Intubation Decision Based on Illness Severity and Mortality in COVID-19: An International Study.

OBJECTIVES: To evaluate the impact of intubation timing, guided by severity criteria, on mortality in critically ill COVID-19 patients, amidst existing uncertainties regarding optimal intubation practices. DESIGN: Prospective, multicenter, observational study conducted from February 1, 2020, to November 1, 2022. SETTING: Ten academic institutions in the United States and Europe. PATIENTS: Adults (≥ 18 yr old) confirmed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and hospitalized specifically for COVID-19, requiring intubation postadmission. Exclusion criteria included patients hospitalized for non-COVID-19 reasons despite a positive SARS-CoV-2 test. INTERVENTIONS: Early invasive mechanical ventilation (EIMV) was defined as intubation in patients with less severe organ dysfunction (Sequential Organ Failure Assessment [SOFA] < 7 or Pa o2 /F io2 ratio > 250), whereas late invasive mechanical ventilation (LIMV) was defined as intubation in patients with SOFA greater than or equal to 7 and Pa o2 /F io2 ratio less than or equal to 250. MEASUREMENTS AND MAIN RESULTS: The primary outcome was mortality within 30 days of hospital admission. Among 4464 patients, 854 (19.1%) required mechanical ventilation (mean age 60 yr, 61.7% male, 19.3% Black). Of those, 621 (72.7%) were categorized in the EIMV group and 233 (27.3%) in the LIMV group. Death within 30 days after admission occurred in 278 patients (42.2%) in the EIMV and 88 patients (46.6%) in the LIMV group ( p = 0.28). An inverse probability-of-treatment weighting analysis revealed a statistically significant association with mortality, with patients in the EIMV group being 32% less likely to die either within 30 days of admission (adjusted hazard ratio [HR] 0.68; 95% CI, 0.52-0.90; p = 0.008) or within 30 days after intubation irrespective of its timing from admission (adjusted HR 0.70; 95% CI, 0.51-0.90; p = 0.006). CONCLUSIONS: In severe COVID-19 cases, an early intubation strategy, guided by specific severity criteria, is associated with a reduced risk of death. These findings underscore the importance of timely intervention based on objective severity assessments.

Association between mean arterial pressure and sublingual microcirculation during major non-cardiac surgery: Post hoc analysis of a prospective cohort.

OBJECTIVE: To test the hypothesis that there is an association between mean arterial pressure (MAP) and sublingual perfusion during major surgery, and perhaps an identifiable harm threshold. METHODS: This post hoc analysis of a prospective cohort included patients who had elective major non-cardiac surgery with a duration of ≥2 h under general anesthesia. We assessed sublingual microcirculation every 30 min using SDF+ imaging and determined the De Backer score, Consensus Proportion of Perfused Vessels (Consensus PPV), and the Consensus PPV (small). Our primary outcome was the relationship between MAP and sublingual perfusion which was evaluated with linear mixed effects modeling. RESULTS: A total of 100 patients were included, with MAP ranging between 65 mmHg and 120 mmHg during anesthesia and surgery. Over a range of intraoperative MAPs between 65 and 120 mmHg, there were no meaningful associations between blood pressure and various measures of sublingual perfusion. There were also no meaningful changes in microcirculatory flow over 4.5 h of surgery. CONCLUSIONS: In patients having elective major non-cardiac surgery with general anesthesia, sublingual microcirculation is well maintained when MAP ranges between 65 and 120 mmHg. It remains possible that sublingual perfusion will be a useful marker of tissue perfusion when MAP is lower than 65 mmHg.

Effects of Etomidate on Postintubation Hypotension, Inflammatory Markers, and Mortality in Critically Ill Patients with COVID-19: An International, Multicenter, Retrospective Study.

