Intraoperative Ventilation/Perfusion Mismatch and Postoperative Pulmonary Complications after Major non-cardiac surgery: a prospective cohort study.

BACKGROUND: Postoperative pulmonary complications (PPCs) can increase hospital length of stay, postoperative morbidity and mortality. Despite many factors can increase the risk of PPCs, it is not known whether intraoperative ventilation/perfusion (V/Q) mismatch can be associated with an increased risk of PPCs after major non-cardiac surgery. METHODS: We enrolled patients undergoing general anesthesia for non-cardiac surgery and evaluated intraoperative V/Q distribution using the Automatic Lung Parameter Estimator technique. The assessment was done after anesthesia induction (T1), after 1 hour from surgery start (T2) and at the end of surgery (T3). We collected demographic and procedural information and measured intraoperative ventilatory and hemodynamic parameters at each time-point. Patients were followed up for 7 days after surgery and assessed daily for PPCs occurrence. RESULTS: We enrolled 101 patients with a median age of 71 [62-77] years, a BMI of 25 [22.4-27.9] kg/m 2 and a preoperative ARISCAT score of 41 [34-47]. Of them, 29 (29%) developed PPCs, mainly acute respiratory failure (23%) and pleural effusion (11%). Patients with and without PPCs did not differ in levels of shunt at T1 (PPCs:22.4[10.4-35.9] % vs No PPCs:19.3[9.4-24.1] %, p=0.18) or during the protocol, while significantly different levels of high V/Q were found during surgery (PPCs:13[11-15] mmHg vs No PPCs:10[8-13.5] mmHg, p=0.007) and before extubation (PPCs:13[11-14]mmHg vs No PPCs:10[8-12] mmHg, p=0.006). After adjusting for age, ARISCAT, BMI, smoking, fluid balance, anesthesia type, laparoscopic procedure and surgery duration, high V/Q before extubation was independently associated with the development of PPCs (OR 1.147, CI 95% [1.021-1.289], p=0.02). The sensitivity analysis showed an E-value of 1.35 (CI=1.11). CONCLUSIONS: In patients with intermediate/high risk of PPCs undergoing major non-cardiac surgery, intraoperative V/Q mismatch is associated with the development of PPCs. Increased high V/Q before extubation is independently associated with the occurrence of PPCs in the first 7 days after surgery.

Physiological effects of two driving pressure-based methods to set positive end-expiratory pressure during one lung ventilation.

During one-lung ventilation (OLV), titrating the positive end-expiratory pressure (PEEP) to target a low driving pressure (∆P) could reduce postoperative pulmonary complications. However, it is unclear how to conduct PEEP titration: by stepwise increase starting from zero PEEP (PEEPINCREMENTAL) or by stepwise decrease after a lung recruiting manoeuvre (PEEPDECREMENTAL). In this randomized trial, we compared the physiological effects of these two PEEP titration strategies on respiratory mechanics, ventilation/perfusion mismatch and gas exchange. Patients undergoing video-assisted thoracoscopic surgery in OLV were randomly assigned to a PEEPINCREMENTAL or PEEPDECREMENTAL strategy to match the lowest ∆P. In the PEEPINCREMENTAL group, PEEP was stepwise titrated from ZEEP up to 16 cm H2O, whereas in the PEEPDECREMENTAL group PEEP was decrementally titrated, starting from 16 cm H2O, immediately after a lung recruiting manoeuvre. Respiratory mechanics, ventilation/perfusion mismatch and blood gas analyses were recorded at baseline, after PEEP titration and at the end of surgery. Sixty patients were included in the study. After PEEP titration, shunt decreased similarly in both groups, from 50 [39-55]% to 35 [28-42]% in the PEEPINCREMENTAL and from 45 [37-58]% to 33 [25-45]% in the PEEPDECREMENTAL group (both p < 0.001 vs baseline). The resulting ∆P, however, was lower in the PEEPDECREMENTAL than in the PEEPINCREMENTAL group (8 [7-11] vs 10 [9-11] cm H2O; p = 0.03). In the PEEPDECREMENTAL group the PaO2/ FIO2 ratio increased significantly after intervention (from 140 [99-176] to 186 [152-243], p < 0.001). Both the PEEPINCREMENTAL and the PEEPDECREMENTAL strategies were able to decrease intraoperative shunt, but only PEEPDECREMENTAL improved oxygenation and lowered intraoperative ΔP.Clinical trial number NCT03635281; August 2018; "retrospectively registered".

Personalized Positive End-Expiratory Pressure in Acute Respiratory Distress Syndrome: Comparison Between Optimal Distribution of Regional Ventilation and Positive Transpulmonary Pressure.

