Ultrasound guidance for urgent arterial and venous catheterisation: randomised controlled study.

BACKGROUND: Haemodynamically unstable patients often require arterial and venous catheter insertion urgently. We hypothesised that ultrasound-guided arterial and venous catheterisation would reduce mechanical complications. METHODS: We performed a prospective RCT, where patients requiring both urgent arterial and venous femoral catheterisation were randomised to either ultrasound-guided or landmark-guided catheterisation. Complications and characteristics of catheter insertion (procedure duration, number of punctures, and procedure success) were recorded at the time of insertion (immediate complications). Late complications were investigated by ultrasound examination performed between the third and seventh days after randomisation. Primary outcome was the proportion of patients with at least one mechanical complication (immediate or late), by intention-to-treat analysis. Secondary outcomes included success rate, procedure time, and number of punctures. RESULTS: We analysed 136 subjects (102 [75%] male; age range: 27-62 yr) by intention to treat. The proportion of subjects with one or more complications was lower in 22/67 (33%) subjects undergoing ultrasound-guided catheterisation compared with landmark-guided catheterisation (40/69 [58%]; odds ratio: 0.35 [95% confidence interval: 0.18-0.71]; P=0.003). Ultrasound-guided catheterisation reduced both immediate (27%, compared with 51% in the landmark approach group; P=0.004) and late (10%, compared with 23% in the landmark approach group; P=0.047) complications. Ultrasound guidance also reduced the proportion of patients who developed deep vein thrombosis (4%, compared with 22% following landmark approach; P=0.012), and achieved a higher procedural success rate (96% vs 78%; P=0.004). CONCLUSIONS: An ultrasound-guided approach reduced mechanical complications after urgent femoral arterial and venous catheterisation, while increasing procedural success. CLINICAL TRIAL REGISTRATION: NCT02820909.

Proof of concept study of mass cytometry in septic shock patients reveals novel immune alterations.

Innovative single cell technologies such as mass cytometry (CyTOF) widen possibilities to deeply improve characterisation of immune alterations mechanisms in human diseases. So far, CyTOF has not been used in sepsis - a condition characterized by complex immune disorders. Here, we evaluated feasibility of CyTOF analysis in patients with septic shock. We designed a mass cytometry panel of 25 extracellular markers to study mononuclear cells from 5 septic shock patients and 5 healthy donors. We explored single-cell data with global and specific unsupervised approaches such as heatmaps, SPADE and viSNE. We first validated relevance of our CyTOF results by highlighting established immune hallmarks of sepsis, such as decreased monocyte HLA-DR expression and increased expressions of PD1 and PD-L1 on CD4 T cells and monocytes. We then showed that CyTOF analysis reveals novel aspects of sepsis-induced immune alterations, e.g. B cell shift towards plasma cell differentiation and uniform response of several monocyte markers defining an immune signature in septic patients. This proof of concept study demonstrates CyTOF suitability to analyse immune features of septic patients. Mass cytometry could thus represent a powerful tool to identify novel pathophysiological mechanisms and therapeutic targets for immunotherapy in septic shock patients.

Change in cardiac output during Trendelenburg maneuver is a reliable predictor of fluid responsiveness in patients with acute respiratory distress syndrome in the prone position under protective ventilation.

