Updated guidelines for prescribing opioids to treat patients with chronic non-cancer pain in Korea: developed by committee on hospice and palliative care of the Korean Pain Society.

There are growing concerns regarding the safety of long-term treatment with opioids of patients with chronic non-cancer pain. In 2017, the Korean Pain Society (KPS) developed guidelines for opioid prescriptions for chronic non-cancer pain to guide physicians to prescribe opioids effectively and safely. Since then, investigations have provided updated data regarding opioid therapy for chronic non-cancer pain and have focused on initial dosing schedules, reassessment follow-ups, recommended dosage thresholds considering the risk-benefit ratio, dose-reducing schedules for tapering and discontinuation, adverse effects, and inadvertent problems resulting from inappropriate application of the previous guidelines. Herein, we have updated the previous KPS guidelines based on a comprehensive literature review and consensus development following discussions among experts affiliated with the Committee on Hospice and Palliative Care in the KPS. These guidelines may assist physicians in prescribing opioids for chronic non-cancer pain in adult outpatient settings, but should not to be regarded as an inflexible standard. Clinical judgements by the attending physician and patient-centered decisions should always be prioritized.

Analgesic Efficacy of Epidural Patient-Controlled Analgesia on Cancer Pain: A Retrospective Observational Study.

BACKGROUND: In patients with severe cancer pain, systemic analgesics are often refractory or have limited application due to the side effects of opioids. In these cases, epidural analgesia may be effective. However, data on the effects of epidural patient-controlled analgesia (PCA) on cancer pain are limited. OBJECTIVES: To evaluate the analgesic efficacy of epidural PCA in patients with cancer pain through a retrospective chart review. STUDY DESIGN: Retrospective analysis. SETTING: A single academic center in Daegu, South Korea. METHODS: The analgesic efficacy of epidural PCA on cancer pain was analyzed in patients who underwent epidural PCA using a disposable balloon pump with a flow regulator between 2012 and 2021. The pump was filled with a 600-mL mixture of 6 ampoules of 0.2% ropivacaine, 1 mg fentanyl, and normal saline. For the first use of epidural PCA, the basal rate, bolus dose, and lockout time were set as 4 mL/h, 2 mL, and 15 min, respectively. The basal rate was increased and decreased depending on the degree of pain relief effect and occurrence of side effects, respectively. To increase the usage time of epidural PCA and reduce the patient's cost burden, the fentanyl dose was increased by 1 mg when the disposable balloon pump was replaced with a new one after exhaustion of the drug if no side effects from the previous dose were observed. Analgesic efficacy was confirmed by comparing the number of types and the total amount of opioids used in patients before and after epidural PCA application in terms of the equivalent dose of oral morphine. RESULTS: Epidural catheterization was performed 105 times, and PCA was refilled 257 times in 88 patients. On average, epidural catheterization was performed 1.2 ± 0.4 (1-3) times, and epidural PCA was refilled 3.2 ± 2.3 (1-11) times per patient. The mean duration of PCA use was 15.6 ± 13.4 (1-82) days. The mean number of opioid types used the day before the procedure and the mean smallest number of opioids used per day up to 5 days after the procedure were 3.4 ± 1.2 and 2.4 ± 1.4, respectively (P < 0.05). The total amount of opioids used the day before the procedure and the smallest total amount of opioids used per day up to 5 days after the procedure were converted into oral morphine equivalent doses, respectively, and the mean doses were 449.5 ± 555.9 and 331.9 ± 462.8 mg, respectively (P < 0.05). LIMITATIONS: The study results are the author's observations from a single center. Epidural PCA was performed only on hospitalized patients. Individual differences were not considered in the composition of drugs for PCA. Transmucosal immediate-release fentanyl was not accurately converted to oral morphine; thus, it was excluded from the analysis of the total amount used, and the effect of adjuvant analgesics could not be considered. CONCLUSION: Epidural PCA using subcutaneous tunneling is a useful cancer pain control method. Furthermore, it can be safely used for a longer duration owing to its low infection risk.

Effect of Dexmedetomidine Preconditioning on Hepatic Ischemia-Reperfusion Injury in Acute Hyperglycemic Rats.

