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.

Carbon Dioxide Elimination During Veno-Venous Extracorporeal Membrane Oxygenation Weaning: A Pilot Study.

Veno-venous extracorporeal membrane oxygenation (V-V ECMO) represents a component of the treatment strategy for severe respiratory failure. Clinical evidence on the management of the lung during V-V ECMO are limited just as the consensus regarding timing of weaning. The monitoring of the carbon dioxide (CO2) removal (V'CO2TOT) is subdivided into two components: the membrane lung (ML) and the native lung (NL) are both taken into consideration to evaluate the improvement of the function of the lung and to predict the time to wean off ECMO. We enrolled patients with acute respiratory distress syndrome (ARDS). The V'CO2NL ratio (V'CO2NL/V'CO2TOT) value was calculated based on the distribution of CO2 between the NL and the ML. Of 18 patients, 15 were successfully weaned off of V-V ECMO. In this subgroup, we observed a significant increase in the V'CO2NL ratio comparing the median values of the first and last quartiles (0.32 vs. 0.53, p = 0.0045), without observing any modifications in the ventilation parameters. An increase in the V'CO2NL ratio, independently from any change in ventilation could, despite the limitations of the study, indicate an improvement in pulmonary function and may be used as a weaning index for ECMO.

Brief Report: A Case of Tramadol Overdose: Extracorporeal Life Support and Hemoperfusion as Life-Saving Treatment.

We describe the case of a 49-year-old woman with a Tramadol intoxication associated with multiorgan failure. Veno-arterial femoro-femoral extracorporeal life support (VA-ECLS) and hemoperfusion (HP) were used as rescue treatments. The emergency medical service found a woman at home unconscious. Once in the hospital, she was intubated and catecholamines support was immediately started for a severe shock. Brain CT was normal, whereas EEG revealed a metabolic encephalopathy pattern. Toxic levels of Tramadol and Quetiapine were detected. VA-ECLS was implanted due to persistent multiorgan failure, and HP with a charcoal cartridge was set to increase the Tramadol clearance. To quantify the charcoal cartridge's removal efficiency of Tramadol, Tramadol concentration was measured before and after the cartridge and before and after the treatment in the patient's blood. The charcoal cartridge showed good extraction ratio during the treatment and no significant rebound effect. VA-ECLS and HP allowed the patient to be weaned from vasoconstrictors and the resolution of the organ failures. These treatments might be lifesaving in the Tramadol intoxication.

EA-DIVA score (Enhanced Adult DIVA score): A new scale to predict difficult preoperative venous cannulation in adult surgical patients.

INTRODUCTION: Providing peripheral intravenous access is one of the most commonly performed technical procedures in hospitals and it is mandatory for all patients undergoing surgery. Obtaining peripheral intravenous access may be difficult and this may cause delays in patient management, increased risk of adverse events and hospitalization costs. The aim of this study is to develop and validate a scale to identify patients at risk of peripheral difficult intravenous access, applicable to any adult patient undergoing surgery. METHODS: A monocentric, observational study was conducted on adult surgical patients between September 2015 and April 2016. The primary outcome was the identification of parameters that could detect peripheral difficult intravenous access. Several parameters were taken into consideration, including patient details, healthcare professionals, and setting. The sample data were randomly divided into two subsets: a multivariate analysis was performed on the first one to define the Enhanced Adult DIVA score; the second subset was used for its validation. RESULTS: We included 1006 patients (607 in the derivation, 399 in the validation cohorts respectively). The peripheral intravenous access was difficult in 127 patients (12.6%). The EA-DIVA score was devised with a score ranging from 0 to 12. The receiver operating characteristic (ROC) curve area under the curve (AUC) in the validation subset was 0.94. The validation study suggested a cut-off score of 8, which maximizes sensitivity (85.5%) and specificity (89.2%) in detecting difficult peripheral intravenous access, with a positive predictive value of 56% and a negative predictive value of 97.5%. DISCUSSION: The EA-DIVA score is a simple tool to identify patients at high risk of peripheral difficult intravenous access. Its implementation is recommended in order to optimize peripheral intravenous access procedures.

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.

Results of a prospective study (CATS) on the effects of thalamic stimulation in minimally conscious and vegetative state patients.