BACKGROUND: Predicting fluid responsiveness may help to avoid unnecessary fluid administration during acute respiratory distress syndrome (ARDS). The aim of this study was to evaluate the diagnostic performance of the following methods to predict fluid responsiveness in ARDS patients under protective ventilation in the prone position: cardiac index variation during a Trendelenburg maneuver, cardiac index variation during an end-expiratory occlusion test, and both pulse pressure variation and change in pulse pressure variation from baseline during a tidal volume challenge by increasing tidal volume (VT) to 8 ml.kg-1. METHODS: This study is a prospective single-center study, performed in a medical intensive care unit, on ARDS patients with acute circulatory failure in the prone position. Patients were studied at baseline, during a 1-min shift to the Trendelenburg position, during a 15-s end-expiratory occlusion, during a 1-min increase in VT to 8 ml.kg-1, and after fluid administration. Fluid responsiveness was deemed present if cardiac index assessed by transpulmonary thermodilution increased by at least 15% after fluid administration. RESULTS: There were 33 patients included, among whom 14 (42%) exhibited cardiac arrhythmia at baseline and 15 (45%) were deemed fluid-responsive. The area under the receiver operating characteristic (ROC) curve of the pulse contour-derived cardiac index change during the Trendelenburg maneuver and the end-expiratory occlusion test were 0.90 (95% CI, 0.80-1.00) and 0.65 (95% CI, 0.46-0.84), respectively. An increase in cardiac index ≥ 8% during the Trendelenburg maneuver enabled diagnosis of fluid responsiveness with sensitivity of 87% (95% CI, 67-100), and specificity of 89% (95% CI, 72-100). The area under the ROC curve of pulse pressure variation and change in pulse pressure variation during the tidal volume challenge were 0.52 (95% CI, 0.24-0.80) and 0.59 (95% CI, 0.31-0.88), respectively. CONCLUSIONS: Change in cardiac index during a Trendelenburg maneuver is a reliable test to predict fluid responsiveness in ARDS patients in the prone position, while neither change in cardiac index during end-expiratory occlusion, nor pulse pressure variation during a VT challenge reached acceptable predictive performance to predict fluid responsiveness in this setting. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01965574 . Registered on 16 October 2013. The trial was registered 6 days after inclusion of the first patient.

Prevalence and risk factors of hypotension associated with preload-dependence during intermittent hemodialysis in critically ill patients.

BACKGROUND: Hypotension is a frequent complication of intermittent hemodialysis (IHD) performed in intensive care units (ICUs). Passive leg raising (PLR) combined with continuous measurement of cardiac output is highly reliable to identify preload dependence, and may provide new insights into the mechanisms involved in IHD-related hypotension. The aim of this study was to assess prevalence and risk factors of preload dependence-related hypotension during IHD in the ICU. METHODS: A single-center prospective observational study performed on ICU patients undergoing IHD for acute kidney injury and monitored with a PiCCO® device. Primary end points were the prevalence of hypotension (defined as a mean arterial pressure below 65 mm Hg) and hypotension associated with preload dependence. Preload dependence was assessed by the passive leg raising test, and considered present if the systolic ejection volume increased by at least 10% during the test, as assessed continuously by the PiCCO® device. RESULTS: Forty-seven patients totaling 107 IHD sessions were included. Hypotension was observed in 61 IHD sessions (57%, CI95%: 47-66%) and was independently associated with inotrope administration, higher SOFA score, lower time lag between ICU admission and IHD session, and lower MAP at IHD session onset. Hypotension associated with preload dependence was observed in 19% (CI95%: 10-31%) of sessions with hypotension, and was associated with mechanical ventilation, lower SAPS II, higher pulmonary vascular permeability index (PVPI) and dialysate sodium concentration at IHD session onset. ROC curve analysis identified PVPI and mechanical ventilation as the only variables with significant diagnostic performance to predict hypotension associated with preload dependence (respective AUC: 0.68 (CI95%: 0.53-0.83) and 0.69 (CI95%: 0.54-0.85). A PVPI ≥ 1.6 at IHD session onset predicted occurrence of hypotension associated with preload dependence during IHD with a sensitivity of 91% (CI95%: 59-100%), and a specificity of 53% (CI95%: 42-63%). CONCLUSIONS: The majority of hypotensive episodes occurring during intermittent hemodialysis are unrelated to preload dependence and should not necessarily lead to reduction of fluid removal by hemodialysis. However, high PVPI at IHD session onset and mechanical ventilation are risk factors of preload dependence-related hypotension, and should prompt reduction of planned fluid removal during the session, and/or an increase in session duration.

Preload dependence indices to titrate volume expansion during septic shock: a randomized controlled trial.

