Can the values of the venous-to-arterial PCO2 difference (pCO2 gap) be negative?

In this manuscript, we discussed if it is physiologically sound that the difference between venous-to-arterial carbon dioxide partial pressure difference (pCO2 gap) can yield negative values.

Under-The-Nose Versus Over-The-Nose Face Mask to Prevent Facial Pressure Sores During Face Mask-Delivered Noninvasive Ventilation for Acute Hypercapnic Respiratory Failure: A Randomized Controlled Trial.

OBJECTIVES: To determine whether an under-the-nose face mask (FM) as the first-line interface strategy reduces the incidence of facial pressure sores with the same clinical improvement as the one obtained by standard over-the-nose face mask-noninvasive ventilation (FM-NIV) in patients with acute hypercapnic respiratory failure (AHRF). DESIGN: A multicenter, prospective randomized controlled study. SETTING: Two ICUs from two French tertiary hospitals. PATIENTS: A total of 108 patients needed NIV for AHRF. INTERVENTIONS: participants were randomized (1/1) to receive either the under-the-nose FM (intervention group) or the over-the-nose FM (control group). The primary endpoint was the reduction of facial pressure sores. Secondary endpoints included patients outcome, NIV failure (intubation or death), arterial blood gas improvement, and interface failure (the need to switch to a total face mask). MEASUREMENTS AND MAIN RESULTS: Despite less protective dressings in the intervention group ( n = 4, 5% vs n = 27, 51%; p < 0.001), pressure sores developed less frequently than in the control group ( n = 3, 5% vs n = 39, 74%; p < 0.001). Similar mortality, NIV failure, and arterial blood gas improvement occurred in the two groups. However, under-the-nose FM resulted in a higher interface failure rate than conventional FM ( n = 18, 33% vs n = 5, 9%; p = 0.004), mainly because of excessive unintentional air leaks ( n = 15, 83% vs n = 0, 0%; p < 0.001). CONCLUSIONS: In patients with AHRF, under-the-nose FM significantly reduced the incidence of facial pressure sores compared to the most commonly used first-line interface, the standard FM. However, with this new mask, excessive unintentional air leaks more often compelled the attending clinician to switch to another interface to pursue NIV.

Clinical outcomes of ceftolozane-tazobactam dosing in patients with sepsis undergoing renal replacement therapies.

Ceftolozane-tazobactam (C/T) recommended dosing in patients undergoing renal replacement therapies (RRT) is lacking evidence. The objective of this study was to evaluate the clinical outcomes of C/T dosing in patients on RRT. MATERIALS AND METHODS: A retrospective descriptive study conducted at our institution between May 1, 2017, and March 15, 2022. The primary endpoint was to determine the clinical cure for patients who received C/T for documented infection while on RRT. The secondary endpoints were the microbiologic cure, 30-day infection recurrence, and 30-day crude mortality. RESULTS: Of the 27 patients who met the inclusion criteria, 17 (63%) were males, median age was 69 (62 - 82) years, and weight 67 (57 - 79) kg. The majority of patients had pneumonia 19 (70.4%) followed by bacteremia 5 (18.5%). Multidrug resistant Pseudomonas spp. was the causative organism of infection in 22 subjects (81.5%). Clinical cure was achieved in 17 subjects (63%). Of the 14 subjects who had their culture repeated, 10 (71.4%) patients had microbiologic cure vs. 4 (28.5%) patients who had a microbiologic failure (p = 0.327). 30-day infection recurrence occurred in 6 (35.3%) patients of the clinical cure group and 2 (20%) patients in the clinical failure group (p = 0.362), while mortality occurred in 5 (29.4%) subjects vs. 7 (70%) in both groups, respectively (p = 0.049). The most frequently used doses of C/T were 1.5 g IV q8h while undergoing continuous venovenous hemodiafiltration and 0.75 g IV q8h while undergoing hemodialysis (p = 0.209). The median duration of therapy was 9 (4.5 - 13) days in the clinically cured group vs. 5 (3.75 - 5.5) days in those who had clinical failure (p = 0.038). There was no adverse event reported using these doses during the study period. CONCLUSION: The used doses of C/T in this study were higher than those approved by the U.S. FDA, while clinical success is uncertain. Larger outcomes and pharmacokinetics studies are needed to establish effective dosing and therapy duration.

Hypertriglyceridemia in Critically Ill Patients With SARS-CoV-2 Infection.

