Effects of perioperative dexmedetomidine on delayed graft function following renal transplant: a systematic review and meta-analysis.

BACKGROUND: Dexmedetomidine, a highly selective alpha-2 adrenoceptor agonist with sedative and analgesic effects, has been suggested in recent studies to possess renoprotective properties. Dexmedetomidine may reduce the incidence of delayed graft function and contribute to effective pain control post-renal transplantation. The primary objective of this systematic review was to assess whether dexmedetomidine decreases the occurrence of delayed graft function in renal transplant patients. METHODS: Databases including MEDLINE, EMBASE, and CENTRAL were comprehensively searched from their inception until March 2023. The inclusion criteria covered all Randomized Clinical Trials (RCTs) and observational studies comparing dexmedetomidine to control in adult patients undergoing renal transplant surgery. Exclusions comprised case series and case reports. RESULTS: Ten RCTs involving a total of 1,358 patients met the eligibility criteria for data synthesis. Compared to the control group, the dexmedetomidine group demonstrated a significantly lower incidence of delayed graft function (OR = 0.71, 95% CI 0.52-0.97, p = 0.03, GRADE: Very low, I2 = 0%). Dexmedetomidine also significantly prolonged time to initiation of rescue analgesia (MD = 6.73, 95% CI 2.32-11.14, p = 0.003, GRADE: Very low, I2 = 93%) and reduced overall morphine consumption after renal transplant (MD = -5.43, 95% CI -7.95 to -2.91, p < 0.0001, GRADE: Very low, I2 = 0%). The dexmedetomidine group exhibited a significant decrease in heart rate (MD = -8.15, 95% CI -11.45 to -4.86, p < 0.00001, GRADE: Very low, I2 = 84%) and mean arterial pressure compared to the control group (MD = -6.66, 95% CI -11.27 to -2.04, p = 0.005, GRADE: Very low, I2 = 87%). CONCLUSIONS: This meta-analysis suggests that dexmedetomidine may potentially reduce the incidence of delayed graft function and offers a superior analgesia profile as compared to control in adults undergoing renal transplants. However, the high degree of heterogeneity and inadequate sample size underscore the need for future adequately powered trials to confirm these findings.

Diarrhoea of unknown cause: medical treatment in a stepwise mannerManagement of Idiopathic Diarrhoea Based on Experience of Step-Up Medical Treatment.

The basic principle for the treatment of idiopathic diarrhoea (functional diarrhoea K59.1) is to delay transit through the gut in order to promote the absorption of electrolytes and water. Under mild conditions, bulking agents may suffice. With increasing severity, antidiarrhoeal pharmaceuticals may be added in a stepwise manner. In diarrhoea of unknown aetiology, peripherally-acting opioid receptor agonists, such as loperamide, are first-line treatment and forms the pharmaceutical basis of antidiarrheal treatment. As second-line treatment opium drops have an approved indication for severe diarrhoea when other treatment options fail. Beyond this, various treatment options are built on experience with more advanced treatments using clonidine, octreotide, as well as GLP-1 and GLP-2 analogs which require specialist knowledge the field.

Chronic diarrhoea without an established cause is common.There are a small number of clinical trials, often with a limited number of patients or healthy volunteers.Treatment is often carried out on a trial-and-error basis, with considerable variation in the choice of treatment.There is a paucity of guidelines, and there is a gap in knowledge concerning treatment goals, such as the frequency, consistency and form of stool.The stepwise approach to the treatment of chronic idiopathic diarrhoea described in this article is based on clinical knowledge and experience.

Preliminary evaluation of the efficacy and safety of brimonidine for deep sedation.

BACKGROUND: Although brimonidine is currently used in the clinical treatment of glaucoma and rosacea, research of the deep sedative effect on animals after systemic administration is reported firstly and has shown promising results. METHODS: The median effective dose (ED50 ), the median lethal dose (LD50 ), and the therapeutic index of brimonidine for deep sedation and formalin stimulation assay were determined by various animal experiments. The effect of synergistic anesthesia in rabbits with brimonidine and chloral hydrate was preliminarily evaluated. RESULTS: The ED50 of brimonidine for highly effective sedation by intraperitoneal injection in rats was calculated to be 2.05 mg kg-1 with a 95% confidence interval (CI) of 1.87 to 2.25 mg kg-1 . The ED50 of brimonidine for deep sedation by intravenous and intrarectal injection in rabbits was calculated to be 0.087 mg kg-1 with a 95% CI of 0.084 to 0.091 mg kg-1 and 1.65 mg kg-1 with a 95% CI of 1.43 to 1.91 mg kg-1 , respectively. The LD50 of intraperitoneal brimonidine injection in rats was calculated to be 468 mg kg-1 with a 95% CI of 441 to 497 mg kg-1 and a therapeutic index of 228. Brimonidine has a certain analgesic and heart rate lowering effects. CONCLUSION: The results confirmed that brimonidine has deep sedation and analgesic effects after systemic administration and has high safety. It can be used in combination with other types of sedative drugs to achieve better effects.

