Evaluation of the Toxicity of Sugammadex in Zebrafish Larvae.

BACKGROUND: Sugammadex is a new neuromuscular blockade reversal agent. Recently, it has been used in patients under general anesthesia. However, sugammadex could be toxic to fetuses and pediatric patients under 3 years of age. In this study, we demonstrated the safety of sugammadex in fetuses, using zebrafish larvae. Furthermore, its neurotoxicity was evaluated using neuronal cell lines. METHODS: We used SH-SY5Y cells to determine the viability of neuronal cells treated with sugammadex. Zebrafish larvae were used to determine the teratogenic effects of sugammadex. RESULTS: Sugammadex showed no adverse effects on neuronal cells and zebrafish larvae. The survival rates of neuronal cells were not different in all concentrations. In addition, the heart formation of zebrafish embryos, which were exposed to various concentrations of sugammadex, were not different. CONCLUSION: This study demonstrated the feasibility of using sugammadex during pregnancy. However, further clinical studies will be required to extrapolate these results to humans.

Investigating preoperative myoglobin level as predictive factor for acute kidney injury following cardiac surgery with cardiopulmonary bypass: a retrospective observational study.

BACKGROUND: Early identification of patients at risk of AKI after cardiac surgery is of critical importance for optimizing perioperative management and improving outcomes. This study aimed to identify the association between preoperative myoglobin levels and postoperative acute kidney injury (AKI) in patients undergoing valve surgery or coronary artery bypass graft surgery (CABG) with cardiopulmonary bypass. METHODS: This retrospective study included 293 patients aged over 17 years who underwent valve surgery or CABG with cardiopulmonary bypass. We excluded 87 patients as they met the exclusion criteria. Therefore, 206 patients were included in the final analysis. The patients... demographics as well as intraoperative and postoperative data were collected from electronic medical records. AKI was defined according to the Acute Kidney Injury Network classification system. RESULTS: Of the 206 patients included in this study, 77 developed AKI. The patients who developed AKI were older, had a history of hypertension, underwent valve surgery with concomitant CABG, had lower preoperative hemoglobin levels, and experienced prolonged extracorporeal circulation (ECC) times. Multivariate logistic regression analysis revealed that preoperative myoglobin levels and ECC time were correlated with the development of AKI. A higher preoperative myoglobin level was an independent risk factor for the development of cardiac surgery-associated AKI. CONCLUSIONS: Higher preoperative myoglobin levels may enable physicians to identify patients at risk of developing AKI and optimize management accordingly.

Intrathecal hydromorphone added to hyperbaric bupivacaine for postoperative pain relief after knee arthroscopic surgery: a prospective, randomised, controlled trial.

BACKGROUND AND OBJECTIVE: Adding opioid to spinal anaesthetic provides additional analgesia during the postoperative period. The purpose of this study was to determine the dose of intrathecal hydromorphone necessary to achieve postoperative pain relief after arthroscopic knee surgery. METHODS: In a prospective, double-blinded parallel, placebo-controlled manner, 60 patients who were undergoing unilateral knee arthroscopy randomly received unilateral spinal anaesthesia with 0.5% hyperbaric bupivacaine 6 mg combined with 0.0, 2.5, 5.0 or 10.0 µg per 0.05 ml hydromorphone. Fifteen patients were assigned to receive each dose. The visual analogue pain scores (VAPSs) were measured at 30 min and 2, 4, 6, 12 and 24 h postoperatively, and the side-effects of hydromorphone were recorded. RESULTS: The postoperative VAPSs at 4, 6 and 12 h for the 5 and 10 µg hydromorphone groups were significantly decreased, compared to the control group. The 2.5 µg hydromorphone group had lower VAPS only at 4 and 6 h postoperatively. Nausea was significantly increased in the 10 µg hydromorphone group (46.6%). CONCLUSION: The analgesic effects of 5 and 10 µg intrathecal hydromorphone provided satisfactory pain relief for 12 h postoperatively and nausea increased significantly in a dose-dependent manner.

The state of anesthesia in South Korea: a national survey of the status of anesthetic service activity in 2014-2016.

