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Opioid analgesia in mechanically ventilated children: results from the multicenter Measuring Opioid Tolerance Induced by Fentanyl study.

ABSTRACT: To examine the clinical factors associated with increased opioid dose among mechanically ventilated children in the pediatric intensive care unit.Prospective, observational study with 100% accrual of eligible patients.Seven pediatric intensive care units from tertiary-care children's hospitals in the Collaborative Pediatric Critical Care Research Network.Four hundred nineteen children treated with morphine or fentanyl infusions.None.Data on opioid use, concomitant therapy, demographic and explanatory variables were collected. Significant variability occurred in clinical practices, with up to 100-fold differences in baseline opioid doses, average daily or total doses, or peak infusion rates. Opioid exposure for 7 or 14 days required doubling of the daily opioid dose in 16% patients (95% confidence interval 12%-19%) and 20% patients (95% confidence interval 16%-24%), respectively. Among patients receiving opioids for longer than 3 days (n = 225), this occurred in 28% (95% confidence interval 22%-33%) and 35% (95% confidence interval 29%-41%) by 7 or 14 days, respectively. Doubling of the opioid dose was more likely to occur following opioid infusions for 7 days or longer (odds ratio 7.9, 95% confidence interval 4.3-14.3; p < 0.001) or co-therapy with midazolam (odds ratio 5.6, 95% confidence interval 2.4-12.9; p < 0.001), and it was less likely to occur if morphine was used as the primary opioid (vs. fentanyl) (odds ratio 0.48, 95% confidence interval 0.25-0.92; p = 0.03), for patients receiving higher initial doses (odds ratio 0.96, 95% confidence interval 0.95-0.98; p < 0.001), or if patients had prior pediatric intensive care unit admissions (odds ratio 0.37, 95% confidence interval 0.15-0.89; p = 0.03).Mechanically ventilated children require increasing opioid doses, often associated with prolonged opioid exposure or the need for additional sedation. Efforts to reduce prolonged opioid exposure and clinical practice variation may prevent the complications of opioid therapy.

SUBMITTER: Anand KJ

PROVIDER: S-EPMC3581608 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Opioid analgesia in mechanically ventilated children: results from the multicenter Measuring Opioid Tolerance Induced by Fentanyl study.

Anand Kanwaljeet J S KJ Clark Amy E AE Willson Douglas F DF Berger John J Meert Kathleen L KL Zimmerman Jerry J JJ Harrison Rick R Carcillo Joseph A JA Newth Christopher J L CJ Bisping Stephanie S Holubkov Richard R Dean J Michael JM Nicholson Carol E CE

Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies 20130101 1

<h4>Objective</h4>To examine the clinical factors associated with increased opioid dose among mechanically ventilated children in the pediatric intensive care unit.<h4>Design</h4>Prospective, observational study with 100% accrual of eligible patients.<h4>Setting</h4>Seven pediatric intensive care units from tertiary-care children's hospitals in the Collaborative Pediatric Critical Care Research Network.<h4>Patients</h4>Four hundred nineteen children treated with morphine or fentanyl infusions.<h ...[more]

