Prognostic effects of microcirculation-assisted adjustment of venoarterial blood flow in extracorporeal membrane oxygenation: A prospective, pilot, randomized controlled trial.

OBJECTIVE: The study explored the clinical efficacy of microcirculation-assisted blood flow adjustment in patients receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO). METHODS: This prospective, pilot, randomized controlled trial was conducted from 2018 to 2021; enrolled patients were randomly assigned to the microcirculation or control group at a 1:1 ratio. Microcirculatory and clinical data were collected within 24 h (T1) and at 24-48 h (T2), 48-72 h (T3), and 72-96 h (T4) after ECMO initiation and were compared between the groups following the intention-to-treat (ITT) principle. The primary outcome was the Sequential Organ Failure Assessment (SOFA) score at T2. In addition to ITT analysis, analysis based on the as-treated (AT) principle was performed. RESULTS: A total of 35 patients were enrolled in this study. At T2, the SOFA score did not significantly differ between the microcirculation and control groups (16 [14.8-17] vs. 16 [12.5-18], P = 0.782). Generalized estimating equation analysis demonstrated a significantly greater reduction in the SOFA score over time in the microcirculation-AT group than in the control-AT group (estimated difference: -0.767, standard error: 0.327, P = 0.019). The lactate level at T2 was significantly lower in the microcirculation-AT group (2.7 [2.0-3.6] vs. 4.1 [3.0-6.6] mmol/L, P = 0.029). No significant difference in the 30-day survival rate was noted between the groups. CONCLUSION: This prospective pilot study demonstrated the feasibility of microcirculation-assisted VA-ECMO blood flow adjustment despite no significant clinical benefit for critically ill patients. More efforts in personnel training and newer technologies may help achieve microcirculation optimization.

Effects of Goal-Directed Hemodynamic Therapy Using a Noninvasive Finger-Cuff Monitoring Device on Intraoperative Cerebral Oxygenation and Early Delayed Neurocognitive Recovery in Patients Undergoing Beach Chair Position Shoulder Surgery: A Randomized Controlled Trial.

BACKGROUND: Perioperative cerebral desaturation events (CDEs) and delayed neurocognitive recovery are common among patients undergoing beach chair position (BCP) shoulder surgery and may be caused by cerebral hypoperfusion. This study tested the hypothesis that the application of goal-directed hemodynamic therapy (GDHT) would attenuate these conditions. METHODS: We randomly assigned 70 adult patients undergoing BCP shoulder surgery to GDHT group or control at a 1:1 ratio. Cerebral oxygenation was monitored using near-infrared spectroscopy, and GDHT was administered using the ClearSight pulse wave analysis system. The primary outcome was CDE duration, whereas the secondary outcomes were CDE occurrence, delayed neurocognitive recovery occurrence, and Taiwanese version of the Quick Mild Cognitive Impairment (Qmci-TW) test score on the first postoperative day (T 2 ) adjusted for the baseline score (on the day before surgery; T 1 ). RESULTS: CDE duration was significantly shorter in the GDHT group (0 [0-0] vs 15 [0-75] min; median difference [95% confidence interval], -8 [-15 to 0] min; P = .007). Compared with the control group, fewer patients in the GDHT group experienced CDEs (23% vs 51%; relative risk [95% confidence interval], 0.44 [0.22-0.89]; P = .025) and mild delayed neurocognitive recovery (17% vs 40%; relative risk [95% confidence interval], 0.60 [0.39-0.93]; P = .034). The Qmci-TW scores at T 2 adjusted for the baseline scores at T 1 were significantly higher in the GDHT group (difference in means: 4 [0-8]; P = .033). CONCLUSIONS: Implementing GDHT using a noninvasive finger-cuff monitoring device stabilizes intraoperative cerebral oxygenation and is associated with improved early postoperative cognitive scores in patients undergoing BCP shoulder surgery.

Changes in the quick mild cognitive impairment test over time: A normative study in an adult sample in Taiwan.

