Postoperative intravenous patient-controlled analgesia improves pain management after subcutaneous implantable defibrillator implantation.

Objective: Postoperative pain is a major issue with subcutaneous implantable cardioverter defibrillators (S-ICD). In 2020, we introduced intravenous patient-controlled analgesia (IV-PCA) in addition to the conventional, request-based analgesia for postoperative pain control in S-ICD. To determine the effect and safety, we quantitatively assessed the effect of IV-PCA after S-ICD surgery over conventional methods. Methods: During the study period, a total of 113 consecutive patients (age, 50.1 ± 15.5 years: males, 101) underwent a de novo S-ICD implantation under general anesthesia. While the postoperative pain was addressed with either request-based analgesia (by nonsteroid anti-inflammatory drugs, N = 68, dubbed as "PCA absent") or fentanyl-based IV-PCA in addition to the standard care (N = 45, dubbed as "PCA present"). The degree of postoperative pain from immediately after surgery to 1 week were retrospectively investigated by the numerical rating scale (NRS) divided into four groups at rest and during activity (0: no pain, 1-3: mild pain, 4-6: moderate pain, 7-10: severe pain). Results: Although IV-PCA was removed on Day 1, it was associated with continued better pain control compared to PCA absent group. At rest, the proportion of patients expressing pain (mild or more) was significantly lower in the PCA present group from Day 0 to Day 4. In contrast to at rest, a better pain control continued through the entire study period of 7 days. No serious adverse events were observed. A few patients experienced nausea in both groups and the inter-group difference was not found significant. Conclusion: IV-PCA suppresses postoperative pain in S-ICD without major safety concerns.

Induction of Non-Apoptotic Cell Death by Adrenergic Agonists in Human Oral Squamous Cell Carcinoma Cell Lines.

BACKGROUND/AIM: Although adrenergic agonists have been used in dental treatments and oral surgery for general anesthesia, their cytotoxicity against human oral malignant and non-malignant cell has not been well- understood. The present study was undertaken to investigate the cytotoxicity of five adrenergic agonists against human oral squamous cell carcinoma (OSCC), glioblastoma, promyelocytic leukemia, and normal oral mesenchymal cells (gingival fibroblast, pulp cell, periodontal ligament fibroblast) and normal epidermal keratinocytes. MATERIALS AND METHODS: Tumor-specificity (TS) was calculated by the ratio between the mean 50% cytotoxic concentration against normal cells to that of tumor cells. Internucleosomal DNA fragmentation was detected using agarose gel electrophoresis. Caspase-3 activity was measured by substrate cleavage. RESULTS: Both cytotoxicity and tumor-specificity of adrenergic agonists against OSCC cell lines was in the order of isoprenaline>dexmedetomidine> adrenaline>clonidine and phenylephrine. Isoprenaline and dexmedetomidine did not induce apoptosis markers, such as internucleosomal DNA fragmentation and caspase-3 activation, but induced a smear pattern of DNA fragmentation in OSCC cell lines. Their cytotoxicity was not reduced by pretreatment with autophagy inhibitors, or by adrenoceptors antagonists. Addition of superoxide dismutase and catalase significantly reduced the cytotoxicity of isoprenaline, but not that of dexmedetomidine. CONCLUSION: Isoprenaline and dexmedetomidine induce non-apoptotic cell death by different mechanisms.

[General anesthesia for a pregnant patient with PAPA syndrome].

A 31-year-old female, with 22 weeks of pregnancy, presented with sudden onset of severe headache. CT scan showed diffuse subarachnoid hemorrhage. A cerebral angiogram showed dissecting aneurysm of right cerebral artery. To obliterate the aneurysm and prevent rupture, the patient underwent coil embolization via an endovascular approach under general anesthesia because the procedure under sedation with local anesthesia was too risky for re-bleeding. The patient has been diagnosed as PAPA syndrome. Although the arthritis was now stable and she was taking no drug, remarkable osteoarthritis was observed. The cervical spine X ray demonstrated no cervical ankylosis. As patient was sedated with propofol, airway examination could not be done except noticing thyromental distance of seven centimeters. Patient's trachea was intubated using Macintosh size #3 laryngoscope blade and a 7.0 non-styletted tracheal tube at the first attempt without any problems (Cormack grade I). Anesthesia was maintained with sevoflurane, fentanyl and remifentanil. After the end of endovascular surgery, the patient was transferred to the intensive care unit under mechanical ventilation. She was weaned from mechanical ventilation 2 days later but consciousness was unclear. Right incomplete paralysis was also observed. MRI revealed vasospasm on the bilateral internal carotid artery. The patient underwent percutaneous tansluminalangioplasty coil and intraarterial injection of fasudil hydrochloride under local anesthesia. The consciousness recovered fully and the paralysis was improved. The patient delivered the baby by Caesarean sections under combined spinal and epidural anesthesia at 36 weeks without any problems with both the mother and baby.

