Non-invasive assessment of respiratory muscle activity during pressure support ventilation: accuracy of end-inspiration occlusion and least square fitting methods.

Pressure support ventilation (PSV) should be titrated considering the pressure developed by the respiratory muscles (Pmusc) to prevent under- and over-assistance. The esophageal pressure (Pes) is the clinical gold standard for Pmusc assessment, but its use is limited by alleged invasiveness and complexity. The least square fitting method and the end-inspiratory occlusion method have been proposed as non-invasive alternatives for Pmusc assessment. The aims of this study were: (1) to compare the accuracy of Pmusc estimation using the end-inspiration occlusion (Pmusc,index) and the least square fitting (Pmusc,lsf) against the reference method based on Pes; (2) to test the accuracy of Pmusc,lsf and of Pmusc,index to detect overassistance, defined as Pmusc ≤ 1 cmH2O. We studied 18 patients at three different PSV levels. At each PSV level, Pmusc, Pmusc,lsf, Pmusc,index were calculated on the same breaths. Differences among Pmusc, Pmusc,lsf, Pmusc,index were analyzed with linear mixed effects models. Bias and agreement were assessed by Bland-Altman analysis for repeated measures. The ability of Pmusc,lsf and Pmusc,index to detect overassistance was assessed by the area under the receiver operating characteristics curve. Positive and negative predictive values were calculated using cutoff values that maximized the sum of sensitivity and specificity. At each PSV level, Pmusc,lsf was not different from Pmusc (p = 0.96), whereas Pmusc,index was significantly lower than Pmusc. The bias between Pmusc and Pmusc,lsf was zero, whereas Pmusc,index systematically underestimated Pmusc of 6 cmH2O. The limits of agreement between Pmusc and Pmusc,lsf and between Pmusc and Pmusc,index were ± 12 cmH2O across bias. Both Pmusc,lsf ≤ 4 cmH2O and Pmusc,index ≤ 1 cmH2O had excellent negative predictive value [0.98 (95% CI 0.94-1) and 0.96 (95% CI 0.91-0.99), respectively)] to identify over-assistance. The inspiratory effort during PSV could not be accurately estimated by the least square fitting or end-inspiratory occlusion method because the limits of agreement were far above the signal size. These non-invasive approaches, however, could be used to screen patients at risk for absent or minimal respiratory muscles activation to prevent the ventilator-induced diaphragmatic dysfunction.

Are single-lumen 5Fr and triple-lumen 6Fr PICCs suitable for hemodynamic assessment by trans-pulmonary thermodilution? A pilot study.

BACKGROUND: Single-lumen 4Fr or double-lumen 5Fr power injectable peripherally inserted central catheters (PICCs) are not accurate for trans-pulmonary thermodilution (TPTD), since they overestimate cardiac index and other TPTD-derived parameters when compared with centrally inserted central catheters (CICCs) because of the smaller size of their lumen. We hypothesize that PICCs with larger lumen size may be reliable for the cardiac index assessment using the TPTD. METHODS: This is a single-centre, prospective method-comparison study that included adult patients admitted in ICU who required a calibrated Pulse Contour hemodynamic monitoring system (VolumeView/EV1000™) for circulatory shock and had both PICC and CICC in place. We compared TPTD measurements via single-lumen 5Fr or triple-lumen 6Fr polyurethane power injectable PICCs with triple-lumen 7Fr CICC (reference standard). To rule out biases related to manual injection, measurements were repeated using an automated rapid injection system. We performed Bland-Altman analysis accounting for multiple observations per patient. RESULTS: A total of 320 measurements were performed in 15 patients. During the manual phase, the cardiac index measured with either single-lumen 5Fr or triple-lumen 6Fr PICCs were comparable with cardiac index measured with triple-lumen 7Fr CICC (3.2 ± 1.04 vs. 3.2 ± 1.06 L/min/m2, bias 2.2% and 3.3 ± 0.8 vs. 3.0 ± 0.7 L/min/m2, bias 8.5%, respectively). During the automated phase, triple-lumen 6Fr PICC slightly overestimated the cardiac index when compared to triple-lumen 7Fr CICC (CI 3.4 ± 0.7 vs. 3.0 ± 0.7 L/min/m2, bias 12.5%; p = 0.012). For both single-lumen 5Fr and triple-lumen 6Fr PICCs, percentage error vs. triple-lumen 7Fr CICC was below 20% (14.7% and 19% during the manual phase and 14.4% and 13.8% during the automated phase, respectively). Similar results were observed for TPTD-derived parameters. CONCLUSIONS: During hemodynamic monitoring with TPTD, both single-lumen 5Fr PICCs and triple-lumen 6Fr PICCs can be used for cold fluid bolus injection as an alternative to CICC (ClinicalTrials.gov NCT04241926).

