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.

Effect of remimazolam versus sevoflurane on intraoperative hemodynamics in noncardiac surgery: a retrospective observational study using propensity score matching.

BACKGROUND: This study compared the effects of remimazolam and sevoflurane on intraoperative hemodynamics including intraoperative hypotension (IOH). RESULTS: This study involved adult patients undergoing noncardiac surgery using remimazolam (Group R) or sevoflurane (Group S) for maintenance anesthesia, and invasive arterial pressure measurements, from September 2020 to March 2023 at our hospital. IOH was defined as a mean blood pressure < 65 mmHg occurring for a cumulative duration of at least 10 min. A 1:1 propensity score-matching method was used. The primary endpoint was the occurrence of IOH, and the secondary endpoints were the cumulative hypotensive time, incidence of vasopressor use, and dose of vasopressor used (ephedrine, phenylephrine, dopamine, and noradrenaline). Group R comprised 169 patients, Group S comprised 393 patients, and a matched cohort of 141 patients was created by propensity score matching. There was no significant difference in the incidence of IOH between the two groups (85.1% in Group R vs. 91.5% in Group S, p = 0.138). Patients in Group R had a significantly lower cumulative hypotension duration (55 [18-119] vs. 83 [39-144] min, p = 0.005), vasopressor use (81.6% vs. 91.5%, p = 0.023), and dose of ephedrine (4 [0-8] vs. 12 [4-20] mg, p < 0.001) than those in Group S. There were no significant differences in the doses of other vasopressors between groups. CONCLUSIONS: Compared with sevoflurane, the maintenance of anesthesia with remimazolam was not associated with a decreased incidence of IOH; however, it reduced the cumulative hypotension time, incidence of vasopressor use, and dose of ephedrine.

Recall of extubation after remimazolam anesthesia with flumazenil antagonism during emergence: a retrospective clinical study.

PURPOSE: This study was performed to examine and compare the incidence of extubation recall in surgical patients who underwent remimazolam anesthesia with flumazenil antagonism during emergence and in those who underwent propofol anesthesia. METHODS: One hundred sixty-three patients who underwent surgery using general endotracheal or supraglottic airway anesthesia with propofol (n = 97) or remimazolam (n = 66) were retrospectively analyzed. Remimazolam was antagonized by flumazenil after discontinuation of remimazolam at the end of surgery. The endotracheal tube or supraglottic airway was removed after surgery was complete, and consciousness and adequate spontaneous breathing were confirmed. The incidence of extubation recall was compared between the remimazolam and propofol anesthesia groups using propensity score matching. RESULTS: Extubation recall was observed in 28 patients (17%). After propensity score matching, the incidence of extubation recall did not significantly differ between the remimazolam and propofol anesthesia groups (15.6% vs. 18.8%; p = 1.000). CONCLUSION: The incidence of extubation recall after remimazolam anesthesia with flumazenil antagonism during emergence did not significantly differ from that after propofol anesthesia.

Dexmedetomidine suppresses serum syndecan-1 elevation and improves survival in a rat hemorrhagic shock model.

Hemorrhagic shock causes vascular endothelial glycocalyx (EGCX) damage and systemic inflammation. Dexmedetomidine (DEX) has anti-inflammatory and EGCX-protective effects, but its effect on hemorrhagic shock has not been investigated. Therefore, we investigated whether DEX reduces inflammation and protects EGCX during hemorrhagic shock. Anesthetized Sprague-Dawley rats were randomly assigned to five groups (n=7 per group): no shock (SHAM), hemorrhagic shock (HS), hemorrhagic shock with DEX (HS+DEX), hemorrhagic shock with DEX and the α7 nicotinic type acetylcholine receptor antagonist methyllycaconitine citrate (HS+DEX/MLA), and hemorrhagic shock with MLA (HS+MLA). HS was induced by shedding blood to a mean blood pressure of 25-30 mmHg, which was maintained for 30 min, after which rats were resuscitated with Ringer's lactate solution at three times the bleeding volume. The survival rate was assessed up to 3 h after the start of fluid resuscitation. Serum tumor necrosis factor-alpha (TNF-α) and syndecan-1 concentrations, and wet-to-dry ratio of the heart were measured 90 min after the start of fluid resuscitation. The survival rate after 3 h was significantly higher in the HS+DEX group than in the HS group. Serum TNF-α and syndecan-1 concentrations, and the wet-to-dry ratio of heart were elevated by HS, but significantly decreased by DEX. These effects were antagonized by MLA. DEX suppressed the inflammatory response and serum syndecan-1 elevation, and prolonged survival in rats with HS.

