Assessment of the fatality rate and transmissibility taking account of undetected cases during an unprecedented COVID-19 surge in Taiwan.

BACKGROUND: During the COVID-19 outbreak in Taiwan between May 11 and June 20, 2021, the observed fatality rate (FR) was 5.3%, higher than the global average at 2.1%. The high number of reported deaths suggests that many patients were not treated promptly or effectively. However, many unexplained deaths were subsequently identified as cases, indicating a few undetected cases, resulting in a higher estimate of FR. Whether the true FR is exceedingly high and what factors determine the detection of cases remain unknown. Estimating the true number of total infected cases (i.e. including undetected cases) can allow an accurate estimation of FR and effective reproduction number ([Formula: see text]). METHODS: We aimed at quantifying the time-varying FR and [Formula: see text] using the estimated true numbers of cases; and, exploring the relationship between the true case number and test and trace data. After adjusting for reporting delays, we developed a model to estimate the number of undetected cases using reported deaths that were and were not previously detected. The daily FR and [Formula: see text] were calculated using the true number of cases. Afterwards, a logistic regression model was used to assess the impact of daily testing and tracing data on the detection ratio of deaths. RESULTS: The estimated true daily case number at the peak of the outbreak on May 22 was 897, which was 24.3% higher than the reported number, but the difference became less than 4% on June 9 and afterwards. After taking account of undetected cases, our estimated mean FR (4.7%) was still high but the daily rate showed a large decrease from 6.5% on May 19 to 2.8% on June 6. [Formula: see text] reached a maximum value of 6.4 on May 11, compared to 6.0 estimated using the reported case number. The decreasing proportion of undetected cases was found to be associated with the increases in the ratio of the number of tests conducted to reported cases, and the proportion of cases that are contact traced before symptom onset. CONCLUSIONS: Increasing testing capacity and contact tracing coverage without delays not only improve parameter estimation by reducing hidden cases but may also reduce fatality rates.

Typhaneoside Suppresses Glutamate Release Through Inhibition of Voltage-Dependent Calcium Entry in Rat Cerebrocortical Nerve Terminals.

Glutamate is the major excitatory neurotransmitter in the brain and is involved in many brain functions. In this study, we investigated whether typhaneoside, a flavonoid from Typhae angustifolia pollen, affects endogenous glutamate release from rat cortical synaptosomes. Using a one-line enzyme-coupled fluorometric assay, glutamate release stimulated by the K+ channel blocker 4-aminopyridine was monitored to explore the possible underlying mechanisms. The vesicular transporter inhibitor bafilomycin A1 and chelation of extracellular Ca2+ ions with EGTA suppressed the effect of typhaneoside on the induced glutamate release. Nevertheless, the typhaneoside activity has not been affected by the glutamate transporter inhibitor dl-threo-beta-benzyloxyaspartate. The synaptosomal plasma membrane potential was assayed using a membrane potential-sensitive dye DiSC3(5), and cytosolic Ca2+ concentrations ([Ca2+]C) was monitored by a Ca2+ indicator Fura-2. Results showed that typhaneoside did not alter the synaptosomal membrane potential but lowered 4-aminopyridine-induced increases in [Ca2+]C. Furthermore, the Cav2.2 (N-type) channel blocker ω-conotoxin GVIA blocked Ca2+ entry and inhibited the effect of typhaneoside on 4-aminopyridine-induced glutamate release. However, the inhibitor of intracellular Ca2+ release dantrolene and the mitochondrial Na+/Ca2+ exchanger blocker 7-chloro-5-(2-chloropheny)-1,5-dihydro-4,1-benzothiazepin-2(3H)-one have no effect on the suppression of glutamate release mediated by typhaneoside. Moreover, inhibition of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) prevented the inhibitory effect of typhaneoside on induced glutamate release. Typhaneoside reduced 4-aminopyridine-induced phosphorylation of ERK1/2 and the major presynaptic ERK target synapsin I, which is a synaptic vesicle-associated protein. In conclusion, these findings suggest a role for typhaneoside in modulating glutamate release by suppressing voltage-dependent Ca2+ channel mediated presynaptic Ca2+ influx and the MAPK/ERK/synapsin I signaling cascade.

