Andexanet alpha-induced heparin resistance treated by nafamostat mesylate in a patient undergoing total aortic arch repair for Stanford type A acute aortic dissection: a case report.

BACKGROUND: Andexanet alfa, an anti-Xa inhibitor antagonist, induces heparin resistance. Here, we report a case of successful management of cardiopulmonary bypass with andexanet alfa-induced heparin resistance using nafamostat mesylate. CASE PRESENTATION: An 84-year-old female, with Stanford type A acute aortic dissection, underwent an emergency surgery for total aortic arch replacement. Andexanet alfa 400 mg was administered preoperatively to antagonize edoxaban, an oral Xa inhibitor. Heparin 300 IU/kg was administered before cardiopulmonary bypass, and the activated clotting time (ACT) was 291 s. The ACT was 361 s after another administration of heparin 200 IU/kg. According to our routine therapy for heparin resistance, an initial dose of nafamostat mesylate 10 mg was administered intravenously, followed by a continuous infusion of 20-30 mg/h. The ACT was prolonged to 500 s, and cardiopulmonary bypass was successfully established thereafter. CONCLUSIONS: This case report presents the successful management of cardiopulmonary bypass with andexanet alfa-induced heparin resistance using nafamostat mesilate. This report presents the successful management of cardiopulmonary bypass with andexanet alfa-induced heparin resistance using nafamostat mesilate.

IMPACT OF HIGH-DOSE VASOPRESSOR DURING ENDOTOXIC SHOCK ON THE CEREBRAL, LINGUAL, HEPATIC, AND RENAL MICROCIRCULATION EVALUATED BY NEAR-INFRARED SPECTROSCOPY IN SWINE.

ABSTRACT: Background: High-dose vasopressors maintain blood pressure during septic shock but may adversely reduce microcirculation in vital organs. We assessed the effect of high-dose norepinephrine and vasopressin on the microcirculation of the brain, tongue, liver, and kidney during endotoxic shock using near-infrared spectroscopy (NIRS). Methods: Thirteen pigs (24.5 ± 1.8 kg) were anesthetized, and an NIRS probe was attached directly to each organ. Approximately 0.2, 0.5, 1, and 2 µg/kg/min of norepinephrine were administered in a stepwise manner, followed by 0.5, 1, 2, and 5 µg/kg/min of sodium nitroprusside in normal condition. Moreover, 1 µg/kg/h of lipopolysaccharide was administered continuously after 100 µg bolus to create endotoxic shock and after 1,000 mL of crystalloid infusion and high-dose norepinephrine (2, 5, 10, and 20 µg/kg/min) and vasopressin (0.6, 1.5, 3, and 6 U/min) were administered in a stepwise manner. The relationship between the MAP and each tissue oxygenation index (TOI) during vasopressor infusion was evaluated. Results: Three pigs died after receiving lipopolysaccharides, and 10 were analyzed. An increase of >20% from the baseline MAP induced by high-dose norepinephrine during endotoxic shock reduced the TOI in all organs except the liver. The elevation of MAP to baseline with vasopressin alone increased the kidney and liver TOIs and decreased the tongue TOI. Conclusion: Forced blood pressure elevation with high-dose norepinephrine during endotoxic shock decreased the microcirculation of vital organs, especially the kidney. Cerebral TOI may be useful for identifying the upper limit of blood pressure, at which norepinephrine impairs microcirculation.

Hydrogen attenuates endothelial glycocalyx damage associated with partial cardiopulmonary bypass in rats.

Cardiopulmonary bypass (CPB) causes systemic inflammation and endothelial glycocalyx damage. Hydrogen has anti-oxidant and anti-inflammatory properties; therefore, we hypothesized that hydrogen would alleviate endothelial glycocalyx damage caused by CPB. Twenty-eight male Sprague-Dawley rats were randomly divided into four groups (n = 7 per group), as follows: sham, control, 2% hydrogen, and 4% hydrogen. The rats were subjected to 90 minutes of partial CPB followed by 120 minutes of observation. In the hydrogen groups, hydrogen was administered via the ventilator and artificial lung during CPB, and via the ventilator for 60 minutes after CPB. After observation, blood collection, lung extraction, and perfusion fixation were performed, and the heart, lung, and brain endothelial glycocalyx thickness was measured by electron microscopy. The serum syndecan-1 concentration, a glycocalyx component, in the 4% hydrogen group (5.7 ± 4.4 pg/mL) was lower than in the control (19.5 ± 6.6 pg/mL) and 2% hydrogen (19.8 ± 5.0 pg/mL) groups (P < 0.001 for each), but it was not significantly different from the sham group (6.2 ± 4.0 pg/mL, P = 0.999). The endothelial glycocalyces of the heart and lung in the 4% hydrogen group were thicker than in the control group. The 4% hydrogen group had lower inflammatory cytokine concentrations (interleukin-1ß and tumor necrosis factor-α) in serum and lung tissue, as well as a lower serum malondialdehyde concentration, than the control group. The 2% hydrogen group showed no significant difference in the serum syndecan-1 concentration compared with the control group. However, non-significant decreases in serum and lung tissue inflammatory cytokine concentrations, as well as in serum malondialdehyde concentration, were observed. Administration of 4% hydrogen via artificial and autologous lungs attenuated endothelial glycocalyx damage caused by partial CPB in rats, which might be mediated by the anti-inflammatory and anti-oxidant properties of hydrogen.