BACKGROUND: Because the quality of anesthesia affects the surgical outcome, the aim of this study was to investigate the current status of anesthetic services performed by anesthesiologists and non-anesthesiologists in South Korea from 2014 to 2016 and to compare the results with data from 2011 to 2013. METHODS: The claimed anesthesia services at medical institutions with employed anesthesiologists and the claims for an invitation fee for an anesthesiologist at medical institutions without employed anesthesiologists were regarded as anesthetic services performed by an anesthesiologist. From 2014 to 2016, the employment of anesthesiologists according to the type of medical institution, the status of anesthetic services according to the presence or absence of employed anesthesiologists, and status of anesthetic services at medical institutions without employed anesthesiologists were analyzed. RESULTS: The proportion of medical institutions that employed anesthesiologists slightly increased from 27.8% in 2014 to 28.8% in 2016. General anesthesia was more concentrated at higher medical institutions, and most anesthesias were performed by an anesthesiologist. The proportion of spinal anesthesia, epidural anesthesia, and brachial plexus performed by non-anesthesiologists was 11%, 15%, and 16.5%, respectively. Intravenous anesthesia performed by non-anesthesiologists was 58% and has increased compared to the past. CONCLUSIONS: The employment of anesthesiologists has increased with time, and general anesthesiology was mostly performed by anesthesiologists. However, since the proportion of anesthetic services performed by non-anesthesiologists in regional anesthesia and intravenous anesthesia was maintained high, it is necessary to find ways to expand the safety of anesthetic services.

Comparison of the effects of cranial electrotherapy stimulation and midazolam as preoperative treatment in geriatric patients: A CONSORT-compliant randomized controlled trial.

BACKGROUND: Although midazolam is widely administered as an anxiolytic premedication, it may cause over-sedation and hypoxia in geriatric patients. Cranial electrotherapy stimulation (CES) is a nonpharmacological device with anxiolytic effect. This study compared the effects of CES and midazolam as a preoperative treatment in geriatric patients. METHODS: Eighty patients, under the age of 65 to 79 years, undergoing general anesthesia were randomly assigned into midazolam premedication group (M group, n = 40) or CES pretreatment group (CES group, n = 40). The patients in the M group were intramuscularly injected with midazolam (0.07 mg/kg) 30 minutes before receiving general anesthesia. The patients in the CES group received 20 minutes of CES pretreatment on the day before and on the morning of the surgery. RESULTS: In the preoperative holding area, the anxiety score (P = .02) and the sedation score (P < .001) were significantly lower in the CES group compared with those in the M group. The oxygen saturations at the preoperative holding area and the operating room were significantly higher in the CES group than those in the M group (P < .001). CONCLUSION: CES pretreatment relieved preoperative anxiety with less risk of over-sedation and respiratory depression than midazolam premedication in geriatric patients.

Morphine attenuates endothelial cell adhesion molecules induced by the supernatant of LPS-stimulated colon cancer cells.

A large reservoir of bacterial lipopolysaccharide (LPS) is available in the colon and this could promote colon cancer metastasis by enhancing tumor cell adhesion, intravasation, and extravasation. Furthermore, adhesion molecules like ICAM-1, VCAM-1, and E-selectin play important roles in the adhesion of tumor cells to endothelium. This study was designed to determine whether morphine can attenuate the expressions of adhesion molecules up-regulated by the supernatant of LPS-stimulated HCT 116 colon cancer cells (LPS-Sup). In this study, we divided to three groups by cell-growth medium of human umbilical vascular endothelial cells (HUVECs): the control group was incubated in growth factor-free endothelial medium, the Sup group was incubated in the supernatant of HCT 116 cells (Sup), and the LPS-Sup group was incubated in LPS-Sup. To observe effect of morphine to the adhesion molecules expressions in the LPS-Sup group, we co-treated morphine with LPS or added it to LPS-Sup. Adhesion molecule expressions on HUVECs in all three groups were measured during incubation period. Consquentially, ICAM-1, VCAM-1, and E-selectin expressions on HUVECs were significantly lower when morphine was co-treated with LPS than not co-treated. Thus, we suggest that morphine affects the expressions of adhesion molecules primarily by attenuating LPS stimuli on tumor cells.

