In-line filtration reduces severe complications and length of stay on pediatric intensive care unit: a prospective, randomized, controlled trial.
ABSTRACT: PURPOSE:Particulate contamination due to infusion therapy carries a potential health risk for intensive care patients. METHODS:This single-centre, prospective, randomized controlled trial assessed the effects of filtration of intravenous fluids on the reduction of complications in critically ill children admitted to a pediatric intensive care unit (PICU). A total of 807 subjects were randomly assigned to either a control (n = 406) or filter group (n = 401), with the latter receiving in-line filtration. The primary endpoint was reduction in the rate of overall complications, which included the occurrence of systemic inflammatory response syndrome (SIRS), sepsis, organ failure (circulation, lung, liver, kidney) and thrombosis. Secondary objectives were a reduction in the length of stay on the PICU and overall hospital stay. Duration of mechanical ventilation and mortality were also analyzed. FINDINGS:Analysis demonstrated a significant reduction in the overall complication rate (n = 166 [40.9 %] vs. n = 124 [30.9 %]; P = 0.003) for the filter group. In particular, the incidence of SIRS was significantly lower (n = 123 [30.3 %] vs. n = 90 [22.4 %]; P = 0.01). Moreover the length of stay on PICU (3.89 [95 % confidence interval 2.97-4.82] vs. 2.98 [2.33-3.64]; P = 0.025) and duration of mechanical ventilation (14.0 [5.6-22.4] vs. 11.0 [7.1-14.9] h; P = 0.028) were significantly reduced. CONCLUSION:In-line filtration is able to avert severe complications in critically ill patients. The overall complication rate during the PICU stay among the filter group was significantly reduced. In-line filtration was effective in reducing the occurrence of SIRS. We therefore conclude that in-line filtration improves the safety of intensive care therapy and represents a preventive strategy that results in a significant reduction of the length of stay in the PICU and duration of mechanical ventilation (ClinicalTrials.gov number: NCT00209768).
Project description:Cardiac surgery with cardiopulmonary bypass (CPB) frequently leads to systemic inflammatory response syndrome (SIRS) with concomitant organ malfunction. Infused particles may exacerbate inflammatory syndromes since they activate the coagulation cascade and alter inflammatory response or microvascular perfusion. In a randomized, controlled, prospective trial, we have previously shown that particle-retentive in-line filtration prevented major complications in critically ill children. Now, we investigated the effect of in-line filtration on major complications in the subgroup of cardiac patients. Children admitted to tertiary pediatric intensive care unit were randomized to either control or filter group obtaining in-line filtration throughout complete infusion therapy. Risk differences and 95 % confidence intervals (CI) of several complications such as SIRS, sepsis, mortality, various organ failure and dysfunction were compared between both groups using the Wald method. 305 children (n = 150 control, n = 155 filter group) with cardiac diseases were finally analyzed. The majority was admitted after cardiac surgery with CPB. Risk of SIRS (-11.3 %; 95 % CI -21.8 to -0.5 %), renal (-10.0 %; 95 % CI -17.0 to -3.0 %) and hematologic (-8.1 %; 95 % CI -14.2 to -0.2 %) dysfunction were significantly decreased within the filter group. No risk differences were demonstrated for occurrence of sepsis, any other organ failure or dysfunctions between both groups. Infused particles might aggravate a systemic hypercoagulability and inflammation with subsequent organ malfunction in pediatric cardiac intensive care patients. Particle-retentive in-line filtration might be effective in preventing SIRS and maintaining renal and hematologic function. In-line filtration offers a novel therapeutic option to decrease morbidity in cardiac intensive care.
