Reviewing COVID-19 from an anesthesiologist's perspective in 2022: JA symposium.

The COVID-19 pandemic is ongoing as of September 2022. Since January 2020 when the first case was reported in Japan, the medical community faced a variety of problems both domestically and internationally. It is meaningful to review the impact of COVID-19 from an anesthesiologist's perspective to clarify our policy for future infectious disease outbreaks. In this year's Journal of Anesthesia (JA) symposium, five experts who were deeply involved in the COVID-19 response reviewed the past 2.5 years and made recommendations for potential future pandemics. Anesthesiologists are specialists in airway management and their role in intubating patients with COVID-19 has received much attention. However, they have also played an important backup role in intensive care as critical care physicians and must be more involved in critical care in regular (non-pandemic) times to properly fulfill this role. It is especially important for the Japan Society of Anesthesiologists and JA to quickly disseminate accurate information on unknown infectious diseases to the medical community and wider society. Therefore, it is important to promptly publish papers that are quality-assured through peer review.

Lipid emulsion facilitates reversal from volatile anesthetics in a rodent model.

BACKGROUND: Lipid emulsion infusion is a first-line therapy against the toxicity of local anesthetics and is a potential treatment for other drug overdoses, especially for highly lipophilic drugs. Considering the lipophilic property of volatile anesthetics, we hypothesized that lipid emulsion could reverse general anesthesia. METHODS: Using adult rats, we tested the effect of lipid emulsion infusion on time to emergence after discontinuation of sevoflurane and isoflurane, and further evaluated restoration of righting reflex under continuous sevoflurane anesthesia. Electroencephalogram during lipid emulsion infusion was also investigated under continuous sevoflurane inhalation. The effect of lipid emulsion on sevoflurane-induced respiratory and hemodynamic depressions was evaluated by measuring respiratory rate, PaCO2 (arterial partial pressure of CO2), blood pressure, and heart rate. The binding property of lipid emulsion on sevoflurane and isoflurane was assessed using in vitro setting with a conical flask. RESULTS: Lipid emulsion infusion significantly decreased time to emergence from sevoflurane anesthesia (131 ± 53 vs. 237 ± 69 s) and restored righting reflex during continuous sevoflurane inhalation, by comparing normal saline infusion. Consistent with the behavioral findings, the electroencephalogram under continuous sevoflurane showed decreased power of the δ bands at 5 min after the initiation of lipid emulsion infusion. In addition to reversing hypnosis, lipid emulsion recovered respiratory as well as hemodynamic depressions induced by sevoflurane. Decreased time to emergence was observed also in isoflurane anesthesia (203 ± 111 vs. 314 ± 154 s). To investigate the binding mechanism of lipid emulsion infusion, in vitro experiments revealed significantly decreased anesthetic concentrations of sevoflurane and isoflurane by mixing with lipid emulsion. CONCLUSIONS: Lipid emulsion facilitated reversal from volatile anesthetics, as shown by several parameters. As lipid emulsion could bind to volatile anesthetics and simply decrease their effects, our findings suggest that lipid emulsion is a potentially useful agent to reverse general anesthesia.

Treatment and outcome of COVID-19 patients in a specialized hospital during the third wave: advance of age and increased mortality compared with the first/second waves.

