Application of propofol-remifentanil intravenous general anesthesia combined with regional block in pediatric ophthalmic surgery.

OBJECTIVE: The aim of this study is to observe the anesthetic effect and safety of intravenous anesthesia without muscle relaxant with propofol-remifentanil combined with regional block under laryngeal mask airway in pediatric ophthalmologic surgery. METHODS: A total of 90 undergoing ophthalmic surgery were anesthetized with general anesthesia using the laryngeal mask airway without muscle relaxant. They were randomly divided into two groups: 45 children who received propofol-remifentanil intravenous anesthesia combined with regional block (LG group), and 45 children who received total intravenous anesthesia (G group). The peri-operative circulatory indicators, awakening time after general anesthesia, postoperative analgesic effect and the incidence of anesthesia-related adverse events were respectively compared between the two groups. RESULTS: All the children successfully underwent the surgical procedure. The awakening time after general anesthesia and removal time of laryngeal mask were significantly shorter in the LG group than in the G group (P < 0.05). There was no statistically significant difference in the heart rates in the perioperative period between the two groups (P > 0.05). There was no statistically significant difference in the incidence of intraoperative physical response, respiratory depression, postoperative nausea and vomiting (PONV) and emergence agitation (EA) between the two groups (P > 0.05). The pain score at the postoperative hour 2 was lower in the LG group than in the G group (P < 0.05). CONCLUSION: Propofol-remifentanil intravenous anesthesia combined with long-acting local anesthetic regional block anesthesia, combined with laryngeal mask ventilation technology without muscle relaxants, can be safely used in pediatric eye surgery to achieve rapid and smooth recovery from general anesthesia and better postoperative analgesia. This anesthesia scheme can improve the comfort and safety of children in perioperative period, and has a certain clinical popularization value.

The comparison of the effect of non-pharmacological pain relief and pharmacological analgesia with remifentanil on fear of childbirth and postpartum depression: a randomized controlled clinical trial.

INTRODUCTION: Childbirth may be associated with psychological, social, and emotional effects and provide the background for women's health or illness throughout their life. This research aimed at comparing the impact of non-pharmacological pain relief and pharmacological analgesia with remifentanil on childbirth fear and postpartum depression. MATERIALS AND METHOD: This randomized clinical trial with two parallel arms was conducted on 66 women with term pregnancy referred to Taleghani Hospital in Tabriz for vaginal delivery during September 2022 to September 2023. First, all of the eligible participants were selected through Convenience Sampling. Then, they were randomly assigned into two groups of pharmacological analgesia with remifentanil and non-pharmacological analgesia with a ratio of 1:1 using stratified block randomization based on the number of births. Before the intervention, fear of childbirth (FOC) was measured using Delivery Fear Scale (DFS) between 4 and 6 cm cervical dilatation. Pain and fear during labor in dilatation of 8 cm were measured in both groups using VAS and DFS. After delivery, FOC was assessed using Delivery Fear Scale (W DEQ Version B) and postpartum depression using the Edinburgh's postpartum depression scale (EPDS). Significance level was considered 0.05. Mean difference (MD) was compared with Independent T-test and ANCOVA pre and post intervention. RESULTS: The mean score of FOC in the non-pharmacological analgesia group was significantly lower than that in the pharmacological analgesia group after the intervention by controlling the effect of the baseline score (MD: -6.33, 95%, Confidence Interval (CI): -12.79 to -0.12, p = 0.04). In the postpartum period, the mean score of FOC in the non-pharmacological analgesia group was significantly lower than that in the pharmacological analgesia group after controlling the effect of the baseline score (MD: -21.89; 95% CI: -35.12 to -8.66; p = 0.002). The mean score of postpartum depression in the non-pharmacological analgesia group was significantly lower than that in the pharmacological analgesia group (MD: -1.93, 95% CI: -3.48 to -0.37, p = 0.01). TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT): IRCT20170506033834N10. Date of registration: 05/07/2022 Date of first registration: 05/07/2022. URL: https://www.irct.ir/trial/61030; Date of recruitment start date05/07/2022. CONCLUSION: The study results indicated a reduction in FOC and postpartum depression among parturient women receiving non-pharmacological strategies with active participation in childbirth compared to women receiving pharmacological analgesia. Owing to the possible side effects of pharmacological methods for mother and fetus, non-pharmacological strategies with active participation of the mother in childbirth are recommended to reduce the FOC and postpartum depression.

Neonatal Outcomes in Labor After Intravenous Remifentanil Analgesia vs. Epidural Analgesia: A Retrospective Observational Study.