OBJECTIVES: Different techniques exist to select personalized positive end-expiratory pressure in patients affected by the acute respiratory distress syndrome. The positive end-expiratory transpulmonary pressure strategy aims to counteract dorsal lung collapse, whereas electrical impedance tomography could guide positive end-expiratory pressure selection based on optimal homogeneity of ventilation distribution. We compared the physiologic effects of positive end-expiratory pressure guided by electrical impedance tomography versus transpulmonary pressure in patients affected by acute respiratory distress syndrome. DESIGN: Cross-over prospective physiologic study. SETTING: Two academic ICUs. PATIENTS: Twenty ICU patients affected by acute respiratory distress syndrome undergoing mechanical ventilation. INTERVENTION: Patients monitored by an esophageal catheter and a 32-electrode electrical impedance tomography monitor underwent two positive end-expiratory pressure titration trials by randomized cross-over design to find the level of positive end-expiratory pressure associated with: 1) positive end-expiratory transpulmonary pressure (PEEPPL) and 2) proportion of poorly or nonventilated lung units (Silent Spaces) less than or equal to 15% (PEEPEIT). Each positive end-expiratory pressure level was maintained for 20 minutes, and afterward, lung mechanics, gas exchange, and electrical impedance tomography data were collected. MEASUREMENTS AND MAIN RESULTS: PEEPEIT and PEEPPL differed in all patients, and there was no correlation between the levels identified by the two methods (Rs = 0.25; p = 0.29). PEEPEIT determined a more homogeneous distribution of ventilation with a lower percentage of dependent Silent Spaces (p = 0.02), whereas PEEPPL was characterized by lower airway-but not transpulmonary-driving pressure (p = 0.04). PEEPEIT was significantly higher than PEEPPL in subjects with extrapulmonary acute respiratory distress syndrome (p = 0.006), whereas the opposite was true for pulmonary acute respiratory distress syndrome (p = 0.03). CONCLUSIONS: Personalized positive end-expiratory pressure levels selected by electrical impedance tomography- and transpulmonary pressure-based methods are not correlated at the individual patient level. PEEPPL is associated with lower dynamic stress, whereas PEEPEIT may help to optimize lung recruitment and homogeneity of ventilation. The underlying etiology of acute respiratory distress syndrome could deeply influence results from each method.

Using arterial-venous oxygen difference to guide red blood cell transfusion strategy.

BACKGROUND: Guidelines recommend a restrictive red blood cell transfusion strategy based on hemoglobin (Hb) concentrations in critically ill patients. We hypothesized that the arterial-venous oxygen difference (A-V O2diff), a surrogate for the oxygen delivery to consumption ratio, could provide a more personalized approach to identify patients who may benefit from transfusion. METHODS: A prospective observational study including 177 non-bleeding adult patients with a Hb concentration of 7.0-10.0 g/dL within 72 h after ICU admission. The A-V O2diff, central venous oxygen saturation (ScvO2), and oxygen extraction ratio (O2ER) were noted when a patient's Hb was first within this range. Transfusion decisions were made by the treating physician according to institutional policy. We used the median A-V O2diff value in the study cohort (3.7 mL) to classify the transfusion strategy in each patient as "appropriate" (patient transfused when the A-V O2diff > 3.7 mL or not transfused when the A-V O2diff ≤ 3.7 mL) or "inappropriate" (patient transfused when the A-V O2diff ≤ 3.7 mL or not transfused when the A-V O2diff > 3.7 mL). The primary outcome was 90-day mortality. RESULTS: Patients managed with an "appropriate" strategy had lower mortality rates (23/96 [24%] vs. 36/81 [44%]; p = 0.004), and an "appropriate" strategy was independently associated with reduced mortality (hazard ratio [HR] 0.51 [95% CI 0.30-0.89], p = 0.01). There was a trend to less acute kidney injury with the "appropriate" than with the "inappropriate" strategy (13% vs. 26%, p = 0.06), and the Sequential Organ Failure Assessment (SOFA) score decreased more rapidly (p = 0.01). The A-V O2diff, but not the ScvO2, predicted 90-day mortality in transfused (AUROC = 0.656) and non-transfused (AUROC = 0.630) patients with moderate accuracy. Using the ROC curve analysis, the best A-V O2diff cutoffs for predicting mortality were 3.6 mL in transfused and 3.5 mL in non-transfused patients. CONCLUSIONS: In anemic, non-bleeding critically ill patients, transfusion may be associated with lower 90-day mortality and morbidity in patients with higher A-V O2diff. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03767127. Retrospectively registered on 6 December 2018.

Impaired platelet reactivity in patients with septic shock: a proof-of-concept study.

