The use of laser photobiomodulation as pre-anesthetic tissue management technique in reducing injection pain in children.

BACKGROUND: One of the main goals for pediatric dentists is to offer a painless anesthesia experience. Laser photobiomodulation is among the suggested strategies to decrease injection pain. So, this study aimed to assess the impact of laser photobiomodulation on local anesthesia (LA) injection pain in children and its effect on the efficacy of LA during pulpotomy and SSC procedures. METHODS: The research was carried out as a randomized controlled clinical trial with two parallel group design. It involved 64 cooperative healthy children, age range from 5 to 7 years, each having at least one maxillary molar indicated for pulpotomy. Children were randomly allocated to one of the two groups based on the pre-anesthetic tissue management technique used: test group received laser photobiomodulation, while control group received topical anesthetic gel. Pain during injection, pulpotomy, and SSC procedures was assessed using physiological measures (Heart Rate (HR)), subjective evaluation (modified Face-Pain-Scale (FPS), and objective analysis (Sound-Eye-Motor scale (SEM)). RESULTS: A total of 64 children with mean age 6.23 ± 0.78 participated in this research. The mean HR scores were significantly lower in the laser PBM group during buccal and palatal infiltration injections. The SEM mean scores were significantly lower in the laser PBM group during both injections. For the FPS scale, the number of children who recorded satisfaction during injection was significantly higher in laser PBM group. There was no statistically significant difference in mean HR as well as in SEM and FPS scores between the two groups during pulpotomy and SSC procedures. Comparisons between the two study groups were performed using independent samples t- and Mann-Whitney U tests. Significance was set at p value < 0.05. CONCLUSION: Laser photobiomodulation is a promising non-pharmacological pre-anesthetic tissue management technique in children that offered less painful injection compared to topical anesthetic gel without compromising the effectiveness of LA. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05861154. Registered on 16/5/2023.

Towards more tolerable subcutaneous administration: Review of contributing factors for improving combination product design.

Subcutaneous (SC) injections can be associated with local pain and discomfort that is subjective and may affect treatment adherence and overall patient experience. With innovations increasingly focused on finding ways to deliver higher doses and volumes (≥2 mL), there is a need to better understand the multiple intertwined factors that influence pain upon SC injection. As a priority for the SC Drug Development & Delivery Consortium, this manuscript provides a comprehensive review of known attributes from published literature that contribute to pain/discomfort upon SC injection from three perspectives: (1) device and delivery factors that cause physical pain, (2) formulation factors that trigger pain responses, and (3) human factors impacting pain perception. Leveraging the Consortium's collective expertise, we provide an assessment of the comparative and interdependent factors likely to impact SC injection pain. In addition, we offer expert insights and future perspectives to fill identified gaps in knowledge to help advance the development of patient-centric and well tolerated high-dose/high-volume SC drug delivery solutions.

Efficacy and safety of Ciprofol compared with Propofol during general anesthesia induction: A systematic review and meta-analysis of randomized controlled trials (RCT).

BACKGROUND: Ciprofol, a newer entrant with similarities to propofol, has shown promise with a potentially improved safety profile, making it an attractive alternative for induction of general anesthesia. This meta-analysis aimed to assess the safety and efficacy of ciprofol compared with propofol during general anesthesia induction. METHODS: A comprehensive literature search was conducted using PubMed, Clinical Trial.gov, and Cochrane Library databases from inception to July 2023 to identify relevant studies. All statistical analyses were conducted using R statistical software version 4.1.2. RESULTS: Thirteen Randomized Controlled Trials (RCTs) encompassing a total of 1998 participants, were included in our analysis. The pooled analysis indicated that Ciprofol was associated with a notably lower incidence of pain upon injection [RR: 0.15; 95% CI: 0.10 to 0.23; I^2 = 43%, p < 0.0000001] and was non-inferior to propofol in terms of anesthesia success rate [RR: 1.00; 95% CI: 0.99 to 1.01; I^2 = 0%; p = 0.43]. In terms of safety, the incidence of hypotension was significantly lower in the ciprofol group [RR:0.82; 95% CI:0.68 to 0.98; I^2 = 48%; p = 0.03]. However, no statistically significant differences were found for postoperative hypertension, bradycardia, or tachycardia. CONCLUSION: In conclusion, Ciprofol is not inferior to Propofol in terms of its effectiveness in general anesthesia. Ciprofol emerges as a valuable alternative sedative with fewer side effects, especially reduced injection pain, when compared to Propofol. SUMMARY: Propofol, frequently utilized as an anesthetic, provides swift onset and quick recovery. However, it has drawbacks such as a narrow effective dosage range and a high occurrence of adverse effects, particularly pain upon injection. Ciprofol, a more recent drug with propofol-like properties, has demonstrated promise and may have an improved safety profile, making it a compelling alternative for inducing general anesthesia. This meta-analysis compared the safety and effectiveness of Ciprofol with Propofol for general anesthesia induction in a range of medical procedures, encompassing thirteen Randomized Controlled Trials (RCTs) and 1998 individuals. The pooled analysis indicated that Ciprofol was associated with a notably lower incidence of pain upon injection [RR: 0.15; 95% CI: 0.10 to 0.23; I^2 = 43%, p < 0.0000001] and was non-inferior to propofol in terms of anesthesia success rate [RR: 1.00; 95% CI: 0.99 to 1.01; I^2 = 0%; p = 0.43]. In terms of safety, the incidence of hypotension was significantly lower in the ciprofol group [RR:0.82; 95% CI:0.68 to 0.98; I^2 = 48%; p = 0.03]. However, no statistically significant differences were found for hypertension, bradycardia, or tachycardia. In conclusion, ciprofol is equally effective at inducing and maintaining general anesthesia as propofol. When compared to propofol, ciprofol is a better alternative sedative for operations including fiberoptic bronchoscopy, gynecological procedures, gastrointestinal endoscopic procedures, and elective surgeries because it has less adverse effects, most notably less painful injections.

