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Brazilian Journal of Anesthesiology... May 2024Midazolam is routinely used as preanesthetic medication in pediatric patients. Recently, dexmedetomidine has emerged as an alternative as a premedicant. We aimed to add... (Review)
Review
BACKGROUND
Midazolam is routinely used as preanesthetic medication in pediatric patients. Recently, dexmedetomidine has emerged as an alternative as a premedicant. We aimed to add more evidence about the efficacy and safety of two common routes of administration for pediatric premedication: oral midazolam versus intranasal dexmedetomidine.
METHODS
We systematically searched Randomized Controlled Trials (RCTs) involving patients ≤ 18 years old undergoing preanesthetic medication and comparing intranasal dexmedetomidine with oral midazolam. Risk Ratio (RR) and Mean Difference (MD) with 95% Confidence Intervals (95% CI) were computed using a random effects model. Trial-sequential analyses were performed to assess inconsistency.
RESULTS
Sixteen RCTs (1,239 patients) were included. Mean age was 5.5 years old, and most procedures were elective. There was no difference in satisfactory induction or mask acceptance (RR = 1.15, 95% CI 0.97-1.37; p = 0.11). There was a higher incidence of satisfactory separation from parents in the dexmedetomidine group (RR = 1.40; 95% CI 1.13-1.74; p = 0.002). Dexmedetomidine was also associated with a reduction in the incidence of emergence agitation (RR = 0.35; 95% CI 0.14-0.88; p = 0.02). Heart rate and mean arterial pressure were marginally lower in the dexmedetomidine group but without clinical repercussions.
CONCLUSION
Compared with oral midazolam, intranasal dexmedetomidine demonstrated better separation from parents and lower incidence of emergence agitation in pediatric premedication, without a difference in satisfactory induction. Intranasal dexmedetomidine may be a safe and effective alternative to oral midazolam for premedication in pediatric patients.
PubMed: 38801889
DOI: 10.1016/j.bjane.2024.844520 -
Frontiers in Surgery 2024The efficacy of non-invasive mechanical ventilation (NIMV) on the postoperative ARF is conflicting and the failure rate of NIMV in this patient population is high. In...
OBJECTIVE
The efficacy of non-invasive mechanical ventilation (NIMV) on the postoperative ARF is conflicting and the failure rate of NIMV in this patient population is high. In our study, we hypothesized that the use of dexmedetomidine during NIMV in major abdominal surgical patients can reduce NIMV failure without significant side affect.
METHODS
Medical records of patients who underwent major abdominal surgery, admitted to our general surgery intensive care unit (ICU), developed postoperative ARF, received NIMV (with oro-nasal mask) and dexmedetomidine infusion were enrolled in this study. The infusion rate was adjusted to maintain a target sedation level of a Richmond Agitation-Sedation Scale (RASS) (-2)-(-3). The sedation was stopped when NIMV was discontinued.
RESULTS
A total of 60 patients, 42 (70.0%) male, and 18 (30.0%) female, with a mean age of 68 ± 11 years were included in the study. The mean APACHE II score was 20 ± 6. Dexmedetomidine was infused for a median of 25 h (loading dose of 0.2 mcg/kg for 10 min, maintained at 0.2-0.7 mcg/kg/h, titrated every 30 min). RASS score of all study group significantly improved at the 2 h of dexmedetomidine initiation (+3 vs. -2, = 0.01). A targeted sedation level was achieved in 92.5% of patients. Six (10.0%) patients developed bradycardia and 5 (8.3%) patients had hypotension. The mean NIMV application time was 23.4 ± 6.1 h. Seven (11.6%) patients experienced NIMV failure, all due to worsening pulmonary conditions, and required intubation and invasive ventilation. Fifty-three (88.3%) patients were successfully weaned from NIMV with dexmedetomidine sedation and discharged from ICU. The duration of NIMV application and ICU stay was shorter in NIMV succeded group (21.4 ± 3.2 vs. 29.9 ± 6.4; = 0.012).
CONCLUSION
Our study suggests that dexmedetomidine demonstrates effective sedation in patients with postoperative ARF during NIMV application after abdominal surgery. Dexmedetomidine can be considered safe and capable of improving NIMV success.