Background Some evidence indicates that maternal analgesia during labor may have adverse effects on neonates due to exposure to specific drugs or the potential effects of analgesia on the course of labor. We assessed the clinical outcome of term neonates born to mothers who received epidural analgesia (E) or systemic analgesia with remifentanil (R) during labor. Methods Data was collected retrospectively over one year. We have evaluated the medical records of 247 full-term neonates; 208 were born to mothers who received E and 39 to mothers who received R. Data on Apgar scores and neonatal complications (perinatal asphyxia, respiratory distress, infection, hyperbilirubinemia, and birth injuries), and average hospital stay were collected. Mann-Whitney U test, chi-square test, and logistic regression analysis were used where appropriate. Results The values of the mean Apgar scores between E and R at 1 and 5 minutes were similar (8.83 vs. 8.97, p = 0.252; 9.81 vs. 9.87, p = 0.762, respectively). The average length of neonatal hospitalization did not differ between groups (4.19 vs. 4; p = 0.557). The percentages of neonates with any complication were similar between groups (28.3% vs. 32.5%, p = 0.598). Neonates born by cesarean delivery (CD) had significantly worse outcomes than those born vaginally (p = 0.008, OR 2.8, 95% CI [1.30, 6.17]). Conclusion We did not find a statistically significant difference in mean Apgar scores and neonatal complications between neonates who received epidural vs. remifentanil analgesia. An increased rate of complications in neonates born via CD was found. Future studies should have a larger sample size and be powered to detect associations in these findings.

Ciprofol alleviates remifentanil-induced hyperalgesia by regulating α2GABAARs, NR2B, and P-CaMKIIα levels in the spinal cord and hippocampus.

OBJECTIVES: Several studies have shown that propofol administration during surgery effectively attenuates remifentanil-induced hyperalgesia (RIH). Ciprofol, a novel intravenous sedative agent analogous to propofol, has not yet been proven efficacious in alleviating RIH. The present study aimed to investigate the effect of ciprofol on RIH and the possible mechanisms involved. METHODS: The RIH model was established by an infusion of remifentanil (1 µg·kg-1·min-1) 60 min in rats with incisional pain. Ciprofol (0.1, 0.25, and 0.4 mg·kg-1·min-1) was simultaneously infused to evaluate its effect on RIH. The antinociception of ciprofol was verified by measured paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL). γ-aminobutyric acid type A receptor α2 subunit (α2GABAAR), N-methyl-d-aspartate receptor NR2B subunit (NR2B), calcium/calmodulin-dependent protein kinase II α (CaMKIIα), and phosphorylated CaMKIIα (P-CaMKIIα) in the spinal cord and hippocampus of rats were assessed by western blotting and immunohistochemistry. KEY FINDINGS: The results showed that ciprofol dose-dependently increased PWMT and PWTL values in RIH rats. Moreover, ciprofol upregulated α2GABAAR and downregulated NR2B and P-CaMKIIα in the rat spinal cord and hippocampus. CONCLUSIONS: Ciprofol alleviates RIH effectively, and the anti-hyperalgesic mechanisms may involve increasing α2GABAAR levels and decreasing NR2B and P-CaMKIIα levels in the spinal cord and hippocampus.

Reversal of Opioid-Induced Respiratory Depression in Healthy Volunteers: Comparison of Intranasal Nalmefene and Intranasal Naloxone.

An open-label, randomized, crossover study in healthy volunteers compared the reversal of remifentanil-induced respiratory depression by intranasal (IN) naloxone hydrochloride (4 mg) to IN nalmefene (2.7 mg) (NCT04828005). Subjects were administered a hypercapnic gas mixture which produces an elevation in minute ventilation (MV), a result of the ventilatory response to hypercapnia. Subjects breathed a hypercapnic gas mixture through a tight-fitting mask for an initial period of 46 min prior to a series of mask "holidays" introduced to reduce subject discomfort and encourage study completion. Ten minutes after initiating the hypercapnic gas mixture, a remifentanil bolus was administered, and an infusion continued for the study duration. Subjects were administered either naloxone or nalmefene 15 min after initiating the remifentanil infusion and MV monitored for 21 min followed by a mask holiday. Both nalmefene and naloxone produced a time-dependent reversal of remifentanil-induced reductions in MV measured 2.5-20 min post administration. At the primary endpoint (5 min post administration), nalmefene increases in MV (5.75 L/min) were nearly twice that produced by naloxone (3.01 L/min) (P < .0009); the point estimate favors nalmefene, demonstrating non-inferiority and superiority. In this model of opioid-induced respiratory depression, nalmefene has a more rapid onset of action than naloxone, which required 20 min to achieve a comparable reversal of respiratory depression. Both nalmefene and naloxone were well tolerated by healthy volunteers. This rapid onset of action may prove particularly valuable in an era when over 90% of fatalities are linked to synthetic opioid overdose.

