Approaches and techniques to avoid development or progression of acute respiratory distress syndrome

PURPOSE OF REVIEW: Despite major improvement in ventilation strategies, hospital mortality and morbidity of the acute respiratory distress syndrome (ARDS) remain high. A lot of therapies have been shown to be ineffective for established ARDS. There is a growing interest in strategies aiming at avoiding development and progression of ARDS. RECENT FINDINGS: Recent advances in this field have explored identification of patients at high-risk, nonspecific measures to limit the risks of inflammation, infection and fluid overload, prevention strategies of ventilator-induced lung injury and patient self-inflicted lung injury, and pharmacological treatments. SUMMARY: There is potential for improvement in the management of patients admitted to intensive care unit to reduce ARDS incidence. Apart from nonspecific measures, prevention of ventilator-induced lung injury and patient self-inflicted lung injury are of major importance

A diaphragmatic electrical activity-based optimization strategy during pressure support ventilation improves synchronization but does not impact work of breathing.

Poor patient-ventilator synchronization is often observed during pressure support ventilation (PSV) and has been associated with prolonged duration of mechanical ventilation and poor outcome. Diaphragmatic electrical activity (Eadi) recorded using specialized nasogastric tubes is a surrogate of respiratory brain stem output. This study aimed at testing whether adapting ventilator settings during PSV using a protocolized Eadi-based optimization strategy, or Eadi-triggered and -cycled assisted pressure ventilation (or PSVN) could (1) improve patient-ventilator interaction and (2) reduce or normalize patient respiratory effort as estimated by the work of breathing (WOB) and the pressure time product (PTP). This was a prospective cross-over study. Patients with a known chronic pulmonary obstructive or restrictive disease, asynchronies or suspected intrinsic positive end-expiratory pressure (PEEP) who were ventilated using PSV were enrolled in the study. Four different ventilator settings were sequentially applied for 15 minutes (step 1: baseline PSV as set by the clinician, step 2: Eadi-optimized PSV to adjust PS level, inspiratory trigger, and cycling settings, step 3: step 2 + PEEP adjustment, step 4: PSVN). The same settings as step 3 were applied again after step 4 to rule out a potential effect of time. Breathing pattern, trigger delay (Td), inspiratory time in excess (Tiex), pressure-time product (PTP), and work of breathing (WOB) were measured at the end of each step. Eleven patients were enrolled in the study. Eadi-optimized PSV reduced Td without altering Tiex in comparison with baseline PSV. PSVN reduced Td and Tiex in comparison with baseline and Eadi-optimized PSV. Respiratory pattern did not change during the four steps. The improvement in patient-ventilator interaction did not lead to changes in WOB or PTP. Eadi-optimized PSV allows improving patient ventilator interaction but does not alter patient effort in patients with mild asynchrony. Clinicaltrials.gov identifier: NCT 02067403 . Registered 7 February 2014

Target blood pressure in sepsis: between a rock and a hard place

The optimal target blood pressure in septic shock is still unknown. Therefore, in a long-term, resuscitated porcine model of fecal peritonitis-induced septic shock, Correa and colleagues tested whether different titrations of mean arterial pressure (50 to 60 and 75 to 85 mm Hg) would produce different effects on sepsis-related organ dysfunction. The higher blood pressure window was associated with increased needs for fluid resuscitation and norepinephrine support. However, titrating the lower blood pressure range coincided with an increased incidence of acute kidney injury. In contrast, neither the inflammatory response nor tissue mitochondrial activity showed any difference. This research paper in a clinically relevant model elegantly demonstrates that any standard resuscitation strategy may be a double-edged sword with respect to various therapeutic endpoints. Furthermore, it adds an important piece to the puzzle of the complex pathophysiology of sepsis-related acute kidney injury

Does vasopressor therapy have an indication in hemorrhagic shock?