Project description:BACKGROUND:In critically ill children, in-line microfilters may reduce the incidence of the systemic inflammatory response syndrome (SIRS), the overall complication and organ dysfunction rate. No data on the use of in-line microfilters exist in critically ill adults. METHODS:In this prospective, randomized, controlled open-label study, we evaluated the influence of in-line microfilters on systemic immune activation in 504 critically ill adults with a central venous catheter in place and an expected length of stay in the intensive care unit >24 h. Patients were randomized to have in-line microfilters placed into all intravenous lines (intervention group) or usual care (control group). The primary endpoint was the number of intensive care unit days with SIRS. Secondary endpoints were the incidence of SIRS, SIRS criteria per day, duration of invasive mechanical ventilation, intensive care unit length of stay, the incidence of acute lung injury, maximum C-reactive protein, maximum white blood cell count, incidence of new candida and/or central-line-associated bloodstream infections, incidence of new thromboembolic complications, cumulative insulin requirements and presence of hyper- or hypoglycemia. RESULTS:The study groups did not differ in any baseline variable. There was no difference in the number of days in the intensive care unit with SIRS between microfilter and control patients [2 (0.8-4.7) vs. 1.8 (0.7-4.4), p = 0.62]. Except for a higher incidence of SIRS in microfilter patients (99.6 vs. 96.8 %, p = 0.04), no difference between the groups was observed in any secondary outcome parameter. Results did not change when only patients with an intensive care unit length of stay of greater than 7 days were included in the analysis. The rate of adverse events was comparable between microfilter and control patients. In two patients allocated to the microfilter group, the study intervention was discontinued for technical reasons. Use of in-line microfilters was associated with additional costs. CONCLUSIONS:The use of in-line microfilters failed to modulate systemic inflammation and clinical outcome parameters in critically ill adults. TRIAL REGISTRATION:Clinical Trials NCT01534390.
Project description:Tracheal intubation in PICUs is a common procedure often associated with adverse events. The aim of this study is to evaluate the association between immediate events such as tracheal intubation associated events or desaturation and ICU outcomes: length of stay, duration of mechanical ventilation, and mortality.Prospective cohort study with 35 PICUs using a multicenter tracheal intubation quality improvement database (National Emergency Airway Registry for Children: NEAR4KIDS) from January 2013 to June 2015. Desaturation defined as Spo2 less than 80%.PICUs participating in NEAR4KIDS.All patients less than18 years of age undergoing primary tracheal intubations with ICU outcome data were analyzed.Five thousand five hundred four tracheal intubation encounters with median 108 (interquartile range, 58-229) tracheal intubations per site. At least one tracheal intubation associated event was reported in 892 (16%), with 364 (6.6%) severe tracheal intubation associated events. Infants had a higher frequency of tracheal intubation associated event or desaturation than older patients (48% infants vs 34% for 1-7 yr and 18% for 8-17 yr). In univariate analysis, the occurrence of tracheal intubation associated event or desaturation was associated with a longer mechanical ventilation (5 vs 3 d; p < 0.001) and longer PICU stay (14 vs 11 d; p < 0.001) but not with PICU mortality. The occurrence of severe tracheal intubation associated events was associated with longer mechanical ventilation (5 vs 4 d; p < 0.003), longer PICU stay (15 vs 12 d; p < 0.035), and PICU mortality (19.9% vs 9.6%; p < 0.0001). In multivariable analyses, the occurrence of tracheal intubation associated event or desaturation was significantly associated with longer mechanical ventilation (+12%; 95% CI, 4-21%; p = 0.004), and severe tracheal intubation associated events were independently associated with increased PICU mortality (OR = 1.80; 95% CI, 1.24-2.60; p = 0.002), after adjusted for patient confounders.Adverse tracheal intubation associated events and desaturations are common and associated with longer mechanical ventilation in critically ill children. Severe tracheal intubation associated events are associated with higher ICU mortality. Potential interventions to decrease tracheal intubation associated events and oxygen desaturation, such as tracheal intubation checklist, use of apneic oxygenation, and video laryngoscopy, may need to be considered to improve ICU outcomes.