Effect of Enteral Guanfacine on Dexmedetomidine Use in the ICU.

Describe the efficacy and safety of guanfacine for dexmedetomidine weaning in critically ill patients. DESIGN: Retrospective descriptive analysis. SETTING: Six hundred thirteen-bed academic medical center from October 2020 to October 2021. PATIENT/SUBJECTS: All Adult patients on IV dexmedetomidine who received at least one dose of guanfacine for sedation or agitation were included. INTERVENTIONS: Enteral guanfacine. MEASUREMENTS AND MAIN RESULTS: The primary outcome was discontinuation of dexmedetomidine therapy within 48 hours after guanfacine initiation. Secondary outcomes assessed included adjunctive medication use, rate of dexmedetomidine reinitiation, and safety outcomes. One hundred five patients were included in the analysis. Median age was 59 years old, 66% were male, and median daily dose of guanfacine was 1.5 mg. Dexmedetomidine was discontinued within 48 hours in 58% of patients (n = 61) and within 72 hours in 71% of patients (n = 75). Fifty-five percent of patients (n = 58) required rescue medications for poorly controlled agitation, sedation, or pain while on guanfacine. Dexmedetomidine withdrawal occurred in 2% of patients (n = 2) while on guanfacine. Adverse effects attributed to guanfacine occurred in 8% of patients (n = 8), all experiencing hypotension leading to medication discontinuation. CONCLUSION: Dexmedetomidine was successfully weaned within 48 hours of guanfacine initiation in 58% of patients with minimal withdrawal or adverse effects. Guanfacine may be an effective and safe enteral option for dexmedetomidine weaning in critically ill patients.

Alpha2 -receptor agonists as adjuvants for brachial plexus nerve blocks-A systematic review with meta-analyses.

BACKGROUND: We review the efficacy and safety of dexmedetomidine and clonidine as perineural or systemic adjuvants for brachial plexus blocks (BPB). METHODS: We included randomised controlled trials on upper limb surgery with BPBs in adults, comparing dexmedetomidine with clonidine or either drug with placebo. The primary outcome was duration of analgesia. Secondary outcomes included adverse and serious adverse events. The review was conducted using Cochrane standards, trial sequential analyses (TSA) and Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: We included 101 trials with 6248 patients. Overall, duration of analgesia was prolonged with both clonidine (176 min [TSA adj. 95% CI: 118, 205, p < .00001; 33 trials]) and dexmedetomidine (292 min [TSA adj. 95% CI: 245 329, p < .00001; 53 trials]), but was longer for dexmedetomidine than clonidine (205 min [TSA adj. 95% CI: 157, 254, p < .00001; 19 trials]). Compared with placebo, dexmedetomidine was associated with bradycardia (RR 4.2 [95% CI 2.2, 8.3]), and both clonidine (RR 4.5 [95% CI 1.1, 18.3]) and dexmedetomidine (RR 3.9 [95% CI 2.0, 7.5]) were associated with hypotension. Serious adverse events were mostly related to block technique. GRADE-rated quality of evidence was low or very low. CONCLUSION: Alpha2-receptor agonists used as adjuvants for BPBs lead to a prolonged duration of analgesia, with dexmedetomidine as the most efficient. Alpha2-receptor agonists were associated with increased risk of cardiovascular adverse events. The quality of evidence was low to very low.

Preliminary evaluation of the efficacy and safety of brimonidine for general anesthesia.