BACKGROUND: Patients with SARS-CoV-2 infection could develop severe disease requiring critical care admission. Case reports indicated high incidence of hypertriglyceridemia (HTG) in critically ill patients infected with SARS-CoV-2, which might be related to the drugs. OBJECTIVE: We sought to determine the risk factors associated with HTG in this population and to investigate the relationship between HTG and lipase. METHODS: A retrospective observational study was conducted at our hospital between March 1 and June 30, 2020. Patients were included if they were ≥18 years old, admitted to the intensive care unit (ICU), tested positive for SARS-CoV-2, and had triglycerides (TG) checked during their hospital stay. RESULTS: Of the 111 critically ill patients, 103 patients were included. Males comprised 88.3% of the sample. The median TG at baseline was 197.4 (IQR: 139.8-283) mg/dL. The lipase median level at baseline was 23.00 (IQR: 0.00-69.50) IU/L. The results of the mixed-effects logistic regression analysis indicated that patient-level variables, favipiravir use, blood glucose level, and propofol use were significantly associated with HTG. There was no relationship between lipase and TG levels over time. Furthermore, TG concentrations over time showed a similar trend to inflammatory markers. CONCLUSION AND RELEVANCE: The incidence of clinically significant HTG was high and was associated with propofol and favipiravir use. HTG might reflect the high inflammatory state in these patients. Clinicians should look at the full picture before changing therapies based only on HTG. Our findings need to be replicated in a larger prospective study.

Extravascular lung water levels are associated with mortality: a systematic review and meta-analysis.

BACKGROUND: The prognostic value of extravascular lung water (EVLW) measured by transpulmonary thermodilution (TPTD) in critically ill patients is debated. We performed a systematic review and meta-analysis of studies assessing the effects of TPTD-estimated EVLW on mortality in critically ill patients. METHODS: Cohort studies published in English from Embase, MEDLINE, and the Cochrane Database of Systematic Reviews from 1960 to 1 June 2021 were systematically searched. From eligible studies, the values of the odds ratio (OR) of EVLW as a risk factor for mortality, and the value of EVLW in survivors and non-survivors were extracted. Pooled OR were calculated from available studies. Mean differences and standard deviation of the EVLW between survivors and non-survivors were calculated. A random effects model was computed on the weighted mean differences across the two groups to estimate the pooled size effect. Subgroup analyses were performed to explore the possible sources of heterogeneity. RESULTS: Of the 18 studies included (1296 patients), OR could be extracted from 11 studies including 905 patients (464 survivors vs. 441 non-survivors), and 17 studies reported EVLW values of survivors and non-survivors, including 1246 patients (680 survivors vs. 566 non-survivors). The pooled OR of EVLW for mortality from eleven studies was 1.69 (95% confidence interval (CI) [1.22; 2.34], p < 0.0015). EVLW was significantly lower in survivors than non-survivors, with a mean difference of -4.97 mL/kg (95% CI [-6.54; -3.41], p < 0.001). The results regarding OR and mean differences were consistent in subgroup analyses. CONCLUSIONS: The value of EVLW measured by TPTD is associated with mortality in critically ill patients and is significantly higher in non-survivors than in survivors. This finding may also be interpreted as an indirect confirmation of the reliability of TPTD for estimating EVLW at the bedside. Nevertheless, our results should be considered cautiously due to the high risk of bias of many studies included in the meta-analysis and the low rating of certainty of evidence. Trial registration the study protocol was prospectively registered on PROSPERO: CRD42019126985.

Passive leg raising-induced changes in pulse pressure variation to assess fluid responsiveness in mechanically ventilated patients: a multicentre prospective observational study.

BACKGROUND: Passive leg raising-induced changes in cardiac index can be used to predict fluid responsiveness. We investigated whether passive leg raising-induced changes in pulse pressure variation (ΔPPVPLR) can also predict fluid responsiveness in mechanically ventilated patients. METHODS: In this multicentre prospective observational study, we included 270 critically ill patients on mechanical ventilation in whom volume expansion was indicated because of acute circulatory failure. We did not include patients with cardiac arrythmias. Cardiac index and PPV were measured before/during a passive leg raising test and before/after volume expansion. A volume expansion-induced increase in cardiac index of >15% defined fluid responsiveness. To investigate whether ΔPPVPLR can predict fluid responsiveness, we determined areas under the receiver operating characteristic curves (AUROCs) and grey zones for relative and absolute ΔPPVPLR. RESULTS: Of the 270 patients, 238 (88%) were on controlled mechanical ventilation with no spontaneous breathing activity and 32 (12%) were on pressure support ventilation. The median tidal volume was 7.1 (inter-quartile range [IQR], 6.6-7.6) ml kg-1 ideal body weight. One hundred sixty-four patients (61%) were fluid responders. Relative and absolute ΔPPVPLR predicted fluid responsiveness with an AUROC of 0.92 (95% confidence interval [95% CI], 0.88-0.95; P<0.001) each. The grey zone for relative and absolute ΔPPVPLR included 4.8% and 22.6% of patients, respectively. These results were not affected by ventilatory mode and baseline characteristics (type of shock, centre, vasoactive treatment). CONCLUSIONS: Passive leg raising-induced changes in pulse pressure variation accurately predict fluid responsiveness with a small grey zone in critically ill patients on mechanical ventilation. CLINICAL TRIAL REGISTRATION: NCT03225378.

