Postoperative hyperammonemic encephalopathy due to unexpected constipation in a patient with hyperornithinemia-hyperammonemia-homocitrullinuria syndrome: a case report.

BACKGROUND: Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is a rare autosomal recessive urea cycle disorder associated with a high risk of exacerbation of hyperammonemia during the perioperative period. Here, we describe an adult patient with HHH syndrome who developed hyperammonemic encephalopathy secondary to postoperative constipation. CASE PRESENTATION: A 52-year-old patient with HHH syndrome underwent intrathecal baclofen pump insertion for lower limb spasticity under general anesthesia. The surgery was uneventful, without any increase in serum ammonia levels. However, after surgery, he was constipated, and on postoperative day (POD) 3, he fell into a coma with an exacerbation of hyperammonemia (894 µg/dL). After administering a glycerin enema, he defecated, leading to a rapid decrease in serum ammonia levels to 165 µg/dL. He regained consciousness, and serum ammonia levels remained stable as long as he defecated. CONCLUSIONS: We suggest strict management of defecation during the perioperative period to prevent hyperammonemia in patients with HHH syndrome.

A randomized, double-blinded, placebo-controlled, crossover study of the HCN channel blocker ivabradine in a capsaicin-induced pain model in healthy volunteers.

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels have been focused on as a potential therapeutic target for inflammatory and neuropathic pain in rodent models. However, roles of HCN channels in human pain states have been scarcely investigated. We evaluated analgesic effects of 2-day administration of ivabradine, the only clinically available HCN channel blocker, on a capsaicin pain model in a randomized, double-blinded, placebo-controlled, crossover study. Twenty healthy adult subjects (18 males, 2 females) received ivabradine (5-7.5 mg) or a placebo 3 times in 2 days. Then capsaicin (0.5%) was topically applied on the volar forearm for 30 min. The primary outcome was capsaicin-induced spontaneous pain. The secondary outcomes included heat-pain threshold (HPT), flare size, and areas of secondary punctate mechanical hyperalgesia (PMH) and secondary dynamic mechanical allodynia (DMA). There was no significant difference in spontaneous pain (p = 0.7479), HPT (p = 0.7501), area of PMH (p = 0.1052) or flare size (p = 0.5650) at 30 min after capsaicin application between the groups. In contrast, the area of DMA in the ivabradine group was significantly smaller (p < 0.001) than that in the placebo group. HCN channels may be differentially involved in the various pain signal transmission pathways in humans.

An unusual foreign body in the oral cavity: a case report from a patient safety point of view and literature review.

Accidental foreign bodies (FBs) in the oral cavity, airway, esophagus and breathing circuit associated with anesthetic procedures are rare but can cause serious and life-threatening complications. We here present a case in which an unusual FB in the oral cavity was found after emergence from general anesthesia. The FB was later identified as a melted cap of a felt-tip pen. We investigated the cleaning process for reusable materials and concluded that the FB was accidentally placed in the inner lumen of the reusable bite block during the cleaning process. We then performed a review of the literature on FBs other than those of dental origin which were entrapped in the oral cavity, pharynx, larynx, trachea, esophagus, and anesthetic breathing circuit due to anesthetic procedures. From our case and 53 cases found in the search, we concluded that 1) use of disposable medical devices is recommended, 2) FBs can easily migrate into the oral cavity and airway during anesthesia, 3) delayed FB recognition may be associated with difficult intubation situations, and 4) more attention should be paid to the possibility of any medical or non-medical device becoming an FB during anesthesia.

Preoperative and postoperative complications of cerebrospinal fluid drainage in descending thoracic and thoraco-abdominal aortic aneurysm surgery: a single-center retrospective study.

PURPOSE: Cerebrospinal-fluid drainage (CSFD) has been performed to prevent paraplegia in descending thoracic or thoraco-abdominal aortic aneurysm (DTA/TAAA) surgery; however, CSFD itself has a risk of severe complications. We retrospectively investigated the incidence rates of CSFD-related preoperative and postoperative complications. METHODS: Patients who underwent DTA/TAAA surgery with a CSFD catheter that was inserted on the day before surgery were enrolled. The incidence rates of complications from spinal puncture until DTA/TAAA surgery were investigated as preoperative CSFD complications, and the incidence rates from DTA/TAAA surgery to postoperative day 7 were investigated as CSFD-related postoperative complications. RESULTS: Preoperative CSFD complications were analyzed in 123 cases. DTA/TAAA surgery was postponed due to bloody cerebrospinal fluid (2.5%) and due to meningitis (1.7%). The incidence rate of mild preoperative complications was 32.4%. Postoperative CSFD complications were analyzed in 108 cases. Intracranial hemorrhage occurred in 3.9% of cases in open surgery and other postoperative severe CSFD complications did not occur. The incidence rates of moderate/mild complications in open surgery were 2.6%/14.3% and those in TEVAR were 3.2%/19.4%. CONCLUSION: Bloody cerebrospinal fluid and meningitis, which are severe complications associated with spinal puncture, occurred within 1 day after spinal puncture. The incidence rates of moderate/mild complications were high in both the preoperative and postoperative periods. These results showed that CSFD catheter insertion and management should be performed carefully with consideration given to the risks and benefits of CSFD.