BACKGROUND: To determine the hypnotic and analgesic effects of brimonidine, and evaluate its efficacy and safety for general anesthesia. Potentiation of pentobarbital sleeping time following brimonidine administration was observed in mice, as was the analgesic activity of brimonidine. METHODS: The median effective dose (ED50) and lethal dose (LD50) of intraperitoneally injected brimonidine were determined in hypnotized mice. In addition, the LD50 of intravenously injected brimonidine, and ED50 of intravenously, intramuscularly, and intrarectally injected brimonidine in hypnotized rabbits were determined. Finally, the synergistic anesthetic effect of brimonidine and chloral hydrate was evaluated in rabbits. RESULTS: Intraperitoneal injection of 10 mg/kg brimonidine enhanced the hypnotic effect of a threshold dose of pentobarbital. Intraperitoneally injected brimonidine produced dose-related analgesic effects in mice. The ED50 of intraperitoneally administered brimonidine in hypnotized mice was 75.7 mg/kg and the LD50 was 379 mg/kg. ED50 values of intravenous, intramuscular, and intrarectal brimonidine for hypnosis in rabbits were 5.2 mg/kg, 8.8 mg/kg, and 8.7 mg/kg, respectively; the LD50 of intravenous brimonidine was 146 mg/kg. Combined intravenous administration of 0.6 mg/kg brimonidine and 0.03 g/kg chloral hydrate had a synergistic anesthetic effect. CONCLUSIONS: Brimonidine elicited hypnotic and analgesic effects after systemic administration and exhibited safety. Moreover, brimonidine enhanced the effects of other types of narcotics when combined.

Cardiopulmonary function and intestinal blood flow in anaesthetised, experimentally endotoxaemic horses given a constant rate infusion of dexmedetomidine.

BACKGROUND: Endotoxaemia causes untoward inflammatory-mediated effects that might be attenuated by dexmedetomidine. OBJECTIVES: To evaluate the effects of a dexmedetomidine intravenous (IV) infusion on systemic and intestinal haemodynamics and arterial blood gas values in sevoflurane-anaesthetised horses administered Escherichia coli O55:B5 lipopolysaccharides (LPS). STUDY DESIGN: Randomised controlled in vivo experiment. METHODS: A total of 13 horses weighing 456 ± 86 kg (mean ± standard deviation) and aged 13.9 ± 9.0 years donated for euthanasia underwent ventral midline celiotomy using sevoflurane anaesthesia. Baseline physiological variables were recorded after a 90-minute equilibration period. All horses were given 0.1 mcg/kg bwt LPS IV. Horses were randomly assigned to no further treatment (group LPS; seven horses) or IV administration of dexmedetomidine (loading dose 1.75 mcg/kg bwt followed by 1.75 mcg/kg bwt/h; group LPS-Dex; six horses) with concurrent target sevoflurane dose reduction of 50%. Cardiac index (CI; thermodilution), intestinal blood flow, arterial blood parameters and plasma dexmedetomidine concentration measurements were recorded every 30 minutes until euthanasia at 390 minutes. Data were compared between and within groups to baseline using a mixed model analysis (significance P < .05). RESULTS: In LPS-Dex horses, intestinal blood flow and CI were transiently decreased after the dexmedetomidine loading dose, but no significant differences were found compared with baseline during the infusion. Sevoflurane dose was reliably reduced by approximately 40%. Significant differences were identified in creatinine (115  umol/L LPS-Dex; 195 umol/L LPS), bicarbonate (29.7 mmol/L LPS-Dex; 23 mmol/L LPS) and base excess (2.0 mmol/L LPS-Dex; -5.3 mmol/L LPS). Dexmedetomidine plasma concentrations were highest after the loading dose and stable during infusion dosing. MAIN LIMITATIONS: Experimental conditions are not reflective of clinical colic management. CONCLUSIONS: A dexmedetomidine infusion with sevoflurane dose reduction attenuated some deleterious changes in anaesthetised horses administered LPS without sustained negative cardiovascular effects and may be beneficial during colic surgery.

Prevention of Withdrawal in Pediatric Patients Receiving Long-term Dexmedetomidine Infusions.