BACKGROUND: The Quick Mild Cognitive Impairment (Qmci) test has been suggested to be an easy-to-use and precise screening tool for detecting postoperative cognitive dysfunction (POCD). To provide essential information for future POCD studies in Taiwan, the present study provided data regarding the Taiwan version of the Qmci (Qmci-TW) test conducted in the normative Taiwanese population and changes in them over time. METHODS: The present study recruited adult native Taiwanese volunteers without known neurologic or psychiatric diseases. All enrolled participants received protocolized serial Qmci-TW test at baseline, 2-day follow-up, and 6-month follow-up. RESULTS: In total, 30 participants, 15 men and 15 women, were enrolled in this study. The baseline Qmci-TW score ranged from 55 to 80, with a mean of 68.9 and a standard deviation (SD) of 7. At 2-day follow-up, the mean Qmci-TW test score was significantly higher (by 5.3; SD = 7.3) than that at baseline (P = 0.001). At 6-month follow-up, the mean Qmci-TW score was 71.3 (SD = 6.1), with no significant difference compared with that at baseline. The decline in Qmci-TW scores by > 9 points on postoperative day 1 and by > 11 points at 6-month follow-up was the criterion for POCD. CONCLUSION: The present study provided data regarding the Qmci-TW test conducted in the normative Taiwanese population and its time trajectory during the 6-month follow-up.

Endotoxin Activity in Patients With Extracorporeal Membrane Oxygenation Life Support: An Observational Pilot Study.

Background: Extracorporeal membrane oxygenation (ECMO) life support has become an integral part of intensive care. The endotoxin activity assay (EAA) is a useful test to measure endotoxemia severity in whole blood. To date, no information is available regarding the EAA levels and their effect on clinical outcomes in critically ill patients with ECMO support. Methods: This prospective observational pilot study enrolled adult critically ill patients with ECMO support from August 2019 to December 2020. The EAA levels were measured within 24 h (T1), and at 25-48 (T2), 49-72 (T3), and 73-96 h (T4) after ECMO initiation. This study primarily aimed to investigate the incidence of high EAA levels (≥0.6) at each time point. Subsequent exploratory analyses were conducted to compare the EAA levels of venoarterial ECMO (VA-ECMO) patients between 30-day survivors and non-survivors. Post-hoc analysis was performed to compare the clinical outcomes of VA-ECMO patients with elevated EAA levels at T3 (vs. T1) and those without elevated EAA levels. Results: A total of 39 VA-ECMO patients and 15 venovenous ECMO (VV-ECMO) patients were enrolled. At T1, the incidence of high EAA level (≥0.6) was 42% in VV-ECMO patients and 9% in VA-ECMO patients (P = 0.02). At T2, the incidence of high EAA level was 40% in VV-ECMO patients and 5% in VA-ECMO patients (P = 0.005). In VA-ECMO patients, EAA levels at T3 were significantly higher in 30-day non-survivors than in survivors (median [interquartile range]: 0.49 [0.37-0.93] vs. 0.31 [0.19-0.51], median difference 0.16 [95% confidence interval [CI], 0.02-0.31]; P = 0.024). Moreover, VA-ECMO patients with elevated EAA levels at T3 (vs. T1) had lower 30-day survival than patients without elevated EAA levels (39 vs. 83%, P = 0.026) and fewer ECMO free days by day 30 (median: 3 vs. 23 days, median difference 12 days [95% CI, 0-22]; P = 0.028). Conclusions: A certain proportion of patients experienced high EAA levels (≥0.6) after VV-ECMO or VA-ECMO initiation. VA-ECMO patients with an elevated EAA level at 49-72 h were associated with poor clinical outcomes.

Neuroprotective effects of intraoperative dexmedetomidine versus saline infusion combined with goal-directed haemodynamic therapy for patients undergoing cranial surgery: A randomised controlled trial.

