Prospective Randomized Controlled Trial Comparing Anesthetic Management With Remimazolam Besylate and Flumazenil Versus Propofol During Awake Craniotomy Following an Asleep-awake-asleep Method.

BACKGROUND: Awake craniotomy is performed to resect brain tumors in eloquent brain areas to maximize tumor reduction and minimize neurological damage. Evidence suggests that intraoperative anesthetic management of awake craniotomy with remimazolam is safe. We compared the time to arousal and efficacy of anesthetic management with remimazolam and propofol during awake craniotomy. METHODS: In a single-institution randomized, prospective study, patients who underwent elective awake craniotomy were randomized to receive remimazolam and reversal with flumazenil (group R) or propofol (group P). The primary end point was time to awaken. Secondary end points were time to loss of consciousness during induction of anesthesia, the frequency of intraoperative complications (pain, hypertension, seizures, nausea, vomiting, and delayed arousal), and postoperative nausea and vomiting. Intraoperative task performance was assessed using a numerical rating scale (NRS) score. RESULTS: Fifty-eight patients were recruited, of which 52 (26 in each group) were available for the efficacy analysis. Patients in group R had faster mean (±SD) arousal times than those in the P group (890.8±239.8 vs. 1075.4±317.5 s; P=0.013)and higher and more reliable intraoperative task performance (NRS score 8.81±1.50 vs. 7.69±2.36; P=0.043). There were no significant intraoperative complications. CONCLUSIONS: Compared with propofol, remimazolam was associated with more rapid loss of consciousness and, after administration of flumazenil, with faster arousal times and improved intraoperative task performance.

Elevated level of urinary tellurium is a potential risk for increase of blood pressure in humans and mice.

BACKGROUND: People worldwide are routinely exposed to tellurium mainly via dietary ingestion. There has been no study to clarify the contribution of tellurium to blood pressure in humans or animals. METHODS: In this cross-sectional study conducted in a general population of 2592 residents in Japan, the associations of urinary tellurium levels with blood pressure and prevalence of hypertension were investigated. The potential sources of tellurium were also investigated. An interventional study in mice confirmed the effect of tellurium exposure on blood pressure. RESULTS: Linear and logistic regression analyses with consideration of confounders including urinary sodium-potassium ratio showed significant positive associations of urinary tellurium level with prevalence of hypertension and blood pressure. Cereals/beans and vegetables/fruits were determined to be potential dietary sources of tellurium exposure. Intermediary analysis suggested that increased intake of cereals/beans, but not that of vegetables/fruits, is positively associated with the tellurium-mediated risk of hypertension. Correspondingly, the mouse study showed that exposure to a putative human-equivalent dose of tellurium via drinking water increased blood pressure with an elevated level of urinary tellurium. The temporally increased blood pressure was decreased to the normal level by a break of tellurium exposure with a reduced level of urinary tellurium. CONCLUSIONS: The interdisciplinary approach provided the first evidence that tellurium exposure is a potential risk for increase of blood pressure. Since the human urinary tellurium level in this study is comparable with the levels in general populations in other Asian and European countries in previous studies, exposure to tellurium may be a latent universal risk for hypertension.

Use of Thromboelastography in Coronary Artery Bypass Grafting in a Patient With Factor â ¤ Deficiency With Platelet Function Disorders: A Case Report and Literature Review.

Reports on cases of factor Ⅴ (FⅤ) deficiency complicated by platelet function disorders in patients undergoing cardiac surgery are rare, and the utilization of thromboelastography in such cases is limited. This case presents a unique case of FⅤ deficiency complicated by platelet function disorders, highlighting the significance of tailored transfusion strategies guided by thromboelastography (TEG). A 64-year-old hemodialysis patient who was diagnosed with FⅤ deficiency 24 years prior presented for an on-pump coronary artery bypass graft. The decrease in FⅤ activity on preoperative examination was mild. Based on this finding, it was determined that preoperative fresh frozen plasma supplementation was not required. However, the case was complicated by platelet function disorders; therefore, a preoperative transfusion of platelet concentrate was performed to correct the decreased platelet function, enabling subsequent surgery. Intraoperative and postoperative transfusion strategies were guided by TEG. This study highlights TEG-guided transfusion management as a viable option for patients with FⅤ deficiency complicated by platelet function disorders.

Anxiety evaluated by the Hospital Anxiety and Depression Scale as a predictor of postoperative nausea and vomiting: a pilot study.