Puerarin attenuates remifentanil­induced postoperative hyperalgesia via targeting PAX6 to regulate the transcription of TRPV1.

Remifentanil­induced hyperalgesia (RIH) is characterized by the emergence of stimulation­induced pain, including phenomena such as allodynia and thermal hyperalgesia following remifentanil infusion. As a sequence­specific DNA binding transcription factor, PAX6 positively and negatively regulates transcription and is expressed in multiple cell types in the developing and adult central nervous system. It was hypothesized that puerarin could relieve RIH via targeting PAX6 to regulate transcription of transient receptor potential cation channel subfamily V Member 1 (TRPV1). A total of 32 rats were randomly divided into five groups, namely control group, RI group, RI + 10 mg/kg puerarin group (RI + puerarin10), RI + 20 mg/kg puerarin group (RI + puerarin20), and RI + 40 mg/kg puerarin group (RI + puerarin40). Mechanical and thermal hyperalgesia were tested at ­24, 2, 6, 24 and 48 h after remifentanil infusion. Following the sacrifice of rats after the last behavioral test, western blot was used to detect the expression levels of TRPV1 in the tissues; Immunofluorescence staining and western blotting were used to detect the expression of PAX6 in the spinal cord. PharmMapper and JASPAR were used to predict the binding sites of puerarin/PAX6/TRPV1. Chromatin immunoprecipitation­PCR and dual luciferase reporter assay were used to verify the targeting relationship between PAX6 and TRPV1. Immunofluorescence was used to detect the expression levels of TRPV1 and p­NR2B. The results revealed that puerarin (10, 20, 40 mg/kg) dose­dependently reduced thermal and mechanical hyperalgesia from 2 to 48 h after remifentanil infusion. Remifentanil infusion remarkably stimulated the expression of phosphorylated (p­)NR2B. Nevertheless, the increased amount of p­NR2B by RIH was dose­dependently suppressed by puerarin in rats. In conclusion, puerarin was revealed to attenuate postoperative RIH via targeting PAX6 to regulate the transcription of TRPV1.

Safety and efficacy of remifentanil target-controlled infusion for conscious sedation in a pregnant woman: a case report.

BACKGROUND: Every year 2% of pregnant women undergo nonobstetric surgical interventions worldwide. According to the American College of Obstetricians and Gynecologists Committee on Obstetric Practice, pregnant women should never be denied the most appropriate surgical treatment, regardless of the trimester of pregnancy. However, additional attention should be paid during the first trimester since it has the highest risk of inducing teratogenic mutations; additionally, during the third trimester, due to the possibility of preterm birth and low birth weight of the newborn, great care should be paid. CASE PRESENTATION: We present the case of a Caucasian 36-year-old woman during her 21st week of pregnancy, with a normal-sized fetus, according to the gestational age on ultrasound exam, and with no additional risk factors. The patient referred to an increasing nasal obstruction associated with rhinorrhea of the left nasal cavity. She also reported episodes of sleep apnea and hyposmia. The patient received a detailed otolaryngological examination, which allowed for identification of a mass within the left nasal cavity. The subsequent nasal endoscopy confirmed a grayish polypoid mass lesion with a multinodular surface occupying the entire left nasal fossa. The lesion totally obliterated the left maxillary sinus, resulting in obstruction of the anterior osteomeatal unit and ethmoidal sinusitis. She was referred for a functional endoscopic sinus surgery using analgosedation with remifentanil target-controlled infusion. DISCUSSION AND CONCLUSION: To the very best of our knowledge, this is the first case described in English literature about the use of analgosedation with remifentanil target-controlled infusion for otolaryngology surgery, specifically in functional endoscopic sinus surgery. It could be an interesting option to avoid the use of inhaled anesthetics that could induce fetal damage, especially during the first months of pregnancy. Furthermore, patient intubation is not necessary, which avoids cases of difficult intubation or any trauma to the airways. An adequate informed consent and appropriate compliance are elements of paramount importance in tailoring the anesthetic strategy for pregnant women who need nonobstetric surgical management.

The effect of dexmedetomidine, remifentanil and metoral in reducing patient bleeding during rhinoplasty surgery.