OBJECTIVE: Determine if the addition of clonidine was associated with a decreased incidence of dexmedetomidine withdrawal in patients who received prolonged dexmedetomidine infusions. METHODS: This was a retrospective observational cohort study conducted at a single-center PICU in an academic children's hospital. Children 1 month to 18 years of age who received dexmedetomidine infusion for 5 days or longer were included in the study. RESULTS: Fifty patients met the inclusion criteria with 15 patients who received clonidine and 35 who received a dexmedetomidine wean alone. Withdrawal criteria included blood pressure changes, heart rate changes, and documented agitation. Overall, there was no difference in change in blood pressure or documented agitation between groups. Patients who did not receive clonidine had a greater number of heart rate readings above normal for age following discontinuation of the infusion, yet this was not statistically significant. Potentially more importantly, the addition of clonidine did not impact the duration of dexmedetomidine wean or the PICU length of stay after dexmedetomidine discontinuation. CONCLUSIONS: The addition of clonidine while weaning a long-term dexmedetomidine infusion did not lead to lower blood pressures or agitation, but did lead to decreased percentage of heart rates above the age-appropriate range. The clinical significance of this is unknown, and further investigation is warranted. The addition of clonidine did not decrease time to weaning off dexmedetomidine or shorten PICU length of stay.

Safety and Efficacy of Dexmedetomidine in Breast Surgeries: A Systematic Review and Meta-Analysis.

PURPOSE: Pain control during and after breast surgery is still a challenging task. Dexmedetomidine (DEX) is considered as a sedative agent that is widely used perineurally or intravenously as an adjuvant in general anesthesia and critical care medicine practice. The aim of this study is to evaluate the efficacy of perineural DEX and intravenous (IV) DEX and their effects on postoperative complications in breast surgeries. DESIGN: Systematic review and meta-analysis. METHODS: The present study systematically reviewed all identified randomized controlled trials for efficacy and safety of IV and perineural use of DEX in breast surgeries. Databases were searched for articles published before October 2019. FINDINGS: Twelve trials were identified including 803 patients undergoing breast surgery. Although administration of IV DEX and its use with pectoral nerve (Pecs) block significantly postponed time for first analgesic request and decreased pain score at 1 and 12 hours after surgery, paravertebral use of DEX had no statistically significant effect. Pooled data about perineural DEX showed no significant effect on postoperative nausea and vomiting (PONV), whereas IV DEX significantly reduced PONV. Pooled analysis also showed that DEX administration did not significantly affect postoperative complications, such as postoperative itching, bradycardia, and pneumothorax in patients undergoing breast surgery. CONCLUSIONS: The results showed that unlike paravertebral DEX, both DEX use with Pecs blocks and IV DEX were effective in control of postoperative pain in patients undergoing breast surgeries. Unlike perineural DEX, IV DEX significantly reduced PONV.

Evaluation of dexmedetomidine withdrawal in critically ill adults.

BACKGROUND: Dexmedetomidine (DEX) withdrawal syndrome has been reported in the pediatric population, but literature describing DEX withdrawal in critically ill adults is limited. The purpose of this study was to determine the incidence of DEX withdrawal in adult patients and to identify factors associated with DEX withdrawal syndrome. METHODS: A retrospective chart review was performed in the adult intensive care units of two tertiary medical centers. Eligible patients were at least 18 years of age and received DEX for 24 h or more. Patients were excluded if they presented with a primary neurologic diagnosis, had a history of substance abuse, or received any other α2-agonists 24 h before discontinuation of DEX. The primary outcome was the percentage of patients who developed withdrawal as defined by the presence of two or more symptoms (tachycardia, hypertension, vomiting, agitation) within the 24 h following DEX discontinuation. RESULTS: Of the 165 patients included, 50 patients experienced withdrawal (30.3%), lasting a median of two days. The incidence of withdrawal was higher in surgical (40%) compared to medical (28%) or cardiac (32%) patients (p = 0.004). Median duration of infusion was 52.5 h (interquartile range [IQR], 37.8 to 102.8) in the withdrawal group and 52 h (IQR, 41 to 87) in the non-withdrawal group (p = 0.887). Median DEX dose was 0.56 µg/kg/h (IQR, 0.39 to 0.83) in the withdrawal group and 0.48 µg/kg/h (0.36 to 0.65) in the non-withdrawal group (p = 0.12). Weaning did not reduce the incidence of withdrawal as compared to abrupt discontinuation (p = 0.68). The withdrawal group was more likely to have concomitantly discontinued opioids (54% vs 12.2%) and benzodiazepines (36% vs 0%) at the time of DEX discontinuation compared to the non-withdrawal group (p = 0.004). CONCLUSION: Development of DEX-associated withdrawal occurred in approximately 30% of adult patients, comparable to rates reported in pediatric literature. There appeared to be no correlation between dose, exposure, and weaning in the occurrence of withdrawal, but concomitant discontinuation of opioids or benzodiazepines as well as ICU admission type could highlight cases requiring closer monitoring.

