Factors affecting propofol dosage for sedation in pediatric oncology.

BACKGROUND: There is limited reference data for determining the appropriate dose of propofol for individual patients. Therefore, we investigated the factors affecting propofol dosage for pediatric patients undergoing sedation for computed tomography (CT) simulation. METHODS: We retrospectively analyzed the electronic medical records of pediatric patients who underwent CT simulation for proton therapy following a cancer diagnosis at the National Cancer Center (Korea) between 1 May 2012 and 30 April 2016. We evaluated the following factors, which reflect comorbidities or chronic illness in pediatric oncology patients: age, tumor lesion, preterm birth, American Society of Anesthesiologists (ASA) classification, pre-sedation temperature, history of propofol use, nothing by mouth time, chemotherapy history, pre-sedation laboratory findings, regular medication (opioids, anticonvulsants), and use of diuretics. A regression analysis was performed and P < 0.05 was considered statistically significant. RESULTS: Electronic medical records of 84 pediatric cancer patients were used in the analysis. Patients in ASA classes 1-2 required approximately 43% more propofol than patients in classes 3-4 (exp(ß), 1.43; 95%CI: 1.21-1.69, P < 0.001). CONCLUSION: American Society of Anesthesiologists class 3 or 4 is an independent indicator of decreased propofol dosage for pediatric oncology patients during sedation.

Effects of preoperative ultrasound-guided transversus abdominis plane block on pain after laparoscopic surgery for colorectal cancer: a double-blind randomized controlled trial.

BACKGROUND: Although laparoscopic colorectal surgery decreases postoperative pain and facilitates a speedier recovery compared with laparotomy, postoperative pain at trocar insertion sites remains a clinical concern. The objective of this study was to assess the effects of a preoperative ultrasound-guided transversus abdominis plane (TAP) block on pain after laparoscopic surgery for colorectal cancer. METHODS: In total, 58 patients scheduled to undergo laparoscopic surgery following a diagnosis of colorectal cancer were included in this study. The patients were randomized into TAP and control groups; the TAP group patients received a preoperative ultrasound-guided bilateral TAP block with 0.5 mL/kg of 0.25 % bupivacaine, while the control patients received the block with an equal amount of saline. Pain on coughing and at rest was assessed during postanesthetic recovery (PAR; 1 h after surgery) and on postoperative days (PODs) 1 (24 h), 2 (48 h), and 3 (72 h) by an investigator blinded to group allocations using the numeric rating scale (NRS). The primary outcome was pain on coughing on postoperative day (POD) 1. RESULTS: Fifty-five patients were included in the final analysis, including 28 in the TAP and 27 in the control groups. The pain intensity on coughing and at rest during PAR and on PODs 1, 2, and 3 showed no significant differences between groups. Furthermore, there was no significant difference in postoperative opioid consumption, sedation scores, nausea scores at the four time points, complication rates, and length of hospital stay between groups. CONCLUSIONS: In colorectal cancer patients undergoing laparoscopic colorectal surgery, a TAP block did not offer enough benefit for clinical efficacy in terms of postoperative pain or analgesic consumption.

The Effect of Chronic Opioid Use on End-Tidal Concentration of Sevoflurane Necessary to Maintain a Bispectral Index Below 50: A Prospective, Single-Blind Study.

BACKGROUND: Opioid analgesics decrease the minimum alveolar concentration of inhalation agents during the acute phase response. However, the effect of chronic opioid exposure on minimum alveolar concentration of inhalation agents remains unknown. This study aimed to determine the concentration of sevoflurane necessary to maintain a bispectral index (BIS) <50 (SEVOBIS50) in patients with chronic opioid use compared with those naïve to opioid use. METHODS: We included chronic opioid users who received a stable dose of oral morphine of at least 60 mg/d according to the morphine equivalent daily dose for at least 4 weeks and opioid-naïve patients. General anesthesia that included thiopental, vecuronium, and sevoflurane in oxygen was administered to all patients. Anesthesia was maintained using predetermined end-tidal sevoflurane concentrations. Fifteen minutes after achieving the determined end-tidal sevoflurane concentration through closed circuit anesthesia, BIS was measured for 1 minute in both groups. SEVOBIS50 was determined using Dixon's up-down method and probit analysis. RESULTS: Nineteen and 18 patients from the chronic opioid and control groups, respectively, were included in the final analysis. SEVOBIS50values for the chronic opioid and control patients were 0.84 (95% confidence interval, 0.58-1.11) and 1.18 (95% confidence interval, 0.96-1.40), respectively (P = .0346). CONCLUSIONS: Our results suggest that the end-tidal concentration of sevoflurane necessary to maintain a BIS <50 is lower for chronic opioid users than for opioid-naïve patients.

