Nebulized antibiotics in mechanically ventilated patients: a challenge for translational research from technology to clinical care.
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ABSTRACT:
SUBMITTER: Ehrmann S
PROVIDER: S-EPMC5539056 | biostudies-other | 2017 Dec
REPOSITORIES: biostudies-other
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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.
| S-EPMC7539278 | biostudies-literature
Project description:Knowledge of clinical demographics and outcomes of mechanically ventilated patients is important but there are few prospectively collected data in Korea. The objective of the present study was to describe the current status of mechanically ventilated patients in Korea as of 2010. We analyzed the data of Korean patients (275 patients in 12 Korean intensive care units [ICU]) participating in a multinational prospective cohort study on mechanical ventilation. The most common indication for mechanical ventilation was pneumonia (23%). Pressure-limited ventilation modes were preferred over volume-cycled ventilation modes. Non-invasive positive pressure ventilation was used in only seven (2%) patients as the initial ventilatory support. Median duration of mechanical ventilation was 7 days and ICU mortality was 36%. The multiple logistic regression model revealed that the Simplified Acute Physiology Score II (SAPS II) score at ICU admission (odds ratio [OR], 1.034; 95% confidence interval [CI], 1.001-1.036; P=0.033), peak pressure (OR, 1.054; 95% CI, 1.016-1.095; P=0.006), and the number of failed organs (OR, 2.132; 95% CI, 1.634-2.781; P<0.001) were independently associated with ICU mortality. This study provides a snapshot of current practice of mechanical ventilation in Korea.
| S-EPMC4055823 | biostudies-literature
Project description:Regionalization has been proposed as a method to improve outcomes for medical patients receiving mechanical ventilation in the intensive care unit.To determine the number of patients who would be affected by regionalization and the potential mortality reduction under a regionalized system of care.We performed a retrospective cohort study with Monte Carlo simulation, using 2001 state discharge data from eight states representing 42% of the U.S. population. Adult medical patients undergoing invasive mechanical ventilation were identified. Patient location and hospital mortality rates were obtained from the discharge data; estimates of the relative risk reduction in hospital mortality for high-volume hospitals compared with low-volume hospitals were obtained from the published literature and applied to the cohort.Of 180,976 adult medical patients who underwent mechanical ventilation at 1,170 nonfederal hospitals, 83,050 (46%) received mechanical ventilation at 887 (76%) hospitals with low annual volumes (fewer than 275 patients per year). Using published risk estimates, approximately 4,720 lives per year (95% range, 2,522-6,744) could potentially be saved in the 8 states by routinely transferring patients from low- to high-volume hospitals, representing a number needed to treat of 15.7. The median distance that patients would need to travel to reach a high-volume hospital was 8.5 miles (interquartile range, 4.0-21.2 mi).Regionalization of intensive care could potentially improve survival for patients undergoing mechanical ventilation. Transfer distances are modest for most patients.
| S-EPMC2218846 | biostudies-other
Project description:Background Mechanically ventilated patients with coronavirus disease 2019 (COVID-19) have a mortality of 24-53%, in part due to distal mucopurulent secretions interfering with ventilation. Dornase alfa is recombinant human DNase 1 and digests DNA in mucoid sputum. Nebulized dornase alfa is FDA-approved for cystic fibrosis treatment. DNA from neutrophil extracellular traps (NETs) contributes to the viscosity of mucopurulent secretions. NETs are found in the serum of patients with severe COVID-19, and targeting NETs reduces mortality in animal models of acute respiratory distress syndrome (ARDS). Thus, dornase alfa may be beneficial to patients with severe COVID-19, acting as a mucolytic and targeting NETs. However, delivery of nebulized drugs can aerosolize SARS-CoV-2, which causes COVID-19, increasing the infection risk for staff. Here, we report a single center case series where dornase alfa was administered through an in-line nebulizer system to minimize risk of virus aerosolization. Methods Demographic, clinical data, and outcomes were collected from the electronic medical records of five mechanically ventilated patients with COVID-19, including three requiring veno-venous extracorporeal membrane oxygenation (VV-ECMO), treated with nebulized in-line endotracheal dornase alfa co-administered with albuterol (used to increase delivery to the alveoli), between March 31 and April 24, 2020. Data on tolerability and responses, including longitudinal values capturing respiratory function and inflammatory status, were analyzed. Results Following nebulized in-line administration of dornase alfa with albuterol, the fraction of inspired oxygen requirements was reduced for all five patients. All patients remain alive and two patients have been discharged from the intensive care unit. No drug associated toxicities were identified. Conclusions The results presented in this case series suggest that dornase alfa will be well-tolerated by critically ill patients with COVID-19. Clinical trials are required to formally test the dosing, safety, and efficacy of dornase alfa in COVID-19, and two have recently been registered ( NCT04359654 and NCT04355364 ). With this case series, we hope to contribute to the development of management approaches for critically ill patients with COVID-19.
