Genome-Wide Association Study Identifies Novel Candidate Variants Associated with Postoperative Nausea and Vomiting.

Considerable individual differences are widely observed in the incidence of postoperative nausea and vomiting (PONV). We conducted a genome-wide association study (GWAS) to identify potential candidate single-nucleotide polymorphisms (SNPs) that contribute to PONV by utilizing whole-genome genotyping arrays with more than 950,000 markers. The subjects were 806 patients who provided written informed consent and underwent elective surgery under general anesthesia with propofol or desflurane. The GWAS showed that two SNPs, rs2776262 and rs140703637, in the LOC100506403 and CNTN5 gene regions, respectively, were significantly associated with the frequency of nausea. In another GWAS conducted only on patients who received propofol, rs7212072 and rs12444143 SNPs in the SHISA6 and RBFOX1 gene regions, respectively, were significantly associated with the frequency of nausea as well as the rs2776262 SNP, and the rs45574836 and rs1752136 SNPs in the ATP8B3 and LOC105370198 gene regions, respectively, were significantly associated with vomiting. Among these SNPs, clinical and SNP data were available for the rs45574836 SNP in independent subjects who underwent laparoscopic gynecological surgery, and the association was replicated in these subjects. These results indicate that these SNPs could serve as markers that predict the vulnerability to PONV. Our findings may provide valuable information for achieving satisfactory prophylactic treatment for PONV.

Practical guide for safe sedation.

This practical guide has been developed to ensure safe and effective sedation performed in adult patients outside of the operating room, for instance in intensive care units and dental treatment rooms and in the field of palliative care. Sedation levels are classified based on level of consciousness, airway reflex, spontaneous ventilation, and cardiovascular function. Deep sedation induces loss of consciousness and protective reflexes, and can cause respiratory depression and pulmonary aspiration. Invasive medical procedures necessitating deep sedation include cardiac ablation, endoscopic submucosal dissection, and internal radiation therapy. Appropriate analgesia is necessary for procedures that require deep sedation. The sedationist should evaluate the risks of the planned procedure, explain the sedation process to the patient, and obtain the patient's informed consent. Major parameters to be evaluated preoperatively are the patient's airway and general condition. Equipment, instruments, and drugs necessary for emergency situations should be defined and routinely maintained. To prevent aspiration, patients scheduled for moderate or deep sedation should fast preoperatively. In both inpatients and outpatients, biological monitoring should be continued until the discharge criteria are met. Anesthesiologists should be involved in management systems that ensure safe and effective sedation even if they do not personally perform all sedation procedures.

Early postoperative pulmonary complications after minimally invasive esophagectomy in the prone position: incidence and perioperative risk factors from the perspective of anesthetic management.

OBJECTIVES: To investigate the incidence of and the risk factors for early postoperative pulmonary complications (PPC) after minimally invasive esophagectomy (MIE) in the prone position from the perspective of anesthetic management. METHODS: We conducted a historical cohort study of patients who underwent MIE in the prone position between September 2010 and August 2018. PPC was defined as pneumonia, atelectasis, acute respiratory distress syndrome (ARDS), respiratory failure, and pulmonary embolism (Clavien-Dindo Classification Grade II or higher) that occurred within 7 days after MIE. RESULTS: Out of 489 patients, there were 90 patients (18.4%) with PPC: 75 patients with pneumonia, 24 patients with atelectasis, 13 patients with respiratory failure, 6 patients with ARDS, and 2 patients with pulmonary embolism. Twenty-eight patients suffered from 2 or more components of PPC. PPC patients were older (66.6 vs. 63.6 year, P = 0.038) and had higher amount of crystalloid (4200 vs. 3550 mL, P < 0.0001), and longer duration of anesthesia (670 vs. 625 min, P = 0.0062) than non-PPC patients. PPC patients were more likely to have had chronic obstructive pulmonary disease (COPD) (26.7 vs. 7.8%, P < 0.001). Incidence of PPC was significantly higher in patients with one-lung ventilation than with two-lung ventilation (37.1 vs. 15.3%, P < 0.001). Multivariable logistic regression analysis showed that PPC was associated with age (per 10 years, odds ratio (OR) = 1.41), COPD (OR = 3.43), one-lung ventilation (OR = 1.94), and volume of crystalloid (per 500 mL, OR = 1.22). CONCLUSIONS: Two-lung rather than one-lung ventilation should be chosen and fluid overload should be avoided in patients undergoing MIE in the prone position.

Guidelines for sedation in gastroenterological endoscopy (second edition).

