Impact of positive end-expiratory pressure on renal resistive index in mechanical ventilated patients.

PURPOSE: Growing evidence shows the complex interaction between lung and kidney in critically ill patients. The renal resistive index (RRI) is a bedside measurement of the resistance of the renal blood flow and it is correlated with kidney injury. The positive end-expiratory pressure (PEEP) level could affect the resistance of renal blood flow, so we assumed that RRI could help to monitoring the changes in renal hemodynamics at different PEEP levels. Our hypothesis was that the RRI at ICU admission could predict the risk of acute kidney injury in mechanical ventilated critically ill patients. METHODS: We performed a prospective study including 92 patients requiring mechanical ventilation for ≥ 48 h. A RRI ≥ 0.70, was deemed as pathological. RRI was measured within 24 h from ICU admission while applying 5,10 and 15 cmH2O of PEEP in random order (PEEP trial). RESULTS: Overall, RRI increased from 0.62 ± 0.09 at PEEP 5 to 0.66 ± 0.09 at PEEP 15 (p < 0.001). The mean RRI value during the PEEP trial was able to predict the occurrence of AKI with AUROC = 0.834 [95%CI 0.742-0.927]. Patients exhibiting a RRI ≥ 0.70 were 17/92(18%) at PEEP 5, 28/92(30%) at PEEP 10, 38/92(41%) at PEEP 15, respectively. Thirty-eight patients (41%) exhibited RRI ≥ 0.70 at least once during the PEEP trial. In these patients, AKI occurred in 55% of the cases, versus 13% remaining patients, p < 0.001. CONCLUSIONS: RRI seems able to predict the risk of AKI in mechanical ventilated patients; further, RRI values are influenced by the PEEP level applied. TRIAL REGISTRATION: Clinical gov NCT03969914 Registered 31 May 2019.

Estimation of the transpulmonary pressure from the central venous pressure in mechanically ventilated patients.

Transpulmonary pressure (PL) calculation requires esophageal pressure (PES) as a surrogate of pleural pressure (Ppl), but its calibration is a cumbersome technique. Central venous pressure (CVP) swings may reflect tidal variations in Ppl and could be used instead of PES, but the interpretation of CVP waveforms could be difficult due to superposition of heartbeat-induced pressure changes. Thus, we developed a digital filter able to remove the cardiac noise to obtain a filtered CVP (f-CVP). The aim of the study was to evaluate the accuracy of CVP and filtered CVP swings (ΔCVP and Δf-CVP, respectively) in estimating esophageal respiratory swings (ΔPES) and compare PL calculated with CVP, f-CVP and PES; then we tested the diagnostic accuracy of the f-CVP method to identify unsafe high PL levels, defined as PL>10 cmH2O. Twenty patients with acute respiratory failure (defined as PaO2/FiO2 ratio below 200 mmHg) treated with invasive mechanical ventilation and monitored with an esophageal balloon and central venous catheter were enrolled prospectively. For each patient a recording session at baseline was performed, repeated if a modification in ventilatory settings occurred. PES, CVP and airway pressure during an end-inspiratory and -expiratory pause were simultaneously recorded; CVP, f-CVP and PES waveforms were analyzed off-line and used to calculate transpulmonary pressure (PLCVP, PLf-CVP, PLPES, respectively). Δf-CVP correlated better than ΔCVP with ΔPES (r = 0.8, p = 0.001 vs. r = 0.08, p = 0.73), with a lower bias in Bland Altman analysis in favor of PLf-CVP (mean bias - 0.16, Limits of Agreement (LoA) -1.31, 0.98 cmH2O vs. mean bias - 0.79, LoA - 3.14, 1.55 cmH2O). Both PLf-CVP and PLCVP correlated well with PLPES (r = 0.98, p < 0.001 vs. r = 0.94, p < 0.001), again with a lower bias in Bland Altman analysis in favor of PLf-CVP (0.15, LoA - 0.95, 1.26 cmH2O vs. 0.80, LoA - 1.51, 3.12, cmH2O). PLf-CVP discriminated high PL value with an area under the receiver operating characteristic curve 0.99 (standard deviation, SD, 0.02) (AUC difference = 0.01 [-0.024; 0.05], p = 0.48). In mechanically ventilated patients with acute respiratory failure, the digital filtered CVP estimated ΔPES and PL obtained from digital filtered CVP represented a reliable value of standard PL measured with the esophageal method and could identify patients with non-protective ventilation settings.

