts postopératoires. RéSULTATS: Notre étude a inclus 487 personnes (âge moyen [écart type] 68 [11] ans et 47,0 % de femmes) ayant bénéficié d'une chirurgie non cardiaque entre le 13 juin 2013 et le 8 mars 2016. Dans l'ensemble, le coût médian [écart interquartile] engagé dans l'année qui a suivi l'opération était de 27 587 CAD [13 902­32 590], dont 12 928 CAD [10 253­12 810] ont été encourus à l'hôpital et 14 497 CAD [10 917­15 017] ont été encourus dans les premiers 30 jours. Aucune des quatre mesures préopératoires de l'évaluation du risque cardiaque n'était associée aux coûts engagés à l'hôpital ou un an après l'opération. Cette absence d'association forte persistait dans les analyses de sensibilité tenant compte du type d'intervention chirurgicale, du fardeau des coûts préopératoires et lorsque les coûts étaient classés en quantiles. CONCLUSION: Chez la patientèle bénéficiant d'une chirurgie non cardiaque majeure, les mesures courantes de la capacité fonctionnelle ne sont pas systématiquement associées au coût postopératoire total. Jusqu'à ce qu'il existe d'autres données qui diffèrent de cette analyse, les cliniciens et cliniciennes et les organismes finançant les soins de santé ne devraient pas présumer que les mesures préopératoires du risque cardiaque sont associées aux coûts annuels des soins de santé ou des hôpitaux pour de telles chirurgies.

Effect of inhaled anaesthetics on cognitive and psychiatric outcomes in critically ill adults: a systematic review and meta-analysis.

BACKGROUND: Sedation of critically ill patients with inhaled anaesthetics may reduce lung inflammation, time to extubation, and ICU length of stay compared with intravenous (i.v.) sedatives. However, the impact of inhaled anaesthetics on cognitive and psychiatric outcomes in this population is unclear. In this systematic review, we aimed to summarise the effect of inhaled anaesthetics on cognitive and psychiatric outcomes in critically ill adults. METHODS: We searched MEDLINE, EMBASE, and PsycINFO for case series, retrospective, and prospective studies in critically ill adults sedated with inhaled anaesthetics. Outcomes included delirium, psychomotor and neurological recovery, long-term cognitive dysfunction, ICU memories, anxiety, depression, post-traumatic stress disorder (PTSD), and instruments used for assessment. RESULTS: Thirteen studies were included in distinct populations of post-cardiac arrest survivors (n=4), postoperative noncardiac patients (n=3), postoperative cardiac patients (n=2), and mixed medical-surgical patients (n=4). Eight studies reported delirium incidence, two neurological recovery, and two ICU memories. One study reported on psychomotor recovery, long-term cognitive dysfunction, anxiety, depression, and PTSD. A meta-analysis of five trials found no difference in delirium incidence between inhaled and i.v. sedatives (relative risk 0.95 [95% confidence interval: 0.59-1.54]). Compared with i.v. sedatives, inhaled anaesthetics were associated with fewer hallucinations and faster psychomotor recovery but no differences in other outcomes. There was heterogeneity in the instruments used and timing of these assessments. CONCLUSIONS: Based on the limited evidence available, there is no difference in cognitive and psychiatric outcomes between adults exposed to volatile sedation or intravenous sedation in the ICU. Future studies should incorporate outcome assessment with validated tools during and after hospital stay. SYSTEMATIC REVIEW PROTOCOL: PROSPERO CRD42021236455.

Tracheostomy timing and outcome in critically ill patients with stroke: a meta-analysis and meta-regression.

