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Clinical Journal of the American... Oct 2021AKI is a common complication after pediatric cardiac surgery and has been associated with higher morbidity and mortality. We aimed to compare the efficacy of available... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVES
AKI is a common complication after pediatric cardiac surgery and has been associated with higher morbidity and mortality. We aimed to compare the efficacy of available pharmacologic and nonpharmacologic strategies to prevent AKI after pediatric cardiac surgery.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
PubMed/MEDLINE, Embase, Cochrane Controlled Trials Register, and reference lists of relevant articles were searched for randomized controlled trials from inception until August 2020. Random effects traditional pairwise, Bayesian network meta-analyses, and trial sequential analyses were performed.
RESULTS
Twenty randomized controlled trials including 2339 patients and 11 preventive strategies met the eligibility criteria. No overall significant differences were observed compared with control for corticosteroids, fenoldopam, hydroxyethyl starch, or remote ischemic preconditioning in traditional pairwise meta-analysis. In contrast, trial sequential analysis suggested a 80% relative risk reduction with dexmedetomidine and evidence of <57% relative risk reduction with remote ischemic preconditioning. Nonetheless, the network meta-analysis was unable to demonstrate any significant differences among the examined treatments, including also acetaminophen, aminophylline, levosimendan, milrinone, and normothermic cardiopulmonary bypass. Surface under the cumulative ranking curve probabilities showed that milrinone (76%) was most likely to result in the lowest risk of AKI, followed by dexmedetomidine (70%), levosimendan (70%), aminophylline (59%), normothermic cardiopulmonary bypass (57%), and remote ischemic preconditioning (55%), although all showing important overlap.
CONCLUSIONS
Current evidence from randomized controlled trials does not support the efficacy of most strategies to prevent AKI in the pediatric population, apart from limited evidence for dexmedetomidine and remote ischemic preconditioning.
Topics: Acute Kidney Injury; Adrenergic alpha-2 Receptor Agonists; Age Factors; Bayes Theorem; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Child, Preschool; Dexmedetomidine; Female; Humans; Infant; Infant, Newborn; Ischemic Preconditioning; Male; Network Meta-Analysis; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome
PubMed: 34620647
DOI: 10.2215/CJN.05800421 -
European Journal of Anaesthesiology Oct 2023Pain after craniotomy can be intense and its management is often suboptimal.
BACKGROUND
Pain after craniotomy can be intense and its management is often suboptimal.
OBJECTIVES
We aimed to evaluate the available literature and develop recommendations for optimal pain management after craniotomy.
DESIGN
A systematic review using procedure-specific postoperative pain management (PROSPECT) methodology was undertaken.
DATA SOURCES
Randomised controlled trials and systematic reviews published in English from 1 January 2010 to 30 June 2021 assessing pain after craniotomy using analgesic, anaesthetic or surgical interventions were identified from MEDLINE, Embase and Cochrane Databases.
ELIGIBILITY CRITERIA
Each randomised controlled trial (RCT) and systematic review was critically evaluated and included only if met the PROSPECT requirements. Included studies were evaluated for clinically relevant differences in pain scores, use of nonopioid analgesics, such as paracetamol and NSAIDs, and current clinical relevance.
RESULTS
Out of 126 eligible studies identified, 53 RCTs and seven systematic review or meta-analyses met the inclusion criteria. Pre-operative and intra-operative interventions that improved postoperative pain were paracetamol, NSAIDs, intravenous dexmedetomidine infusion, regional analgesia techniques, including incision-site infiltration, scalp nerve block and acupuncture. Limited evidence was found for flupirtine, intra-operative magnesium sulphate infusion, intra-operative lidocaine infusion, infiltration adjuvants (hyaluronidase, dexamethasone and α-adrenergic agonist added to local anaesthetic solution). No evidence was found for metamizole, postoperative subcutaneous sumatriptan, pre-operative oral vitamin D, bilateral maxillary block or superficial cervical plexus block.