Comparison of the Effectiveness of Different Methods for Pain Reduction During Injection Procedures in the Frontalis Muscle.

BACKGROUND: Forehead aesthetic injections are a well-known source of discomfort, and many analgesic non-invasive techniques have been proposed to ameliorate pain. However, no study has compared all these techniques for aesthetic purposes. Therefore, this study aimed to compare the effectiveness of topical cream anesthesia, vibratory stimulus, cryotherapy, pressure, and even no intervention, on pain during and immediately after injection, when considering aesthetic injections in the forehead. METHODS: Seventy patients were selected and had their foreheads divided into 5 parts, which received four different analgesic techniques, and one control zone was added. A numeric rating scale was used to assess pain, two direct questions were asked to evaluate patients' preference and discomfort with the techniques, and the adverse events were quantified. The injections were performed in the same sequence, with three minutes of rest between them and in a single session. Comparisons among analgesic methods for pain relief were performed by the one-way analysis of variance (ANOVA), considering a significance level of 5%. RESULTS: No significant differences were found among the analgesic methods, and between the methods and the control zone, both during and immediately after the injections (p > 0.05). The preferred method for pain relief was the use of topical anesthetic cream (47%), while the most uncomfortable technique was manual distraction (pressure) (36%). Only one patient reported an adverse event. CONCLUSIONS: No analgesic method to diminish pain was superior to the others or was better than no method. Nevertheless, the topical anesthetic cream was the preferred technique, causing less discomfort. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Effects of photobiomodulation with different application parameters on injection pain in children: a randomized clinical trial.

Photobiomodulation (PBM) has gained increasing interest due to its effectiveness in pain reduction in various fields of dentistry. However, the number of studies evaluating the effect of PBM on injection pain in children is very limited. The aim of the study was to evaluate the efficacy of PBM with three different application parameters (doses) + topical anesthesia on reducing injection pain and to compare these results with the placebo PBM + topical anesthesia in children during supraperiosteal anesthesia administration. 160 children were randomly divided into 4 groups, 3 experimental and 1 control, with 40 subjects in each. In the experimental groups, before the anesthesia administration, PBM with a power of 0.3 W was applied for 20, 30 and 40 s in groups 1, 2 and 3, respectively. In group 4, a placebo application of laser was performed. The pain felt during the injection was assessed using the Wong-Baker Faces Pain Rating Scale (PRS), and also the Face, Legs, Activity, Cry, Consolability (FLACC) Scale. Statistical analyses were performed to evaluate the data (p < 0.05). The mean FLACC Scale pain scores were 3.02 ± 2.93, 2.92 ± 2.54, 2.12 ± 1.89 and 1.77 ± 1.90 for the placebo group, and Groups 1, 2, and 3, respectively. Furthermore, the mean PRS scores were 1 ± 1.03, 0.95 ± 0.98, 0.80 ± 0.822 and 0.65 ± 0.921 for the placebo group, and Groups 1, 2 and 3, respectively. The "no pain response" rate was higher in Group 3 as compared to Groups 1, 2, and placebo according to the FLACC Scale and PRS; however, no difference was found between the groups (p = 0.109, p = 0.317). Injection pain in children did not differ with placebo and PBM applied with a power of 0.3 W for 20, 30 and 40 s.

Evaluation of Peripheral Versus Central Route of Ondansetron as Pretreatment to Prevent Pain on the Injection of Propofol: A Randomized Controlled Study.