BACKGROUND: Acute hyperglycemia frequently occurs in stressful situations, including liver transplantation or hepatic surgery, which may affect the protective effects of dexmedetomidine preconditioning and increase postoperative mortality. Therefore, this study aimed to investigate the effects of dexmedetomidine on hepatic ischemia-reperfusion injury in acute hyperglycemia. METHODS: Thirty-six Sprague-Dawley rats were randomly assigned to 6 groups, including a combination between 2 glycemic (normo- and hyperglycemia) and 3 ischemia-reperfusion conditions (sham, ischemia-reperfusion only, and dexmedetomidine plus ischemia-reperfusion). Dexmedetomidine 70 µg/kg was preconditioned 30 minutes before ischemic injury. After 6 hours of reperfusion, serum aminotransferase levels were measured to confirm the hepatic tissue injury. Furthermore, inflammatory (nuclear factor-κb, tumor necrosis factor-α, and interleukin-6) and oxidative stress markers (malondialdehyde and superoxide dismutase) were detected. RESULTS: Ischemia-reperfusion injury significantly increased the serum levels of aminotransferase and inflammatory and oxidative stress markers. These ischemia-reperfusion-induced changes were further exacerbated in hyperglycemia and were significantly attenuated by dexmedetomidine preconditioning. However, the effects of dexmedetomidine in hyperglycemia were lesser than those in normoglycemia (P < .05 for aminotransferases, inflammatory markers, malondialdehyde, and superoxide dismutase). CONCLUSIONS: These findings suggest that the protective effects of dexmedetomidine preconditioning may be intact against hepatic ischemia-reperfusion injury in acute hyperglycemia. Although its effects appeared to be relatively reduced, this may be because of the increase in oxidative stress and inflammatory response caused by acute hyperglycemia. To determine whether the effects of dexmedetomidine itself would be impaired in hyperglycemia, further study is needed.

Comparison of the effects of sevoflurane and desflurane on the severity score of postoperative pain and discomfort after thyroidectomy: A prospective, double-blinded, randomized controlled study.

BACKGROUND: Thyroidectomy is performed under general anesthesia using inhaled anesthetics such as sevoflurane or desflurane in many cases. The objective of this study was to investigate whether the incidence of postoperative pain and discomfort after thyroidectomy differed with the type of inhaled anesthetic. METHODS: Eighty-one female patients who underwent thyroidectomy were randomly assigned to the Sevo group (n = 42) or the Des group (n = 39). On the day of surgery and on the first, third, and seventh days after surgery, one registered nurse in charge of the entire questionnaire survey conducted the questionnaire assessment through face-to-face interviews or phone calls with the patients. The questionnaire evaluated the severity scores for seven items (sore throat, wound pain, nausea and vomiting, dizziness, occipital headache, posterior neck pain, and shoulder pain) regarding postoperative pain and discomfort experienced by patients and assessed which of these seven items caused the greatest discomfort to the patient on each day. RESULTS: Except for the severity score for dizziness on the day of surgery, the severity scores of postoperative pain and discomfort experienced by patients on the day of surgery and on the first, third, and seventh days after surgery showed no statistically significant differences between the two groups. In addition, on the day of surgery and on the first, third, and seventh days after surgery, patients reported that sore throat caused the greatest discomfort. CONCLUSION: In patients undergoing thyroidectomy under general anesthesia using sevoflurane or desflurane, except for dizziness on the day of surgery, no other manifestation of postoperative pain and discomfort was influenced by the type of inhaled anesthetic. Moreover, after thyroidectomy, postoperative sore throat caused the greatest discomfort to patients from the day of surgery to the seventh day after surgery.

Effect of transversus abdominis plane block on the quality of recovery in laparoscopic nephrectomy: A prospective double-blinded randomized controlled clinical trial.