Project description:Background: Recent attempts to translate Sepsis-3 criteria to children have been restricted to PICU patients and did not target children in emergency departments (ED). We assessed the prognostic accuracy of the age-adjusted quick Sequential Organ Failure Assessment score (qSOFA) and compared the performance to SIRS and the quick Pediatric Logistic Organ Dysfunction-2 score (qPELOD-2). We studied whether the addition of lactate (qSOFA-L) would increase prognostic accuracy. Methods: Non-academic, single-center, retrospective study in children visiting the ED and admitted with suspected bacterial infection between March 2013 and January 2018. We defined suspected bacterial infection as initiation of antibiotic therapy within 24 h after ED entry. Age-adjusted qSOFA, SIRS, qPELOD-2, and qSOFA-L scores were compared by area under the receiver operating characteristics curve (AUROC) analysis. Primary outcome measure was PICU transfer and/or mortality and secondary outcome was prolonged hospital length of stay. Results: We included 864 ED visits [474 (55%) male; median age 2.5 years; IQR 9 months-6 years], of which 18 were transferred to a PICU and 6 ended in death [composite outcome PICU transfer and/or mortality; 23 admissions (2.7%)]. 179 (22.2%) admissions resulted in prolonged hospital length of stay. PICU transfer and/or death was present in 22.5% of visits with qSOFA?2 (n = 40) compared to 2.0% of visits with qSOFA<2 (n = 444) (p < 0.01). qSOFA tends to be the best predictor of PICU transfer and/or mortality (AUROC 0.72 (95% CI, 0.57-0.86) compared to SIRS [0.64 (95% CI, 0.53-0.74), p = 0.23] and qPELOD-2 [0.60 (95% CI, 0.45-0.76), p = 0.03)]. Prolonged hospital length of stay was poorly predicted by qSOFA (AUROC 0.53, 95% CI 0.46-0.59), SIRS (0.49, 95% CI 0.44-0.54), and qPELOD-2 (0.51, 95%CI 0.45-0.57). qSOFA-L resulted in an AUROC of 0.67 (95% CI, 0.50-0.84) for PICU transfer and/or mortality and an AUROC of 0.56 (95% CI, 0.46-0.67) for prolonged hospital length of stay. Conclusion: The currently proposed bedside risk-stratification tool of Sepsis-3 criteria, qSOFA, shows moderate prognostic accuracy for PICU transfer and/or mortality in children visiting the ED with suspected bacterial infection. The addition of lactate did not improve prognostic accuracy. Future prospective studies in larger ED populations are needed to further determine the utility of the qSOFA score.
Project description:Since early antimicrobial therapy is mandatory in septic patients, immediate diagnosis and distinction from non-infectious SIRS is essential but hampered by the similarity of symptoms between both entities. We aimed to develop a diagnostic model for differentiation of sepsis and non-infectious SIRS in critically ill children based on routinely available parameters (baseline characteristics, clinical/laboratory parameters, technical/medical support).This is a secondary analysis of a randomized controlled trial conducted at a German tertiary-care pediatric intensive care unit (PICU). Two hundred thirty-eight cases of non-infectious SIRS and 58 cases of sepsis (as defined by IPSCC criteria) were included. We applied a Random Forest approach to identify the best set of predictors out of 44 variables measured at the day of onset of the disease. The developed diagnostic model was validated in a temporal split-sample approach.A model including four clinical (length of PICU stay until onset of non-infectious SIRS/sepsis, central line, core temperature, number of non-infectious SIRS/sepsis episodes prior to diagnosis) and four laboratory parameters (interleukin-6, platelet count, procalcitonin, CRP) was identified in the training dataset. Validation in the test dataset revealed an AUC of 0.78 (95% CI: 0.70-0.87). Our model was superior to previously proposed biomarkers such as CRP, interleukin-6, procalcitonin or a combination of CRP and procalcitonin (maximum AUC?=?0.63; 95% CI: 0.52-0.74). When aiming at a complete identification of sepsis cases (100%; 95% CI: 87-100%), 28% (95% CI: 20-38%) of non-infectious SIRS cases were assorted correctly.Our approach allows early recognition of sepsis with an accuracy superior to previously described biomarkers, and could potentially reduce antibiotic use by 30% in non-infectious SIRS cases. External validation studies are necessary to confirm the generalizability of our approach across populations and treatment practices.ClinicalTrials.gov number: NCT00209768; registration date: September 21, 2005.
