Timing of inspiratory muscle activity detected from airway pressure and flow during pressure support ventilation: the waveform method.

BACKGROUND: Whether respiratory efforts and their timing can be reliably detected during pressure support ventilation using standard ventilator waveforms is unclear. This would give the opportunity to assess and improve patient-ventilator interaction without the need of special equipment. METHODS: In 16 patients under invasive pressure support ventilation, flow and pressure waveforms were obtained from proximal sensors and analyzed by three trained physicians and one resident to assess patient's spontaneous activity. A systematic method (the waveform method) based on explicit rules was adopted. Esophageal pressure tracings were analyzed independently and used as reference. Breaths were classified as assisted or auto-triggered, double-triggered or ineffective. For assisted breaths, trigger delay, early and late cycling (minor asynchronies) were diagnosed. The percentage of breaths with major asynchronies (asynchrony index) and total asynchrony time were computed. RESULTS: Out of 4426 analyzed breaths, 94.1% (70.4-99.4) were assisted, 0.0% (0.0-0.2) auto-triggered and 5.8% (0.4-29.6) ineffective. Asynchrony index was 5.9% (0.6-29.6). Total asynchrony time represented 22.4% (16.3-30.1) of recording time and was mainly due to minor asynchronies. Applying the waveform method resulted in an inter-operator agreement of 0.99 (0.98-0.99); 99.5% of efforts were detected on waveforms and agreement with the reference in detecting major asynchronies was 0.99 (0.98-0.99). Timing of respiratory efforts was accurately detected on waveforms: AUC for trigger delay, cycling delay and early cycling was 0.865 (0.853-0.876), 0.903 (0.892-0.914) and 0.983 (0.970-0.991), respectively. CONCLUSIONS: Ventilator waveforms can be used alone to reliably assess patient's spontaneous activity and patient-ventilator interaction provided that a systematic method is adopted.

Frequency of respiratory virus infections and next-generation analysis of influenza A/H1N1pdm09 dynamics in the lower respiratory tract of patients admitted to the ICU.

Recent molecular diagnostic methods have significantly improved the diagnosis of viral pneumonia in intensive care units (ICUs). It has been observed that 222G/N changes in the HA gene of H1N1pdm09 are associated with increased lower respiratory tract (LRT) replication and worse clinical outcome. In the present study, the frequency of respiratory viruses was assessed in respiratory samples from 88 patients admitted to 16 ICUs during the 2014-2015 winter-spring season in Lombardy. Sixty-nine out of 88 (78.4%) patients were positive for a respiratory viral infection at admission. Of these, 57/69 (82.6%) were positive for influenza A (41 A/H1N1pdm09 and 15 A/H3N2), 8/69 (11.6%) for HRV, 2/69 (2.9%) for RSV and 2/69 (2.9%) for influenza B. Phylogenetic analysis of influenza A/H1N1pdm09 strains from 28/41 ICU-patients and 21 patients with mild respiratory syndrome not requiring hospitalization, showed the clear predominance of subgroup 6B strains. The median influenza A load in LRT samples of ICU patients was higher than that observed in the upper respiratory tract (URT) (p<0.05). Overall, a greater number of H1N1pdm09 virus variants were observed using next generation sequencing on partial HA sequences (codons 180-286) in clinical samples from the LRT as compared to URT. In addition, 222G/N/A mutations were observed in 30% of LRT samples from ICU patients. Finally, intra-host evolution analysis showed the presence of different dynamics of viral population in LRT of patients hospitalized in ICU with a severe influenza infection.

Modified Lung Ultrasound Score for Assessing and Monitoring Pulmonary Aeration.