Objective: We evaluated whether systemic ondansetron was also useful in the attenuation of propofol injection pain similar to ondansetron pretreatment. Methods: Eighty patients were enrolled. Patients in group S received ondansetron 4 mg in saline in the right hand followed 30 min later by 5 mL saline in the left hand along with venous occlusion. Group L patients received 4 mL of saline in the right hand followed by 5 mL 4 mg ondansetron in the left hand after 30 min. Two minutes later the occlusion was released. Patients received one-fourth of the calculated total dose of propofol, and their level of pain was graded on a scale of 0 to 3, with 0 denoting no discomfort. Mean blood pressure and heart rates were also recorded. Continuous variables were checked for normality using Shapiro-Wilks test. Normal continuous variables were expressed as mean standard deviation and non-normal continuous variables were expressed as median interquartile range. T-test for the difference in the mean and paired test were used for normally distributed continuous variable whereas Mann-Whitney U test-Wilcoxon test and sign test were used for non-normally distributed variables. Repeated measure analysis of variance was used for a variable measured over different periods of time to control for the baseline effect on subsequent measures. Results: Our results demonstrated that both systemic administration 30 min before and local venous pretreatment with ondansetron were equally beneficial in reducing pain during propofol injection. Conclusion: A systemic administration of ondansetron may play a role in the attenuation of propofol injection pain.

Prevention of pain on injection of propofol using ice gel pack versus pre-treatment with lignocaine: a randomized controlled trial.

PURPOSE: Regardless of the positive attributes of propofol, it is frequently associated with pain on injection. We compared the efficacy of topical cold thermotherapy using an ice gel pack with intravenous lignocaine pre-treatment for reducing pain on propofol injection. METHODS: This single-blinded randomized controlled trial was conducted in 200 American Society of Anesthesiologists physical status I, II, and III patients scheduled for elective/emergency surgery under general anesthesia. The patients were randomized into two groups: the Thermotherapy group- receiving an ice gel pack proximal to the intravenous cannula for 1 min, or the Lignocaine group-receiving 0.5 mg/kg of lignocaine administered intravenously, with occlusion proximal to the site of the intravenous cannula for 30 s. The primary objective was to compare the overall incidence of pain after propofol injection. The secondary objectives included the incidence of discomfort on the application of an ice gel pack, comparison of dose of propofol needed for induction, and hemodynamic changes at induction, between the two groups. RESULTS: Fourteen patients in the lignocaine group and 15 patients in the thermotherapy group reported pain. The incidence of pain and the distribution of pain scores were comparable among groups (p = 1.00). Patients of the lignocaine group required significantly less amount of propofol for induction as compared to the thermotherapy group (p = 0.001). CONCLUSION: Topical thermotherapy using an ice gel pack was not found superior to lignocaine pre-treatment in alleviating pain on injection of propofol injection. However, topical cold therapy using an ice pack remains a non-pharmacological technique that is easily available, reproducible, and cost-effective. Further studies are required to prove its equivalence to lignocaine pre-treatment. TRIAL REGISTRATION: CTRI (CTRI/2021/04/032950).

Insulin syringe for anesthesia in ptosis surgery: a randomized, fellow eye-controlled clinical study.

PURPOSE: Unlike ordinary 30-gauge needles, insulin syringe needles are thinner and shorter and have a comparatively blunt tip. Therefore, insulin syringes may reduce injection discomfort, bleeding, and edema by minimizing tissue damage and vascular penetration. This study aimed to evaluate the potential benefits of using insulin syringes for local anesthesia in ptosis surgery. METHODS: This randomized, fellow eye-controlled study included 60 patients (120 eyelids), conducted at a university-based hospital. An insulin syringe was used on one eyelid, and a conventional 30-gauge needle was used on the other. Patients were instructed to score pain in both eyelids using a visual analog scale (VAS) ranging from 0 (no pain) to 10 (unbearable pain). Ten minutes after the injection, two observers scored degrees of hemorrhage and edema in both eyelids on five- and four-pointing grading scales (0-4 and 0-3) for each value, and the average score between the two observers was calculated and compared. RESULTS: The VAS score was 5.17 in the insulin syringe group and 5.35 in the 30-gauge needle group (p = 0.282). Ten minutes after the anesthesia, the median hemorrhage scores were 1.00 and 1.75 (p = 0.010), and the median eyelid edema scores were 1.25 and 2.00 (p = 0.007) in the insulin syringe and 30-gauge needle groups, respectively (Fig. 1). CONCLUSION: Injecting local anesthesia using an insulin syringe significantly reduces hemorrhage and eyelid edema, but not injection pain, before skin incision. Insulin syringes are useful in patients at high risk of bleeding because they can reduce the penetrative tissue damage caused by needle insertion.

Median Effective Dose of Remifentanil for the Prevention of Pain Caused by the Injection of Rocuronium: An Age-Stratified Study.