Project description:BACKGROUND:The potential harmful effects of particle-contaminated infusions for critically ill adult patients are yet unclear. So far, only significant improved outcome in critically ill children and new-borns was demonstrated when using in-line filters, but for adult patients, evidence is still missing. METHODS:This single-centre, retrospective controlled cohort study assessed the effect of in-line filtration of intravenous fluids with finer 0.2 or 1.2??m vs 5.0??m filters in critically ill adult patients. From a total of n?=?3215 adult patients, n?=?3012 patients were selected by propensity score matching (adjusting for sex, age, and surgery group) and assigned to either a fine filter cohort (with 0.2/1.2??m filters, n?=?1506, time period from February 2013 to January 2014) or a control filter cohort (with 5.0??m filters, n?=?1506, time period from April 2014 to March 2015). The cohorts were compared regarding the occurrence of severe vasoplegia, organ dysfunctions (lung, kidney, and brain), inflammation, in-hospital complications (myocardial infarction, ischemic stroke, pneumonia, and sepsis), in-hospital mortality, and length of ICU and hospital stay. RESULTS:Comparing fine filter vs control filter cohort, respiratory dysfunction (Horowitz index 206 (119-290) vs 191 (104.75-280); P?=?0.04), pneumonia (11.4% vs 14.4%; P?=?0.02), sepsis (9.6% vs 12.2%; P?=?0.03), interleukin-6 (471.5 (258.8-1062.8) ng/l vs 540.5 (284.5-1147.5) ng/l; P?=?0.01), and length of ICU (1.2 (0.6-4.9) vs 1.7 (0.8-6.9) days; P?<? 0.01) and hospital stay (14.0 (9.2-22.2) vs 14.8 (10.0-26.8) days; P?=?0.01) were reduced. Rate of severe vasoplegia (21.0% vs 19.6%; P?>?0.20) and acute kidney injury (11.8% vs 13.7%; P?=?0.11) was not significantly different between the cohorts. CONCLUSIONS:In-line filtration with finer 0.2 and 1.2??m filters may be associated with less organ dysfunction and less inflammation in critically ill adult patients. TRIAL REGISTRATION:The study was registered at ClinicalTrials.gov (number: NCT02281604).
Project description:Infused particles induce thrombogenesis, impair microcirculation and modulate immune response. We have previously shown in critically ill children, that particle-retentive in-line filtration reduced the overall complication rate of severe events, length of stay and duration of mechanical ventilation. We now evaluated the influence of in-line filtration on different organ function and thereby elucidated the potential underlying pathophysiological effects of particle infusion.In this single-centre, prospective, randomized controlled trial 807 critically ill children were assigned to either control (n = 406) or filter group (n = 401), the latter receiving in-line filtration for complete infusion therapy. Both groups were compared regarding the differences of incidence rates and its 95% confidence interval (CI) of different organ dysfunction as defined by the International Pediatric Sepsis Consensus Conference 2005.The incidence rates of respiratory (-5.06%; 95% CI, -9.52 to -0.59%), renal (-3.87%; 95% CI, -7.58 to -0.15%) and hematologic (-3.89%; 95% CI, -7.26 to -0.51%) dysfunction were decreased in the filter group. No difference was demonstrated for the occurrence rates of cardiovascular, hepatic, or neurologic dysfunction between both groups.In-line filtration has beneficial effects on the preservation of hematologic, renal and respiratory function in critically ill patients. The presented clinical data further support our hypothesis regarding potential harmful effects of particles. In critically ill patients infused particles may lead to further deterioration of the microcirculation, induce a systemic hypercoagulability and inflammation with consecutive negative effects on organ function.ClinicalTrials.gov number; NCT00209768.
Project description:Enteral nutrition has been implicated as a risk factor for ventilator-associated pneumonia. We explored the prevalence of ventilator-associated pneumonia and its association with clinical and nutrition-related therapies in mechanically ventilated children.Prospective, multicenter, cohort study.Fifty-nine PICU in 15 countries.Children less than 18 years old, mechanically ventilated for more than 48 hours.None. Multivariable logistic regression to determine factors associated with ventilator-associated pneumonia.Data are presented as median (interquartile range) or counts (%). We enrolled 1,245 subjects (45% women; 42% surgical), age 20 months (4-84 mo), and duration of mechanical ventilation 7 days (3-13 d). Culture-positive ventilator-associated pneumonia was diagnosed in 80 patients (6.4%); duration of mechanical ventilation for this subgroup was 17 days (8-39 d). Enteral nutrition was delivered in 985 patients (79%), initiated within 48 hours in 592 patients (60%), and via postpyloric route in 354 patients (36%). Acid-suppressive agents were used in 763 patients (61%). The duration of enteral nutrition (p = 0.21), route (gastric vs postpyloric) of delivery (p = 0.94), severity of illness (p = 0.17), and diagnostic category on admission (p = 0.31) were not associated with ventilator-associated pneumonia. After adjusting for enteral nutrition days, illness severity, and site, ventilator-associated pneumonia was significantly associated with mechanical ventilation more than 10 days (odds ratio, 3.7; 95% CI, 2.2-6.5; p < 0.001), PICU length of stay more than 10 days (odds ratio, 1.8; 95% CI, 1.1-3.1; p = 0.029), and the use of acid-suppressive medication (odds ratio, 2.0; 95% CI, 1.2-3.6; p = 0.011).Ventilator-associated pneumonia was diagnosed in 6.5% of mechanically ventilated children in a heterogeneous multicenter cohort. We did not find a link between enteral nutrition duration or route of delivery and ventilator-associated pneumonia. In addition to duration of mechanical ventilation and length of PICU stay, the use of acid-suppressive therapy independently increased the likelihood of developing ventilator-associated pneumonia in this population. This association must be further explored in clinical trials.