INTRODUCTION: Rhinoplasty is one of the most common surgeries in the ENT department. Rhinoplasty hemorrhage is one of the complications that different strategies have been used to reduce it. Reduction of bleeding reduces the risk of complications such as hemolytic and non-hemolytic reactions, acute lung damage, viral and bacterial infections, hypothermia and coagulation disorders. Therefore, the aim of this study was to compare the effect of dexmedetomidine, remifentanil and metoral in reducing patient bleeding during rhinoplasty surgery. MATERIALS AND METHODS: This randomized, double-blind trial was performed on rhinoplasty patients. Rhinoplasty candidates who had the inclusion and exclusion criteria were divided into three groups of remifentanil, metoral and dexmedetomidine according to the random number table. Then 0.5 mg/kg/h of dexmedetomidine in the first group was administered, followed by 100-150 kg/h remifentanil in the second group and 50 mg metoral in the third group. Mean blood pressure, heart rate, mean bleeding and surgeon satisfaction were recorded in designed form. Data were analyzed by Spss-22 software. RESULTS: The mean blood pressure of patients in remifentanil group was lower than the other two groups (P = 0.03). In all three times during surgery, recovery and overall time, the amount of bleeding in the remifentanil group was found to be less than the other two groups. Furthermore, the rate of bleeding in the dexmedetomidine group was found to be less than the metoral group (P = 0.03, P = 0.02). The surgeon's satisfaction score in the remifentanil group was higher than the other two groups. Satisfaction score was higher in dexmedetomidine group than metoral group (P = 0.03). The recovery time in the metoral group was shorter than the other two groups (P = 0.02). CONCLUSION: Remifentanil caused a good and appropriate reduction of blood pressure in rhinoplasty surgery, causing less bleeding and higher satisfaction.

Effect of opioid-free versus opioid-based strategies during multimodal anaesthesia on postoperative morphine consumption after bariatric surgery: a randomised double-blind clinical trial.

Background: The efficacy and safety of opioid-free anaesthesia during bariatric surgery remain debated, particularly when administering multimodal analgesia. As multimodal analgesia has become the standard of care in many centres, we aimed to determine if such a strategy coupled with either dexmedetomidine (opioid-free anaesthesia) or remifentanil with a morphine transition (opioid-based anaesthesia), would reduce postoperative morphine requirements and opioid-related adverse events. Methods: In this prospective double-blind study, 172 class III obese patients having laparoscopic gastric bypass surgery were randomly allocated to receive either sevoflurane-dexmedetomidine anaesthesia with a continuous infusion of lidocaine and ketamine (opioid-free group) or sevoflurane-remifentanil anaesthesia with a morphine transition (opioid-based group). Both groups received at anaesthesia induction a bolus of magnesium, lidocaine, ketamine, paracetamol, diclofenac, and dexamethasone. The primary outcome was 24-h postoperative morphine consumption. Secondary outcomes included postoperative quality of recovery (QoR40), incidence of hypoxaemia, bradycardia, and postoperative nausea and vomiting (PONV). Results: Eighty-six patients were recruited in each group (predominantly women, 70% had obstructive sleep apnoea). There was no significant difference in postoperative morphine consumption (median [inter-quartile range]: 16 [13-26] vs 15 [10-24] mg, P=0.183). The QoR40 up to postoperative day 30 did not differ between groups, but PONV was less frequent in the opioid-free group (37% vs 59%, P=0.005). Hypoxaemia and bradycardia were not different between groups. Conclusions: During bariatric surgery, a multimodal opioid-free anaesthesia technique did not decrease postoperative morphine consumption when compared with a multimodal opioid-based strategy. Quality of recovery did not differ between groups although the incidence of PONV was less in the opioid-free group. Clinical trial registration: NCT05004519.

Effects of Remifentanil Gradual Withdrawal Combined with Postoperative Infusion on Postoperative Hyperalgesia in Patients Undergoing Laparoscopic hysterectomy: A Factorial Design, Double-Blind, Randomized Controlled Trial.