Subfascial infiltration of 0.5% ropivacaine, but not 0.25% ropivacaine, exacerbates damage and inflammation in surgically incised abdominal muscles of rats.

Ropivacaine-induced myotoxicity in surgically incised muscles has not been fully investigated. We evaluated the effects of infiltration anesthesia with ropivacaine on damage, inflammation and regeneration in the incised muscles of rats undergoing laparotomy. Ropivacaine or saline was infiltrated below the muscle fascia over the incised muscles. Pain-related behaviors and histological muscle damage were assessed. Macrophage infiltration at days 2 and 5 and proliferation of satellite cells at day 5 were detected by CD68 and MyoD immunostaining, respectively. Pain-related behaviors were inhibited by 0.25% and 0.5% of ropivacaine for 2 h after surgery. Single infiltration of 0.5% ropivacaine did not induce injury in intact muscles without incision, but single and repeated infiltration of 0.5% ropivacaine significantly augmented laparotomy-induced muscle injury and increased the numbers of CD68-positve macrophages and MyoD-positive cells compared to those in rats with infiltration of saline or 0.25% ropivacaine. In contrast, there were no significant differences in them between rats with saline infusion and rats with 0.25% ropivacaine infiltration. In conclusion, single or repeated subfascial infiltration of 0.25% ropivacaine can be used without exacerbating the damage and inflammation in surgically incised muscles, but the use of 0.5% ropivacaine may be a concern because of potentially increased muscle damage.

Calcitonin gene-related peptide is not involved in neuropathic pain induced by partial sciatic nerve ligation in mice.

BACKGROUND: Optimal neuropathic pain (NeP) therapy has still not been established despite great efforts to develop new strategies for NeP analgesia. One possible target might be calcitonin gene-related peptide (CGRP). This is because the expression of CGRP and its receptors in the dorsal horn of the spinal cord might be associated with the persistence of pain symptoms including symptoms of NeP. We previously developed αCGRP knockout mice, and we aimed in this study to clarify the roles of CGRP in NeP by partial sciatic nerve ligation (PSNL) using the knockout mice. METHODS: PSNL was performed in αCGRP knockout mice and wild-type (WT) mice, and spontaneous pain behavior and mechanical and thermal hyperalgesia were evaluated after PSNL. CGRP immunoreactivity (IR) was also observed in the superficial dorsal horn and deep dorsal horn of L4 to L5 segments of the spinal cord in WT mice after PSNL. RESULTS: Spontaneous pain behavior and mechanical and thermal hyperalgesia after PSNL were not different between αCGRP knockout mice and WT mice throughout the observation period. The expression of CGRP-IR was not different between the PSNL model and the sham operation model at 1 day and 7 days after surgery. CONCLUSION: The results suggest that the involvement of αCGRP may differ depending on the type and site of nerve injury, and clinical indications for anti-CGRP treatment of NeP should be carefully based on various pathophysiological conditions of NeP.

Plantar incision with severe muscle injury can be a cause of long-lasting postsurgical pain in the skin.

AIMS: Although chronic local inflammation in deeper tissues after skin wound healing might produce chronification of acute postsurgical pain, its mechanisms have not been fully elucidated. We hypothesized that muscle injury and severe inflammation would prolong acute postsurgical pain by its central nervous system mechanisms. MAIN METHODS: After approval of the Animal Care Committee, experiments were performed in Male Sprague-Dawley rats weighing 250-300 g. Plantar incision and plantar incision combined with cryoinjury of the plantar flexor digitorum brevis muscle were made in the plantar incision group and muscle injury group, respectively. Pain-related behaviors were assessed, and inflammatory cells were isolated from injured muscle and analyzed by flow cytometry. Spinal microglial activation was assessed with Iba-1 staining. KEY FINDINGS: Mechanical hyperalgesia from day 5 to day 8 and spontaneous pain-related behavior from day 3 to day 7 were significantly greater in the muscle injury group than in the plantar incision group (P < 0.05), whereas there was no significant difference between the two groups in thermal hyperalgesia. In the muscle injury group, the number of inflammatory cells on day 4 was significantly larger and spinal Iba-1 expression levels on days 4 and 7 were significantly higher than those in the plantar incision group (P < 0.05). SIGNIFICANCE: Surgical injury in deep tissues accompanying severe muscle inflammation induced prolonged postsurgical pain in the healing wound of the skin not by the persistence of muscle inflammation but by a central mechanism involving microglial activation at the level of the spinal cord.