Robotic Transmitral Approach for Hypertrophic Cardiomyopathy With Systolic Anterior Motion.

BACKGROUND: Surgical intervention is indicated in symptomatic hypertrophic cardiomyopathy (HCM) patients with a ventricular outflow pressure gradient more than 50 mmHg. The transmitral approach, along with the transapical and transaortic approaches, is routinely used for myectomy, but all are open procedures. We describe a robotic transmitral approach that can be used to resolve septal hypertrophied muscle and eliminate mitral regurgitation (MR) using 1 cardiac incision. Methods and Results: We retrospectively analyzed 20 adult patients with obstructive HCM who exhibited concomitant severe MR and systolic anterior motion (SAM). The 2 groups comprised 12 standard full-sternotomy transaortic and 8 robotic transmitral approaches. The pre-intraventricular pressure gradient was 69±14.2 mmHg in the robotic transmitral group and 70.2±17.4 mmHg in the transaortic group (P=0.876). Both groups had a similar left ventricular ejection fraction (65±8% vs. 72±9%, P=0.901) and maximal ventricular wall thickness (22.3±4.5 and 21.7±6.0, P=0.835). Postoperative MR was reduced to less than grade II in all patients. In the robotic group, the postoperative pressure gradient was 1.5±2.6 mmHg, which was lower than that of the transaortic group at 10.6±10.8 mmHg (P=0.019). The cross-clamp time was 95.3±7.7 min in the robotic group and 104.7±20.8 min in the transaortic group (P=0.193). The operation time was 237.5±22.4 and 309.6±28.5 min (P<0.01) in the robotic transmitral and transaortic groups, respectively. CONCLUSIONS: Using a robotic transmitral approach to treat with patients with HCM, SAM, and MR is feasible and reliable. Through 1 atrial incision, it is possible to resolve hypertrophy of the septum and eliminate both severe MR and SAM.

Ropivacaine Protects against Memory Impairment and Hippocampal Damage in a Rat Neurodegeneration Model.

BACKGROUND: Ropivacaine, a long-acting amide local anesthetic agent, has been demonstrated to inhibit glutamatergic transmission. Glutamate neurotoxicity plays a pivotal role in the pathogenesis of brain disorders. The purpose of this study is to investigate the neuroprotective effect of ropivacaine against brain damage induced by kainic acid (KA), an analogue of glutamate. METHODS: Rats were injected with ropivacaine (0.4 or 2 mg/kg, intraperitoneal) 30 min before KA treatment (15 mg/kg, intraperitoneal). KA-induced memory impairment was evaluated using the Morris water maze test. Extracellular hippocampal glutamate levels were assessed using high-performance liquid chromatography. Neuronal death was verified using Fluoro-Jade B and neutral red staining, and apoptosis was determined through terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Western blotting was conducted to assay the levels of activated (cleaved) caspase-3 and the phosphorylation of different mitogen-activated protein kinases (MAPKs). -Results: Ropivacaine pretreatment effectively prevented KA-induced memory impairment. KA-induced elevations of -glutamate release in rat hippocampi were inhibited by pretreatment with ropivacaine. Histopathological and TUNEL staining analyzes showed that ropivacaine inhibited KA-induced neuronal death and apoptosis in the hippocampal CA3 region. KA-induced caspase-3 activation and MAPKs phosphorylation in the hippocampus were also reduced by ropivacaine pretreatment. CONCLUSIONS: This study -demonstrates that ropivacaine executes a protective action against KA-induced neuronal damage and apoptosis in vivo. Protective effects may be caused by glutamate level reduction, caspase-3 activation suppression, and MAPKs phosphorylation reduction. Our findings indicate that ropivacaine can benefit prevention or treatment of glutamate excitotoxicity-related neurodegenerative diseases.

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.

Protective effects of bupivacaine against kainic acid-induced seizure and neuronal cell death in the rat hippocampus.