Coagulation disorders and thrombocytopenia are common in patients with septic shock, but only few studies have focused on platelet variables beyond platelet count. The aim of this study was to evaluate whether platelets reactivity predicts sepsis-induced thrombocytopenia in patients with septic shock. We therefore enrolled consecutive patients with septic shock and platelets count >150*103/µL on the day of the diagnosis. Platelets reactivity tests were performed daily from the diagnosis of septic shock until day five; platelet volume distribution and mean platelet volume were also recorded daily. Sepsis-induced thrombocytopenia was defined as a platelet count <150*103/µL. Thirty patients were included; sepsis-induced thrombocytopenia occurred in 11 (31%) patients. Platelets reactivity and platelet count at day of septic shock diagnosis were not correlated. Patients who experienced thrombocytopenia had lower maximal aggregation at diagnosis than others. Maximal aggregation tests were predictors of thrombocytopenia (AUROC from 0.756 to 0.797, depending on the agonist used). Both platelet volume distribution width and mean platelet volume were predictors of 90-day mortality (AUROC 0.866 and 0.735, respectively). In this pilot study, impaired platelets reactivity was more common in patients who subsequently developed sepsis-induced thrombocytopenia; also, platelet volume distribution width and mean platelet volume were predictors of 90-day mortality.

Expiratory flow limitation in intensive care: prevalence and risk factors.

BACKGROUND: Expiratory flow limitation (EFL) is characterised by a markedly reduced expiratory flow insensitive to the expiratory driving pressure. The presence of EFL can influence the respiratory and cardiovascular function and damage the small airways; its occurrence has been demonstrated in different diseases, such as COPD, asthma, obesity, cardiac failure, ARDS, and cystic fibrosis. Our aim was to evaluate the prevalence of EFL in patients requiring mechanical ventilation for acute respiratory failure and to determine the main clinical characteristics, the risk factors and clinical outcome associated with the presence of EFL. METHODS: Patients admitted to the intensive care unit (ICU) with an expected length of mechanical ventilation of 72 h were enrolled in this prospective, observational study. Patients were evaluated, within 24 h from ICU admission and for at least 72 h, in terms of respiratory mechanics, presence of EFL through the PEEP test, daily fluid balance and followed for outcome measurements. RESULTS: Among the 121 patients enrolled, 37 (31%) exhibited EFL upon admission. Flow-limited patients had higher BMI, history of pulmonary or heart disease, worse respiratory dyspnoea score, higher intrinsic positive end-expiratory pressure, flow and additional resistance. Over the course of the initial 72 h of mechanical ventilation, additional 21 patients (17%) developed EFL. New onset EFL was associated with a more positive cumulative fluid balance at day 3 (103.3 ml/kg) compared to that of patients without EFL (65.8 ml/kg). Flow-limited patients had longer duration of mechanical ventilation, longer ICU length of stay and higher in-ICU mortality. CONCLUSIONS: EFL is common among ICU patients and correlates with adverse outcomes. The major determinant for developing EFL in patients during the first 3 days of their ICU stay is a positive fluid balance. Further studies are needed to assess if a restrictive fluid therapy might be associated with a lower incidence of EFL.

Heterogeneity of regional inflection points from pressure-volume curves assessed by electrical impedance tomography.

BACKGROUND: The pressure-volume (P-V) curve has been suggested as a bedside tool to set mechanical ventilation; however, it reflects a global behavior of the lung without giving information on the regional mechanical properties. Regional P-V (PVr) curves derived from electrical impedance tomography (EIT) could provide valuable clinical information at bedside, being able to explore the regional mechanics of the lung. In the present study, we hypothesized that regional P-V curves would provide different information from those obtained from global P-V curves, both in terms of upper and lower inflection points. Therefore, we constructed pressure-volume curves for each pixel row from non-dependent to dependent lung regions of patients affected by acute hypoxemic respiratory failure (AHRF) and acute respiratory distress syndrome (ARDS). METHODS: We analyzed slow-inflation P-V maneuvers data from 12 mechanically ventilated patients. During the inflation, the pneumotachograph was used to record flow and airway pressure while the EIT signals were recorded digitally. From each maneuver, global respiratory system P-V curve (PVg) and PVr curves were obtained, each one corresponding to a pixel row within the EIT image. PVg and PVr curves were fitted using a sigmoidal equation, and the upper (UIP) and lower (LIP) inflection points for each curve were mathematically identified; LIP and UIP from PVg were respectively called LIPg and UIPg. From each measurement, the highest regional LIP (LIPrMAX) and the lowest regional UIP (UIPrMIN) were identified and the pressure difference between those two points was defined as linear driving pressure (ΔPLIN). RESULTS: A significant difference (p < 0.001) was found between LIPrMAX (15.8 [9.2-21.1] cmH2O) and LIPg (2.9 [2.2-8.9] cmH2O); in all measurements, the LIPrMAX was higher than the corresponding LIPg. We found a significant difference (p < 0.005) between UIPrMIN (30.1 [23.5-37.6] cmH2O) and UIPg (40.5 [34.2-45] cmH2O), the UIPrMIN always being lower than the corresponding UIPg. Median ΔPLIN was 12.6 [7.4-20.8] cmH2O and in 56% of cases was < 14 cmH2O. CONCLUSIONS: Regional inflection points derived by EIT show high variability reflecting lung heterogeneity. Regional P-V curves obtained by EIT could convey more sensitive information than global lung mechanics on the pressures within which all lung regions express linear compliance. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02907840 . Registered on 20 September 2016.