Dynamics of disease characteristics and clinical management of critically ill COVID-19 patients over the time course of the pandemic: an analysis of the prospective, international, multicentre RISC-19-ICU registry.

BACKGROUND: It remains elusive how the characteristics, the course of disease, the clinical management and the outcomes of critically ill COVID-19 patients admitted to intensive care units (ICU) worldwide have changed over the course of the pandemic. METHODS: Prospective, observational registry constituted by 90 ICUs across 22 countries worldwide including patients with a laboratory-confirmed, critical presentation of COVID-19 requiring advanced organ support. Hierarchical, generalized linear mixed-effect models accounting for hospital and country variability were employed to analyse the continuous evolution of the studied variables over the pandemic. RESULTS: Four thousand forty-one patients were included from March 2020 to September 2021. Over this period, the age of the admitted patients (62 [95% CI 60-63] years vs 64 [62-66] years, p < 0.001) and the severity of organ dysfunction at ICU admission decreased (Sequential Organ Failure Assessment 8.2 [7.6-9.0] vs 5.8 [5.3-6.4], p < 0.001) and increased, while more female patients (26 [23-29]% vs 41 [35-48]%, p < 0.001) were admitted. The time span between symptom onset and hospitalization as well as ICU admission became longer later in the pandemic (6.7 [6.2-7.2| days vs 9.7 [8.9-10.5] days, p < 0.001). The PaO2/FiO2 at admission was lower (132 [123-141] mmHg vs 101 [91-113] mmHg, p < 0.001) but showed faster improvements over the initial 5 days of ICU stay in late 2021 compared to early 2020 (34 [20-48] mmHg vs 70 [41-100] mmHg, p = 0.05). The number of patients treated with steroids and tocilizumab increased, while the use of therapeutic anticoagulation presented an inverse U-shaped behaviour over the course of the pandemic. The proportion of patients treated with high-flow oxygen (5 [4-7]% vs 20 [14-29], p < 0.001) and non-invasive mechanical ventilation (14 [11-18]% vs 24 [17-33]%, p < 0.001) throughout the pandemic increased concomitant to a decrease in invasive mechanical ventilation (82 [76-86]% vs 74 [64-82]%, p < 0.001). The ICU mortality (23 [19-26]% vs 17 [12-25]%, p < 0.001) and length of stay (14 [13-16] days vs 11 [10-13] days, p < 0.001) decreased over 19 months of the pandemic. CONCLUSION: Characteristics and disease course of critically ill COVID-19 patients have continuously evolved, concomitant to the clinical management, throughout the pandemic leading to a younger, less severely ill ICU population with distinctly different clinical, pulmonary and inflammatory presentations than at the onset of the pandemic.

Focus on renal blood flow in mechanically ventilated patients with SARS-CoV-2: a prospective pilot study.

Mechanically ventilated patients with ARDS due to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) seem particularly susceptible to AKI. Our hypothesis was that the renal blood flow could be more compromised in SARS-CoV-2 patients than in patients with "classical" ARDS. We compared the renal resistivity index (RRI) and the renal venous flow (RVF) in ARDS patients with SARS-CoV-2 and in ARDS patients due to other etiologies. Prospective, observational pilot study performed on 30 mechanically ventilated patients (15 with SARS-COV-2 ARDS and 15 with ARDS). Mechanical ventilation settings included constant-flow controlled ventilation, a tidal volume of 6 ml/kg of ideal body weight and the PEEP level titrated to the lowest driving pressure. Ultrasound Doppler measurements of RRI and RVF pattern were performed in each patient. Patients with SARS-COV-2 ARDS had higher RRI than patients with ARDS (0.71[0.67-0.78] vs 0.64[0.60-0.74], p = 0.04). RVF was not-continuous in 9/15 patients (71%) in the SARS-COV-2 ARDS group and in and 5/15 (33%) in the ARDS group (p = 0.27). A linear correlation was found between PEEP and RRI in patients with SARS-COV-2 ARDS (r2 = 0.31; p = 0.03) but not in patients with ARDS. Occurrence of AKI was 53% in patients with SARS-COV-2 ARDS and 33% in patients with ARDS (p = 0.46). We found a more pronounced impairment in renal blood flow in mechanically ventilated patients with SARS-COV-2 ARDS, compared with patients with "classical" ARDS.