PURPOSE: To elucidate the clinical course of patients with coronavirus disease 2019 (COVID-19) treated at a specialized hospital mainly for those with mild and moderate severity during the third wave, and to compare that with the first and second (1st/2nd) waves. METHODS: We retrospectively reviewed the severity on admission, treatment, and outcome of a total of 581 patients from September, 2020, to March, 2021, and examined the risk factors for deterioration of respiratory condition, defined as requiring oxygen ≥ 7 L/min for 12 h. RESULTS: The median age was 78 (interquartile range 62-83) years, older than in the 1st/2nd waves (53 years), and 50% of the patients was male. The number of patients classified as mild (peripheral oxygen saturation (SpO2) ≥ 96%), moderate I, II, and severe (requiring admission to the ICU or mechanical ventilation) was 121, 324, 132, and 4, respectively. Favipiravir, ciclesonide, dexamethasone, and/or heparin were administered for treatment. Respiratory condition recovered in 496 (85%) patients. It worsened in 81 patients (14%); 51 (9%) of whom were transferred to tertiary hospitals and 30 (5%) died. Mortality rate increased by fivefold compared during the 1st/2nd waves. Age, male sex, increased body mass index, and C-reactive protein (CRP) on admission were responsible for worsening of the respiratory condition. CONCLUSION: Patients were older in the third wave compared with the 1st/2nd waves. Respiratory condition recovered in 85%; whereas 5% of the patients died. Old age, male sex, increased body mass index, and CRP would be responsible for worsening of the respiratory condition.

Clinical profiles and outcome of patients with COVID-19 in a specialized hospital in Japan.

PURPOSE: To characterize the clinical features and outcome of patients treated at a specialized hospital for coronavirus disease 2019 (COVID-19). METHODS: We retrospectively reviewed the symptoms on admission, treatment, and outcome of a total of 300 patients with mild (peripheral oxygen saturation (SpO2) ≥ 96%), moderate I (93% < SpO2 < 96%), moderate II (SpO2 ≤ 93%) and severe (requiring admission to the ICU or mechanical ventilation) COVID-19. RESULTS: Median age was 53 (interquartile range [IQR] 33-72) years and 57% was male. The number of patients with mild, moderate I, II and severe condition was 85, 138, 61 and 16, respectively. Common presenting symptoms were cough (n = 71), loss of taste (42), loss of smell (39), fever ≥ 37.5 °C (36). Dyspnea was observed only 21 cases; 57 reported no symptoms on admission. Favipiravir, ciclesonide, dexamethasone, and heparin were administered in 106, 168, 65, and 38 patients, respectively, but not remdesivir. The median duration of hospitalization was 10 (7-15) days. All patients with mild and moderate I severity were discharged. Among the 77 patients classified as moderate II or severe, 3 were transferred to tertiary hospitals for further treatment on the day of admission. The respiratory condition worsened in 21 patients; 18 required transfer to tertiary hospitals 3 (median) days after admission and 3 died. CONCLUSION: Respiratory condition recovered in 92%; whereas it worsened in 7% and the mortality rate was 1%. The ratios of male patients, of patients with diabetes mellitus in those with the decreased respiratory condition, were significantly higher than recovered.

COVID-19: review of case reports.

Recently published case reports relating to anesthesia in patients with coronavirus disease (COVID-19) were reviewed. The diagnosis of COVID-19 was confirmed by positive results of reverse transcriptase polymerase chain reaction test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Numerous reports handled emergency cesarean delivery. Primary symptoms and laboratory data of pregnant women with COVID-19 were similar to those of non-pregnant patients. Although the mortality rate is reported to be high after surgery in patients with COVID-19, cesarean delivery was successfully performed under regional anesthesia in most cases and postoperative course was favorable both in the parents and newborns. There is no direct evidence of vertical mother-to-child transmission of SARS-CoV-2; however, a diagnosis of COVID-19 was made in a newborn two hours after delivery from a pregnant woman with COVID-19, based on the increased immunoglobulin levels and deranged liver function, suggesting that its possibility cannot be completely eliminated. Emergency cerebral shunt reconstruction was performed repeatedly in an eight-month-old boy with COVID-19. The tracheal tube was removed in the operating room after surgery and postoperative course was uneventful. All the procedures should be performed in isolated operating rooms with medical staff with level-3 personal protection to ensure the safety of patients and health care providers.

Impact of intraoperative goal-directed fluid therapy on major morbidity and mortality after transthoracic oesophagectomy: a multicentre, randomised controlled trial.