CONCLUSIONS
The analgesic regimen for craniotomy should include paracetamol, NSAIDs, intravenous dexmedetomidine infusion and a regional analgesic technique (either incision-site infiltration or scalp nerve block), with opioids as rescue analgesics. Further RCTs are required to confirm the influence of the recommended analgesic regimen on postoperative pain relief.
Topics: Humans; Pain Management; Dexmedetomidine; Acetaminophen; Analgesics; Pain, Postoperative; Craniotomy; Anti-Inflammatory Agents, Non-Steroidal
PubMed: 37417808
DOI: 10.1097/EJA.0000000000001877 -
Pediatric Critical Care Medicine : a... Jan 2024To systematically review literature describing the clinical presentation, risk factors, and treatment for dexmedetomidine withdrawal in the PICU (PROSPERO:... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To systematically review literature describing the clinical presentation, risk factors, and treatment for dexmedetomidine withdrawal in the PICU (PROSPERO: CRD42022307178).
DATA SOURCES
MEDLINE/PubMed, Cochrane, Web of Science, and Scopus databases were searched.
STUDY SELECTION
Eligible studies were published from January 2000 to January 2022 and reported clinical data for patients younger than 21 years old following discontinuation of dexmedetomidine after greater than or equal to 24 hours of infusion.
DATA EXTRACTION
Abstracts identified during an initial search were screened and data were manually abstracted after full-text review of eligible articles. The Newcastle-Ottawa Scale was used to assess study quality. Summary statistics were provided and Spearman rank correlation coefficient was used to identify relationships between covariates and withdrawal signs. A weighted prevalence for each withdrawal sign was generated using a random-effects model.
DATA SYNTHESIS
Twenty-three studies (22 of which were retrospective cohort studies) containing 28 distinct cohorts were included. Median cumulative dexmedetomidine exposure by dose was 105.95 μg/kg (range, 30-232.7 μg/kg), median dexmedetomidine infusion duration was 131.75 hours (range, 20.5-525.6 hr). Weighted estimates for proportion (95% CI) of subjects experiencing withdrawal signs across all cohorts were: hypertension 0.34 (range, 0.0-0.92), tachycardia 0.26 (range, 0.0-0.87), and agitation 0.26 (range, 0.09-0.77). Meta-analysis revealed no correlation between dexmedetomidine exposure variables and withdrawal signs. A moderate negative monotonic relationship existed between the proportion of patients who had undergone cardiac surgery and the proportion experiencing hypertension (correlation coefficient, -0.47; p = 0.048) and tachycardia (correlation coefficient, -0.57; p = 0.008), indicating that in cohorts with a higher proportion of patients who were postcardiac surgery, there were fewer occurrences of hypertension and or tachycardia.
CONCLUSIONS
On review of the 2000-2022 literature, dexmedetomidine withdrawal may be characterized by tachycardia, hypertension, or agitation, particularly with higher cumulative doses or prolonged durations. Since most studies included in the review were retrospective, prospective studies are needed to further clarify risk factors, establish diagnostic criteria, and identify optimal management strategies.