OBJECTIVE: To evaluate the association of etomidate with postintubation hypotension, inflammation, and mortality in critically ill patients with COVID-19. DESIGN: International, multicenter, retrospective study. PARTICIPANTS: Critically ill patients hospitalized specifically for COVID-19 from three major academic institutions in the US and Europe. MAIN OUTCOME AND MEASURES: Patients were allocated into the etomidate (ET) group or another induction agent (OA) group. The primary outcome was postintubation hypotension. Secondary outcomes included postintubation inflammatory status, in-hospital mortality, and mortality at 30 days. RESULTS: 171 patients with a median age of 68 (IQR 58-73) years were included (ET, n = 98; OA, n = 73). Etomidate was associated with lower postintubation mean arterial pressure [74.33 (64-85) mm Hg versus 81.84 (69.75-94.25) mm Hg, p = 0.005] compared to other agents. No statistically significant differences were generally observed in inflammatory markers between the two groups at 7- and 14-days after admission to the intensive care unit. In-hospital mortality [77 (79%) versus 41 (56%), p = 0.003] and mortality at 30-days [78 (80%) versus 43 (59%), p = 0.006] were higher in the ET group. In multivariate logistic regression analysis, only etomidate (p = 0.009) and postintubation mean arterial pressure (p < 0.001) had a statistically significant effect on mortality, in contrast to stress-dose steroids (p = 0.301), after adjusting for creatinine (p = 0.695), blood urea nitrogen (p = 0.153), age (p = 0.055), oxygen saturation of hemoglobin (SpO2) (p = 0.941), and fraction of inspired oxygen (FiO2) (p = 0.712). CONCLUSIONS: Administration of a single-bolus dose of etomidate in critically ill patients with COVID-19 is associated with lower postintubation mean arterial pressure and higher in-hospital and 30-day mortality compared to other induction agents.

Circulating suPAR associates with severity and in-hospital progression of COVID-19.

BACKGROUND: COVID-19 disease progression is characterized by hyperinflammation and risk stratification may aid in early aggressive treatment and advanced planning. The aim of this study was to assess whether suPAR and other markers measured at hospital admission can predict the severity of COVID-19. METHODS: The primary outcome measure in this international, multi-centre, prospective, observational study with adult patients hospitalized primarily for COVID-19 was the association of WHO Clinical Progression Scale (WHO-CPS) with suPAR, ferritin, CRP, albumin, LDH, eGFR, age, procalcitonin, and interleukin-6. Admission plasma suPAR levels were determined using the suPARnostic® ELISA and suPARnostic® Turbilatex assays. RESULTS: Seven hundred and sixty-seven patients, 440 (57.4%) males and 327 (42.6%) females, were included with a median age of 64 years. Log-suPAR levels significantly correlated with WHO-CPS score, with each doubling of suPAR increasing the score by one point (p < .001). All the other markers were also correlated with WHO-CPS score. Admission suPAR levels were significantly lower in survivors (7.10 vs. 9.63, 95% CI 1.47-3.59, p < .001). A linear model (SALGA) including suPAR, serum albumin, serum lactate dehydrogenase, eGFR, and age can best estimate the WHO-CPS score and survival. Combining all five parameters in the SALGA model can improve the accuracy of discrimination with an AUC of 0.80 (95% CI: 0.759-0.836). CONCLUSIONS: suPAR levels significantly correlated with WHO-CPS score, with each doubling of suPAR increasing the score by one point. The SALGA model may serve as a quick tool for predicting disease severity and survival at admission.

Soluble Urokinase Receptor Levels Are Not Affected by the Systemic Inflammatory Response to Anesthesia and Operative Trauma.

INTRODUCTION: Soluble urokinase plasminogen activator receptor (suPAR) is an emerging biomarker of the level of chronic systemic inflammation and the general condition of the patient. We aimed to investigate the impact of general anesthesia and major surgery on perioperative suPAR and C-reactive protein (CRP) levels. METHODS: This study included patients undergoing elective major noncardiac surgery with an expected duration of ≥2 h under general anesthesia. Inclusion criteria were age ≥18 years and American Society of Anesthesiologists' physical status I-IV. Blood was drawn 30 min prior to induction of anesthesia (preoperatively), as well as 30 min after emergence from anesthesia (postoperatively). Plasma suPAR levels were determined using the suPARnostic® Quick Triage lateral flow assay. CRP measurements were performed by particle-enhanced immunoturbidimetric assay. RESULTS: The difference in preoperative and postoperative suPAR levels was not statistically significant (7.7 [5.28-10.4] ng/mL vs. 7.15 [5.68-9.8] ng/mL, p = 0.462). CRP levels increased significantly during surgery (0.81 [0.24-2.1] mg/dL vs. 5.76 [2.2-8.75] mg/dL, p < 0.001). No correlation was observed between CRP and suPAR levels, both preoperatively (rho = 0.127; p = 0.208) and postoperatively (rho = 0.017; p = 0.87). A statistically significant increase was also observed in postoperative white blood cell count (7.576 vs. 10.711, p < 0.001). CONCLUSION: General anesthesia and operative trauma did not affect perioperative suPAR levels despite the activation of systemic inflammatory response.