BACKGROUND: Transthoracic oesophagectomy is associated with major morbidity and mortality, which may be reduced by goal-directed therapy (GDT). The aim of this multicentre, RCT was to evaluate the impact of intraoperative GDT on major morbidity and mortality in patients undergoing transthoracic oesophagectomy. METHODS: Adult patients undergoing transthoracic oesophagectomy were randomised to receive either minimally invasive intraoperative GDT (stroke volume variation <8%, plus systolic BP maintained >90 mm Hg by pressors as necessary) or haemodynamic management left to the discretion of attending senior anaesthetists (control group; systolic BP >90 mm Hg alone). The primary outcome was the incidence of death or major complications (reoperation for bleeding, anastomotic leakage, pneumonia, reintubation, >48 h ventilation). A Cox proportional hazard model was used to examine whether the effects of GDT on morbidity and mortality were independent of other potential confounders. RESULTS: A total of 232 patients (80.6% male; age range: 36-83 yr) were randomised to either GDT (n=115) or to the control group (n=117). After surgery, major morbidity and mortality were less frequent in 22/115 (19.1%) subjects randomised to GDT, compared with 41/117 (35.0%) subjects assigned to the control group {absolute risk reduction: 15.9% (95% confidence interval [CI]: 4.7-27.2%); P=0.006}. GDT was also associated with fewer episodes of atrial fibrillation (odds ratio [OR]: 0.18 [95% CI: 0.05-0.65]), respiratory failure (OR: 0.27 [95% CI: 0.09-0.83]), use of mini-tracheotomy (OR: 0.29 [95% CI: 0.10-0.81]), and readmission to ICU (OR: 0.09 [95% CI: 0.01-0.67]). GDT was independently associated with morbidity and mortality (hazard ratio: 0.51 [95% CI: 0.30-0.87]; P=0.013). CONCLUSIONS: Intraoperative GDT may reduce major morbidity and mortality, and shorten hospital stay, after transthoracic oesophagectomy. CLINICAL TRIAL REGISTRATION: UMIN000018705.

LOX-1 deficient mice show resistance to zymosan-induced arthritis.

Recent data suggest that the lectin-like oxidized low-density lipoprotein (ox-LDL) receptor-1 (LOX-1)/ox-LDL system may be involved in the pathogenesis of arthritis. We aimed to demonstrate the roles of the LOX-1/ox-LDL system in arthritis development by using LOX-1 knockout (KO) mice. Arthritis was induced in the right knees of C57Bl/6 wild-type (WT) and LOX-1 KO mice via zymosan injection. Saline was injected in the left knees. Arthritis development was evaluated using inflammatory cell infiltration, synovial hyperplasia, and cartilage degeneration scores at 1, 3, and 7 days after administration. LOX-1, ox-LDL, and matrix metalloproteinase-3 (MMP-3) expression in the synovial cells and chondrocytes was evaluated by immunohistochemistry. The LOX-1, ox-LDL, and MMP-3 expression levels in synovial cells were scored on a grading scale. The positive cell rate of LOX-1, ox-LDL, and MMP-3 in chondrocytes was measured. The correlation between the positive cell rate of LOX-1 or ox-LDL and the cartilage degeneration score was also examined. Inflammatory cell infiltration, synovial hyperplasia, and cartilage degeneration were significantly reduced in the LOX-1 KOmice with zymosan-induced arthritis (ZIA) compared to WT mice with ZIA. In the saline-injected knees, no apparent arthritic changes were observed. LOX-1 and ox-LDL expression in synovial cells and chondrocytes were detected in the knees of WT mice with ZIA. No LOX-1 and ox-LDL expression was detected in the knees of LOX-1 KOmice with ZIA or the saline-injected knees of both mice. MMP-3 expression in the synovial cells and chondrocytes was also detected in knees of both mice with ZIA, and was significantly less in the LOX-1 KO mice than in WT mice. The positive cell rate of LOX-1 or ox-LDL and the cartilage degeneration score showed a positive correlation. Our data show the involvement of the LOX-1/ox-LDL system in murine ZIA development. LOX-1-positive synovial cells and chondrocytes are potential therapeutic targets for arthritis prevention.