The excessive release of glutamate is a critical element in the neuropathology of epilepsy, and bupivacaine, a local anesthetic agent, has been shown to inhibit the release of glutamate in rat cerebrocortical nerve terminals. This study investigated whether bupivacaine produces antiseizure and antiexcitotoxic effects using a kainic acid (KA) rat model, an animal model used for temporal lobe epilepsy, and excitotoxic neurodegeneration experiments. The results showed that administering bupivacaine (0.4 mg/kg or 2 mg/kg) intraperitoneally to rats 30 min before intraperitoneal injection of KA (15 mg/kg) increased seizure latency and reduced the seizure score. In addition, bupivacaine attenuated KA-induced hippocampal neuronal cell death, and this protective effect was accompanied by the inhibition of microglial activation and production of proinflammatory cytokines such as interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α in the hippocampus. Moreover, bupivacaine shortened the latency of escaping onto the platform in the Morris water maze learning performance test. Collectively, these data suggest that bupivacaine has therapeutic potential for treating epilepsy.

Antimicrobial effect of continuous lidocaine infusion in a Staphylococcus aureus-induced wound infection in a mouse model.

Continuous infusion of local anesthetics in surgical wounds has been shown to be an effective technique for postoperative analgesia. To investigate the potential antimicrobial effect of continuous local anesthetic infusion, we adapted a mouse model of surgical wound infection to examine effects on antibacterial response. Forty male BALB/c mice were randomized into 2 groups. An incision wound was made over the dorsal flank and instilled with Staphylococcus aureus. An osmotic pump was then implanted to deliver either 0.9% NaCl or 2% lidocaine continuously. Each wound was cultured postoperatively at 2 days, and the colony count of S. aureus was determined. Results showed that the number of colony-forming units of S. aureus measured in wounds treated with lidocaine displayed a nearly 10-fold reduction compared to the wounds in the saline group (P=0.009). The demonstrated antibacterial activity indicates that local anesthetic infusion may play a role in prophylaxis for surgical wound infections.

Correlation between early sublingual small vessel density and late blood lactate level in critically ill surgical patients.

BACKGROUND: Surgical stress may cause excessive inflammation and lead to microcirculatory dysfunction. The hypothesis of this study was that early microcirculatory dysfunction may result in anaerobic glycolysis and lead to elevated blood lactate levels in patients admitted to surgical intensive care units. METHODS: This prospective observational study enrolled adult patients admitted to surgical intensive care units after general surgery or thoracic surgery. We measured blood lactate levels before the operation and at 1 h and 24 h after the operation. We obtained images of sublingual microcirculation using a sidestream dark field video microscope and analyzed them employing automated analysis software. RESULTS: A total of 31 patients completed the study. Perioperative total and perfused small vessel densities were lower in patients with a blood lactate level ≥3 mmol/L. We observed a significant correlation between the total small vessel density at 1 h and the blood lactate level at 24 h (r = -0.573; P = 0.001). In addition, we saw a significant correlation between the perfused small vessel density at 1 h and the blood lactate level at 24 h (r = -0.476; P = 0.008). CONCLUSIONS: Early total and perfused small vessel density may be used as an early predictor or therapeutic goal for critically ill surgical patients in further studies.

Hypothermia is an independent risk factor for prolonged ICU stay in coronary artery bypass surgery: an observational study.

Maintenance of normothermia is a critical perioperative issue. The warming process after hypothermia tends to increase oxygen demand, which may lead to myocardial ischemia. This study explored whether hypothermia was an independent risk factor for increased morbidity and mortality in patients receiving CABG. We conducted a retrospective observational study of CABG surgeries performed from January 2018 to June 2019. The outcomes of interest were mortality, surgical site infection rate, ventilator dependent time, intensive care unit (ICU) stay, and hospitalization duration. Data from 206 patients were analysed. Hypothermic patients were taller (p = 0.012), had lower left ventricular ejection fraction (p = 0.016), and had off-pump CABG more frequently (p = 0.04). Our analysis noted no incidence of mortality within 30 days. Hypothermia was not associated with higher surgical site infection rate or longer intubation time. After adjusting for sex, age, cardiopulmonary bypass duration, left ventricular ejection fraction, and EuroSCORE II, higher EuroSCORE II (p < 0.001; odds ratio 1.2) and hypothermia upon ICU admission (p = 0.04; odds ratio 3.8) were independent risk factors for prolonged ICU stay. In addition to EuroSCORE II, hypothermia upon ICU admission was an independent risk factor for prolonged ICU stay in patients receiving elective CABG.

Results of streamlining TAVR procedure towards a minimalist approach: a single center experience in Taiwan.