An Open-Loop, Physiologic Model-Based Decision Support System Can Provide Appropriate Ventilator Settings.

OBJECTIVES: To evaluate the physiologic effects of applying advice on mechanical ventilation by an open-loop, physiologic model-based clinical decision support system. DESIGN: Prospective, observational study. SETTING: University and Regional Hospitals' ICUs. PATIENTS: Varied adult ICU population. INTERVENTIONS: Advice were applied if accepted by physicians for a period of up to 4-8 hours. MEASUREMENTS AND MAIN RESULTS: Seventy-two patients were included for data analysis. Acceptance of advice was high with 95.7% of advice applied. In 41 patients in pressure support ventilation, following system advice led to significant decrease in PS, with PS reduced below 8 cm H2O in 15 patients (37%), a level not prohibiting extubation. Fraction of end-tidal CO2 values did not change, and increase in respiratory rate/VT was within clinical limits, indicating that in general, the system maintained appropriate patient breathing effort. In 31 patients in control mode ventilation, pressure control and tidal volume settings were decreased significantly, with tidal volume reduced below 8 mL/kg predicted body weight in nine patients (29%). Minute ventilation was maintained by a significant increase in respiratory rate. Significant reductions in FIO2 were seen on elevated baseline median values of 50% in both support and control mode-ventilated patients, causing clinically acceptable reductions in oxygen saturation. CONCLUSIONS: The results indicate that during a short period, the clinical decision support system provided appropriate suggestions of mechanical ventilation in a varied ICU population, significantly reducing ventilation to levels which might be considered safe and beneficial.

The effects of blood transfusion on red blood cell distribution width in critically ill patients: a pilot study.

BACKGROUND: Red blood cell distribution width (RDW) is a measure of anisocytosis, generally used in the differential diagnosis of anemia. Recently, RDW was associated with increased mortality in critically ill patients. Red blood cell (RBC) transfusions are potential confounders on RDW values interpretation. The aim of this study was to analyze the changes in RDW after RBC transfusion in intensive care unit (ICU) patients. STUDY DESIGN AND METHODS: This was a prospective, observational study including patients admitted to ICU requiring 1 RBC unit. We analyzed RDW values of the patients at four study points: before RBC transfusion (T1), immediately after transfusion (T2), 24 hours after transfusion (T3), and 48 hours after transfusion (T4). We also collected laboratory data from donors and RBC units. Changes of RDW (ΔRDW) were computed as the difference between baseline RDW value and RDW at each time point after transfusion. RESULTS: We enrolled 36 patients. RDW values increased after transfusion (p < 0.001 at all points vs. baseline), with the highest level at T3. At T3, 34 of 36 patients (94%) had an abnormal RDW value (vs. 26/36, 72%) at baseline (p = 0.023). The maximum ΔRDW for each patient was moderately correlated with the difference between mean corpuscular volume (MCV)donors and MCVpatient (r = 0.478, p = 0.005). Subgroups analysis showed that the maximum ΔRDW was greater in patients with baseline MCV lower than 80 fL or higher than 100 fL (n = 7) or baseline RDW of more than 14.5% (n = 19). CONCLUSION: RBC transfusion significantly increased RDW values. This intervention should be accurately reported in the studies evaluating the prognostic role of RDW.

Physiologic Evaluation of Ventilation Perfusion Mismatch and Respiratory Mechanics at Different Positive End-expiratory Pressure in Patients Undergoing Protective One-lung Ventilation.