This review aimed to answer whether the vasopressors are useful at the early phase of hemorrhagic shock. Data were taken from published experimental studies and clinical trials. Published case reports were discarded. A search of electronic database PubMed was conducted using keywords of hemorrhagic shock, vasopressors, vasoconstrictors, norepinephrine, epinephrine, vasopressin. The redundant papers were not included. We identified 15 experimental studies that compared hemorrhagic shock resuscitated with or without vasopressors, three retrospective clinical studies, and one controlled trial. The experimental and clinical studies are discussed in the clinical context, and their strengths as well as limitations are highlighted. There is a strong rationale for a vasopressor support in severe hemorrhagic shock. However, this should be tempered by the risk of excessive vasoconstriction during such hypovolemic state. The experimental models must be analyzed within their own limits and cannot be directly translated into clinical practice. In addition, because of many biases, the results of clinical trials are debatable. Therefore, based on current information, further clinical trials comparing early vasopressor support plus fluid resuscitation versus fluid resuscitation alone are warranted

Determinants of Doppler-based renal resistive index in patients with septic shock: impact of hemodynamic parameters, acute kidney injury and predisposing factors

BACKGROUND: Increased renal resistive index (RI) measured by Doppler ultrasonography has been shown to be associated with acute kidney injury (AKI) in septic patients. However, its clinical use is limited by poor sensitivity and specificity which may be explained by its numerous determinants [in particular mean arterial pressure (MAP)]. We measured, in patients with septic shock, RI at different MAP levels over a short period of time on the admission day to ICU (D1) and every 3 days until day 10 (D10) to define the determinants of RI and study specifically the relationship between RI and MAP. RESULTS: Consecutive patients with septic shock without preexisting chronic renal dysfunction were included in this prospective cohort study in two ICUs. Sixty-five patients were included in the study. Thirty-three (50.8%) and 15 (23.1%) patients had a history of chronic hypertension or diabetes, respectively. At D3, 35 patients presented AKI with AKIN 2 or 3 criteria (severe AKI, AKIN2-3 group) and 30 presented no AKIN or AKIN 1 criteria (AKIN0-1 group). As previously described, RI at D1 was higher in the AKIN2-3 group than in the AKIN0-1 group (0.73 interquartile range [0.67; 0.78] vs. 0.67 [0.59; 0.72], p = 0.001). A linear mixed model for predicting RI from D1 to D10 showed that an increase in pulse pressure, presence of severe AKI and additional day of ICU hospitalization were associated with an increase in RI. An increase in MAP and recovery from severe AKI were associated with a decrease in RI. In the presence of chronic hypertension or diabetes, an increase in MAP resulted in a lower decrease in RI, than in the absence of such factors. Presence of AKI at D3 did not impact the relationship between MAP and RI. CONCLUSIONS: Severe AKI was associated with a reversible increase in RI without significant interaction with the relationship between MAP and RI. Conversely, the presence of chronic hypertension and/or diabetes interacted with this relationship

Information conveyed by electrical diaphragmatic activity during unstressed, stressed and assisted spontaneous breathing: a physiological study.

The electrical activity of the crural diaphragm (Eadi), a surrogate of respiratory drive, can now be measured at the bedside in mechanically ventilated patients with a specific catheter. The expected range of Eadi values under stressed or assisted spontaneous breathing is unknown. This study explored Eadi values in healthy subjects during unstressed (baseline), stressed (with a resistance) and assisted spontaneous breathing. The relation between Eadi and inspiratory effort was analyzed. Thirteen healthy male volunteers were included in this randomized crossover study. Eadi and esophageal pressure (Peso) were recorded during unstressed and stressed spontaneous breathing and under assisted ventilation delivered in pressure support (PS) at low and high assist levels and in neurally adjusted ventilatory assist (NAVA). Overall eight different situations were assessed in each participant (randomized order). Peak, mean and integral of Eadi, breathing pattern, esophageal pressure-time product (PTPeso) and work of breathing (WOB) were calculated offline. Median [interquartile range] peak Eadi at baseline was 17 [13-22] μV and was above 10 μV in 92% of the cases. Eadi <sub>max</sub> defined as Eadi measured at maximal inspiratory capacity reached 90 [63 to 99] μV. Median peak Eadi/Eadi <sub>max</sub> ratio was 16.8 [15.6-27.9]%. Compared to baseline, respiratory rate and minute ventilation were decreased during stressed non-assisted breathing, whereas peak Eadi and PTPeso were increased. During unstressed assisted breathing, peak Eadi decreased during high-level PS compared to unstressed non-assisted breathing and to NAVA (p = 0.047). During stressed breathing, peak Eadi was lower during all assisted ventilation modalities compared to stressed non-assisted breathing. During assisted ventilation, across the different conditions, peak Eadi changed significantly, whereas PTPeso and WOB/min were not significantly modified. Finally, Eadi signal was still present even when Peso signal was suppressed due to high assist levels. Eadi analysis provides complementary information compared to respiratory pattern and to Peso monitoring, particularly in the presence of high assist levels. Trial registration The study was registered as NCT01818219 in clinicaltrial.gov. Registered 28 February 2013