Trans-femoral transcatheter aortic valve replacement (TF-TAVR) performed under conscious sedation (LACS) is not yet become routine practice in Taiwan. We aimed to compared the results between patients received general anesthesia (GA) versus LACS. Our cohort was divided into 3 groups: initial 48 patients received TF-TAVR under routine GA (GA group), subsequent 50 patients under routine LACS (LACS group 1), and recent 125 patients under LACS (LACS group 2). The baseline, procedural characteristics and all outcomes were prospectively collected and retrospectively compared. From Sep 2010 to July 2019, a total of 223 patients were included. The procedure time (157.6 ± 39.4 min vs 131.6 ± 30.3 vs 95.2 ± 40.0, < 0.0001), contrast medium consumption (245.6 ± 92.6 ml vs 207.8 ± 77.9 vs 175.1 ± 64.6, < 0.0001), length of intensive care unit (2 [1-5] days vs 2 [1-3] vs 1 [1-1], P = 0.0001) and hospital stay (9 [7-13] days vs 8 [6-11] vs 6 [5-9], P = 0.0001) decreased significantly with LACS, combined with a trend of less hospital acquired pneumonia (12.5% vs 6.0% vs 5.6%, P = 0.427). 1-year survival rate were also different among 3 groups (83.3% vs 90.0% vs 93.6%, P = 0.053). In our single center experience, a "minimalist" approach of TF-TAVR procedure resulted in less medical resources usage, along with more favorable clinical outcomes.

Quantification of cardiac pumping mechanics in TAVI patients: A pilot study utilizing minimally invasive method for pressure-volume analysis.

The ventriculo-arterial coupling (VAC) and left ventricle (LV) mechanics are crucial and play an important role in the pathophysiology of aortic stenosis (AS). The pressure-volume (PV) analysis is a powerful tool to study VAC and LV mechanics. We proposed a novel minimally-invasive method for PV analysis in patients with severe AS receiving transcatheter aortic valve implantation (TAVI). Patients with severe AS were prospectively enrolled in a single center. LV pressure and cardiac output were recorded before and after TAVI. We constructed the PV loop for analysis by analyzing LV pressure and the assumed flow. 26 patients were included for final analysis. The effective arterial elastance (Ea) decreased after TAVI (3.7 ± 1.3 vs. 2.9 ± 1.1 mmHg/mL, p < 0.0001). The LV end-systolic elastance (Ees) did not change immediately after TAVI (2.4 ± 1.3 vs. 2.6 ± 1.1 mmHg/mL, p = 0.3670). The Ea/Ees improved after TAVI (1.8 ± 0.8 vs. 1.2 ± 0.4, p < 0.0001), demonstrating an immediate improvement of VAC. The stroke work (SW) did not change (7669.6 ± 1913.8 vs. 7626.2 ± 2546.9, p = 0.9330), but the pressure-volume area (PVA) decreased (14469.0 ± 4974.1 vs. 12177.4 ± 4499.9, p = 0.0374) after TAVI. The SW/PVA increased after TAVI (0.55 ± 0.12 vs. 0.63 ± 0.08, p < 0.0001) representing an improvement of LV efficiency. We proposed a novel minimally invasive method for PV analysis in patients with severe AS receiving TAVI. The VAC and LV efficiency improved immediately after TAVI.

Enoxaparin sodium prevents intestinal microcirculatory dysfunction in endotoxemic rats.