Thromboelastography findings in critically ill COVID-19 patients.

The rate of venous and arterial thrombotic events among patients infected with severe acute respiratory syndrome coronavirus-2 (SAR-CoV-2) is high. This may be due to a hypercoagulable state induced by the severe inflammation that results from the SAR-CoV-2 infection. We aimed to determine hypercoagulable states' incidence based on thromboelastography study and its association with thrombotic events in critically ill patients with coronavirus disease 2019 (COVID-19). Fifty-two COVID-19 patients who had thromboelastography study were retrospectively included. All patients received pharmacologic thromboprophylaxis. The hypercoagulable state was observed in 16 patients (30.8%). Among them, maximum amplitude and a-angle were elevated in 75% and 25%, respectively. Reaction time and K were low in only 12.5% for both of them. Inflammatory and coagulation markers, as well as thromboprophylaxis regimens, were not associated with a hypercoagulable state. Fourteen patients (27%) experienced a total of 16 thrombotic events, including 8 (57%) deep venous thrombosis, 6 (43%) pulmonary embolism, and 2 (14.3%) arterial thrombosis. The hypercoagulable state was not significantly associated with thrombotic events. In summary, we observed a lower rate of hypercoagulable state on thromboelastography study in critically ill COVID-19 patients. Also, the hypercoagulable state was not associated with the occurrence of thrombotic events.

Central venous-to-arterial CO2 difference is a poor tool to predict adverse outcomes after cardiac surgery: a retrospective study.

PURPOSE: The venous-to-arterial carbon dioxide partial pressure difference (CO2 gap) has been reported to be a sensitive indicator of cardiac output adequacy. We aimed to assess whether the CO2 gap can predict postoperative adverse outcomes after cardiac surgery. METHODS: A retrospective study was conducted of 5,151 patients from our departmental database who underwent cardiac surgery from 1 January 2008 to 31 December 2018. Lactate level (mmol·L-1), central venous oxygen saturation (ScVO2) (%), and the venous-to-arterial carbon dioxide difference (CO2 gap) were measured at intensive care unit (ICU) admission and on days 1 and 2 after cardiac surgery. The following postoperative adverse outcomes were collected: ICU mortality, hemopericardium or tamponade, resuscitated cardiac arrest, acute kidney injury, major bleeding, acute hepatic failure, mesenteric ischemia, and pneumonia. The primary outcome was the presence of at least one postoperative adverse outcome. Logistic regression was used to assess the association between ScVO2, lactate, and the CO2 gap with adverse outcomes. Their diagnostic performance was compared using a receiver operating characteristic (ROC) curve. RESULTS: There were 1,933 patients (38%) with an adverse outcome. Cardiopulmonary bypass (CPB) parameters were similar between groups. The CO2 gap was slightly higher for the "adverse outcomes" group than for the "no adverse outcomes" group. Arterial lactate at admission, day 1, and day 2 was also slightly higher in patients with adverse outcomes. Central venous oxygen saturation was not significantly different between patients with and without adverse outcomes. The area under the ROC curve to predict outcomes after CPB for the CO2 gap at admission, day 1, and day 2 were 0.52, 0.55, and 0.53, respectively. CONCLUSION: After cardiac surgery with CPB, the CO2 gap at ICU admission, day 1, and day 2 was associated with postoperative adverse outcomes but showed poor diagnostic performance.