Phospholipase Cß3 Expressed in Mouse DRGs is Involved in Inflammatory and Postoperative Pain.

BACKGROUND: Previous studies suggested that phospholipase Cß3 (PLCß3), which is a common downstream component in the signaling cascade, plays an important role in peripheral mechanisms of perception including nociception. However, detailed profiles of PLCß3-expressing dorsal root ganglion (DRG) neurons and involvement of PLCß3 in inflammatory and postoperative pain have not been fully investigated. PURPOSE: We evaluated neurochemical char0acteristics of PLCß3-expressing DRG neurons in mice and then we examined the effects of selective knockdown of PLCß3 expression in DRGs on inflammatory and postoperative pain. METHODS: Male C57BL/6-strain mice were used. For the inflammatory model, each mouse received subcutaneous injection of complete Freund's adjuvant (CFA) in the left hindpaw. For the postoperative pain model, a plantar incision was made in the left hindpaw. PLCß3 antisense oligodeoxynucleotide or PLCß3 mismatch oligodeoxynucleotide was intrathecally administered once a day for three consecutive days in each model. The time courses of thermal hyperalgesia and mechanical hyperalgesia were investigated. Changes in PLCß3 protein levels in DRGs were evaluated by Western blotting. RESULTS: Immunohistochemical analysis showed that high proportion of the PLCß3-positive profiles were biotinylated isolectin B4-positive or transient receptor potential vanilloid subfamily 1-positive. PLCß3 protein level in DRGs during CFA-induced inflammation was comparable to that at baseline. Intrathecal administration of PLCß3 antisense oligodeoxynucleotide, which significantly suppressed PLCß3 expression in DRGs, did not affect pain thresholds in normal conditions but inhibited CFA-induced thermal and mechanical hyperalgesia both at the early and late phases compared to that in mismatch oligodeoxynucleotide-treated mice. Intrathecal administration of PLCß3 antisense oligodeoxynucleotide also inhibited surgical incision-induced thermal and mechanical hyperalgesia. CONCLUSION: Our results uncover a unique role of PLCß3 in the development and maintenance of inflammatory pain induced by CFA application and in those of surgical incision-induced pain, although PLCß3 does not play a major role in thermal nociception or mechanical nociception in normal conditions.

Acute postoperative pain is correlated with the early onset of postpartum depression after cesarean section: a retrospective cohort study.

The primary purpose of this study was to evaluate the correlation between the intensity of acute postoperative pain and development of postpartum depression (PPD) after cesarean section (CS). The secondary purpose was to investigate perioperative risk factors for PPD detected in the postoperative period after CS. We retrospectively reviewed 615 women who had undergone CS between January 2017 and October 2019 in our hospital. The incidence of PPD was 22.7% on postoperative day (POD) 5 in the 247 women whose numerical rating scale (NRS) scores on POD3 were available. The severity of acute postoperative pain evaluated by NRS was higher in women with than in those without PPD on POD3 (P < 0.02). The independent risk factors for the onset of PPD on POD5 were being a primipara [adjusted odds ratio (aOR), 2.08; 95% confidence interval (CI), 1.03-4.20, P < 0.05], preoperative presence of chronic pain (OR, 4.44; 95% CI 1.82-10.81, P < 0.001), and NRS ≥ 2 on POD3 (aOR, 4.90; 95% CI 1.06-22.61, P < 0.05). Our findings suggest that assessing both acute postoperative pain and presence of PPD can inform the introduction of interventions in the early phase to prevent development of PPD after CS.

Differential effects of sevoflurane and propofol on an electroretinogram and visual evoked potentials.

