Anesthetic Management of an Adult Patient Post a Fontan Procedure in Laparoscopic Surgery: A Case Report.

We report the successful anesthetic management of laparoscopic surgery in a 21-year-old female patient with Fontan circulation. A preoperative careful review of cardiac catheterization results helped assess the risk of the surgery and implement anesthetic management. Intraoperative management focused on minimizing the impact on pulmonary vascular resistance and venous return by optimizing ventilation and applying lower pneumoperitoneum pressure without tilting the position. Milrinone was administered to reduce pulmonary vascular resistance and provide inotropic support with minimally invasive monitoring. The patient remained stable throughout the procedure without complications. This case highlights the importance of thorough preoperative assessment, individualized intraoperative management, and collaboration with the surgical team when caring for adult Fontan patients undergoing laparoscopic surgery.

Early-life midazolam exposure persistently changes chromatin accessibility to impair adult hippocampal neurogenesis and cognition.

Linkage between early-life exposure to anesthesia and subsequent learning disabilities is of great concern to children and their families. Here we show that early-life exposure to midazolam (MDZ), a widely used drug in pediatric anesthesia, persistently alters chromatin accessibility and the expression of quiescence-associated genes in neural stem cells (NSCs) in the mouse hippocampus. The alterations led to a sustained restriction of NSC proliferation toward adulthood, resulting in a reduction of neurogenesis that was associated with the impairment of hippocampal-dependent memory functions. Moreover, we found that voluntary exercise restored hippocampal neurogenesis, normalized the MDZ-perturbed transcriptome, and ameliorated cognitive ability in MDZ-exposed mice. Our findings thus explain how pediatric anesthesia provokes long-term adverse effects on brain function and provide a possible therapeutic strategy for countering them.

Antinociceptive effect of selective G protein-gated inwardly rectifying K+ channel agonist ML297 in the rat spinal cord.

The G protein-gated inwardly rectifying K+ (GIRK) channels play important signaling roles in the central and peripheral nervous systems. However, the role of GIRK channel activation in pain signaling remains unknown mainly due to the lack of potent and selective GIRK channel activators until recently. The present study was designed to determine the effects and mechanisms of ML297, a selective GIRK1/2 activator, on nociception in the spinal cord by using behavioral studies and whole-cell patch-clamp recordings from substantia gelatinosa (SG) neurons. Rats were prepared for chronic lumber catheterization and intrathecal administration of ML297. The nociceptive flexion reflex was tested using an analgesy-meter, and the influence on motor performance was assessed using an accelerating rotarod. We also investigated pre- and post-synaptic actions of ML297 in spinal cord preparations by whole-cell patch-clamp recordings. Intrathecal administration of ML297 increased the mechanical nociceptive threshold without impairing motor function. In voltage-clamp mode of patch-clamp recordings, bath application of ML297 induced outward currents in a dose-dependent manner. The ML297-induced currents demonstrated specific equilibrium potential like other families of potassium channels. At high concentration, ML297 depressed miniature excitatory postsynaptic currents (mEPSCs) but not their amplitude. The ML297-induced outward currents and suppression of mEPSCs were not inhibited by naloxone, a µ-opioid receptor antagonist. These results demonstrated that intrathecal ML297 showed the antinociceptive effect, which was mediated through direct activation of pre- and post-synaptic GIRK channels. Selective GIRK channel activation is a promising strategy for the development of new agents against chronic pain and opioid tolerance.

Sodium thiosulfate prevents doxorubicin-induced DNA damage and apoptosis in cardiomyocytes in mice.