RéSUMé: OBJECTIF: La différence de pression partielle de dioxyde de carbone veineux versus artériel (gradient de CO2) a été rapportée comme étant un indicateur sensible d'un débit cardiaque adéquat. Nous avons tenté d'évaluer si le gradient de CO2 pouvait prédire les devenirs postopératoires défavorables après une chirurgie cardiaque. MéTHODE: Une étude rétrospective a été réalisée en se basant sur les dossiers de 5151 patients issus de notre base de données départementale ayant subi une chirurgie cardiaque entre le 1er janvier 2008 et le 31 décembre 2018. Les taux de lactate (mmol·L−1), la saturation en oxygène veineux central (ScVO2) (%), et la différence de dioxyde de carbone veineux versus artériel (gradient de CO2) ont été mesurés lors de l'admission en réanimation (ICU) et aux jours 1 et 2 après la chirurgie cardiaque. Les complications postopératoires suivantes ont été colligées : mortalité en réanimation, hémopéricarde ou tamponnade, arrêt cardiaque récupéré, insuffisance rénale aiguë, saignements majeurs, insuffisance hépatique aiguë, ischémie mésentérique et pneumonie. Le critère d'évaluation principal était la présence d'au moins une complication postopératoire. La régression logistique a été utilisée pour évaluer l'association entre ScVO2, taux de lactate et gradient de CO2 et les complications. Leur performance diagnostique a été comparée à l'aide d'une courbe ROC (receiver operating characteristic). RéSULTATS: Des complications sont survenues chez 1933 patients (38 %). Les paramètres de circulation extracorporelle (CEC) étaient semblables entre les groupes. Le gradient de CO2 était légèrement plus élevé dans le groupe « complications ¼ que dans le groupe « pas de complication ¼. Les taux de lactate artériels à l'admission, au jour 1 et au jour 2 étaient également légèrement plus élevés chez les patients ayant subi des complications. La différence de saturation en oxygène veineux central n'était pas significative entre les patients avec ou sans complications. L'aire sous la courbe ROC pour prédire les devenirs après la CEC pour le gradient de CO2 à l'admission, au jour 1 et au jour 2 était de 0,52, 0,55 et 0,53, respectivement. CONCLUSION: Après une chirurgie cardiaque avec CEC, le gradient de CO2 à l'admission en réanimation, au jour 1 et au jour 2 était associé aux complications postopératoires, mais sa performance diagnostique était médiocre.

Implications of Obesity for the Management of Severe Coronavirus Disease 2019 Pneumonia.

OBJECTIVES: To investigate patients' characteristics, management, and outcomes in the critically ill population admitted to the ICU for severe acute respiratory syndrome coronavirus disease 2019 pneumonia causing an acute respiratory distress syndrome. DESIGN: Retrospective case-control study. SETTING: A 34-bed ICU of a tertiary hospital. PATIENTS: The first 44 coronavirus disease 2019 acute respiratory distress syndrome patients were compared with a historical control group of 39 consecutive acute respiratory distress syndrome patients admitted to the ICU just before the coronavirus disease 2019 crisis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Obesity was the most frequent comorbidity exhibited by coronavirus disease 2019 patients (n = 32, 73% vs n = 11, 28% in controls; p < 0.001). Despite the same severity of illness and level of hypoxemia at admission, coronavirus disease 2019 patients failed more high flow oxygen via nasal cannula challenges (n = 16, 100% vs n = 5, 45% in controls; p = 0.002), were more often intubated (n = 44, 100% vs n = 22, 56% in controls; p < 0.001) and paralyzed (n = 34, 77% vs n = 3, 14% in controls; p < 0.001), required higher level of positive end-expiratory pressure (15 vs 8 cm H2O in controls; p < 0.001), more prone positioning (n = 33, 75% vs n = 6, 27% in controls; p < 0.001), more dialysis (n = 16, 36% vs n = 3, 8% in controls; p = 0.003), more hemodynamic support by vasopressors (n = 36, 82% vs n = 22, 56% in controls; p = 0.001), and had more often a prolonged weaning from mechanical ventilation (n = 28, 64% vs n = 10, 26% in controls; p < 0.01) resulting in a more frequent resort to tracheostomy (n = 18, 40.9% vs n = 2, 9% in controls; p = 0.01). However, an intensive management requiring more staff per patient for positioning coronavirus disease 2019 subjects (6 [5-7] vs 5 [4-5] in controls; p < 0.001) yielded the same ICU survival rate in the two groups (n = 34, 77% vs n = 29, 74% in controls; p = 0.23). CONCLUSIONS: In its most severe form, coronavirus disease 2019 pneumonia striked preferentially the vulnerable obese population, evolved toward a multiple organ failure, required prolonged mechanical ventilatory support, and resulted in a high workload for the caregivers.

Central Venous-to-Arterial PCO2 Difference and Central Venous Oxygen Saturation in the Detection of Extubation Failure in Critically Ill Patients.