Electrocardiogram Cream Reduces Skin-Electrode Impedance Upon Neuromuscular Monitoring Using TOF-Cuff®.

Background Mechanistic insight into the high failure rate of TOF-Cuff® (RGB Medical Devices, Madrid, Spain) measurements on the lower leg is unclear. Aims We aimed to determine whether materials applied to pseudo-skin can reduce the impedance between a model arm and TOF-Cuff® electrodes and whether a material between TOF-Cuff® electrodes and the patient's skin surface decreases the skin-TOF-Cuff® electrode impedance within the appropriate range. Methods This was a combination of an in vitro study using non-living materials and a prospective observational clinical study. Eight patients aged > 70 years who had undergone elective surgery were eligible. One of the primary outcomes was whether water, electrocardiogram (ECG) cream, or ECG gel applied on the pseudo-skin could reduce the impedance between the model arm and the TOF-Cuff® electrodes in the in vitro study. Another was whether a material between the TOF-Cuff® electrodes and the patient's skin surface decreased the skin-TOF-Cuff® electrode impedance to an appropriate level of less than 5,000 Ω in the clinical study. Results The application of water, ECG cream, and ECG gel similarly reduced the impedance values within the electrical circuit in the in vitro study. ECG cream application between the patient's skin surface and the TOF-Cuff® electrodes decreased the skin-TOF-Cuff® electrode impedance (median (interquartile range (IQR)) Ω) from 8,600 (6,450 to 9,775) to 2,000 (1,600 to 2,600) (P = 0.012) in surgical patients. Conclusion ECG cream application between the patient's skin surface and the TOF-Cuff® electrodes decreased the skin-TOF-Cuff® electrode impedance appropriately, and thus, the application can facilitate precise TOF-Cuff® measurements in patients.

Thromboelastography with platelet mapping to guide anesthetic management of emergency cesarean delivery in a patient with thrombasthenia: a case report.

BACKGROUND: Perinatal management of congenital platelet dysfunction represents a challenge. One of the major concerns is whether neuraxial anesthesia can be applicable for cesarean delivery. We present a patient with thrombasthenia who underwent emergency cesarean delivery. CASE PRESENTATION: A 34-year-old primipara was diagnosed with autosomal dominant thrombasthenia, which was not classified as any known type. A thorough examination revealed that adenosine diphosphate aggregation and collagen aggregation were suppressed. Platelet mapping of viscoelastic testing was used to observe the trajectory of platelet function during pregnancy, which was found to be normal to hypercoagulable until 38 weeks of gestation. On the basis of the results of testing and physiological status, we commenced spinal anesthesia and avoided prophylactic platelet transfusion. CONCLUSION: The platelet mapping of viscoelastic testing was rapid and simple, allowing repeated examinations. We could choose the appropriate anesthesia method and determine the necessity of blood transfusion for a pregnant patient with thrombasthenia.

Stomach, liver, kidney and skeletal muscle autoregulation evaluated by near-infrared spectroscopy in a swine model.