Effect of preoperative administration of systemic alpha-2 agonists on postoperative pain: a systematic review and meta-analysis.

BACKGROUND: Alpha-2 agonists have sedative, analgesic, and opioid-sparing effects. Moreover, intraoperative or postoperative systemic administration of alpha-2 adrenergic agonists is known to reduce postoperative pain and opioid consumption. This meta-analysis investigated whether preoperative administration of alpha-2 agonists can affect postoperative pain and opioid consumption. METHODS: We searched the MEDLINE, EMBASE, Cochrane Library (CENTRAL), KoreaMed, and KMbase databases through March 2019 to identify relevant randomized controlled trials (RCTs) on the effect of preoperative systemic administration of alpha-2 agonists on postoperative pain and opioid consumption. We conducted a meta-analysis according to the Cochrane Collaboration guidelines. Standardized mean differences (SMDs) of postoperative pain intensity or dose of opioid consumption in the alpha-2 agonist group were extracted and combined using a random-effect model and were compared to those of the control group. RESULTS: Eleven RCTs involving 748 participants were included in this meta-analysis. Preoperative administration of systemic alpha-2 agonists significantly reduced cumulative opioid consumption up to 6 h (SMD, -0.52; 95% confidence interval [-0.90 to -0.14]) and 24 h (SMD, -0.68 [-1.27 to -0.09]) after surgery. Moreover, preoperative administration of alpha-2 agonists significantly reduced postoperative pain intensity at 6 h (SMD, -0.50 [-0.78 to -0.21]) and 24 h (SMD, -0.44 [-0.86 to -0.03]). CONCLUSIONS: In this meta-analysis, high degree of heterogeneity limits the preoperative administration of alpha-2 agonists in reducing postoperative opioid consumption and pain intensity. Future powered large RCTs are required to increase the certainty of evidence on the effect in reducing postoperative opioid consumption and pain intensity.

Effects of a Clonidine Taper on Dexmedetomidine Use and Withdrawal in Adult Critically Ill Patients-A Pilot Study.

OBJECTIVES: Prolonged use of dexmedetomidine has become increasingly common due to its favorable sedative and anxiolytic properties. Hypersympathetic withdrawal symptoms have been reported with abrupt discontinuation of prolonged dexmedetomidine infusions. Clonidine has been used to transition patients off dexmedetomidine infusions for ICU sedation. The objective of this study was to compare the occurrence of dexmedetomidine withdrawal symptoms in ICU patients transitioning to a clonidine taper versus those weaned off dexmedetomidine alone after prolonged dexmedetomidine infusion. DESIGN: This was a single-center, prospective, double cohort observational study conducted from November 2017 to December 2018. SETTING: Medical-surgical, cardiothoracic, and neurosurgical ICUs in a tertiary care hospital. PATIENTS: We included adult ICU patients being weaned off dexmedetomidine after receiving continuous infusions for at least 3 days. INTERVENTIONS: Patients were either weaned off dexmedetomidine alone or with a clonidine taper at the discretion of the providers. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the incidence of at least two dexmedetomidine withdrawal symptoms during a single assessment within 24 hours of dexmedetomidine discontinuation. Time on dexmedetomidine after wean initiation and difference in medication cost were also evaluated. Forty-two patients were included in this study: 15 received clonidine (Group C) and 27 weaned off dexmedetomidine alone (Group D). There was no significant difference in the incidence of two or more withdrawal symptoms between groups (73% in Group C vs 59% in Group D; p = 0.51). Patients in Group C spent less time on dexmedetomidine after wean initiation compared with patients in Group D (19 vs 42 hr; p = 0.02). An average cost savings of $1,553.47 per patient who received clonidine was observed. No adverse effects were noted. CONCLUSIONS: Our study demonstrated that patients receiving clonidine were able to wean off dexmedetomidine more rapidly, with a considerable cost savings and no difference in dexmedetomidine withdrawal symptoms, compared with patients weaned off dexmedetomidine alone. Clonidine may be a safe, effective, and practical option to transition patients off prolonged dexmedetomidine infusions.