BACKGROUND: Stroke patients requiring mechanical ventilation often have a poor prognosis. The optimal timing of tracheostomy and its impact on mortality in stroke patients remains uncertain. We performed a systematic review and meta-analysis of tracheostomy timing and its association with reported all-cause overall mortality. Secondary outcomes were the effect of tracheostomy timing on neurological outcome (modified Rankin Scale, mRS), hospital length of stay (LOS), and intensive care unit (ICU) LOS. METHODS: We searched 5 databases for entries related to acute stroke and tracheostomy from inception to 25 November 2022. We adhered to PRISMA guidance for reporting systematic reviews and meta-analyses. Selected studies included (1) ICU-admitted patients who had stroke (either acute ischaemic stroke, AIS or intracerebral haemorrhage, ICH) and received a tracheostomy (with known timing) during their stay and (2) > 20 tracheotomised. Studies primarily reporting sub-arachnoid haemorrhage (SAH) were excluded. Where this was not possible, adjusted meta-analysis and meta-regression with study-level moderators were performed. Tracheostomy timing was analysed continuously and categorically, where early (< 5 days from initiation of mechanical ventilation to tracheostomy) and late (> 10 days) timing was defined per the protocol of SETPOINT2, the largest and most recent randomised controlled trial on tracheostomy timing in stroke patients. RESULTS: Thirteen studies involving 17,346 patients (mean age = 59.8 years, female 44%) met the inclusion criteria. ICH, AIS, and SAH comprised 83%, 12%, and 5% of known strokes, respectively. The mean time to tracheostomy was 9.7 days. Overall reported all-cause mortality (adjusted for follow-up) was 15.7%. One in five patients had good neurological outcome (mRS 0-3; median follow-up duration was 180 days). Overall, patients were ventilated for approximately 12 days and had an ICU LOS of 16 days and a hospital LOS of 28 days. A meta-regression analysis using tracheostomy time as a continuous variable showed no statistically significant association between tracheostomy timing and mortality (ß = - 0.3, 95% CI = - 2.3 to 1.74, p = 0.8). Early tracheostomy conferred no mortality benefit when compared to late tracheostomy (7.8% vs. 16.4%, p = 0.7). Tracheostomy timing was not associated with secondary outcomes (good neurological outcome, ICU LOS and hospital LOS). CONCLUSIONS: In this meta-analysis of over 17,000 critically ill stroke patients, the timing of tracheostomy was not associated with mortality, neurological outcomes, or ICU/hospital LOS. TRIAL REGISTRATION: PROSPERO-CRD42022351732 registered on 17th of August 2022.

Effect of Selective Decontamination of the Digestive Tract on Hospital Mortality in Critically Ill Patients Receiving Mechanical Ventilation: A Randomized Clinical Trial.

Importance: Whether selective decontamination of the digestive tract (SDD) reduces mortality in critically ill patients remains uncertain. Objective: To determine whether SDD reduces in-hospital mortality in critically ill adults. Design, Setting, and Participants: A cluster, crossover, randomized clinical trial that recruited 5982 mechanically ventilated adults from 19 intensive care units (ICUs) in Australia between April 2018 and May 2021 (final follow-up, August 2021). A contemporaneous ecological assessment recruited 8599 patients from participating ICUs between May 2017 and August 2021. Interventions: ICUs were randomly assigned to adopt or not adopt a SDD strategy for 2 alternating 12-month periods, separated by a 3-month interperiod gap. Patients in the SDD group (n = 2791) received a 6-hourly application of an oral paste and administration of a gastric suspension containing colistin, tobramycin, and nystatin for the duration of mechanical ventilation, plus a 4-day course of an intravenous antibiotic with a suitable antimicrobial spectrum. Patients in the control group (n = 3191) received standard care. Main Outcomes and Measures: The primary outcome was in-hospital mortality within 90 days. There were 8 secondary outcomes, including the proportion of patients with new positive blood cultures, antibiotic-resistant organisms (AROs), and Clostridioides difficile infections. For the ecological assessment, a noninferiority margin of 2% was prespecified for 3 outcomes including new cultures of AROs. Results: Of 5982 patients (mean age, 58.3 years; 36.8% women) enrolled from 19 ICUs, all patients completed the trial. There were 753/2791 (27.0%) and 928/3191 (29.1%) in-hospital deaths in the SDD and standard care groups, respectively (mean difference, -1.7% [95% CI, -4.8% to 1.3%]; odds ratio, 0.91 [95% CI, 0.82-1.02]; P = .12). Of 8 prespecified secondary outcomes, 6 showed no significant differences. In the SDD vs standard care groups, 23.1% vs 34.6% had new ARO cultures (absolute difference, -11.0%; 95% CI, -14.7% to -7.3%), 5.6% vs 8.1% had new positive blood cultures (absolute difference, -1.95%; 95% CI, -3.5% to -0.4%), and 0.5% vs 0.9% had new C difficile infections (absolute difference, -0.24%; 95% CI, -0.6% to 0.1%). In 8599 patients enrolled in the ecological assessment, use of SDD was not shown to be noninferior with regard to the change in the proportion of patients who developed new AROs (-3.3% vs -1.59%; mean difference, -1.71% [1-sided 97.5% CI, -∞ to 4.31%] and 0.88% vs 0.55%; mean difference, -0.32% [1-sided 97.5% CI, -∞ to 5.47%]) in the first and second periods, respectively. Conclusions and Relevance: Among critically ill patients receiving mechanical ventilation, SDD, compared with standard care without SDD, did not significantly reduce in-hospital mortality. However, the confidence interval around the effect estimate includes a clinically important benefit. Trial Registration: ClinicalTrials.gov Identifier: NCT02389036.