Morphine postconditioning attenuates ICAM-1 expression on endothelial cells.

The purpose of this study is to determine 1) whether morphine post condition (MPostC) can attenuate the intercellular adhesion molecules-1 (ICAM-1) expression after reoxygenation injury and 2) the subtype(s) of the opioid receptors (ORs) that are involved with MPostC. Human umbilical vein endothelial cells (HUVECs) were subjected to 6 hr anoxia followed by 12 hr reoxygenation. Three morphine concentrations (0.3, 3, 30 µM) were used to evaluate the protective effect of MPostC. We also investigated blockading the OR subtypes' effects on MPostC by using three antagonists (a µ-OR antagonist naloxone, a κ-OR antagonist nor-binaltorphimine, and a δ-OR antagonist naltrindole) and the inhibitor of protein kinase C (PKC) chelerythrine. As results, the ICAM-1 expression was significantly reduced in the MPostC (3, 30 µM) groups compared to the control group at 1, 6, 9, and 12 hours reoxygenation time. As a consequence, neutrophil adhesion was also decreased after MPostC. These effects were abolished by co administering chelerythrine, nor-binaltorphimine or naltrindole, but not with naloxone. In conclusion, it is assumed that MPostC could attenuate the expression of ICAM-1 on endothelial cells during reoxygenation via the κ and δ-OR (opioid receptor)-specific pathway, and this also involves a PKC-dependent pathway.

Effects of cranial electrotherapy stimulation on preoperative anxiety and blood pressure during anesthetic induction in patients with essential hypertension.

OBJECTIVE: Cranial electrotherapy stimulation (CES) is a non-invasive treatment that improves symptoms such as anxiety and pain. The purpose of this study was to analyze the effect of CES pretreatment on levels of preoperative anxiety, pain, and hemodynamic responses-especially changes in blood pressure-during anesthetic induction in patients with essential hypertension. METHODS: Eighty patients undergoing general anesthesia were randomly assigned to receive either no pretreatment (control group, n = 40) or CES pretreatment (CES group, n = 40). Anxiety scores, systolic and diastolic blood pressures, mean arterial pressure, and heart rate were measured in the general ward the evening before surgery, as well as in the preoperative holding area, operating room, and after intubation. Withdrawal responses to rocuronium injection were also measured. RESULTS: Anxiety scores in the operating room were significantly lower in the CES group. Withdrawal responses to rocuronium injection were also significantly lower in the CES group. There were no significant differences in hemodynamic values between the two groups. CONCLUSIONS: CES pretreatment reduces both preoperative anxiety levels and withdrawal responses to rocuronium injection. However, it does not have a significant effect on hemodynamic responses.

Sugammadex affects emergence agitation in children undergoing strabismus surgery.

Objective Emergence agitation (EA) has a multifactorial origin, and the effect of sugammadex on EA has not been established. We investigated the effect of sugammadex on EA incidence and severity. Methods We performed a retrospective study of children aged 1 to 13 years who underwent strabismus surgery. Patients received sugammadex or conventional neuromuscular reversal agents. The primary outcome variables were EA incidence and severity. Secondary outcome variables were postoperative fentanyl use, postoperative nausea and vomiting, time from reversal agent administration to extubation, time from the end of surgery to arrival in the post-anesthesia care unit (PACU) and time spent in the PACU. We used propensity score matching to eliminate baseline imbalances. Results Age, sex, use of desflurane, and intraoperative fentanyl were significant predictors of agitation severity using a multivariable analysis. Sugammadex did not significantly affect EA in logistic regression and multiple regression analyses. In the propensity-matched analysis, patients in the sugammadex group showed rapid recovery, but there was no difference in the EA incidence or severity. Conclusion Sugammadex did not affect EA incidence or severity compared with conventional cholinesterase inhibitors, although it showed a favorable recovery profile in children undergoing strabismus surgery.

Correlation between regional tissue perfusion saturation and lactate level during cardiopulmonary bypass.