Project description:Optimal sedation and analgesia is a challenge in paediatric intensive care units (PICU) because of difficulties in scoring systems and specific metabolism inducing tolerance and withdrawal. Excessive sedation is associated with prolonged mechanical ventilation and hospitalisation. Adult and paediatric data suggest that goal-directed sedation algorithms reduce the duration of mechanical ventilation. We implemented a nurse-driven sedation protocol in a PICU and evaluated its impact.We conducted a before and after protocol implementation study in a population of children aged 0-18 years who required mechanical ventilation for at least 24 h between January 2013 and March 2015. After the protocol implementation in January 2014, nurses managed analgesia and sedation following an algorithm that included the COMFORT behaviour scale (COMFORT-B). Duration of mechanical ventilation was the primary outcome; secondary outcomes were total doses and duration of medications, PICU length of stay, incidence of ventilator-associated pneumonia, and occurrence of withdrawal symptoms. Pre-post analysis followed with segmented regression analysis of interrupted time series was used to assess the effect of protocol.A total of 200 children were analysed, including 107 before implementation and 93 children after implementation of the protocol. After implementation of the protocol, the total number of COMFORT-B scores per day of mechanical ventilation significantly increased from 3.9 ± 2.5 times during the pre-implementation period to 6.6 ± 3.5 times during the post-implementation period (p < 10-3). Mean duration of mechanical ventilation tended to be lower in the post-implementation period (8.3 ± 7.3 vs 6.6 ± 5.6 days, p = 0.094), but changes in either the trend per trimester from pre-implementation to post-implementation (p = 0.933) or the immediate change after implementation (p = 0.923) were not significant with segmented regression analysis. No significant change between pre- and post-implementation was shown for total dose of sedatives, withdrawal symptoms, agitation episodes, or unplanned endotracheal extubations.These results were promising and suggested that implementation of a nurse-driven sedation protocol in a PICU was feasible. Evaluation of sedation and analgesia was better after the protocol implementation; duration of mechanical ventilation and occurrence of withdrawal symptoms tended to be reduced.
Project description:BACKGROUND:Reaching the bedside of a critically ill child within three hours of agreeing the child requires intensive care is a key target for Paediatric Critical Care Transport teams (PCCTs) to achieve in the United Kingdom. Whilst timely access to specialist care is necessary for these children, it is unknown to what extent time taken for the PCCT to arrive at the bedside affects clinical outcome. METHODS:Data from transports of critically ill children who were admitted to Paediatric Intensive Care Units (PICUs) in England and Wales from 1 January 2014 to 31 December 2016 were extracted from the Paediatric Intensive Care Audit Network (PICANet) and linked with adult critical care data and Office for National Statistics mortality data. Logistic regression models, adjusted for pre-specified confounders, were fitted to investigate the impact of time-to-bedside on mortality within 30?days of admission and other key time points. Negative binomial models were used to investigate the impact of time-to-bedside on PICU length of stay and duration of invasive ventilation. RESULTS:There were 9116 children transported during the study period, and 645 (7.1%) died within 30?days of PICU admission. There was no evidence that 30-day mortality changed as time-to-bedside increased. A similar relationship was seen for mortality at other pre-selected time points. In children who waited longer for a team to arrive, there was limited evidence of a small increase in PICU length of stay (expected number of days increased from: 7.17 to 7.58). CONCLUSION:There is no evidence that reducing the time-to-bedside target for PCCTs will improve the survival of critically ill children. A shorter time to bedside may be associated with a small reduction in PICU length of stay.