INTRODUCTION: In septic shock, pulse pressure or cardiac output variation during passive leg raising are preload dependence indices reliable at predicting fluid responsiveness. Therefore, they may help to identify those patients who need intravascular volume expansion, while avoiding unnecessary fluid administration in the other patients. However, whether their use improves septic shock prognosis remains unknown. The aim of this study was to assess the clinical benefits of using preload dependence indices to titrate intravascular fluids during septic shock. METHODS: In a single-center randomized controlled trial, 60 septic shock patients were allocated to preload dependence indices-guided (preload dependence group) or central venous pressure-guided (control group) intravascular volume expansion with 30 patients in each group. The primary end point was time to shock resolution, defined by vasopressor weaning. RESULTS: There was no significant difference in time to shock resolution between groups (median (interquartile range) 2.0 (1.2 to 3.1) versus 2.3 (1.4 to 5.6) days in control and preload dependence groups, respectively). The daily amount of fluids administered for intravascular volume expansion was higher in the control than in the preload dependence group (917 (639 to 1,511) versus 383 (211 to 604) mL, P = 0.01), and the same held true for red cell transfusions (178 (82 to 304) versus 103 (0 to 183) mL, P = 0.04). Physiologic variable values did not change over time between groups, except for plasma lactate (time over group interaction, P <0.01). Mortality was not significantly different between groups (23% in the preload dependence group versus 47% in the control group, P = 0.10). Intravascular volume expansion was lower in the preload dependence group for patients with lower simplified acute physiology score II (SAPS II), and the opposite was found for patients in the upper two SAPS II quartiles. The amount of intravascular volume expansion did not change across the quartiles of severity in the control group, but steadily increased with severity in the preload dependence group. CONCLUSIONS: In patients with septic shock, titrating intravascular volume expansion with preload dependence indices did not change time to shock resolution, but resulted in less daily fluids intake, including red blood cells, without worsening patient outcome. TRIAL REGISTRATION: Clinicaltrials.gov NCT01972828. Registered 11 October 2013.

Open lung biopsy in nonresolving ARDS frequently identifies diffuse alveolar damage regardless of the severity stage and may have implications for patient management.

PURPOSE: The aim of the present study was to assess the rate of diffuse alveolar damage (DAD) on open lung biopsy (OLB) performed in the ICU for nonresolving ARDS. METHODS: A single-center retrospective study of patients meeting the Berlin definition criteria for ARDS who had undergone OLB for nonresolving ARDS. Patients were classified into mild, moderate and severe ARDS categories and according to the presence or absence of DAD on the OLB. The ARDS categories were assessed at baseline and at the time of the OLB. The OLBs were reviewed by two pathologists blinded to the ARDS classification. The primary endpoint was the rate of DAD according to the ARDS stage in the patients with nonresolving ARDS who had OLB. The secondary endpoint was the ability of DAD to predict ARDS among all the patients who had OLB. The same clinico-histopathological confrontation was cross validated in another ICU. RESULTS: From January 1998 to August 2013, 113 patients underwent OLB for acute hypoxemic respiratory failure, 83 of whom met the inclusion criteria for ARDS. At the time the OLB was performed, 11 of these patients had mild, 56 moderate, and 16 severe ARDS, respectively. The median (1st-3rd quartiles) time to OLB was 13 (10-18) and 9 (6-14) days from the onset of respiratory symptoms and from ARDS onset, respectively, with no statistical difference between the three ARDS groups. DAD was found in 48 (58 %) patients with ARDS, 4 (36 %) in the mild, 33 (59 %) in the moderate, and 11 (69 %) in the severe stage (P = 0.23). For the 113 patients who underwent OLB, the sensitivity and specificity of DAD to the Berlin definition was 0.58 (0.46-0.69) and 0.73 (0.54-0.88), respectively. Similar results were found in the other ICU. CONCLUSIONS: DAD is present in the majority of patients with nonresolving ARDs and its frequency is no different across the three ARDS stages. On this basis, the systematic use of steroids in nonresolving ARDS is not recommended.

Evaluation of recruited lung volume at inspiratory plateau pressure with PEEP using bedside digital chest X-ray in patients with acute lung injury/ARDS.