BACKGROUND: Cardiopulmonary bypass (CPB) can cause systemic hypoperfusion, which remains undetected by routine monitoring of physiological parameters. Noninvasive tissue perfusion monitoring offers a clinical benefit by detecting low systemic perfusion. In this study, we tried to evaluate whether regional tissue perfusion saturation reflects systemic hypoperfusion during CPB. METHODS: This retrospective study included 29 patients with American Society of Anesthesiologists physical status II-III, who required cardiac surgery with CPB. We evaluated the correlations of serum lactate and delivery oxygen with organ perfusion values of peripheral tissue oxygen saturation and cerebral oxygen saturation. Data were recorded at different stages of CPB: T1 (pre-CPB), T2 (cooling), T3 (hypothermia), T4 (rewarming), and T5 (post-CPB). RESULTS: Lactate levels were elevated after CPB and up to weaning (P < 0.05). The levels of peripheral and tissue oxygen saturation decreased after the start of CPB (P < 0.05). Lactate levels were negatively correlated with peripheral tissue oxygen saturation levels at T4 (R = -0.384) and T5 (R = -0.370) and positively correlated with cerebral oxygen saturation at T3 (R = 0.445). Additionally, delivery oxygen was positively correlated with peripheral tissue oxygen saturation at T4 (R = 0.466). CONCLUSIONS: In this study, we demonstrated that peripheral tissue oxygen saturation can be a reliable tool for monitoring systemic hypoperfusion during CPB period. We also believe that peripheral tissue oxygen saturation is a valuable marker for detecting early stages of hypoperfusion during cardiac surgery.

Investigating preoperative myoglobin level as predictive factor for acute kidney injury following cardiac surgery with cardiopulmonary bypass: a retrospective observational study

Abstract Background: Early identification of patients at risk of AKI after cardiac surgery is of critical importance for optimizing perioperative management and improving outcomes. This study aimed to identify the association between preoperative myoglobin levels and postoperative acute kidney injury (AKI) in patients undergoing valve surgery or coronary artery bypass graft surgery (CABG) with cardiopulmonary bypass. Methods: This retrospective study included 293 patients aged over 17 years who underwent valve surgery or CABG with cardiopulmonary bypass. We excluded 87 patients as they met the exclusion criteria. Therefore, 206 patients were included in the final analysis. The patients' demographics as well as intraoperative and postoperative data were collected from electronic medical records. AKI was defined according to the Acute Kidney Injury Network classification system. Results: Of the 206 patients included in this study, 77 developed AKI. The patients who developed AKI were older, had a history of hypertension, underwent valve surgery with concomitant CABG, had lower preoperative hemoglobin levels, and experienced prolonged extracorporeal circulation (ECC) times. Multivariate logistic regression analysis revealed that preoperative myoglobin levels and ECC time were correlated with the development of AKI. A higher preoperative myoglobin level was an independent risk factor for the development of cardiac surgery-associated AKI. Conclusions: Higher preoperative myoglobin levels may enable physicians to identify patients at risk of developing AKI and optimize management accordingly.

Lidocaine does not prevent bispectral index increases in response to endotracheal intubation.

We investigated the effect of IV lidocaine on the hemodynamic and bispectral index responses to induction of general anesthesia and endotracheal intubation. Forty patients (ASA I) were randomly allocated into 2 groups of 20 to receive normal saline or lidocaine 1.5 mg/kg IV 30 s after induction. Ninety seconds later, endotracheal intubation was performed. Systolic blood pressure, heart rate, and bispectral index were measured at baseline, 1 min after induction, at preintubation, and every minute until 5 min after endotracheal intubation. Bispectral index at 1 min after induction and preintubation in the lidocaine group were significantly lower compared with the control group (P < 0.05). Systolic blood pressure increased significantly at 1 and 2 min after intubation in the control group compared with the baseline value (P < 0.05) but did not increase significantly in the lidocaine group. Heart rate increased at 1 to 3 min in both groups (P < 0.05), but there was no significant difference between the two groups. One patient in the control group had recall of the procedure. We conclude that the administration of IV lidocaine (1.5 mg/kg) does not suppress the hypnotic response to endotracheal intubation.

The protective effect of hydromorphone to ischemia in rat glial cells.