BACKGROUND: Poorly controlled acute postoperative pain after laparoscopic nephrectomy may adversely affect surgical outcomes and increase morbidity rates. In addition, excessive use of opioids during surgery may slow postoperative endocrine and metabolic responses and cause opioid-related side effects and opioid-induced hyperalgesia. The purpose of this study was to evaluate the effect of ultrasound-guided transversus abdominis plane (TAP) block on the postoperative quality of recovery and intraoperative remifentanil requirement in laparoscopic nephrectomy. METHODS: Sixty patients who underwent laparoscopic nephrectomy were randomly divided into 2 groups: TAP and Control groups. After induction of anesthesia and before awakening from anesthesia, the TAP group was administered 40 mL of 0.375% ropivacaine and the Control group was administered 40 mL of normal saline to deliver ultrasound-guided TAP block using 20 mL of each of the above drugs. The main objectives of this study were to evaluate the effect of the TAP block on quality of recovery using the Quality of Recovery 40 (QoR-40) questionnaire and assessments of intraoperative remifentanil requirement. In addition, to evaluate the postoperative analgesic effect of the TAP block, the total usage time for patient-controlled analgesia (PCA) and the number of PCA bolus buttons used in both groups were analyzed. RESULTS: The QoR-40 score, measured when visiting the ward on the third day after surgery, was significantly higher in the TAP group (171.9 ±â€…23.1) than in the Control group (151.9 ±â€…28.1) (P = .006). The intraoperative remifentanil requirement was not significantly different between the groups (P = .439). In the TAP group, the frequency of bolus dose accumulation at 1, 2, 3, 6, 12, 24, 48, and 72 hours after surgery was low enough to show a significant difference, and the total usage time for PCA was long enough to show a significant difference. CONCLUSION: In conclusion, we determined that ultrasound-guided TAP block during laparoscopic nephrectomy improves the quality of postoperative recovery and is effective for postoperative pain control but does not affect the amount of remifentanil required for adequate anesthesia during surgery.

Inferior mesenteric plexus block under computed tomography guidance: A case report.

RATIONALE: Inferior mesenteric plexus block is indicated for left-sided lower abdominal pain. However, in patients with terminal cancer, severe abdominal pain can prevent the patient from maintaining the necessary posture during the procedure, and considerable anatomic deformation owing to extensive growth, invasion, and metastasis of the tumor in the abdominal cavity can make the procedure difficult. In these cases, performing the procedures under computed tomography (CT) guidance can ensure greater safety and accuracy. PATIENT CONCERNS: A 63-year-old man was referred for severe left-sided lower abdominal pain. He was unable to lie prone owing to severe lower abdominal pain and right hip surgery performed 15 years ago. His visual analog scale score was 9 out of 10. DIAGNOSES: The patient had terminal pancreatic tail cancer. Compared with abdominal CT findings obtained 50 days ago, hepatic metastasis and peritoneal seeding were still present, infiltration to the tissues around the pancreas and retrogastric area was increased, and most of the abdominal aorta was encased. In addition, metastatic lymph nodes were identified in several areas on the left including the left para-aortic area. However, the lesion causing the pain could not be identified. Therefore, an inferior mesenteric plexus block was performed according to the patient's complaint. INTERVENTIONS: Epidural patient-controlled analgesia was performed first. The patient's pain consequently reduced to a certain level, and the prone position became possible to some extent, so a CT-guided inferior mesenteric plexus block was performed 2 days later. OUTCOMES: After the CT-guided inferior mesenteric plexus block, it became possible to control the patient's pain with a fentanyl patch 75 mcg/hour only, and his visual analog scale score was reduced to 4. After 4 weeks, the patient died without complaints of severe pain as before. LESSONS: CT-guided inferior mesenteric plexus block can be performed in patients with left-sided lower abdominal pain, enabling a safer and more accurate procedure especially in patients with terminal cancer who are unable to lie prone owing to severe lower abdominal pain or with considerable anatomic deformation due to extensive growth, invasion, and metastasis of the tumor in the abdominal cavity.

Mechanism of action of the trastuzumab biosimilar CT-P6.