INTRODUCTION: Rocuronium intravenous pain is common in induction of general anesthesia. The aim of our study was to determine the median effective dose (ED50) of prophylactic intravenous remifentanil for the prevention of rocuronium injection pain and to explore the effect of age on the ED50. METHODS: Eighty-nine adult patients undergoing elective general anesthesia, ASA I or II, regardless of gender or weight, were stratified according to age: group R1 18-44 years, group R2 45-59 years, and group R3 60-80 years. The initial dose of prophylactic remifentanil before rocuronium injection was set at 1 µg/kg lean body weight (LBW). The remifentanil doses were adjusted according to the degree of injection pain using the Dixon sequential method, with a ratio of 1.1 between adjacent doses. Injection pain was graded, and the occurrence of injection pain and adverse reactions were recorded. The ED50 and 95% confidence intervals (CIs) of remifentanil were calculated using the Dixon-Massey formula. Patients were asked whether they recalled feeling any injection pain in the post-anesthesia care unit (PACU). RESULTS: The ED50 (95% CIs) of prophylactic remifentanil for the prevention of rocuronium injection pain were 1.266 µg/kg (1.186-1.351 µg/kg), 1.188 µg/kg (1.065-1.324 µg/kg), and 1.070 µg/kg (1.014-1.129 µg/kg) LBW in group R1, group R2, and group R3, respectively. No adverse reactions to remifentanil occurred in any group. In PACU, 84.6, 86.7, and 85.7% of patients who experienced injection pain had memories of the pain in group R1, group R2, and group R3, respectively. CONCLUSIONS: Prophylactic intravenous remifentanil can prevent rocuronium injection pain, and its ED50 decreases with age, with 1.266 µg/kg (18-44 years), 1.188 µg/kg (45-59 years), and 1.070 µg/kg LBW (60-80 years), respectively. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05217238 (registration date 18 Dec 2021).

Plasma Creatine Kinase and Aspartate Aminotransferase Activities Before, During, and After 5 Days of Intramuscular Penicillin Administration in Sedentary Horses.

Muscle damage can result in leakage of intracellular enzymes such as creatine kinase (CK) and aspartate transaminase (AST) into plasma. There are no controlled documentations of the effects of intramuscular antibiotic drug administration on plasma CK and AST activities in horses. The objective of this experiment was to test the hypothesis that 5 days of intramuscular procaine penicillin G injection in normal horses would result in increased plasma activities of CK and AST. Nine healthy adult horses were sampled for 7 days preceding, 5 days during, and 32 days following procaine penicillin G (22,000 IU/kg) administration intramuscularly twice daily. Heparinized jugular venous blood samples were obtained daily before treatment and were analyzed the same day for plasma activities of CK and AST. Repeated measures ANOVA and post hoc Tukey's Test were used to identify days where CK or AST were elevated compared to control means at a significance level of P < .05. Beginning the day after first injection, plasma CK increased above the reference range, peaking at 2,046 ± 627 U/L after 3 days, and returned to 227 ± 57.3 U/L (within the reference range) 9 days after treatment began. Beginning the day after first injection, plasma AST increased, peaking at 703 ± 135 U/L on the day after the last injection. Plasma AST did not return to the reference range in all individual horses until 29 days after the last injection (mean 247 ± 33 U/L). Compared to the control period, plasma CK and AST elevations lasted for 8 and 28 days, respectively, after the onset of treatment (P < .001 to P = .03) and lasted for 4 and 24 days, respectively, after the last day of treatment (P < .001 to P = .03).

Subcutaneous C.E.R.A. for the Maintenance Treatment of Anemia in Pediatric Patients With CKD: A Phase 2, Open-Label, Single-Arm, Multicenter Study.

RATIONALE & OBJECTIVE: The optimum starting dose of intravenous continuous erythropoietin receptor activator (C.E.R.A.) has been previously determined; this study ascertains the optimum starting dose of subcutaneous C.E.R.A. administration in pediatric patients. STUDY DESIGN: Phase 2, open-label, single-arm, multicenter study. SETTING & PARTICIPANTS: Patients aged 3 months to 17 years with renal anemia and chronic kidney disease (CKD; including those treated with maintenance dialysis and those not treated with dialysis) who were receiving maintenance treatment with erythropoiesis-stimulating agents (ESAs). INTERVENTION: Subcutaneous C.E.R.A. administration every 4 weeks (starting dose was based on defined conversion factors). OUTCOME: The primary outcome was the change in hemoglobin concentration between the baseline and evaluation period for each patient. Secondary efficacy measures and safety were also evaluated. RESULTS: Forty patients aged 0.4-17.7 years were enrolled. The study achieved its primary outcome: the mean change in hemoglobin concentration was an increase of 0.48g/dL; the 95% confidence interval (0.15-0.82) and standard deviation (±1.03) were within the prespecified boundaries (-1 to 1g/dL and<1.5g/dL, respectively). Mean hemoglobin concentrations were maintained within the target 10-12g/dL range in 24 of 38 patients and within±1g/dL of the baseline in 19 of 38 patients, and the median C.E.R.A. subcutaneous dose decreased over time. Efficacy in key subgroups (age group, dialysis type, prior ESA treatment) was consistent with the primary outcome. Thirty-eight patients completed the core period; 25 chose to enter the safety extension period. Safety was consistent with prior studies, with no new signals. LIMITATIONS: Single-arm and open-label study; small sample size. CONCLUSIONS: Pediatric patients with anemia secondary to CKD who were on, or not on, dialysis could be safely and effectively switched from maintenance ESAs to subcutaneous C.E.R.A. administered every 4 weeks, using defined dose-conversion factors to determine the optimum starting dose. FUNDING: F. Hoffmann-La Roche Ltd. TRIAL REGISTRATION: The SKIPPER trial registered at ClinicalTrials.gov with study number NCT03552393. PLAIN-LANGUAGE SUMMARY: Anemia, a complication of chronic kidney disease, is associated with poor quality of life and an increased risk of hospitalization and mortality. The current treatments for anemia include iron therapy and erythropoiesis-stimulating agents (ESAs); however, the relatively short half-lives of the ESAs epoetin alfa/beta or darbepoetin alfa may require more frequent dosing and hospital visits compared with the ESA known as continuous erythropoietin receptor activator (C.E.R.A.). A previous study demonstrated that children aged 5 years or more with anemia associated with chronic kidney disease who were on hemodialysis could be switched to intravenous C.E.R.A. from their existing epoetin alfa/beta or darbepoetin alfa treatment. This study provides evidence that subcutaneous C.E.R.A. can safely and effectively treat anemia in children, including those aged<5 years and regardless of whether they were on dialysis or the type of dialysis they received (peritoneal dialysis or hemodialysis).