Video Laryngoscopy Improves Intubation Times With Level C Personal Protective Equipment in Novice Physicians: A Randomized Cross-Over Manikin Study.

BACKGROUND: The use of video laryngoscopes by novice physicians may improve first-pass success rates compared with direct laryngoscopy. OBJECTIVE: The aim of the present study was to assess whether time to intubation, number of laryngoscopy attempts, and first-pass success rate during laryngoscopy with the video laryngoscope or conventional Macintosh laryngoscope are affected by personal protective equipment (PPE) donning. METHODS: Seventy inexperienced physicians were randomly assigned to video laryngoscope or Macintosh groups and were instructed to perform intubation with both devices on a manikin, using PPE or a standard uniform. The primary outcomes were insertion time, number of laryngoscopy attempts, and first-pass success rates for each device with or without donning PPE. RESULTS: In the Macintosh group, significantly less time was needed for the first successful intubation without PPE vs. with PPE (12.17 ± 3.69 s vs. 24.07 ± 5.09 s, respectively; p < 0.0001). On the other hand, such difference was not observed in the video laryngoscope group (14.99 ± 3.01 s vs. 14.01 ± 3.35 s, respectively; p = 0.07). With PPE, the first-pass success rate was significantly higher in the video laryngoscope group [41 (58.6%) vs. 66 (94.3%), p < 0.001]. The use of the video laryngoscope resulted in a significant decrease in insertion time compared with the Macintosh blade (14.01 ± 3.35 s vs. 24.07 ± 5.09 s, respectively; p < 0.0001). CONCLUSION: First-pass success and insertion time with the video laryngoscope were not affected by PPE donning. However, both were negatively affected with the Macintosh laryngoscope.

Detection of Neuropathic Pain in End-Stage Cancer Patients: Diagnostic Accuracy of Two Questionnaires.

INTRODUCTION: Neuropathic pain is a frequent consequence of cancer pain. Quite often, in the end stage, it is difficult to discern its presence and delineate its characteristics in the context of painful cancer complications. The aim of this study was to compare the diagnostic accuracy of the Douleur Neuropathique en 4 Questions (DN4) and painDETECT questionnaires, which were translated to the patient's native language, for the diagnosis of peripheral neuropathic pain in oncology patients. METHODS: End-stage cancer patients who presented to the outpatient pain clinic were prospectively followed. At presentation, all patients completed the DN4 and painDETECT questionnaires, which had been translated to their native language, and the output was compared to the pain specialist's diagnosis of the neuropathic or non-neuropathic nature of the pain, which was considered as the gold standard. The diagnostic accuracy of both questionnaires was tested with receiver operating characteristic curves plotted from the data collected. RESULTS: Ninety patients (48.5% of 185 in total) presented with severe pain. Seventy-six had neuropathic pain (41.1%) and 109 had non-neuropathic pain. Of those with neuropathic pain, most had a mixed pain (bone or visceral in addition to neuropathic pain). The DN4 questionnaire had a sensitivity of 71.1% and a specificity of 88.7% in detecting neuropathic pain, with a cutoff value of ≥ 4, while the painDETECT questionnaire had a sensitivity of 26.3% and a specificity of 100%, with a cutoff value of ≥ 19. CONCLUSION: At standard cutoff values, the DN4 and painDETECT questionnaires, despite having been translated to the patient's native language, failed to adequately discriminate between neuropathic and non-neuropathic pain in our end-stage cancer patients.

Protease-Activated Receptors (PARs): Biology and Therapeutic Potential in Perioperative Stroke.

Perioperative stroke is a devastating complication that occurs during surgery or within 30 days following the surgical procedure. Its prevalence ranges from 0.08 to 10% although it is most likely an underestimation, as sedatives and narcotics can substantially mask symptomatology and clinical presentation. Understanding the underlying pathophysiology and identifying potential therapeutic targets are of paramount importance. Protease-activated receptors (PARs), a unique family of G-protein-coupled receptors, are widely expressed throughout the human body and play essential roles in various physiological and pathological processes. This review elucidates the biology and significance of PARs, outlining their diverse functions in health and disease, and their intricate involvement in cerebrovascular (patho)physiology and neuroprotection. PARs exhibit a dual role in cerebral ischemia, which underscores their potential as therapeutic targets to mitigate the devastating effects of stroke in surgical patients.

