Towards Evidence-Based Weaning: a Mechanism-Based Pharmacometric Model to Characterize Iatrogenic Withdrawal Syndrome in Critically Ill Children.
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SUBMITTER: Goulooze SC
PROVIDER: S-EPMC8128736 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundIatrogenic withdrawal syndrome, after exposure medication known to cause withdrawal is recognised, yet under described in adult intensive care.AimTo investigate, opioid, sedation, and preadmission medication practice in critically ill adults with focus on aspects associated with iatrogenic withdrawal syndrome.MethodOne-day point prevalence study in UK intensive care units (ICUs). We collected ICU admission medication and/or substances with withdrawal potential, sedation policy, opioid and sedative use, dose, and duration.ResultsThirty-seven from 39 participating ICUs contributed data from 386 patients. The prevalence rate for parenteral opioid and sedative medication was 56.1% (212 patients). Twenty-three ICUs (59%) had no sedation/analgesia policy, and no ICUs screened for iatrogenic withdrawal. Patient admission medications with withdrawal-potential included antidepressants or antipsychotics (43, 20.3%) and nicotine (41, 19.3%). Of 212 patients, 202 (95.3%) received opioids, 163 (76.9%) sedatives and 153 (72.2%) both. Two hundred and two (95.3%) patients received opioids: 167 (82.7%) by continuous infusions and 90 (44.6%) patients for longer than 96-h. One hundred and sixty-three (76.9%) patients received sedatives: 157 (77.7%) by continuous infusions and 74 (45.4%) patients for longer than 96-h.ConclusionOpioid sedative and admission medication with iatrogenic withdrawal syndrome potential prevalence rates were high, and a high proportion of ICUs had no sedative/analgesic policies. Nearly half of patients received continuous opioids and sedatives for longer than 96-h placing them at high risk of iatrogenic withdrawal. No participating unit reported using a validated tool for iatrogenic withdrawal assessment.
| S-EPMC10600273 | biostudies-literature
Project description:Analgesia and sedation are common therapies in pediatric critical care, and rapid titration of these medications is associated with iatrogenic withdrawal syndrome. We performed a systematic review of the literature to identify all common and salient risk factors associated with iatrogenic withdrawal syndrome and build a conceptual model of iatrogenic withdrawal syndrome risk in critically ill pediatric patients.Multiple databases, including PubMed/Medline, EMBASE, CINAHL, and the Cochrane Central Registry of Clinical Trials, were searched using relevant terms from January 1, 1980, to August 1, 2014.Articles were included if they were published in English and discussed iatrogenic withdrawal syndrome following either opioid or benzodiazepine therapy in children in acute or intensive care settings. Articles were excluded if subjects were neonates born to opioid- or benzodiazepine-dependent mothers, children diagnosed as substance abusers, or subjects with cancer-related pain; if data about opioid or benzodiazepine treatment were not specified; or if primary data were not reported.In total, 1,395 articles were evaluated, 33 of which met the inclusion criteria. To facilitate analysis, all opioid and/or benzodiazepine doses were converted to morphine or midazolam equivalents, respectively. A table of evidence was developed for qualitative analysis of common themes, providing a framework for the construction of a conceptual model. The strongest risk factors associated with iatrogenic withdrawal syndrome include duration of therapy and cumulative dose. Additionally, evidence exists linking patient, process, and system factors in the development of iatrogenic withdrawal syndrome.Most articles were prospective observational or interventional studies.Given the state of existing evidence, well-designed prospective studies are required to better characterize iatrogenic withdrawal syndrome in critically ill pediatric patients. This review provides data to support the construction of a conceptual model of iatrogenic withdrawal syndrome risk that, if supported, could be useful in guiding future research.