Purpose Lung Ultrasound Score (LUSS) is a useful tool for lung aeration assessment but presents two theoretical limitations. First, standard LUSS is based on longitudinal scan and detection of number/coalescence of B lines. In the longitudinal scan pleura visualization is limited by intercostal space width. Moreover, coalescence of B lines to define severe loss of aeration is not suitable for non-homogeneous lung pathologies where focal coalescence is possible. We therefore compared longitudinal vs. transversal scan and also cLUSS (standard coalescence-based LUSS) vs. qLUSS (quantitative LUSS based on % of involved pleura). Materials and methods 38 ICU patients were examined in 12 thoracic areas in longitudinal and transversal scan. B lines (number, coalescence), subpleural consolidations (SP), pleural length and pleural involvement (> or ≤ 50 %) were assessed. cLUSS and qLUSS were computed in longitudinal and transversal scan. Results Transversal scan visualized wider (3.9 [IQR 3.8 - 3.9] vs 2.0 [1.6 - 2.5] cm, p < 0.0001) and more constant (variance 0.02 vs 0.34 cm, p < 0.0001) pleural length, more B lines (70 vs 59 % of scans, p < 0.0001), coalescence (39 vs 28 %, p < 0.0001) and SP (22 vs 14 %, p < 0.0001) compared to longitudinal scan. Pleural involvement > 50 % was observed in 17 % and coalescence in 33 % of cases. Focal coalescence accounted for 52 % of cases of coalescence. qLUSS-transv generated a different distribution of aeration scores compared to cLUSS-long (p < 0.0001). Conclusion In unselected ICU patients, variability of pleural length in longitudinal scans is high and focal coalescence is frequent. Transversal scan and quantification of pleural involvement are simple measures to overcome these limitations of LUSS.

Patent foramen ovale diagnosis: The importance of provocative maneuvers.

Patent foramen ovale (PFO) is a frequent congenital anomaly, but massive right-to-left shunt (RTLS) is normally prevented by higher pressures in left heart chambers. However, mechanical ventilation with positive end-expiratory pressure (PEEP) can significantly increase right atrial pressure, accentuating the RTLS, mainly after major cardiothoracic surgery. We report a patient admitted to the intensive care unit after cardiac surgery. Pre- and intraoperative transesophageal echocardiography only described an aneurysmal interatrial septum with no shunt. However, high-PEEP ventilation induced a paradoxical response with life-threatening hypoxemia, triggering further echocardiographic evaluation, revealing massive RTLS across a stretch PFO. Provocative maneuvers (Valsalva/PEEP) significantly increase echocardiographic sensitivity, unmasking silent PFO. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:58-61, 2017.

Whole lung lavage therapy for pulmonary alveolar proteinosis: a global survey of current practices and procedures.

BACKGROUND: Whole lung lavage (WLL) is the current standard of care treatment for patients affected by pulmonary alveolar proteinosis (PAP). However, WLL is not standardized and international consensus documents are lacking. Our aim was to obtain a factual portrayal of WLL as currently practiced with respect to the procedure, indications for its use, evaluation of therapeutic benefit and complication rate. METHODS: A clinical practice survey was conducted globally by means of a questionnaire and included 27 centers performing WLL in pediatric and/or adult PAP patients. RESULTS: We collected completed questionnaires from 20 centres in 14 countries, practicing WLL in adults and 10 centers in 6 countries, practicing WLL in pediatric patients. WLL is almost universally performed under general anesthesia, with a double-lumen endobronchial tube in two consecutive sessions, with an interval of 1-2 weeks between sessions in approximately 50 % of centres. The use of saline warmed to 37 °C, drainage of lung lavage fluid by gravity and indications for WLL therapy in PAP were homogenous across centres. There was great variation in the choice of the first lung to be lavaged: 50 % of centres based the choice on imaging, whereas 50 % always started with the left lung. The choice of position was also widely discordant; the supine position was chosen by 50 % of centres. Other aspects varied significantly among centres including contraindications, methods and timing of follow up, use of chest percussion, timing of extubation following WLL and lung isolation and lavage methods for small children. The amount of fluid used to perform the WLL is a critical aspect. Whilst a general consensus exists on the single aliquot of fluid for lavage (around 800 ml of warm saline, in adults) great variability exists in the total volume instilled per lung, ranging from 5 to 40 liters, with an average of 15.4 liters/lung. CONCLUSIONS: This international survey found that WLL is safe and effective as therapy for PAP. However these results also indicate that standardization of the procedure is required; the present survey represents the a first step toward building such a document.