OBJECTIVES: To evaluate the ability of central venous-to-arterial carbon dioxide pressure difference, central venous oxygen saturation, and the combination of these two parameters to detect extubation failure in critically ill patients. DESIGN: Multicentric, prospective, observational study. SETTING: Three ICUs. PATIENTS: All patients who received mechanical ventilation for more than 48 hours and tolerated spontaneous breathing trials with a T-piece for 60 minutes. INTERVENTIONS: Extubation after successful spontaneous breathing trials. Extubation failure was defined as the need for mechanical ventilation within 48 hours. MEASUREMENTS AND MAIN RESULTS: The oxygen delivery index, oxygen consumption index, central venous oxygen saturation, central venous-to-arterial carbon dioxide pressure difference, and oxygen extraction were measured immediately before spontaneous breathing trials and at 60 minutes after spontaneous breathing trials initiation. Seventy-five patients were enrolled, and extubation failure was noted in 18 (24%) patients. Oxygen consumption index increased significantly during spontaneous breathing trials in the failure group. Oxygen delivery index increased in both success and failure groups. Oxygen extraction increased in the failure group (p = 0.005) and decreased in the success group (p = 0.001). Central venous oxygen saturation decreased in the failure group and increased in the success group (p = 0.014). ΔPCO2 value increased in the extubation failure group and decreased in the success group (p = 0.002). Changes in ΔPCO2 (Δ - ΔPCO2) and central venous oxygen saturation (ΔScvO2) during spontaneous breathing trials were independently associated with extubation failure (odds ratio, 1.02; 95% CI, 1.01-1.05; p = 0.006, and odds ratio, 0.84; 95% CI, 0.70-0.95; p = 0.02, respectively). Δ - ΔPCO2 and central venous oxygen saturation could predict extubation failure with areas under the curve of 0.865 and 0.856, respectively; however, their combined areas under the curve was better at 0.940. CONCLUSIONS: We found that Δ - ΔPCO2 and central venous oxygen saturation, during spontaneous breathing trials, were independent predictors of weaning outcomes. Combination analysis of both parameters enhanced their diagnostic performance and provided excellent predictability in extubation failure detection in critically ill patients.

Thrombotic events following tocilizumab therapy in critically ill COVID-19 patients: a Façade for prognostic markers.

BACKGROUND: Hospitals in the Middle East Gulf region have experienced an influx of COVID-19 patients to their medical wards and intensive care units. The hypercoagulability of these patients has been widely reported on a global scale. However, many of the experimental treatments used to manage the various complications of COVID-19 have not been widely studied in this context. The effect of the current treatment protocols on patients' diagnostic and prognostic biomarkers may thus impact the validity of the algorithms adopted. CASE PRESENTATION: In this case series, we report four cases of venous thromboembolism and 1 case of arterial thrombotic event, in patients treated with standard or intensified prophylactic doses of unfractionated heparin or low molecular weight heparin at our institution. Tocilizumab has been utilized as an add-on therapy to the standard of care to treat patients with SARS-CoV-2 associated acute respiratory distress syndrome, in order to dampen the hyperinflammatory response. It is imperative to be aware that this drug may be masking the inflammatory markers (e.g. IL6, CRP, fibrinogen, and ferritin), without reducing the risk of thrombotic events in this population, creating instead a façade of an improved prognostic outcome. However, the D-dimer levels remained prognostically reliable in these cases, as they were not affected by the drug and continued to be at the highest level until event occurrence. CONCLUSIONS: In the setting of tocilizumab therapy, traditional prognostic markers of worsening infection and inflammation, and thus potential risk of acute thrombosis, should be weighed carefully as they may not be reliable for prognosis and may create a façade of an improved prognostic outcome insteasd. Additionally, the fact that thrombotic events continued to be observed despite decrease in inflammatory markers and the proactive anticoagulative approach adopted, raises more questions about the coagulative mechanisms at play in COVID-19, and the appropriate management strategy.

Central venous-to-arterial carbon dioxide partial pressure difference in early resuscitation from septic shock: a prospective observational study.

BACKGROUND: Central venous-to-arterial carbon dioxide partial pressure difference (ΔPCO2) can be used as a marker for the efficacy of venous blood in removing the total CO2 produced by the tissues. To date, this role of ΔPCO2 has been assessed only in patients after resuscitation from septic shock with already normalised central venous oxygen saturation (ScvO2 ≥70%). There are no reports on the behaviour of ΔPCO2 and its relationship to cardiac index (CI) and clinical outcome before normal ScvO2 has been achieved. OBJECTIVES: To investigate the behaviour of ΔPCO2 and its relationship to CI, blood lactate concentration and 28-day mortality during resuscitation in the very early phase of septic shock. To examine whether patients who normalise both ΔPCO2 and ScvO2 during the first 6  h of resuscitation will have a greater percentage decrease in blood lactate concentration than those who only achieve normal ScvO2. DESIGN: Prospective observational study. SETTING: Intensive Care Unit (ICU) in a university hospital. PATIENTS: Eighty patients with septic shock were consecutively recruited. INTERVENTIONS: Patients were resuscitated in accordance with the recommendations of the Surviving Sepsis Campaign. MAIN OUTCOME MEASURES: Blood lactate concentrations, and haemodynamic and oxygen-derived variables were obtained at ICU admission (T0) and 6  h after admission (T6). Lactate decrease was defined as the percentage decrease in lactate concentration from T0 to T6. All cause 28-day mortality was also recorded. RESULTS: Data are presented as median (interquartile range). At T0, there were significant differences (P < 0.0001) between normal (ΔPCO2 ≤0.8 kPa) and high ΔPCO2 groups for CI (3.9 [3.3 to 4.7] vs. 2.9 [2.3 to 3.1] l min m) and ScvO2 (73 [65 to 80] vs. 61 [53 to 63]%). The correlation between changes in CI and ΔPCO2 was r  =  -0.62, P < 0.0001. Patients who reached a normal ΔPCO2 at T6 had larger decreases in blood lactate concentration and Sequential Organ Failure Assessment scores on day 1. The lactate decrease was greatest in the subgroup achieving both normal ScvO2 and ΔPCO2 at T6. Lactate decrease, unlike ΔPCO2 and ScvO2, was an independent predictor of 28-day mortality. CONCLUSION: Monitoring ΔPCO2 may be a useful tool to assess the adequacy of tissue perfusion during resuscitation. The normalisation of both ΔPCO2 and ScvO2 is associated with a greater decrease in blood lactate concentration than ScvO2 alone. The lactate decrease is an independent predictor of 28-day mortality. Further research is needed to confirm this hypothesis.