PubMed: 38800629
DOI: 10.3389/fsurg.2024.1357492 -
Experimental Animals May 2024Ischemia/reperfusion (I/R) is a pathological process that occurs in numerous organs and is often associated with severe cellular damage and death. Ectodysplasin-A2...
Ischemia/reperfusion (I/R) is a pathological process that occurs in numerous organs and is often associated with severe cellular damage and death. Ectodysplasin-A2 receptor (EDA2R) is a member of the TNF receptor family that has anti-inflammatory and antioxidant effects. However, to the best of our knowledge, its role in the progression of myocardial I/R injury remains unclear. The present study aimed to investigate the role of EDA2R during myocardial I/R injury and the molecular mechanisms involved. In vitro, dexmedetomidine (DEX) exhibited a protective effect on hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury and downregulated EDA2R expression. Subsequently, EDA2R silencing enhanced cell viability and reduced the apoptosis of cardiomyocytes. Furthermore, knockdown of EDA2R led to an elevated mitochondrial membrane potential (MMP), repressed the release of Cytochrome C and upregulated Bcl-2 expression. EDA2R knockdown also resulted in downregulated expression of Bax, and decreased activity of Caspase-3 and Caspase-9 in cardiomyocytes, reversing the effects of H/R on mitochondria-mediated apoptosis. In addition, knockdown of EDA2R suppressed H/R-induced oxidative stress. Mechanistically, EDA2R knockdown inactivated the NF-κB signaling pathway. Additionally, downregulation of EDA2R weakened myocardial I/R injury in mice, as reflected by improved left ventricular function and reduced infarct size, as well as suppressed apoptosis and oxidative stress. Additionally, EDA2R knockdown repressed the activation of NF-κB signal in vivo. Collectively, knockdown of EDA2R exerted anti-apoptotic and antioxidant effects against I/R injury in vivo and in vitro by suppressing the NF-κB signaling pathway.
PubMed: 38797667
DOI: 10.1538/expanim.24-0020 -
The British Journal of Oral &... Apr 2024The aim of this study was to determine what is considered a long oral surgery and conduct a cost-effective analysis of sedative agents used for intravenous sedation... (Review)
Review
The aim of this study was to determine what is considered a long oral surgery and conduct a cost-effective analysis of sedative agents used for intravenous sedation (IVS) and sedation protocols for such procedures. Pubmed and Google Scholar databases were used to identify human studies employing IVS for extractions and implant-related surgeries, between 2003 and July/2023. Sedation protocols and procedure lengths were documented. Sedative satisfaction, operator satisfaction, and sedation assessment were also recorded. Cost estimation was based on The British National Formulary (BNF). To assess bias, the Cochrane Risk of Bias tools were employed. This review identified 29 randomised control trials (RCT), six cohorts, 14 case-series, and one case-control study. The study defined long procedures with an average duration of 31.33 minutes for extractions and 79.37 minutes for implant-related surgeries. Sedative agents identified were midazolam, dexmedetomidine, propofol, and remimazolam. Cost analysis revealed midazolam as the most cost-effective option (<10 pence per procedure per patient) and propofol the most expensive option (approximately £46.39). Bias analysis indicated varying degrees of bias in the included studies. Due to diverse outcome reporting, a comparative network approach was employed and revealed benefits of using dexmedetomidine, propofol, and remimazolam over midazolam. Midazolam, dexmedetomidine, propofol, and remimazolam demonstrated safety and efficacy as sedative agents for conscious IVS in extended procedures like extractions or implant-related surgeries. While midazolam is the most cost-effective option, dexmedetomidine, propofol, and remimazolam offer subjective and clinical benefits. The relatively higher cost of propofol may impede its widespread use. Dexmedetomidine and remimazolam stand out as closely priced options, necessitating further clinical investigations for comparative efficacy assessment.
PubMed: 38797651
DOI: 10.1016/j.bjoms.2024.04.006 -
BMC Anesthesiology May 2024Perioperative Neurocognitive Disorders (PND) is a common neurological complication after radical colorectal cancer surgery, which increases adverse outcomes. So, our... (Randomized Controlled Trial)
Randomized Controlled Trial
The influence of dexmedetomidine added to ropivacaine for transversus abdominis plane block on perioperative neurocognitive disorders after radical colorectal cancer surgery: randomized, double-blind, controlled trial.
