Effect of tranexamic acid on blood loss reduction in patients undergoing orthognathic surgery under hypotensive anesthesia: a single-center, retrospective, observational study.

Objectives: Orthognathic surgery is a surgical procedure performed by intraoral approach with established and safe techniques; however, excessive blood loss has been reported in rare cases. In response, investigative efforts to identify methods to reduce the amount of blood loss have been made. Among such methods, the administration of tranexamic acid was reported to reduce the amount of intraoperative blood loss. However, few studies to date have reported the effect of tranexamic acid in orthognathic surgery under hypotensive anesthesia. The present study aimed to investigate the effect of the administration of tranexamic acid on intraoperative blood loss in patients undergoing bimaxillary (maxillary and mandibular) orthognathic surgery under hypotensive anesthesia. Patients andMethods: A total of 156 patients (mean age, 27.0±10.8 years) who underwent bimaxillary orthognathic surgery under hypotensive anesthesia performed by the same surgeon between June 2013 and February 2022 were included in this study. The following data were collected from the medical records of each patient: background factors (age, sex, and body mass index), use of tranexamic acid, surgical procedures, previous medical history, duration of surgery, American Society of Anesthesiology physical status findings before surgery, intraoperative blood loss as a primary outcome, in-out balance, and blood test results. Descriptive statistics were calculated for statistical analysis, and a t -test and the chi-squared test were used for between-group comparisons. Group comparisons were performed after 1:1 propensity score matching to adjust for confounding factors. Statistical significance was set at P<0.05. Results: Comparison between the groups based on the use of tranexamic acid revealed a significant difference in operation time. Propensity score matching analysis revealed that intraoperative blood loss was significantly lower in the tranexamic acid group. Conclusion: The administration of tranexamic acid was effective in reducing intraoperative blood loss in patients undergoing bimaxillary orthognathic surgery under hypotensive anesthesia.

Use of EMLA cream for skin anesthesia and epidural insertion in the patients with cesarean delivery: A prospective double-blind randomized clinical trial.

Background: Pain relief of epidural anesthesia in cesarean delivery is difficult. EMLA, a eutectic mixture of lidocaine and prilocaine, is effective for pain reduction during venipuncture and superficial surgery. However, its effectiveness during epidural insertion is not well elucidated. The aim of this randomized, double-blind study was to evaluate the efficacy of EMLA for epidural insertion in elective cesarean delivery. Methods: With Institutional Review Board approval and written patients' informed consent, forty-two ASA physical status 2 patients (aged 23-45) scheduled for elective cesarean section were included in this study. The patients were randomized to applied ELMA (EMLA group) or placebo cream (Placebo group) about one hour prior to anesthesia. Pain during skin infiltration with 1% mepivacaine and subsequent insertion of Tuohy needle was assessed immediately after each procedure. The presence of patient's response with physical withdrawal on both procedures was recorded. Statistical analysis was performed using Mann-Whitney U test and Fisher's exact test. A value of P < 0.05 was considered significant. Results: Median VAS values on skin infiltration and on insertion of Tuohy needle did not differ between groups. The incidence of patient's response with physical withdrawal on skin infiltration was not different between groups. However, that on insertion of Tuohy needle was significantly lower in EMLA group than in Placebo group (0%, 21%). Conclusions: EMLA cream could not reduce the pain during epidural insertion.

Ultrasound-assisted intrathecal injection of nusinersen in a patient with severe vertebral deformity: a case report.

BACKGROUND: Spinal muscular atrophy (SMA) is a mostly autosomal recessive genetic disease characterized by progressive muscle weakness from anterior horn degeneration. Nusinersen has recently been approved as a disease-modifying drug for SMA that needs to be administered intrathecally. Its injection is often associated with extreme difficulty since patients with SMA have severe vertebral deformity and may be with vertebral instrumentation. CASE DESCRIPTION: A 21-year-old female with type 2 SMA and spinal deformity underwent a series of intrathecal injections of nusinersen. The intrathecal injections have been safely and successfully done by using computed tomography imaging and ultrasonography-assisted technique. CONCLUSION: This the first report in which ultrasound-assisted technique has been used for the injection of nusinersen through a lumbar puncture in patients with severe spinal deformity. Use of preprocedural ultrasound imaging is highly recommended for treatments that repeatedly require intrathecal access.