Topics: Humans; Dexmedetomidine; Hypertension; Intensive Care Units, Pediatric; Retrospective Studies; Substance Withdrawal Syndrome; Tachycardia
PubMed: 37855676
DOI: 10.1097/PCC.0000000000003376 -
AANA Journal Dec 2023Effective control of labor pain is critical to the birthing experience. Dexmedetomidine is an alternative adjunct to labor analgesia without the risk of opioid-related... (Meta-Analysis)
Meta-Analysis
Effective control of labor pain is critical to the birthing experience. Dexmedetomidine is an alternative adjunct to labor analgesia without the risk of opioid-related adverse effects. The purpose of this study was to examine the efficacy and safety of neuraxial dexmedetomidine versus neuraxial opioids in labor analgesia. PubMed, CINAHL, Cochrane, Google Scholar, and grey literature were searched for evidence. Risk ratio and mean difference (MD) were used to estimate outcomes. The quality of evidence was assessed using the Risk of Bias and GRADE system. Sixteen studies including 1,669 patients were analyzed. Compared with opioids, dexmedetomidine prolonged the duration of analgesia (MD, 47.58 minutes; 95% confidence interval [CI], 1.57 to 93.58; = .04), reduced pain score (MD, -0.71; 95% CI, -1.17 to -0.24; = .003), and shortened the onset of analgesia (MD, -1.14 minutes; 95% CI, -1.93 to -0.35; = .005). Dexmedetomidine did not affect the duration of first and second stages of labor, number of spontaneous, assisted, and cesarean delivery. Additionally, dexmedetomidine had little to no effects on maternal and neonatal outcomes. Neuraxial dexmedetomidine is more favorable than neuraxial opioids for labor analgesia. Extrapolation of the findings to clinical practice should take into considerations the review limitations.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Analgesics, Opioid; Dexmedetomidine; Randomized Controlled Trials as Topic; Analgesics; Analgesia
PubMed: 37987724
DOI: No ID Found -
The Cochrane Database of Systematic... Nov 2022Newborn infants affected by hypoxic-ischemic encephalopathy (HIE) undergo therapeutic hypothermia. As this treatment seems to be associated with pain, and intensive and... (Review)
Review
BACKGROUND
Newborn infants affected by hypoxic-ischemic encephalopathy (HIE) undergo therapeutic hypothermia. As this treatment seems to be associated with pain, and intensive and invasive care is needed, pharmacological interventions are often used. Moreover, painful procedures in the newborn period can affect pain responses later in life, impair brain development, and possibly have a long-term negative impact on neurodevelopment and quality of life.
OBJECTIVES
To determine the effects of pharmacological interventions for pain and sedation management in newborn infants undergoing therapeutic hypothermia. Primary outcomes were analgesia and sedation, and all-cause mortality to discharge.
SEARCH METHODS
We searched CENTRAL, PubMed, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and the trial register ISRCTN in August 2021. We also checked the reference lists of relevant articles to identify additional studies.
SELECTION CRITERIA
We included randomized controlled trials (RCT), quasi-RCTs and cluster-randomized trials comparing drugs used for the management of pain or sedation, or both, during therapeutic hypothermia: any opioids (e.g. morphine, fentanyl), alpha-2 agonists (e.g. clonidine, dexmedetomidine), N-Methyl-D-aspartate (NMDA) receptor antagonist (e.g. ketamine), other analgesics (e.g. paracetamol), and sedatives (e.g. benzodiazepines such as midazolam) versus another drug, placebo, no intervention, or non-pharmacological interventions. Primary outcomes were analgesia and sedation, and all-cause mortality to discharge.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed studies identified by the search strategy for inclusion. We planned to use the GRADE approach to assess the certainty of evidence. We planned to assess the methodological quality of included trials using Cochrane Effective Practice and Organisation of Care Group (EPOC) criteria (assessing randomization, blinding, loss to follow-up, and handling of outcome data). We planned to evaluate treatment effects using a fixed-effect model with risk ratio (RR) for categorical data and mean, standard deviation (SD), and mean difference (MD) for continuous data. MAIN RESULTS: We did not find any completed studies for inclusion. Amongst the four excluded studies, topiramate and atropine were used in two and one trial, respectively; one study used dexmedetomidine and was initially reported in 2019 to be a randomized trial. However, it was an observational study (correction in 2021). We identified one ongoing study comparing dexmedetomidine to morphine.
AUTHORS' CONCLUSIONS
We found no studies that met our inclusion criteria and hence there is no evidence to recommend or refute the use of pharmacological interventions for pain and sedation management in newborn infants undergoing therapeutic hypothermia.