BACKGROUND: By inhibiting neuroinflammation dexmedetomidine may be neuroprotective in patients undergoing cranial surgery, but it reduces cardiac output and cerebral blood flow. OBJECTIVE: To investigate whether intra-operative dexmedetomidine combined with goal-directed haemodynamic therapy (GDHT) has neuroprotective effects in cranial surgery. DESIGN: A double-blind, single-institution, randomised controlled trial. SETTING: A single university hospital, from April 2017 to April 2020. PATIENTS: A total of 160 adults undergoing elective cranial surgery. INTERVENTION: Infusion of dexmedetomidine (0.5 µg kg-1 h-1) or saline combined with GDHT to optimise stroke volume during surgery. MAIN OUTCOME MEASURES: The proportion who developed postoperative neurological complications was compared. Postoperative disability was assessed using the Barthel Index at time points between admission and discharge, and also the 30-day modified Rankin Scale (mRS). Postoperative delirium was assessed. The concentration of a peri-operative serum neuroinflammatory mediator, high-mobility group box 1 protein (HMGB1), was compared. RESULTS: Fewer patients in the dexmedetomidine group developed new postoperative neurological complications (26.3% vs. 43.8%; P = 0.031), but the number of patients developing severe neurological complications was comparable between the two groups (11.3% vs. 20.0%; P = 0.191). In the dexmedetomidine group the Barthel Index reduction [0 (-10 to 0)] was less than that in the control group [-5 (-15 to 0)]; P = 0.023, and there was a more favourable 30-day mRS (P = 0.013) with more patients without postoperative delirium (84.6% vs. 64.2%; P = 0.012). Furthermore, dexmedetomidine induced a significant reduction in peri-operative serum HMGB1 level from the baseline (222.5 ±â€Š408.3 pg ml-1) to the first postoperative day (152.2 ±â€Š280.0 pg ml-1) P = 0.0033. There was no significant change in the control group. The dexmedetomidine group had a lower cardiac index than did the control group (3.0 ±â€Š0.8 vs. 3.4 ±â€Š1.8 l min-1 m-2; P = 0.0482) without lactate accumulation. CONCLUSIONS: Dexmedetomidine infusion combined with GDHT may mitigate neuroinflammation without undesirable haemodynamic effects during cranial surgery and therefore be neuroprotective. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT02878707.

Mini-fluid challenge test predicts stroke volume and arterial pressure fluid responsiveness during spine surgery in prone position: A STARD-compliant diagnostic accuracy study.

The study was designed to verify if mini-fluid challenge test is more reliable than dynamic fluid variables in predicting stroke volume (SV) and arterial pressure fluid responsiveness during spine surgery in prone position with low-tidal-volume ventilation.Fifty patients undergoing spine surgery in prone position were included. Fluid challenge with 500 mL of colloid over 15 minutes was given. Changes in SV and systolic blood pressure (SBP) after initial 100 mL were compared with SV, pulse pressure variation (PPV), SV variation (SVV), plethysmographic variability index (PVI), and dynamic arterial elastance (Eadyn) in predicting SV or arterial pressure fluid responsiveness (15% increase or greater).An increase in SV of 5% or more after 100 mL predicted SV fluid responsiveness with area under the receiver operating curve (AUROC) of 0.90 (95% confidence interval [CI], 0.82 to 0.99), which was significantly higher than that of PPV (0.71 [95% CI, 0.57 to 0.86]; P = .01), and SVV (0.72 [95% CI, 0.57 to 0.87]; P = .03). A more than 4% increase in SBP after 100 mL predicted arterial pressure fluid responsiveness with AUROC of 0.86 (95% CI, 0.71-1.00), which was significantly higher than that of Eadyn (0.52 [95% CI, 0.33 to 0.71]; P = .01).Changes in SV and SBP after 100 mL of colloid predicted SV and arterial pressure fluid responsiveness, respectively, during spine surgery in prone position with low-tidal-volume ventilation.

Investigation of microcirculation in patients with venoarterial extracorporeal membrane oxygenation life support.