Effects of an intrathecal TRPV1 antagonist, SB366791, on morphine-induced itch, body temperature, and antinociception in mice.

PURPOSE: Transient receptor potential vanilloid 1 (TRPV1) not only is activated by multiple stimuli but also is involved with histamine-induced itch. The effects of TRPV1 on morphine-induced itch are unknown. We examined the effects of intrathecal administration of TRPV1 antagonist on morphine-induced itch, body temperature, and antinociception for mice. METHODS: Each C57/BL6j mouse was intrathecally administered with one of the following solutions: morphine, SB366791 (as the TRPV1 antagonist), morphine + SB366791, saline, or vehicle. For each mouse, each instance of observed scratching behavior was counted, the body temperature was measured, and the nociceptive threshold was determined using the tail-immersion test. RESULTS: SB366791 dose-dependently reduced the scratching behavior induced by the administration of morphine. SB366791 and the morphine + SB366791 groups did not manifest an increase in body temperature. Antinociceptive effects were observed to occur dose-dependently for morphine but not for SB366791. Compared with morphine alone, the administration of morphine + SB366791 did not reduce significant antinociceptive effects. CONCLUSION: We propose that an intrathecal TRPV1 antagonist, SB366791, reduced morphine-induced itch without causing hyperthermia and did not suppress morphine-induced antinociception for mice.

Anesthetic Management in an Adult Patient With Costello Syndrome: A Case Report.

Costello syndrome is a rare genetic disorder characterized by mental and growth retardation and distinctive coarse facies. A significant proportion of patients with Costello syndrome have hypertrophic cardiomyopathy, papillomata, and malignant tumors. General anesthesia practice, especially airway and cardiac management, in patients with Costello syndrome may be complicated by anatomical features and cardiac abnormalities. There have been several reports on the anesthetic management of children with Costello syndrome, but few have reported on the anesthetic management of adults with Costello syndrome. In adults, careful preoperative evaluation as well as preparation for adult-onset and previously unrecognized medical conditions are key for safe anesthetic management.

Prophylactic Pentazocine Reduces the Incidence of Pruritus After Cesarean Delivery Under Spinal Anesthesia With Opioids: A Prospective Randomized Clinical Trial.

BACKGROUND: The incidence of pruritus after cesarean delivery under spinal anesthesia with opioids is high, ranging from 50% to 100%. Pruritus is difficult to prevent; however, pentazocine has been shown to be an effective treatment. Despite this, the prophylactic effect of pentazocine on pruritus has not been defined. This randomized double-blind trial aimed to evaluate the effect of intraoperative IV pentazocine on the incidence of opioid-induced pruritus within the first 24 hours after administration of neuraxial opioids. METHODS: We obtained institutional review board approval and written informed consent from the 122 patients (American Society of Anesthesiologists [ASA] physical status II; aged 20-40 years) scheduled for elective cesarean delivery who were included in this study. Spinal anesthesia was performed with 10 mg of 0.5% hyperbaric bupivacaine, 10 µg of fentanyl, and 100 µg of morphine. After delivery of the baby and placenta, the parturient women were randomized to intravenously receive 15 mg (1 mL) of pentazocine or 1 mL of saline. All women received postoperative analgesia with the epidural infusion of 0.15% levobupivacaine. The presence of pruritus within the first 24 hours after intrathecal administration of opioids was recorded, and severity of itch, numerical rating scale (NRS) for pain, and adverse effects were also recorded at the time of the arrival on the ward, as well as 3, 6, 12, and 24 hours after the intrathecal administration of opioids. RESULTS: A total of 119 women completed the study. IV pentazocine reduced the overall incidence of pruritus within the first 24 hours compared to IV saline, with an estimated relative risk of 69% (95% confidence interval [CI], 52%, 90%; P = .007). IV pentazocine also reduced the severity of pruritus. The incidence of nausea and vomiting was not significantly different. There were no significant differences in postoperative NRS scores. CONCLUSIONS: A single 15-mg dose of IV pentazocine after delivery can reduce both the incidence and severity of pruritus in women who have received subarachnoid opioids during cesarean delivery.

Effects of Intrathecal κ-Opioid Receptor Agonist on Morphine-Induced Itch and Antinociception in Mice.