BACKGROUND: Arterial oxygenation is often impaired during one-lung ventilation, due to both pulmonary shunt and atelectasis. The use of low tidal volume (VT) (5 ml/kg predicted body weight) in the context of a lung-protective approach exacerbates atelectasis. This study sought to determine the combined physiologic effects of positive end-expiratory pressure and low VT during one-lung ventilation. METHODS: Data from 41 patients studied during general anesthesia for thoracic surgery were collected and analyzed. Shunt fraction, high V/Q and respiratory mechanics were measured at positive end-expiratory pressure 0 cm H2O during bilateral lung ventilation and one-lung ventilation and, subsequently, during one-lung ventilation at 5 or 10 cm H2O of positive end-expiratory pressure. Shunt fraction and high V/Q were measured using variation of inspired oxygen fraction and measurement of respiratory gas concentration and arterial blood gas. The level of positive end-expiratory pressure was applied in random order and maintained for 15 min before measurements. RESULTS: During one-lung ventilation, increasing positive end-expiratory pressure from 0 cm H2O to 5 cm H2O and 10 cm H2O resulted in a shunt fraction decrease of 5% (0 to 11) and 11% (5 to 16), respectively (P < 0.001). The PaO2/FIO2 ratio increased significantly only at a positive end-expiratory pressure of 10 cm H2O (P < 0.001). Driving pressure decreased from 16 ± 3 cm H2O at a positive end-expiratory pressure of 0 cm H2O to 12 ± 3 cm H2O at a positive end-expiratory pressure of 10 cm H2O (P < 0.001). The high V/Q ratio did not change. CONCLUSIONS: During low VT one-lung ventilation, high positive end-expiratory pressure levels improve pulmonary function without increasing high V/Q and reduce driving pressure.

Variation of poorly ventilated lung units (silent spaces) measured by electrical impedance tomography to dynamically assess recruitment.

BACKGROUND: Assessing alveolar recruitment at different positive end-expiratory pressure (PEEP) levels is a major clinical and research interest because protective ventilation implies opening the lung without inducing overdistention. The pressure-volume (P-V) curve is a validated method of assessing recruitment but reflects global characteristics, and changes at the regional level may remain undetected. The aim of the present study was to compare, in intubated patients with acute hypoxemic respiratory failure (AHRF) and acute respiratory distress syndrome (ARDS), lung recruitment measured by P-V curve analysis, with dynamic changes in poorly ventilated units of the dorsal lung (dependent silent spaces [DSSs]) assessed by electrical impedance tomography (EIT). We hypothesized that DSSs might represent a dynamic bedside measure of recruitment. METHODS: We carried out a prospective interventional study of 14 patients with AHRF and ARDS admitted to the intensive care unit undergoing mechanical ventilation. Each patient underwent an incremental/decremental PEEP trial that included five consecutive phases: PEEP 5 and 10 cmH2O, recruitment maneuver + PEEP 15 cmH2O, then PEEP 10 and 5 cmH2O again. We measured, at the end of each phase, recruitment from previous PEEP using the P-V curve method, and changes in DSS were continuously monitored by EIT. RESULTS: PEEP changes induced alveolar recruitment as assessed by the P-V curve method and changes in the amount of DSS (p < 0.001). Recruited volume measured by the P-V curves significantly correlated with the change in DSS (rs = 0.734, p < 0.001). Regional compliance of the dependent lung increased significantly with rising PEEP (median PEEP 5 cmH2O = 11.9 [IQR 10.4-16.7] ml/cmH2O, PEEP 15 cmH2O = 19.1 [14.2-21.3] ml/cmH2O; p < 0.001), whereas regional compliance of the nondependent lung decreased from PEEP 5 cmH2O to PEEP 15 cmH2O (PEEP 5 cmH2O = 25.3 [21.3-30.4] ml/cmH2O, PEEP 15 cmH2O = 20.0 [16.6-22.8] ml/cmH2O; p <0.001). By increasing the PEEP level, the center of ventilation moved toward the dependent lung, returning to the nondependent lung during the decremental PEEP steps. CONCLUSIONS: The variation of DSSs dynamically measured by EIT correlates well with lung recruitment measured using the P-V curve technique. EIT might provide useful information to titrate personalized PEEP. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02907840 . Registered on 20 September 2016.

The effects of storage of red blood cells on the development of postoperative infections after noncardiac surgery.