Thoracic duct cannulation during left internal jugular vein cannulation: A case report.

BACKGROUND: Central venous catheter insertion is an invasive procedure that can cause complications such as infection, embolization due to air or blood clots, pneumothorax, hemothorax, and, rarely, chylothorax due to damage to the thoracic duct. Herein, we report a case of suspected thoracic duct cannulation that occurred during left central venous catheter insertion. Fortunately, the patient was discharged without any adverse events related to thoracic duct cannulation. CASE SUMMARY: A 46-year-old female patient presented at our department to undergo cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. During anesthesia, we decided to insert a central venous catheter through the left internal jugular vein because the patient already had a chemoport through the right central vein. During the procedure, blood reflux was observed when the needle tip was not within the ultrasound field of view. We did not try to find the tip; however, a guide wire and a central venous catheter were inserted without any resistance. Subsequently, when inducing blood reflux from the distal port of the central venous catheter, only clear fluid, suspected to be lymphatic fluid, was regurgitated. Further, chest X-ray revealed an appearance similar to that of the path of the thoracic duct. Given that intravenous fluid administration was not started and no abnormal fluid collection was noted on preoperative chest X-ray, we suspected thoracic duct cannulation. CONCLUSION: It is important to use ultrasound to confirm the exact position of the needle tip and guide wire path.

Combinations of nerve blocks in surgery for post COVID-19 pulmonary sequelae patient: A case report and review of literature.

BACKGROUND: Regional anesthesia is a promising method in patients with post coronavirus disease 2019 (COVID-19) pulmonary sequelae for preserving pulmonary function and preventing postoperative pulmonary complications, compared with general anesthesia. CASE SUMMARY: We provided surgical anesthesia and analgesia suitable for breast surgery by performing pectoral nerve block type II (PECS-II), parasternal, and intercostobrachial nerve blocks with intravenous dexmedetomidine administration in a 61-year-old female patient with severe pulmonary sequelae after COVID-19 infection. CONCLUSION: Sufficient analgesia for 7 h was provided via PECS-II, parasternal, and intercostobrachial blocks perioperatively.

Interactions of midazolam and propofol on α1ß2γ2L and α1ß2γ2S gamma aminobutyric acid type A receptors expressed in human embryonic kidney cells.

BACKGROUND: The gamma aminobutyric acid type A (GABA(A)) receptor is a prime target of many anesthetics, including midazolam and propofol. Although these anesthetics have sedative and hypnotic properties by enhancing GABA(A) receptor activity, their interactions at the GABA(A) receptors have not been explored. We investigated the interaction of midazolam and propofol with α(1)ß(2)γ(2)L and α(1)ß(2)γ(2)S GABA(A) receptors. METHODS: Using the whole-cell patch clamp technique, we tested the effects of midazolam and propofol on GABA-induced currents in human embryonic kidney 293 T cells transfected with α(1)ß(2)γ(2)L and α(1)ß(2)γ(2)S GABA(A) receptors. RESULTS: Midazolam and propofol on their own enhanced the amplitude of GABA(A) receptor responses in a dose-dependent manner, and they had additive effects on α(1)ß(2)γ(2)S GABA(A) receptors, but not on α(1)ß(2)γ(2)L GABA(A) receptors. However, additive interactions of midazolam and propofol on the α(1)ß(2)γ(2)L GABA(A) receptors were observed when protein kinase C was inhibited. CONCLUSIONS: The interaction between midazolam and propofol is affected by receptor subtype, and protein kinase phosphorylation influences their interaction on the α(1)ß(2)γ(2)L receptor.

Musculoskeletal Disorders, Pain Medication, and in-Hospital Mortality among Patients with COVID-19 in South Korea: A Population-Based Cohort Study.

We aimed to investigate whether comorbid musculoskeletal disorders (MSD)s and pain medication use was associated with in-hospital mortality among patients with coronavirus disease 2019 (COVID-19). Adult patients (≥20 years old) with a positive COVID-19 diagnosis until 5 June 2020 were included in this study, based on the National Health Insurance COVID-19 database in South Korea. MSDs included osteoarthritis, neck pain, lower back pain, rheumatoid arthritis, and others, while pain medication included paracetamol, gabapentin, pregabalin, glucocorticoid, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids (strong and weak opioids), and benzodiazepine. Primary endpoint was in-hospital mortality. A total of 7713 patients with COVID-19 were included, and in-hospital mortality was observed in 248 (3.2%) patients. In multivariate logistic regression analysis, no MSDs (p > 0.05) were significantly associated with in-hospital mortality. However, in-hospital mortality was 12.73 times higher in users of strong opioids (odds ratio: 12.73, 95% confidence interval: 2.44-16.64; p = 0.002), while use of paracetamol (p = 0.973), gabapentin or pregabalin (p = 0.424), glucocorticoid (p = 0.673), NSAIDs (p = 0.979), weak opioids (p = 0.876), and benzodiazepine (p = 0.324) was not associated with in-hospital mortality. In South Korea, underlying MSDs were not associated with increased in-hospital mortality among patients with COVID-19. However, use of strong opioids was significantly associated with increased in-hospital mortality among the patients.