The use of mean circulatory filling pressure analogue for monitoring hemodynamic coherence: A post-hoc analysis of the SPARSE data and proof-of-concept study.

BACKGROUND: Dissociation between macrocirculation and microcirculation is often observed in surgical patients. OBJECTIVE: To test the hypothesis that the analogue of mean circulatory filling pressure (Pmca) can monitor hemodynamic coherence during major non-cardiac surgery. METHODS: In this post-hoc analysis and proof-of-concept study, we used the central venous pressure (CVP), mean arterial pressure (MAP), and cardiac output (CO) to calculate Pmca. Efficiency of the heart (Eh), arterial resistance (Rart), effective arterial elastance (Ea), venous compartment resistance (Rven), oxygen delivery (DO2), and oxygen extraction ratio (O2ER) were also calculated. Sublingual microcirculation was assessed using SDF + imaging, and the De Backer score, Consensus Proportion of Perfused Vessels (Consensus PPV), and Consensus PPV (small) were determined. RESULTS: Thirteen patients were included, with a median age of 66 years. Median Pmca was 16 (14.9-18) mmHg and was positively associated with CO [p < 0.001; a 1 mmHg increase in Pmca increases CO by 0.73 L  min-1 (p < 0.001)], Eh (p < 0.001), Rart (p = 0.01), Ea (p = 0.03), Rven (p = 0.005), DO2 (p = 0.03), and O2ER (p = 0.02). A significant correlation was observed between Pmca and Consensus PPV (p = 0.02), but not with De Backer Score (p = 0.34) or Consensus PPV (small) (p = 0.1). CONCLUSION: Significant associations exist between Pmca and several hemodynamic and metabolic variables including Consensus PPV. Adequately powered studies should determine whether Pmca can provide real-time information on hemodynamic coherence.

The Relation of Calculated Plasma Volume Status to Sublingual Microcirculatory Blood Flow and Organ Injury.

BACKGROUND: The calculated plasma volume status (cPVS) was validated as a surrogate of intravascular filling. The aim of this study is to assess the cPVS in relation to sublingual perfusion and organ injury. METHODS: Pre- and postoperative cPVS were obtained by determining the actual and ideal plasma volume levels in surgical patients. The sublingual microcirculation was assessed using SDF imaging, and we determined the De Backer score, the Consensus Proportion of Perfused Vessels (Consensus PPV), and the Consensus PPV (small). Our primary outcome was the assessment of the distribution of cPVS and its association with intraoperative sublingual microcirculation and postoperative complications. RESULTS: The median pre- and postoperative cPVS were -7.25% (IQR -14.29--1.88) and -0.4% (IQR -5.43-6.06), respectively (p < 0.001). The mean intraoperative administered fluid volume was 2.5 ± 2.5 L (1.14 L h-1). No statistically significant correlation was observed between the pre- or postoperative cPVS and sublingual microcirculation variables. Higher preoperative (OR = 1.04, p = 0.098) and postoperative cPVS (OR = 1.057, p = 0.029) were associated with postoperative organ injury and complications (sepsis (30%), anemia (24%), respiratory failure (13%), acute kidney injury (6%), hypotension (6%), stroke (3%)). CONCLUSIONS: The calculated PVS was associated with an increased risk of organ injury and complications in this cohort.

Effects of Vasopressin Receptor Agonists during the Resuscitation of Hemorrhagic Shock: A Systematic Review and Meta-Analysis of Experimental and Clinical Studies.

BACKGROUND: The clinical impact of vasopressin in hemorrhagic shock remains largely unknown. OBJECTIVE: This systematic review and meta-analysis was designed to investigate the effects of vasopressin receptor agonists during the resuscitation of hemorrhagic shock. METHODS: A systematic search of PubMed (MEDLINE), Scopus, and PubMed Central was conducted for relevant articles. Experimental (animal) and clinical studies were included. The primary objective was to investigate the correlation of vasopressin receptor agonist use with mortality and various hemodynamic parameters. RESULTS: Data extraction was possible in thirteen animal studies and two clinical studies. Differences in risk of mortality between patients who received a vasopressin receptor agonist were not statistically significant when compared to those who were not treated with such agents [RR (95% CI): 1.17 (0.67, 2.08); p = 0.562; I2 = 50%]. The available data were insufficient to conduct a meta-analysis assessing the effect of vasopressin receptor agonists on hemodynamics. Drawing safe conclusions from animal studies was challenging, due to significant heterogeneity in terms of species and dosage of vasopressin receptor agonists among studies. CONCLUSIONS: Differences in risk of mortality between patients who received a vasopressin receptor agonist were not statistically significant when compared to those who were not treated with such agents after hemorrhagic shock. More data are needed to deduce certain conclusions.