AIM: Doxorubicin (DOX) induces dose-dependent cardiotoxicity due to reactive oxygen species (ROS)-mediated oxidative stress and subsequent apoptosis of cardiomyocytes. We aimed to assess whether sodium thiosulfate (STS), which has antioxidant and antiapoptotic properties, exerts cardioprotective effects on DOX-induced cardiomyopathy. MAIN METHODS: Male C57BL/6N mice were divided into four groups, control, DOX, STS, and DOX + STS, and administered DOX (20 or 30 mg/kg) or normal saline intraperitoneally, followed by an injection of STS (2 g/kg) or normal saline 4 h later. KEY FINDINGS: The DOX group showed a poorer 6-day survival and decreased cardiac function than the DOX + STS group. The DOX group showed a marked increase in the plasma creatine kinase isoenzyme myocardial band (CK-MB) and lactate dehydrogenase (LDH) levels 10 h after DOX injection, while the DOX + STS group showed suppression of DOX-induced elevation of CK-MB and LDH levels. The DOX group showed increased 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in the heart, whereas the DOX + STS group showed increased catalase and superoxide dismutase (SOD) activities and decreased 8-OHdG levels in the heart compared with DOX group, suggesting that STS reduces DOX-induced DNA damage by improving antioxidant enzymes activities in cardiomyocytes. Additionally, the DOX + STS group showed attenuation of cleaved caspase-3 and DNA fragmentation in cardiomyocytes compared with the DOX group, suggesting that STS suppresses DOX-induced apoptosis in cardiomyocytes. SIGNIFICANCE: STS exerts cardioprotective effects against DOX-induced cardiac dysfunction partly by improving antioxidant defense and suppressing apoptosis, indicating the therapeutic potential of STS against DOX-induced cardiomyopathy.

Visceral fat, but not subcutaneous fat, is associated with lower core temperature during laparoscopic surgery.

BACKGROUND: Previous studies suggest that lower BMI is a risk factor for intraoperative core hypothermia. Adipose tissue has a high insulation effect and is one of the major explanatory factors of core hypothermia. Accordingly, determining the respective influence of visceral and subcutaneous fat on changes in core temperature during laparoscopic surgery is of considerable interest. METHODS: We performed a prospective study of 104 consecutive donors who underwent laparoscopic nephrectomy. Temperature data were collected from anesthesia records. Visceral and subcutaneous fat were calculated by computed tomography (CT) or ultrasound. For ultrasound measurements, preperitoneal fat thickness was used as an index of visceral fat. Multiple linear regression analysis was performed at 30, 60, and 120 minutes after the surgical incision to identify the predictive factors of body temperature change. The potential explanatory valuables were age, sex, BMI, visceral fat, and subcutaneous fat. RESULTS: BMI (ß = 0.010, 95%CI: 0.001-0.019, p = 0.033) and waist-to-hip ratio (ß = 0.424, 95%CI: 0.065-0.782, p = 0.021) were associated with increased core temperature at 30 minutes after the surgical incision. Ultrasound measured-preperitoneal fat was significantly associated with increased core temperature at 30 and 60 minutes after the surgical incision (ß = 0.012, 95%CI: 0.003-0.021, p = 0.009 and ß = 0.013, 95%CI: 0.002-0.024, p = 0.026). CT-measured visceral fat was also associated with increased core temperature at 30 minutes after the surgical incision (ß = 0.005, 95%CI: 0.000-0.010, p = 0.046). Conversely, subcutaneous fat was not associated with intraoperative core temperature. Male sex and younger age were associated with lower intraoperative core temperature. CONCLUSIONS: Visceral fat protects against core temperature decrease during laparoscopic donor nephrectomy.

What is the predictor of the intraoperative body temperature in abdominal surgery?

PURPOSE: Inadvertent hypothermia is a relatively common intraoperative complication. Few studies have investigated predictors of body temperature change or the effect of the blanket type used with a forced-air warming device during the intraoperative period. We investigated the predictive factors of intraoperative body temperature change in scheduled abdominal surgery. METHODS: We retrospectively reviewed the data from 2574 consecutive adult patients who underwent scheduled abdominal surgery in the supine position. Temperature data were collected from anesthesia records. Multiple regression analysis was performed at 60, 120, and 180 min after the surgical incision to identify the factors influencing body temperature change. We conducted nonlinear regression analysis using the equation ΔT = α (e-γt-1) + ßt, where ΔT represented the change in intraoperative core temperature (°C), t represented the surgical duration (minutes), and α, ß, and γ were constants. RESULTS: The intraoperative core temperature change was explained by the equation ΔT = 0.59 (e- 0.018t - 1) + 0.0043t. Younger age, higher body mass index (BMI), male sex, laparoscopic surgery, and use of an underbody blanket were associated with increased core temperature at 1 or 2 h after surgical incision. Male sex and an underbody blanket remained strong predictive variables even 3 h after surgical incision, whereas BMI had little explanatory power at this timepoint. The difference in the heating effect of an underbody versus an overbody blanket was 0.0012 °C per minute. CONCLUSIONS: The blanket type of the forced-air warmer, age, sex, laparoscopic surgery, and BMI are predictors of intraoperative core temperature change.