PMID: 23132396

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Project description:The prone position (PP) is increasingly used in mechanically ventilated coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS) patients. However, studies investigating the influence of the PP are currently lacking in these patients. This is the first study to investigate the influence of the PP on the oxygenation and decarboxylation in COVID-19 patients. A prospective bicentric study design was used, and in mechanically ventilated COVID-19 patients, PP was indicated from a partial pressure of oxygen in arterial blood (PaO2)/fraction of inspired oxygen (FIO2) ratio of <200. Patients were left prone for 16 h each. Pressure levels, FIO2, were adjusted to ensure a PaO2 greater than 60 mmHg. Blood gas analyses were performed before (baseline 0.5 h), during (1/2/5.5/9.5/13 h), and after being in the PP (1 h), the circulatory/ventilation parameters were continuously monitored, and lung compliance (LC) was roughly calculated. Responders were defined compared to the baseline value (PaO2/FIO2 ratio increase of ≥15%; partial pressure of carbon dioxide (PaCO2) decrease of ≥2%). 13 patients were included and 36 PP sessions were conducted. Overall, PaO2/FIO2 increased significantly in the PP (p < 0.001). Most PaO2/FIO2 responders (29/36 PP sessions, 77%) were identified 9.5 h after turning prone (14% slow responders), while most PaCO2 responders (15/36 PP sessions, 42%) were identified 13 h after turning prone. A subgroup of patients (interval intubation to PP ≥3 days) showed less PaO2/FIO2 responders (16% vs. 77%). An increase in PaCO2 and minute ventilation in the PP showed a significant negative correlation (p < 0.001). LC (median before the PP = 38 mL/cm H2O; two patients with LC >80 mL/cm H2O) showed a significant positive correlation with the 28 day survival of patients (p = 0.01). The PP significantly improves oxygenation in COVID-19 ARDS patients. The data suggest that they also benefit most from an early PP. A decrease in minute ventilation may result in fewer PaCO2 responders. LC may be a predictive outcome parameter in COVID-19 patients. Retrospectively registered.

Project description:BackgroundRecurrent delivery of tidal mechanical energy (ME) inflicts ventilator-induced lung injury (VILI) when stress and strain exceed the limits of tissue tolerance. Mechanical power (MP) is the mathematical description of the ME delivered to the respiratory system over time. It is unknown how ME relates to underlying lung pathology and outcome in mechanically ventilated children. We therefore tested the hypothesis that ME per breath with tidal volume (Vt) normalized to bodyweight correlates with underlying lung pathology and to study the effect of resistance on the ME dissipated to the lung.MethodsWe analyzed routinely collected demographic, physiological, and laboratory data from deeply sedated and/or paralyzed children < 18 years with and without lung injury. Patients were stratified into respiratory system mechanic subgroups according to the Pediatric Mechanical Ventilation Consensus Conference (PEMVECC) definition. The association between MP, ME, lung pathology, and duration of mechanical ventilation as a primary outcome measure was analyzed adjusting for confounding variables and effect modifiers. The effect of endotracheal tube diameter (ETT) and airway resistance on energy dissipation to the lung was analyzed in a bench model with different lung compliance settings.ResultsData of 312 patients with a median age of 7.8 (1.7-44.2) months was analyzed. Age (p < 0.001), RR p < 0.001), and Vt < 0.001) were independently associated with MPrs. ME but not MP correlated significantly (p < 0.001) better with lung pathology. Competing risk regression analysis adjusting for PRISM III 24 h score and PEMVECC stratification showed that ME on day 1 or day 2 of MV but not MP was independently associated with the duration of mechanical ventilation. About 33% of all energy generated by the ventilator was transferred to the lung and highly dependent on lung compliance and airway resistance but not on endotracheal tube size (ETT) during pressure control (PC) ventilation.ConclusionsME better related to underlying lung pathology and patient outcome than MP. The delivery of generated energy to the lung was not dependent on ETT size during PC ventilation. Further studies are needed to identify injurious MErs thresholds in ventilated children.