Pulmonary embolism caused by ovarian vein thrombosis during cesarean section: a case report.

BACKGROUND: Ovarian vein thrombosis is a rare complication of pregnancy. The representative complaints of patients with ovarian vein thrombosis are abdominal pain and fever. In some cases, however, fatal pulmonary embolism may develop. We report a case of pulmonary embolism presenting with severe hypotension and loss of consciousness during cesarean section possibly caused by ovarian vein thrombosis. CASE PRESENTATION: A 25-year-old woman at 38 weeks 4 days of gestation was scheduled for repeat cesarean section. Her past history was unremarkable, and the progress of her pregnancy was uneventful. She did not experience any symptoms indicative of deep vein thrombosis. Cesarean section was performed under spinal anesthesia, and a healthy newborn was delivered. After removal of the placenta, she suddenly developed dyspnea, hypotension, and loss of consciousness with decreased peripheral oxygen saturation. Blood pressure, heart rate, and oxygen saturation recovered after tracheal intubation and mechanical ventilation with oxygen. Postoperative computed tomography revealed no abnormality in the brain or in the pulmonary artery, but a dilated right ovarian vein with thrombi, extending up to the inferior vena cava, was found. A diagnosis of pulmonary embolism caused by ovarian vein thrombosis was made, and heparin was administered. The tracheal tube was removed on the first postoperative day. Her postoperative course was uneventful, and she was discharged with no complications. CONCLUSION: Fatal pulmonary embolism might be caused by ovarian vein thrombosis during cesarean section. Careful and continuous observation of the patient after delivery and prompt treatment are important.

Use of desflurane during anesthesia for resection of extra-adrenal pheochromocytoma: a case report.

BACKGROUND: Although various agents are used during anesthesia for surgical resection of pheochromocytoma, application of desflurane has rarely been reported. We report the use of desflurane in a case receiving resection of extra-adrenal pheochromocytoma. CASE PRESENTATION: A 51-year-old female was transferred to our hospital for sustained hypertension. A diagnosis of extra-adrenal pheochromocytoma was made based on increased plasma catecholamine levels and radiographic findings. Surgical resection was planned after controlling blood pressure. General anesthesia was induced with propofol and fentanyl, followed by maintenance with desflurane 4.3% and remifentanil 0.2-0.4 µg/kg/min. Blood pressure and heart rate were stable during induction, tracheal intubation, and tumor manipulation. Blood pressure abruptly decreased to 62/40 mmHg after removal of the tumor, which was treated with noradrenaline. The surgery was completed uneventfully and the postoperative course was also uneventful. CONCLUSION: Desflurane was safely used in combination with remifentanil during anesthesia for resection of extra-adrenal pheochromocytoma.

Electroencephalographic effect of age-adjusted 1 MAC desflurane and sevoflurane in young, middle-aged, and elderly patients.

PURPOSE: We examined the hypothesis that 1 minimum alveolar concentration (MAC) of desflurane and sevoflurane provides different depth of anesthesia. METHODS: One hundred and twenty young (20-30 years), middle-aged (31-65 years), and elderly (66-80 years) patients were randomly allocated to receive either desflurane or sevoflurane (n = 20, each group). General anesthesia was induced with propofol 2 mg/kg bolus and remifentanil 0.25 µg/kg/min, which was stopped after tracheal intubation. Maintenance of anesthesia was started with an end-tidal concentration of desflurane or sevoflurane at age-adjusted 1 MAC and maintained for 10 min, followed by 1-min assessment of bispectral index (BIS), 95% spectral edge frequency (SEF95), and amplitude of the electroencephalogram taken at 10-s intervals. RESULTS: BIS and SEF95 in patients receiving 1 MAC desflurane were significantly lower than those receiving 1 MAC sevoflurane including all age groups [35 (29, 39) vs. 41 (38, 49); 12.53 (10.99, 13.95) Hz vs. 14.42 (12.99, 17.17) Hz median (25, 75 percentile), respectively, P < 0.001 for both]. Both BIS and SEF95 in young patients were lower than in middle-aged and elderly patients receiving either desflurane or sevoflurane (P < 0.001 for both). There were no differences in amplitude between patients receiving desflurane and sevoflurane. CONCLUSIONS: BIS as well as SEF95 were lower in patients receiving 1 MAC desflurane than those receiving 1 MAC sevoflurane, suggesting that desflurane provides higher depth of anesthesia than sevoflurane at 1 MAC.