| S-EPMC5304939 | biostudies-literature
Project description:ImportanceAlthough most critically ill patients receive invasive mechanical ventilation (IMV), few studies have characterized how IMV is discontinued in practice.ObjectiveTo describe practice variation in IMV discontinuation internationally, associations between initial discontinuation events and outcomes, and factors associated with the use of select discontinuation strategies and failed initial spontaneous breathing trials (SBTs).Design, setting, and participantsProspective, multinational, observational study of critically ill adults who received IMV for at least 24 hours from 142 intensive care units (ICUs) in 19 countries within 6 regions (27 in Canada, 23 in India, 22 in the UK, 26 in Europe, 21 in Australia/New Zealand, and 23 in the US).ExposuresReceiving IMV.Main outcomes and measuresPrimary analyses characterized types of initial IMV discontinuation events (extubation, SBT, or tracheostomy) and associations with clinical outcomes (including duration of ventilation, ICU and hospital mortality, and ICU and hospital length of stay). Secondary analyses examined the associations between SBT outcome and SBT timing and clinical outcomes.ResultsAmong 1868 patients (median [interquartile range] age, 61.8 [48.9-73.1] years; 1173 [62.8%] men) 424 (22.7%) underwent direct extubation, 930 (49.8%) had an initial SBT (761 [81.8%] successful), 150 (8.0%) underwent direct tracheostomy, and 364 (19.5%) died before a weaning attempt. Across regions, there was variation in the use of written directives to guide care, daily screening, SBT techniques, ventilator modes, and the roles played by clinicians involved in weaning. Compared with initial direct extubation, patients who had an initial SBT had higher ICU mortality (20 [4.7%] vs 96 [10.3%]; absolute difference, 5.6% [95% CI, 2.6%-8.6%]), longer duration of ventilation (median of 2.9 vs 4.1 days; absolute difference, 1.2 days [95% CI, 0.7-1.6]), and longer ICU stay (median of 6.7 vs 8.1 days; absolute difference, 1.4 days [95% CI, 0.8-2.4]). Patients whose initial SBT failed (vs passed) had higher ICU mortality (29 [17.2%] vs 67 [8.8%]; absolute difference, 8.4% [95% CI, 2.0%-14.7%]), longer duration of ventilation (median of 6.1 vs 3.5 days; absolute difference, 2.6 days [95% CI, 1.6-3.6]), and longer ICU stay (median of 10.6 vs 7.7 days; absolute difference, 2.8 days [95% CI, 1.1-5.2]). Compared with patients who underwent early initial SBTs, patients who underwent late initial SBTs (>2.3 days after intubation) had longer duration of ventilation (median of 2.1 vs 6.1 days; absolute difference, 4.0 days [95% CI, 3.7-4.5]), longer ICU stay (median of 5.9 vs 10.8 days; absolute difference, 4.9 days [95% CI, 4.0-6.3]), and longer hospital stay (median of 14.3 vs 22.8 days; absolute difference, 8.5 days [95% CI, 6.0-11.0]).Conclusions and relevanceIn this observational study of invasive mechanical ventilation discontinuation in 142 ICUs in Canada, India, the UK, Europe, Australia/New Zealand, and the US from 2013 to 2016, weaning practices varied internationally.Trial registrationClinicalTrials.gov Identifier: NCT03955874.
| S-EPMC7988370 | biostudies-literature
Project description: Not available
| S-EPMC7491392 | biostudies-literature
Project description:IntroductionSmoking is highly addictive, and nicotine abstinence is associated with withdrawal syndrome in hospitalized patients. In this study, we aimed to evaluate the impact of sudden nicotine abstinence on the development of agitation and delirium, and on morbidities and outcomes in critically ill patients who required respiratory support, either noninvasive ventilation or intubation, and mechanical ventilation.MethodsWe conducted a prospective, observational study in two intensive care units (ICUs). The 144 consecutive patients admitted to ICUs and requiring mechanical ventilation for >48 hours were included. Smoking status was assessed at ICU admission by using the Fagerström Test of Nicotine Dependence (FTND). Agitation, with the Sedation-Agitation Scale (SAS), and delirium, with the Intensive Care Delirium Screening Checklist (ICDSC), were tested twice daily during the ICU stay. Agitation and delirium were defined by SAS >4 and ICDSC >4, respectively. Nosocomial complications and outcomes were evaluated.ResultsSmokers (n = 44) were younger and more frequently male and were more likely to have a history of alcoholism and to have septic shock as the reason for ICU admission than were nonsmokers. The incidence of agitation, but not delirium, increased significantly in the smoker group (64% versus 32%; P = 0.0005). Nicotine abstinence was associated with higher incidences of self-removal of tubes and catheters, and with more interventions, including the need for supplemental sedatives, analgesics, neuroleptics, and physical restraints. Sedation-free days, ventilator-free days, length of stay, and mortality in ICUs did not differ between groups. Multivariate analysis identified active smoking (OR, 3.13; 95% CI, 1.45-6.74; P = 0.003) as an independent risk factor for agitation. Based on a subgroup of 56 patients, analysis of 28 pairs of patients (smokers and nonsmokers in a 1:1 ratio) matched for age, gender, and alcoholism status found similar results regarding the role of nicotine withdrawal in increasing the risk of agitation during an ICU stay.ConclusionsNicotine withdrawal was associated with agitation and higher morbidities in critically ill patients. These results suggest the need to look specifically at those patients with tobacco dependency by using the FTND in ICU settings. Identifying patients at risk of behavioral disorders may lead to earlier interventions in routine clinical practice.