Antinociceptive Action of Moringa peregrina is Mediated by an Interaction with α2-Adrenergic Receptor

Background: Moringa peregrina (M. peregrina) is an edible, drought-resistant tree that is native to semi-arid countries. It is used as a painkiller in folk medicine. Aims: To study the antinociceptive effects of the leaf extract of M. peregrina in mice. Study Design: Animal experimentation. Methods: We employed thermal (hot plate and tail-immersion tests) and chemical (writhing and formalin tests) pain models in male BALB/c mice (eight animals per group) to investigate the mechanisms involved in the antinociceptive actions of M. peregrina. Additionally, we identified the chemical constituents present in the extract of M. peregrina by using liquid chromatography-mass spectrometry analysis, and predicted the possible active constituents that interact with the receptor based on molecular docking simulations. Results: In the writhing test, 200 mg/kg of M. peregrina extract restricted abdominal cramps by up to 55.97% (p<0.001). Further, it reduced the time of paw-licking in the early and late phases of formalin test by up to 56.8% and 65.5%, respectively, as compared to the percentage inhibitions of 50.5% and 48.4% produced by 30 mg/kg diclofenac sodium in the early and late phases, respectively (p<0.05). This effect was abrogated by yohimbine (1 mg/kg, intraperitoneally), but not by methysergide (5 mg/kg, intraperitoneally), in the late phase only, which indicates that the action of M. peregrina in formalin test is not mediated by 5-HT2 serotonin receptors, but rather via α2-adrenergic receptors. In the hot plate test, but not on tail-immersion test, the high dose (400 mg/kg) of the extract increased the latency time after 30 minutes of its administration. Yohimbine antagonized the action of M. peregrina in the hot plate test. Based on LC-MS analysis, the major constituents found in M. peregrina methanolic extract were chrysoeriol 7-O-diglucoside, lupeol acetate, quercetin, and rutin. Depending on the molecular docking results, the activity of M. peregrina extract could be due to the binding of chrysoeriol 7-O-diglucoside, quercetin, and rutin to the α2-adrenergic receptor. Conclusion: Interaction with the α2-adrenergic receptor serves as a possible mechanism of the M. peregrina analgesic effect.

An Experimental Study on Spinal Cord µ-Opioid and α2-Adrenergic Receptors mRNA Expression Following Stress-Induced Hyperalgesia in Male Rats.

BACKGROUND: Intense stress can change pain perception and induce hyperalgesia; a phenomenon called stress-induced hyperalgesia (SIH). However, the neurobiological mechanism of this effect remains unclear. The present study aimed to investigate the effect of the spinal cord µ-opioid receptors (MOR) and α2-adrenergic receptors (α2-AR) on pain sensation in rats with SIH. METHODS: Eighteen Sprague-Dawley male rats, weighing 200-250 g, were randomly divided into two groups (n=9 per group), namely the control and stress group. The stress group was evoked by random 1-hour daily foot-shock stress (0.8 mA for 10 seconds, 1 minute apart) for 3 weeks using a communication box. The tail-flick and formalin tests were performed in both groups on day 22. The real-time RT-PCR technique was used to observe MOR and α2-AR mRNA levels at the L4-L5 lumbar spinal cord. Statistical analysis was performed using the GraphPad Prism 5 software (San Diego, CA, USA). Student's t test was applied for comparisons between the groups. P<0.05 was considered statistically significant. RESULTS: There was a significant (P=0.0014) decrease in tail-flick latency in the stress group compared to the control group. Nociceptive behavioral responses to formalin-induced pain in the stress group were significantly increased in the acute (P=0.007) and chronic (P=0.001) phases of the formalin test compared to the control group. A significant reduction was also observed in MOR mRNA level of the stress group compared to the control group (P=0.003). There was no significant difference in α2-AR mRNA level between the stress and control group. CONCLUSION: The results indicate that chronic stress can affect nociception and lead to hyperalgesia. The data suggest that decreased expression of spinal cord MOR causes hyperalgesia.

Effects of Dexmedetomidine Infusion During Sevoflurane Anesthesia on Otoacoustic Emissions.

BACKGROUND AND OBJECTIVES: Knowing the ototoxic potential of the agents used in medical treatments is important for the protection of hearing. Although we have knowledge regarding some effects of dexmedetomidine, which is an anesthetic-sparing drug, its influence over the hearing system has never been studied and is obscure yet. The aim of this study is to determine the effects of intravenous dexmedetomidine application during sevoflurane anesthesia on otoacoustic emissions (OAEs). SUBJECT AND METHODS: This prospective randomized study was performed on 60 patients (34 male, 26 female, mean age: 30.6±9.2 years) who were scheduled for an elective surgery under general anesthesia and the patients were enrolled and randomly divided into 2 groups. They received dexmedetomidine (Group D) or Saline (Group S) infusion during a standardized Sevoflurane anesthesia. Transient and distortion product OAEs were measured preoperatively and postoperatively (24th hour). OAE results were compared within and between groups. RESULTS: In group D postoperative OAEs were lower than preoperative OAEs and postoperative levels of group S, especially at low frequencies (p<0.05). CONCLUSIONS: Dexmedetomidine infusion affects the micromechanical function of cochlea especially in the low-frequency region. Dexmedetomidine should be carefully used during general anesthesia to avoid its probable harmful effects on cochlear micromechanics.