Cytotoxicity and type of cell death induced by midazolam in human oral normal and tumor cells.

BACKGROUND: Intravenous anesthetics have been used during the treatment of various malignant tumors, however, their effects on oral tissues is not well-understood. In the present study, the cytotoxicity of five intravenous anesthetics towards oral tumor and normal cells was compared. MATERIALS AND METHODS: Tumor specificity index was determined by the ratio of the mean 50% cytotoxic concentration for normal cells to that for tumor cells. Apoptosis induction was monitored by internucleosomal DNA fragmentation and caspase-3, -8, and -9 activation. Fine cell structure was observed under transmission electron microscopy. RESULTS: Benzodiazepines (midazolam and diazepam) exhibited higher cytotoxicity than barbiturates (thiopental and thiamylal), whereas propofol had the intermediate range of cytotoxicity. Midazolam showed the highest cytotoxicity. HL-60 cells were the most sensitive to midazolam, followed by epidermal keratinocytes, oral squamous cell carcinoma (OSCC), glioblastoma and then oral normal cells. Midazolam did not induce the production of apoptosis markers such as internucleosomal DNA fragmentation and activation of caspase-3, -8 and -9, but did induce the appearance of many vacuoles, mitochondrial swelling and cell membrane rupture in OSCC cell lines (HSC-2 and HSC-4) cells. The cytotoxicity of midazolam was not reduced by pre-treatment with autophagy inhibitors (3-methyladenine and bafilomycin A1). CONCLUSION: These results suggest that midazolam may induce necrotic cell death, rather than apoptosis or autophagy, in OSCC cell lines.

Cytotoxicity and type of cell death induced by local anesthetics in human oral normal and tumor cells.

BACKGROUND: Local anesthetics are often administered to tumors and surrounding tissues during the surgery of the head and neck area, however their effects on oral tissues is not well understood. In the present study, the cytotoxicity of a total of seven local anesthetics towards oral tumor and normal cells was compared. MATERIALS AND METHODS: Tumor-specificity index was determined by the ratio of the mean 50% cytotoxic concentration against normal cells to that for tumor cells. Apoptosis induction was monitored by internucleosomal DNA fragmentation and caspase-3, -8, and - 9 activation. Fine cell structure was observed under transmission electron microscopy. RESULTS: All local anesthetics showed slightly higher cytotoxicity towards oral squamous cell carcinoma (OSCC) cell lines than towards normal oral cells. Dibucaine, with a log p-value of approximately 3, was the most cytotoxic, followed by tetracaine, bupivacaine or ethylaminobenzoate, whereas lidocaine, procaine and mepivacain were much less cytotoxic. When the tumor-specificity was evaluated between OSCC and human skin keratinocytes, the index was 6.6. Dibucaine did not induce apoptosis of OSCC cells. On the other hand, dibucaine did induce mitochondrial injury and swelling, formation of secondary lysosomes, and at high concentrations, rupture of the cell membrane. Autophagy inhibitors did not reduce the cytotoxicity of dibucaine. CONCLUSION: Necrosis may be involved in the induction of antitumor activity by dibucaine.

[Effect of anesthetics on malignant tumor cells (A review)].

The influence of surgery and anesthesia on aspects of malignant tumor has received considerable attention in recent years. It is suggested that in vitro studies, clinically available anesthetics, such as intravenous anesthetics, local anesthetics and opioids have, more or less, possible antitumor potential against human malignant tumor cells. Although natural killer (NK) cells play an important role in tumor and metastasis surveillance, the reported effects of the anesthetics on the NK cell activity in human are controversial. Animal studies indicate that the neuroendocrine stress response to the surgery suppresses the immune function, particularly NK cell cytotoxicity, and increases the metastatic burden under inhalational anesthesia alone. Moreover, animal studies indicate that the addition of spinal block and optimum postoperative analgesia independently reduce the metastatic burden by blocking the stress response under inhalational anesthesia alone. Considering inconclusive results, especially in human, about evaluating the influence of anesthetics on malignant tumor, further studies in basic and clinical settings are required to study the effects of anesthetics on malignant tumor.