Accuracy of P0.1 measurements performed by ICU ventilators: a bench study.

Occlusion pressure at 100 ms (P0.1), defined as the negative pressure measured 100 ms after the initiation of an inspiratory effort performed against a closed respiratory circuit, has been shown to be well correlated with central respiratory drive and respiratory effort. Automated P0.1 measurement is available on modern ventilators. However, the reliability of this measurement has never been studied. This bench study aimed at assessing the accuracy of P0.1 measurements automatically performed by different ICU ventilators. Five ventilators set in pressure support mode were tested using a two-chamber test lung model simulating spontaneous breathing. P0.1 automatically displayed on the ventilator screen (P0.1 <sub>vent</sub> ) was recorded at three levels of simulated inspiratory effort corresponding to P0.1 of 2.5, 5 and 10 cm H <sub>2</sub> O measured directly at the test lung and considered as the reference values of P0.1 (P0.1 <sub>ref</sub> ). The pressure drop after 100 ms was measured offline on the airway pressure-time curves recorded during the automated P0.1 measurements (P0.1 <sub>aw</sub> ). P0.1 <sub>vent</sub> was compared to P0.1 <sub>ref</sub> and to P0.1 <sub>aw</sub> . To assess the potential impact of the circuit length, P0.1 were also measured with circuits of different lengths (P0.1 <sub>circuit</sub> ). Variations of P0.1 <sub>vent</sub> correlated well with variations of P0.1 <sub>ref</sub> . Overall, P0.1 <sub>vent</sub> underestimated P0.1 <sub>ref</sub> except for the Löwenstein <sup>®</sup> ventilator at P0.1 <sub>ref</sub> 2.5 cm H <sub>2</sub> O and for the Getinge group <sup>®</sup> ventilator at P0.1 <sub>ref</sub> 10 cm H <sub>2</sub> O. The agreement between P0.1 <sub>vent</sub> and P0.1 <sub>ref</sub> assessed with the Bland-Altman method gave a mean bias of - 1.3 cm H <sub>2</sub> O (limits of agreement: 1 and - 3.7 cm H <sub>2</sub> O). Analysis of airway pressure-time and flow-time curves showed that all the tested ventilators except the Getinge group <sup>®</sup> ventilator performed an occlusion of at least 100 ms to measure P0.1. The agreement between P0.1 <sub>vent</sub> and P0.1 <sub>aw</sub> assessed with the Bland-Altman method gave a mean bias of 0.5 cm H <sub>2</sub> O (limits of agreement: 2.4 and - 1.4 cm H <sub>2</sub> O). The circuit's length impacted P0.1 measurements' values. A longer circuit was associated with lower P0.1 <sub>circuit</sub> values. P0.1 <sub>vent</sub> relative changes are well correlated to P0.1 <sub>ref</sub> changes in all the tested ventilators. Accuracy of absolute values of P0.1 <sub>vent</sub> varies according to the ventilator model. Overall, P0.1 <sub>vent</sub> underestimates P0.1 <sub>ref</sub> . The length of the circuit may partially explain P0.1 <sub>vent</sub> underestimation

Identifying associations between diabetes and acute respiratory distress syndrome in patients with acute hypoxemic respiratory failure: an analysis of the LUNG SAFE database