Correction to: What is the predictor of the intraoperative body temperature in abdominal surgery?

In the Original publication of the article, the Table 1 was incorrectly published.

Prediction of hemodynamic fluctuations after induction of general anesthesia using propofol in non-cardiac surgery: a retrospective cohort study.

BACKGROUND: Although propofol is a common anesthetic agent for the induction of general anesthesia, hemodynamic fluctuations are occasionally prominent during induction/intubation. The aims of this study were to determine the influential factors on enhanced hemodynamic fluctuation and to establish a prediction formula to quickly determine the dose of propofol to protect against hemodynamic fluctuations. METHODS: This retrospective cohort study patients (n = 2097) were 18 years or older. They underwent general anesthesia induction using propofol and orotracheal intubation for non-cardiac surgery at Kyushu University Hospital during April 2015 to March 2016. Preoperative patient clinical information was collected from anesthesia preoperative evaluation records. Intraoperative data were obtained from computerized anesthesia records. If patients' post-induction mean arterial blood pressure (MAP) decreased or increased 30% or more from their pre-induction MAP, they were determined to have enhanced hemodynamic fluctuations. Unconditional logistic regression was used to assess the adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Structural equation modeling (SEM) was conducted to simultaneously examine the direct and indirect effect (path coefficient = r) of potential variables. RESULTS: In the SEM analysis, age was significantly associated with enhanced hemodynamic fluctuations (adjusted odds ratio = 1.008, 95% CI = 1.001-1.015, P = 0.03). Age (path coefficient (r) = - 0.0113, 95% CI = - 0.0126-0.010, P < 0.001), American Society of Anesthesiologists physical status (ASA-PS) (r = - 0.0788, 95% CI = - 0.1431-0.0145, P = 0.02), sex (r = 0.057, 95% CI = 0.0149-0.9906, P = 0.01), and fentanyl dose (r = 0.1087, 95% CI = 0.0707-0.1467, P < 0.001) influenced the dose of propofol in induction. The prediction formula of "Propofol dose (mg) = [2.374 - 0.0113 × age (year) - 0.0788 (if ASA-PS 3 or 4) + 0.057 (if female) + 0.1087 × fentanyl dose (µg/kg)] × body weight (kg)" was derived. CONCLUSIONS: Age was associated with hemodynamic fluctuations in induction. Although the prediction formula is considered to be acceptable, future studies validating whether it can decrease patients' risk of enhanced hemodynamic fluctuations in clinical situations are necessary.

The relationship between seizure in electroconvulsive therapy and pupillary response using an automated pupilometer.

OBJECTIVES: Seizure duration and morphology, postictal suppression, and sympathetic nervous system activation are all recommended as assessments of adequate seizure in electroconvulsive therapy (ECT). However, blood pressure and heart rate are not typically assessed as part of sympathetic nervous system activation because of the administration of anesthetic or cardiovascular agents during ECT. Although the pupils are known to reflect to the activity of autonomic nervous system and the degree of brain damage, previous studies have not examined the relationship between seizure of electroconvulsive therapy and pupillary response. METHODS: We conducted 98 sessions of ECT with 13 patients, divided into two groups according to seizure quality: (1) adequate or (2) inadequate. Pupillary light reflex [% constriction = (maximum resting pupil size {MAX} - minimum pupil size after light stimulation)/MAX × 100] was measured using a portable infrared quantitative pupilometer before anesthesia induction and immediately after electrical stimulation. RESULTS: The number regarded as adequate was 67 times and as inadequate was 31 times. Maximum pupil size at the control and immediately after electrical stimulation was similar between the adequate and inadequate groups. Pupillary light reflex was similar at the control between both groups, but significantly smaller immediately after stimulation in the adequate group (2.5 ± 3.6%) compared with the inadequate group (10.6 ± 11.5%). Receiver operating characteristic curve analysis revealed that pupillary light reflex (> 5.5%) predicted adequate seizure. CONCLUSIONS: The current findings suggest that pupillary constriction immediately after ECT could provide a helpful method for assessing the efficacy of ECT.