BACKGROUND: We wanted to assess whether there was a significant relationship between recruited lung volume (V(rec)) and change in density on digital processed chest x-ray measured at 2 different levels of inspiratory plateau pressure corresponding to 2 PEEP levels in patients with acute lung injury or ARDS. METHODS: In 14 subjects, PEEP 5 cm H2O and 15 cm H2O were prospectively applied in a random order for 10 min. At the end of each period, chest x-ray was taken using a digital portable device, and a pressure-volume curve of the respiratory system was performed. We also assessed P(aO2), and the static and the dynamic (C(dyn,rs)) compliance of the respiratory system. Change in end-expiratory lung volume between tidal breath and relaxation volume of the respiratory system was determined. Radiological attenuation was measured on chest x-rays in 4 regions of interest in the right lung, and in 3 regions of interest in the left lung, drawn in posterior intercostal spaces from top to bottom, by using dedicated software. The ratio of lung density in each region between PEEP 15 and PEEP 5 (rP15/P5) and their arithmetic mean (µP15/P5) were computed. V(rec) was determined from the pressure-volume curves. RESULTS: The median value of rP15/P5 in the 98 lung levels was 0.91 (0.80-1.01), which was significantly different from 1 (P < .001). The values of rP15/P5 were not significantly different between the lung levels. The median values of V(rec) and µP15/P5 were 288 (173-402) mL and 0.90 (0.80-0.97), respectively. There was a significant negative correlation between V(rec) and µP15/P5 (R = -0.77, P = .01). The reduction in µP15/P5 tended to correlate with the increase in C(dyn,rs) (R = -0.49, P = .077) or in P(aO2) (R = -0.53, P = .05) between PEEP 15 cm H2O and PEEP 5 cm H2O. CONCLUSIONS: Digital chest x-ray done at the bedside in acute lung injury/ARDS subjects was able to detect a reduction in density between PEEP 5 cm H2O and PEEP 15 cm H2O, which correlated with V(rec).

Comparison of Alpha 200 and CoughAssist as intermittent positive pressure breathing devices: a bench study.

BACKGROUND: Intermittent positive pressure breathing (IPPB) is used in non-intubated patients to increase lung volume and to enhance coughing. Alpha 200 (Salvia Lifetec, Kronberg, Germany) is a specific IPPB device. CoughAssist (Respironics France, Carquefou, France) is a mechanical insufflator-exsufflator used to remove secretions in patients with inefficient cough. Both can also be used for intubated or tracheotomized patients. We assessed the impact of various artificial airways on the ability of the Alpha 200 and CoughAssist to generate insufflated volume. METHODS: We measured the insufflated volume and pressure at the airway opening in a lung model under 2 conditions of compliance (30 or 60 mL/cm H(2)O) at single resistance of 5 cm H(2)O/L/s. The devices were used at 2 set pressures: 30 and 40 cm H(2)O. The Alpha 200 was set at 2 inflation flows: 0.5 and 1 L/s, whereas CoughAssist was set at its highest value of 10 L/s. Measurements were done without (control) and with different size endotracheal tubes and tracheostomy cannulae. The relationships between insufflated volume and measured pressure were analyzed using linear regressions. RESULTS: The slopes and intercepts of the control relationship between insufflated volume and pressure were significantly greater with Alpha 200 at each set flow than with CoughAssist. As artificial airways were used, the insufflated volume did not differ from the control with CoughAssist, while with Alpha 200 it increased at each flow setting and for all mechanical conditions. The largest differences in insufflated volume between the 2 devices were observed for the largest endotracheal tubes and tracheostomy cannulas and for the lowest inflation flow setting in Alpha 200. These results can be explained in terms of how the devices function, as CoughAssist adapts by increasing flow, while Alpha 200 adapts by increasing inspiratory time. CONCLUSIONS: This bench study has shown that in the presence of artificial airways the value of the insufflated volume generated by the CoughAssist device was significantly lower than that generated by the Alpha 200 device.

Efficacy and safety of recruitment maneuvers in acute respiratory distress syndrome.

Recruitment maneuvers (RM) consist of a ventilatory strategy that increases the transpulmonary pressure transiently to reopen the recruitable lung units in acute respiratory distress syndrome (ARDS). The rationales to use RM in ARDS are that there is a massive loss of aerated lung and that once the end-inspiratory pressure surpasses the regional critical opening pressure of the lung units, those units are likely to reopen. There are different methods to perform RM when using the conventional ICU ventilator. The three RM methods that are mostly used and investigated are sighs, sustained inflation, and extended sigh. There is no standardization of any of the above RM. Meta-analysis recommended not to use RM in routine in stable ARDS patients but to run them in case of life-threatening hypoxemia. There are some concerns regarding the safety of RM in terms of hemodynamics preservation and lung injury as well. The rapid rising in pressure can be a factor that explains the potential harmful effects of the RM. In this review, we describe the balance between the beneficial effects and the harmful consequences of RM. Recent animal studies are discussed.

Viscoelastic properties of lungs and thoracic wall of anesthetized mechanically ventilated piglets.