The µ-opioid receptor (MOR) agonist-induced itch is a significant issue associated with analgesic therapies. Research suggested that systemically administered κ-opioid receptor (KOR) agonists inhibit intrathecal morphine-induced itch in primates. However, serious adverse effects induced by systemically administered KOR agonists may restrict their usefulness in humans. We investigated the effects of intrathecal KOR agonists on intrathecal morphine-mediated itch and antinociception in mice.Mice received intrathecal injections of one of the following drugs: morphine (0.1-1.0 nmol), the selective KOR agonist TRK-820 100 pmol, the combination of morphine 0.3 nmol + TRK-820 (10-100 pmol), and 5 µL of saline. One hour after intraperitoneal administration of the selective KOR antagonist nor-binaltorphimine 1.0 µmol, the effect of TRK-820 100 pmol on intrathecal morphine 0.3 nmol-induced scratching was tested. Total numbers of scratches after intrathecal injection were analyzed. After observing scratching behavior, sedation level was evaluated subjectively. Nociceptive threshold was determined by tail immersion test with intrathecal injections of the following agents: morphine (0.1-1.0 nmol), TRK-820 (10-100 pmol), morphine 0.1 nmol + TRK-820 10 pmol, and 5 µL of saline.Intrathecal TRK-820 dose-dependently inhibited intrathecal morphine-induced scratching compared with that in the saline group. Intraperitoneal nor-binaltorphimine completely inhibited the antiscratching effect of intrathecal TRK-820 100 pmol. The combination of morphine 0.3 nmol and TRK-820 did not alter the sedation score compared with that in the morphine 0.3 nmol group. Morphine 0.1 nmol + TRK-820 10 pmol significantly produced greater thermal antinociceptive effects than morphine 0.1 nmol.We demonstrated that intrathecal KOR agonists exert antipruritic effects on intrathecal morphine-induced itch without affecting sedation. The combination of intrathecal morphine and intrathecal KOR agonists produces more potent antinociceptive effects against a thermal stimulus compared with morphine alone.

[Treatment of intrathecal fentanyl-induced itch with pentazocine: a case report].

Pentazocine has activities both of kappa-opioid receptor agonist and weak micro-opioid receptor antagonist. Recent study has suggested that kappa-opioid receptor agonists have antipruritic effects. We experienced a case of pentazocine inhibiting itch evoked by intrathecal fentanyl in a patient with idiopathic pulmonary fibrosis (IPF). A 50-year-old woman with IPF was diagnosed with fallopian tube abscess and which necessitated emergency surgery. We mainly performed regional anesthetic management to prevent acute exacerbation of IPF by tracheal intubation under general anesthesia. About 30 minutes after intrathecal administration of a combination of bupivacaine and fentanyl, she began to complain of itch. Although propofol was given intravenously, pruritus still recurred. Following that, when pentazocine was administered intravenously, pruritus disappeared immediately and then never recurred. Therefore, it is suggested that pentazocine can be useful in reducing pruritus on intrathecal opioid-induced itch. Future studies are necessary to evaluate the efficacy of pentazocine for the treatment and prevention of opioid-induced itch.

[A case report: perioperative management of adenotonsillectomy in a morbidly obese patient with severe obstructive sleep apnea syndrome].

A male patient in his thirties was scheduled to undergo adenotonsillectomy due to dyspnea from bilateral tonsillar hypertrophy. He was morbidly obese (body mass index 56 kg x m(-2)) with severe obstructive sleep apnea syndrome (OSAS), and thus was evaluated with extreme risk for difficult ventilation and intubation. We planned awake intubation via video-assisted laryngoscopy and fiberoptic bronchoscopy under dexmedetomidine sedation, and the intubation was successfully performed. After adenotonsillectomy, upper airway obstruction due to hemorrhage and oropharyngeal swelling can be life-threatening requiring emergent airway management. Thus for postoperative airway management, due to the possibility of "cannot intubate, cannot ventilate" (CICV) and presumed difficult tracheotomy, we scheduled to perform tracheotomy during adenotonsillectomy, right after anesthetic induction and awake intubation. On postoperative day 1, he started walking with no need of sedative drugs. On day 4, after confirmation of minimal oropharyngeal swelling, tracheal cannulae was removed, and no further complications were observed in his postoperative course. We conclude that careful preoperative evaluation of the airway, retention of spontaneous breathing via awake intubation, and preventive tracheotomy for postoperative airway management are important points in perioperative management of a morbidly obese patient with severe obstructive sleep apnea syndrome.