Effects of preoperative plasma exchange therapy with albumin replacement fluid on blood coagulation in patients undergoing ABO-incompatible living-donor kidney transplantation using rotational thromboelastometry.

BACKGROUND: ABO-incompatible living-donor kidney transplantation (LDKT) requires immunotherapy and plasma exchange therapy (PEX). PEX with albumin replacement fluid reportedly decreases fibrinogen levels. However, no reports have described the effects of PEX with albumin replacement fluid on blood coagulation parameters and blood loss during the perioperative period. Therefore, we investigated the effects of preoperative PEX on blood coagulation parameters and blood loss during the perioperative period in patients undergoing ABO-incompatible LDKT as measured by rotational thromboelastometry (ROTEM®). METHODS: Twenty-eight patients undergoing LDKT were divided into the PEX group (ABO incompatible with PEX, n = 13) and non-PEX group (ABO compatible without PEX, n = 15). ROTEM® parameters, standard laboratory test parameters, bleeding volume, and transfusion volume were compared between PEX and non-PEX group. MCEplatelet, which represents platelet contribution to clot strength and where "MCE" stands for maximum clot elasticity, was calculated from the difference in MCE between EXTEM and FIBTEM. RESULTS: The bleeding volume during surgery and the intensive care unit (ICU) stay was significantly higher in the PEX than non-PEX group (p < 0.01). Maximum clot firmness (MCF) of EXTEM (MCFEXTEM), MCFFIBTEM, and MCEplatelet was significantly lower in the PEX than non-PEX group (p < 0.01). In the PEX group, the bleeding volume during surgery was very strongly correlated with the baseline MCFEXTEM and MCEplatelet, and the bleeding volume during the ICU stay was strongly correlated with the postoperative MCFEXTEM and MCEplatelet. CONCLUSIONS: These results suggest that the increased blood loss in the PEX group during surgery and the ICU stay was associated with decreased platelet contribution to clot strength as measured by ROTEM®. TRIAL REGISTRATION: UMIN-Clinical Trial Registry UMIN000018355 . Registered 21 July 2015.

Effectiveness of arginine vasopressin for the management of refractory hemorrhagic shock in a patient with autonomic dysreflexia caused by spinal cord injury.

BACKGROUND: Arginine vasopressin has been used for the management of refractory vasodilatory shock. However, it is still unclear whether arginine vasopressin is useful for hypotension in patients with spinal cord injury. CASE DESCRIPTION: A 78-year-old man with autonomic dysreflexia and paralysis below the level corresponding to Th2 due to spinal cord injury previously underwent cholecystectomy. During the surgery, accidental hemorrhage led him to refractory hemorrhagic shock unresponsive to fluid resuscitation and catecholamine. Lasting hypotension was improved with arginine vasopressin. CONCLUSION: We described a rare case report on the use of arginine vasopressin for management of refractory hemorrhagic shock in a patient with autonomic dysreflexia.

Effects of Forced Air Warming on Airflow around the Operating Table.

BACKGROUND: Forced air warming systems are used to maintain body temperature during surgery. Benefits of forced air warming have been established, but the possibility that it may disturb the operating room environment and contribute to surgical site contamination is debated. The direction and speed of forced air warming airflow and the influence of laminar airflow in the operating room have not been reported. METHODS: In one institutional operating room, we examined changes in airflow speed and direction from a lower-body forced air warming device with sterile drapes mimicking abdominal surgery or total knee arthroplasty, and effects of laminar airflow, using a three-dimensional ultrasonic anemometer. Airflow from forced air warming and effects of laminar airflow were visualized using special smoke and laser light. RESULTS: Forced air warming caused upward airflow (39 cm/s) in the patient head area and a unidirectional convection flow (9 to 14 cm/s) along the ceiling from head to foot. No convection flows were observed around the sides of the operating table. Downward laminar airflow of approximately 40 cm/s counteracted the upward airflow caused by forced air warming and formed downward airflow at 36 to 45 cm/s. Downward airflows (34 to 56 cm/s) flowing diagonally away from the operating table were detected at operating table height in both sides. CONCLUSIONS: Airflow caused by forced air warming is well counteracted by downward laminar airflow from the ceiling. Thus it would be less likely to cause surgical field contamination in the presence of sufficient laminar airflow.