[Background and current use of adjuvants for regional anesthesia : From research to evidence-based patient treatment]. / Hintergrund und aktueller Einsatz von Adjuvanzien für die Regionalanästhesie : Aus der Forschung in die evidenzbasierte Patientenversorgung.

The discovery of the local anaesthetic effect by blocking sodium ion channels was a milestone in anaesthesia but was soon limited by sometimes life-threatening toxic effects of the local anaesthetics. By developing novel local anaesthetics and also by adding so-called adjuvants, attempts have been made to limit these life-threatening events. This article focuses on the historic background and the current state of the use of these adjuvants for regional anaesthesia. Adding epinephrine, clonidine or dexmedetomidine, but only as a single dose, results in a faster onset, longer duration of action and increased intensity of neuronal blockade of regional anaesthesia. The benefits of adding sodium bicarbonate, on the other hand, are relatively minor and, therefore, clinically negligible. Although increasing evidence in the literature suggests an improvement and prolongation of the analgesic effect after axonal administration of opioids, which can also be given continuously, systemic effects are not fully ruled out due to the increased incidence of central side effects. The partial local anaesthetic effects of opioids cannot always be distinguished from opioid receptor-specific effects. Mechanistic studies postulate a functional coupling of opioid receptors in injured rather than in intact peripheral nerves. Recent studies have identified glucocorticoid and mineralocorticoid receptors predominantly on peripheral nociceptive nerve fibers. This is consistent with numerous clinical reports of a marked prolongation of the local anaesthetic effect. In addition to the known genomic effects of steroids that occur via a change in gene expression of pain-sustaining protein structures, faster non-genomic effects are also discussed, which occur via a change in intracellular signaling pathways. In summary, new insights into mechanisms and novel results from clinical trials will help the anaesthesiologist in the decision to use adjuvants for regional anaesthesia which, however, requires to weigh the individual patient's benefits against the risks.

Effects of Dexmedetomidine Infusion During Sevoflurane Anesthesia on Otoacoustic Emissions

BACKGROUND AND OBJECTIVES: Knowing the ototoxic potential of the agents used in medical treatments is important for the protection of hearing. Although we have knowledge regarding some effects of dexmedetomidine, which is an anesthetic-sparing drug, its influence over the hearing system has never been studied and is obscure yet. The aim of this study is to determine the effects of intravenous dexmedetomidine application during sevoflurane anesthesia on otoacoustic emissions (OAEs). SUBJECTS AND METHODS: This prospective randomized study was performed on 60 patients (34 male, 26 female, mean age: 30.6±9.2 years) who were scheduled for an elective surgery under general anesthesia and the patients were enrolled and randomly divided into 2 groups. They received dexmedetomidine (Group D) or Saline (Group S) infusion during a standardized Sevoflurane anesthesia. Transient and distortion product OAEs were measured preoperatively and postoperatively (24th hour). OAE results were compared within and between groups. RESULTS: In group D postoperative OAEs were lower than preoperative OAEs and postoperative levels of group S, especially at low frequencies (p<0.05). CONCLUSIONS: Dexmedetomidine infusion affects the micromechanical function of cochlea especially in the low-frequency region. Dexmedetomidine should be carefully used during general anesthesia to avoid its probable harmful effects on cochlear micromechanics.