| S-EPMC2887179 | biostudies-literature
Project description:BackgroundPredicting the successful weaning of acute kidney injury (AKI) patients from renal replacement therapy (RRT) has emerged as a research focus, and we successfully built predictive models for RRT withdrawal in patients with severe AKI by machine learning.MethodsThis retrospective single-center study utilized data from our general intensive care unit (ICU) Database, focusing on patients diagnosed with severe AKI who underwent RRT. We evaluated RRT weaning success based on patients being free of RRT in the subsequent week and their overall survival. Multiple logistic regression (MLR) and machine learning algorithms were adopted to construct the prediction models.ResultsA total of 976 patients were included, with 349 patients successfully weaned off RRT. Longer RRT duration (7.0 vs. 9.6 d, p = 0.002, OR = 0.94), higher serum cystatin C levels (1.2 vs. 3.2 mg/L, p < 0.001, OR = 0.46), and the presence of septic shock (28.1% vs. 41.5%, p < 0.001, OR = 0.63) were associated with reduced likelihood of RRT weaning. Conversely, a positive furosemide stress test (FST) (60.2% vs. 40.7%, p < 0.001, OR = 2.75) and higher total urine volume 3 d before RRT withdrawal (755 vs. 125 mL/d, p < 0.001, OR = 2.12) were associated with an increased likelihood of successful weaning from RRT. Next, we demonstrated that machine learning models, especially Random Forest and XGBoost, achieving an AUROC of 0.95. The XGBoost model exhibited superior accuracy, yielding an AUROC of 0.849.ConclusionHigh-risk factors for unsuccessful RRT weaning in severe AKI patients include prolonged RRT duration. Machine learning prediction models, when compared to models based on multivariate logistic regression using these indicators, offer distinct advantages in predictive accuracy.
| S-EPMC10903749 | biostudies-literature
Project description:BACKGROUND:Critically ill patients are at high risk of iatrogenic withdrawal syndrome (IWS), due to exposure to high doses or prolonged periods of opioids and benzodiazepines. PURPOSE:To examine pharmacological management strategies designed to prevent and/or treat IWS from opioids and/or benzodiazepines in critically ill neonates, children and adults. METHODS:We included non-randomised studies of interventions (NRSI) and randomised controlled trials (RCTs), reporting on interventions to prevent or manage IWS in critically ill neonatal, paediatric and adult patients. Database searching included: PubMed, CINAHL, Embase, Cochrane databases, TRIP, CMA Infobase and NICE evidence. Additional grey literature was examined. Study selection and data extraction were performed in duplicate. Data collected included: population, definition of opioid, benzodiazepine or mixed IWS, its assessment and management (drug or strategy, route of administration, dosage and titration), previous drug exposures and outcomes measures. Methodological quality assessment was performed by two independent reviewers using the Cochrane risk of bias tool for RCTs and the ROBINS-I tool for NRSI. A qualitative synthesis of the results is provided. For the subset of studies evaluating multifaceted protocolised care, we meta-analysed results for 4 outcomes and examined the quality of evidence using GRADE post hoc. RESULTS:Thirteen studies were eligible, including 10 NRSI and 3 RCTs; 11 of these included neonatal and paediatric patients exclusively. Eight studies evaluated multifaceted protocolised interventions, while 5 evaluated individual components of IWS management (e.g. clonidine or methadone at varying dosages, routes of administration and duration of tapering). IWS was measured using an appropriate tool in 6 studies. Ten studies reported upon occurrence of IWS, showing significant reductions (n?=?4) or no differences (n?=?6). Interventions failed to impact duration of mechanical ventilation, ICU length of stay, and adverse effects. Impact on opioid and/or benzodiazepine total doses and duration showed no differences in 4 studies, while 3 showed opioid and benzodiazepine cumulative doses were significantly reduced by 20-35% and 32-66%, and treatment durations by 1.5-11 and 19 days, respectively. Variable effects on intervention drug exposures were found. Weaning durations were reduced by 6-12 days (n?=?4) for opioids and/or methadone and by 13 days (n?=?1) for benzodiazepines. In contrast, two studies using interventions centred on transition to enteral routes or longer tapering durations found significant increases in intervention drug exposures. Interventions had overall non-significant effects on additional drug requirements (except for one study). Included studies were at high risk of bias, relating to selection, detection and reporting bias. CONCLUSION:Interventions for IWS management fail to impact duration of mechanical ventilation or ICU length of stay, while effect on occurrence of IWS and drug exposures is inconsistent. Heterogeneity in the interventions used and methodological issues, including inappropriate and/or subjective identification of IWS and bias due to study design, limited the conclusions.