BACKGROUND: Ischemic insults during operation can cause ischemic-reperfusion injuries in brain as well as memory impairments. Total intravenous anesthesia (TIVA) is the preferred anesthetic method in brain surgery, as it utilizes motor evoked potential monitoring. And the use of opioids is common in TIVA. However there are few studies about ischemic protective effect of opioids to glial cells. METHODS: We used mixed cultures of rat glial cells, which were harvested from the brain of 1-day old rat. We divided the experimental groups according to their hydromorphone conditioning period: (a) pre-culture, (b) per-culture, or (c) pre- and per-culture. We measured the levels of the reactive oxygen species (ROS) induced by tert-butyl hydroperoxide (TBH) using flow cytometry. The ROS levels in the glial cells were also measured after the administration of 100 nM hydromorphone and selective opioid receptor antagonists. RESULTS: The ROS levels were reduced in the hydromorphone-treated group, as compared to the control group (only TBH treated). There were no differences between pre-conditioned and per-conditioned groups. However, the ROS levels were more reduced in pre- and per-conditioned group compared to pre-conditioned or per-conditioned only groups. Furthermore, selective antagonists for the delta, kappa, or mu opioid receptor partially negated the hydromorphone effect. CONCLUSION: This study demonstrated that hydromorphone can have additional protective effects on oxidative stress when pre- and per-conditioning is combined. Furthermore we proved that µ, δ, κ opioid receptors participate in protective mechanism of hydromorphone to glial cells.

Corrigendum: Occurrence bilateral bronchospasm consequently after unilateral bronchospasm (Korean J Anesthesiol 2013 December 65(6 Suppl): S28-S29).

[This corrects the article on p. S28 in vol. 65, PMID: 24478860.].

Dexmedetomidine preconditioning attenuates Cisplatin-induced ototoxicity in zebrafish.

OBJECTIVES: Utilisation of high-frequency drills is known to increase noise induced hearing loss due to increasing the damages of inner ear cells. This study aimed to investigate whether preconditioning by using dexmedetomidine (DEX) decreased the occurrence of ischemia in inner cells of the ear. METHODS: We utilised a transgenic zebrafish line Brn3C, and the embryos were collected from breeding adult zebrafish. Five-day-old larvae were cultured at the density of 50 embryos, and the larvae were classified into 4 groups: control, cisplatin group, DEX group, and DEX+yohimbine; adrenoreceptor blocker group. The DEX group was categorised into 3 subgroups by dosage; 0.1, 1, and 10 µM. Preconditioning was performed for 150 minutes and then exposed to cisplatin for 6 hours. The experiment was performed in 7 replicates for each group and the number of hair cells in 3 parts of the neuromasts of each fish was determined. RESULTS: Hair cell apoptosis by cisplatin was attenuated more significantly in the DEX preconditioning group than in the control group. However, the preconditioning effects were not blocked by yohimbine. CONCLUSION: The results of this study suggest that hearing loss caused by vibration-induced noise could be reduced by using DEX and may occur through other mechanisms rather than adreno-receptors.

Anesthetic management of hypertensive crisis in a three-year-old patient with undiagnosed severe renal artery stenosis: a case report.

Pediatric hypertensive crisis is a potentially life threatening medical emergency, usually secondary to an underlying disease. Hypertension commonly occurs during general anesthesia, and is usually promptly and appropriately treated by anesthesiologists. However in children with severe, unexplained, or refractory hypertension, it has the potential to cause morbidity and even mortality in susceptible patients. We report an anesthetic management of an unexpected hypertensive crisis that developed during general anesthesia in a three-year-old girl with undiagnosed severe left renal artery stenosis.

Effects of cranial electrotherapy stimulation on preoperative anxiety, pain and endocrine response.