Are Peripherally Inserted Central Catheters Suitable for Cardiac Output Assessment With Transpulmonary Thermodilution?

OBJECTIVES: Peripherally inserted central catheters are increasingly used in ICU as an alternative to centrally inserted central catheters for IV infusion. However, their reliability for hemodynamic measurements with transpulmonary thermodilution is currently unknown. We investigated the agreement between transpulmonary thermodilution measurements obtained with bolus injection through peripherally inserted central catheter and centrally inserted central catheter (reference standard) using a transpulmonary thermodilution-calibrated Pulse Contour hemodynamic monitoring system (VolumeView/EV1000). DESIGN: Prospective method-comparison study. SETTING: Twenty-bed medical-surgical ICU of a teaching hospital. PATIENTS: Twenty adult ICU patients who required hemodynamic monitoring because of hemodynamic instability and had both peripherally inserted central catheter and centrally inserted central catheter in place. INTERVENTION: The hemodynamic measurements obtained by transpulmonary thermodilution after injection of a cold saline bolus via both centrally inserted central catheter and either a single-lumen 4F or a double-lumen 5F peripherally inserted central catheter using were compared. In order to rule out bias related to manual injection, measurements were repeated using an automated rapid injection system. MEASUREMENTS AND MAIN RESULTS: A total of 320 measurements were made. Cardiac index was significantly higher when measured with double-lumen 5F peripherally inserted central catheter than with centrally inserted central catheter (mean, 4.5 vs 3.3 L/min/m; p < 0.0001; bias, 1.24 L/min/m [0.27, 2.22 L/min/m]; bias percentage, 31%). Global end-diastolic index, extravascular lung water index, and stroke volume index were also overestimated (853 ± 240 vs 688 ± 175 mL/m, 12.2 ± 4.2 vs 9.4 ± 2.9 mL/kg, and 49.6 ± 14.9 vs 39.5 ± 9.6 mL/m, respectively; p < 0.0001). Lower, albeit significant differences were found using single-lumen 4F peripherally inserted central catheter (mean cardiac index, 4.2 vs 3.7 L/min/m; p = 0.043; bias, 0.51 L/min/m [-0.53, 1.55 L/min/m]; bias percentage, 12.7%). All differences were confirmed, even after standardization of bolus speed with automated injection. CONCLUSIONS: Bolus injection through peripherally inserted central catheter for transpulmonary thermodilution using EV1000 led to a significant overestimation of cardiac index, global end-diastolic index, extravascular lung water index, and stroke volume index, especially when double-lumen 5F peripherally inserted central catheter was used (ClinicalTrial.gov NCT03834675).

Incidence and outcome of invasive candidiasis in intensive care units (ICUs) in Europe: results of the EUCANDICU project.

BACKGROUND: The objective of this study was to assess the cumulative incidence of invasive candidiasis (IC) in intensive care units (ICUs) in Europe. METHODS: A multinational, multicenter, retrospective study was conducted in 23 ICUs in 9 European countries, representing the first phase of the candidemia/intra-abdominal candidiasis in European ICU project (EUCANDICU). RESULTS: During the study period, 570 episodes of ICU-acquired IC were observed, with a cumulative incidence of 7.07 episodes per 1000 ICU admissions, with important between-center variability. Separated, non-mutually exclusive cumulative incidences of candidemia and IAC were 5.52 and 1.84 episodes per 1000 ICU admissions, respectively. Crude 30-day mortality was 42%. Age (odds ratio [OR] 1.04 per year, 95% CI 1.02-1.06, p < 0.001), severe hepatic failure (OR 3.25, 95% 1.31-8.08, p 0.011), SOFA score at the onset of IC (OR 1.11 per point, 95% CI 1.04-1.17, p 0.001), and septic shock (OR 2.12, 95% CI 1.24-3.63, p 0.006) were associated with increased 30-day mortality in a secondary, exploratory analysis. CONCLUSIONS: The cumulative incidence of IC in 23 European ICUs was 7.07 episodes per 1000 ICU admissions. Future in-depth analyses will allow explaining part of the observed between-center variability, with the ultimate aim of helping to improve local infection control and antifungal stewardship projects and interventions.