Sedation in gastroenterological endoscopy has become an important medical option in routine clinical care. Here, the Japan Gastroenterological Endoscopy Society and the Japanese Society of Anesthesiologists together provide the revised "Guidelines for sedation in gastroenterological endoscopy" as a second edition to address on-site clinical questions and issues raised for safe examination and treatment using sedated endoscopy. Twenty clinical questions were determined and the strength of recommendation and evidence quality (strength) were expressed according to the "MINDS Manual for Guideline Development 2017." We were able to release up-to-date statements related to clinical questions and current issues relevant to sedation in gastroenterological endoscopy (henceforth, "endoscopy"). There are few reports from Japan in this field (e.g., meta-analyses), and many aspects have been based only on a specialist consensus. In the current scenario, benzodiazepine drugs primarily used for sedation during gastroenterological endoscopy are not approved by national health insurance in Japan, and investigations regarding expense-related disadvantages have not been conducted. Furthermore, including the perspective of beneficiaries (i.e., patients and citizens) during the creation of clinical guidelines should be considered. These guidelines are standardized based on up-to-date evidence quality (strength) and supports on-site clinical decision-making by patients and medical staff. Therefore, these guidelines need to be flexible with regard to the wishes, age, complications, and social conditions of the patient, as well as the conditions of the facility and discretion of the physician.

Efficacy of novel sedation using the combination of dexmedetomidine and midazolam during endoscopic submucosal dissection for esophageal squamous cell carcinoma.

BACKGROUND: Endoscopic submucosal dissection (ESD) is the preferred treatment for esophageal squamous cell carcinoma (ESCC). However, ESD can be difficult when patients move due to insufficient sedation. We conducted a prospective confirmatory single arm study to evaluate the efficacy of using dexmedetomidine (DEX) in combination with midazolam as a novel sedation for ESD. METHODS: Endoscopic submucosal dissection was performed without intubation in 65 patients. The primary outcome was the proportion of patients who did not move or require restraint during ESD, compared to historical control of ESD performed under midazolam sedation. Secondary outcomes included the frequency of complications and self-report questionnaires from patients and endoscopists. RESULTS: Restraint was not required in 97% of patients sedated using the combination of DEX and midazolam. Depressed respiration, low blood pressure, and bradycardia occurred in 23, 37, and 26% of patients, respectively. All patients recovered without severe complication. Occurrence of low blood pressure and bradycardia were higher, while respiratory depression was lower for the combination group than for the historical control group. The amount of midazolam used was significantly lower than in the control. Of note, 94% of patients had no painful sensations, with 3 reporting chest pain and 3 having a recollection of the procedure. Endoscopists were satisfied with the sedation in 94% of cases. All lesions were resected in en bloc fashion, without perforation. CONCLUSIONS: The combination of DEX and midazolam provided effective sedation for ESD for ESCC.

Guidelines for the use of cerebral oximetry by near-infrared spectroscopy in cardiovascular anesthesia: a report by the cerebrospinal Division of the Academic Committee of the Japanese Society of Cardiovascular Anesthesiologists (JSCVA).

Cerebral Oximetry by Near-infrared Spectroscopy (NIRS) has been used in cardiovascular anesthesia, but there was no guideline of regional cerebral oxygen saturation measured by cerebral oximetry by NIRS. This guideline provides recommendations applicable to patients at a risk of developing cerebral ischemia in cardiovascular surgery. Guidelines are intended to define practices meeting the needs of patients in most, but not all, circumstances, and should not replace clinical judgment. The Japanese Society of Cardiovascular Anesthesiologists (JSCVA) Task Force on Guidelines make an effort to ensure that the guideline writing committee contains broad views in using cerebral oximetry. Adherence to recommendations could be enhanced by shared decision making between healthcare providers and patients. This guideline was focused on cerebral oximetry of pediatric and adult cardiovascular disease. We hope this guideline would play an important role in using cerebral oximetry by measured NIRS.

[Anesthesia and Anti-cancer Therapeutic Agents].

An increasing number of cancer patients are treated with anti-cancer chemotherapy and may require not only elective but also emergency surgery. Anti-cancer agents may have adverse effects on various organs and negative effects on subsequent anesthetic management Anesthesiologists must therefore be aware of potential toxicity of anti-cancer agents. The common toxicities include cardiac, pulmonary, bone marrow, renal and hepatic effects. Cardiopulmonary toxicity caused by drugs such as anthracylines and bleomycin is of major concern for anesthesiologists. Other toxicities, however, also require special anesthetic considerations in anes- thesia. Toxicities can be cumulative and irreversible as with anthracyclines, and therefore, attention also has to be paid to the past history of chemotherapy. Preoperative assessment is key to consistent and uncomplicated management of anesthesia. Anesthesi- ologists should take a detailed history of cancer man- agement and understand precise chemotherapy regi- mens and specific side effects experienced by the patient.