Persistency and pathway of isoflurane-induced inhibition of superoxide production by neutrophils.

BACKGROUND: Our previous work has demonstrated that treatment with isoflurane has a preconditioning-like inhibitory effect on superoxide production (SOP) by polymorphonuclear neutrophils. The current objectives were to determine persistency of this effect and to clarify where in the signalling pathway this inhibition of SOP occurred. The latter was accomplished using two receptor-dependent neutrophil agonists, platelet activating factor (PAF) and formyl-methionyl-leucyl-phenylalanine (fMLP), and two receptor-independent neutrophil stimuli, the protein-kinase C stimulator, phorbol myristate acetate (PMA), and the calcium ionophore, A23187. METHODS: Arterial blood samples were obtained from eight dogs under baseline condition (conscious state), during isoflurane (1 MAC) administration, and 24 and 48 hr post-isoflurane (also in conscious state). Neutrophils were isolated and stimulated with 1 muM concentrations of PAF, fMLP, PMA, and A23187. SOP was measured spectrophotometrically. RESULTS: Isoflurane administration caused (1) an approximate 50% decrease in SOP during PAF or fMLP (P < 0.01 vs baseline), which remained evident from 24 to 48 hr following isoflurane; (2) an initial 29% decrease in SOP during PMA (P < 0.05 vs baseline), which returned to baseline by 24 hr following isoflurane; and (3) no change in SOP during A23187 (P > 0.05 vs baseline). CONCLUSIONS: Isoflurane administration caused prolonged (from 24 to 48 hr) decreases in agonist-induced SOP by neutrophils. This effect involved inhibition at site(s) in the signalling pathway upstream from protein kinase C. The current findings suggest that the intraoperative use of isoflurane may result in an extended impairment to the antibacterial host defense mechanism and that neutrophil inhibition may play a role in the delayed tissue protection afforded by treatment with volatile anesthetics.

Chronic Smoking is Not Associated with Increased Postoperative Opioid Use in Patients with Lung Cancer or Esophageal Cancer.

BACKGROUND: Chronic smokers show differences in pain sensitivity compared to healthy non-smokers. Yet, no study to date has examined whether smoker status has an effect on postoperative pain. OBJECTIVE: We aim to examine a possible correlation between preoperative smoking and postoperative opioid dose based on the hypothesis that smokers would use higher doses of opioids to manage increased postoperative pain. STUDY DESIGN: A retrospective observational cohort study. SETTING: The National Cancer Center in Korea. METHODS: We examined medical record data for patients who had undergone curative resection for either lung or esophageal cancer (lobectomy or bilobectomy for lung cancer or an Ivor Lewis operation for esophageal cancer) between January 1, 2006 and December 31, 2010. We examined the correlation between the total preoperative average number of packs per day multiplied by years of cigarette smoking (pack-years) and morphine equivalent daily doses administered to patients after surgery, considering each type of cancer both individually and together. Partial correlation and regression analyses were performed to determine the causality of a possible relationship between pack-years of cigarette smoking and postoperative opioid dose. RESULTS: A total of 1,129 patients (871 patients with lung cancer and 258 patients with esophageal cancer) were included in the final analysis. There was no significant correlation between total pack-years of cigarette smoking and postoperative opioid dose for lung cancer, esophageal cancer, or both cancer types combined (r = 0.042, -0.012, and 0.037, respectively). In the analysis of both cancer types combined, video-assisted thoracic surgery (VATS) was associated with an 11.1% decrease in opioid dose (ß = -0.111, P = 0.003) and epidural analgesia was associated with a 7.2% increase in opioid dose (ß = 0.072, P = 0.042). LIMITATIONS: The retrospective design of this study is a limitation. CONCLUSION: Our study did not observe a correlation between preoperative smoking and postoperative opioid dose in patients with lung or esophageal cancer. KEY WORDS: Smoking, postoperative pain, opioid, lung cancer, esophageal cancer, analgesia.

Investigation of opioid use and long-term oncologic outcomes for non-small cell lung cancer patients treated with surgery.