The effect of dexmedetomidine on the acute pain after cardiothoracic surgeries: a systematic review

Abstract Introduction: Acute post-operative pain remains a troublesome complication of cardiothoracic surgeries. Several randomized controlled trials have examined the efficacy of dexmedetomidine as a single or as an adjuvant agent before, during and after surgery. However, no evidence-based conclusion has been reached regarding the advantages of dexmedetomidine over the other analgesics. Objective: To review the effect of dexmedetomidine on acute post-thoracotomy/sternotomy pain. Methods: Medline, SCOPUS, Web of Science, and Cochrane databases were used to search for randomized controlled trials that investigated the analgesia effect of dexmedetomidine on post-thoracotomy/sternotomy pain in adults' patients. The outcomes were postoperative pain intensity or incidence, postoperative analgesia duration, and the number of postoperative analgesic requirements. Results: From 1789 citations, 12 trials including 804 subjects met the inclusion criteria. Most studies showed that pain score was significantly lower in the dexmedetomidine group up to 24 hours after surgery. Two studies reported the significant lower postoperative analgesia requirements and one study reported the significant lower incidence of acute pain after surgery in dexmedetomidine group. Ten studies found that the total consumption of narcotics was significantly lower in the dexmedetomidine group. The most reported complications of dexmedetomidine were nausea/vomiting, bradycardia and hypotension. Conclusion: Dexmedetomidine can be used as a safe and efficient analgesic agent for reducing the postoperative pain and analgesic requirements up to 24 hours after cardiothoracic surgeries. However, further well-designed trials are needed to find the optimal dosage, route, time, and duration of dexmedetomidine administration.

The impact of neuraxial clonidine on postoperative analgesia and perioperative adverse effects in women having elective Caesarean section-a systematic review and meta-analysis.

Neuraxial clonidine improves postoperative analgesia in the general surgical population. The efficacy and safety of neuraxial clonidine as a postoperative analgesic adjunct in the Caesarean section population still remains unclear. This systematic review and meta-analysis aims to evaluate the effect of perioperative neuraxial clonidine on postoperative analgesia in women having Caesarean section under neuraxial anaesthesia. We included randomized controlled trials comparing the analgesic efficacy of the perioperative administration of neuraxial clonidine alone or in combination with a local anaesthetic and/or opioids in women having elective Caesarean section under neuraxial anaesthesia when compared with placebo. PubMed, the Cochrane Central Register of Controlled Trials, and EMBASE were searched until February 2017. Eighteen studies were included in the meta-analysis. Neuraxial clonidine reduced 24 h morphine consumption [mean difference (MD): -7.2 mg; 95% confidence interval (CI): -11.4, -3.0 mg; seven studies] and prolonged time to first analgesic request (MD: 135 min; 95% CI: 102, 168 min; 16 studies) when compared with the control group. Neuraxial clonidine increased intraoperative hypotension [odds ratio (OR): 2.849; 95% CI: 1.363, 5.957], intraoperative sedation (OR: 2.355; 95% CI: 1.016, 5.459), but reduced the need for intraoperative analgesic supplementation (OR: 0.224; 95% CI: 0.076, 0.663). The effect of clonidine on intraoperative bradycardia, intraoperative and postoperative nausea and vomiting, postoperative sedation, and pruritus were inconclusive. Neuraxial clonidine did not negatively impact neonatal umbilical artery pH or Apgar scores. This review demonstrates that neuraxial clonidine enhances postoperative analgesia in women having Caesarean section with neuraxial anaesthesia, but this has to be balanced against increased maternal adverse effects.

Influence of sedation on onset and quality of euthanasia in sheep.

The purpose of this study was to determine if dexmedetomidine administered IV prior to euthanasia in sheep affected the speed or quality of euthanasia. Twenty clinically healthy Dorset-cross adult ewes between 1 and 3years of age were enrolled in a randomized blinded experimental trial. The subjects were randomly assigned to receive dexmedetomidine 5µg/kg IV or an equivalent volume of saline. Five minutes later, euthanasia was accomplished with a pentobarbital/phenytoin overdose given IV. The time to apnea, asystole, cessation of audible heartbeat, and absence of corneal reflex were recorded by two blinded investigators. If any muscle spasms, contractions, vocalization, and/or dysrhythmias were noted, the time was recorded and type of ECG abnormality was described. An overall score of the euthanasia event was assigned using a numeric rating scale (NRS) after the animal was declared dead. The time to loss of corneal reflex was significantly longer in sheep given dexmedetomidine compared with those who received saline (P=0.03). Although vocalization was observed only in some animals premedicated with dexmedetomidine, no significance was found for this event and no other significant differences between groups were noted. Dexmedetomidine at 5µg/kg IV 5min prior to injection of pentobarbital/phenytoin for euthanasia did not substantially affect the progress of euthanasia. Dexmedetomidine may be given to sedate sheep prior to euthanasia without concern for it adversely affecting the progress of euthanasia, however vocalization may occur.