| S-EPMC7317263 | biostudies-literature
Project description:INTRODUCTION:Multiple studies have shown that diaphragmatic ultrasound can better predict the outcome of weaning in adults. However, there are few studies focusing on children, leading to a lack of sufficient clinical evidence for the application of diaphragmatic ultrasound in children. The purpose of this study was to investigate the predictive value of diaphragm ultrasound for weaning outcomes in critically ill children. METHODS:The study included 50 cases whose mechanical ventilation (MV) time was > 48 h, and all eligibles were divided into either the weaning success group (n = 39) or the weaning failure group (n = 11). Diaphragm thickness, diaphragmatic excursion (DE), and diaphragmatic thickening fraction (DTF) were measured in the zone of apposition. The maximum inspiratory pressure (PImax) was also recorded. RESULTS:The ventilatory treatment time (P = 0.002) and length of PICU stay (P = 0.013) in the weaning failure group was longer than the success group. Cut-off values of diaphragmatic measures associated with successful weaning were ≥ 21% for DTF with a sensitivity of 0.82 and a specificity of 0.81, whereas it was ≥0.86 cm H2O/kg for PImax with a sensitivity of 0.51 and a specificity of 0.82. The linear correlation analysis showed that DTF had a significant positive correlation with PImax in children (P = 0.003). CONCLUSIONS:Diaphragm ultrasound has potential value in predicting the weaning outcome of critically ill children. DTF and PImax presented better performance than other diaphragmatic parameters. However, DE has limited value in predicting weaning outcomes of children with MV. TRIAL REGISTRATION:Current Controlled Trials ChiCTR1800020196, (Dec 2018).
| S-EPMC6937936 | biostudies-literature
Project description:Introduction: Pain impacts brain development for neonates, causing deleterious neurodevelopmental outcomes. Prescription opioids for analgesia or sedation are common; however, prolonged opioid exposure in neonates is associated with neurodevelopmental impairment. Balancing the impact of inadequate pain control against prolonged opioid exposure in neonates is a clinical paradox. Therefore, we sought to decrease the average days of opioids used for analgesia or sedation in critically ill neonates at a level IV Neonatal Intensive Care Unit by 10% within 1 year. Methods: A multidisciplinary quality improvement team used the model for improvement, beginning with a Pareto analysis, and identified a lack of consistent approach to weaning opioids as a primary driver for prolonged exposure. The team utilized 2 main interventions: (1) a standardized withdrawal assessment tool-1 and (2) a risk-stratified opioid weaning guideline. Results: We demonstrated a reduction in mean opioid duration from 34.3 to 14.1 days, an increase in nursing withdrawal assessment tool-1 documentation from 20% to 90%, and an increase in the documented rationale for daily opioid dose in provider notes from 20% to 70%. Benzodiazepine use did not change. Conclusion: Standardized withdrawal assessments combined with risk-stratified weaning guidelines can decrease opioid use in critically ill neonates.
| S-EPMC9197367 | biostudies-literature
Project description:Several single-center studies have evaluated the predictive performance of mechanical power (MP) on weaning outcomes in prolonged invasive mechanical ventilation (IMV) patients. The relationship between MP and weaning outcomes in all IMV patients has rarely been studied. A retrospective study was conducted on MIMIC-IV patients with IMV for more than 24 h to investigate the correlation between MP and weaning outcome using logistic regression model and subgroup analysis. The discriminative ability of MP, MP normalized to dynamic lung compliance (Cdyn-MP) and MP normalized to predicted body weight (PBW-MP) on weaning outcome were evaluated by analyzing the area under the receiver-operating characteristic (AUROC). Following adjustment for confounding factors, compared with the reference group, the Odds Ratio of weaning failure in the maximum MP, Cdyn-MP, and PBW-MP groups increased to 3.33 [95%CI (2.04-4.53), P < 0.001], 3.58 [95%CI (2.27-5.56), P < 0.001] and 5.15 [95%CI (3.58-7.41), P < 0.001], respectively. The discriminative abilities of Cdyn-MP (AUROC 0.760 [95%CI 0.745-0.776]) and PBW-MP (AUROC 0.761 [95%CI 0.744-0.779]) were higher than MP (AUROC 0.745 [95%CI 0.730-0.761]) (P < 0.05). MP is associated with weaning outcomes in IMV patients and is an independent predictor of the risk of weaning failure. Cdyn-MP and PBW-MP showed higher ability in weaning failure prediction than MP.
| S-EPMC9669041 | biostudies-literature