BACKGROUND: Prolonged storage of red blood cells (RBCs) is a potential risk factor for postoperative infections. The objective of this study was to examine the effect of age of RBCs transfused on development of postoperative infection. STUDY DESIGN AND METHODS: In this prospective, double-blind randomized trial, 199 patients undergoing elective noncardiac surgery and requiring RBC transfusion were assigned to receive nonleukoreduced RBCs stored for not more than 14 days ("fresh blood" group, n = 101) or for more than 14 days ("old blood" group, n = 98). The primary outcome was occurrence of infection within 28 days after surgery; secondary outcomes were postoperative acute kidney injury (AKI), in-hospital and 90-day mortality, admission to intensive care unit, and hospital length of stay (LOS). As older blood was not always available, an "as-treated" (AT) analysis was also performed according to actual age of the RBCs transfused. RESULTS: The median [interquartile range] storage time of RBCs was 6 [5-10] and 15 [11-20] days in fresh blood and in old blood groups, respectively. The occurrence of postoperative infection did not differ between groups (fresh blood 22% vs. old blood 25%; relative risk [RR], 1.17; confidence interval [CI], 0.71-1.93), although wound infections occurred more frequently in old blood (15% vs. 5%; RR, 3.09; CI, 1.17- 8.18). Patients receiving older units had a higher rate of AKI (24% vs. 6%; p < 0.001) and, according to AT analysis, longer LOS (mean difference, 3.6 days; CI, 0.6-7.5). CONCLUSION: Prolonged RBC storage time did not increase the risk of postoperative infection. However, old blood transfusion increased wound infections rate and incidence of AKI.

Expiratory Flow Limitation as a Risk Factor for Pulmonary Complications After Major Abdominal Surgery.

BACKGROUND: Postoperative pulmonary complications are major causes of postoperative morbidity and mortality. Although several risk factors have been associated with postoperative pulmonary complications, they are not consistent between studies and, even in those studies in which these factors were identified, the predictive power is low. We hypothesized that postoperative pulmonary complications would correlate with the presence of intraoperative expiratory flow limitation. METHODS: Candidates for this prospective observational study were patients undergoing general anesthesia for major abdominal surgery. Preoperative data collection included age, body mass index, American Society of Anesthesiologists class, smoking and dyspnea history, and room air PO2. Expiratory flow limitation was assessed intraoperatively using the positive end-expiratory pressure test. Postoperative data collection included the incidence of postoperative pulmonary complications. RESULTS: Of the 330 patients we enrolled, 31% exhibited expiratory flow limitation. On univariate analysis, patients with expiratory flow limitation were more likely to have postoperative pneumonia (5% vs 0%, P < .001) and acute respiratory failure (11% vs 1%, P < .001) and a longer length of hospital stay (7 vs 9 days, P < .01). Multivariate analysis identified that expiratory flow limitation increased the risk of developing postoperative pulmonary complications by >50% (risk ratio, 2.7; 95% confidence interval, 1.7-4.2). Age and Medical Research Council dyspnea score were also significant multivariate risk factors for pulmonary complications. CONCLUSIONS: Our results show that intraoperative expiratory flow limitation correlates with that of postoperative pulmonary complication after major abdominal surgery. Further work is needed to better understand the relevance of expiratory flow limitation on postoperative pulmonary outcomes.

Can diaphragmatic ultrasonography performed during the T-tube trial predict weaning failure? The role of diaphragmatic rapid shallow breathing index.

BACKGROUND: The rapid shallow breathing index (RSBI), which is the ratio between respiratory rate (RR) and tidal volume (VT), is one of the most widely used indices to predict weaning outcome. Whereas the diaphragm plays a fundamental role in generating VT, in the case of diaphragmatic dysfunction the inspiratory accessory muscles may contribute. If this occurs during a weaning trial, delayed weaning failure is likely since the accessory muscles are more fatigable than the diaphragm. Hence, we hypothesised that the traditional RSBI could be implemented by substituting VT with the ultrasonographic evaluation of diaphragmatic displacement (DD). We named the new index the diaphragmatic-RSBI (D-RSBI). The aim of this study was to compare the ability of the traditional RSBI and D-RSBI to predict weaning failure in ready-to-wean patients. METHODS: We performed a prospective observational study. During a T-tube spontaneous breathing trial (SBT) we simultaneously evaluated right hemidiaphragm displacement (i.e., DD) by using M-mode ultrasonography as well as the RSBI. Outcome of the weaning attempt, length of mechanical ventilation, length of intensive care unit and hospital stay, and hospital mortality were recorded. Receiver operator characteristic (ROC) curves were used to evaluate the diagnostic accuracy of D-RSBI and RSBI. RESULTS: We enrolled 51 patients requiring mechanical ventilation for more than 48 h who were ready to perform a SBT. Most of the patients, 34 (66 %), were successfully weaned from mechanical ventilation. When considering the 17 patients that failed the weaning attempt, 11 (64 %) had to be reconnected to the ventilator during the SBT, three (18 %) had to be re-intubated within 48 h of extubation, and three (18 %) required non-invasive ventilation support within 48 h of extubation. The areas under the ROC curves for D-RSBI and RSBI were 0.89 and 0.72, respectively (P = 0.006). CONCLUSIONS: D-RSBI (RR/DD) was more accurate than traditional RSBI (RR/VT) in predicting the weaning outcome. TRIAL REGISTRATION: Our clinical trial was retrospectively registered with ClinicalTrials.gov (identifier: NCT02696018 ). ClinicalTrials.gov processed our record on 25 February 2016.