Background: Remifentanil-induced hyperalgesia (RIH) increases the risk of persistent postoperative pain, making early postoperative analgesic therapy ineffective and affecting postoperative patient satisfaction. This study aimed to verify the effects of gradual withdrawal of remifentanil combined with postoperative pump infusion of remifentanil on postoperative hyperalgesia and pain in patients undergoing laparoscopic hysterectomy. Methods: This trial was a factorial design, double-blind, randomized controlled trial. Patients undergoing laparoscopic hysterectomy were randomly allocated to the control group, postoperative pump infusion of remifentanil group, gradual withdrawal of remifentanil group, or gradual withdrawal plus postoperative pump infusion of remifentanil group (n = 35 each). The primary outcome was postoperative mechanical pain thresholds in the medial forearm. The secondary outcomes included postoperative mechanical pain thresholds around the incision, pain numeric rating scale scores, analgesic utilization, awakening agitation or sedation scores, a 15-item quality of recovery survey, and postoperative complications. Results: Gradual withdrawal of remifentanil significantly increased postoperative pain thresholds versus abrupt discontinuation (P < 0.05), whereas postoperative infusion did not show significant differences compared to the absence of infusion (P > 0.05). The combined gradual withdrawal and postoperative infusion group exhibited the highest thresholds and had the lowest postoperative pain scores and analgesic requirements as well as the highest quality of recovery scores (P < 0.05). No significant differences were observed for agitation scores, sedation scores, or complication rates (P > 0.05). Conclusion: The novel combined gradual withdrawal and postoperative infusion of remifentanil uniquely attenuates postoperative hyperalgesia, pain severity, analgesic necessity, and improves recovery quality after laparoscopic hysterectomy.

Postoperative pain at Landspitali: A prospective study.

BACKGROUND: Moderate or severe postoperative pain is common despite advances in surgical technique and perioperative analgesia. This study aimed to assess the prevalence and severity of postoperative pain following procedures requiring anaesthesia and identify factors associated with increased risk of postoperative pain. METHODS: Surgical patients ≥18 years of age were prospectively questioned on level of current pain on a numerical rating scale (NRS) from 0 to 10 in the post-anaesthesia care unit (PACU) and on resting, active and worst pain experienced in the first 24 h postoperatively. Clinical data was obtained from medical records. Descriptive statistics were applied, and predictors of worst pain assessed as moderate/severe (NRS ≥ $$ \ge $$ 5) on postoperative day one were assessed using multivariable logistic regression. RESULTS: Of 438 included participants, moderate/severe pain occurred in 29% on the day of surgery and 70% described their worst pain as moderate/severe on postoperative day one. Procedures with the highest incidence of moderate/severe pain on the day of surgery were gynaecology-, plastic-, abdominal-, breast-, and orthopaedic procedures. On postoperative day one, patients undergoing vascular-, orthopaedic-, and abdominal operations most commonly rated their worst pain as moderate/severe. Female sex (OR = 2.15, 95% Cl 1.21-3.88, p = .010), chronic preoperative pain (OR = 4.20, 95% Cl 2.41-7.51, p < .001), undergoing a major procedure (OR = 2.07, 95% Cl 1.15-3.80, p = .017), and any intraoperative remifentanil administration (OR = 2.16, 95% Cl 1.20-3.94, p = .01) had increased odds of rating the worst pain as moderate/severe. Increased age (OR = 0.66 per 10 years (95% Cl 0.55-0.78, p < .001)) and undergoing breast-, gynaecology-, otolaryngology-, and neurosurgery (OR = 0.15-0.34, p < .038) was associated with lower odds of moderate/severe pain on postoperative day one. DISCUSSION: In our cohort, patients rated their current pain in the PACU similarly to other studies. However, the ratio of patients rating the worst pain experienced as moderate/severe on postoperative day one was relatively high. The identified patient- and procedural-related factors associated with higher odds of postoperative pain highlight a subgroup of patients who may benefit from enhanced perioperative monitoring and pain management strategies.

Predicting the optimal concentration of remifentanil for skull pin fixation with hemodynamic and analgesia nociception index monitoring.

Inadequate antinociception during skull pin fixation may cause hemodynamic instability in intracranial surgery. The optimal concentration of remifentanil to provide adequate antinociception and stable hemodynamics during skull pin fixation under analgesia nociception index monitoring is unknown. This study is to assess the 90% effective concentration of remifentanil for skull pin fixation under hemodynamic and analgesia nociception index monitoring. Twenty-six patients were enrolled for intracranial surgery, anesthesia was induced and maintained under total intravenous anesthesia using target-controlled infusion for remifentanil and propofol under analgesia nociception index and bispectral index monitoring. Skull pin fixation was performed at different effect-site concentrations of remifentanil required for Dixon's up-and-down method with a step size of 0.5 ng/ml under bispectral index 40-60. Inadequate antinociception is defined when either ANI < 30 or > 20% in hemodynamic changes from baseline (e.g. heart rate > 100 beats/min, or blood pressure > 180/100 mmHg) and the effect-site concentration of remifentanil is considered as failure. It is considered success as ANI > 30 and < 20% hemodynamic changes from baseline simultaneously. Seven pairs of failure/success were used for probit analysis. The 90% effective concentration of remifentanil for skull pin fixation with adequate antinociception and hemodynamic stability was 4.7 ng/ml.