Cardiotonic actions of quercetin and its metabolite tamarixetin through a digitalis-like enhancement of Ca2+ transients.

The plant-derived flavonoid, quercetin (QCT), has many biological actions, including cardioprotective actions, resulting from its antioxidant and anti-inflammatory effects. In this study, effects of QCT and its metabolites on the contraction and Ca2+ transients (CaT) of mouse single cardiomyocytes were simultaneously measured and compared with those of isoproterenol and digoxin. Furthermore, cardiac function and plasma concentrations were analyzed after bolus intravenous administration of QCT in mice. QCT and its metabolite, tamarixetin, as well as isoproterenol and digoxin, enhanced the contraction and CaT of cardiomyocytes. The inotropic action of isoproterenol was accompanied by an increase in the velocities of sarcomere shortening and relengthening and CaT decay through activation of cAMP-dependent protein kinase; however, no such lusitropic effects accompanied the inotropic action of QCT, tamarixetin or digoxin. Intravenous administration of QCT to mice resulted in a sustained increase in cardiac systolic function; QCT was rapidly metabolized to tamarixetin and its plasma concentration was maintained at high levels over a similar time frame as the enhancement of cardiac systolic function. These results suggest that QCT exerts a cardiotonic action in vivo at least, in part, through digitalis-like enhancement of CaT by itself and its metabolite tamarixetin.

Inhibition of nitric oxide synthase unmasks vigorous vasoconstriction in established pulmonary arterial hypertension.

It is widely accepted that impaired bioavailability of endothelial nitric oxide (NO) plays a critical role in the pathophysiology of pulmonary arterial hypertension (PAH). However, there are published data that show that relatively many PAH patients respond favorably to acetylcholine-induced pulmonary vasodilation during their follow-up period, when diverse stages of the disorder are included. We hypothesized that NO bioavailability varies depending on the progression of PAH Adult rats were exposed to the VEGF receptor blocker Sugen5416 and 3 weeks of hypoxia followed by return to normoxia for various additional weeks. All rats developed increased right ventricular systolic pressure (RVSP) and occlusive lesion formation at 1, 3, 5, and 8 weeks after the Sugen5416 injection. Acute NO synthase blockade did not change the elevated RVSP at the 1-week time point, while it further increased RVSP markedly at the 3-, 5-, and 8-week time points, leading to death in all rats tested at 8 weeks. Acetylcholine caused significant reduction in RVSP at the 8-week but not the 1-week time point, whereas sodium nitroprusside decreased the pressure similarly at both time points. Increased NO-mediated cGMP production was found in lungs from the 8-week but not the 1-week time point. In conclusion, despite its initial impairment, NO bioavailability is restored and endogenous NO plays a critical protective role by counteracting severe pulmonary vasoconstriction in established stages of PAH in the Sugen5416/hypoxia/normoxia-exposed rats. Our results provide solid pharmacological evidence for a major contribution of a NO-suppressed vasoconstrictor component in the pathophysiology of established PAH.

TRPC3-Nox2 complex mediates doxorubicin-induced myocardial atrophy.

Myocardial atrophy is a wasting of cardiac muscle due to hemodynamic unloading. Doxorubicin is a highly effective anticancer agent but also induces myocardial atrophy through a largely unknown mechanism. Here, we demonstrate that inhibiting transient receptor potential canonical 3 (TRPC3) channels abolishes doxorubicin-induced myocardial atrophy in mice. Doxorubicin increased production of ROS in rodent cardiomyocytes through hypoxic stress-mediated upregulation of NADPH oxidase 2 (Nox2), which formed a stable complex with TRPC3. Cardiomyocyte-specific expression of TRPC3 C-terminal minipeptide inhibited TRPC3-Nox2 coupling and suppressed doxorubicin-induced reduction of myocardial cell size and left ventricular (LV) dysfunction, along with its upregulation of Nox2 and oxidative stress, without reducing hypoxic stress. Voluntary exercise, an effective treatment to prevent doxorubicin-induced cardiotoxicity, also downregulated the TRPC3-Nox2 complex and promoted volume load-induced LV compliance, as demonstrated in TRPC3-deficient hearts. These results illustrate the impact of TRPC3 on LV compliance and flexibility and, focusing on the TRPC3-Nox2 complex, provide a strategy for prevention of doxorubicin-induced cardiomyopathy.