Lectin-like, oxidized low-density lipoprotein receptor-1-deficient mice show resistance to age-related knee osteoarthritis.

The lectin-like, oxidized low-density lipoprotein (ox-LDL) receptor-1 (LOX-1)/ox-LDL system contributes to atherosclerosis and may be involved in cartilage degeneration. The purpose of this study was to determine whether the LOX-1/ox-LDL system contributes to age-related osteoarthritis (OA) in vivo, using LOX-1 knockout (LOX-1 KO) mice. Knee cartilage from 6, 12, and 18-month old (n = 10/group) C57Bl/6 wild-type (WT) and LOX-1 KO mice was evaluated by determining the Osteoarthritis Research Society International (OARSI) score of Safranin-O stained samples. The prevalence of knee OA in both mouse strains was also investigated. Expression levels of LOX-1, ox-LDL, runt-related transcription factor-2 (Runx2), type-X collagen (COL X), and matrix metalloproteinase-13 (MMP-13) in the articular chondrocytes were analyzed immunohistologically. No significant difference was observed in the mean scores of WT (2.00±0.61) and LOX-1 KO mice (2.00±0.49) at 6 months of age (P=1.00, n=10). At 12 and 18 months of age, the mean scores of LOX-1 KO mice (3.75±0.93 and 5.50±0.78) were significantly lower than those of WT mice (5.25±1.14 and 9.00±1.01; P<0.001 in both cases; n=10). The prevalence of OA in LOX-1 KO mice was lower than that in WT mice at 12 and 18 months of age (40 vs 70%, 70 vs 90%, respectively; n=10). The expression levels of Runx2, COL X, and MMP-13 in articular chondrocytes significantly decreased in LOX-1 KO, mice compared with those in WT mice. The study indicated that the LOX-1/ox-LDL system in chondrocytes plays a role in the pathogenesis of age-related knee OA, which is potentially a target for preventing OA progression.

The effect of sevoflurane on electrocorticographic spike activity in pediatric patients with epilepsy.

BACKGROUND: Electrocorticogram (ECoG) spike activity is enhanced under general anesthesia with 1.5 minimum alveolar concentration (MAC) sevoflurane compared with lower concentrations in adult patients with epilepsy. However, the effect of concentration of sevoflurane on ECoG in children with epilepsy is less known. AIMS: The primary endpoint was to investigate the effects of sevoflurane on ECoG spike activity in pediatric patients undergoing epilepsy surgery. The secondary endpoint was to examine its effects on baseline ECoG including burst suppression. METHODS: Children of age 3-18 years with medically intractable epilepsy undergoing corpus callosotomy or resection of the epileptic foci (n = 11) were enrolled. Electrodes were placed on the brain surface and ECoG was recorded under anesthesia with endtidal carbon dioxide tension at 30 mmHg and sevoflurane at 2.5%, followed by age-adjusted 1.5 MAC (3.1-3.4%) for 10 min. The number of leads with spikes, the average number of spikes per lead per minute, median frequency of ECoG, and duration of suppression of ECoG ≥ 1 s were compared between 2.5% and 1.5 MAC sevoflurane. RESULTS: The number of leads with spikes increased [11 vs 14, P = 0.003, difference in mean (95% CI) is 3 (2-5)], and the average number of spikes increased [9 vs 14·lead-1 ·min-1 , P = 0.003, difference in mean (95% CI) is 5 (2-8) lead-1 ·min-1 ] under anesthesia with 1.5 MAC compared with 2.5% sevoflurane. Median frequency was decreased [2.8 Hz vs 2.0 Hz, P = 0.003, difference in mean (95% CI) is 0.8 (0.4-1.2) Hz], and the duration of suppression was increased [105 s vs 262 s, P < 0.001, difference in mean (95% CI) is 156 (90-223) s] with 1.5 MAC compared with 2.5% sevoflurane. CONCLUSIONS: Sevoflurane at 1.5 MAC significantly increased the extent and the number of spikes, prolonged the duration of suppression, and decreased median frequency of ECoG compared with those at 2.5% sevoflurane.

