Relationship Between Age and Frequency of Side Effects Associated with Postoperative Analgesia

Study Objective: Although patient-controlled analgesia (PCA) is a valid analgesic method, it is necessary to pay attention to associated side effects, especially in elderly patients. It is unclear whether the incidence of side effects increases with age. In this study, we examined the incidence of side effects by age to confirm whether the frequency of side effects varies depending on age group. Patients: Patients who underwent gastroenterological surgery at Hiroshima University Hospital between 2009 and 2013 and received postoperative analgesia using PCA [either epidural PCA (PCEA) or intravenous PCA (IVPCA) were included]. Measurements: The degree of pain using the visual analog scale, number of PCA requests, and frequency of side effects, including nausea, vomiting, pruritus, urinary disturbance, drowsiness, low blood pressure, delirium, and respiratory depression, was determined from PCA records. Main Results: A total of 2,881 patients were enrolled and categorized into PCEA (n = 1,965) or IVPCA (n = 916) group based on postoperative analgesia. The incidence of delirium significantly increased with age in both groups (P < 0.001). In the PCEA group, the incidence of nausea, vomiting, and itching decreased, whereas that of hypotension significantly increased with age. Visual analog scale scores both at rest and during activity on postoperative day 2 were not correlated with age in either group. There was a significant negative correlation with age in both groups for the number of PCA requests on postoperative day 2. Conclusions: The incidence of postoperative delirium increases with age regardless of pain relief method. Side effects related to postoperative analgesia are not necessarily more likely to occur with age

Branched-chain amino acids-induced cardiac protection against ischemia/reperfusion injury

Aims: Amino acids, especially branched chain amino acids (BCAAs), have important regulatory roles in protein synthesis. Recently studies revealed that BCAAs protect against ischemia/reperfusion (I/R) injury. We studied the signaling pathway and mitochondrial function affecting a cardiac preconditioning of BCAAs. Main methods: An in vivo model of I/R injury was tested in control, mTOR+/+, and mTOR+/−. Mice were randomly assigned to receive BCAAs, rapamycin, or BCAAs + rapamycin. Furthermore, isolated cardiomyocytes were subjected to simulated ischemia and cell death was quantified. Biochemical and mitochondrial swelling assays were also performed. Key findings: Mice treated with BCAAs had a significant reduction in infarct size as a percentage of the area at risk compared to controls (34.1 ± 3.9% vs. 44.7 ± 2.6%, P = 0.001), whereas mice treated with the mTOR inhibitor rapamycin were not protected by BCAA administration (42.2 ± 6.5%, vs. control, P = 0.015). This protection was not detected in our hetero knockout mice of mTOR. Western blot analysis revealed no change in AKT signaling whereas activation of mTOR was identified. Furthermore, BCAAs prevented swelling which was reversed by the addition of rapamycin. In myocytes undergoing simulated I/R, BCAA treatment significantly preserved cell viability (71.7 ± 2.7% vs. 34.5 ± 1.6%, respectively, p < 0.0001), whereas rapamycin prevented this BCAA-induced cardioprotective effect (43.5 ± 3.4% vs. BCAA, p < 0.0001). Significance: BCAA treatment exhibits a protective effect in myocardial I/R injury and that mTOR plays an important role in this preconditioning effect.This work was supported by JSPS KAKENHI, Japan [grant number 19K09353]

Leucine imparts cardioprotective effects by enhancing mTOR activity and mitochondrial fusion in a myocardial ischemia/reperfusion injury murine model

Background: Coronary artery disease is a leading cause of morbidity and mortality among patients with diabetes. Previously, we demonstrated that branched-chain amino acids (BCAAs) showed cardioprotective effects against cardiac ischemia/reperfusion (I/R) injury. A recent study suggested that leucine (Leu), a BCAA, is a key amino acid involved in mammalian target of rapamycin (mTOR) activity and mitochondrial function. However, whether Leu has cardioprotective effects on diabetic hearts is unclear. In this study, we examined the preconditioning effect of Leu treatment on high-fat diet (HFD)-induced obese mouse which simulate prediabetic heart. Methods: In vivo mice models of I/R injury were divided into the following groups: control, mTOR+/−, and high-fat diet (HFD)-induced obese groups. Mice were randomly administered with Leu, the mTOR inhibitor rapamycin (Rap), or Leu with Rap. Isolated rat cardiomyocytes were subjected to simulated I/R injury. Biochemical and mitochondrial functional assays were performed to evaluate the changes in mTOR activity and mitochondrial dynamics caused by Leu treatment. Results: Leu-treated mice showed a significant reduction in infarct size when compared with the control group (34.8% ± 3.8% vs. 43.1% ± 2.4%, n = 7, p < 0.05), whereas Rap-treated mice did not show the protective effects of Leu. This preconditioning effect of Leu was attenuated in mTOR+/− mice. Additionally, Leu increased the percentage of fused mitochondria and the mitochondrial volume, and decreased the number of mitochondria per cell in isolated cardiomyocytes. In HFD-induced obese mice, Leu treatment significantly reduced infarct size (41.0% ± 1.1% vs. 51.0% ± 1.4%, n = 7, p < 0.05), which was not induced by ischemic preconditioning, and this effect was inhibited by Rap. Furthermore, we observed enhanced mTOR protein expression and mitochondrial fusion with decreased reactive oxygen species production with Leu treatment in HFD-induced obese mice, but not in mTOR+/− mice. Conclusions: Leu treatment improved the damage caused by myocardial I/R injury by promoting mTOR activity and mitochondrial fusion on prediabetic hearts in mice