Fatigue in intensive care survivors one year after discharge.

BACKGROUND: Fatigue has not been investigated in long-term Intensive Care Unit (ICU) survivors. This study aimed to assess fatigue through a specific instrument, namely the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) scale, in ICU survivors one year after hospital discharge. A secondary aim was to compare the findings of FACIT-F with those of the Vitality domain (VT) of the 36-item Short-Form Health Survey (SF-36). METHODS: This prospective cohort study was performed on 56 adult patients with a Length Of Stay (LOS) in ICU longer than 72 h. At one year after hospital discharge, FACIT-F and SF-36 questionnaires were administered to consenting patients by direct interview. FACIT-F was measured as raw (range 0-52), and FACIT-F-trans value (range 0-100). Past medical history, and demographic and clinical ICU-related variables were collected. RESULTS: The patients' median age was 67.5, Simplified Acute Physiology Score II 31, and LOS in ICU 5 days. The median raw FACIT-F of the patients was 41, and Cronbach's α was 0.937. The correlation coefficient between FACIT-F-trans and VT of SF-36 was 0.660 (p < 0.001). Both FACIT-F and VT were related to dyspnoea scale (p = 0.01). A Bland-Altman plot of VT vs FACIT-F-trans showed a bias of -0.8 with 95 % limits of agreement from 35.7 to -34.1. The linear regression between differences and means was 0.639, suggesting a significant proportional bias. CONCLUSIONS: The 13-item FACIT-F questionnaire is valid to assess fatigue of long-term ICU survivors. VT of SF-36 relates to FACIT-F, but consists of only four items assessing two positive and two negative aspects. FACIT-F grasps the negative aspects of fatigue better than VT. Specific tools assess specific conditions better that general tools. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02684877 .

Evaluation of a protocol for vancomycin administration in critically patients with and without kidney dysfunction.

BACKGROUND: Administration of vancomycin in critically ill patients needs close regulation. While subtherapeutical vancomycin serum concentration (VSC) is associated with increased mortality, accumulation is responsible for nephrotoxicity. Our study aimed to estimate the efficacy of a vancomycin-dosing protocol in reaching appropriate serum concentration in patients with and without kidney dysfunction. METHODS: This was a retrospective study in critically ill patients treated with continuous infusion of vancomycin. Patients with creatinine clearance > 50 ml/min (Group A) were compared to those with creatinine clearance ≤ 50 ml/min (Group B). RESULTS: 348 patients were enrolled (210 in Group A, 138 in Group B). At first determination, patients with kidney dysfunction (Group B) had a statistically higher percentage of vancomycin in target range, while the percentage of patients with a VSC under the range was almost equal. These percentages differed at the subsequent measurements. The number of patients with low vancomycin concentration progressively decreased, except in those with augmented renal clearance; the percentage of patients with VSC over 30 mg/L was about 28 %, irrespective of the presence or absence of kidney dysfunction. Patients who reached a subtherapeutic level at the first VSC measurement had a significant correlation with in-hospital mortality. CONCLUSIONS: Our protocol seems to allow a rapid achievement of a target VSC particularly in patients with kidney dysfunction. In order to avoid subtherapeutical VSC, our algorithm should be implemented by the estimation of the presence of an augmented renal clearance.

Incidence and Determinants of Acute Kidney Injury after Prone Positioning in Severe COVID-19 Acute Respiratory Distress Syndrome.

(1) Background: Acute kidney injury (AKI) is common among critically ill COVID-19 patients, but its temporal association with prone positioning (PP) is still unknown, and no data exist on the possibility of predicting PP-associated AKI from bedside clinical variables. (2) Methods: We analyzed data from 93 COVID-19-related ARDS patients who underwent invasive mechanical ventilation (IMV) and at least one PP cycle. We collected hemodynamic variables, respiratory mechanics, and circulating biomarkers before, during, and after the first PP cycle. PP-associated AKI (PP-AKI) was defined as AKI diagnosed any time from the start of PP to 48 h after returning to the supine position. A t-test for independent samples was used to test for the differences between groups, while binomial logistical regression was performed to assess variables independently associated with PP-associated AKI. (3) Results: A total of 48/93 (52%) patients developed PP-AKI, with a median onset at 24 [13.5-44.5] hours after starting PP. No significant differences in demographic characteristics between groups were found. Before starting the first PP cycle, patients who developed PP-AKI had a significantly lower cumulative fluid balance (CFB), even when normalized for body weight (p = 0.006). Central venous pressure (CVP) values, measured before the first PP (OR 0.803, 95% CI [0.684-0.942], p = 0.007), as well as BMI (OR 1.153, 95% CI = [1.013-1.313], p = 0.031), were independently associated with the development of PP-AKI. In the multivariable regression analysis, a lower CVP before the first PP cycle was independently associated with ventilator-free days (OR 0.271, 95% CI [0.123-0.936], p = 0.011) and with ICU mortality (OR:0.831, 95% CI [0.699-0.989], p = 0.037). (4) Conclusions: Acute kidney injury occurs frequently in invasively ventilated severe COVID-19 ARDS patients undergoing their first prone positioning cycle. Higher BMI and lower CVP before PP are independently associated with the occurrence of AKI during prone positioning.