The Relationship between Pre-Anesthetic Analgesia and Nociception (ANI) and Propofol Injection Pain among Patients Receiving Remifentanil: A Prospective, Randomized, Controlled Study.

Background and Objectives: The analgesia/nociception index (ANI) potentially monitors nociceptive status during anesthesia, but its link to preoperative pain sensitivity is unclear. We investigated the relationship between pre-anesthetic ANI scores and propofol injection pain (PIP) in patients receiving remifentanil. Materials and Methods: This study included 124 male patients aged 19-60 undergoing general anesthesia (ASA class I or II). Patients were randomized to group R (n = 62, remifentanil 4 ng/mL) or group C (n = 62, saline). The primary outcome was the association between PIP and ANI. Secondary outcomes included the incidence and severity of PIP or rocuronium-induced withdrawal movement (RIWM) and their association with ANI. Results: PIP and RIWM incidence and severity were lower in group R than in group C. A weak negative correlation between PIP and ANI at pre-induction (rpb = -0.21, p = 0.02, rpb = -0.37, p < 0.01) and a moderate negative correlation during propofol injection (rpb = -0.48, p = 0.02) were observed. A significant negative correlation was found between RIWM and ANI during rocuronium injection (τb = -0.61, p < 0.01). AUC, cut-off value, specificity, and sensitivity in ANI at pre-induction for predicting PIP were 0.67 (p = 0.02), 59, 76%, and 55%, respectively. AUC, cut-off value, specificity, and sensitivity in ANI during propofol injection for PIP were 0.77 (p < 0.01), 65, 81%, and 67%, respectively. Conclusions: ANI scores demonstrated significant differences between groups, suggesting potential predictive value for PIP despite the low pre-induction AUC value. This study highlights the potential of using ANI scores to predict and manage PIP in patients receiving remifentanil.

Remifentanil for tracheal intubation without neuromuscular blocking drugs in adult patients: a systematic review and meta-analysis.

There is increasing interest in the use of short-acting opioids such as remifentanil to facilitate tracheal intubation. The aim of this systematic review was to determine the efficacy and safety of remifentanil for tracheal intubation compared with neuromuscular blocking drugs in adult patients. We conducted a systematic search for randomised controlled trials evaluating remifentanil for tracheal intubation. Primary outcomes included tracheal intubation conditions and adverse events. Twenty-one studies evaluating 1945 participants were included in the analysis. Use of remifentanil (1.5-4.0 µg.kg-1 ) showed no evidence of a difference in tracheal intubation success rate compared with neuromuscular blocking drugs (risk ratio (95%CI) 0.97 (0.94-1.01); six studies; 1232 participants; I2 28%; p = 0.16; moderate-certainty evidence). Compared with neuromuscular blocking drugs, the use of remifentanil (2.0-4.0 µg.kg-1 ) makes little to no difference in terms of producing excellent tracheal intubation conditions (risk ratio (95%CI) 1.16 (0.72-1.87); two studies; 121 participants; I2 31%, p = 0.54; moderate-certainty of evidence). There was no evidence of an effect between remifentanil (2.0-4.0 µg.kg-1 ) and neuromuscular blocking drugs for bradycardia (risk ratio (95%CI) 0.44 (0.01-13.90); two studies; 997 participants; I2 81%; p = 0.64) and hypotension (risk ratio (95%CI) 1.05 (0.44-2.49); three studies; 1071 participants; I2 92%; p = 0.92). However, the evidence for these two outcomes was judged to be of very low-certainty. We conclude that remifentanil may be used as an alternative drug for tracheal intubation in cases where neuromuscular blocking drugs are best avoided, but more studies are required to evaluate the haemodynamic adverse events of remifentanil at different doses.

Effect of fentanyl and remifentanil on neuron damage and oxidative stress during induction neurotoxicity.

Opioids can be used for medical and non-medical purposes. Chronic pain such as cancer, as well as the frequent use of such drugs in places such as operating rooms and intensive care units, and in non-medical areas like drug abuse the effects and side effects of these drugs need to be examined in more detail. For this purpose, the effects of fentanyl and remifentanil drugs on neuroinflammation, oxidative stress and cholinesterase metabolism were investigated. Neuron cells (CRL-10742) were used for the evaluation of the toxicity of fentanyl and remifentanil. MTT, PON1 activity and total thiol levels for its effect on oxidative stress, AChE and BChE activities for its effect on the cholinergic system, and TNF, IL-8 and IL-10 gene levels for its neuroinflammation effect were determined. The highest neurotoxic dose of fentanyl and remifentanil was determined as 10 µg/mL. It was observed that the rate of neuron cells in this dose has decreased by up to 61.80% and 56.89%, respectively. The IL-8 gene expression level in both opioids was down-regulated while IL 10 gene level was up-regulated in a dose-dependent manner compared to the control. In our results, the TNF gene expression level differs between the two opioids. In the fentanyl group, it was seen to be up-regulated in a dose-dependent manner compared to the control. Fentanyl and remifentanil showed an inhibitory effect against PON1, while remifentanil showed an increase in total thiol levels. PON1, BChE and total thiol activities showed similarity with MTT.