BACKGROUND: Diabetes mellitus is a common co-existing disease in the critically ill. Diabetes mellitus may reduce the risk of acute respiratory distress syndrome (ARDS), but data from previous studies are conflicting. The objective of this study was to evaluate associations between pre-existing diabetes mellitus and ARDS in critically ill patients with acute hypoxemic respiratory failure (AHRF). METHODS: An ancillary analysis of a global, multi-centre prospective observational study (LUNG SAFE) was undertaken. LUNG SAFE evaluated all patients admitted to an intensive care unit (ICU) over a 4-week period, that required mechanical ventilation and met AHRF criteria. Patients who had their AHRF fully explained by cardiac failure were excluded. Important clinical characteristics were included in a stepwise selection approach (forward and backward selection combined with a significance level of 0.05) to identify a set of independent variables associated with having ARDS at any time, developing ARDS (defined as ARDS occurring after day 2 from meeting AHRF criteria) and with hospital mortality. Furthermore, propensity score analysis was undertaken to account for the differences in baseline characteristics between patients with and without diabetes mellitus, and the association between diabetes mellitus and outcomes of interest was assessed on matched samples. RESULTS: Of the 4107 patients with AHRF included in this study, 3022 (73.6%) patients fulfilled ARDS criteria at admission or developed ARDS during their ICU stay. Diabetes mellitus was a pre-existing co-morbidity in 913 patients (22.2% of patients with AHRF). In multivariable analysis, there was no association between diabetes mellitus and having ARDS (OR 0.93 (0.78-1.11); p = 0.39), developing ARDS late (OR 0.79 (0.54-1.15); p = 0.22), or hospital mortality in patients with ARDS (1.15 (0.93-1.42); p = 0.19). In a matched sample of patients, there was no association between diabetes mellitus and outcomes of interest. CONCLUSIONS: In a large, global observational study of patients with AHRF, no association was found between diabetes mellitus and having ARDS, developing ARDS, or outcomes from ARDS. TRIAL REGISTRATION: NCT02010073 . Registered on 12 December 2013

IgG subclass deficiency and vaccination antibody titers : a paediatric study

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Effect on comfort of administering bubble-humidified or dry oxygen: the Oxyrea non-inferiority randomized study.

The clinical interest of using bubble humidification of oxygen remains controversial. This study was designed to further explore whether delivering dry oxygen instead of bubble-moistened oxygen had an impact on discomfort of ICU patients. This randomized multicenter non-inferiority open trial included patients admitted in intensive care unit and receiving oxygen. Any patient receiving non-humidified oxygen (between 0 and 15 L/min) for less than 2 h could participate in the study. Randomization was stratified based on the flow rate at inclusion (less or more than 4 L/min). Discomfort was assessed 6-8 and 24 h after inclusion using a dedicated 15-item scale (quoted from 0 to 150). Three hundred and fifty-four ICU patients receiving non-humidified oxygen were randomized either in the humidified (HO) (n = 172), using bubble humidifiers, or in the non-humidified (NHO) (n = 182) arms. In modified intention-to-treat analysis at H6-H8, the 15-item score was 26.6 ± 19.4 and 29.8 ± 23.4 in the HO and NHO groups, respectively. The absolute difference between scores in both groups was 3.2 [90% CI 0.0; + 6.5] for a non-inferiority margin of 5.3, meaning that the non-inferiority analysis was not conclusive. This was also true for the subgroups of patients receiving either less or more than 4 L/min of oxygen. At H24, using NHO was not inferior compared to HO in the general population and in the subgroup of patients receiving 4 L/min or less of oxygen. However, for patients receiving more than 4 L/min, a post hoc superiority analysis suggested that patients receiving dry oxygen were less comfortable. Oxygen therapy-related discomfort was low. Dry oxygen could not be demonstrated as non-inferior compared to bubble-moistened oxygen after 6-8 h of oxygen administration. At 24 h, dry oxygen was non-inferior compared to bubble-humidified oxygen for flows below 4 L/min