Effect of a needle-free system versus traditional anesthesia on pain perception during palatal injections in children.

BACKGROUND: Needle-free injection systems can contribute to the prevention of needle-related pain during palatal infiltration anesthesia (PIA) in children. Research on this topic in children is required. AIM: The purpose of this clinical study was to evaluate the effectiveness and patient preference of a needle-free system versus traditional anesthesia (TA) on pain perception during PIA in children. DESIGN: The study was designed as a randomized, controlled crossover clinical study with 48 children aged 6-12 years requiring dental treatment with PIA in bilateral maxillary primary molars. TA was applied on one side and the Comfort-in™ injection system (CIS) on the other side in two separate sessions. Then, patient preference was recorded. The pain perception during PIA was evaluated using the Wong-Baker FACES Pain Rating Scale (PRS) and the Face, Legs, Activity, Cry, Consolability (FLACC) Scale. The data were analyzed for statistical significance (p < .05). RESULTS: There were statistically significant differences between the TA and the CIS according to the PRS and FLACC Scale scores. On both scales, significantly higher pain ratings were observed in the TA group during PIA (p < .001). There was a statistically significant difference in terms of patient preference (p < .001). Although 77.1% (n = 37) of the children preferred the CIS, 22.9% (n = 11) preferred the TA. Moreover, patient preference for the CIS was significantly higher in older children (p < .01). CONCLUSIONS: The application of a needle-free system during PIA ensured a decrease in pain perception in children.

Comparison of effects of different anticoagulants on the release of growth factor and injection pain of platelet-rich plasma in SD rats / 中国输血杂志

【Objective】 To investigate the effects of different anticoagulants on platelet-rich plasma(PRP) release content of growth factor and injection pain. 【Methods】 A total of 15 voluntary blood donors were selected, with each blood donor using four kinds of anticoagulant tubes with EDTA-K2 anticoagulation, EDTA-NA2 anticoagulation, citrate anticoagulation, ACD-A anticoagulation respectively as group A, B, C and D. PRP was isolated and prepared by the rich plasma method, and the contents of PDGF-AA, TGF-β, IGF-1, VEGF, and PF-4 were detected by enzyme-linked immunosorbent assay. Meanwhile, SD rats (20, 4 / group) were injected subcutaneously or intradermally with the supernatant of PRP and PG gel prepared in the 4 groups and normal saline in the control group. The pain status of SD rats during the injection was observed and recorded. The pain status of the 5 groups of experimental animals was evaluated according to the American Laboratory Animal Pain Guide. 【Results】 The platelet counts in PRP in group D was the highest [(1 294.53±277.37) × 109/L], which was significantly higher than that in group A [ (789.13±377.13) ×109/L] and group C [ (990.94±493.12) ×109/L] (P<0.05). The OD value of PDGF-AA in group A, B, C, and D were 1.51± 0.18, 1.69±0.21, 0.66±0.19and 1.72±0.13, respectively, with statistically significant difference between groups (P<0.05 ) and group D better than the other three groups. The OD value of PF-4 was 1.18±0.24, 1.61±0.14, 0.65±0.26 and 1.72±0.10 respectively, with statistically significant difference between groups (P<0.05) and group D better than other three groups. The OD value of IGF-1 was 1.02±0.08, 0.98±0.11, 1.06±0.11 and 1.32±0.65 respectively, with no significant difference between groups (P>0.05). The OD value of VEGF was 0.13±0.04, 0.21±0.14, 0.08±0.02 and 0.13±0.04 respectively, with statistically significant difference between group B and C (P<0.05). The OD value of TGF-β was 0.14±0.01, 0.15±0.01, 0.28±0.17 and 1.10±0.37 respectively, with statistically significant difference between groups (P<0.05) and group D better than other three groups. Comparison of injection pain: when the supernatant of PRP and PG gel was injected, there were significant differences between group A, B, C and D, and the control group (P<0.05) . The median pain scores of PRP injection of group A, B, C, and D were 6 (1.5), 5 (0.75), 4.5 (2.5), and 3(3) respectively, with group D lower than other three groups, and no statistically significant difference was noticed (P>0.05) . The median pain scores of the PG supernatant injection of group A, B, C, and D were 4 (2.25), 3 (2.75), 4 (3), 1 (1.5), and the difference was not statistically significant (P>0.05). There was no significant difference between the PRP injection group and the PG supernatant group (P> 0.05). 【Conclusion】 PRP prepared by two-step centrifugation with ACD-A anticoagulant can obtain the higher platelet counts and the maximum release of PDGF-AA, PF-4, IGF-1, and TGF-β. In terms of pain, ACD-A anticoagulant injection has the lowest pain with the animals.