Inhalation of 2% Hydrogen Improves Survival Rate and Attenuates Shedding of Vascular Endothelial Glycocalyx in Rats with Heat Stroke.

ABSTRACT: Heat stroke is characterized by excessive oxidative stress and inflammatory responses, both of which are implicated in vascular endothelial glycocalyx shedding and heat-stroke mortality. Although molecular hydrogen has antioxidation and anti-inflammatory potency, its effect on the vascular endothelial glycocalyx in heat stroke has not been examined. Therefore, the aim of this study was to investigate the influence of hydrogen inhalation on the survival and thickness of the vascular endothelial glycocalyx of rats subjected to heat stroke. Altogether, 98 Wistar rats were assigned to the experiments. A heat-controlled chamber set at 40°C temperature and 60% humidity was used to induce heat stroke. After preparation, the anesthetized rats that underwent the heating process were subjected to an hour of stabilization in which 0%, 2%, or 4% hydrogen gas was inhaled and maintained until the experiment ended. In addition to survival rate assessments, blood samples and left ventricles were collected to evaluate the thickness of the vascular endothelial glycocalyx and relevant biomarkers. The results showed that 2% hydrogen gas significantly improved survival in the heat-stroked rats and partially preserved the thickness of the endothelial glycocalyx. In addition, serum levels of endotoxin, syndecan-1, malondialdehyde, and tumor necrosis factor-α decreased, whereas superoxide dismutase levels increased, indicating that inhalation of 2% hydrogen attenuated the damage to the vascular endothelial glycocalyx through its antioxidative and anti-inflammatory effects.

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.

1.2% Hydrogen gas inhalation protects the endothelial glycocalyx during hemorrhagic shock: a prospective laboratory study in rats.

PURPOSE: Hydrogen gas (H2) inhalation improved the survival rate of hemorrhagic shock. However, its mechanisms are unknown. We hypothesized that H2 protected the endothelial glycocalyx during hemorrhagic shock and prolonged survival time. METHODS: 83 Sprague-Dawley rats were anesthetized with isoflurane. The animals were randomly assigned to 5 groups: room air with no shock, 1.2% H2 with no shock, room air with shock (Control-S), 1.2% H2 with shock (H21.2%-S), and 3.0% H2 with shock (H23.0%-S). Shock groups were bled to a mean arterial pressure of 30-35 mmHg and held for 60 min, then resuscitated with normal saline at fourfold the amount of the shed blood volume. RESULTS: The syndecan-1 level was significantly lower in the H21.2%-S [8.3 ± 6.6 ng/ml; P = 0.01; 95% confidence interval (CI), 3.2-35.8] than in the Control-S (27.9 ± 17.0 ng/ml). The endothelial glycocalyx was significantly thicker in the H21.2%-S (0.15 ± 0.02 µm; P = 0.007; 95% CI, 0.02-0.2) than in the Control-S (0.06 ± 0.02 µm). The survival time was longer in the H21.2%-S (327 ± 67 min, P = 0.0160) than in the Control-S (246 ± 69 min). The hemoglobin level was significantly lower in the H21.2%-S (9.4 ± 0.5 g/dl; P = 0.0034; 95% CI, 0.6-2.9) than in the Control-S (11.1 ± 0.8 g/dl). However, the H23.0%-S was not significant. CONCLUSIONS: Inhalation of 1.2% H2 gas protected the endothelial glycocalyx and prolonged survival time during hemorrhagic shock. Therapeutic efficacy might vary depending on the concentration.

Dexmedetomidine preserves the endothelial glycocalyx and improves survival in a rat heatstroke model.