PURPOSE: Different organs have different autoregulatory capacities for blood pressure changes and/or circulatory volume changes. This study assessed the autoregulation of the stomach, liver, kidney and skeletal muscle, under baseline, hypovolemic, and post-fluid-resuscitation conditions using near-infrared spectroscopy (NIRS). METHODS: Ten pigs (bodyweight 24.5 ± 0.5 kg) were anesthetized with 2.5% isoflurane and administered 0.5, 1, 2 and 5 µg kg- 1 min- 1 of phenylephrine at 10-min intervals, followed by similar stepwise infusion of sodium nitroprusside (SNP) to induce a wide range of mean arterial pressures (MAPs). A 600-ml bleed was induced to create the hypovolemic condition, and only phenylephrine was re-administered. Hydroxyethyl starch (600 ml) was infused to create the post-fluid-resuscitation condition, and phenylephrine and SNP were re-administered. Average relationships between mean arterial pressure (MAP) and each tissue oxygenation index (TOI) were assessed, and the individual relationships were evaluated based on the correlation coefficients between MAP and TOI during each vasoactive drug infusion. RESULTS: Based on the evaluation using each TOI as a substitute of blood flow, the kidney autoregulation was robust, similar to muscle, but had a prominent lower limit. The stomach had weaker autoregulation than the kidney and muscle. The liver had no autoregulation. The kidney TOI showed 2-fold greater changes in response to volume condition changes than the stomach and liver TOIs. CONCLUSION: In our NIRS-based assessment of autoregulatory capacity, the liver oxygenation is highly blood pressure dependent, and the kidney is highly susceptible and the skeletal muscle is highly tolerable to low blood pressure and volume loss.

Comparison of postoperative nausea and vomiting between remimazolam and propofol: a propensity score-matched, retrospective, observational, single-center cohort study.

BACKGROUND: Remimazolam is a novel ultrashort-acting benzodiazepine that has recently become available for general anesthesia. However, the incidence of postoperative nausea and vomiting (PONV) associated with remimazolam remains unknown. In this propensity score-matched, retrospective, observational study, we compared the rates of PONV between remimazolam and propofol. METHODS: In this retrospective observational study, propensity score-matching was performed to minimize selection bias. Patients who received total intravenous anesthesia with remimazolam or propofol at the Hamamatsu University Hospital between August 2020 and July 2021 were enrolled in the study. Data on patient demographics, anesthetic agents, and PONV within the first 24 h were collected and analyzed. RESULTS: Of the 1,239 patients who met the study selection criteria, 585 received remimazolam and 684 received propofol. After propensity score matching, 333 matched pairs were further analyzed. Patient demographics and the anesthetic agents used were comparable between the matched cohorts. The incidence of PONV was significantly higher in the remimazolam group than in the propofol group (35% vs. 21%, P < 0.001). CONCLUSIONS: The incidence of PONV is higher with remimazolam anesthesia than with propofol anesthesia. The findings of this study require confirmation in larger prospective randomized controlled trials.

Influence of hemorrhage and subsequent fluid resuscitation on transcranial motor-evoked potentials under desflurane anesthesia in a swine model.

PURPOSE: Hemorrhage increases the effect of propofol and could contribute to false-positive transcranial motor-evoked potential (TcMEP) responses under total intravenous anesthesia (TIVA). We investigated the influence of hemorrhage and subsequent fluid resuscitation on TcMEPs under desflurane anesthesia. METHODS: Sixteen swine (25.4 ± 0.4 kg) were anesthetized with a 4% end-tidal desflurane concentration (EtDes), which was incrementally increased to 6%, 8%, and 10% and then returned to 4% every 15 min. This procedure was repeated twice (baseline). After baseline measurements, animals were allocated to either the hemorrhage (n = 12) or control (n = 4) group. In the hemorrhage group, 600 ml of blood was removed and the EtDes protocol described above was applied. Hypovolemia was resuscitated using 600 ml of hydroxyethyl starch and the EtDes protocol was applied again. TcMEPs were measured at each EtDes. In the control group, measurements were performed without hemorrhage or fluid infusion. RESULTS: TcMEP responses were observed in all conditions in all limbs with 4% EtDes (0.4 MAC). TcMEP amplitudes decreased according to the EtDes to a greater degree in the lower limbs compared with the upper limbs. Hemorrhage enhanced the effect of desflurane on TcMEP amplitudes, and decreased TcMEP by 41 ± 12% in upper limbs and 63 ± 17% in lower limbs compared with baseline. Subsequent fluid resuscitation did not reverse TcMEP amplitudes. CONCLUSIONS: TcMEP amplitudes decrease during hemorrhage under desflurane anesthesia. This phenomenon might result from an enhanced effect of desflurane on the spinal motor pathway without increasing the desflurane concentration.

Human Vascular Smooth Muscle Function and Oxidative Stress Induced by NADPH Oxidase with the Clinical Implications.