Frequency-dependent changes in sensorimotor and pain affective systems induced by empathy for pain.

BACKGROUND: Empathy for pain helps us to understand the pain of others indirectly. To better comprehend the processing of empathic pain, we report the frequency-dependent modulation of cortical oscillations induced by watching movies depicting pain using high-density electroencephalography (EEG), magnetoencephalography (MEG), and motor evoked potentials (MEP). METHODS: Event-related desynchronization of EEG and MEG was assessed while participants viewed videos of painful (needle) or neutral (cotton swab) situations. The amplitudes of MEPs were also compared between the needle and cotton swab conditions. RESULTS: The degree of suppression in α/ß band power was significantly increased, whereas that of γ band power was significantly decreased, in the needle condition compared with the cotton swab condition. EEG revealed that significant differences in α/ß band were distributed in the right frontocentral and left parietooccipital regions, whereas significant γ band differences were distributed predominantly over the right hemisphere, which were confirmed by source estimation using MEG. There was a significant positive correlation between the difference in γ power of the two conditions and the visual analog scale subjective rating of aversion, but not in the α/ß band. The amplitude of MEPs decreased in the needle condition, which confirmed the inhibition of the primary motor cortex. CONCLUSION: MEP suppression supports that modulation of cortical oscillations by viewing movies depicting pain involves sensorimotor processing. Our results suggest that α/ß oscillations underlie the sensory qualities of others' pain, whereas the γ band reflects the cognitive aspect. Therefore, α/ß and γ band oscillations are differentially involved in empathic pain processing under the condition of motor cortical suppression.

Incidental Cerebral Acute Subdural Hematoma After Transforaminal Lumbar Interbody Fusion: A Case Report.

We present a 68-year-old woman who developed acute cerebral subdural hematoma (SDH) early after transforaminal lumbar interbody fusion. Four hours postoperatively, the patient complained of headache and nausea. Enhanced cranial computed tomography showed cerebral SDH. Despite no obvious intraoperative dural damage, we suggest that cerebrospinal fluid leakage by incidental dural tear likely caused the SDH. To our knowledge, this is the first report of detected cerebral SDH immediately after spinal surgery in spite of no neurological deficits.

Association Between Serum Vitamin D and All-Cause and Cause-Specific Death in a General Japanese Population　- The Hisayama Study.

BACKGROUND: Few studies have investigated the association between serum vitamin D levels and mortality in general Asian populations.Methods and Results:We examined the association of serum 1,25-dihydroxyvitamin D (1,25(OH)2D) levels with the risk of all-cause and cause-specific death in an average 9.5-year follow-up study of 3,292 community-dwelling Japanese subjects aged ≥40 years (2002-2012). The multivariable-adjusted hazard ratio (HR) for all-cause death increased significantly with lower serum 1,25(OH)2D levels (HR 1.54 [95% confidence interval, 1.18-2.01] for the lowest quartile, 1.31 [0.99-1.73] for the 2nd quartile, 0.94 [0.70-1.25] for the 3rd quartile, 1.00 [Ref.] for highest quartile; P for trend <0.001). A similar association was observed for cardiovascular and respiratory infection death (both P for trend <0.01), but not for cancer death or death from other causes. In the stratified analysis, the association between lower serum 1,25(OH)2D levels and the risk of respiratory infection death was stronger in subjects with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2than in those with eGFR ≥60 mL/min/1.73 m2; there was a significant heterogeneity in the association between eGFR levels (P for heterogeneity=0.04). CONCLUSIONS: The findings suggested that a lower serum 1,25(OH)2D level is a potential risk factor for all-cause death, especially cardiovascular and respiratory infection death, in the general Japanese population, and that lower serum 1,25(OH)2D levels greatly increase the risk of respiratory infection death in subjects with kidney dysfunction.