BACKGROUND: Microcirculatory dysfunction develops in both septic and cardiogenic shock patients, and it is associated with poor prognosis in patients with septic shock. Information on the association between microcirculatory dysfunction and prognosis in cardiogenic shock patients with venoarterial extracorporeal membrane oxygenation (VA-ECMO) support is limited. METHODS: Sublingual microcirculation images were recorded using an incident dark-field video microscope at the following time points: within 12 h (T1), 24 h (T2), 48 h (T3), 72 h (T4), and 96 h (T5) after VA-ECMO placement. If a patient could be weaned off VA-ECMO, sublingual microcirculation images were recorded before and after VA-ECMO removal. Microcirculatory parameters were compared between 28-day nonsurvivors and survivors with VA-ECMO support. In addition, the microcirculation and clinical parameters were assessed as prognostic tests of 28-day mortality, and patients were divided into three subgroups according to microcirculation parameters for survival analysis. RESULTS: Forty-eight patients were enrolled in this study. At T1, the observed heart rate, mean arterial pressure, inotropic score and lactate level of 28-day nonsurvivors and survivors did not differ significantly, but the perfused small vessel density (PSVD) and proportion of perfused vessels (PPV) were lower in the 28-day nonsurvivors than in the survivors. The PSVD and PPV were slightly superior to lactate levels in predicting 28-day mortality (area under curve of 0.68, 0.70, and 0.62, respectively). The subgroup with the lowest PSVD (< 15 mm/mm2) and PPV (< 64%) values exhibited less favorable survival compared with the other two subgroups. CONCLUSIONS: Early microcirculatory parameters could be used to predict the survival of cardiogenic shock patients with VA-ECMO support. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02393274 . Registered on 19 March 2015.

Matched Comparison of Microcirculation Between Healthy Volunteers and Patients with Sepsis.

OBJECTIVE: Sepsis-related systemic inflammation resulted in microcirculatory dysfunction. However, information of normal ranges of microcirculatory parameters in the healthy population remain limited. The primary aim of this study was to investigate the differences in microcirculatory parameters between healthy volunteers and patients with sepsis. METHODS: This observational study enrolled 45 healthy female and 45 healthy male volunteers, and divided them equally into three age groups: young (20-39 years), middle-age (40-59 years), and elderly (60-79 years). In addition, we enrolled 32 patients with sepsis. Images of sublingual microcirculation were obtained through sidestream dark field videomicroscopy and were analyzed using automated analysis software. Microcirculation parameters, namely the total small vessel density (TSVD), perfused small vessel density (PSVD), proportion of perfused vessel (PPV), microvascular flow index (MFI) score, and heterogeneity index (HI), were evaluated. One-to-one matching between the septic patients and the healthy volunteers was performed on the basis of demographic data including age and gender. RESULTS: The elderly group had lower MFI scores and a higher HI. Age was positively correlated with the HI (r = 0.38, p < 0.001) and negatively correlated with the PPV and MFI scores (r = -0.26, p = 0.014 and r = -0.37, p < 0.001, respectively). TSVD was higher in female participants than in male participants. Body mass index (BMI) was negatively correlated with TSVD. In multivariate regression analysis, the independent factors associated with PPV are age and sex, however age is the only independent factor associated with MFI and HI. In patients with sepsis, TSVD (17.5 [3.3] vs. 21.7 [3.0]; p = 0.002), PSVD (15.0 [3.0] vs. 21.1 [2.5]; p < 0.001), and MFI score (2.0 [1.6-2.5] vs. 2.9 [2.5-3.0]; p < 0.001) were lower in the 28-day nonsurvivors than in the survivors. Matched comparison revealed that the TSVD (20.7 [3.7] vs. 25.2 [2.3]; p < 0.001), PSVD (19.8 [3.0] vs. 24.3 [2.7]; p < 0.001), and MFI score (2.7 [2.4-3.0] vs. 3.0 [2.7-3.0]; p = 0.019) were lower in the patients with sepsis than in the healthy volunteers. CONCLUSIONS: Age and sex were correlated with microcirculatory parameters of the healthy volunteers. In the patients with sepsis, microcirculatory dysfunction was more severe in the 28-day nonsurvivor group than in the 28-day survivor group. Furthermore, the patients with sepsis exhibited significantly lower TSVD, PSVD, and MFI scores than the healthy volunteers.

Comparison of dexmedetomidine versus propofol on hemodynamics in surgical critically ill patients.