Objectives: Therapeutic monoclonal antibody biosimilars are expected to help reduce the sizeable economic burden of targeted treatments. Trastuzumab (Herceptin®), a recombinant humanized monoclonal antibody that binds to the extracellular domain of HER2, is approved for use in HER2-overexpressing breast cancer (in both the adjuvant and metastatic settings) and HER2-positive gastric cancer. CT-P6 (Herzuma®) is a biosimilar of trastuzumab, designed to bind with high affinity and specificity to the same HER2 epitope as the reference product. We investigated whether CT-P6 exerts its effects through the same mechanism of action as trastuzumab. Methods: The mechanism of action of CT-P6 and trastuzumab, both as monotherapy and in combination with paclitaxel or pertuzumab, was compared in HER2-overexpressing breast cancer and gastric cancer cell models. Results: We confirmed that CT-P6 functions in a manner similar to trastuzumab by binding to the HER2 receptor, which is central to the effects of trastuzumab in all indications. Conclusions: Collectively, the results of this study show that the mechanisms of action of CT-P6 and trastuzumab are similar in HER2-positive breast cancer and gastric cancer models and, therefore, CT-P6 can be expected to perform similarly in the clinical setting.

False localizing sign caused by schwannoma in cervical spinal canal at C1-2 level: A case report.

RATIONALE: False localizing sign means that the lesion, which is the cause of the symptom, is remote or distant from the anatomical site predicted by neurological examination. This concept contradicts the classical clinicoanatomical correlation paradigm underlying neurological examinations. PATIENT CONCERNS: A 54-year-old man consulted for the right sciatica-like leg pain that had aggravated 1 year ago. Radiological examinations revealed degenerative spondylolisthesis with instability and right-sided recess stenosis at the L4-5 level. After initial improvement following 3 transforaminal epidural steroid injections with gabapentin and antidepressant medication, there was a recurrence of the symptoms a year later, along with wasting of the right leg for several months. Physical examination revealed difficulty in heel-walking and a weakness of extension of the right big toe; tendon reflexes were normal. Lumbar spine radiographs revealed no new findings. The initial course of treatment was repeated, but was ineffective. DIAGNOSES: Further cervicothoracic spine evaluations revealed a right-sided intradural-extramedullary mass and myelopathy at the C1-2 level. INTERVENTIONS: The cervical mass was surgically resected and identified histopathologically as a schwannoma. OUTCOMES: Immediately after surgery, sciatica-like pain and weakness of right leg were completely resolved. LESSONS: It is difficult to make an accurate diagnosis if there are symptoms caused by false localizing sign. Additionally, it is even more difficult to diagnose false localizing sign accurately when there is a co-existing lumbar lesion that can cause the similar symptoms.

The effect of preoperative nefopam treatment on postoperative catheter-related bladder discomfort in patients undergoing transurethral bladder tumor resection: a randomized double-blind study.

BACKGROUND: Catheter-related bladder discomfort (C.R.B.D.) is a risk factor for emergence agitation and delirium in postoperative phase. It may be resistant to conventional analgesic therapy such as opioids. This study evaluated the role of preoperative treatment using intravenous 20 mg nefopam in reducing the incidence and severity of C.R.B.D. during the first postoperative 24 h after urinary catheterization when compared with placebo. METHODS: Seventy adult males undergoing elective transurethral resection of bladder tumor requiring urinary bladder catheterization intraoperatively were randomly divided into two groups of 35 patients. In the intervention group (Group N), intravenous 20 mg nefopam in 100 mL normal saline was administered before spinal anesthesia. The placebo group (Group P) received intravenous normal saline 100 mL instead. The incidence and severity of side-effects, including C.R.B.D. at 1, 2, 6, and 24 h after surgery, was evaluated. RESULTS: The incidence of C.R.B.D. was reduced in Group N compared with Group P during the first postoperative 24 h (6/33 [18.2%] vs 22/35 [62.9%], Group N vs Group P, p = .000). The severity of C.R.B.D. also varied significantly at postoperative 1, 2, and 6 h. The use of postoperative analgesics was reduced in Group N compared with Group P (8/33 [24.2%] vs 25/35 [71.4%], Group N vs Group P, p = .000). CONCLUSIONS: The preoperative administration of single-dose intravenous nefopam reduced the incidence and severity of C.R.B.D. in the early postoperative period in patients undergoing T.U.R.-B. under spinal anesthesia.