| S-EPMC7273282 | biostudies-literature
Project description:BackgroundMechanically ventilated patients with COVID-19 have a mortality of 24-53%, in part due to distal mucopurulent secretions interfering with ventilation. DNA from neutrophil extracellular traps (NETs) contribute to the viscosity of mucopurulent secretions and NETs are found in the serum of COVID-19 patients. Dornase alfa is recombinant human DNase 1 and is used to digest DNA in mucoid sputum. Here, we report a single-center case series where dornase alfa was co-administered with albuterol through an in-line nebulizer system.MethodsDemographic and clinical data were collected from the electronic medical records of five mechanically ventilated patients with COVID-19-including three requiring veno-venous extracorporeal membrane oxygenation-treated with nebulized in-line endotracheal dornase alfa and albuterol, between March 31 and April 24, 2020. Data on tolerability and response were analyzed.ResultsThe fraction of inspired oxygen requirements was reduced for all five patients after initiating dornase alfa administration. All patients were successfully extubated, discharged from hospital and remain alive. No drug-associated toxicities were identified.ConclusionsResults suggest that dornase alfa will be well-tolerated by patients with severe COVID-19. Clinical trials are required to formally test the dosing, safety, and efficacy of dornase alfa in COVID-19, and several have been recently registered.
| S-EPMC7522910 | biostudies-literature
Project description:ObjectivesThe aims of this study were, first, to compare the predicted (calculated) energy requirements based on standard equations with target energy requirement based on indirect calorimetry (IC) in critically ill, obese mechanically ventilated patients; and second, to compare actual energy intake to target energy requirements.MethodsWe conducted a prospective cohort study of mechanically ventilated critically ill patients with body mass index ≥30.0 kg/m2 for whom enteral feeding was planned. Clinical and demographic data were prospectively collected. Resting energy expenditure was measured by open-circuit IC. American Society of Parenteral and Enteral Nutrition (APSPEN)/Society of Critical Care Medicine (SCCM) 2016 equations were used to determine predicted (calculated) energy requirements. Target energy requirements were set at 65% to 70% of measured resting energy expenditure as recommended by ASPEN/SCCM. Nitrogen balance was determined via simultaneous measurement of 24-h urinary nitrogen concentration and protein intake.ResultsTwenty-five patients (mean age: 64.5 ± 11.8 y, mean body mass index: 35.2 ± 3.6 kg/m2) underwent IC. The mean predicted energy requirement was 1227 kcal/d compared with mean measured target energy requirement of 1691 kcal/d. Predicted (calculated) energy requirements derived from ASPEN/SCCM equations were less than the target energy requirements in most cases. Actual energy intake from enteral nutrition met 57% of target energy requirements. Protein intake met 25% of target protein requirement and the mean nitrogen balance was -2.3 ± 5.1 g/d.ConclusionsPredictive equations underestimated target energy needs in this population. Further, we found that feeding to goal was often delayed resulting in failure to meet both protein and energy intake goals.