Risk factors for mortality and cost implications of complicated intra-abdominal infections in critically ill patients.

PURPOSE: To assess risk factors for 28-day mortality and cost implications in intensive care unit (ICU) patients with complicated intra-abdominal infections (cIAIs). METHODS: Single-center retrospective cohort study of prospectively collected data analysing ICU patients with a microbiologically confirmed complicated intra-abdominal infections. RESULTS: 137 complicated intra-abdominal infections were included and stratified according to the adequacy of antimicrobial therapy (initial inadequate antimicrobial therapy [IIAT], n = 44; initial adequate antimicrobial therapy [IAAT], n = 93). The empirical use of enterococci/methicillin-resistant Staphylococcus aureus active agents and of carbapenems was associated with a higher rate of therapeutic adequacy (p = 0.016 and p = 0.01, respectively) while empirical double gram-negative and antifungal therapy did not. IAAT showed significantly lower mortality at 28 and 90 days and increased clinical cure and microbiological eradication (p < 0.01). In the logistic and Cox-regression models, IIAT and inadequate source control were the unique predictors of 28-day mortality. No costs differences were related to the adequacy of empirical therapy and source control. The empirical double gram-negative and antifungal therapy (p = 0.03, p = 0.04) as well as the isolation of multidrug-resistant (MDR) bacteria and the microbiological failure after targeted therapy were drivers of increased costs (p = 0.004, p = 0.04). CONCLUSIONS: IIAT and inadequate source control are confirmed predictors of mortality in ICU patients with complicated intra-abdominal infections. Empirical antimicrobial strategies and MDR may drive hospital costs.

Ultrasound assessment of rectus femoris and anterior tibialis muscles in young trauma patients.

PURPOSE: Quantitative and qualitative changes of skeletal muscle are typical and early findings in trauma patients, being possibly associated with functional impairment. Early assessment of muscle changes-as evaluated by muscle ultrasonography-could yield important information about patient's outcome. METHODS: In this prospective observational study, we used ultrasonography to evaluate the morphological changes of rectus femoris (RF) and anterior tibialis (AT) muscles in a group of young, previously healthy trauma patients on enteral feeding. RESULTS: We studied 38 severely injured patients (median Injury Severity Score = 34; median age = 40 y.o.) over the course of the ICU stay up to 3 weeks after trauma. We found a progressive loss of muscle mass from day 0 to day 20, that was more relevant for the RF (45%) than for the AT (22%); this was accompanied by an increase in echogenicity (up to 2.5 by the Heckmatt Scale, where normal echogenicity = 1), which is an indicator of myofibers depletion. CONCLUSIONS: Ultrasound evaluation of skeletal muscles is inexpensive, noninvasive, simple and easily repeatable. By this method, we were able to quantify the morphological changes of skeletal muscle in trauma patients. Further studies may rely on this technicque to evaluate the impact of different therapeutic strategies on muscle wasting.

Assessment of the worldwide burden of critical illness: the intensive care over nations (ICON) audit.

BACKGROUND: Global epidemiological data regarding outcomes for patients in intensive care units (ICUs) are scarce, but are important in understanding the worldwide burden of critical illness. We, therefore, did an international audit of ICU patients worldwide and assessed variations between hospitals and countries in terms of ICU mortality. METHODS: 730 participating centres in 84 countries prospectively collected data on all adult (>16 years) patients admitted to their ICU between May 8 and May 18, 2012, except those admitted for fewer than 24 h for routine postoperative monitoring. Participation was voluntary. Data were collected daily for a maximum of 28 days in the ICU and patients were followed up for outcome data until death or hospital discharge. In-hospital death was analysed using multilevel logistic regression with three levels: patient, hospital, and country. FINDINGS: 10,069 patients were included from ICUs in Europe (5445 patients; 54·1%), Asia (1928; 19·2%), the Americas (1723; 17·1%), Oceania (439; 4·4%), the Middle East (393; 3·9%), and Africa (141; 1·4%). Overall, 2973 patients (29·5%) had sepsis on admission or during the ICU stay. ICU mortality rates were 16·2% (95% CI 15·5-16·9) across the whole population and 25·8% (24·2-27·4) in patients with sepsis. Hospital mortality rates were 22·4% (21·6-23·2) in the whole population and 35·3% (33·5-37·1) in patients with sepsis. Using a multilevel analysis, the unconditional model suggested significant between-country variations (var=0·19, p=0·002) and between-hospital variations (var=0·43, p<0·0001) in the individual risk of in-hospital death. There was a stepwise increase in the adjusted risk of in-hospital death according to decrease in global national income. INTERPRETATION: This large database highlights that sepsis remains a major health problem worldwide, associated with high mortality rates in all countries. Our findings also show a significant association between the risk of death and the global national income and suggest that ICU organisation has an important effect on risk of death. FUNDING: None.