BACKGROUND: Sedation with dexmedetomidine and propofol may cause hypotension or bradycardia. This study aimed to compare the effects of dexmedetomidine and propofol on hemodynamics and clinical outcomes in surgical intensive care unit (ICU) patients after major abdominal surgery. MATERIALS AND METHODS: Enrolled patients were randomly allocated to the dexmedetomidine or propofol group. Cardiac index was measured using a continuous noninvasive cardiac output monitor on the basis of chest bioreactance. Heart rate, blood pressure, opioid requirement, urine output, delirium incidence, ICU length of stay, and total hospital length of stay were compared between the two groups. The incidences of bradycardia, hypotension, and severe low cardiac index were compared. RESULTS: We enrolled 60 patients. Heart rate and mean arterial pressure were significantly lower in the dexmedetomidine group than in the propofol group. Cardiac index did not differ significantly between the two groups (dexmedetomidine group 3.1 L/min/m2, [95% confidence interval {95% CI} 2.8-3.3] versus propofol group 3.2 L/min/m2 [95% CI 2.9-3.5], P = 0.578). The incidences of bradycardia, hypotension, and severe low cardiac index did not differ significantly between the two groups. CONCLUSIONS: Cardiac index did not differ significantly between the dexmedetomidine and propofol groups in surgical ICU patients after major abdominal surgery.

Effects of polymyxin B hemoperfusion on hemodynamics and prognosis in septic shock patients.

PURPOSE: We designed this study to examine the clinical effects of polymyxin B hemoperfusion (PMX-HP) in septic shock patients. MATERIAL AND METHODS: We retrospectively examined the effects of PMX-HP in septic shock patients with intra-abdominal or gram-negative bacterial infection during October 2013-May 2016. A one-to-one matching between the PMX-HP and conventional groups was performed, and 28-day mortality, and change in inotropic score, Sequential Organ Failure Assessment (SOFA) score, and Acute Physiology and Chronic Health Evaluation II (APACHE II) score at 24h in the two groups were compared. In addition, multivariable regression analysis and Cox proportional hazards regression model were applied in all eligible patients. RESULTS: Sixty-nine patients were eligible, of whom fifty patients were enrolled for matched cohort analysis. In matched cohort analysis, change in inotropic score after 24h (-24.8 [19.7] vs. -6.4 [20.0], p=0.002) differed significantly between the PMX-HP and conventional groups. Multivariable regression analysis revealed that PMX-HP was associated with lower 28-day mortality (odds ratio 0.18, 95% CI 0.04-0.92, p=0.039) and greater improvement in inotropic and APACHE II scores. CONCLUSIONS: PMX-HP may have potential benefits for hemodynamic and prognostic outcomes in septic shock patients with intra-abdominal or gram-negative bacterial infection.

An observational study of microcirculation in dialysis patients and kidney transplant recipients.

BACKGROUND: Microcirculatory dysfunction contributes to acute and chronic kidney diseases. To the best of our knowledge, no study has compared differences in microcirculation among healthy volunteers, dialysis patients and kidney transplant recipients. MATERIALS AND METHODS: Sublingual microcirculation was examined using sidestream dark field imaging and was compared among 90 healthy volunteers, 40 dialysis patients and 40 kidney transplant recipients. The gender effect on microcirculation and the correlations among the microcirculation parameters, age, body mass index, heart rate and blood pressure were analysed. RESULTS: Total small vessel density, perfused small vessel density and the proportion of perfused small vessels were lower in the dialysis patients than in the healthy volunteers and kidney transplant recipients [total small vessel density; healthy volunteers vs. dialysis patients vs. kidney transplant recipients, 25·2 (2·3) vs. 22·8 (2·6) vs. 24·2 (2·9) mm/mm2 , P < 0·001]. Systolic blood pressure showed a weak negative correlation with the microvascular flow index scores in the healthy volunteers. By contrast, systolic blood pressure, diastolic blood pressure and mean arterial pressure showed weak positive correlations with proportion of perfused small vessels and the microvascular flow index scores in the dialysis patients. CONCLUSIONS: Microcirculatory dysfunction is noted in dialysis patients, and this alteration is ameliorated in KT recipients. The positive correlation between blood pressure and microcirculation in dialysis patients suggests that additional studies should investigate the optimal goal of blood pressure management for dialysis patients.