Tracheostomy outcomes in critically ill patients with COVID-19: a systematic review, meta-analysis, and meta-regression.

BACKGROUND: We performed a systematic review of mechanically ventilated patients with COVID-19, which analysed the effect of tracheostomy timing and technique (surgical vs percutaneous) on mortality. Secondary outcomes included intensive care unit (ICU) and hospital length of stay (LOS), decannulation from tracheostomy, duration of mechanical ventilation, and complications. METHODS: Four databases were screened between January 1, 2020 and January 10, 2022 (PubMed, Embase, Scopus, and Cochrane). Papers were selected according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the Population or Problem, Intervention or exposure, Comparison, and Outcome (PICO) guidelines. Meta-analysis and meta-regression for main outcomes were performed. RESULTS: The search yielded 9024 potentially relevant studies, of which 47 (n=5268 patients) were included. High levels of between-study heterogeneity were observed across study outcomes. The pooled mean tracheostomy timing was 16.5 days (95% confidence interval [CI]: 14.7-18.4; I2=99.6%). Pooled mortality was 22.1% (95% CI: 18.7-25.5; I2=89.0%). Meta-regression did not show significant associations between mortality and tracheostomy timing, mechanical ventilation duration, time to decannulation, and tracheostomy technique. Pooled mean estimates for ICU and hospital LOS were 29.6 (95% CI: 24.0-35.2; I2=98.6%) and 38.8 (95% CI: 32.1-45.6; I2=95.7%) days, both associated with mechanical ventilation duration (coefficient 0.8 [95% CI: 0.2-1.4], P=0.02 and 0.9 [95% CI: 0.4-1.4], P=0.01, respectively) but not tracheostomy timing. Data were insufficient to assess tracheostomy technique on LOS. Duration of mechanical ventilation was 23.4 days (95% CI: 19.2-27.7; I2=99.3%), not associated with tracheostomy timing. Data were insufficient to assess the effect of tracheostomy technique on mechanical ventilation duration. Time to decannulation was 23.8 days (95% CI: 19.7-27.8; I2=98.7%), not influenced by tracheostomy timing or technique. The most common complications were stoma infection, ulcers or necrosis, and bleeding. CONCLUSIONS: In patients with COVID-19 requiring tracheostomy, the timing and technique of tracheostomy did not clearly impact on patient outcomes. SYSTEMATIC REVIEW PROTOCOL: PROSPERO CRD42021272220.

Co-designed and consensus based development of a quality improvement checklist of patient and family-centered actionable processes of care for adults with persistent critical illness.

PURPOSE: Few quality improvement tools specific to patients with persistent or chronic critical illness exist to aid delivery of high-quality care. Using experience-based co-design methods, we sought consensus from key stakeholders on the most important actionable processes of care for inclusion in a quality improvement checklist. METHODS: Item generation methods: systematic review, semi-structured interviews (ICU survivors and family) members, touchpoint video creation, and semi-structured interviews (ICU clinicians). Consensus methods: modified online Delphi and a virtual meeting using nominal group technique methods. RESULTS: We enrolled 138 ICU interprofessional team, patients, and family members. We obtained consensus on a quality improvement checklist comprising 11 core domains: patient and family involvement in decision-making; patient communication; physical comfort and complication prevention; promoting self-care and normalcy; ventilator weaning; physical therapy; swallowing; pharmacotherapy; psychological issues; delirium; and appropriate referrals. An additional 27 actionable processes are contained within 6 core domains that provide more specific direction on the actionable process to be targeted. CONCLUSIONS: Using a highly collaborative and methodologically rigorous process, we generated a quality improvement checklist of actionable processes to improve patient and family-centred care considered important by key stakeholders. Future research is needed to understand optimal implementation strategies and impact on outcomes and experience.