Validation of a new HPLC-UV method for determination of the antibiotic linezolid in human plasma and in bronchoalveolar lavage.

A rapid and selective HPLC-UV method was developed for the quantification of linezolid (LNZ) in human plasma and bronchoalveolar lavage (BAL) at the concentrations associated with therapy. Plasma samples were extracted by solid-phase extraction followed by evaporation to dryness and reconstitution in mobile phase solution. The chromatographic separation was carried out on a C18 column with an isocratic mobile phase consisting of dihydrogen phosphate buffer 50 mm (pH 3.5) and acetonitrile (60:40 v/v). The detection was performed using a photodiode array. Under these conditions, a single chromatographic run could be completed within 12 min. The method was validated by estimating the precision and the accuracy for inter- and intra-day analysis in the concentration range of 25-25600 ng/mL. The method was linear over the investigated range with all the correlation coefficients R > 0.999. The intra- and inter-day precision was within 8.90% and the accuracy ranged from -4.76 to +5.20%. This rapid and sensitive method was fully validated and could be applied to pharmacokinetic study for the determination of LNZ levels in human plasma and BAL samples.

Cost-effectiveness analysis of polymyxin-B immobilized fiber column and conventional medical therapy in the management of abdominal septic shock in Italy.

INTRODUCTION: Severe abdominal sepsis and septic shock are common problems in intensive care units (ICUs), and carry high mortality. The purpose of this economic analysis was to determine the cost-effectiveness of polymyxin B immobilized fiber column (PMX-F) plus conventional therapy (CT) (PMX-F-CT) versus CT alone for patients with severe sepsis/septic shock of abdominal origin, in the perspective of the Italian hospital. METHODS: This was a retrospective cost-effectiveness analysis (CEA) based on data of clinical efficacy and consumption of resources collected alongside an Italian randomized clinical trial. 64 patients were enrolled following emergency surgery for intra-abdominal infection in 10 tertiary care ICUs from December 2004 to December 2007. Direct medical costs analyzed in the study included the consumption of hospital days, ICU days, catecholamine treatment days, renal replacement therapy days, mechanical ventilation treatment days, and the use of the PMX-F device. Resources were valued using published 2010 tariffs and market values. All-cause hospital mortality was extrapolated to survival as expected life years (LY) per patient/arm: for each survivor, average age-gender-related years of life expectancy were retrieved from national life tables; for deceased patients, only the number of CRF reported survival days was retained. Baseline expected years of survival were weighed by the severity of sepsis, according to individual Acute Physiology and Chronic Health Evaluation (Apache) II scores, showing that age/disease severity were comparable in the two groups before treatment initiation. Life expectancy per patient in each treatment group was thus calculated as the combination of life expectancy from Italian National Statistics Institute life tables and intra-hospital mortality detected in the Early Use of Polymyxin B Hemoperfusion in Abdominal Septic Shock (EUPHAS) study. After all costs and 3% discounted survival years were calculated per patient per treatment arm, the incremental CEA was run to obtain the incremental cost-effectiveness ratio (ICER). Univariate sensitivity analyses and 2,000 bootstrap replications were run to test the robustness of the study results. RESULTS: Based on the expected survival years (mean discounted PMX-F-CT 9.37 LY/patient, CT 4.92 LY/patient; difference for PMX-F-CT 4.45 LY/patient; mean undiscounted PMX-F-CT 13.92 LY/patient, CT 7.19 LY/patient; difference +6.73 LY/patient), and the expected mean cost (PMX-F-CT mean 59,922 EUR/patient, CT mean 42,712 EUR/patient; difference for PMX-F-CT 17,211 EUR/patient), the mean ICER for PMX- F-CT resulted in 3,864 EUR/life year gained (LYG; ICER 2,558/undiscounted LYG). Results of the base-case CEA were confirmed by all sensitivity analyses, with ICER values always well below commonly accepted value thresholds. CONCLUSION: PMX-F-CT versus CT is a cost-effective intervention for treatment of severe sepsis/septic shock of abdominal origin and could be considered for use in the Italian National Health System hospital setting.