Markers of endothelial and epithelial pulmonary injury in mechanically ventilated COVID-19 ICU patients.

BACKGROUND: Biomarkers can be used to detect the presence of endothelial and/or alveolar epithelial injuries in case of ARDS. Angiopoietin-2 (Ang-2), soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion protein-1 (VCAM-1), P-selectin and E-selectin are biomarkers of endothelial injury, whereas the receptor for advanced glycation end-products (RAGE) reflects alveolar epithelial injury. The aims of this study were to evaluate whether the plasma concentration of the above-mentioned biomarkers was different 1) in survivors and non-survivors of COVID-19-related ARDS and 2) in COVID-19-related and classical ARDS. METHODS: This prospective study was performed in two COVID-19-dedicated Intensive Care Units (ICU) and one non-COVID-19 ICU at Ferrara University Hospital. A cohort of 31 mechanically ventilated patients with COVID-19 ARDS and a cohort of 11 patients with classical ARDS were enrolled. Ang-2, ICAM-1, VCAM-1, P-selectin, E-selectin and RAGE were determined with a bead-based multiplex immunoassay at three time points: inclusion in the study (T1), after 7 ± 2 days (T2) and 14 ± 2 days (T3). The primary outcome was to evaluate the plasma trend of the biomarker levels in survivors and non-survivors. The secondary outcome was to evaluate the differences in respiratory mechanics variables and gas exchanges between survivors and non-survivors. Furthermore, we compared the plasma levels of the biomarkers at T1 in patients with COVID-19-related ARDS and classical ARDS. RESULTS: In COVID-19-related ARDS, the plasma levels of Ang-2 and ICAM-1 at T1 were statistically higher in non-survivors than survivors, (p = 0.04 and p = 0.03, respectively), whereas those of P-selectin, E-selectin and RAGE did not differ. Ang-2 and ICAM-1 at T1 were predictors of mortality (AUROC 0.650 and 0.717, respectively). At T1, RAGE and P-selectin levels were higher in classical ARDS than in COVID-19-related ARDS. Ang-2, ICAM-1 and E-selectin were lower in classical ARDS than in COVID-19-related ARDS (all p < 0.001). CONCLUSIONS: COVID-19 ARDS is characterized by an early pulmonary endothelial injury, as detected by Ang-2 and ICAM-1. COVID-19 ARDS and classical ARDS exhibited a different expression of biomarkers, suggesting different pathological pathways. Trial registration NCT04343053 , Date of registration: April 13, 2020.

Implications of early respiratory support strategies on disease progression in critical COVID-19: a matched subanalysis of the prospective RISC-19-ICU cohort.

BACKGROUND: Uncertainty about the optimal respiratory support strategies in critically ill COVID-19 patients is widespread. While the risks and benefits of noninvasive techniques versus early invasive mechanical ventilation (IMV) are intensely debated, actual evidence is lacking. We sought to assess the risks and benefits of different respiratory support strategies, employed in intensive care units during the first months of the COVID-19 pandemic on intubation and intensive care unit (ICU) mortality rates. METHODS: Subanalysis of a prospective, multinational registry of critically ill COVID-19 patients. Patients were subclassified into standard oxygen therapy ≥10 L/min (SOT), high-flow oxygen therapy (HFNC), noninvasive positive-pressure ventilation (NIV), and early IMV, according to the respiratory support strategy employed at the day of admission to ICU. Propensity score matching was performed to ensure comparability between groups. RESULTS: Initially, 1421 patients were assessed for possible study inclusion. Of these, 351 patients (85 SOT, 87 HFNC, 87 NIV, and 92 IMV) remained eligible for full analysis after propensity score matching. 55% of patients initially receiving noninvasive respiratory support required IMV. The intubation rate was lower in patients initially ventilated with HFNC and NIV compared to those who received SOT (SOT: 64%, HFNC: 52%, NIV: 49%, p = 0.025). Compared to the other respiratory support strategies, NIV was associated with a higher overall ICU mortality (SOT: 18%, HFNC: 20%, NIV: 37%, IMV: 25%, p = 0.016). CONCLUSION: In this cohort of critically ill patients with COVID-19, a trial of HFNC appeared to be the most balanced initial respiratory support strategy, given the reduced intubation rate and comparable ICU mortality rate. Nonetheless, considering the uncertainty and stress associated with the COVID-19 pandemic, SOT and early IMV represented safe initial respiratory support strategies. The presented findings, in agreement with classic ARDS literature, suggest that NIV should be avoided whenever possible due to the elevated ICU mortality risk.