The incidence of postoperative nausea and vomiting (PONV) remains high, and improving the accuracy of PONV prediction remains challenging. The primary aim of this study is to examine the impact of anxiety scores evaluated using the Hospital Anxiety and Depression Scale (HADS) on the PONV prediction model. We hypothesized that anxiety and depression, quantified using the HADS, could improve the accuracy of the PONV predictive model. This pilot study evaluated 100 patients. The HADS was conducted by a self-evaluation method before thoracoscopic surgery for lung tumors, and the anesthesia method was standardized. The criterion was whether the nurse in charge of the patient who complained of PONV assessed that drug administration was necessary. As the main analysis, the odds ratio of the HADS score for predicting PONV was evaluated using multivariable logistic regression models. Further, the receiver operating characteristic (ROC) curves of the model with the HADS score added to the variables of without-anxiety predictors and the model with the variables of without-anxiety predictors only were compared. The anxiety score was significantly higher in the PONV group than in the no PONV group (P = 0.021). For predictive accuracy, the model that included age, sex, smoking history, history of PONV, and anxiety score had a higher area under the ROC curve than did the model excluding the anxiety score (P = 0.021). In conclusion, the findings indicate that the HADS is worth investigating as a predictor of PONV.

Amplitude at 10 min in thromboelastography predicts maximum amplitude: a single-center observational study.

Thromboelastography is a quantitative test widely used to measure the efficiency of blood clotting. However, awaiting the results of maximum amplitude (MA) is necessary for determining the need for platelet- and fibrinogen-containing products. A more rapid prediction of MA could facilitate faster preparation and administration of blood transfusion products, thereby resulting in coagulation improvement. In this retrospective study, we hypothesized that early amplitude at 10 min (A10) could be a predictor of MA. Therefore, we investigated whether MA can be rapidly inferred from thromboelastographic 6 s (TEG6s) measurements and evaluated its correlation with A10. We extracted TEG6s measurements obtained in operating rooms and intensive care units of our hospital between January 2018 and December 2022. The correlation of MA with display items of TEG6s results, including reaction time, kinetics, α angle, activated clotting time, and A10, was evaluated. The relationship between citrated rapid TEG (CRT)-A10 and CRT-MA, as well as between citrated functional fibrinogen (CFF)-A10 and CFF-MA, were evaluated if A10 and MA showed a good correlation. The results showed good correlations between CRT-A10 and CRT-MA, as well as between CFF-A10 and CFF-MA. Therefore, evaluating A10 using TEG6s could predict MA.

Thromboelastographic evaluation after cardiac surgery optimizes transfusion requirements in the intensive care unit: a single-center retrospective cohort study using an inverse probability weighting method.

OBJECTIVE: There are no reports from Japan showing the effects of using the thromboelastography algorithm on transfusion requirements after Intensive Care Unit (ICU) admission, and post-implementation knowledge regarding the thromboelastography algorithm under the Japanese healthcare system is insufficient. Therefore, this study aimed to clarify the effect of the TEG6s thromboelastography algorithm on transfusion requirements for patients in the ICU after cardiac surgery. METHODS: We retrospectively compared the requirements for blood transfusion up to 24 h after ICU admission using the thromboelastography algorithm (January 2021 to April 2022) (thromboelastography group; n = 201) and specialist consultation with surgeons and anesthesiologists (January 2018 to December 2020) (non-thromboelastography group; n = 494). RESULTS: There were no significant between-group differences in terms of age, height, weight, body mass index, operative procedure, duration of surgery or cardiopulmonary bypass, body temperature, or urine volume during surgical intervention. Moreover, there was no significant between-group difference in the amount of drainage at 24 h after ICU admission. However, crystalloid and urine volumes were significantly higher in the thromboelastography group than in the non-thromboelastography group. Additionally, fresh-frozen plasma (FFP) transfusion volumes were significantly lower in the thromboelastography group. However, there were no significant between-group differences in red blood cell count or platelet transfusion volume. After variable adjustment, the amount of FFP used from the operating room to 24 h after ICU admission was significantly reduced in the thromboelastography group. CONCLUSIONS: The thromboelastography algorithm optimized transfusion requirements at 24 h after admission to the ICU following cardiac surgery.

Intraoperative hypotension affects postoperative acute kidney injury depending on the invasiveness of abdominal surgery: A retrospective cohort study.