Assessment of Dynamic Changes in Stressed Volume and Venous Return during Hyperdynamic Septic Shock.

The present work investigated the dynamic changes in stressed volume (Vs) and other determinants of venous return using a porcine model of hyperdynamic septic shock. Septicemia was induced in 10 anesthetized swine, and fluid challenges were started after the diagnosis of sepsis-induced arterial hypotension and/or tissue hypoperfusion. Norepinephrine infusion targeting a mean arterial pressure (MAP) of 65 mmHg was started after three consecutive fluid challenges. After septic shock was confirmed, norepinephrine infusion was discontinued, and the animals were left untreated until cardiac arrest occurred. Baseline Vs decreased by 7% for each mmHg decrease in MAP during progression of septic shock. Mean circulatory filling pressure (Pmcf) analogue (Pmca), right atrial pressure, resistance to venous return, and efficiency of the heart decreased with time (p < 0.001 for all). Fluid challenges did not improve hemodynamics, but noradrenaline increased Vs from 107 mL to 257 mL (140%) and MAP from 45 mmHg to 66 mmHg (47%). Baseline Pmca and post-cardiac arrest Pmcf did not differ significantly (14.3 ± 1.23 mmHg vs. 14.75 ± 1.5 mmHg, p = 0.24), but the difference between pre-arrest Pmca and post-cardiac arrest Pmcf was statistically significant (9.5 ± 0.57 mmHg vs. 14.75 ± 1.5 mmHg, p < 0.001). In conclusion, the baseline Vs decreased by 7% for each mmHg decrease in MAP during progression of hyperdynamic septic shock. Significant changes were also observed in other determinants of venous return. A new physiological intravascular volume existing at zero transmural distending pressure was identified, termed as the rest volume (Vr).

Sublingual microcirculatory alterations during the immediate and early postoperative period: A systematic review and meta-analysis.

BACKGROUND: The incidence of postoperative microcirculatory flow alterations and their effect on outcome have not been studied extensively. OBJECTIVE: This systematic review and meta-analysis were designed to investigate the presence of sublingual microcirculatory flow alterations during the immediate and early postoperative period and their correlation with complications and survival. METHODS: A systematic search of PubMed, Scopus, Embase, PubMed Central, and Google Scholar was conducted for relevant articles from January 2000 to March 2021. Eligibility criteria were randomized controlled and non-randomized trials. Case reports, case series, review papers, animal studies and non-English literature were excluded. The primary outcome was the assessment of sublingual microcirculatory alterations during the immediate and early postoperative period in adult patients undergoing surgery. Risk of bias was assessed with the Ottawa-Newcastle scale. Standard meta-analysis methods (random-effects models) were used to assess the difference in microcirculation variables. RESULTS: Thirteen studies were included. No statistically significant difference was found between preoperative and postoperative total vessel density (p = 0.084; Standardized Mean Difference (SMD): -0.029; 95%CI: -0.31 to 0.26; I2 = 22.55%). Perfused vessel density significantly decreased postoperatively (p = 0.035; SMD: 0.344; 95%CI: 0.02 to 0.66; I2 = 65.66%), while perfused boundary region significantly increased postoperatively (p = 0.031; SMD: -0.415; 95%CI: -0.79 to -0.03; I2 = 37.21%). Microvascular flow index significantly decreased postoperatively (p = 0.028; SMD: 0.587; 95%CI: 0.06 to 1.11; I2 = 86.09%), while no statistically significant difference was found between preoperative and postoperative proportion of perfused vessels (p = 0.089; SMD: 0.53; 95%CI: -0.08 to 1.14; I2 = 70.71%). The results of the non-cardiac surgery post-hoc analysis were comparable except that no statistically significant difference in perfused vessel density was found (p = 0.69; SMD: 0.07; 95%CI: -0.26 to 0.39; I2 = 0%). LIMITATIONS: The included studies investigate heterogeneous groups of surgical patients. There were no randomized controlled trials. CONCLUSIONS: Significant sublingual microcirculatory flow alterations are present during the immediate and early postoperative period. Further research is required to estimate the correlation of sublingual microcirculatory flow impairment with complications and survival.