Over time relationship between platelet reactivity, myocardial injury and mortality in patients with SARS-CoV-2-associated respiratory failure.

The aim of this study (NCT04343053) is to investigate the relationship between platelet activation, myocardial injury, and mortality in patients affected by Coronavirus disease 2019 (COVID-19). Fifty-four patients with respiratory failure due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were enrolled as cases. Eleven patients with the same clinical presentation, but negative for SARS-CoV-2 infection, were included as controls. Blood samples were collected at three different time points (inclusion [T1], after 7 ± 2 days [T2] and 14 ± 2 days [T3]). Platelet aggregation by light transmittance aggregometry and the circulating levels of soluble CD40 ligand (sCD40L) and P-selectin were measured. Platelet biomarkers did not differ between cases and controls, except for sCD40L which was higher in COVID-19 patients (p = .003). In COVID-19 patients, P-selectin and sCD40L levels decreased from T1 to T3 and were higher in cases requiring admission to intensive care unit (p = .004 and p = .008, respectively). Patients with myocardial injury (37%), as well as those who died (30%), had higher values of all biomarkers of platelet activation (p < .05 for all). Myocardial injury was an independent predictor of mortality. In COVID-19 patients admitted to hospital for respiratory failure, heightened platelet activation is associated with severity of illness, myocardial injury, and mortality.ClinicalTrials.gov number: NCT04343053.

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".

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.

Electrical impedance tomography in perioperative medicine: careful respiratory monitoring for tailored interventions.

BACKGROUND: Electrical impedance tomography (EIT) is a non-invasive radiation-free monitoring technique that provides images based on tissue electrical conductivity of the chest. Several investigations applied EIT in the context of perioperative medicine, which is not confined to the intraoperative period but begins with the preoperative assessment and extends to postoperative follow-up. MAIN BODY: EIT could provide careful respiratory monitoring in the preoperative assessment to improve preparation for surgery, during anaesthesia to guide optimal ventilation strategies and to monitor the hemodynamic status and in the postoperative period for early detection of respiratory complications. Moreover, EIT could further enhance care of patients undergoing perioperative diagnostic procedures. This narrative review summarizes the latest evidence on the application of this technique to the surgical patient, focusing also on possible future perspectives. CONCLUSIONS: EIT is a promising technique for the perioperative assessment of surgical patients, providing tailored adaptive respiratory and haemodynamic monitoring. Further studies are needed to address the current technological limitations, confirm the findings and evaluate which patients can benefit more from this technology.

Correction to: Electrical impedance tomography in perioperative medicine: careful respiratory monitoring for tailored interventions.

Following publication of the original article [1], the authors reported that one of the co-authors has a mistake in the author name; the middle name and surname are switched. This is the correct information.

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.

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.

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.

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.

The Underestimated Role of Platelets in Severe Infection a Narrative Review.

Beyond their role in hemostasis, platelets have emerged as key contributors in the immune response; accordingly, the occurrence of thrombocytopenia during sepsis/septic shock is a well-known risk factor of mortality and a marker of disease severity. Recently, some studies elucidated that the response of platelets to infections goes beyond a simple fall in platelets count; indeed, sepsis-induced thrombocytopenia can be associated with-or even anticipated by-several changes, including an altered morphological pattern, receptor expression and aggregation. Of note, alterations in platelet function and morphology can occur even with a normal platelet count and can modify, depending on the nature of the pathogen, the pattern of host response and the severity of the infection. The purpose of this review is to give an overview on the pathophysiological interaction between platelets and pathogens, as well as the clinical consequences of platelet dysregulation. Furthermore, we try to clarify how understanding the nature of platelet dysregulation may help to optimize the therapeutic approach.