Resin Bonding of Self-Etch Adhesives to Bovine Dentin Bleached from Pulp Chamber.

This study evaluated the microtensile bond strength (µTBS) of 1-step self-etch adhesives (1-SEAs) and 2-step self-etch adhesives (2-SEAs) to pulp chamber dentin immediately after bleaching with 2 types of common bleaching techniques. Pulp chamber dentin of bovine teeth was bleached using 30% hydrogen peroxide (H2O2) solution with quartz-tungsten-halogen light-curing unit (Group 1) and 3.5% H2O2-containing titanium dioxide (TiO2) (Pyrenees®) activated with 405-nm violet diode laser for 15 min (Group 2). Unbleached specimens were placed in distilled water for 15 min and used as controls. After treatment, dentin was bonded with resin composite using 1-SEA or 2-SEA and stored in water at 37°C for 24 h. Each specimen was sectioned and trimmed to an hourglass-shape and µTBS was measured. Fractured specimens were examined under a scanning electron microscope to determine fracture modes. All specimens in Group 1 failed before proper bonding tests. In Group 2, the µTBS of 2-SEA was significantly greater (with no failed specimens) than 1-SEA (where 21 out of 36 failed). These results indicate that 2-SEA is a better adhesive system than 1-SEA on bleached dentin. Our results also demonstrated that application of H2O2 significantly decreases bond strength of resin to dentin; however, in the case of nonvital tooth bleaching, Pyrenees® is a better alternative to the conventional 30% H2O2 bleaching.

The Pharmacokinetics of Atomized Lidocaine Administered via the Trachea: A Randomized Trial.

BACKGROUND: Under emergent conditions, endotracheal drug administration may be an effective method of delivering emergency drugs. A common technique is to administer these drugs using a nonatomized spray. Atomized drug delivery may be an attractive alternative to nonatomized delivery because atomized particles are small, cover a large surface area, and may better adhere to endotracheal membrane resulting in more effective drug absorption. In this study, we compared the pharmacokinetic profile of lidocaine administered into the trachea using an atomized or a nonatomized technique. METHODS: Twenty patients were anesthetized using propofol and remifentanil. Ten minutes after rocuronium was administered, patients received 4% lidocaine (2 mg/kg) intratracheally over 2 seconds before tracheal intubation. Ten patients received atomized lidocaine using a mucosal atomization device, and the other 10 patients received nonatomized lidocaine using a traditional spray tube. Arterial lidocaine plasma concentrations were measured before; at 1, 3, 5, 7, 10, 15, 20, 30, 45, and 60 minutes; and then every 60 minutes after the administration of lidocaine until the end of the operation. We developed a pharmacokinetic model to examine whether bioavailability or absorption rate was different between atomized versus nonatomized lidocaine administration. The total body clearance was fixed at a published value to determine the bioavailability. RESULTS: Peak plasma concentrations were larger using the mucosal atomization device (median [range]: 1.9 [1.4-3.2] µg/mL) than the spray tube (1.1 [0.6-2.0] µg/mL; P = 0.0021). Our pharmacokinetic model estimated a difference of bioavailability between the atomized and the nonatomized lidocaine (0.801 and 0.559 respectively, P = 0.0005), whereas our model estimated no difference in the absorption rate constant (0.00688/min). CONCLUSIONS: Our results suggest that when using atomized delivery of lidocaine, less drug is required to achieve a near equivalent plasma lidocaine concentration. Atomized drug administration may be a more efficient method for endotracheal drug administration.