Microcirculation-guided treatment improves tissue perfusion and hemodynamic coherence in surgical patients with septic shock.

PURPOSE: Severe sepsis and septic shock may impair microcirculatory perfusion and cause organ dysfunction. The aim of this pilot study was to assess a new microcirculation-guided resuscitation strategy in patients with septic shock undergoing emergency abdominal surgery. METHODS: A microcirculation-guided treatment algorithm was developed and applied intraoperatively following restoration of systemic hemodynamics. Sublingual microcirculation was monitored with Sidestream DarkField (SDF +) imaging technique. The primary objective was to investigate the change in De Backer score, Consensus Proportion of Perfused Vessels (Consensus PPV), and Consensus PPV (small) and its association with venous-to-arterial carbon dioxide difference (v-aPCO2). RESULTS: Thirteen consecutive patients were included in the study. Microcirculation-guided resuscitation resulted in an increase of 0.49 mm-1 in the De Backer score (p < 0.001), an increase of 2.28% in the Consensus PPV (p < 0.001), and an increase of 2.26% in the Consensus PPV (small) (p < 0.001) for every 30 min of additional intraoperative time. All microcirculation variables were negatively correlated with v-aPCO2 (rho = - 0.656, adj-p < 0.001; rho = - 0.623; adj-p < 0.001; rho = - 0.597, adj-p < 0.001, respectively) at each intraoperative time point. Lactate levels were negatively correlated with Consensus PPV (rho = - 0.464; adj-p = 0.002) and Consensus PPV (small) (rho = - 0.391, adj-p < 0.001). Survival at 30 days, 90 days, and 1 year were 76.9%, 76.9%, and 61.5%, respectively. CONCLUSIONS: The intraoperative use of microcirculation-guided resuscitation strategy may improve tissue perfusion and hemodynamic coherence in patients with septic shock.

Determinants of venous return in steady-state physiology and asphyxia-induced circulatory shock and arrest: an experimental study.

BACKGROUND: Mean circulatory filling pressure (Pmcf) provides information on stressed volume and is crucial for maintaining venous return. This study investigated the Pmcf and other determinants of venous return in dysrhythmic and asphyxial circulatory shock and arrest. METHODS: Twenty Landrace/Large-White piglets were allocated into two groups of 10 animals each. In the dysrhythmic group, ventricular fibrillation was induced with a 9 V cadmium battery, while in the asphyxia group, cardiac arrest was induced by stopping and disconnecting the ventilator and clamping the tracheal tube at the end of exhalation. Mean circulatory filling pressure was calculated using the equilibrium mean right atrial pressure at 5-7.5 s after the onset of cardiac arrest and then every 10 s until 1 min post-arrest. Successful resuscitation was defined as return of spontaneous circulation (ROSC) with a MAP of at least 60 mmHg for a minimum of 5 min. RESULTS: After the onset of asphyxia, a ΔPmca increase of 0.004 mmHg, 0.01 mmHg, and 1.26 mmHg was observed for each mmHg decrease in PaO2, each mmHg increase in PaCO2, and each unit decrease in pH, respectively. Mean Pmcf value in the ventricular fibrillation and asphyxia group was 14.81 ± 0.5 mmHg and 16.04 ± 0.6 mmHg (p < 0.001) and decreased by 0.031 mmHg and 0.013 mmHg (p < 0.001), respectively, for every additional second passing after the onset of cardiac arrest. With the exception of the 5-7.5 s time interval, post-cardiac arrest right atrial pressure was significantly higher in the asphyxia group. Mean circulatory filling pressure at 5 to 7.5 s after cardiac arrest predicted ROSC in both groups, with a cut-off value of 16 mmHg (AUC = 0.905, p < 0.001). CONCLUSION: Mean circulatory filling pressure was higher in hypoxic hypercapnic conditions and decreased at a lower rate after cardiac arrest compared to normoxemic and normocapnic state. A Pmcf cut-off point of 16 mmHg at 5-7.5 s after cardiac arrest can highly predict ROSC.

Elevated preoperative suPAR is a strong and independent risk marker for postoperative complications in patients undergoing major noncardiac surgery (SPARSE).