PURPOSE: Heatstroke causes systemic inflammation, followed by vascular endothelial damage. The normal vascular endothelium is coated by endothelial glycocalyx (EGCX). Dexmedetomidine (DEX) has an anti-inflammatory effect, but there has been little investigation on the influence of heatstroke on EGCX and the effect of DEX on this condition. Therefore, we examined whether EGCX was disrupted in heatstroke and if DEX improved survival and preserves EGCX. METHODS: Anesthetized Wistar rats were randomly assigned to three groups: a DEX group treated with DEX (5 µg/kg/h) and 0.9% saline infused continuously at 10 ml/kg/h during heat exposure; a NSS group given 0.9% saline during heat exposure; and a SHAM group given 0.9% saline alone without heat exposure. Heatstroke was induced by exposure to an ambient temperature of 40 °C with relative humidity of 60%. The survival rate was assessed up to 2 h after the start of heat exposure. Plasma levels of syndecan-1 and the thickness of EGCX using electron microscopy were measured when the systolic blood pressure fell to less than 80 mmHg. RESULTS: The survival rate after 2 h of heat exposure was significantly higher in the DEX group compared to the NSS group (89% vs. 22%, P = 0.004). Plasma levels of syndecan-1 were 0.6 ± 1.3, 9.7 ± 5.9, and 2.1 ± 3.4 ng/ml in the SHAM, NSS and DEX groups, respectively (P = 0.013). The thickness of EGCX was significantly higher in the DEX group compared with the NSS group (P = 0.001). CONCLUSIONS: EGCX was disrupted in heatstroke, and DEX improved survival and preserved EGCX.

[Assessment of Fibrinogen Replacement Therapy by the Combined Simulation of the Fibrinogen Concentration and Fibrin Polymerization].

BACKGROUND: Fibrinogen replacement therapy is effective for attaining perioperative hemostasis in critical bleeding due to acquired hypofibrinogenemia. By simulating the fibrinogen level and fibrin polymerization, we compared the effect of fibrinogen replacement therapy using cryoprecipitate or fibrinogen concentrate versus the effect of fresh frozen plasma. METHODS: We simulated the plasma concentration of fibrinogen during fibrinogen replacement therapy in a model of cardiopulmonary bypass (CPB) and intensive care unit (ICU). We estimated fibrin polymerization (FIBTEM A10, thromboelastometry) by the simulated fibrinogen level, and compared this value with the fibrinogen level and FIBTEM in clinical patients. RESULTS: In the simulation model of CPB and ICU, cryoprecipitate and fibrinogen concentrate both effectively restored the fibrinogen level and FIBTEM, compared to fresh frozen plasma. In clinical patients, the simulated values of the fibrinogen level and FIBTEM after administering the fibrinogen concentrate were similar to the measured values. CONCLUSIONS: In the simulation model, which combines the fibrinogen level and fibrin polymerization, cryoprecipitate and fibrinogen concentrate effectively normalize the fibrinogen level and fibrin polymerization, compared to fresh frozen plasma. The fibrinogen concentrate also demonstrated efficacy in treating hypofibrinogenemia in clinical patients. The combined simulation model is useful in assessing the efficacy of fibrinogen replacement therapy by cryoprecipitate or by fibrinogen concentrate.

Four-Group Classification Based on Fibrinogen Level and Fibrin Polymerization Associated With Postoperative Bleeding in Cardiac Surgery.

Fibrinogen and fibrin formation have a key role in perioperative hemostasis. The aim of this study is to examine the association of postoperative hemostasis with a combined evaluation of the fibrinogen level and fibrin polymerization in cardiac surgery. We retrospectively classified 215 consecutive cardiac surgery patients into 4 groups (Fuji-san classification) that were divided by fibrinogen level <150 mg/dL (ie, hypofibrinogenemia) and fibrinogen thromboelastometry value at 10 minutes with rotational thromboelastometry <6 mm (ie, low fibrin polymerization) at the warming of cardiopulmonary bypass. Four groups resulted; group I, the acceptable range (n = 85); group II, only hypofibrinogenemia (<150 mg/dL, ≥6 mm, n = 63); group III, hypofibrinogenemia and low fibrin polymerization (<150 mg/dL, <6 mm, n = 60); and group IV, only low fibrin polymerization (≥150 mg/dL, <6 mm, n = 7). The risk of chest tube drainage volume greater than 500 mL within the first 24 hours after surgery (with group I as the reference) was increased in group II (odds ratio [OR], 3.3; 95% confidence interval [CI], 1.5-7.4; P < .01) and group III (OR, 8.5; 95% CI, 3.5-21.7; P < .01), and the risk greater than 1000 mL (with group I as the reference) was increased in group III (OR, 4.0; 95% CI, 1.1-17.3; P = .03) and group IV (OR, 23.1; 95% CI, 3.2-201.0; P < .01). Intraoperative blood transfusions were decreased by 24.5%, after stratifying the starting amount of fresh frozen plasma by the 4-group classification in the recent consecutive 65 (30.2%) patients (P < .01). The 4-group classification is associated with postoperative bleeding and may improve the quality of perioperative blood transfusion in cardiac surgery.

[Vocal cord paralysis associated with tracheal intubation: incidence, risk analysis, and classification of severity].