In vivo calibration of esophageal pressure in the mechanically ventilated patient makes measurements reliable.

BACKGROUND: Esophageal pressure (Pes) can provide information to guide mechanical ventilation in acute respiratory failure. However, both relative changes and absolute values of Pes can be affected by inappropriate filling of the esophageal balloon and by the elastance of the esophagus wall. We evaluated the feasibility and effectiveness of a calibration procedure consisting in optimization of balloon filling and subtraction of the pressure generated by the esophagus wall (Pew). METHODS: An esophageal balloon was progressively filled in 36 patients under controlled mechanical ventilation. VBEST was the filling volume associated with the largest tidal increase of Pes. Esophageal wall elastance was quantified and Pew was computed at each filling volume. Different filling strategies were compared by performing a validation occlusion test. RESULTS: Fifty series of measurements were performed. VBEST was 3.5 ± 1.9 ml (range 0.5-6.0). Esophagus elastance was 1.1 ± 0.5 cmH2O/ml (0.3-3.1). Both Pew and the result of the occlusion test differed among filling strategies. At filling volumes of 0.5, VBEST and 4.0 ml respectively, Pew was 0.0 ± 0.1, 2.0 ± 1.9, and 3.0 ± 1.7 cmH2O (p < 0.0001), whereas the occlusion test was satisfactory in 22%, 98%, and 88% of cases (p < 0.0001). CONCLUSIONS: Under mechanical ventilation, an increase of balloon filling above the conventionally recommended low volumes warrants complete transmission of Pes swings, but is associated with significant elevation of baseline. A simple calibration procedure allows finding the filling volume associated with the best transmission of tidal Pes change and subtracting the associated baseline artifact, thus making measurement of absolute values of Pes reliable.

Lung Ultrasound for Early Diagnosis of Ventilator-Associated Pneumonia.

BACKGROUND: Lung ultrasound (LUS) has been successfully applied for monitoring aeration in ventilator-associated pneumonia (VAP) and to diagnose and monitor community-acquired pneumonia. However, no scientific evidence is yet available on whether LUS reliably improves the diagnosis of VAP. METHODS: In a multicenter prospective study of 99 patients with suspected VAP, we investigated the diagnostic performance of LUS findings of infection, subpleural consolidation, lobar consolidation, and dynamic arborescent/linear air bronchogram. We also evaluated the combination of LUS with direct microbiologic examination of endotracheal aspirates (EA). Scores for LUS findings and EA were analyzed in two ways. First, the clinical-LUS score (ventilator-associated pneumonia lung ultrasound score [VPLUS]) was calculated as follows: ≥ 2 areas with subpleural consolidations, 1 point; ≥ 1 area with dynamic arborescent/linear air bronchogram, 2 points; and purulent EA, 1 point. Second, the VPLUS-direct gram stain examination (EAgram) was scored as follows: ≥ 2 areas with subpleural consolidations, 1 point; ≥ 1 area with dynamic arborescent/linear air bronchogram, 2 points; purulent EA, 1 point; and positive direct gram stain EA examination, 2 points. RESULTS: For the diagnosis of VAP, subpleural consolidation and dynamic arborescent/linear air bronchogram had a positive predictive value of 86% with a positive likelihood ratio of 2.8. Two dynamic linear/arborescent air bronchograms produced a positive predictive value of 94% with a positive likelihood ratio of 7.1. The area under the curve for VPLUS-EAgram and VPLUS were 0.832 and 0.743, respectively. VPLUS-EAgram ≥ 3 had 77% (58-90) specificity and 78% (65-88) sensitivity; VPLUS ≥ 2 had 69% (50-84) specificity and 71% (58-81) sensitivity. CONCLUSIONS: By detecting ultrasound features of infection, LUS was a reliable tool for early VAP diagnosis at the bedside. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02244723; URL: www.clinicaltrials.gov.

Effect of postoperative analgesia on acute and persistent postherniotomy pain: a randomized study.