Genetic screening for malignant hyperthermia and comparison of clinical symptoms in Japan

Malignant hyperthermia (MH) is an anaesthetic complication that causes an abnormal hypermetabolic state. RYR1 encoding ryanodine receptors of the sarcoplasmic reticulum and CACNA1S encoding α subunits of dihydropyridine receptors are known to be associated with MH pathogenicity. We performed genetic screening using next-generation sequencing to evaluate the prevalence of genes associated with MH pathogenicity and clinical symptoms. This was a retrospective cohort study wherein next-generation sequencing data of 77 families diagnosed with MH predisposition by calcium-induced calcium release (CICR) tests from 1995 to 2019 was used to search for RYR1 and CACNA1S variants. Furthermore, the clinical symptoms and predisposition tests in participants with RYR1 and CACNA1S variants were compared. In the 77 families, 44.2%, 7.8%, and 48.1% individuals had RYR1, CACNA1S, and neither RYR1 nor CACNA1S variants, respectively. Clinically significant differences were found in the maximum body temperature, maximum elevated body temperature for 15 min, creatinine kinase level, and CICR rate between the RYR1 and CACNA1S groups. The prevalence of pathogenic CACNA1S variants appears to be prominent in Japan. The severity of clinical symptoms and the CICR rate were greater in individuals with RYR1 variants than in those with CACNA1S variants, likely due to more direct regulation of calcium levels by ryanodine receptors than by dihydropyridine receptors. Genetic analysis of MH in future studies may help identify other genes associated with MH, which will further clarify the relationship between genotypes and MH symptoms and contribute to safer anaesthesia practice.This study was supported by a Grant-in-Aid for Young Scientists (grant number: 17K16733 to Y.N. and 20K17783 to R.K.) from the Japan Society for the Promotion of Science and by the Takeda Science Foundation (H.K.)

Evaluation of Hemodynamics During Posture Change to Knee-Chest Position by FloTracTM

In order to evaluate changes in hemodynamics, a FloTracTM system was used during posture change from supine to knee-chest position. Thirty-five patients undergoing lumbar surgery participated in this study. Anesthesia was performed with total intravenous anesthesia using propofol and remifentanil. Cardiac index (CI), stroke volume index (SVI), and stroke volume variation (SVV) were measured by using FloTracTM in addition with heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean blood pressure (MBP). The values before and after postural change were compared. SVV increased immediately after posture change and remained high. With posture change to the knee-chest position, HR, DBP and SVV increased and SBP, CI and SVI decreased. An increase in SVV from immediately after postural change indicated that SVV did not reflect circulating blood volume

Comparison of Prone Position and Knee-Chest Position in Hemodynamics During Postural Change

全静脈麻酔下で腹臥位または膝胸位へ体位変換した際の循環動態を両体位で比較するため，腰部脊椎手術を受けた患者を後方視的に調査した。体位変換の直前，体位変換直後， ３分後， ５分後の心拍数（HR）および収縮期血圧（SBP），拡張期血圧（DBP），平均血圧（MBP）を測定した。各パラメーターを体位変換前の値を基準とし体位変換後の変化率を算出し膝胸位（Knee-chest群）と腹臥位（Prone群）で比較した。統計はt検定を用いた。対象患者はKnee-chest群３０名，Prone群３０名であった。SBPは体位変換直後から５分後までKnee-chest群で有意に低く，MBPは５分後でKnee-chest群で有意に低く，HRは体位変換直後から５分後までKnee-chest群で有意に高かった。このため，全静脈麻酔管理下で膝胸位への体位変換は，腹臥位への体位変換よりも血圧の低下に注意する必要があると結論した。We compared the hemodynamics of posture change under general anesthesia between prone position and knee chest position. Patients who underwent lumbar spinal surgery were retrospectively investigated.　Heart rate (HR) and systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP) were measured before and after postural change, 3 minutes and 5 minutes after postural change.　The rate of change of each parameter was calculated and compared in both groups of knee-chest and prone position.　Student’s t-test was used as statistical methods. We analyzed 60 patients (30 Knee-chest, 30 Prone).　SBP was significantly lower in the Knee-chest group from immediately after postural change to 5 minutes after postural change. MBP was significantly lower in the Knee-chest group 5 minutes after postural change. HR was significantly higher in the Knee-chest group from immediately after body change to 5 minutes after postural change.　In conclusion, SBP and MBP were significantly lower in the knee-chest position than in the prone position during postural change. Postural change to the kneechest position requires attention to lowering of blood pressure than postural change to the prone position