[The importance of preanesthetic evaluation: malignant tumors discovered on preoperative chest radiography, in patients scheduled for operation of benign tumors].

Preanesthetic evaluation is essential for the perioperative period. We report 2 preoperative patients with benign disease, whose preoperative chest radiography revealed intrathoracic malignant tumors. Case 1: A woman in her eighties with vascular necrosis of the femoral head was scheduled for bipolar hip arthroplasty under general anesthesia. On preanesthetic evaluation, widened mediastinum was detected on preoperative chest radiography. Instead of the scheduled operation, she underwent thoracoscopic surgery under general and epidural anesthesia. She was diagnosed with malignant thymoma. Case 2: A woman in her thirties with bilateral oviduct obstruction was scheduled for laparoscopic surgery. On preanesthetic evaluation, right middle lung lesion was detected. She underwent thoracoscopic biopsy under general and epidural anesthesia, and was diagnosed with malignant lymphoma. The result of preanesthetic chest radiography is reported to change the perioperative treatment only in 0.1%; our cases indicate the importance of preanesthetic evaluation of chest radiography in detecting possible underlying disease in the preoperative patient.

Gabapentin augments the antihyperalgesic effects of diclofenac sodium through spinal action in a rat postoperative pain model.

BACKGROUND: Gabapentin and nonsteroidal antiinflammatory drugs (NSAIDs) attenuate postoperative pain and neuropathic pain in humans. The combination of gabapentin and NSAIDs is effective for postoperative pain and enhances functional recovery after surgery. Intrathecal administration of gabapentin or NSAIDs inhibits hyperalgesia in a rat postoperative pain model. However, there is no information on the effects of intrathecal administration of a combination of gabapentin and NSAIDs. We therefore investigated the effects of intrathecal administration of gabapentin and NSAIDs in a rat model of postoperative pain. METHODS: Rats were prepared for intrathecal catheters under halothane anesthesia. Two days after catheterization, gabapentin (4, 40, or 400 µg per 20 µL of saline), diclofenac sodium, a nonselective cyclooxygenase inhibitor (2, 20, or 200 µg per 20 µL of 6% glucose), 20 µL saline, 20 µL 6% glucose, and a combination of gabapentin and diclofenac (40 µg gabapentin + 20 µg diclofenac and 4 µg gabapentin + 2 µg diclofenac per 20 µL 6% glucose) were injected intrathecally. We performed a hindpaw incision 30 minutes after injection. Each group consisted of 6 rats. The mechanical threshold was measured to evaluate secondary hyperalgesia using von Frey filaments before intrathecal catheterization and at 2 hours, and 1, 3, 5, and 7 days after paw incision. RESULTS: Gabapentin 400 µg attenuated mechanical hyperalgesia for 7 days compared with the control group. Diclofenac 200 µg inhibited hyperalgesia for 5 days compared with the control group. The 40 µg gabapentin + 20 µg diclofenac group had a significantly reduced secondary hyperalgesic response in 2 hours and 1 day compared with 40 µg gabapentin and 20 µg diclofenac, respectively. The 4 µg gabapentin + 2 µg diclofenac group had a significantly reduced secondary hyperalgesic response in 2 hours and 1 day compared with 2 µg diclofenac. The withdrawal threshold on the contralateral paw did not change compared with the preincision threshold. CONCLUSION: Intrathecal administration of gabapentin and diclofenac in combination reduced secondary hyperalgesia at doses having no antihyperalgesic effects when given individually. Our results suggest that gabapentin and diclofenac have an important role in postoperative pain reduction at the spinal level, and that gabapentin augments the antihyperalgesic effects of diclofenac through action in the spinal cord.

[Risk management in epidural anesthesia].

Epidural anesthesia has many advantages, including block of surgical stress, postoperative pain management and prevention of postoperative complications. Therefore, we should use epidural anesthesia when indicated. However, patients with preexisting spinal stenosis or lumbar radiculopathy have higher incidence of neurologic complications after epidural anesthesia. Epidural abscesses caused by epidural anesthesia are rare. However, epidural abscesses are serious complications in patients. Knowing the risk factor of epidural abscesses is important to prevent epidural abscesses, and early diagnosis and early treatment are needed when suspected. It is important to have measures for safety in performing epidural anesthesia at every hospital. Recently, we have many anesthetic techniques, including epidural anesthesia, remifentanil infusion, ultrasound-guided peripheral nerve blocks and intravenous PCA. Therefore, we should choose an anesthesia method based on the careful evaluation of the benefit and risk balance for the patient's safety to reduce the incidence of complications.