Vocal cord paralysis after tracheal intubation is rare. It causes severe hoarseness and aspiration, and delays recovery and discharge. Arytenoid cartilage dislocation and recurrent nerve paralysis are main causes of vocal cord paralysis. Physical stimulation of the tracheal tube as well as patient and surgical characteristics also contribute. Vocal cord paralysis occurs in 1 (0.07%) of 1,500 general surgery patients and on the left side in 70% of cases. It is associated with surgery/anesthesia time (two-fold, 3-6 hours; 15-fold, over 6 hours), age (three-fold, over 50 years), and diabetes mellitus or hypertension (two-fold). Symptoms resolve in 2-3 months. In adult cardiovascular surgery, vocal cord paralysis occurs in 1 (0.7-2%) of 50-100 cardiac surgery patients and 1 (8.6-32%) of 3-10 thoracic aortic surgery patients. In pediatric cardiac surgery, vocal cord paralysis occurs in 1 (0.1-0.5%) of 200-1,000 patients. We classified the severity of vocal cord paralysis as I, severe hoarseness; II, aspiration or dysphagia; and III, bilateral vocal cord paralysis, aspiration pneumonia, or the need for tracheal re-intubation or tracheotomy. We discuss the importance of informed consent for the patient and family.

The characteristics of postoperative fentanyl effect-site concentration during intravenous fentanyl analgesia after posterior lumbar spine fusion.

OBJECTIVE: To examine the characteristics of postoperative fentanyl effect-site concentrations during intravenous analgesia in patients requiring or not requiring a fentanyl bolus and in patients with or without postoperative nausea and vomiting (PONV). DESIGN: Retrospective observational study. SETTING: University-affiliated general hospital. PATIENTS: Sixty patients who underwent posterior lumbar spine fusion. MAIN OUTCOME MEASURES: The authors simulated the fentanyl effect-site concentration for 48 postoperative hours and compared it between patients who did and did not require a fentanyl bolus and between patients who did and did not experience PONV. RESULTS: At the end of anesthesia, the fentanyl effect-site concentration was similar between 37 (61.7 percent) patients requiring and 23 (38.3 percent) patients not requiring a postoperative fentanyl bolus (p=0.97). Within the first 12 postoperative hours, the concentration decreased in both groups (p < 0.01). The fentanyl effect-site concentration was higher in patients requiring a postoperative fentanyl bolus (within 12 hours, 1.4 ± 0.32 ng/mL vs 0.89 ± 0.35 ng/mL; between 12 and 48 hours, 0.94 ± 0.19 ng/mL vs 0.57 ± 0.09 ng/mL) (p < 0.05). PONV occurred in 22 (36.6 percent) patients, but more so in women (68.2 percent; p < 0.01); PONV was similar between patients requiring and not requiring a fentanyl bolus (p=0.78). Between the 12th and 48th postoperative hours, fentanyl effect-site concentrations were higher in patients with PONV (0.61 ± 0.10 ng/mL vs 0.57 ± 0.10 ng/mL, p=0.03). CONCLUSIONS: Patients needing a postoperative fentanyl bolus require a higher fentanyl effect-site concentration possibly because of individual variations, and PONV depends on the postoperative fentanyl effect-site concentration.

[Perioperative management of two patients with renal malignant tumor involving the vena cava].

Two patients underwent resection of renal malignant tumors involving vena cava. Such tumors occasionally extend to the inferior vena cava with tumor thrombus and invasion to the lymph nodes and adjacent organs. Perioperative management of patients with these tumors is difficult because of the risk of pulmonary embolism and massive bleeding, and requires appropriate cooperation among the surgical team. In case 1, a 56-year-old man, renal cell carcinoma with tumor thrombus had extended into the intrahepatic vena cava. It was resected after isolating the liver from vena cava and incising the cross-clamped inferior vena cava without extracorporeal circulation or blood transfusion. A prosthetic graft replaced the inferior vena cava. In case 2, a 64-year-old woman, renal pelvis cancer adhered to the inferior vena cava and the mesentery with enlarged lymph nodes. It was separated from the inferior vena cava and removed with the ascending colon. The patient received a blood transfusion of approximately 2,000ml. Cardiomyopathy associated with a left ventricular outflow tract pressure gradient of 100mmHg required perioperative management. After surgery, both patients underwent controlled ventilation in the intensive care unit. After recovery, they were discharged without complications. We discuss perioperative management, with regard to the level of the tumor extension and perioperative complications.