OBJECTIVE: To investigate the viscoelastic properties of lungs and thoracic wall in piglets. STUDY DESIGN: Prospective experimental study. ANIMALS: Six piglets weighting 30 kg. METHODS: Animals were tracheotomized, anesthetized and mechanically ventilated under controlled conditions. After control measurements of the mechanical properties of the lung of the pigs had been taken, acute lung injury (ALI) was induced by saline lavage. Lung and thoracic wall tissue resistance (DeltaR), which reflects viscoelastic properties and/or time constant inequalities, were determined by using a rapid airway occlusion technique during constant flow inflation (V), at constant tidal volume. was varied from 0.1-0.2 to 1.2 L second(-1) on a single breath. Multiple data sets of DeltaR of lung (DeltaR(L)) and thoracic wall (DeltaR(w)) to inspiratory time (T(I) = V(T)/V) were fitted to a model whose prediction equation was DeltaR = R(2)[1 -exp(-T(I)/tau(2))], where R(2) and tau(2) are the 'viscoelastic' resistance and time constant, respectively. Subscripts (L) and (W) are used to represent lung and thoracic wall, respectively (R(2L), R(2W), tau(2L), tau(2W)). Two more sets of physiological measurements were then taken--the first under zero end-expiratory pressure (ZEEP) and the second under a positive end-expiratory pressure (PEEP) of 10 cmH(2)O. RESULTS: Data of DeltaR adequately fitted to the prediction equation in all instances. In control, R(2,L) was 15.3 (10.7-22.6) cmH(2)O L(-1) second(-1) (median, interquartile range), tau(2,L) 3.3 (1.9-5.5) seconds, R(2,w) 6.5 (2.2-10.3) cmH(2)O L(-1) second(-1) and tau(2,w) 2.9 (1.1-4.3) seconds. In ALI, R(2,L) significantly increased to 129.6 (105.9-171.3) cmH(2)O L(-1) second(-1) on ZEEP but not significantly decreased to 48.9 (17.8-109.6) cmH(2)O L(-1) second(-1) with PEEP. The corresponding values of tau(2,L) were 7.1 (5.1-11.6) and 4.4 (3.1-5.5) seconds. The values pertaining to thoracic wall did not change significantly among conditions. CONCLUSIONS AND CLINICAL RELEVANCE: Viscoelastic properties of the lung and thoracic wall in piglets can be described by a viscoelastic model. Values of parameters of this model were markedly increased in ALI and decreased with PEEP.

Assessment of airway closure from deflation lung volume-pressure curve: sigmoidal equation revisited.

OBJECTIVE: To assess a sigmoidal equation for describing airway closure. DESIGN: Experimental study. SETTING: University laboratory. PARTICIPANTS: Eight piglets mechanically ventilated on zero end-expiratory pressure (ZEEP). INTERVENTIONS: Control and lung saline lavage. MEASUREMENTS AND RESULTS: Lungs were inflated up to transpulmonary pressure of 30 cmH(2)O at constant flow (0.12l s(-1)) then deflated at the same flow rate up to the point at which oesophageal pressure was constant, which was assumed to represent complete airway closure. The deflation volume-transpulmonary pressure curve was fitted to: (1) a sigmoidal equation focusing on inflexion point and pressure at maximal compliance increase and (2) an exponential equation above an inflexion point determined by eyeballing. Data deviate from the exponential equation at the point of airway closure onset. The zero-volume intercept was determined. Complete airway closure was reached at -8.3+/-3.5cmH(2)O in control conditions and at -1.3+/-3.7 cmH(2)O after lavage (p < 0.05). Between control and lavage, onset of airway closure was 3.0+/-1.9 vs. 6.0+/-2.8 cmH(2)O (p <0.05), inflexion point 3.2+/-1.8 vs. 7.7+/-2.6 cmH(2)O (p <0.001), pressure at maximal compliance increase -1.9+/-0.7 vs. -0.03+/-2.1cmH(2)O (p <0.05) and zero-volume intercept -1.5+/-1.4 vs. 0.3+/-2.3cmH(2)O (p <0.05). CONCLUSIONS: During mechanical ventilation airways stay open and close around ZEEP in control but are closed above ZEEP after lavage. Inflexion point might reflect onset of airways closure in control. Pressure at maximal compliance increase was not a marker of complete airways closure. In control and lavage, pressure at maximal compliance increase and zero-volume intercept were reasonably equivalent.