Effects of endotoxin absorber hemoperfusion on microcirculation in septic pigs.

BACKGROUND: Endotoxins contribute to systemic inflammatory response and microcirculatory dysfunctions under conditions of sepsis. Polymyxin B hemoperfusion (PMX-HP) is used to remove circulating endotoxins and improve clinical outcomes. This study aims to investigate the effect of PMX-HP on microcirculation in septic pigs. MATERIALS AND METHODS: By using a septic pig model, we tested the hypothesis that PMX-HP can correct intestinal microcirculation, tissue oxygenation saturation, and histopathologic alterations. A total of 18 male pigs were divided into three groups: (1) sham; (2) sepsis (fecal peritonitis); and (3) sepsis + PMX-HP groups. A sidestream dark field video microscope was used to record microcirculation throughout the terminal ileal mucosa, colon mucosa, kidney surface, and sublingual area. A superficial tissue oxygenation monitor employing the light reflectance spectroscopy technique was used to measure the tissue oxygen saturation. Hematoxylin and eosin staining was used for histologic examination. RESULTS: The perfused small vessel density and tissue oxygen saturation of the ileal mucosa at 6 h were higher in the sepsis + PMX-HP group than those in the sepsis group. The fluid amount and norepinephrine infusion rate between the sepsis group and sepsis + PMX-HP groups did not differ significantly. The histologic score for the ileal mucosa was lower in the sepsis + PMX-HP group than that in the sepsis group. Finally, the urine output was higher in the sepsis + PMX-HP group than it was in the sepsis group. CONCLUSIONS: This study demonstrates that PMX-HP attenuates microcirculatory dysfunction, tissue desaturation, and histopathologic alterations in the ileal mucosa in septic pigs.

Effects of Polymyxin B Hemoperfusion on Mortality in Patients With Severe Sepsis and Septic Shock: A Systemic Review, Meta-Analysis Update, and Disease Severity Subgroup Meta-Analysis.

OBJECTIVE: Several studies have reported a survival benefit for polymyxin B hemoperfusion treatment in patients with severe sepsis and septic shock. However, recently, a propensity-matched analysis and a randomized controlled trial reported no survival benefit for polymyxin B hemoperfusion treatment. We performed an up-to-date meta-analysis to determine the effect of polymyxin B hemoperfusion treatment on mortality in patients with severe sepsis and septic shock. DATA SOURCES: PubMed, Embase, and Cochrane Library were searched from inception to May 2016. STUDY SELECTION: Studies investigating the effect of polymyxin B hemoperfusion on mortality were considered eligible. We searched for terms related to severe sepsis and septic shock and terms related to polymyxin B hemoperfusion. DATA EXTRACTION: The following data were extracted from the original articles: the name of the first author and publication year, subjects and setting, inclusion and exclusion criteria, mean age and size of the study population, male percentage, mortality, blood pressure, Sequential Organ Failure Assessment score, pulmonary oxygenation, and levels of endotoxin and humoral cytokines. DATA SYNTHESIS: A total of 17 trials were included. The pooled risk ratio for overall mortality was 0.81 (95% CI, 0.70-0.95), favoring polymyxin B hemoperfusion (p = 0.007). Disease severity subgroup meta-analysis revealed a significant reduction of mortality in the intermediate- and high-risk groups (risk ratio, 0.84; 95% CI, 0.77-0.92 and risk ratio, 0.64; 95% CI, 0.52-0.78, respectively), but not in the low-risk group (risk ratio, 1.278; 95% CI, 0.888-1.839). The nonlinear meta-regression with restricted cubic spline showed an almost linear inverse association between the baseline mortality rate and reduction in the risk of mortality. CONCLUSION: The present study demonstrated that polymyxin B hemoperfusion treatment may reduce mortality in patients with severe sepsis and septic shock in specific disease severity subgroups.