BACKGROUND: Patients undergoing major surgery are often at risk of developing postoperative complications. We investigated whether a preoperative marker of chronic inflammation, soluble urokinase plasminogen activator receptor, can aid in identifying patients at high risk for postoperative complications, morbidity, and mortality. METHODS: In this prospective observational study (ClinicalTrials.gov identifier: NCT03851965), EDTA blood was collected from consecutive adult White patients scheduled for major noncardiac surgery with expected duration ≥2 hours under general anesthesia. Inclusion criteria were age ≥18 years and American Society of Anesthesiologists physical status I to IV. Plasma soluble urokinase plasminogen activator receptor levels were determined using the suPARnostic quick triage lateral flow assay. The primary endpoint was postoperative complications defined as presence of any complication and/or admission to intensive care unit and/or mortality within the first 90 postoperative days. RESULTS: Preoperative soluble urokinase plasminogen activator receptor had an odds ratio of 1.50 (95% confidence interval: 1.24-1.82) for every ng/mL increase. When including age, sex, American Society of Anesthesiologists score, C-reactive protein, and grouped soluble urokinase plasminogen activator receptor in multivariate analysis, patients with soluble urokinase plasminogen activator receptor between 5.5 and 10 ng/mL had an odds ratio of 11.2 (confidence interval: 3.1-40.8) and patients with soluble urokinase plasminogen activator receptor >10 ng/mL had an odds ratio of 19.9 (95% confidence interval: 4.3-92.9) compared to patients with soluble urokinase plasminogen activator receptor ≤5.5 ng/mL, respectively. Receiver operating characteristic analysis of soluble urokinase plasminogen activator receptor showed an area under the curve of 0.82 (confidence interval: 0.72-0.91). Receiver operating characteristic analysis combining age, sex, C-reactive protein levels, and American Society of Anesthesiologists score and had an area under the curve of 0.71 (95% confidence interval: 0.61-0.82). Adding soluble urokinase plasminogen activator receptor to this model increased the area under the curve to 0.83 (95% confidence interval: 0.74-0.92) (P = .033). CONCLUSION: Preoperative soluble urokinase plasminogen activator receptor provided strong and independent predictive value on postoperative complications in White patients undergoing major noncardiac surgery.

Blood Biomarkers and Metabolomic Profiling for the Early Diagnosis of Vancomycin-Associated Acute Kidney Injury: A Systematic Review and Meta-Analysis of Experimental Studies.

BACKGROUND: several blood-based biomarkers have been proposed for predicting vancomycin-associated kidney injury (VIKI). However, no systematic analysis has compared their prognostic value. OBJECTIVE: this systematic review and meta-analysis was designed to investigate the role of blood biomarkers and metabolomic profiling as diagnostic and prognostic predictors in pre-clinical studies of VIKI. METHODS: a systematic search of PubMed was conducted for relevant articles from January 2000 to May 2022. Animal studies that administered vancomycin and studied VIKI were eligible for inclusion. Clinical studies, reviews, and non-English literature were excluded. The primary outcome was to investigate the relationship between the extent of VIKI as measured by blood biomarkers and metabolomic profiling. Risk of bias was assessed with the CAMARADES checklist the SYRCLE's risk of bias tool. Standard meta-analysis methods (random-effects models) were used. RESULTS: there were four studies for the same species, dosage, duration of vancomycin administration and measurement only for serum creatine and blood urea nitrogen in rats. A statistically significant increase was observed between serum creatinine in the vancomycin group compared to controls (pooled p = 0.037; Standardized Mean Difference: 2.93; 95% CI: 0.17 to 5.69; I2 = 92.11%). Serum BUN levels were not significantly different between control and vancomycin groups (pooled p = 0.11; SMD: 3.05; 95% CI: 0.69 to 6.8; I2 = 94.84%). We did not identify experimental studies using metabolomic analyses in animals with VIKI. CONCLUSIONS: a total of four studies in rodents only described outcomes of kidney injury as defined by blood biomarkers. Blood biomarkers represented included serum creatinine and BUN. Novel blood biomarkers have not been explored.

Association of Preoperative Basal Inflammatory State, Measured by Plasma suPAR Levels, with Intraoperative Sublingual Microvascular Perfusion in Patients Undergoing Major Non-Cardiac Surgery.