INTRODUCTION: During severe sepsis or septic shock, activation of the inflammatory and coagulatory systems can result in microcirculatory dysfunction as well as microvascular thrombosis, culminating in multiple organ dysfunction and death. Enoxaparin can inhibit factor Xa and attenuate endothelial damage. The primary purpose of this study was to investigate the effect of enoxaparin on intestinal microcirculation in endotoxemic rats. METHODS: Thirty male Wistar rats were divided into the following three groups: sham operated (OP); lipopolysaccharide (LPS); and LPS + Enoxaparin group. The rats received a midline laparotomy to exteriorize a segment of terminal ileum for microcirculation examination by full-field laser perfusion imager and sidestream dark field video microscope on mucosa, muscle, and Peyer's patch. In the LPS and LPS + Enoxaparin groups, 15 mg/kg LPS was administered intravenously to induce endotoxemia, and 400 IU/kg enoxaparin sodium was also administered in the LPS + Enoxaparin group. RESULTS: At 240 minutes, the mean arterial pressure was higher in the LPS + Enoxaparin group than in the LPS group (93 ± 9 versus 64 ± 16 mm Hg, P < 0.001). Microcirculatory blood flow intensity was higher in the LPS + Enoxaparin group than in the LPS group as follows: mucosa (1085 ± 215 versus 617 ± 214 perfusion unit [PU], P < 0.001); muscle (760 ± 202 versus 416 ± 223 PU, P = 0.001); and Peyer's patch (1,116 ± 245 versus 570 ± 280 PU, P < 0.001). Enoxaparin inhibited LPS-induced reduction in perfused small vessel density and increase in heterogeneity of microcirculation. CONCLUSIONS: Enoxaparin can prevent intestinal microcirculatory dysfunction in endotoxemic rats by preventing microvascular thrombosis formation and maintaining normal mean arterial pressure.

Early prediction of survival at different time intervals in sepsis patients: A visualized prediction model with nomogram and observation study.

OBJECTIVES: Sepsis is a major cause of death around the world. Complicated scoring systems require time to have data to predict short-term survival. Intensivists need a tool to predict survival in sepsis patients easily and quickly. MATERIALS AND METHODS: This retrospective study reviewed the medical records of adult patients admitted to the surgical intensive care units between January 2009 and December 2011 in National Taiwan University Hospital. For this study, 739 patients were enrolled. We recorded the demographic and clinical variables of patients diagnosed with sepsis. A Cox proportional hazard model was used to analyze the survival data and determine significant risk factors to develop a prediction model. This model was used to create a nomogram for predicting the survival rate of sepsis patients up to 3 months. RESULTS: The observed 28-day, 60-day, and 90-day survival rates were 71.43%, 52.53%, and 46.88%, respectively. The principal risk factors for survival prediction included age; history of dementia; Glasgow Coma Scale score; and lactate, creatinine, and platelet levels. Our model showed more favorable prediction than did Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment at sepsis onset (concordance index: 0.65 vs. 0.54 and 0.59). This model was used to create the nomogram for predicting the mortality at the onset of sepsis. CONCLUSION: We suggest that developing a nomogram with several principal risk factors can provide a quick and easy tool to early predict the survival rate at different intervals in sepsis patients.

Effects of perioperative dexmedetomidine infusion on renal function and microcirculation in kidney transplant recipients: a randomised controlled trial.

OBJECTIVE: Ischemia-reperfusion injury affects postoperative transplanted kidney function in kidney transplant recipients. Dexmedetomidine was reported to attenuate ischemia-reperfusion injury and improve microcirculation, but its propensity to cause bradycardia and hypotension may adversely affect microcirculation. This study investigated the effect of dexmedetomidine on postoperative renal function and sublingual microcirculation in kidney recipients. METHODS: The enrolled kidney transplant recipients were randomly allocated to the control group or dexmedetomidine group. After anaesthesia induction, patients in the dexmedetomidine group received dexmedetomidine infusion until 2 h after surgery. Sublingual microcirculation was recorded using an incident dark-field video microscope and analysed. The primary outcomes were the creatinine level on a postoperative day 2 and total vessel density at 2 h after surgery. RESULTS: A total of 60 kidney recipients were analysed, and the creatinine levels on postoperative day 2 were significantly lower in the dexmedetomidine group than in the control group (1.5 (1.1-2.4) vs. 2.2 (1.7-3.0) mg/dL, median difference -0.6 (95% CI, -0.7 to -0.5) mg/dL, p = .018). On a postoperative day 7, the creatinine levels did not differ significantly between the two groups. Total vessel density at 2 h after surgery did not differ significantly between the two groups. CONCLUSION: We found that early postoperative renal function was better in kidney transplant recipients receiving dexmedetomidine infusion, but total vessel density was not significantly different between the intervention and control groups. Key messagesIschemia-reperfusion injury affects postoperative transplanted kidney function, and dexmedetomidine was reported to attenuate ischemia-reperfusion injury and improve microcirculation in other clinical conditions.This study showed that early postoperative renal function was better in kidney transplant recipients receiving dexmedetomidine.Dexmedetomidine's side effect of bradycardia and hypotension may affect microcirculation, our results revealed that the perioperative sublingual microcirculation did not differ significantly in kidney transplant recipients receiving dexmedetomidine.