Haemodynamic effects of remifentanil during induction of general anaesthesia with propofol. A randomised trial.

BACKGROUND: Remifentanil may have a dose-dependent haemodynamic effect during the induction of general anaesthesia combined with propofol. Our objective was to investigate whether systolic arterial blood pressure (SAP) was reduced to a greater extent when the remifentanil dose was increased. METHODS: This randomised, double-blind, dose-controlled study was conducted at the Day Surgery Unit of Haugesund Hospital, Norway. Ninety-nine healthy women scheduled for gynaecological surgery were randomly allocated in a 1:1:1 ratio to receive remifentanil induction with a low, medium or high dose corresponding to maximum effect-site concentrations (Ce) of 2, 4 and 8 ng/mL. The induction dose of propofol was 1.8 mg/kg, with a Ce of 2.9 µg/mL. Anaesthesia was induced using target-controlled infusion. After 150 s of sedation, a bolus of remifentanil and propofol was administered. Baseline was defined as 55-5 s before the bolus dose, and the total observation time was 450 s. We used beat-to-beat haemodynamic monitoring with LiDCOplus. The primary outcome variable was the maximum decrease in SAP within 5 min after bolus administration of remifentanil and propofol. Absolute and relative changes from baseline to minimal values and the area under the curve (AUC) were used as effect measures. Comparisons of groups were performed using analysis of variance (ANOVA). RESULTS: Median remifentanil doses were 0.75, 1.5 and 3.0 µg/kg in the low-, medium- and high-dose groups, respectively. The absolute changes (mean ± standard deviation) in SAP in the low-, medium- and high-dose groups of remifentanil were -39 ± 9.6 versus -43 ± 9.1, and -41 ± 10 mmHg, respectively. No difference (95% confidence interval) in the absolute change in SAP was observed between the groups (ANOVA, p = .29); medium versus low dose 3.7 (-2.0, 9.4) mmHg, and high versus medium dose -2.2 (-8.0; 3.5) mmHg. The relative changes from baseline to minimum SAP values were -30% versus -32% versus -32% (p = .52). The between-group differences in the AUC were not statistically significant. Relative changes in heart rate (-20% vs. -21% vs. -21%), stroke volume (-19% vs. -16% vs. -16%), cardiac output (-32% vs. -32% vs. -32%), systemic vascular resistance (-24% vs. -27% vs. -28%), and AUC were not statistically significant. CONCLUSION: This trial demonstrated major haemodynamic changes during the induction of anaesthesia with remifentanil and propofol. However, we did not observe any statistically significant differences between low, medium or high doses of remifentanil when using continuous invasive high-accuracy beat-to-beat monitoring.

Remifentanil is Superior to Propofol for Treating Emergence Agitation in Adults After General Anesthesia.

Background: Emergence agitation (EA) is one of the most common complications in clinical general anesthesia during recovery in adults. Remifentanil and propofol can reduce the incidence of EA, but with no randomized controlled trial to evaluate their effectiveness for treating EA. This study aims to compare the effectiveness of remifentanil and propofol for treating EA following general anesthesia. Patients and methods: Among 152 randomized patients with a mean of 49.5 years, and 99 (65.1%) of them being male, 149 were divided into two groups for subsequent analysis. The remifentanil group (Group R, n = 74) received a 0.5µg kg-1 remifentanil infusion followed by a 0.05µg kg-1 min-1 infusion until 15 minutes, after the onset of agitation. The propofol group (Group P, n = 75) received a 1mg kg-1 propofol infusion once agitation occurred. Emergence agitation was assessed using the Riker Sedation Agitation Score, with a score of ≥5 defining emergence agitation. During the post-anesthesia care unit (PACU), the recurrence of emergence agitation, time to extubation, and discharge from PACU were evaluated. Results: The incidence of reoccurring emergence agitation was lower in Group R (29.7%) compared with Group P (49.3%), with an odds ratio of 0.44 (95% CI 0.22-0.85; P=0.014). The time to extubation was shorter in Group R (mean 12min, range 8-15 min) compared with Group P (mean 17min, range 13-21 min) (P<0.001), as was the time discharge from the PACU (mean 30.5 min, range 25-40 min) vs Group P (mean 37.5 min, range 31-50 min) (P=0.001). Conclusion: Treatment of emergence agitation in adults with remifentanil infusion is more effective than propofol, with a shorter time to extubation and discharge from PACU.