Intraoperative hypotension (IOH) or highly invasive surgery adversely affects postoperative clinical outcomes. It is, however, unclear whether IOH affects postoperative acute kidney injury (AKI) depending on the invasiveness of abdominal surgery. We speculated that IOH in highly invasive abdominal surgery is a significant risk factor for postoperative AKI. We retrospectively reviewed the data of 448 patients who underwent abdominal surgery. Patients were divided into 3 groups: highly (such as pancreaticoduodenectomy and hepatectomy), moderately (open abdominal surgery), and minimally (laparoscopic surgery) invasive surgeries. The association between the time-weighted average (TWA) of mean arterial pressure (MAP) values (≤60 and ≤ 55 mm Hg) and AKI occurrences in each group was assessed. Postoperative AKI occurred after highly, moderately, and minimally invasive surgeries in 33 of 222 (14.9%), 14 of 110 (12.7%), and 12 of 116 (10.3%) cases, respectively (P = .526). The median [interquartile range] of TWA-MAP ≤ 60 mm Hg, as an IOH parameter, was 0.94 [0.33-2.08] mm Hg in highly, 0.54 [0.16-1.46] mm Hg in moderately, and 0.14 [0.03-0.57] mm Hg in minimally invasive surgeries (P < 0001). In addition, there was a significant association between TWA-MAP and AKI in highly invasive surgery, unlike in moderately and minimally invasive surgery, with adjusted odds ratios (95% confidence interval) for TWA-MAP ≤ 60 and ≤ 55 mm Hg associated with AKI of 1.23 [1.00-1.52] (P = .049) and 1.55 [1.02-2.36] (P = .041), respectively. Intraoperative MAP ≤ 60 mm Hg in highly invasive abdominal surgery is associated with postoperative AKI, compared to moderately and minimally invasive surgeries. Additionally, low MAP thresholds in highly invasive surgery increase postoperative AKI risk.

Propofol elicits apoptosis and attenuates cell growth in esophageal cancer cell lines.

Propofol is a pharmaceutical agent commonly used as an intravenous anesthetic in surgical treatments and a sedative in intensive care. However, it is largely unknown how exposure to propofol affects the proliferation, invasion, and apoptosis of neoplastic cells in esophageal cancer. In this study, we sought to elucidate the impact of propofol exposure on the growth properties of human esophageal cancer cell lines in vitro. We treated two human esophageal cancer cell lines, KYSE30 and KYSE960, with up to 10 µg/mL of propofol for 12-36 h. The treated cells were then analyzed by cell proliferation assay, Matrigel invasion assay, quantification of caspase-3/7 and -9 activities, and cell staining with Annexin V and 7-aminoactinomycin D to detect early apoptosis and cell death, respectively, via flow cytometry. We found that 3-5 µg/mL propofol reduced the growth and Matrigel invasion of both cell lines in a dose-dependent manner. Executioner caspase-3/7, but not caspase-9 involved in intrinsic apoptosis pathway, was activated by cell exposure to 3-5 µg/mL propofol. In addition, 3-5 µg/mL propofol augmented early apoptosis in both cell lines and increased cell death in the KYSE30 cell line. In summary, exposure to propofol, at concentrations up to 5 µg/mL, led to the reduction of cell growth and Matrigel invasion, as well as the augmentation of apoptosis in esophageal cancer cell lines. These data will help define a methodology to safely utilize propofol, a common general anesthetic and sedative, with esophageal cancer patients.

Fibcare® shows correlation with fibrinogen levels by the Clauss method during cardiopulmonary bypass.

Central laboratory measurements are time consuming, while rapid fibrinogen level measurements within the operating room improve transfusion strategies. We aimed to clarify the correlation between fibrinogen concentrations (measured using Fibcare® and the Clauss fibrinogen assay in a central laboratory) during cardiovascular surgery with cardiopulmonary bypass. Data of patients whose Fibcare, traditional laboratory-based testing, and thromboelastographic results were measured using the same blood sample during cardiopulmonary bypass from February 2021 to January 2022 were retrospectively examined. We analyzed correlation in categories of body temperature during cardiopulmonary bypass: total cases, mild hypothermia (28-34°C), and moderate or severe hypothermia (<28°C). The Clauss fibrinogen assay was performed in 123 cases, Fibcare in 107, and thromboelastography in 91. For mild hypothermia, moderate or severe hypothermia, and overall, the root mean squared error and R-square in Fibcare were 16.1 and 0.86, 13.1 and 0.87, and 14.9 and 0.87, respectively, and for thromboelastography, they were 3.26 and 0.74, 2.70 and 0.79, and 3.08 and 0.75, respectively. A significant relationship was noted between Fibcare and Claus fibrinogen analysis regardless of body temperature during cardiopulmonary bypass. The measurement of fibrinogen levels using Fibcare allows for faster transfusion preparation than that of the traditional Clauss fibrinogen assay.