STUDY OBJECTIVE: The study objective is to identify differences in postoperative pain management according to different analgesic treatments, targeting 2 main pathways involved in pain perception. DESIGN: The design is a randomized, parallel groups, open-label study. SETTING: The setting is in an operating room, postoperative recovery area, and surgical ward. PATIENTS: There are 200 patients undergoing open inguinal hernia repair (IHR) with tension-free technique (mesh repair). INTERVENTIONS: The intervention is a randomization to receive ketorolac (group K) or tramadol (group T) for 3 days after surgery. MEASUREMENTS: The measurements are differences in analgesic efficacy (numeric rating scale [NRS]) in the postoperative (up to 5 days) period, chronic pain incidence (1 and 3 months), side effects, and complications. MAIN RESULTS: We found no differences in analgesic efficacy (NRS value ≥4 in the first 96 hours: 26% in group K vs 32% in group T, P = .43); the proportion of patients with NRS ≥4 was similar in both groups, and the time trajectories were not significantly different (P for interaction = .24). Side effects were higher (12% vs 6%) in the tramadol group, although not significantly (P = .14), with a case of bleeding in the ketorolac group and higher incidence of constipation in tramadol group. One patient in each group developed chronic pain. CONCLUSIONS: Ketorolac or weak opioids are equally effective on acute pain and on persistent postsurgical pain development after IHR, and drug choice should be based on their potential side effects and patient's comorbidities. Further studies are needed to standardize the most rational approach to prevent persistent postsurgical pain after IHR.

A Comparison of Differences Between the Systemic Pharmacokinetics of Levobupivacaine and Ropivacaine During Continuous Epidural Infusion: A Prospective, Randomized, Multicenter, Double-Blind Controlled Trial.

BACKGROUND: Epidural infusion of levobupivacaine and ropivacaine provides adequate postoperative pain management by minimizing side effects related to IV opioids and improving patient outcome. The safety profile of different drugs can be better estimated by comparing their pharmacokinetic profiles than by considering their objective side effects. Because levobupivacaine and ropivacaine have different pharmacokinetic properties, our aim was to investigate whether there is a difference in the pharmacokinetic variability of the 2 drugs in a homogeneous population undergoing continuous epidural infusion. This double-blind, multicenter, randomized, controlled trial study was designed to compare the pharmacokinetics of continuous thoracic epidural infusion of levobupivacaine 0.125% or ropivacaine 0.2% for postoperative pain management in adult patients who had undergone major abdominal, urological, or gynecological surgery. This study is focused on the evaluation of the coefficient of variation (CV) to assess the equivalence in the systemic exposure and interindividual variability between levobupivacaine and ropivacaine and, therefore, the possible differences in the predictability of the plasmatic concentrations of the 2 drugs during thoracic epidural infusion. METHODS: One hundred eighty-one adults undergoing major abdominal surgery were enrolled in the study. Patients were randomized to receive an epidural infusion of levobupivacaine 0.125% + sufentanil 0.75 µg/mL or of ropivacaine 0.2% + sufentanil 0.75 µg/mL at 5 mL/h for 48 hours. The primary end point of this study was to analyze the variability of plasma concentration of levobupivacaine and ropivacaine via an area under the curve within a range of 15% of the CV during 48 hours of continuous epidural infusion. The CV shows how the concentration values of local anesthetics are scattered around the median concentration value, thus indicating the extent to which plasma concentration is predictable during infusion. Secondary end points were to assess the pharmacologic profile of the local anesthetics used in the study, including an analysis of mean peak plasma concentrations, and also to assess plasma clearance, side effects, pain intensity (measured with a verbal numeric ranging score, i.e., static Numeric Rating Scale [NRS] and dynamic NRS]), and the need for rescue doses. RESULTS: The comparison between the 2 CVs showed no statistical difference: the difference between area under the curve was within the range of 15%. The CV was 0.54 for levobupivacaine and 0.51 for ropivacaine (P = 0.725). The plasma concentrations of ropivacaine approached the Cmax significantly faster than those of levobupivacaine. Clearance of ropivacaine decreases with increasing patient age. There were no significant differences in NRS, dynamic NRS scores, the number of rescue doses, or in side effects between groups. CONCLUSIONS: Considering the CV, the interindividual variability of plasma concentration for levobupivacaine and ropivacaine is equivalent after thoracic epidural infusion in adults. We found a reduction in clearance of ropivacaine depending on patient age, but this finding could be the result of some limitations of our study. The steady-state concentration was not reached during the 48-hour infusion and the behavior of plasma concentrations of ropivacaine and levobupivacaine during continuous infusions lasting more than 48 hours remains to be investigated, because they could reach toxic levels. Finally, no differences in the clinical efficacy or in the incidence of adverse effects between groups were found for either local anesthetic.