Measurement properties of the WHO Disability Assessment Schedule 2.0 for evaluating functional status after inpatient surgery.

BACKGROUND: Expert recommendations propose the WHO Disability Assessment Schedule (WHODAS) 2.0 as a core outcome measure in surgical studies, yet data on its long-term measurement properties remain limited. These were evaluated in a secondary analysis of the Measurement of Exercise Tolerance before Surgery (METS) prospective cohort. METHODS: Participants were adults (40 years of age or older) who underwent inpatient non-cardiac surgery. The 12-item WHODAS and EQ-5DTM-3L questionnaires were administered preoperatively (in person) and 1 year postoperatively (by telephone). Responsiveness was characterized using standardized response means (SRMs) and correlation coefficients between change scores. Construct validity was evaluated using correlation coefficients between 1-year scores and comparisons of WHODAS scores across clinically relevant subgroups. RESULTS: The analysis included 546 patients. There was moderate correlation between changes in WHODAS and various EQ-5DTM subscales. The strongest correlation was between changes in WHODAS and changes in the functional domains of the EQ-5D-3L-for example, mobility (Spearman's rho 0.40, 95 per cent confidence interval [c.i.] 0.32 to 0.48) and usual activities (rho 0.45, 95 per cent c.i. 0.30 to 0.52). When compared across quartiles of EQ-5D index change, median WHODAS scores followed expected patterns of change. In subgroups with expected functional status changes, the WHODAS SRMs ranged from 'small' to 'large' in the expected directions of change. At 1 year, the WHODAS demonstrated convergence with the EQ-5D-3L functional domains, and good discrimination between patients with expected differences in functional status. CONCLUSION: The WHODAS questionnaire has construct validity and responsiveness as a measure of functional status at 1 year after major surgery.

Surgery can have a long-lasting impact on a person's 'functional status', which is their ability to carry out routine functions of daily living (e.g. work, chores, and social activity). International societies now recommend that functional status be routinely measured in research studies of patients having surgery. A potential instrument to measure functional status in patients having surgery is the WHO Disability Assessment Schedule (WHODAS) 2.0. The WHODAS 2.0 was originally designed to measure function and disability in a general population (i.e. not patients having surgery). In this study, we show that the WHODAS 2.0 has acceptable performance when measuring functional status in patients having surgery.

Inclusion, characteristics, and outcomes of male and female participants in large international perioperative studies.

BACKGROUND: We compared baseline characteristics and outcomes and evaluated the subgroup effects of randomised interventions by sex in males and females in large international perioperative trials. METHODS: Nine randomised trials and two cohort studies recruiting adult patients, conducted between 1995 and 2020, were included. Baseline characteristics and outcomes common to six or more studies were evaluated. Regression models included terms for sex, study, and an interaction between the two. Comparing outcomes without adjustment for baseline characteristics represents the 'total effect' of sex on the outcome. RESULTS: Of 54 626 participants, 58% were male and 42% were female. Females were less likely to have ASA physical status ≥3 (56% vs 64%), to smoke (15% vs 23%), have coronary artery disease (21% vs 32%), or undergo vascular surgery (10% vs 23%). The pooled incidence of death was 1.6% in females and 1.8% in males (risk ratio [RR] 0.92; 95% confidence interval [CI]: 0.81-1.05; P=0.20), of myocardial infarction was 4.2% vs 4.5% (RR 0.92; 95% CI: 0.81-1.03; P=0.10), of stroke was 0.5% vs 0.6% (RR 1.03; 95% CI: 0.79-1.35; P=0.81), and of surgical site infection was 8.6% vs 8.3% (RR 1.03; 95% CI: 0.79-1.35; P=0.70). Treatment effects of three interventions demonstrated statistically significant effect modification by sex. CONCLUSIONS: Females were in the minority in all included studies. They were healthier than males, but outcomes were comparable. Further research is needed to understand the reasons for this discrepancy. CLINICAL TRIAL REGISTRATION: International Registry of Meta-Research (UID: IRMR_000011; 5 January 2021).