Life-threatening chlorhexidine anaphylaxis caused by skin preparation before chlorhexidine-free central venous catheter insertion: a case report and literature review.

Chlorhexidine is a common cause of perioperative anaphylaxis, and global regulatory authorities have issued warnings about anaphylaxis due to chlorhexidine-containing central venous catheters (CVC) and its mucosal absorption. We present a case of life-threatening anaphylaxis after CVC insertion caused by chlorhexidine used for skin preparation. The onset of anaphylaxis was rapid and very severe, resulting in pulseless electrical activity. The patient was successfully resuscitated by emergency veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Our case suggests that even skin preparation before chlorhexidine-free CVC insertion can cause life-threatening anaphylaxis. We reviewed the literature on chlorhexidine anaphylaxis cases and categorized all potential routes of chlorhexidine exposure to assess the risk following skin preparation. Our results showed that skin preparation before CVC insertion was the third most common cause of chlorhexidine anaphylaxis after transurethral exposure and chlorhexidine-containing CVCs. However, skin preparation with chlorhexidine before CVC insertion was sometimes overlooked as a cause of chlorhexidine anaphylaxis, and its risk might be underestimated. Further, no previous reports have described life-threatening anaphylaxis solely due to chlorhexidine skin preparation before CVC insertion. CVC insertion might cause the chlorhexidine used for skin preparation to reach the vascular system and should be recognized as a potential cause of life-threatening chlorhexidine anaphylaxis.

Enteral liquid ventilation oxygenates a hypoxic pig model.

The potential of extrapulmonary ventilation pathways remains largely unexplored. Here, we assessed the enteral ventilation approach in hypoxic porcine models under controlled mechanical ventilation. 20 mL/kg of oxygenated perfluorodecalin (O2-PFD) was intra-anally delivered by a rectal tube. We simultaneously monitored arterial and pulmonary arterial blood gases every 2 min up to 30 min to determine the gut-mediated systemic and venous oxygenation kinetics. Intrarectal O2-PFD administration significantly increased the partial pressure of oxygen in arterial blood from 54.5 ± 6.4 to 61.1 ± 6.2 mmHg (mean ± SD) and reduced the partial pressure of carbon dioxide from 38.0 ± 5.6 to 34.4 ± 5.9 mmHg. Early oxygen transfer dynamics inversely correlate with baseline oxygenation status. SvO2 dynamic monitoring data indicated that oxygenation likely originated from the venous outflow of the broad segment of large intestine including the inferior mesenteric vein route. Enteral ventilation pathway offers an effective means for systemic oxygenation, thus warranting further clinical development.

Effect of cerebrospinal fluid drainage pressure in descending and thoracoabdominal aortic repair: a prospective multicenter observational study.

PURPOSE: Cerebrospinal fluid drainage (CSFD) is recommended during open or endovascular thoracic aortic repair. However, the incidence of CSFD complications is still high. Recently, CSF pressure has been kept high to avoid complications, but the efficacy of CSFD at higher pressures has not been confirmed. We hypothesize that CSFD at higher pressures is effective for preventing motor deficits. METHODS: This prospective observational study included 14 hospitals that are members of the Japanese Society of Cardiovascular Anesthesiologists. Patients who underwent thoracic and thoracoabdominal aortic repair were divided into four groups: Group 1, CSF pressure around 10 mmHg; Group 2, CSF pressure around 15 mmHg; Group 3, CSFD initiated when motor evoked potential amplitudes decreased; and Group 4, no CSFD. We assessed the association between the CSFD group and motor deficits using mixed-effects logistic regression with a random intercept for the institution. RESULTS: Of 1072 patients in the study, 84 patients (open surgery, 51; thoracic endovascular aortic repair, 33) had motor deficits at discharge. Groups 1 and 2 were not associated with motor deficits (Group 1, odds ratio (OR): 1.53, 95% confidence interval (95% CI): 0.71-3.29, p = 0.276; Group 2, OR: 1.73, 95% CI: 0.62-4.82) when compared with Group 4. Group 3 was significantly more prone to motor deficits than Group 4 (OR: 2.56, 95% CI: 1.27-5.17, p = 0.009). CONCLUSION: CSFD is not associated with motor deficits in thoracic and thoracoabdominal aortic repair with CSF pressure around 10 or 15 mmHg.