Serial neurocognitive changes following transcatheter aortic valve replacement: comparison between low and intermediate-high risk groups.

BACKGROUND: Data comparing the neurocognitive trajectory between low and intermediate-high risk patients following transcatheter aortic valve replacement (TAVR) is never reported. AIMS: To report serial neurocognitive changes up to 1 year post-TAVR in low and intermediate-high risk groups as well as overall cohort. METHODS: Prospective neurological assessments (NIHSS and Barthel Index), global cognitive tests (MMSE and Alzheimer Disease Assessment Scale-Cognitive Subtest, ADAS-cog) and executive performances (Color Trail Test A and B and verbal fluency), were applied at baseline, 3 months and 1 year post-TAVR. RESULTS: In overall cohort, persistent improvement to 1 year in MMSE, ADAS-cog, Color Trail Test A and B was found. According to the STS score, the study cohort was divided into low (<4%, N = 81) and intermediate-high (≧4%, N = 75) risk groups. The baseline neurologic and cognitive performance was significantly worse in intermediate-high risk group. Slight improvement on general neurological functions (Barthel index and proportion of NIHSS>0 patients) at 1 year could be observed only in intermediate-high risk group. In global cognitive assessments, improvement in MMSE and ADAS-cog at 1 year was found in both groups, but the proportion of cognitive improvement was more obvious in intermediate-high risk group. In Color Trail Tests and verbal fluency, significant and persistent improvement up to 1 year could be observed only in low risk group. CONCLUSIONS: TAVR was associated with persistent improvement in global cognitive function, as well as in attention and psychomotor processing speed, up to 1 year in overall cohort. However, improvement in tests for executive functions can only be seen in low risk group.

Effects of dexmedetomidine on renal microcirculation in ischemia/reperfusion-induced acute kidney injury in rats.

Microcirculatory dysfunction plays a crucial role in renal ischemia/reperfusion (IR)-induced injury. Dexmedetomidine was reported to ameliorate IR-induced acute kidney injury. This study investigated the effects of dexmedetomidine on renal microcirculation after IR-induced acute kidney injury in rats. In total, 50 rats were randomly allocated to the following five groups (10 in each group): Sham, Control‒IR, Dex (dexmedetomidine) ‒Sham, Dex‒IR, and IR‒Dex group. The microcirculation parameters included total small vessel density, perfused small vessel density (PSVD), proportion of perfused small vessels, microvascular flow index, and tissue oxygen saturation (StO2) were recorded. The repeated measures analysis showed that PSVD on renal surface was higher in the Dex‒IR group than in the Control‒IR group (3.5 mm/mm2, 95% confidence interval [CI] 0.6 to 6.4 mm/mm2, P = 0.01). At 240 min, StO2 on renal surface was lower in the Control‒IR group than in the Sham group (- 7%, 95% CI - 13 to - 1%, P = 0.021), but StO2 did not differ significantly among the Sham, Dex‒IR, and IR‒Dex groups. Our results showed that pretreatment with dexmedetomidine improved renal microcirculation in rats with IR-induced acute kidney injury. However, the adverse effects of low mean arterial pressure and heart rate might offset the protective effect of dexmedetomidine on organ injury.

Microcirculatory Response to Changes in Venoarterial Extracorporeal Membrane Oxygenation Pump Flow: A Prospective Observational Study.