Treatment of radiation-induced cystitis and vulvodynia via a ganglion impar block using a lateral approach under computed tomography guidance: a case report.

Adjuvant radiation therapy (RT) after colorectal cancer surgery can prevent local recurrence, but has several side effects. Precise injection of drugs into the affected areas is complicated by radiation-induced fibrosis of soft or connective tissue. A 48-year-old woman experienced severe intractable perineal pain, dysuria, urinary urgency, and frequent urination after rectal cancer surgery and adjuvant RT, and was diagnosed with radiation-induced cystitis and vulvodynia. Her symptoms persisted despite two fluoroscopy-guided ganglion impar blocks. Fluoroscopy revealed atypical needle tip positioning and radiolucent dye distribution, presumably due to radiation-induced fibrosis in the target region. We performed two computed tomography (CT)-guided ganglion impar blocks by using a lateral approach, which allowed more accurate po-sitioning of the needle tip. Her pain visual analog score decreased from 9 to 3, and she recently resumed sexual intimacy. CT guidance is a viable alternative to fluoroscopy guidance when performing ganglion impar blocks in fibrotic areas.

Inhibition of Oxidative Stress in Renal Ischemia-Reperfusion Injury.

BACKGROUND: Superoxide, nitric oxide (NO), and peroxynitrite are important mediators in the pathogenesis of ischemia-reperfusion (I/R) injury. We tested the renoprotective effects of allopurinol (ALP), a xanthine oxidase inhibitor, N-nitro-L-arginine methyl ester (L-NAME), and 5,10,15,20-tetrakis (N-methyl-4-pyridyl) porphyrinato iron (III) (FeTMPyP) by selective inhibition of superoxide, NO, and peroxynitrite, respectively. METHODS: Male Sprague-Dawley rats were randomly assigned to 5 groups (n = 6 per group). Group 1 was a sham-operated group. Group 2 was the renal I/R group (30-minute ischemia followed by 24-hour reperfusion). Rats in groups 3, 4, and 5 received ALP, L-NAME, or FeTMPyP, respectively, at 5 minutes before the reperfusion. Serum creatinine (Cr), blood urea nitrogen (BUN), renal tissue malondialdehyde, superoxide dismutase, histological changes, apoptosis, and monocyte infiltration were evaluated. In addition, the combined treatment with ALP and L-NAME was compared with FeTMPyP in a second independent experiment. RESULTS: The administration of ALP, L-NAME, and FeTMPyP diminished the increase in Cr (P = .0066 for all) and BUN (P = .0066 for ALP; and P = .013 for L-NAME) induced by I/R injury and decreased the histological damage (P = .0066 for all). In addition, ALP, L-NAME, and FeTMPyP attenuated the oxidative stress response as determined by a decrease in malondialdehyde level (P = .0066 for all), apoptotic renal tubular cells (P = .0066 for all), and monocyte infiltration (P = .0066 for all). The combined treatment of ALP and L-NAME decreased Cr and BUN levels to a greater degree than FeTMPyP (P = .016 for Cr; P = .0079 for BUN). CONCLUSIONS: Superoxide, NO, and peroxynitrite are involved in renal I/R injury. The reduction of peroxynitrite formation, via inhibition of superoxide or NO, or the induction of peroxynitrite decomposition may be beneficial in renal I/R injury.

Microarray analysis for genes associated with angiogenesis in diabetic OLETF keratocytes.

The purpose of this study was to identify the differences in angiogenesis gene expression between normal and diabetic keratocytes stimulated with interleukin-1α (IL-1α) and tumor necrosis factor-α (TNF-α). Primarily cultured normal and diabetic keratocytes were treated with 20 ng/mL of IL-1a and TNF-α for 6 hr. cDNA was hybridized to an oligonucleotide microarray. Microarray analysis was used to identify differentially expressed genes that were further evaluated by real-time polymerase chain reaction (RT-PCR). Diabetes keratocytes overexpressed vital components of angiogenesis including Agtr1, and under-expressed components related to the blood vessel maturation, including Dcn. Cytokine-treated diabetic keratocytes differentially expressed components of angiogenesis. OLETF keratocytes after treatment with IL-1α and TNF-α showed the newly expressed 15 and 14 genes, respectively. Newly and commonly under-expressed five genes followed by treatment with both IL-1α and TNF-α were also evident. RT-PCR showed results similar to the microarray results. Agtr1 and Itga1 showed an increased expression in diabetic keratocytes compared with normal corneal keratocytes, especially after TNF-α treatment. Il6 appeared strong expression after interleukin-1α treatment, but showed down expression after TNF-α treatment. Further studies to analyze and confirm the significance of the identified angiogenetic genes of diabetes are needed.