Determining the effective dose of esketamine for mitigating pain during propofol injection by Dixon's up-and-down method: a double-blind, prospective clinical study of drug dose response.

BACKGROUND: Propofol is an intravenous (IV) anesthetic medication widely used for procedural sedation, operative anesthesia, and in intensive care unit (ICU), but the incidence of pain during IV infusion can reach 28-90%. Ketamine can attenuate pain associated with IV propofol injection through local and central analgesic effects. Ketamine is gradually being transitioned to its S-enantiomer, esketamine, which has a similar mechanism of action. The purpose of our study is to determine the half effective dose (ED50), 95% effective dose (ED95), and 99% effective dose (ED99) of esketamine for attenuating propofol injection pain using Dixon's up-and-down method to provide a reference for optimal dose selection for surgeries and procedures. METHODS: Thirty gynecological patients undergoing hysteroscopic surgery were enrolled in a sequential method to determine the effective dose of esticketamine for analgesic propofol injection in order of operation. This study was based on the sequential allocation up-and-down rule designed by Dixon, and each patient was induced by esticketamine combined with propofol. During induction, the target dose of esketamine was first given via venous access in the left hand of the patient, and 30 s later, a fixed dose of 2 mg/kg (1 ml/s) of propofol was given. Patient perception of pain was scored with the verbal rating scale (VRS) every 5 s after the start of the propofol infusion, and the evaluation was stopped once the patient became unresponsive. The dosage of esketamine was increased or decreased up or down according to the patient's pain response. The initial dose of esketamine was 0.2 mg/kg, and the gradient of adjacent dose was 0.02 mg/kg. If the pain response assessment of the upper patient was positive (+), the dose of esselketamine in the next patient was increased by 0.02 mg/kg; if the pain response assessment of the upper patient was negative (-), the dose of esselketamine in the next patient was decreased by 0.02 mg/kg. The tests were carried out sequentially, with the pain response changing from positive to negative or from negative to positive, and the tests were stopped after at least 6 crossover points, and the effective dose of esticketamine was calculated using probit probability regression analysis. RESULTS: The ineffective group comprised patients with a positive pain response and the effective group comprised patients with a negative pain response. The 95% CI was set as the confidence interval of effective dose ED value，and we found esketamine's ED50 = 0.143 mg/kg (0.120, 0.162 mg/kg), ED95 = 0.176 mg/kg (0.159, 0.320 mg/kg), and ED99 = 0.189 mg/kg (0.167, 0.394 mg/kg). The esketamine dose and VRS score during propofol injection were significantly different between the two groups (P < 0.05), whereas surgical duration, emergence time, visual analogue scale (VAS) score of postoperative uterine contraction pain, and Riker sedation/anxiety scale (SAS) score were not significantly different. Bradycardia occurred in only one patient during anesthesia induction, while hemodynamics was stable in the rest of the patients without obvious adverse reactions. CONCLUSION: Small doses of esketamine combined with propofol can be safely and effectively used for hysteroscopic surgery. We recommended a dose of 0.2 mg/kg IV esketamine before induction of anesthesia to reduce the pain of propofol injection. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100048951. Date of registration: July 19, 2021.

Esketamine prevents propofol-induced injection pain: Randomized controlled trial.

Background: Propofol is widely used during anesthesia. However, propofol-induced injection pain (PIP) is considered an unpleasant perioperative outcome. This study aimed to investigate the efficacy of a mixture of esketamine and propofol in preventing propofol injection pain in patients undergoing general anesthesia. Methods: This was a prospective, double-blind, multicenter, and randomized controlled trial. We included 252 adult patients with the American Society of Anesthesiologists physical status I to II who underwent surgery under general anesthesia. Patients were randomly allocated in a 1:1:1:1 ratio to four groups (n = 63 per group). Group NS received a mixture of 1% propofol (20 ml) and 0.9% normal saline (1 ml), group ESK-4 received a mixture of 1% propofol (20 ml) and esketamine 4 mg (diluted with 0.9% normal saline, 1 ml), group ESK-12 received a mixture of 1% propofol (20 ml) and esketamine 12 mg (diluted with 0.9% normal saline, 1 ml), and group ESK-20 received a mixture of 1% propofol (20 ml) and esketamine 20 mg (diluted with 0.9% normal saline, 1 ml) as sedative drugs during anesthesia. The primary outcome was the incidence and distribution of different degrees of PIP. The secondary outcomes were vital signs, characteristics of surgery and anesthesia, and adverse events. Results: The incidence of PIP in group ESK-20 (33.3%) was significantly lower than that in groups NS, ESK-4, and ESK-12 (63.3%, 62.2%, and 49.1%, respectively; p < 0.01). The incidence of moderate PIP in group NS (33.3%) and group ESK-4 (22.6%) was higher than that in groups ESK-12 (7.5%) and ESK-20 (6.7%). The incidence of severe PIP in group NS (6.7%) and group ESK-4 (9.4%) was higher than that in groups ESK-12 (1.9%) and ESK-20 (0%). There were no differences in the vital signs, characteristics of surgery and anesthesia, or adverse events between the groups. Conclusion: Our results indicated that the esketamine-propofol admixture reduced the incidence of PIP in patients undergoing general anesthesia without severe side effects.