OBJECTIVE
Perioperative Neurocognitive Disorders (PND) is a common neurological complication after radical colorectal cancer surgery, which increases adverse outcomes. So, our objective is to explore the influence of dexmedetomidine added to ropivacaine for transversus abdominis plane block (TAPB) on perioperative neurocognitive disorders, and to provide a new way to reduce the incidence of PND.
METHODS
One hundred and eighty patients submitted to radical laparoscopic colorectal cancer surgery were randomly divided into Control group and Dex group. Ultrasound guided TAPB was performed after anesthesia induction: 0.5% ropivacaine 20 ml was injected into each transversus abdominis plane in Control group, 0.5% ropivacaine + 1 μg/kg dexmedetomidine (amounting to 20 ml) in Dex group. We observed the incidence of PND within 30 days after surgery.
RESULTS
One hundred and sixty-nine cases were finally analyzed, including 84 cases in Control group and 85 cases in Dex group. Compared with Control group, there was no significant difference in terms of the incidence of PND on the 3rd day and the 7th day (P > 0.05), but the incidence significantly decreased at the 6th hour, at the 24th hour and on the 30th day after surgery (P < 0.05) in Dex group.
CONCLUSION
Dexmedetomidine added to ropivacaine for TAPB can reduce the incidence of PND in the first 24 h after surgery and on the 30th postoperative day, which may be related to reduce the consumption of general anesthetics and provide satisfactory postoperative analgesia.
TRIAL REGISTRATION
29 /05/ 2021, ChiCTR2100046876.
Topics: Humans; Dexmedetomidine; Ropivacaine; Double-Blind Method; Male; Female; Nerve Block; Middle Aged; Abdominal Muscles; Colorectal Neoplasms; Anesthetics, Local; Aged; Postoperative Cognitive Complications; Drug Therapy, Combination; Laparoscopy
PubMed: 38796412
DOI: 10.1186/s12871-024-02569-8 -
Animals : An Open Access Journal From... May 2024Formosan serows are endemic to the mountainous regions of Taiwan. This crossover study aimed to assess and compare the anesthetic induction and recovery using either...
Formosan serows are endemic to the mountainous regions of Taiwan. This crossover study aimed to assess and compare the anesthetic induction and recovery using either dexmedetomidine-tiletamine-zolazepam (DZ) or dexmedetomidine-ketamine (DK) by intramuscular injection from a blow-dart in a zoo environment. Ten anesthetic procedures were performed with five adult Formosan serows. Each participant was anesthetized with both combinations at least once with a minimal 12-month washout. The average dosages were 22.6 ± 8.3 µg/kg and 35.8 ± 2.5 µg/kg for dexmedetomidine and 185.6 ± 123.6 and 357.8 ± 25.2 µg/kg for atipamezole for the DZ and DK groups, respectively. The doses of tiletamine-zolazepam and ketamine were 2.1 ± 0.25 mg/kg and 3.6 ± 0.3 mg/kg, respectively, in the DZ and DK groups. All participants were induced within 10 min (median: 8 min for both groups), except one serow in the DK group with an induction time of 22 min. Serows in the DZ group had a lower respiratory rate ( = 0.016) and lower rectal temperature ( = 0.008) than those in the DK group. The quality of recovery was poor for DZ because of paddling, prolonged recovery, and ataxia after antagonism of dexmedetomidine with atipamezole. The induction of anesthesia with dexmedetomidine-tiletamine-zolazepam was uneventful and rapid. However, recovery from this combination was not smooth.
PubMed: 38791631
DOI: 10.3390/ani14101413 -
Anesthesiology May 2024Impaired glymphatic clearance of cerebral metabolic products and fluids contribute to traumatic and ischemic brain oedema and neurodegeneration in preclinical models....
BACKGROUND
Impaired glymphatic clearance of cerebral metabolic products and fluids contribute to traumatic and ischemic brain oedema and neurodegeneration in preclinical models. Glymphatic perivascular cerebrospinal fluid (CSF) flow varies between anesthetics possibly due to changes in vasomotor tone and thereby in the dynamics of the periarterial CSF-containing space. To better understand the influence of anesthetics and carbon dioxide levels on CSF dynamics, we studied the effect of periarterial size modulation on CSF distribution by changing blood carbon dioxide levels and anesthetic regimens with opposing vasomotor influences - vasoconstrictive ketamine-dexmedetomidine (K/DEX) and vasodilatory isoflurane (ISO).