OBJECTIVE Deep brain stimulation of the thalamus was introduced more than 40 years ago with the objective of improving the performance and attention of patients in a vegetative or minimally conscious state. Here, the authors report the results of the Cortical Activation by Thalamic Stimulation (CATS) study, a prospective multiinstitutional study on the effects of bilateral chronic stimulation of the anterior intralaminar thalamic nuclei and adjacent paralaminar regions in patients affected by a disorder of consciousness. METHODS The authors evaluated the clinical and radiological data of 29 patients in a vegetative state (unresponsive wakefulness syndrome) and 11 in a minimally conscious state that lasted for more than 6 months. Of these patients, 5 were selected for bilateral stereotactic implantation of deep brain stimulating electrodes into their thalamus. A definitive consensus for surgery was obtained for 3 of the selected patients. All 3 patients (2 in a vegetative state and 1 in a minimally conscious state) underwent implantation of bilateral thalamic electrodes and submitted to chronic stimulation for a minimum of 18 months and a maximum of 48 months. RESULTS In each case, there was an increase in desynchronization and the power spectrum of electroencephalograms, and improvement in the Coma Recovery Scale-Revised scores was found. Furthermore, the severity of limb spasticity and the number and severity of pathological movements were reduced. However, none of these patients returned to a fully conscious state. CONCLUSIONS Despite the limited number of patients studied, the authors confirmed that bilateral thalamic stimulation can improve the clinical status of patients affected by a disorder of consciousness, even though this stimulation did not induce persistent, clinically evident conscious behavior in the patients. Clinical trial registration no.: NCT01027572 ( ClinicalTrials.gov ).

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.

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.

Pharmacokinetics of colistin in cerebrospinal fluid after intraventricular administration of colistin methanesulfonate.

Intraventricular colistin, administered as colistin methanesulfonate (CMS), is the last resource for the treatment of central nervous system infections caused by panresistant Gram-negative bacteria. The doses and daily regimens vary considerably and are empirically chosen; the cerebrospinal fluid (CSF) pharmacokinetics of colistin after intraventricular administration of CMS has never been characterized. Nine patients (aged 18 to 73 years) were treated with intraventricular CMS (daily doses of 2.61 to 10.44 mg). Colistin concentrations were measured using a selective high-performance liquid chromatography (HPLC) assay. The population pharmacokinetics analysis was performed with the P-Pharm program. The pharmacokinetics of colistin could be best described by the one-compartment model. The estimated values (means ± standard deviations) of apparent CSF total clearance (CL/Fm, where Fm is the unknown fraction of CMS converted to colistin) and terminal half-life (t(1/2λ)) were 0.033 ± 0.014 liter/h and 7.8 ± 3.2 h, respectively, and the average time to the peak concentration was 3.7 ± 0.9 h. A positive correlation between CL/Fm and the amount of CSF drained (range 40 to 300 ml) was observed. When CMS was administered at doses of ≥5.22 mg/day, measured CSF concentrations of colistin were continuously above the MIC of 2 µg/ml, and measured values of trough concentration (C(trough)) ranged between 2.0 and 9.7 µg/ml. Microbiological cure was observed in 8/9 patients. Intraventricular administration of CMS at doses of ≥5.22 mg per day was appropriate in our patients, but since external CSF efflux is variable and can influence the clearance of colistin and its concentrations in CSF, the daily dose of 10 mg suggested by the Infectious Diseases Society of America may be more prudent.

Segregation of virulent influenza A(H1N1) variants in the lower respiratory tract of critically ill patients during the 2010-2011 seasonal epidemic.

BACKGROUND: Since its appearance in 2009, the pandemic influenza A(H1N1) virus circulated worldwide causing several severe infections. METHODS: Respiratory samples from patients with 2009 influenza A(H1N1) and acute respiratory distress attending 24 intensive care units (ICUs) as well as from patients with lower respiratory tract infections not requiring ICU admission and community upper respiratory tract infections in the Lombardy region (10 million inhabitants) of Italy during the 2010-2011 winter-spring season, were analyzed. RESULTS: In patients with severe ILI, the viral load was higher in bronchoalveolar lavage (BAL) with respect to nasal swab (NS), (p<0.001) suggesting a higher virus replication in the lower respiratory tract. Four distinct virus clusters (referred to as cluster A to D) circulated simultaneously. Most (72.7%, n = 48) of the 66 patients infected with viruses belonging to cluster A had a severe (n = 26) or moderate ILI (n = 22). Amino acid mutations (V26I, I116M, A186T, D187Y, D222G/N, M257I, S263F, I286L/M, and N473D) were observed only in patients with severe ILI. D222G/N variants were detected exclusively in BAL samples. CONCLUSIONS: Multiple virus clusters co-circulated during the 2010-2011 winter-spring season. Severe or moderate ILI were associated with specific 2009 influenza A(H1N1) variants, which replicated preferentially in the lower respiratory tract.

The Italian ECMO network experience during the 2009 influenza A(H1N1) pandemic: preparation for severe respiratory emergency outbreaks.