The purpose of this study was to simultaneously evaluate the effects of sevoflurane and propofol on an electroretinogram (ERG) and visual evoked potentials (VEPs). Twenty-four patients scheduled for elective surgery under general anesthesia were allocated randomly to receive either sevoflurane (group S) or propofol (group P). An ERG and VEPs were recorded in an awake state and during anesthesia with three different minimum alveolar concentrations (MAC; 0.5, 1.0, and 1.5) of sevoflurane in group S or with three different effect-site concentrations (Ce) of 2, 3, and 4 µg/ml by using a target-controlled infusion technique in group P. Sevoflurane and propofol had little effect on amplitudes of the ERG b-wave. Sevoflurane significantly attenuated the amplitudes of VEP N75-P100 at 0.5, 1.0, and 1.5 MAC. Propofol did not significantly decrease the amplitude of VEPs at Ce of 2 or 3 µg/ml but significantly decreased it at Ce of 4 µg/ml. In summary, propofol and sevoflurane at clinical concentrations had little effect on the amplitude of an ERG. Sevoflurane attenuated the amplitudes of VEPs even at low concentrations. Propofol also attenuated the amplitudes of VEPs to a lesser extent compared to sevoflurane.

Prostanoid EP4 Receptor-Mediated Augmentation of I h Currents in Aß Dorsal Root Ganglion Neurons Underlies Neuropathic Pain.

An injury of the somatosensory system causes neuropathic pain, which is usually refractory to conventional analgesics, thus warranting the development of novel drugs against this kind of pain. The mechanism of neuropathic pain in rats that had undergone left L5 spinal nerve transection was analyzed. Ten days after surgery, these rats acquired neuropathic pain. The patch-clamp technique was used on the isolated bilateral L5 dorsal root ganglion neurons. The current-clamped neurons on the ipsilateral side exhibited significantly higher excitability than those on the contralateral side. However, only neurons with diameters of 40-50 µm on the ipsilateral side exhibited significantly larger voltage sags in response to hyperpolarizing current pulses than those on the contralateral side. Under the voltage clamp, only these neurons on the ipsilateral side showed a significantly larger density of an inward current at < -80 mV [hyperpolarization-activated nonselective cation (I h) current] with a rightward-shifted activation curve than that on the contralateral side. Ivabradine-an I h current inhibitor-inhibited I h currents in these neurons on both sides in a similar concentration-dependent manner, with an IC50 value of ∼3 µM. Moreover, the oral administration of ivabradine significantly alleviated the neuropathic pain on the ipsilateral side. An inhibitor of adenylyl cyclase or an antagonist of prostanoid EP4 receptors (CJ-023423) inhibited ipsilateral, but not contralateral I h, currents in these neurons. Furthermore, the intrathecal administration of CJ-023423 significantly attenuated neuropathic pain on the ipsilateral side. Thus, ivabradine and/or CJ-023423 may be a lead compound for the development of novel therapeutics against neuropathic pain.

Airway obstruction due to a laryngeal polyp following insertion of a laryngeal mask airway.

BACKGROUND: Laryngeal mask airway (LMA) insertion contributes to airway protection in patients with a laryngeal tumor around the glottis. There has been no report of LMA insertion itself exacerbating airway obstruction in such patients. CASE PRESENTATION: A 62-year-old male underwent elective surgical resection of a large laryngeal polyp. The polyp was attached to the right vocal fold and synchronously swung inward into the trachea and outward to the larynx with inspiration and expiration, respectively. Although manual positive pressure ventilation was easily achieved without any airway obstruction after anesthetic induction, the airway was completely obstructed by the polyp lodged between the vocal cords immediately after LMA insertion. Soon after removal of the LMA, patency of the airway was dramatically improved. CONCLUSION: Our experience indicates that we should pay attention to airway obstruction due to lodging of the polyp between the vocal cords after LMA insertion in patients with a laryngeal polyp.

Difficult Management of a Double-Lumen Endotracheal Tube and Difficult Ventilation during Robotic Thymectomy with Carbon Dioxide Insufflation.

Robotic surgery with carbon dioxide (CO2) insufflation to the thorax is frequently performed to gain a better operative field of view, although its intraoperative complications have not yet been discussed in detail. We treated two patients with difficult ventilation caused by distal migration of a double-lumen endotracheal tube (DLT) during robotic thymectomy. In the first case, migration of the DLT during one-lung ventilation (OLV) occurred after CO2 insufflation to the bilateral thoraxes was started. Oxygenation rapidly deteriorated because dependent lung expansion was restricted by CO2 insufflation. In the second case, migration of the DLT during OLV occurred while CO2 insufflation to a unilateral thorax and mediastinum was performed. In both cases, once migration of the DLT during OLV occurred with CO2 insufflation, readjusting the DLT became very difficult because our manipulation of bronchofiberscopy was prevented by the robot arms located above the patient's head and because deformation of the trachea/bronchus induced by CO2 insufflation caused a poor image of the bronchofiberscopic view. Thus, during robotic-assisted thoracoscopic surgery with CO2 insufflation, since there is a potential risk of difficult ventilation with a DLT and since readjustment of the DLT is very difficult, discontinuing CO2 insufflation and switching to double-lung ventilation are needed in such a situation.