OBJECTIVES: Cranial electrotherapy stimulation (CES) is used as a treatment for depression and anxiety, and as an adjunctive intervention for pain management. This prospective study investigated whether CES could decrease preoperative anxiety, the injection pain of rocuronium, postoperative pain and stress hormone levels. METHODS: Female patients undergoing thyroidectomy were randomly assigned to two groups, to receive either no pretreatment (control group) or CES pretreatment. Anxiety score, withdrawal response on rocuronium injection, and pain scores at 1, 4, 12 and 24 h post surgery were evaluated. Adrenocorticotrophic hormone (ACTH), cortisol and glucose levels were measured. Patients were blinded to the treatment condition. RESULTS: Fifty patients entered the study (n = 25 per group). Anxiety score and withdrawal responses during rocuronium injection were significantly reduced in the CES group compared with the control group. Pain score was significantly lower in the CES group than in the control group, 1 h and 4 h post surgery. There were no significant differences in ACTH, cortisol and glucose levels. CONCLUSIONS: CES pretreatment appears to reduce the level of preoperative anxiety, injection pain of rocuronium and postoperative pain. However, CES pretreatment did not affect stress hormone responses.

Beneficial effects of adding ketamine to intravenous patient-controlled analgesia with fentanyl after the Nuss procedure in pediatric patients.

PURPOSE: The aim of this prospective, double-blind, randomized study was to investigate the analgesic effects of low-dose ketamine on intravenous patient-controlled analgesia (IV-PCA) with fentanyl for pain control in pediatric patients following the Nuss procedure for pectus excavatum. MATERIALS AND METHODS: Sixty pediatric patients undergoing the Nuss procedure were randomly assigned to receive fentanyl (Group F, n=30) or fentanyl plus ketamine (Group FK, n=30). Ten minutes before the end of surgery, following the loading dose of each solution, 0.5 µg/kg/hr of fentanyl or 0.5 µg/kg/hr of fentanyl plus 0.15 mg/kg/hr of ketamine was infused via an IV-PCA pump (basal rate, 1 mL/hr; bolus, 0.5 mL; lock out interval, 30 min). Fentanyl consumption, pain score, ketorolac use, nausea/vomiting, ondansetron use, pruritus, respiratory depression, hallucination, dreaming, and parent satisfaction with pain control were measured throughout the 48 hours following surgery. RESULTS: The pain scores, ketorolac use, and fentanyl consumption of Group FK were significantly lower than in Group F (p<0.05). The incidence of nausea/vomiting and ondansetron use in Group FK was significantly lower than in Group F (p<0.05). There were no reports of respiratory depression, hallucination or dreaming. Parent satisfaction with pain control was similar between the two groups. CONCLUSION: We concluded that low-dose ketamine added to IV-PCA with fentanyl after the Nuss procedure in pediatric patients can reduce pain scores, consumption of fentanyl, and incidence of nausea/vomiting without increasing side effects.

The effect of ketamine on the separation anxiety and emergence agitation in children undergoing brief ophthalmic surgery under desflurane general anesthesia.

BACKGROUND: Emergence agitation (EA) frequently occurs after desflurane anesthesia in children. Ketamine, because of its sedative and analgesic properties, might be useful for the management of separation anxiety and EA. We investigated the preventive effect of ketamine on separation anxiety and EA after desflurane anesthesia in children for brief ophthalmic surgery. METHODS: Sixty children, ranging in age from 2-8 years old, undergoing brief ophthalmic surgery were randomly allocated to one of the 3 groups: group C received normal saline, group K1.0 received ketamine 1.0 mg/kg intravenously before entering the operating room, or group K0.5 received ketamine 0.5 mg/kg 10 min before the end of the surgery. Before induction, the separation anxiety score was evaluated. Extubation time, post-anesthesia care unit stay time, postoperative nausea and vomiting, emergence agitation, and pain were assessed. RESULTS: The group K1.0 had a lower separation anxiety score compared with groups K0.5 and C. Extubation time in group K0.5 was significantly prolonged compared with groups K1.0 and C. The incidence of EA and the modified Children's Hospital of Eastern Ontario Pain Scale were significantly lower in group K1.0 and group K0.5 compared to group C, but there was no significant difference between groups K1.0 and K0.5. CONCLUSIONS: In children undergoing brief ophthalmic surgery with desflurane anesthesia, ketamine 1.0 mg/kg administered before entering the operating room reduced separation anxiety, postoperative pain, and incidence of EA without delay in recovery.