A Case of Horner’s Syndrome Caused by Thoracic Epidural Anesthesia

Horner’s syndrome is a syndrome characterized by miosis, eyelid ptosis, narrowing of the eyelids and ocular depression. Diagnosis of the causative disease is important because it may accompany fatal diseases such as brain stem infarction and bleeding, spinal hematoma and neoplastic lesion and internal carotid artery dissection. A woman in her 60s. Left lung lower lobectomy was performed with thoracoscopy assistance for left lung cancer. General anesthesia with epidural anesthesia was performed with propofol and remifentanil. The epidural catheter was punctured from the sixth seventh thoracic vertebrae. Horner’s syndrome occurred on 2 days postoperatively. After reducing epidural anesthesia, symptoms improved. From this, epidural anesthesia proved to be the cause of Horner’s syndrome. Epidural anesthesia can rarely cause Horner’s syndrome

Precise Prediction of Right Atrium Position within Expiratory Phase Thorax

Fifteen patients who underwent CT during both the inspiratory and expiratory phases were retrospectively reviewed. The anterior posterior (AP) diameter of the thorax, the largest vertical distance from the uppermost RA level to the back surface (RA height), and the ratio of RA height to AP diameter of the thorax (RA thorax ratio) were determined. We then attempted to predict the expiratory RA height using the following 2 methods. Formula 1: Predicted expiratory RA height = Average inspiratory RA thorax ratio × Expiratory AP diameter of thorax. Formula 2: Predicted expiratory RA height = Each inspiratory RA thorax ratio × Expiratory AP diameter of thorax. In a Bland-Altman plot with Formula 1, the bias was –0.34 mm and limit of agreement ranged from –19.44 to 18.75 mm, whereas those were –1.31 mm and –9.72 to 7.10 mm with Formula 2. Our findings indicate that inspiratory CT imaging and expiratory phase thorax diameter can be used to precisely predict expiratory phase RA height in individual patients

Three Cases Becoming Difficult to Remove Epidural Catheter Postoperatively Due to Coagulation Defect Associated with Antibiotics

Perioperative vitamin K deficiency can cause severe coagulopathy rapidly. Vitamin K deficiency tends to be overlooked despite the elucidation of pathophysiology and countermeasures. The main causes of vitamin K deficiency are insufficient intake, low supply from intestinal bacteria, and synthesis inhibition of vitamin K by N-methyltetrazolethiol (N - MTT) contained antibiotics. We experienced three cases in which it was difficult to remove epidural catheter because of coagulation abnormality due to vitamin K deficiency after surgery. Vitamin K deficiency should be wary of when epidural catheter is indwelled or withdrawn from a patient who is administered with antibiotic containing N-MTT in the fasted state

Postoperative assessment after AVR and TAVI

Background and aims : Severe aortic stenosis (AS) has been normally treated with surgical aortic valve replacement (AVR) whereas recently, transcatheter aortic valve implantation (TAVI) has been introduced as a minimally invasive operation for patients with high surgical risk and frailty. In this study, we have evaluated postoperative physical function and nutrition intake in the patients following AVR and TAVI. Methods : This prospective observational study involved 9 patients with surgical aortic valve replacement (AVR) and 7 patients with transcatheter aortic valve implantation (TAVI). Body composition was measured one day prior surgery, postoperative day (POD) 1, POD 3, POD 5 and POD 7. Hand grip strength, calf circumference and gait speed were measured one day before surgery and on the day of discharge. Results : Skeletal muscle was significantly decreased in AVR patients at postoperative day 3 and 7, while there was no change in TAVI patients. Patients with TAVI showed higher dietary intake after surgery compared to patients with AVR, and they maintained hand grip strength and calf circumference at discharge. Conclusions : In elderly patients with AS, TAVI can improve post-operative recovery maintaining nutritional status and physical function even