Remifentanil improves left ventricular diastolic parameters in patients with impaired diastolic function: a prospective clinical study.

BACKGROUND: Left ventricular diastolic dysfunction has a significant impact on perioperative morbidity and mortality, and its incidence is high in elderly individuals. Anesthetic agents may impair diastolic function, which may increase the incidence of perioperative complications. The aim of this prospective, clinical, phase 4 study was to investigate the effects of remifentanil on left ventricle (LV) diastolic function in patients with diastolic dysfunction. The study was performed on 30 spontaneously breathing subjects (aged 60-80 years) with diastolic dysfunction. METHODS: Thirty patients (aged 60-80 years) with diastolic dysfunction scheduled for surgery were recruited between November 2019 and March 2023. Left ventricle function was evaluated once the intravenous remifentanil infusion reached a target-controlled concentration of 2 ng/ml with transthoracic echocardiography. Analysis of systolic function focused on left ventricular ejection fraction and mean mitral annular S velocity (Sm), whereas diastolic function focused on changes in transmitral peak flow (E), E/A, mitral septal and lateral e' waves, E/e' ratios and left atrial volume index following remifentanil infusion. RESULTS: Diastolic function measures of LV (mitral E/e', septal and lateral e' waves) statistically significantly improved (E/e' from 10.6 ± 2.9 cm.sn- 1 to 9.5 ± 2.2 cm.sn- 1; p = 0.006) following remifentanil infusion. Left atrial volume index decreased following remifentanil infusion without statistical significance (from 55 ± 14.4 ml.cm- 2 to 51.6 ± 13.3 ml.cm- 2; p = 0.1). Systolic function (ejection fraction and Sm) did not change following remifentanil infusion. CONCLUSIONS: Remifentanil improves left ventricular diastolic parameters in patients with preexisting diastolic dysfunction. Our study suggests that remifentanil at a plasma concentration of 2 ng.ml- 1 might be used safely in patients with left ventricular diastolic dysfunction.

Effect of esketamine on the EC50 of remifentanil for blunting cardiovascular responses to endotracheal intubation in female patients under general anesthesia: a sequential allocation dose-finding study.

BACKGROUND: This study aimed to investigate the effect of esketamine on the dose-effect relationship between remifentanil and the cardiovascular response to endotracheal intubation during target-controlled infusion (TCI) of propofol. METHODS: Patients underwent elective gynecological laparoscopic surgery under general anesthesia with endotracheal intubation, aged 18-65 years, American Society of Anesthesiologists class I or II, 18 kg/m2 ≤ body mass index ≤ 30 kg/m2, were randomly divided into the control (group C) and esketamine groups (group E). Before anesthesia induction, group E received an intravenous injection of 0.3 mg/kg of esketamine, while group C received an equal dose of physiological saline. TCI of propofol to the effect-site concentration (EC) of 3.0 µg/mL, and then TCI of remifentanil to the effect room and intravenous injection of rocuronium 0.6 mg/kg after MOAA/S was 0. Endotracheal intubation was performed after 2 min. Dixon's modified sequential method was used, and the initial EC of remifentanil was 3.0 ng/mL. The EC of remifentanil was determined according to the intubation response of the previous patient, with an adjacent concentration gradient of 0.3 ng/mL. The EC50 and EC95 values and their 95% confidence intervals (CIs) were determined using probit regression analysis. RESULTS: The EC50 for cardiovascular response inhibition to endotracheal intubation using remifentanil was 3.91 ng/mL (95% CI: 3.59-4.33 ng/mL) and EC95 was 4.66 ng/mL (95% CI: 4.27-6.23 ng/mL) with TCI of propofol 3.0 µg/mL. After intravenous administration of 0.3 mg/kg of esketamine, the EC50 of remifentanil was 3.56 ng/mL (95% CI: 3.22-3.99 ng/mL) and EC95 was 4.31 ng/mL (95% CI: 3.91-5.88 ng/mL). CONCLUSIONS: Combined with TCI of propofol 3.0 µg/mL for anesthesia induction, esketamine significantly reduced the EC50 and EC95 of remifentanil to inhibit the cardiovascular response to endotracheal intubation. TRIAL REGISTRATION: The trial was registered in the Chinese Clinical Trials Registry ( www.chictr.org.cn ; registration number: ChiCTR2200064932; date of registration:24/10/2022).