Passive leg raising test induced changes in plethysmographic variability index to assess fluid responsiveness in critically ill mechanically ventilated patients with acute circulatory failure.

BACKGROUND: Passive leg raising (PLR) reliably predicts fluid responsiveness but requires a real-time cardiac index (CI) measurement or the presence of an invasive arterial line to achieve this effect. The plethysmographic variability index (PVI), an automatic measurement of the respiratory variation of the perfusion index, is non-invasive and continuously displayed on the pulse oximeter device. We tested whether PLR-induced changes in PVI (ΔPVIPLR) could accurately predict fluid responsiveness in mechanically ventilated patients with acute circulatory failure. METHODS: This was a secondary analysis of an observational prospective study. We included 29 mechanically ventilated patients with acute circulatory failure in this study. We measured PVI (Radical-7 device; Masimo Corp., Irvine, CA) and CI (Echocardiography) before and during a PLR test and before and after volume expansion of 500 mL of crystalloid solution. A volume expansion-induced increase in CI of >15% defined fluid responsiveness. To investigate whether ΔPVIPLR can predict fluid responsiveness, we determined areas under the receiver operating characteristic curves (AUROCs) and gray zones for ΔPVIPLR. RESULTS: Of the 29 patients, 27 (93.1%) received norepinephrine. The median tidal volume was 7.0 [IQR: 6.6-7.6] mL/kg ideal body weight. Nineteen patients (65.5%) were classified as fluid responders (increase in CI > 15% after volume expansion). Relative ΔPVIPLR accurately predicted fluid responsiveness with an AUROC of 0.89 (95%CI: 0.72-0.98, p < 0.001). A decrease in PVI ≤ -24.1% induced by PLR detected fluid responsiveness with a sensitivity of 95% (95%CI: 74-100%) and a specificity of 80% (95%CI: 44-97%). Gray zone was acceptable, including 13.8% of patients. The correlations between the relative ΔPVIPLR and changes in CI induced by PLR and by volume expansion were significant (r = -0.58, p < 0.001, and r = -0.65, p < 0.001; respectively). CONCLUSIONS: In sedated and mechanically ventilated ICU patients with acute circulatory failure, PLR-induced changes in PVI accurately predict fluid responsiveness with an acceptable gray zone. TRIAL REGISTRATION: ClinicalTrials.govNCT03225378.

Mean systemic filling pressure and venous return to assess the effects of passive leg raising and volume expansion in acute circulatory failure patients: a posthoc analysis of a multi-centre prospective study.

BACKGROUND: The main aim of the study was to investigate the behaviours of the mean systemic filling pressure (Pmsf), calculated by the mathematical method, and its derived variables of venous return after volume expansion (VE) and passive leg raising (PLR), with analysis according to fluid and PLR responsiveness. METHODS: This was a post-hoc analysis of a multicentre prospective study. We included 202 mechanically ventilated patients with acute circulatory failure. Pmsf, dVR (difference between Pmsf and central venous pressure [CVP]), and resistance to venous return (RVR) were calculated before/after PLR and before/after VE. Fluid- and PLR-responsiveness were defined according to the increase in cardiac index (CI) >15% after VE and >10% after PLR, respectively. RESULTS: Pmsf increased significantly after VE and PLR in both fluid and PLR-responder and non-responder groups. In fluid-responder patients, the increase in dVR was significantly higher than in non-responder group (1.5 [IQR:1.0-2.0] vs. 0.3 [IQR:-0.1-0.6] mmHg, p < 0.001) because of the larger increase in CVP relative to Pmsf in the non-responder group. The same findings were observed after PLR. RVR significantly decreased only in the fluid-responder and PLR-responder groups after VE and PLR. CONCLUSIONS: Venous return, derived from the mathematical model, increased in preload-dependent patients after VE and PLR because of the larger increases in Pmsf relative to CVP and the decreases in RVR. In preload-independent patients, VR did not change because of the larger rise in CVP compared to Pmsf after VE and PLR. These findings agree with the physiological model of circulation described by Guyton.