Bell's phenomenon during screening examination for retinopathy of prematurity.

PURPOSE: Bell's phenomenon (BP), which may disturb screening examinations for retinopathy of prematurity (ROP), is known to present infrequently in premature babies. Stress associated with the examinations can influence expression of BP. The authors of the present study evaluated BP during examinations for ROP. METHODS: The present study included 102 eyes of 51 premature babies. Expression of BP was assessed at 3 steps of the examination in the following order: after insertion of a speculum, after illumination of an indirect ophthalmoscope and after scleral depression. The relationship between the expression of BP and the gestational age at the examination was analyzed in each step of the examination. RESULTS: The frequency of BP after the speculum insertion and the illumination was 77% to 92% in infants 32 weeks of age or younger, and decreased significantly to 16% to 57% in infants 42 weeks of age or older (p < 0.005). BP after the scleral depression had no significant association with the gestational age. Frequency of BP increased significantly as the steps of the examination proceeded (p < 0.01). CONCLUSIONS: BP was frequent in premature infants during ROP examination in spite of neurological immaturity. The examiner should take BP into consideration, which frequently occurs in younger infants.

Oxidation of polyvinyl alcohol by persulfate activated with heat, Fe2+, and zero-valent iron.

The oxidation of polyvinyl alcohol (PVA) by persulfate (S(2)O(8)(2-)) activated with heat, Fe(2+), and zero-valent iron (Fe(0)) was investigated via batch experiments. It was hypothesized that elevated temperature and the addition of Fe(2+) or Fe(0) into a persulfate-water system could enhance the oxidation of PVA by activated persulfate. Increasing the temperature from 20 to 60 degrees C or 80 degrees C accelerated the oxidation rate of PVA, which achieved complete oxidation in 30 and 10 min, respectively. At 20 degrees C, the addition of Fe(2+) or Fe(0) to the persulfate-water system significantly enhanced the oxidation of PVA. The optimal persulfate-to-Fe(2+) or Fe(0) molar ratio was found to be 1:1. Complete oxidation of PVA was obtained by Fe(0)-activated persulfate in 2h. Synergistic activation of persulfate by heat and Fe(2+) or Fe(0) was also shown to enhance the oxidation of PVA in the persulfate-water system. By using GC-MS analysis, an oxidation product of PVA was identified as vinyl acetic acid (C(4)H(6)O(2)), which is readily biodegradable. Our results suggest that the oxidative treatment of PVA by activated persulfate is a viable option for the pretreatment of PVA-laden wastewater to enhance its biodegradability.

Intraoperative adjustable suture strabismus surgery under topical and subconjunctival anesthesia.

BACKGROUND AND OBJECTIVE: To assess the postoperative surgical results of intraoperative adjustable suture strabismus surgery under topical and subconjunctival anesthesia. PATIENTS AND METHODS: For 44 patients who had undergone intraoperative adjustable suture technique under topical anesthesia, the deviations were measured preoperatively, at 1 day, 1 month, and 3 months postoperatively, and at the last postoperative follow-up visit. The mean follow-up period was 7.8 months. RESULTS: Thirty-three patients had exotropia and 11 had esotropia. Mean age was 28.8 years. The success rates for exotropia and esotropia at the last follow-up visit were 81.8%. CONCLUSION: Intraoperative adjustable suture strabismus surgery under topical and subconjunctival anesthesia is the recommended surgical technique due to the successful results and various advantages compared with non-adjustable surgery, including the decreased rates of overcorrection or undercorrection that appear immediately after surgery and reoperation. Postoperative "drift" toward the original deviation was observed under longer follow-up periods than other studies.