Project description:The impact of extrapulmonary organ dysfunction, independent from sepsis and lung injury severity, on outcomes in pediatric acute respiratory failure is unclear. We sought to determine the frequency, timing, and risk factors for extrapulmonary organ dysfunction and the independent association of multiple organ dysfunction syndrome with outcomes in pediatric acute respiratory failure.Secondary observational analysis of the Randomized Evaluation of Sedation Titration for Respiratory Failure cluster-randomized prospective clinical trial conducted between 2009 and 2013.Thirty-one academic PICUs in the United States.Two thousand four hundred forty-nine children mechanically ventilated for acute respiratory failure enrolled in Randomized Evaluation of Sedation Titration for Respiratory Failure.Organ dysfunction was defined using criteria published for pediatric sepsis. Multiple organ dysfunction syndrome was defined as respiratory dysfunction one or more extrapulmonary organ dysfunctions. We used multivariable logistic regression to identify risk factors for multiple organ dysfunction syndrome, and logistic or proportional hazards regression to compare clinical outcomes. All analyses accounted for PICU as a cluster variable. Overall, 73% exhibited extrapulmonary organ dysfunction, including 1,547 (63%) with concurrent multiple organ dysfunction syndrome defined by onset on day 0/1 and 244 (10%) with new multiple organ dysfunction syndrome with onset on day 2 or later. Most patients (93%) with indirect lung injury from sepsis presented with concurrent multiple organ dysfunction syndrome, whereas patients with direct lung injury had both concurrent (56%) and new (12%) multiple organ dysfunction syndrome. Risk factors for concurrent multiple organ dysfunction syndrome included older age, illness severity, sepsis, cancer, and moderate/severe lung injury. Risk factors for new multiple organ dysfunction syndrome were moderate/severe lung injury and neuromuscular blockade. Both concurrent and new multiple organ dysfunction syndrome were associated with 90-day in-hospital mortality (concurrent: adjusted odds ratio, 6.54; 95% CI, 3.00-14.25 and new: adjusted odds ratio, 3.21; 95% CI, 1.48-6.93) after adjusting for sepsis, moderate/severe lung injury, and other baseline characteristics.Extrapulmonary organ dysfunction was common, generally occurred concurrent with respiratory dysfunction (especially in sepsis), and was a major risk factor for mortality in pediatric acute respiratory failure.

Project description:ObjectivesWe sought to study the association between sedation status, medications (benzodiazepines, opioids, and antipsychotics), and clinical outcomes in a resource-limited setting.DesignA longitudinal study of critically ill participants on mechanical ventilation.SettingFive intensive care units (ICUs) in four public hospitals in Lima, Peru.PatientsOne thousand six hundred fifty-seven critically ill participants were assessed daily for sedation status during 28 days and vital status by day 90.ResultsAfter excluding data of participants without a Richmond Agitation Sedation Scale score and without sedation, we followed 1338 (81%) participants longitudinally for 18,645 ICU days. Deep sedation was present in 98% of participants at some point of the study and in 12,942 ICU days. Deep sedation was associated with higher mortality (interquartile odds ratio (OR) = 5.42, 4.23-6.95; p < 0.001) and a significant decrease in ventilator (- 7.27; p < 0.001), ICU (- 4.38; p < 0.001), and hospital (- 7.00; p < 0.001) free days. Agitation was also associated with higher mortality (OR = 39.9, 6.53-243, p < 0.001). The most commonly used sedatives were opioids and benzodiazepines (9259 and 8453 patient days respectively), and the latter were associated with a 41% higher mortality in participants with a higher cumulative dose (75th vs 25th percentile, interquartile OR = 1.41, 1.12-1.77; p < 0.01). The overall cumulative dose of benzodiazepines and opioids was high, 774.5 mg and 16.8 g, respectively, by day 7 and by day 28; these doses approximately doubled. Haloperidol was only used in 3% of ICU days; however, the use of it was associated with a 70% lower mortality (interquartile OR = 0.3, 0.22-0.44, p < 0.001).ConclusionsDeep sedation, agitation, and cumulative dose of benzodiazepines were all independently associated with higher 90-day mortality. Additionally, deep sedation was associated with less ventilator-, ICU-, and hospital-free days. In contrast, haloperidol was associated with lower mortality in our study.

Dataset Information

Opioid analgesia in mechanically ventilated children: results from the multicenter Measuring Opioid Tolerance Induced by Fentanyl study.

Publications

Opioid analgesia in mechanically ventilated children: results from the multicenter Measuring Opioid Tolerance Induced by Fentanyl study.

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