Systemic QX-314 Reduces Bone Cancer Pain through Selective Inhibition of Transient Receptor Potential Vanilloid Subfamily 1-expressing Primary Afferents in Mice.

BACKGROUND: The aim of this study was to determine whether systemic administration of QX-314 reduces bone cancer pain through selective inhibition of transient receptor potential vanilloid subfamily 1 (TRPV1)-expressing afferents. METHODS: A mouse model of bone cancer pain was used. The authors examined the effects of bolus (0.01 to 3 mg/kg, n = 6 to 10) and continuous (5 mg kg h, n = 5) administration of QX-314 on both bone cancer pain-related behaviors and phosphorylated cyclic adenosine monophosphate response element-binding protein expression in dorsal root ganglion neurons (n = 3 or 6) and the effects of ablation of TRPV1-expressing afferents on bone cancer pain-related behaviors (n = 10). RESULTS: The numbers of flinches indicative of ongoing pain in QX-314-treated mice were smaller than those in vehicle-treated mice at 10 min (3 mg/kg, 4 ± 3; 1 mg/kg, 5 ± 3 vs. 12 ± 3; P < 0.001; n = 8 to 9), 24 h (3 ± 2 vs. 13 ± 3, P < 0.001), and 48 h (4 ± 1 vs. 12 ± 2, P < 0.001; n = 5 in each group) after QX-314 administration, but impaired limb use, weight-bearing including that examined by the CatWalk system, and rotarod performance indicative of movement-evoked pain were comparable. QX-314 selectively inhibited the increase in phosphorylated cyclic adenosine monophosphate response element-binding protein expression in TRPV1-positive, but not in TRPV1-negative, dorsal root ganglion neurons compared to that in the case of vehicle administration (32.2 ± 3.0% vs. 52.6 ± 5.9%, P < 0.001; n = 6 in each group). Ablation of TRPV1-expressing afferents mimicked the effects of QX-314. CONCLUSION: This study showed that systemic administration of QX-314 in mice inhibits some behavioral aspects of bone cancer pain through selective inhibition of TRPV1-expressing afferents without coadministration of TRPV1 agonists.

Implantable cardioverter defibrillator for progressive hypertrophic cardiomyopathy in a patient with LEOPARD syndrome and a novel PTPN11 mutation Gln510His.

LEOPARD syndrome (LS), generally caused by heterozygous mutations in the PTPN11 gene, is a rare autosomal-dominant multiple congenital anomaly condition, characterized by skin, facial, and cardiac abnormalities. Prognosis appears to be related to the type of structural, myocardial, and arrhythmogenic cardiac disease, especially hypertrophic cardiomyopathy (HCM). We report on a woman with LS and a novel Gln510His mutation in PTPN11, who had progressive HCM with congestive heart failure and nonsustained ventricular tachycardia, successfully treated with implantable cardioverter defibrillator (ICD). Comparing our patient to the literature suggests that specific mutations at codon 510 in PTPN11 (Gln510Glu, Gln510His, but not Gln510Pro) might be a predictor of fatal cardiac events in LS. Molecular risk stratification and careful evaluations for an indication of ICD implantation are likely to be beneficial in managing patients with LS and HCM.

[Mechanisms underlying generation of cancer pain].

As advances in cancer detection and treatment have increased the life expectancy of cancer patients, more attention to improving patient's quality of life (QOL) is needed. Among symptoms accompanying cancer, pain has strong impact on QOL. Most of cancer patients will experience moderate to severe pain and/or neuropathy during the course of their disease. Cancer pain can arise from different processes, either by direct tumor infiltration/involvement, or toxicity relating to chemotherapy used to treat cancer. The World Health Organization (WHO) has proposed a structured approach to drug selection for cancer pain, known as the "WHO analgesic ladder". However, several types of pain including bone cancer pain and chemotherapy-induced painful peripheral neuropathy are difficult to treat. The development of optimal analgesics for cancer pain has been hampered by the lack of understanding basic mechanisms that contribute to cancer pain. Recently, preclinical models of bone cancer pain and paclitaxel-induced painful peripheral neuropathy have been developed. These models have begun to provide insight into the mechanisms by which cancer pain is induced and how cancer pain-related sensory information is processed. In this paper, we review mechanism of cancer pain.