[Sedation as a Part of Monitored Anesthesia Care (MAC) and Its Introduction to Japanese Clinical Practice].

To relieve or eliminate distress caused by invasive medical procedures, sedation is often used in routine clinical practice. Monitored anesthesia care (MAC) is needed in patients who receive increased doses of sedatives and/or analgesics, which may suppress the respiratory, cardiac, and/or vascular systems. Deep sedation, in particular, suppreses the nomal protective reflexes. It requires careful monitoring and intervention for patients. In Japan, sedation is performed in a large number of cases. It is unreasonable that only anesthesiologists administer MAC. In fact, sedation is often performed by non-anesthesiologists. In these circumstances, education and training for non-anesthesiologists are important

Incidence of and risk factors for postoperative nausea and vomiting at a Japanese Cancer Center: first large-scale study in Japan.

PURPOSE: The first purpose of this study was to determine the incidence of postoperative nausea and/or vomiting (PONV) 0-48 h after anesthesia at a Japanese cancer center. The second purpose of this study was to collect information on PONV risk factors, independently, in the categories of patient-related, anesthesia-related, and surgery-related factors. METHODS: The frequency of nausea and vomiting was prospectively investigated from 0 to 48 h after anesthesia in 1645 patients (11-94 years of age) at a single medical institution. The occurrence of nausea and vomiting and the use of antiemetics were recorded up to 48 h after anesthesia. Patient-related, anesthesia-related, and surgery-related factors were also recorded and submitted to multiple logistic regression analysis to determine the relationship of these factors to nausea and vomiting. RESULTS: The incidences of nausea and vomiting from 0 to 24 h after anesthesia were 40 and 22 %, respectively. The incidences 24-48 h after anesthesia were 10 and 3 %, respectively. Female sex, previous history of PONV, prolonged anesthesia, and remifentanil use during surgery were identified as risk factors for both nausea and vomiting. The use of a volatile anesthetic, use of fentanyl during surgery, postoperative use of opioids, nonsmoking status, and drinking alcohol on 4 or fewer days per week were identified as risk factors for nausea alone. CONCLUSION: The incidence of and risk factors for PONV at a Japanese cancer center according to this study are comparable to those reported elsewhere.

Blockade of 5-HT(2A) and/or 5-HT(2C) receptors modulates sevoflurane-induced immobility.

PURPOSE: Blockade of 5-hydroxytryptamine (5-HT)(2A) receptors reportedly mediates or modulates the ability of isoflurane to produce immobility during noxious stimulation and would thereby influence MAC (the minimum alveolar concentration required to suppress movement in response to noxious stimulation in 50% of subjects). However, no data are yet available regarding the role of this receptor in the immobilizing action of sevoflurane. In this study, we examined how prior intraperitoneal administration of either the 5-HT(2A) receptor antagonist altanserin or the 5-HT(2C/2B) receptor antagonist SB 206553 might affect sevoflurane MAC in rats. METHODS: Three groups of six male Wistar rats weighing 250-350 g each received one of the following drugs dissolved in dimethyl sulfoxide intraperitoneally 30 min before MAC testing: (1) altanserin 10 mg/kg; (2) SB 206553 10 mg/kg; (3) no drug (vehicle control). MAC was defined as the average of the concentrations that just prevented or just permitted movement in response to clamping the tail for 1 min. RESULTS: The rank order of MAC values obtained after intraperitoneal drug pretreatment and sevoflurane exposure was altanserin < SB 206553 < vehicle control. CONCLUSION: Considering the low levels of 5-HT(2B) receptors within the CNS, this result suggests that 5-HT(2A) and the 5-HT(2C) receptors are present within the neural circuitry influencing sevoflurane MAC. Blockade of 5-HT(2A) and/or 5-HT(2C) receptors may modulate the immobility produced by sevoflurane during noxious stimulation.

Analysis of the cost-effectiveness of remifentanil-based general anesthesia: a survey of clinical economics under the Japanese health care system.