Among reactive oxygen species, superoxide mediates the critical vascular redox signaling, resulting in the regulation of the human cardiovascular system. The reduced form of nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase, NOX) is the source of superoxide and relates to the crucial intracellular pathology and physiology of vascular smooth muscle cells, including contraction, proliferation, apoptosis, and inflammatory response. Human vascular smooth muscle cells express NOX1, 2, 4, and 5 in physiological and pathological conditions, and those enzymes play roles in most cardiovascular disorders caused by hypertension, diabetes, inflammation, and arteriosclerosis. Various physiologically active substances, including angiotensin II, stimulate NOX via the cytosolic subunits' translocation toward the vascular smooth muscle cell membrane. As we have shown, some pathological stimuli such as high glucose augment the enzymatic activity mediated by the phosphatidylinositol 3-kinase-Akt pathway, resulting in the membrane translocation of cytosolic subunits of NOXs. This review highlights and details the roles of human vascular smooth muscle NOXs in the pathophysiology and clinical aspects. The regulation of the enzyme expressed in the vascular smooth muscle cells may lead to the prevention and treatment of human cardiovascular diseases.

Effect of an assessment of fibrin-based rotational thromboelastometry on blood transfusion and clinical outcomes in cardiovascular surgery: A cohort study.

The clinical importance of viscoelastic testing in patient blood management when performing cardiovascular surgery is increasing. We aimed to examine the effect of a blood transfusion protocol including an assessment of fibrin-based rotational thromboelastometry on transfusion volume, mortality, and bleeding complications in patients undergoing cardiac or thoracic aortic surgery. We retrospectively studied a cohort of 376 consecutive patients who underwent cardiopulmonary bypass before (control group: 150 cardiac and 35 thoracic aortic surgeries) and after (assessment group: 154 cardiac and 37 thoracic aortic surgeries) introducing the fibrin polymerization assessment with thromboelastometry in the blood transfusion protocol. The transfusion volume and clinical outcomes were compared between the control and assessment groups, and the standardized (mean) difference (S[M]D) was calculated as an indicator of statistical effect size. Compared with the control group, the assessment group had a lower total blood transfusion volume (mL) in cardiac (2720 ± 1282 vs. 2034 ± 1330, p < 0.0001, [SMD] = 0.68) and thoracic aortic surgeries (5236 ± 2732 vs. 3714 ± 1768, p < 0.0001, SMD = 0.67). The 1-year mortality rates were 1.9 % and 2.7 % in cardiac and thoracic aortic surgeries, respectively. Significant differences were not observed in the 1-year mortality (3.2 % vs. 1.0 %, p = 0.16, relative risk [RR] = 0.32 with 95 % confidence intervals [CI] = 0.06-1.57, SD = 0.15), re-exploration for bleeding (4.8 % vs. 2.6 %, p = 0.28, RR = 0.53 with 95 % CI = 0.18-1.57, SD = 0.12), and major bleeding (17.3 % vs. 13.0 %, p = 0.31, RR = 0.75 with 95 % CI = 0.46-1.22, SD = 0.12) rates between the control and assessment groups. The assessment of fibrin polymerization with thromboelastometry using the blood transfusion protocol reduced the blood transfusion volume in cardiovascular surgery.

Assessment of the benefits of head-up preoxygenation using near-infrared spectroscopy with pulse oximetry in a swine model.

Compared with supine positioning, head-up positioning improves preoxygenation and prolongs the time to oxygen desaturation. We reevaluated benefits of head-up positioning using near-infrared spectroscopy (NIRS) with pulse oximetry in a pig model. Six pigs (mean ± SD weight: 25.3 ± 0.6 kg) were anesthetized with isoflurane and evaluated in four positions-supine, head-up, head-down, head-up to supine-just before apnea (positions' order after "supine" was randomized). In each position, after 5 min of preoxygenation with 100% oxygen, apnea was induced and the time to SpO2 < 70% measured. Hemodynamic and blood-gas variables and the cerebral tissue oxygenation index (TOI) were evaluated using NIRS and recorded. Hypovolemia was induced by collecting 600 mL blood. Apnea experiment was performed again in each position. The times (seconds) ± SD to SpO2 < 70% were 108 ± 13 (supine), 138 ± 15 (head-up; P < 0.0001 vs all other positions); 101 ± 12 (head-down) and 106 ± 15 (head-up to supine) during normovolemia, and 110 ± 29, 120 ± 7 (not significant vs all other positions), 101 ± 16, and 106 ± 11, respectively, during hypovolemia. Although the TOI was not associated with the positions during normovolemia, the head-up position during hypovolemia decreased TOI from 62% ± 6% (supine) to 50% ± 9% (head-up; P = 0.0019) before preoxygenation, and it remained low during apnea. The head-up position improves preoxygenation, but repositioning to supine negates the benefits. Head-up positioning during evident hypovolemia should be avoided because the cerebral oxygenation could decrease.