New insight into the importance of formulation variables on parenteral growth hormone preparations: potential effect on the injection-site pain.

Reducing injection-site pain (ISP) in patients with chronic conditions such as growth hormone deficiency is a valuable strategy to improve patient compliance and therapeutic efficiency. Thus understanding different aspects of pain induction following subcutaneous injection of biotherapeutics and identifying the responsible factors are vital. Here we have discussed the effects of formulation's viscosity, concentration, osmolality, buffering agents, pH, and temperature as well as injection volume, dosing frequency, and different excipients on ISP following subcutaneous injection of commercially available recombinant human growth hormone products. Our literature review found limited available data on the effects of different components of parenteral rhGH products on ISP. This may be due to high cost associated with conducting various clinical trials to assess each excipient in the formulation or to determine the complex interactions of different components and its impact on ISP. Recently, conducting molecular dynamics simulation studies before formulation design has been recommended as an alternative and less-expensive approach. On the other hand, the observed inconsistencies in the available data is mainly due to different pain measurement approaches used in each study. Moreover, it is difficult to translate data obtained from animal studies to human subjects. Despite all these limitations, our investigation showed that components of parenteral rhGH products can significantly contribute to ISP. We suggest further investigation is required for development of long acting, buffer-free, preservative-free formulations. Besides, various excipients are currently being investigated for reducing ISP which can be used as alternatives for common buffers, surfactants or preservatives in designing future rhGH formulations.

Efficacy and safety of remimazolam besylate in bronchoscopy for adults: A multicenter, randomized, double-blind, positive-controlled clinical study.

Background: With the development of fiberoptic bronchoscopy in the diagnosis and treatment of various pulmonary diseases, the anesthesia/sedation requirements are becoming more demanding, posing great challenges for patient safety while ensuring a smooth examination/surgery process. Remimazolam, a brand-new ultra-short-acting anesthetic, may compensate for the shortcomings of current anesthetic/sedation strategies in bronchoscopy. Methods: This study was a prospective, multicenter, randomized, double-blind, parallel positive controlled phase 3 clinical trial. Subjects were randomized to receive 0.2 mg/kg remimazolam besylate or 2 mg/kg propofol during bronchoscopy to evaluate the efficacy and safety of remimazolam. Results: A total of 154 subjects were successfully sedated in both the remimazolam group and the propofol group, with a success rate of 99.4% (95%CI of the adjusted difference -6.7 × 10%-6% to -5.1 × 10%-6%). The sedative effect of remimazolam was noninferior to that of propofol based on the prespecified noninferiority margin of -5%. Compared with the propofol group, the time of loss of consciousness in the remimazolam group (median 61 vs. 48s, p < 0.001), the time from the end of study drug administration to complete awakening (median 17.60 vs. 12.80 min, p < 0.001), the time from the end of bronchoscopy to complete awakening (median 11.00 vs. 7.00 min, p < 0.001), the time from the end of study drug administration to removal of monitoring (median 19.50 vs. 14.50 min, p < 0.001), and the time from the end of bronchoscopy to removal of monitoring (median 12.70 vs. 8.60 min, p < 0.001) were slightly longer. The incidence of Adverse Events in the remimazolam group and the propofol group (74.8% vs. 77.4%, p = 0.59) was not statistically significant, and none of them had Serious Adverse Events. The incidence of hypotension (13.5% vs. 29.7%, p < 0.001), hypotension requiring treatment (1.9% vs. 7.7%, p = 0.017), and injection pain (0.6% vs. 16.8%, p < 0.001) were significantly lower in the remimazolam group than in the propofol group. Conclusion: Moderate sedation with 0.2 mg/kg remimazolam besylate is effective and safe during bronchoscopy. The incidence of hypotension and injection pain was less than with propofol, but the time to loss of consciousness and recovery were slightly longer. Clinical Trial Registration: clinicaltrials.gov, ChiCTR2000039753.