The Safety and Effectiveness of Apixaban in Patients with End-Stage Kidney Disease on Dialysis: A Retrospective Observational Study.

Background: Apixaban has been increasingly utilized for various FDA-approved indications, including stroke prevention and venous thromboembolism (VTE) treatment in patients with end stage kidney disease (ESKD) on hemodialysis. However, the safety and efficacy of its use in this population is not well established. Hence, the purpose of this study is to evaluate the safety and effectiveness of apixaban by examining outcomes in this population. Methods: This was a retrospective observational study that involved adults with ESKD who were on hemodialysis and prescribed apixaban from our hospital's outpatient pharmacy between 1 May 2015, and 31 March 2022. Demographics, apixaban indications, dose appropriateness, concomitant antiplatelet use, and comorbidities data were collected. Bleeding and thromboembolic events were also collected. Results: Sixty-six patients fulfilled the inclusion criteria, 50% of them males. Median age was 71 (63.5-82) years, and the median BMI 28.2 (59.5-86.25) kg/m2. The median follow-up time was 5 (1.9-12.3) months. Concomitant antiplatelet use (39.4%) and high medication adherence (84.8%) were observed. During follow-up, major bleeding events occurred in 15.2% of cases, with minor bleeding being more common (36.4%), and VTE and stroke events occurred in 4.5% of cases; appropriate dosing was prevalent (62.1%), and there was an overall all-cause mortality rate of 34.8%. Most patients received a 2.5 mg BID apixaban dose (56.1%), including both NVAF and VTE groups. Notably, the multivariate logistic regression analysis indicated that weight, and daily dose were insignificant predictors of bleeding events (p = 0.104, 0.591), however, the BMI was the main independent risk factor for bleeding in this population [OR = 0.9, 95% CI: 0.8-0.99; p = 0.023]. Conclusions: Our analysis of apixaban-treated ESKD patients highlights that the risk of bleeding is significant, and BMI was the main independent risk factor. A larger prospective study is needed to confirm our findings.

Clinical Outcomes of Trimethoprim/Sulfamethoxazole in Critically Ill Patients with Stenotrophomonas maltophilia Bacteremia and Pneumonia Utilizing Renal Replacement Therapies.

Background: The clinical outcomes of usual doses of Trimethoprim-sulfamethoxazole (TMP/SMZ) for treating S. maltophilia in critically ill patients on renal replacement therapies (RRT) have not been established. We sought to assess the clinical outcomes of TMP/SMZ in patients with sepsis utilizing RRT. Methods: A retrospective study was performed on all critically ill adult patients with S. maltophilia infections who received RRT between May 2015 and January 2022. The primary endpoint was clinical cure while the secondary endpoints were microbiologic cure, 30-day infection recurrence, and mortality. Results: Forty-five subjects met the inclusion criteria. The median age was 70.0 [interquartile range (IQR): 63.5-77] years, 57.8% were males, and the median body mass index was 25.7 [IQR: 22-30.2] kg/m2. Clinical success and failure were reported in 18 (40%) and 27 (60%) cases, respectively. There was no significant difference between the 30-day reinfection rates of both groups; however, mortality was significantly higher in the clinical failure group, involving 12 patients (44.4%), versus none in the clinical success group (p = 0.001). The median daily dose of TMP/SMZ upon continuous veno-venous hemofiltration was 1064 [IQR: 776-1380] mg in the clinical cure group vs. 768 [IQR:540-1200] mg in the clinical failure group (p = 0.035). Meanwhile, the median dose for those who received intermittent hemodialysis was 500 [IQR: 320-928] mg in the clinical success group compared to 640 [IQR: 360-1005] mg in the clinical failure group (p = 0.372). A total of 55% experienced thrombocytopenia, 42% hyperkalemia, and 2.2% neutropenia. The multivariable logistic regression analysis showed that the total daily dose at therapy initiation was the only independent factor associated with clinical success after adjusting for different variables including the body mass index [Odds ratio 1.004; 95% confidence interval: (1-1.007), p = 0.044]. Conclusions: Although the S. maltophilia isolates were reported as susceptible, TMP/SMZ with conventional doses to treat bacteremia and pneumonia in critically ill patients utilizing RRT was associated with high rates of clinical and microbiologic failure as well as with mortality. Larger outcomes and pharmacokinetics studies are needed to confirm our findings.