Opioids are commonly used for postoperative pain control in cancer patients. In addition to pain control, an association between opioid use and long-term oncologic outcomes, such as recurrence or overall survival, has been postulated. The aim of this study was to determine whether postoperative opioid use in patients with non-small cell lung cancer is associated with long-term oncologic outcomes, including recurrence and death. Data obtained from 1009 medical records of patients who underwent curative resection at the National Cancer Center, Korea between January 2006 and December 2010 were retrospectively analyzed. Seven-day opioid use was divided into four quartiles to analyze probability of recurrence and death. Multivariate regression analyses of recurrence and death was conducted, including the calculation of odds ratios. A total of 871 patients were analyzed. When opioid dosage was examined by quartiles, the probability of death and recurrence increased gradually with increasing opioid use. However, in the multivariate regression analysis, the amount of opioid usage did not affect the risk of recurrence or death of lung cancer (P = 0.520 for recurrence; P = 0.659 for death). Opioid use was correlated with outcome when stratified by lung cancer stage (P = 0.004 for recurrence; P = 0.049 for death); however, the odds ratios only slightly increased (1.001 for stage IA-IIIA) for both outcomes. In non-small cell lung cancer patients, the amount of opioid usage does not affect the risk of recurrence and death of lung cancer. There was an association with stage (IA-IIIA), but the effect was negligible. A well-designed prospective study is needed.

The administration of high-dose propofol sedation with manual and target-controlled infusion in children undergoing radiation therapy: a 7-year clinical investigation.

BACKGROUND: Radiation therapy requires the patient to remain immobile for a long time, which is challenging in children. This study therefore aimed to determine the adequate target concentration and dosage of propofol in target-controlled infusion (TCI) and manual infusion (MI) in children requiring sedation for proton radiation therapy. Our hypothesis is that the adequate dose of propofol sedation required for proton radiation therapy in pediatric patients was larger than that seen in previous studies. METHODS: We retrospectively analyzed the medical records of Korean children who received proton therapy under propofol sedation. The average target concentration at induction and during maintenance with TCI and the dose with MI were analyzed as primary outcomes. RESULTS: A total of 1296 procedures in 54 children were analyzed (TCI group, 26; MI group, 28). The median bolus dose of propofol in the MI group was 2.6 (2.2-3.0) mg/kg, while the pump speed was 17.0 (13.6-25.8) mg/kg/h. The median target concentration of propofol in the TCI group was 5.3 (4.4-5.7) mcg/mL at induction and 4.2 (3.1-5.1) mcg/mL during maintenance. There were no cases of life-threatening complications in either group over 7 years. There were six cases of transient desaturation, which were managed by using the jaw thrust maneuver. CONCLUSIONS: Compared with those in previous studies, the target concentration of propofol with TCI and the propofol dose with MI required for adequate sedation in children undergoing proton radiation therapy were larger in the present study. Despite concerns regarding overdosage, the complications were managed well. However, safe and adequate sedation for proton radiation therapy remains a challenge. The development of monitoring tools to evaluate the depth of sedation is necessary to adjust the propofol dose and sedation level.

The effects of midazolam and sevoflurane on the GABA(A) receptors with alternatively spliced variants of the γ2 subunit.

BACKGROUND: Emergence agitation after sevoflurane anesthesia in children can be prevented by midazolam. Alternative splicing of the GABA(A) receptor changes with age. Therefore, we hypothesized that alternative splicing of the γ2 subunit affects the GABA current when applying sevoflurane and midazolam. METHODS: We performed the whole-cell patch clamp technique on human embryonic kidney 293 cells that were transfected with α1ß2γ2L or α1ß2γ2S. The concentration-response relations were recorded for midazolam and sevoflurane, and the co-application responses were measured at concentrations of 1.5 nM, 15 nM and 300 nM of midazolam and 0.5%, 2.0% and 4.0% of sevoflurane. Each GABA current was compared with that produced by 5 µM of GABA. RESULTS: The concentration-response relationships for midazolam and sevoflurane were dose-dependent without any differences between the α1ß2γ2L and α1ß2γ2S subtypes. 1.5 nM and 15 nM of midazolam did not significantly enhance the current after treatment with 0.5% sevoflurane for both subtypes. The current after treatment with 2.0% sevoflurane was enhanced by 1.5 nM midazolam for the α1ß2γ2S subtype, but not for the α1ß2γ2L subtype. In the case of 2.0% sevoflurane with 15 nM of midazolam, and 4.0% sevoflurane with 300 nM of midazolam, the GABA currents were significantly enhanced for both subtypes. CONCLUSIONS: These results show that the difference in the γ2 subunit cannot explain the emergence agitation after sevoflurane anesthesia in children in vitro. This suggests that co-application of sevoflurane and midazolam enhances the GABA current according to the alternative splicing of the γ2 subunit and the concentration of both drugs.