Patient Comfort with Various Local Infiltration Anesthetics for Minor Oculoplastic Surgery: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Although local anesthetics have been extensively studied, limited evidence is available regarding the optimal solution for maximizing patient comfort in minor oculoplastic procedures. OBJECTIVES: To determine the optimal anesthetic solution for local infiltration in minor oculoplastic surgeries to maximize patient comfort. METHODS: This systematic review with network meta-analysis of prospective studies was conducted to understand the efficacy of different local anesthetics in combination to maximize patient comfort. The study was designed according to the Cochrane Handbook for Systematic Reviews of Interventions. The population comprised patients receiving local infiltration anesthesia in minor oculoplastic surgeries. Various anesthetics with adjuvants were compared with respect to injection pain, operative bleeding, and complications. Random-effects model was performed. The primary outcome of injection pain was measured using the visual analog scale (VAS) or a preference question (which intervention was the least painful). Other outcomes were operative bleeding and complications, which were evaluated with a similar preference question. RESULTS: Eleven randomized controlled trials (RCTs) of 521 patients (917 eyes) were included. The network meta-analysis revealed that "bicarbonate-buffered lidocaine with epinephrine" led to a significant decrease in injection pain (preference question) compared to "prilocaine with felypressin" and "lidocaine with epinephrine," whereas no significant differences were detected in the analysis of injection pain measured using the VAS. CONCLUSIONS: "Bicarbonate-buffered lidocaine with epinephrine" may be the optimal anesthetic solution for local infiltration in minor oculoplastic surgeries due to reduced injection pain, operative bleeding, and postoperative swelling. However, this should be interpreted cautiously as the confidence in the evidence was very low. THE CLINICAL TRIAL REGISTRATION NUMBER: CRD42021260332 (PROSPERO).

Comparison of Maxillary Lateral Incisor Infiltration Pain Using the Dentapen and a Traditional Syringe: A Prospective Randomized Study.

INTRODUCTION: The anterior maxillary infiltration is one of the more painful dental injections. The Dentapen is an electronic syringe that uses computer-controlled delivery technology to administer dental local anesthesia at a slow controlled rate. The purpose of this prospective, randomized, single-blind study was to evaluate solution deposition pain of a maxillary lateral incisor infiltration using the Dentapen with the slow flow rate (1.8 mL/162 sec) and ramp-up setting compared with a traditional syringe infiltration at a flow rate of 1.8 mL/60 sec. METHODS: One hundred thirty adults were administered a maxillary lateral incisor infiltration with the Dentapen and a traditional syringe at 2 separate appointments in a single-blind manner. The infiltrations of 2% lidocaine with 1:100,000 epinephrine were given at a rate of 1.8 mL/162 sec with the ramp-up feature for the Dentapen and 1.8 mL/60 sec for the traditional infiltration. The pain of solution deposition was recorded on a visual analogue scale. At the conclusion of the study, subjects selected their preferred injection technique. The data were analyzed statistically using paired t tests, a mixed-effect model, and odds ratio. RESULTS: The pain of solution deposition was significantly less for the Dentapen injection than the traditional injection (P < .001). With the Dentapen device, 16% experienced moderate pain, and for the traditional syringe, 39% experienced moderate pain. Overall, 75% of subjects preferred the Dentapen injection over the traditional injection. CONCLUSIONS: The Dentapen, using the slow flow rate and ramp-up mode, significantly reduced the pain of solution deposition for maxillary lateral incisor infiltrations.

A comparison of ondansetron and lidocaine in reducing injection pain of propofol: a randomized controlled study.

BACKGROUND: Direct stimulation of the afferent nerve endings in the venous endothelium is one explanation of propofol injection pain. Previous studies found that ondansetron can also block sodium channels. This effect is similar to that of lidocaine. OBJECTIVE: The primary outcome was the efficacy of ondansetron compared to lidocaine and placebo for the reduction of propofol injection pain. METHOD: This trial was conducted in 240 patients, American Society of Anesthesiologists classification I-III and aged between 18-65 years old, undergoing elective surgery, and having a 20-gauge intravenous catheter at the hand dorsum. Each group of 80 patients received 8 mg. of ondansetron in the O Group, 40 mg. of lidocaine in the L Group and normal saline in the C Group. The study medications were blindly administered to the patients through a 20-gauge intravenous catheter placed on the hand dorsum, and then 1 min later, the small dose of propofol (50 mg.) was infused via the syringe pump at a rate of 600 ml/hr. for 30 s. Following that, the syringe pump of propofol was temporarily stopped, and the patients were asked to rate their pain at the injection site. RESULT: The incidence of pain was lowest in the L group (66.2%) compared with the O (82.5%) and the C groups (85.0%) (P < 0.01). The median pain score in the L, O, and C groups were 2 (0-4), 4 (2-5), and 4.5 (2-6), respectively (P < 0.01). The incidences of no pain, mild, moderate, and severe pain were also significantly different in the L group (33.8%, 37.5%, 21.2%, and 7.5%, respectively) compared with those in the O group (17.5%, 31.2%, 31.2%, and 20.0%, respectively) and the C groups (15.0%, 22.5%, 40.0%, and 22.5%, respectively) (P < 0.01). CONCLUSION: Pretreatment with intravenous lidocaine, rather than ondansetron, can reduce the incidence and intensity of propofol-induced pain.