PURPOSE: Remifentanil has been available in Japan for 3 years. The use of this new opioid is considered a useful adjuvant to general anesthesia. Knowing the exact cost-effectiveness of remifentanil should lead to improved anesthetic outcomes with a reasonable cost. METHODS: This single-blinded, prospective, randomized study compared the cost of remifentanil-based general anesthesia combined with isoflurane, sevoflurane, or propofol with fentanyl-based conventional techniques in 210 women who underwent breast surgeries. RESULTS: Remifentanil-based general anesthesia was no more expensive than fentanyl-based conventional anesthesia. Postoperative nausea and vomiting was significantly less frequent after remifentanil-based than fentanyl-based anesthesia. CONCLUSION: This study shows that remifentanil-based general anesthesia is no more expensive than conventional fentanyl-based anesthesia under the Japanese health care system because of the small difference in price between remifentanil and fentanyl.

Inhibitory effects of landiolol and nicardipine on thiopental-induced yawning in humans.

PURPOSE: Either the calcium (Ca(2+))-channel blocker nicardipine or the beta(1)-adrenoceptor antagonist landiolol may be intravenously (IV) administered to reduce the hemodynamic responses to tracheal intubation. In this study, we examined the effects of these drugs on the yawning response elicited by intravenous thiopental in humans. METHODS: After Institutional Review Board approval, 180 consenting American Society of Anesthesiologists (ASA) I or II patients undergoing elective surgery were recruited. In a double-blind, randomized design, three groups of 60 patients each received one of the following intravenous injections: (1) landiolol 0.1 mg/kg (L-group), (2) nicardipine 0.02 mg/kg (N-group), or (3) saline (S-group). In all patients, anesthesia was subsequently induced IV with 4 mg/kg thiopental. Thereafter, the occurrence of the yawning response (characterized by mouth opening) was continuously assessed as the only clinical endpoint for 1 min. Throughout the study, mean arterial blood pressure and heart rate were also recorded at 1-min intervals. RESULTS: The incidence of the yawning response was lower in both the L-group (6.7%) and the N-group (16.7%) than in the S-group (46.7%) (each, P < 0.01). CONCLUSIONS: Prior intravenous administration of either a Ca(2+)-channel blocker or a beta(1)-adrenoceptor antagonist can greatly reduce the thiopental-induced yawning response in humans.

[Intrathecal morphine treatment in advanced cancer pain patients].

For more than 20 years morphine for spinal analgesia in patients with refractory cancer pain has been one of the cornerstones for the management of chronic, medically intractable pain. In general, most types of cancer pain are treatable following the guideline of Cancer Pain Relief well established by the WHO. However, some patient are unable to tolerate pain only following the guideline and often suffer with side-effects from high doses of opioid and from prescribed multiple adjuvant drugs. Due to the proximity to the receptor sites, the therapeutic efficacy of intrathecal opioid application lasts longer and also reduces systemic side effects. Intrathecal drug application is cost effective and can significantly improve the quality of life in selected patients with limited life expectancy. However, an intensive training of physicians, careful patient selection, awareness of specific complications, and arrangement of social back-up medical system are essential to commence intrathecal morphine application using implantable access port. This article introduces the basic idea of intrathecal morphine therapy with implantable access port (not pumps) as cost effective, alternative therapy for cancer patient suffering from intractable pain.

[Intraoperative management for two patients with malignant tumors in the neck].

We experienced two cases of malignant tumors in the neck with difficulties in airway control. In case 1, difficult airway was anticipated from the CT scan taken before the operation, but the glottis was observed easily by using laryngoscope. Therefore we judged intubation easy and rapid induction was performed, but the tube did not go in farther. When we pushed it in bleeding made the ventilation impossible, and the airway had to be ensured by tracheotomy. In case 2, difficult airway was anticipated from the CT scan. Making use of our experience in case 1, tracheotomy was performed under neuroleptanesthesia, but it was a too heavy burden for the patient. There are various methods of airway control and it is necessary for us to master the skills of them, but it is much safer to anticipate difficult airway by careful preoperative evaluation and manage accordingly than to find a way out of an emergency with these skills.

[Survey of preoperative cardiology consultation].

Cardiology consultations are often requested preoperatively for patients with cardiovascular problems. However, there are frequently differences in the evaluation of preoperative cardiac risks among cardiologists, surgeons and anesthesiologists. In order to obtain possible solutions to this problem, we conducted a survey of preoperative cardiology consultations performed directly by cardiologists. The survey indicates a lack of interaction with anesthesiologists and insufficient information on the surgical procedures and anesthesia for cardiologists to assess compromising cardiac risks. In addition, many cardiologists suggested that exercise tolerance required for surgical procedures should be 7 METs or more for surgical patients.