PURPOSE: In view of the expected 2009 influenza A(H1N1) pandemic, the Italian Health Authorities set up a national referral network of selected intensive care units (ICU) able to provide advanced respiratory care up to extracorporeal membrane oxygenation (ECMO) for patients with acute respiratory distress syndrome (ARDS). We describe the organization and results of the network, known as ECMOnet. METHODS: The network consisted of 14 ICUs with ECMO capability and a national call center. The network was set up to centralize all severe patients to the ECMOnet centers assuring safe transfer. An ad hoc committee defined criteria for both patient transfer and ECMO institutions. RESULTS: Between August 2009 and March 2010, 153 critically ill patients (53% referred from other hospitals) were admitted to the ECMOnet ICU with suspected H1N1. Sixty patients (48 of the referred patients, 49 with confirmed H1N1 diagnosis) received ECMO according to ECMOnet criteria. All referred patients were successfully transferred to the ECMOnet centers; 28 were transferred while on ECMO. Survival to hospital discharge in patients receiving ECMO was 68%. Survival of patients receiving ECMO within 7 days from the onset of mechanical ventilation was 77%. The length of mechanical ventilation prior to ECMO was an independent predictor of mortality. CONCLUSIONS: A network organization based on preemptive patient centralization allowed a high survival rate and provided effective and safe referral of patients with severe H1N1-suspected ARDS.

Steady-state pharmacokinetics and BAL concentration of colistin in critically Ill patients after IV colistin methanesulfonate administration.

BACKGROUND: Infections caused by multidrug-resistant gram-negative bacteria have caused a resurgence of interest in colistin. To date, information about pharmacokinetics of colistin is very limited in critically ill patients, and no attempts have been made to evaluate its concentration in BAL. METHODS: In this prospective, open-label study, 13 adult patients with ventilator-associated pneumonia caused by gram-negative bacteria were treated with colistin methanesulfonate (CMS) IV, 2 million International Units (174 mg) q8h, a usually recommended dose, for at least 2 days. Blood samples were collected from each patient at time intervals after the end of infusion. BAL was performed at 2 h. Colistin was measured by a selective, sensitive high-performance liquid chromatography-based method. Pharmacokinetic parameters were determined by noncompartmental analysis. RESULTS: Patients received 2.19 ± 0.38 mg/kg (range, 1.58-3.16) of CMS per dose. At steady state, mean ± SD plasma colistin maximum (Cmax) and trough (Ctrough) concentrations were 2.21 ± 1.08 and 1.03 ± 0.69 µg/mL, respectively. Mean ± SD area under the plasma concentration-time curve from 0 to 8 h (AUC(0-8)), apparent elimination half-life, and apparent volume of distribution were 11.5 ± 6.2 µg × h/mL, 5.9 ± 2.6 h, and 1.5 ± 1.1 L/kg, respectively. Cmax/minimum inhibitory concentration (MIC) ratio and AUC(0-24)/MIC ratio (MIC = 2 µg/mL) were 1.1 ± 0.5 and 17.3 ± 9.3, respectively. Colistin was undetectable in BAL. Nephrotoxicity was not observed. CONCLUSIONS: Although the pharmacodynamic parameters that better predict the efficacy of colistin are not known in humans, in critically ill adult patients the IV administration of CMS 2 million International Units (174 mg) q8h results in apparently suboptimal plasma concentrations of colistin, which is undetectable in BAL. A better understanding of the pharmacokinetic-pharmacodynamic relationship of colistin is urgently needed to determine the optimal dosing regimen.

Adaptive support ventilation versus conventional ventilation for total ventilatory support in acute respiratory failure.

OBJECTIVE: To compare the short-term effects of adaptive support ventilation (ASV), an advanced closed-loop mode, with conventional volume or pressure-control ventilation in patients passively ventilated for acute respiratory failure. DESIGN: Prospective crossover interventional multicenter trial. SETTING: Six European academic intensive care units. PATIENTS: Eighty-eight patients in three groups: patients with no obvious lung disease (n = 22), restrictive lung disease (n = 36) or obstructive lung disease (n = 30). INTERVENTIONS: After measurements on conventional ventilation (CV) as set by the patients' clinicians, each patient was switched to ASV set to obtain the same minute ventilation as during CV (isoMV condition). If this resulted in a change in PaCO(2), the minute ventilation setting of ASV was readjusted to achieve the same PaCO(2) as in CV (isoCO(2) condition). MEASUREMENTS AND RESULTS: Compared with CV, PaCO(2) during ASV in isoMV condition and minute ventilation during ASV in isoCO(2) condition were slightly lower, with lower inspiratory work/minute performed by the ventilator (p < 0.01). Oxygenation and hemodynamics were unchanged. During ASV, respiratory rate was slightly lower and tidal volume (Vt) slightly greater (p < 0.01), especially in obstructed patients. During ASV there were different ventilatory patterns in the three groups, with lower Vt in patients with restrictive disease and prolonged expiratory time in obstructed patients, thus mimicking the clinicians' choices for setting CV. In three chronic obstructive pulmonary disease patients the resulting Vt was unacceptably high. CONCLUSIONS: Comparison between ASV and CV resulted either in similarities or in minor differences. Except for excessive Vt in a few obstructed patients, all differences were in favor of ASV.