METHODS
End-tidal carbon dioxide (EtCO2) was modulated with either supplemental inhaled carbon dioxide to reach hypercapnia (EtCO2 80 mmHg) or hyperventilation (EtCO2 20 mmHg) in tracheostomized and anesthetized female rats. Distribution of intracisternally infused radiolabeled CSF tracer 111In-diethylamine pentaacetate was assessed for 86 minutes in 1) normoventilated (EtCO2 40 mmHg) K/DEX, 2) normoventilated ISO, 3) hypercapnic K/DEX, and 4) hyperventilated ISO groups using dynamic whole-body single-photon emission tomography. CSF volume changes were assessed with magnetic resonance imaging.
RESULTS
Under normoventilation, cortical CSF tracer perfusion, perivascular space size around middle cerebral arteries (MCAs), and intracranial CSF volume were higher under K/DEX compared with ISO (cortical Cmax ratio 2.33 [95% CI 1.35 to 4.04], perivascular size ratio 2.20 [95% CI 1.09 to 4.45], and intracranial CSF volume ratio 1.90 [95% CI 1.33 to 2.71]). Under ISO, tracer was directed to systemic circulation. Under K/DEX, the intracranial tracer distribution and CSF volume were uninfluenced by hypercapnia compared with normoventilation. Intracranial CSF tracer distribution was unaffected by hyperventilation under ISO despite a 28% increase in CSF volume around MCAs.
CONCLUSIONS
K/DEX and ISO overrode carbon dioxide as a regulator of CSF flow. K/DEX could be used to preserve CSF space and dynamics in hypercapnia whereas hyperventilation was insufficient to increase cerebral CSF perfusion under ISO.
PubMed: 38787687
DOI: 10.1097/ALN.0000000000005039 -
Veterinary Sciences Apr 2024Dexmedetomidine is an a-agonist commonly used in veterinary practice. Occasionally, the administered dose of dexmedetomidine may result in insufficient sedation, and an...
Dexmedetomidine is an a-agonist commonly used in veterinary practice. Occasionally, the administered dose of dexmedetomidine may result in insufficient sedation, and an additional dose or drug may be required. The sedative effects of seven different drugs administered at subsequent time points after an initial, insufficient dose of dexmedetomidine were evaluated. Seven adult cats participated in this crossover, blind, randomised study. The groups consisted of two consecutive doses of dexmedetomidine (15 + 10 μg/kg) (DD) or a dose of dexmedetomidine (15 μg/kg) followed by either NS 0.9% (DC-control group), tramadol 2 mg/kg (DT), butorphanol 0.2 mg/kg (DBT), buprenorphine 20 μg/kg (DBP), ketamine 2 mg/kg (DK), or midazolam 0.1 mg/kg (DM). Sedation was evaluated using the Grint sedation scale. In all groups, atipamezole was administered at the end of the evaluation, and recovery was assessed using the Lozano and Sams recovery scales. The DC and DM groups exhibited minimal sedative effects. The maximum sedative effect was observed in the DD and DK groups, while sedation in the DD and DK groups was significantly higher compared to the DC group. Recovery in all groups was uneventful, except in the DM group, where it was prolonged and difficult, although no statistically significant difference was detected. Therefore, insufficient sedation with dexmedetomidine can be enhanced by a subsequent dose of dexmedetomidine, ketamine, or butorphanol, whereas the addition of midazolam reduces sedation and prolongs recovery.
PubMed: 38787158
DOI: 10.3390/vetsci11050186 -
JPMA. the Journal of the Pakistan... May 2024To compare the effects of bupivacaine alone and in combination with dexmedetomidine following staging laparoscopies. (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
OBJECTIVES
To compare the effects of bupivacaine alone and in combination with dexmedetomidine following staging laparoscopies.