Consistency of data reporting in fluid responsiveness studies in the critically ill setting: the CODEFIRE consensus from the Cardiovascular Dynamic section of the European Society of Intensive Care Medicine.

PURPOSE: To provide consensus recommendations regarding hemodynamic data reporting in studies investigating fluid responsiveness and fluid challenge (FC) use in the intensive care unit (ICU). METHODS: The Executive Committee of the European Society of Intensive Care Medicine (ESICM) commissioned and supervised the project. A panel of 18 international experts and a methodologist identified main domains and items from a systematic literature, plus 2 ancillary domains. A three-step Delphi process based on an iterative approach was used to obtain the final consensus. In the Delphi 1 and 2, the items were selected with strong (≥ 80% of votes) or week agreement (70-80% of votes), while the Delphi 3 generated recommended (≥ 90% of votes) or suggested (80-90% of votes) items (RI and SI, respectively). RESULTS: We identified 5 main domains initially including 117 items and the consensus finally resulted in 52 recommendations or suggestions: 18 RIs and 2 SIs statements were obtained for the domain "ICU admission", 11 RIs and 1 SI for the domain "mechanical ventilation", 5 RIs for the domain "reason for giving a FC", 8 RIs for the domain pre- and post-FC "hemodynamic data", and 7 RIs for the domain "pre-FC infused drugs". We had no consensus on the use of echocardiography, strong agreement regarding the volume (4 ml/kg) and the reference variable (cardiac output), while weak on administration rate (within 10 min) of FC in this setting. CONCLUSION: This consensus found 5 main domains and provided 52 recommendations for data reporting in studies investigating fluid responsiveness in ICU patients.

Rescue therapy by switching to total face mask after failure of face mask-delivered noninvasive ventilation in do-not-intubate patients in acute respiratory failure.

OBJECTIVE: To evaluate the impact of switching to total face mask in cases where face mask-delivered noninvasive mechanical ventilation has already failed in do-not-intubate patients in acute respiratory failure. DESIGN AND SETTING: Prospective observational study in an ICU and a respiratory stepdown unit over a 12-month study period. INTERVENTION: Switching to total face mask, which covers the entire face, when noninvasive mechanical ventilation using facial mask (oronasal mask) failed to reverse acute respiratory failure. PATIENTS: Seventy-four patients with a do-not-intubate order and treated by noninvasive mechanical ventilation for acute respiratory failure. MAIN RESULTS: Failure of face mask-delivered noninvasive mechanical ventilation was associated with a three-fold increase in in-hospital mortality (36% vs. 10.5%; p = 0.009). Nevertheless, 23 out of 36 patients (64%) in whom face mask-delivered noninvasive mechanical ventilation failed to reverse acute respiratory failure and, therefore, switched to total face mask survived hospital discharge. Reasons for switching from facial mask to total face mask included refractory hypercapnic acute respiratory failure (n = 24, 66.7%), painful skin breakdown or facial mask intolerance (n = 11, 30%), and refractory hypoxemia (n = 1, 2.7%). In the 24 patients switched from facial mask to total face mask because of refractory hypercapnia, encephalopathy score (3 [3-4] vs. 2 [2-3]; p < 0.0001), PaCO2 (87 ± 25 mm Hg vs. 70 ± 17 mm Hg; p < 0.0001), and pH (7.24 ± 0.1 vs. 7.32 ± 0.09; p < 0.0001) significantly improved after 2 hrs of total face mask-delivered noninvasive ventilation. Patients switched early to total face mask (in the first 12 hrs) developed less pressure sores (n = 5, 24% vs. n = 13, 87%; p = 0.0002), despite greater length of noninvasive mechanical ventilation within the first 48 hrs (44 hrs vs. 34 hrs; p = 0.05) and less protective dressings (n = 2, 9.5% vs. n = 8, 53.3%; p = 0.007). The optimal cutoff value for face mask-delivered noninvasive mechanical ventilation duration in predicting facial pressure sores was 11 hrs (area under the receiver operating characteristic curve, 0.86 ± 0.04; 95% confidence interval 0.76-0.93; p < 0.0001; sensitivity, 84%; specificity, 71%). CONCLUSION: In patients in hypercapnic acute respiratory failure, for whom escalation to intubation is deemed inappropriate, switching to total face mask can be proposed as a last resort therapy when face mask-delivered noninvasive mechanical ventilation has already failed to reverse acute respiratory failure. This strategy is particularly adapted to provide prolonged periods of continuous noninvasive mechanical ventilation while preventing facial pressure sores.