Background: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) pump flow is crucial for maintaining organ perfusion in patients with cardiogenic shock, but VA-ECMO pump flow optimization remains as a clinical challenge. This study aimed to investigate the response of sublingual microcirculation to changes in VA-ECMO pump flow. Methods: Sublingual microcirculation was measured before and after changing VA-ECMO pump flow according to the treatment plan of ECMO team within 24 h and at 24-48 h after VA-ECMO placement. In clinical events of increasing VA-ECMO pump flow, those events with increased perfused vessel density (PVD) were grouped into group A, and the others were grouped into group B. In clinical events of decreasing VA-ECMO pump flow, those events with increased PVD were grouped into group C, and the others were grouped into group D. Results: Increased PVD was observed in 60% (95% CI, 38.5-81.5%) of the events with increasing VA-ECMO pump flow. The probability of increasing PVD after increasing VA-ECMO pump flow were higher in the events with a PVD < 15 mm/mm2 at baseline than those with a PVD ≥ 15 mm/mm2 [100% (95% CI, 54.1-100%) vs. 42.9% (95% CI, 17.7-71.1%), P = 0.042]. Other microcirculatory and hemodynamic parameters at baseline did not differ significantly between group A and B or between group C and D. Conclusion: This study revealed contradictory and non-contradictory responses of sublingual microcirculation to changes in VA-ECMO pump flow. Tandem measurements of microcirculation before and after changing VA-ECMO pump flow may help to ensure a good microcirculation.

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.

Comparing effects of intraoperative fluid and vasopressor infusion on intestinal microcirculation.

Several studies have revealed that vasopressor may be more appropriate for treating intraoperative hypotension and preventing hypervolemia. This study compared the effects of vasopressor infusion and fluid supplementation on intestinal microcirculation during treating intraoperative hypotension. Thirty-two rats were randomly divided into the following four groups: Light Anesthesia group (LA, 0.8-1% isoflurane); Deep Anesthesia group (DA, 1.5-1.8% isoflurane); Fluid DA group (1.5-1.8% isoflurane and fluid supplementation); and Norepinephrine DA group (1.5-1.8% isoflurane and norepinephrine infusion). At 240 min, perfused small vessel density (PSVD) of the mucosa did not differ significantly between the Fluid DA and Norepinephrine DA groups [26.2 (3.2) vs 28.9 (2.5) mm/mm2, P = 0.077], and tissue oxygen saturation of the mucosa was lower in the Fluid DA groups than in the Norepinephrine DA groups [ 48 (7) vs 57 (6) %, P = 0.02]. At 240 min, TSVD and PSVD of the seromuscular layer were higher in the Norepinephrine DA group than in the Fluid DA group. Fluid administration was higher in the Fluid DA group than in the Norepinephrine DA group [66 (25) vs. 9 (5) µL/g, P = 0.001]. Our results showed that norepinephrine can resuscitate intraoperative hypotension related microcirculatory alteration and avoid fluid overload.

Effects of endotoxin adsorber hemoperfusion on sublingual microcirculation in patients with septic shock: a randomized controlled trial.

BACKGROUND: Endotoxins can induce an excessive inflammatory response and result in microcirculatory dysfunction. Polymyxin-B hemoperfusion (PMX-HP) has been recognized to effectively remove endotoxins in patients with sepsis and septic shock, and a rat sepsis model revealed that PMX-HP treatment can maintain a better microcirculation. The primary aim of this study was to investigate the effect of PMX-HP on microcirculation in patients with septic shock. METHODS: Patients with septic shock were enrolled and randomized to control and PMX-HP groups. In the PMX-HP group, patients received the first session of PMX-HP in addition to conventional septic shock management within 24 h after the onset of septic shock; the second session of PMX-HP was provided after another 24 h as needed. RESULTS: Overall, 28 patients finished the trial and were analyzed. The mean arterial pressure and norepinephrine infusion dose did not differ significantly between the control and PMX-HP groups after PMX-HP treatment. At 48 h after enrollment, total vessel density (TVD) and perfused vessel density (PVD) were higher in the PMX-HP group than in the control group [TVD 24.2 (22.1-24.9) vs. 21.1 (19.9-22.9) mm/mm2; p = 0.007; PVD 22.9 (20.9-24.9) vs. 20.0 (18.9-21.6) mm/mm2, p = 0.008]. CONCLUSIONS: This preliminary study observed that PMX-HP treatment improved microcirculation but not clinical outcomes in patients with septic shock at a low risk of mortality. Nevertheless, larger multicenter trials are needed to confirm the effect of PMX-HP treatment on microcirculation in patients with septic shock at intermediate- and high-risk of mortality. Trial registration ClinicalTrials.gov protocol registration ID: NCT01756755. Date of registration: December 27, 2012. First enrollment: October 6, 2013. https://clinicaltrials.gov/ct2/show/NCT01756755.