Usefulness of combined bedside lung ultrasound and echocardiography to assess weaning failure from mechanical ventilation: a suggestive case*.

OBJECTIVE: Recognition of the cardiac origin of weaning failure is a crucial issue for successful discontinuation of mechanical ventilation. Bedside lung ultrasound and echocardiography have shown a potential in predicting weaning failure. Objective of this report was to describe the case of a patient repeatedly failing to wean from mechanical ventilation, where the combined use of lung ultrasound and echocardiography during a spontaneous breathing trial uncovered an unexpected cause of the failure. DESIGN: Case report. SETTING: General ICU of a university teaching hospital. PATIENTS: Single case, abdominal surgery postoperative patient, not predicted to experience a difficult weaning. INTERVENTIONS: Cardiovascular therapy adjustments consistent with lung ultrasound and echocardiography findings acquired during spontaneous breathing trials. MEASUREMENTS AND MAIN RESULTS: All patient's standard hemodynamic and respiratory parameters, datasets from comprehensive lung ultrasound and echocardiographic examinations, and pertinent data from biochemistry exams, were collected during two spontaneous breathing trials. Data from beginning and end of each of the two ultrasound monitored weaning trials, and from the end of the successful weaning trial following therapy and the previously failed one, were analyzed and qualitatively compared. Lung ultrasound performed at the end of the failed spontaneous breathing trial showed a pattern consistent with increased extravascular lung water (diffuse, bilateral, symmetrical, homogeneous sonographic interstitial syndrome). Concurrent echocardiography diagnosed left ventricular diastolic failure. Ultrasound findings at the end of the successful weaning trial showed normalization of the lung pattern and improvement of the echocardiographic one. The patient eventually returned to spontaneous respiration and was discharged from the ICU. CONCLUSIONS: The use of bedside lung ultrasound and echocardiography disclosed left ventricular diastolic dysfunction as unexpected cardiogenic cause of weaning failure and lead to subsequent correct patient management.

Organ allocation waiting time during extracorporeal bridge to lung transplant affects outcomes.

BACKGROUND: The use of extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplant (LTX) is still being debated. METHODS: We performed a retrospective two-center analysis of the relationship between ECMO bridging duration and survival in 25 patients. Further survival analysis was obtained by dividing the patients according to waiting time on ECMO: up to 14 days (Early group) or longer (Late group). We also analyzed the impact of the ventilation strategy during ECMO bridging (ie, spontaneous breathing and noninvasive ventilation [NIV] or intubation and invasive mechanical ventilation [IMV]). RESULTS: Seventeen of 25 patients underwent a transplant (with a 76% 1-year survival), whereas eight patients died during bridging. In the 17 patients who underwent a transplant, mortality was positively related to waiting days until LTX (hazard ratio [HR], 1.12 per day; 95% CI, 1.02-1.23; P = .02), and the Early group showed better Kaplan-Meier curves (P = .02), higher 1-year survival rates (100% vs 50%, P = .03), and lower morbidity (days on IMV and length of stay in ICU and hospital). During the bridge to transplant, mortality increased steadily with time. Considering the overall outcome of the bridging program (25 patients), bridge duration adversely affected survival (HR, 1.06 per day; 95% CI, 1.01-1.11; P = .015) and 1-year survival (Early, 82% vs Late, 29%; P = .015). Morbidity indexes were lower in patients treated with NIV during the bridge. CONCLUSIONS: The duration of the ECMO bridge is a relevant cofactor in the mortality and morbidity of critically ill patients awaiting organ allocation. The NIV strategy was associated with a less complicated clinical course after LTX.