Spinal cord autoregulation using near-infrared spectroscopy under normal, hypovolemic, and post-fluid resuscitation conditions in a swine model: a comparison with cerebral autoregulation.

BACKGROUND: Few studies have investigated spinal cord autoregulation using near-infrared spectroscopy (NIRS). Here, we assessed spinal cord autoregulation under normal, hypovolemic, and post-fluid resuscitation conditions compared with cerebral autoregulation. METHODS: Ten pigs (36.1 ± 1.1 kg) were anesthetized with 2.5% isoflurane, before phenylephrine administration at 0.5, 1, 2, and 5 µg kg-1 min-1 in a stepwise fashion at 10-min intervals (baseline), followed by similar administration of sodium nitroprusside (SNP). Hypovolemia was induced by a 600-ml bleed (25% estimated total blood volume). Only phenylephrine was readministered (same protocol). Hypovolemia was reversed by infusing 600 ml hydroxyethyl starch, before readministering phenylephrine and SNP. The relationships between mean arterial pressure (MAP) and cerebral, thoracic, and lumbar spinal cord tissue oxygenation indices (TOIs) were evaluated. RESULTS: Thoracic and lumbar spinal cord TOIs were approximately 15% and 10% lower, respectively, than the cerebral TOI at similar MAPs. The average relationship between MAP and each TOI showed an autoregulatory pattern, but negative correlations were observed in the cerebral TOI during phenylephrine infusion. A 600-ml bleed lowered each relationship < 5% and subsequent fluid resuscitation did not change the relationship. Individual oxygenation responses to blood pressure indicated that the spinal cord is more pressure-passive than the cerebrum. Paradoxical responses (an inverse relationship of tissue oxygenation to MAP) were observed particularly in cerebrum during phenylephrine infusion and were rare in the spinal cord. CONCLUSIONS: Spinal cord autoregulation is less robust than cerebral autoregulation and more pressure-dependent. Similar to cerebral oxygenation, spinal cord oxygenation is volume-tolerant but is more sensitive to hypotension.

Assessment of cerebral and renal autoregulation using near-infrared spectroscopy under normal, hypovolaemic and postfluid resuscitation conditions in a swine model: An observational study.

BACKGROUND: The impact of blood pressure changes on tissue oxygenation differs between vital organs and with blood volume conditions. OBJECTIVE: To assess cerebral and renal autoregulation simultaneously and compare the impact of blood pressure, hypovolaemia and fluid resuscitation on tissue oxygenation using near-infrared spectroscopy. DESIGN: Animal observational study. SETTING: An animal laboratory in Hamamatsu University School of Medicine, Hamamatsu, Japan, from April 2018 to August 2018. ANIMALS: Fifteen pigs, (mean ±â€ŠSD) 25.2 ±â€Š0.4 kg. INTERVENTIONS: The pigs were anaesthetised with 2.5% isoflurane and phenylephrine 0.5, 1, 2 and 5 µg kg min was administered in a stepwise fashion at 10-min intervals (baseline), followed by similar administration of sodium nitroprusside. Hypovolaemia was induced by a 600-ml bleed (33% of estimated total blood volume). Then phenylephrine was administered again (same protocol). Hypovolaemia was reversed by infusion of 600-ml hydroxyethyl starch. Phenylephrine and sodium nitroprusside were then administered again (same protocol). MAIN OUTCOME MEASURES: Average of the relation between mean arterial pressure (MAP) and cerebral or renal tissue oxygenation index (TOI) and individual TOI response during vasoactive drug infusions. RESULTS: The average relationship between MAP and cerebral or renal TOI both showed classic autoregulation patterns, whereas the renal TOI was more pressure-dependent than the cerebral TOI. Hypovolaemia shifted the relationship downward, reducing the cerebral and renal TOIs by approximately 5 and 20%, respectively, at similar MAPs. Subsequent fluid resuscitation preserved the autoregulatory pattern in both organs, not changing cerebral TOI but reducing renal TOI to 10% under baseline. TOI responses in both organs included paradoxical changes (tissue oxygenation changed inversely with MAP) in 60% of animals. Animals with paradoxical reactions maintained more stable cerebral and renal oxygenation. CONCLUSION: Renal oxygenation is more pressure-dependent than pressure-tolerant cerebral oxygenation, and autoregulation is not robust. Renal oxygenation decreased four-fold compared with cerebral oxygenation during hypovolaemia and two-fold during isovolaemic anaemia. Thus, paradoxical responses are part of normal autoregulatory function and beneficial for maintaining stable oxygenation.