Accuracy of a noninvasive estimated continuous cardiac output measurement under different respiratory conditions: a prospective observational study.

PURPOSE: The estimated continuous cardiac output (esCCO) system was recently developed as a noninvasive hemodynamic monitoring alternative to the thermodilution cardiac output (TDCO). However, the accuracy of continuous cardiac output measurements by the esCCO system compared to TDCO under different respiratory conditions remains unclear. This prospective study aimed to assess the clinical accuracy of the esCCO system by continuously measuring the esCCO and TDCO. METHODS: Forty patients who had undergone cardiac surgery with a pulmonary artery catheter were enrolled. We compared the esCCO with TDCO from mechanical ventilation to spontaneous respiration through extubation. Patients undergoing cardiac pacing during esCCO measurement, those receiving treatment with an intra-aortic balloon pump, and those with measurement errors or missing data were excluded. In total, 23 patients were included. Agreement between the esCCO and TDCO measurements was evaluated using Bland-Altman analysis with a 20 min moving average of the esCCO. RESULTS: The paired esCCO and TDCO measurements (939 points before extubation and 1112 points after extubation) were compared. The respective bias and standard deviation (SD) values were 0.13 L/min and 0.60 L/min before extubation, and - 0.48 L/min and 0.78 L/min after extubation. There was a significant difference in bias before and after extubation (P < 0.001); the SD before and after extubation was not significant (P = 0.315). The percentage errors were 25.1% before extubation and 29.6% after extubation, which is the criterion for acceptance of a new technique. CONCLUSION: The accuracy of the esCCO system is clinically acceptable to that of TDCO under mechanical ventilation and spontaneous respiration.

Cortical activity during the wind-up of flexion reflex and pain: a magnetoencephalographic study using time-frequency analysis.

Wind-up is a nociceptive-specific phenomenon in which pain sensations are facilitated, in a frequency-dependent manner, by the repeated application of noxious stimuli of constant intensity, with invariant tactile sensations. Thus, cortical activities during wind-up could be an alteration associated with pain potentiation. We aimed to investigate somatosensory-evoked cortical responses and induced brain oscillations during wind-up by recording magnetoencephalograms. Wind-up was produced by the application of 11 consecutive electrical stimuli to the sural nerve, repeated at a frequency of 1 Hz without varying the intensity. The augmentation of flexion reflexes and pain rating scores were measured simultaneously as an index of wind-up. In the time-frequency analyses, the γ-band late event-related synchronization and the ß-band event-related desynchronization were observed in the primary somatosensory region and the bilateral operculo-insular region, respectively. Repetitive exposure to the stimuli enhanced these activities, along with an increase in the flexion reflex magnitude. The evoked cortical activity reflected novelty, with no alteration to these repetitive stimuli. Observed oscillations enhanced by repetitive stimulation at a constant intensity could reflect a pain mechanism associated with wind-up.

Effect of intensive insulin therapy on inflammatory response after cardiac surgery using bedside artificial pancreas: A propensity score-matched analysis.

BACKGROUND: Perioperative hyperglycemia leads to poor postoperative clinical outcomes, including compromised immune function, cardiovascular events, and mortality. The optimal perioperative blood glucose levels during cardiac surgery remain unclear. A closed-loop glycemic control system (artificial pancreas, target blood glucose range:120-150 mg/dl) prevents postoperative inflammatory response more effectively than conventional insulin therapy (<200 mg/dl). However, the clinical effects of intensive insulin therapy with strict glycemic control (80-110 mg/dl) are controversial. This study aimed to determine whether intensive insulin therapy would further suppress postoperative inflammatory reactions. METHODS: This study analyzed 262 patients who underwent cardiovascular surgery with cardiopulmonary bypass. The patients were divided into two groups according to their target blood glucose range: 80-110 mg/dl and 120-150 mg/dl. The primary outcome was the difference in the C-reactive protein levels between the two groups. RESULTS: Propensity score matching resulted in 95 patients in each group based on their covariates. There was no difference in the postoperative maximum C-reactive protein levels between the two groups (14.81 ± 5.93 mg/dl vs. 14.34 ± 5.52 mg/dl; p = 0.571) following propensity score matching. Hypoglycemia did not occur during intensive insulin therapy. CONCLUSIONS: Intensive insulin therapy following cardiac surgery with cardiopulmonary bypass did not demonstrate significant advantages in the suppression of postoperative inflammatory reactions compared to that with mild glycemic control. However, intensive insulin therapy using an artificial pancreas was found to be safe, with no hypoglycemic events.