It remains unknown whether chronic systemic inflammation is associated with impaired microvascular perfusion during surgery. We evaluated the association between the preoperative basal inflammatory state, measured by plasma soluble urokinase-type plasminogen activator receptor (suPAR) levels, and intraoperative sublingual microcirculatory variables in patients undergoing major non-cardiac surgery. Plasma suPAR levels were determined in 100 non-cardiac surgery patients using the suPARnostic® quick triage lateral flow assay. We assessed sublingual microcirculation before surgical incision and every 30 min during surgery using Sidestream Darkfield (SDF+) imaging and determined the De Backer score, the Consensus Proportion of Perfused Vessels (Consensus PPV), and the Consensus PPV (small). Elevated suPAR levels were associated with lower intraoperative De Backer score, Consensus PPV, and Consensus PPV (small). For each ng mL−1 increase in suPAR, De Backer score, Consensus PPV, and Consensus PPV (small) decreased by 0.7 mm−1, 2.5%, and 2.8%, respectively, compared to baseline. In contrast, CRP was not significantly correlated with De Backer score (r = −0.034, p = 0.36), Consensus PPV (r = −0.014, p = 0.72) or Consensus PPV Small (r = −0.037, p = 0.32). Postoperative De Backer score did not change significantly from baseline (5.95 ± 3.21 vs. 5.89 ± 3.36, p = 0.404), while postoperative Consensus PPV (83.49 ± 11.5 vs. 81.15 ± 11.8, p < 0.001) and Consensus PPV (small) (80.87 ± 13.4 vs. 78.72 ± 13, p < 0.001) decreased significantly from baseline. In conclusion, elevated preoperative suPAR levels were associated with intraoperative impairment of sublingual microvascular perfusion in patients undergoing elective major non-cardiac surgery.

Remdesivir-induced Bradycardia is not Associated with Worse Outcome in Patients with COVID-19: A Retrospective Analysis.

BACKGROUND: COVID-19, is primarily a respiratory illness but is known to cause extrapulmonary manifestations, especially on the cardiovascular system. Bradycardia is commonly reported in COVID-19 patients despite no prior history of occurrence, and many studies have shown an association with increased mortality. Multiple case reports have been published showcasing remdesivir potentially causing bradycardia. Our aim was to investigate the incidence of bradycardia in patients receiving remdesivir and examine the association with disease severity and survival outcomes. METHODS: A retrospective study was performed including 160 COVID-19 patients receiving remdesivir for 5 days. Patients' demographics, comorbidities, medication, vital signs, laboratory tests and outcome were recorded. Bradycardia was defined as a heart rate < 60 beats/min and severe bradycardia < 50 beats/min. RESULTS: One hundred eighteen (73.8%) patients experienced at least one episode of bradycardia during hospitalisation. Bradycardia was present in 12 (7.5%) patients before treatment with remdesivir. The rate of bradycardia increased up to the 6th day of hospitalisation (40.6%) and subsequently diminished and normalised within 5 days after the last remdesivir dose (5% at Day 10). Severe bradycardia was observed in 13 (7.5%) patients. No difference was observed in ICU admission between groups (bradycardia vs no bradycardia). When we stratified patients according to the outcome of hospitalisation, no significant difference was observed in the occurrence of bradycardia between groups (alive vs dead) [p = 0.853]. CONCLUSIONS: Treatment with remdesivir may be associated with new-onset bradycardia in hospitalised patients with COVID-19. However, bradycardia is transient and is not associated with ICU admission and mortality.

A Critical Appraisal of the Effects of Anesthetics on Immune-system Modulation in Critically Ill Patients With COVID-19.

PURPOSE: The aim of the present article was to briefly summarize current knowledge about the immunomodulatory effects of general anesthetics and the possible clinical effects of this immunomodulation in patients with COVID-19. METHODS: The PubMed, Scopus, and Google Scholar databases were comprehensively searched for relevant studies. FINDINGS: The novel coronavirus causes a wide spectrum of clinical manifestations, with a large absolute number of patients experiencing severe pneumonia and rapid progression to acute respiratory distress syndrome and multiple organ failure. In these patients, the equilibrium of the inflammatory response is a major determinant of survival. The impact of anesthetics on immune-system modulation may vary and includes both pro-inflammatory and anti-inflammatory effects. IMPLICATIONS: Inhibition of the development of severe inflammation and/or the enhancement of inflammation resolution by anesthetics may limit organ damage and improve outcomes in patients with COVID-19.