TRPV1-expressing primary afferents generate behavioral responses to pruritogens via multiple mechanisms.

The mechanisms that generate itch are poorly understood at both the molecular and cellular levels despite its clinical importance. To explore the peripheral neuronal mechanisms underlying itch, we assessed the behavioral responses (scratching) produced by s.c. injection of various pruritogens in PLCbeta3- or TRPV1-deficient mice. We provide evidence that at least 3 different molecular pathways contribute to the transduction of itch responses to different pruritogens: 1) histamine requires the function of both PLCbeta3 and the TRPV1 channel; 2) serotonin, or a selective agonist, alpha-methyl-serotonin (alpha-Me-5-HT), requires the presence of PLCbeta3 but not TRPV1, and 3) endothelin-1 (ET-1) does not require either PLCbeta3 or TRPV1. To determine whether the activity of these molecules is represented in a particular subpopulation of sensory neurons, we examined the behavioral consequences of selectively eliminating 2 nonoverlapping subsets of nociceptors. The genetic ablation of MrgprD(+) neurons that represent approximately 90% of cutaneous nonpeptidergic neurons did not affect the scratching responses to a number of pruritogens. In contrast, chemical ablation of the central branch of TRPV1(+) nociceptors led to a significant behavioral deficit for pruritogens, including alpha-Me-5-HT and ET-1, that is, the TRPV1-expressing nociceptor was required, whether or not TRPV1 itself was essential. Thus, TRPV1 neurons are equipped with multiple signaling mechanisms that respond to different pruritogens. Some of these require TRPV1 function; others use alternate signal transduction pathways.

Dissociation of the opioid receptor mechanisms that control mechanical and heat pain.

Delta and mu opioid receptors (DORs and MORs) are inhibitory G protein-coupled receptors that reportedly cooperatively regulate the transmission of pain messages by substance P and TRPV1-expressing pain fibers. Using a DOReGFP reporter mouse we now show that the DOR and MOR are, in fact, expressed by different subsets of primary afferents. The MOR is expressed in peptidergic pain fibers, the DOR in myelinated and nonpeptidergic afferents. Contrary to the prevailing view, we demonstrate that the DOR is trafficked to the cell surface under resting conditions, independently of substance P, and internalized following activation by DOR agonists. Finally, we show that the segregated DOR and MOR distribution is paralleled by a remarkably selective functional contribution of the two receptors to the control of mechanical and heat pain, respectively. These results demonstrate that behaviorally relevant pain modalities can be selectively regulated through the targeting of distinct subsets of primary afferent pain fibers.

4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1.

TRPA1 is an excitatory ion channel expressed by a subpopulation of primary afferent somatosensory neurons that contain substance P and calcitonin gene-related peptide. Environmental irritants such as mustard oil, allicin, and acrolein activate TRPA1, causing acute pain, neuropeptide release, and neurogenic inflammation. Genetic studies indicate that TRPA1 is also activated downstream of one or more proalgesic agents that stimulate phospholipase C signaling pathways, thereby implicating this channel in peripheral mechanisms controlling pain hypersensitivity. However, it is not known whether tissue injury also produces endogenous proalgesic factors that activate TRPA1 directly to augment inflammatory pain. Here, we report that recombinant or native TRPA1 channels are activated by 4-hydroxy-2-nonenal (HNE), an endogenous alpha,beta-unsaturated aldehyde that is produced when reactive oxygen species peroxidate membrane phospholipids in response to tissue injury, inflammation, and oxidative stress. HNE provokes release of substance P and calcitonin gene-related peptide from central (spinal cord) and peripheral (esophagus) nerve endings, resulting in neurogenic plasma protein extravasation in peripheral tissues. Moreover, injection of HNE into the rodent hind paw elicits pain-related behaviors that are inhibited by TRPA1 antagonists and absent in animals lacking functional TRPA1 channels. These findings demonstrate that HNE activates TRPA1 on nociceptive neurons to promote acute pain, neuropeptide release, and neurogenic inflammation. Our results also provide a mechanism-based rationale for developing novel analgesic or anti-inflammatory agents that target HNE production or TRPA1 activation.