Assessment and management of pulmonary alveolar proteinosis in a reference center.

Pulmonary alveolar proteinosis (PAP) is a term defining an ultra-rare group of disorders characterised by a perturbation in surfactant homeostasis, resulting in its accumulation within airspaces and impaired gas transfer. In this report we provide data from a cohort of PAP patients (n=81) followed for more than two decades at the San Matteo University Hospital of Pavia, Italy. In agreement with other large series in PAP individuals, 90% of the study subjects were affected by autoimmune/idiopathic PAP, while the remaining subjects were divided as follow: congenital 1%, secondary 4% and PAP-like 5%. The disease affected males and females with a ratio of 2:1 and approximately one third of PAP patients were lifelong nonsmokers. Occupational exposure was reported in 35% of subjects in this series. With reference to the PAP clinical course, in 29 patients (7% with spontaneous remission) disease severity did not necessitate whole lung lavage (WLL) in the long-term follow up. On the other hand, 44 PAP patients underwent therapeutic WLL: in 31 subjects a single WLL was sufficient to provide long term, durable benefit, whereas 13 patients required multiple WLLs. The intra-patient mean interval between two consecutive WLLs was 15.7±13.6 months. When baseline data among never lavaged and PAP patients lavaged at least once were compared, the need for lavage was significantly associated with serum biomarkers (CEA, Cyfra, LDH), lung function parameters forced vital capacity (FVC), and lung diffusing capacity (Dlco). We conclude that patient cohorts with an ultra-rare disease, such as PAP, referred to a single reference center, can provide useful information on the natural history and clinical course of the disease.

An optimized set-up for helmet noninvasive ventilation improves pressure support delivery and patient-ventilator interaction.

OBJECTIVE: To test the effects on mechanical performance of helmet noninvasive ventilation (NIV) of an optimized set-up concerning the ventilator settings, the ventilator circuit and the helmet itself. SUBJECTS AND METHODS: In a bench study, helmet NIV was applied to a physical model. Pressurization and depressurization rates and minute ventilation (MV) were measured under 24 conditions including pressure support of 10 or 20 cm H(2)O, positive end expiratory pressure (PEEP) of 5 or 10 cm H(2)O, ventilator circuit with "high", "intermediate" or "low" resistance, and cushion deflated or inflated. In a clinical study pressurization and depressurization rates, MV and patient-ventilator interactions were compared in six patients with acute respiratory failure during conventional versus an "optimized" set-up (PEEP increased to 10 cm H(2)O, low resistance circuit and cushion inflated). RESULTS: In the bench study, all adjustments simultaneously applied (increased PEEP, inflated cushion and low resistance circuit) increased pressurization rate (46.7 ± 2.8 vs. 28.3 ± 0.6 %, p < 0.05), depressurization rate (82.9 ± 1.9 vs. 59.8 ± 1.1 %, p ≤ 0.05) and patient MV (8.5 ± 3.2 vs. 7.4 ± 2.8 l/min, p < 0.05), and decreased leaks (17.4 ± 6.0 vs. 33.6 ± 6.0 %, p < 0.05) compared to the basal set-up. In the clinical study, the optimized set-up increased pressurization rate (51.0 ± 3.5 vs. 30.8 ± 6.9 %, p < 0.002), depressurization rate (48.2 ± 3.3 vs. 34.2 ± 4.6 %, p < 0.0001) and total MV (27.7 ± 7.0 vs. 24.6 ± 6.9 l/min, p < 0.02), and decreased ineffective efforts (3.5 ± 5.4 vs. 20.3 ± 12.4 %, p < 0.0001) and inspiratory delay (243 ± 109 vs. 461 ± 181 ms, p < 0.005). CONCLUSIONS: An optimized set-up for helmet NIV that limits device compliance and ventilator circuit resistance as much as possible is highly effective in improving pressure support delivery and patient-ventilator interaction.