Effect of expiratory flow limitation on ventilation/perfusion mismatch and perioperative lung function during pneumoperitoneum and Trendelenburg position.

BACKGROUND: Laparoscopic surgery and Trendelenburg position may affect the respiratory function and alter the gas exchange. Further the reduction of the lung volumes may contribute to the development of expiratory flow limitation (EFL). The latter is associated with an increased risk of postoperative pulmonary complications. Our aim was to investigate the incidence of EFL and to evaluate its effect on pulmonary function and intraoperative V/Q mismatch. METHODS: This is a prospective study on patients undergoing elective laparoscopic gynecological surgery. We evaluated respiratory mechanics, V/Q mismatch and presence of EFL after anesthesia induction, during pneumoperitoneum and Trendelenburg position and at the end of surgery. Intraoperative gas exchange and hemodynamic were also recorded. Clinical data were collected until seven days after surgery to evaluate the onset of pulmonary postoperative complications (PPCs). RESULTS: Among the 66 patients enrolled, 25/66 (38%) exhibited EFL during surgery, of whom 10/66 (15%) after anesthesia induction, and the remaining 15 patients after pneumoperitoneum and Trendelenburg position. Median PEEP able to reverse flow limitation was 7 [7-10] cmH2O after anesthesia induction and 9 [8-15] cmH2O after pneumoperitoneum and Trendelenburg position. Patients with EFL had significantly higher shunt (17 [2-25] vs. 9 [1-19]; P=0.05), low V̇/Q̇ (27 [20-70] vs. 15 [10-22]; P=0.05) and high V̇/Q̇ (10 [7-14] vs. 6 [4-7]; P=0.024). At the end of surgery, only high V/Q was significantly higher in EFL patients. Further, they exhibited higher incidence of postoperative pulmonary complication (48% (12/25) vs. 15% (6/41), P=0.005), hypoxemia and hypercapnia (80% [20/25] vs. 32% [13/41]; P<0.001). CONCLUSIONS: Expiratory flow limitation is a common phenomenon during gynecological laparoscopic surgery associated with worsen gas exchange, increased V/Q mismatch and altered lung mechanics. Our study showed that patients experiencing EFL during surgery showed a higher risk for PPCs.

Pulmonary function and expiratory flow limitation in acute cervical spinal cord injury.

OBJECTIVE: To identify the nature of the changes of respiratory mechanics in patients with middle cervical spinal cord injury (SCI) and their correlation with posture. DESIGN: Clinical trial. SETTING: Acute SCI unit. PARTICIPANTS: Patients with SCI (N=34) at C4-5 level studied within 6 months of injury. INTERVENTIONS: Patients were assessed by the negative expiratory pressure test, maximal static respiratory pressure test, and standard spirometry. MAIN OUTCOME MEASURES: The following respiratory variables were recorded in both the semirecumbent and supine positions: (1) tidal expiratory flow limitation (TEFL); (2) airway resistances; (3) mouth occlusion pressure developed 0.1 seconds after occluded inspiration at functional residual capacity (P(0.1)); (4) maximal static inspiratory pressure (MIP) and maximal static expiratory pressure (MEP); and (5) spirometric data. RESULTS: TEFL was detected in 32% of the patients in the supine position and in 9% in the semirecumbent position. Airway resistances and P(0.1) were much higher compared with normative values, while MIP and MEP were markedly reduced. The ratio of forced expiratory volume in 1 second to forced vital capacity was less than 70%, while the other spirometric data were reduced up to 30% of predicted values. CONCLUSIONS: Patients with middle cervical SCI can develop TEFL. The presence of TEFL, associated with increased airway resistance, could increase the work of breathing in the presence of a reduced capacity of the respiratory muscles to respond to the increased load. The semirecumbent position and the use of continuous positive airway pressure can be helpful to (1) reduce the extent of TEFL and avoid the opening/closure of the small airways; (2) decrease airway resistance; and (3) maintain the expiratory flow as high as possible, which aids in the removal of secretions.