METHODS
This triple-blinded, prospective study was conducted from June to September 2021 at a tertiary care cancer hospital in Lahore, Pakistan, and comprised adult patients having American Society of Anaesthesiologists grade I-III, weighing >30kg and undergoing diagnostic staging laparoscopy. The subjects were randomised into two equal groups. Group A received 6ml of 2mg/kg bupivacaine at each of the four laparoscopic port sites before skin closure, while group B additionally received 2μg/kg dexmedetomidine. The presence and severity of pain were recorded and assessed at 15 min, 1, 2 and 4 hours as well as at the time of discharge from the post-anaesthesia care unit. The time to first request for rescue analgesia, total morphine consumption, and the occurrence of any side effects during their stay were also recorded. Data was analysed using SPSS 23.
RESULTS
Of the 30 patients, 15(50%) were in group A; 10(66.6%) males and 5(33.3%) females with mean age 43.27±7.59 years. There were 15(50%) patients in group B; 12(80%) males and 3(20%) females with mean age 41.36±12.42 years (p>0.05). Of the total, 29(96.66%) patients were classified as American Society of Anaesthesiologists grade II, and 1(3.33%) patient in group A was grade III. There was no significant difference between the groups in any of the outcome measures assessed (p>0.05), and none of the patients experienced any side effect throughout the post-operative stay.
CONCLUSIONS
The combination of dexmedetomidine and bupivacaine had no significant improvement in pain relief compared to bupivacaine alone.
Topics: Humans; Bupivacaine; Female; Male; Laparoscopy; Anesthetics, Local; Adult; Dexmedetomidine; Middle Aged; Prospective Studies; Pain, Postoperative; Pain Measurement; Pakistan; Analgesics, Non-Narcotic; Neoplasm Staging
PubMed: 38783430
DOI: 10.47391/JPMA.8483 -
Drug Design, Development and Therapy 2024Remimazolam, an ultra-short-acting and fast-metabolized sedative, has only been sporadically investigated in children. This study was performed to determine the... (Randomized Controlled Trial)
Randomized Controlled Trial
Preoperative Anxiolytic and Sedative Effects of Intranasal Remimazolam and Dexmedetomidine: A Randomized Controlled Clinical Study in Children Undergoing General Surgeries.
PURPOSE
Remimazolam, an ultra-short-acting and fast-metabolized sedative, has only been sporadically investigated in children. This study was performed to determine the beneficial effects of intranasal remimazolam or dexmedetomidine on preoperative anxiety in children undergoing general surgeries.
PATIENTS AND METHODS
Ninety children were randomly and equally assigned to Group R (intranasal remimazolam 1.5mg kg), Group D (intranasal dexmedetomidine 2 mcg kg), and Group C (intranasal distilled water). The primary outcomes were the preoperative anxiety scores using the modified Yale preoperative anxiety scale (m-Ypas). The secondary outcomes included the cooperation behaviour of intranasal drug application, preoperative sedation levels, parental separation anxiety scores (PSAS), and mask acceptance scores (MAS).
RESULTS
Group R showed a significant low anxiety at 10 min after intranasal premedication (vs group C, P=0.010; vs group D, P = 0.002) and at anaesthesia induction (vs group C, P = 0.004). Group D showed a significantly low anxiety score only prior to anaesthesia induction (vs group C, P = 0.005). Most children in group R achieved mild sedation at 10 min (vs group C, P < 0.001; vs group D, P < 0.001), with a few progressing to deep sedation afterwards, while group D tended toward deep sedation. Compared to Group C, patients in Group R performed significantly better on the MAS (P = 0.014) and PSAS (P = 0.008). However, remimazolam did cause poor cooperation behavior to the intranasal application due to its mucosal irritation (vs group C, P = 0.001; vs group D, P = 0.010).
CONCLUSION
Both intranasal remimazolam and dexmedetomidine can effectively alleviate preoperative anxiety in children. While intranasal remimazolam has a rapid onset, it produces only mild sedation and causes substantial nasal irritation.
TRIAL REGISTRATION
NCT04720963, January 22, 2021, ClinicalTrials.Gov.
Topics: Humans; Administration, Intranasal; Dexmedetomidine; Hypnotics and Sedatives; Male; Female; Anti-Anxiety Agents; Child; Child, Preschool; Anxiety; Benzodiazepines; Double-Blind Method
PubMed: 38774484
DOI: 10.2147/DDDT.S461122