| S-EPMC6702036 | biostudies-literature
Project description:Standardized clinical measurements of edema do not exist.ObjectivesTo describe a 19-point clinical edema score (CES), investigate its interobserver agreement, and compare changes between such CES and body weight.Design setting and participantsProspective observational study in a tertiary PICU of mechanically ventilated children with congenital heart disease.Main outcomes and measuresDifferences in the median CES between observer groups.ResultsWe studied 61 children, with a median age of 8.0 days (interquartile range, 1.0-14.0 d). A total of 539 CES were performed by three observer groups (medical 1 [reference], medical 2, and bedside nurse) at 0, 24, and 48 hours from enrollment. Overall, there was close agreement between observer groups in mean, median, and upper quartile of CES scores, with least agreement observed in the lower quartile of scores. Across all quartiles of CES, after adjusting for baseline weight, cardiac surgical risk, duration of cardiopulmonary bypass, or peritoneal dialysis during the study, observer groups returned similar mean scores (medical 2: 25th centile +0.1 [95% CI, -0.2 to 0.5], median +0.6 [95% CI, -0.4 to 1.5], 75th centile +0.1 [95% CI, -1.1 to 1.4] and nurse: 25th centile +0.5 [95% CI, 0.0-0.9], median +0.7 [95% CI, 0.0-1.5], 75th centile -0.2 [95% CI, -1.3 to 1.0]) Within a multivariable mixed-effects linear regression model, including adjustment for baseline CES, each 1 point increase in CES was associated with a 12.1 grams (95% CI, 3.2-21 grams) increase in body weight.Conclusions and relevanceIn mechanically ventilated children with congenital heart disease, three groups of observers tended to agree when assessing overall edema using an ordinal clinical score assessed in six body regions, with agreement least at low edema scores. An increase in CES was associated with an increase in body weight, suggesting some validity for quantifying edema. Further exploration of the CES as a rapid clinical tool is indicated.
| S-EPMC10456982 | biostudies-literature
Project description:Protocolized sedation improves clinical outcomes in critically ill adults, but its effect in children is unknown.To determine whether critically ill children managed with a nurse-implemented, goal-directed sedation protocol experience fewer days of mechanical ventilation than patients receiving usual care.Cluster randomized trial conducted in 31 US pediatric intensive care units (PICUs). A total of 2449 children (mean age, 4.7 years; range, 2 weeks to 17 years) mechanically ventilated for acute respiratory failure were enrolled in 2009-2013 and followed up until 72 hours after opioids were discontinued, 28 days, or hospital discharge.Intervention PICUs (17 sites; n = 1225 patients) used a protocol that included targeted sedation, arousal assessments, extubation readiness testing, sedation adjustment every 8 hours, and sedation weaning. Control PICUs (14 sites; n = 1224 patients) managed sedation per usual care.The primary outcome was duration of mechanical ventilation. Secondary outcomes included time to recovery from acute respiratory failure, duration of weaning from mechanical ventilation, neurological testing, PICU and hospital lengths of stay, in-hospital mortality, sedation-related adverse events, measures of sedative exposure (wakefulness, pain, and agitation), and occurrence of iatrogenic withdrawal.Duration of mechanical ventilation was not different between the 2 groups (intervention: median, 6.5 [IQR, 4.1-11.2] days; control: median, 6.5 [IQR, 3.7-12.1] days). Sedation-related adverse events including inadequate pain and sedation management, clinically significant iatrogenic withdrawal, and unplanned endotracheal tube/invasive line removal were not significantly different between the 2 groups. Intervention patients experienced more postextubation stridor (7% vs 4%; P =?.03) and fewer stage 2 or worse immobility-related pressure ulcers (<1% vs 2%; P =?.001). In exploratory analyses, intervention patients had fewer days of opioid administration (median, 9 [IQR, 5-15] days vs 10 [IQR, 4-21] days; P =?.01), were exposed to fewer sedative classes (median, 2 [IQR, 2-3] classes vs 3 [IQR, 2-4] classes; P <?.001), and were more often awake and calm while intubated (median, 86% [IQR, 67%-100%] of days vs 75% [IQR, 50%-100%] of days; P =?.004) than control patients, respectively; however, intervention patients had more days with any report of a pain score ? 4 (median, 50% [IQR, 27%-67%] of days vs 23% [IQR, 0%-46%] of days; P <?.001) and any report of agitation (median, 60% [IQR, 33%-80%] vs 40% [IQR, 13%-67%]; P =?.003), respectively.Among children undergoing mechanical ventilation for acute respiratory failure, the use of a sedation protocol compared with usual care did not reduce the duration of mechanical ventilation. Exploratory analyses of secondary outcomes suggest a complex relationship among wakefulness, pain, and agitation.clinicaltrials.gov Identifier: NCT00814099.
| S-EPMC4955566 | biostudies-literature
Project description:BackgroundIn recent years, the number of elderly patients receiving mechanical ventilation (MV) in intensive care units (ICUs) has increased. However, the evidence on the outcomes of elderly mechanically ventilated patients is scant in China. Our objective was to evaluate the characteristics and outcomes in elderly patients (≥65 years) receiving MV in the ICU.MethodsWe performed a multicentre retrospective study involving adult patients who were admitted to the ICU and received at least 24 hours of MV. Patients were divided into three age groups: under 65, 65-79, and ≥80 years. The primary outcome was hospital mortality. We performed univariate and multivariate logistic regression analysis to identify factors associated with hospital mortality.ResultsA total of 853 patients were analysed. Of those, 61.5% were ≥65 years of age, and 26.0% were ≥80 years of age. There were significant differences in the principal reason for MV among the three age groups (P<0.001). Advanced age was significantly associated with total duration of MV, ICU length of stay (LOS), and ICU costs (all P<0.001), but not with hospital LOS and hospital costs (P>0.05). In addition, mortality rates in the ICU, hospital, and at 60 days significantly increased with age (all P<0.001). In the age group of 80 years and older, the mortality rates were 47.7%, 49.5%, and 50.0%, respectively. Multivariate logistic regression analysis had found that age, Acute Physiology and Chronic Health Evaluation (APACHE) II score, partial pressure of oxygen in arterial blood/fraction of inspired oxygen (PaO2/FiO2) ratio, total duration of MV, ICU LOS, and the decision to withhold/withdraw life-sustaining treatments were independent influence factors for mortality rates.ConclusionsMechanically ventilated elderly patients (≥65 years) have a higher ICU and hospital mortality, but the hospital LOS and hospital costs are similar to younger patients. Advanced age should be considered as a significant independent risk factor for hospital mortality of mechanically ventilated ICU patients.
| S-EPMC8107518 | biostudies-literature
Project description:ObjectiveTo assess the impact of different vertical positions on lung aeration in patients receiving invasive mechanical ventilation.MethodsAn open-label randomized crossover clinical trial was conducted between January and July 2020. Adults receiving invasive mechanical ventilation for > 24 hours and < 7 days with hemodynamic, respiratory and neurological stability were randomly assigned at a 1:1 ratio to the sitting position followed by passive orthostasis condition or the passive orthostasis followed by the sitting position condition. The primary outcome was lung aeration assessed using the lung ultrasound score (score ranges from 0 [better] to 36 [worse]).ResultsA total of 186 subjects were screened; of these subjects, 19 were enrolled (57.8% male; mean age, 73.2 years). All participants were assigned to receive at least one verticalization protocol. Passive orthostasis resulted in mean lung ultrasound scores that did not differ significantly from the sitting position (11.0 versus 13.7; mean difference, -2.7; [95%CI -6.1 to 0.71; p = 0.11). Adverse events occurred in three subjects in the passive orthostasis group and in one in the sitting position group (p = 0.99).ConclusionThis analysis did not find significant differences in lung aeration between the sitting and passive orthostasis groups. A randomized crossover clinical trial assessing the impact of vertical positioning on lung aeration in patients receiving invasive mechanical ventilation is feasible. Unfortunately, the study was interrupted due to the need to treat COVID-19 patients.ClinicalTrials.gov registry: NCT04176445.
| S-EPMC10802776 | biostudies-literature