Topics: Infant, Newborn; Humans; Dexmedetomidine; Clonidine; Hypothermia, Induced; Pain; Morphine Derivatives; Observational Studies as Topic
PubMed: 36354070
DOI: 10.1002/14651858.CD015023.pub2 -
Annals of Intensive Care Aug 2022Dexmedetomidine is widely used in patients with sepsis. However, its effect on septic patients remains controversial. The objective of this study was to summarize all... (Review)
Review
BACKGROUND
Dexmedetomidine is widely used in patients with sepsis. However, its effect on septic patients remains controversial. The objective of this study was to summarize all randomized controlled trials (RCTs) examining dexmedetomidine use in sepsis patients.
METHODS
This systematic review and meta-analysis included RCTs comparing dexmedetomidine with other sedatives in adult sepsis patients. We generated pooled relative risks (RRs) and standardized mean differences and performed trial sequential analysis and a cumulative meta-analysis. The primary outcome was mortality, and the secondary outcomes were the length of the intensive care unit stay, duration of mechanical ventilation, number of ventilation-free days, incidence of total adverse event, incidence of delirium, and levels of interleukin 6, tumor necrosis factor alpha, and alanine aminotransferase.
RESULTS
We included 19 RCTs that enrolled 1929 patients. Compared with other sedatives, dexmedetomidine decreased the all-cause mortality (RR 0.83; 95% confidence interval [CI] [0.69, 0.99]) and inflammatory response (interleukin 6 and tumor necrosis factor alpha levels at 24 h: standardized mean difference (SMD) - 2.15; 95% CI [- 3.25, - 1.05] and SMD - 1.07, 95% CI [- 1.92, - 0.22], respectively). Trial sequential analysis showed that it is not up to required information size. The overall risk adverse events was similar between dexmedetomidine and the other sedatives (RR 1.27, 95% CI [0.69, 2.36]), but dexmedetomidine increased the risk of arrhythmias (RR 1.43, 95% CI [0.59, 3.51]). Length of intensive care unit stay (SMD - 0.22; 95% CI [- 0.85, - 0.41]), duration of mechanical ventilation (SMD 0.12; 95% CI [- 1.10, 1.35]), incidence of delirium (RR 0.98; 95% CI [0.72, 1.33]), and levels of alanine aminotransferase and creatinine at 24 h were not significantly reduced.
CONCLUSIONS
Dexmedetomidine in sepsis patients could significantly reduce mortality compared with benzodiazepines but not with propofol. In addition, dexmedetomidine can significantly decrease inflammatory response in patients with sepsis compared with other sedatives. Dexmedetomidine might lead to an increased incidence of arrhythmias, but its safety profile did not show significant differences in the incidence of total adverse events. Future RCTs are needed to determine the sepsis patient population that would benefit most from dexmedetomidine and its optimal dosing regimen.
PubMed: 36029410
DOI: 10.1186/s13613-022-01052-2 -
Cureus Dec 2022Dexmedetomidine has been approved as a sedative agent in critical patients. It is also frequently used as an adjuvant with local anesthetic in spinal anesthesia.... (Review)
Review
BACKGROUND
Dexmedetomidine has been approved as a sedative agent in critical patients. It is also frequently used as an adjuvant with local anesthetic in spinal anesthesia. However, its use as an adjuvant has not been approved due to the paucity of data. The present systematic review and meta-analysis were undertaken to synthesize evidence for efficacy and safety when dexmedetomidine is combined with bupivacaine in spinal anesthesia.
METHODS
A literature search was done using PubMed, Google Scholar, Embase, and Cochrane Library. Search results were screened and eligible studies were included to perform a systematic review and meta-analysis using the software 'Review Manager (RevMan) version 5.4.1' using a random effect model. Cochrane's' Risk of Bias tool (RoB2)' was used for quality assessment. Mean and standard deviation was used to calculate the standardized mean difference and its forest plot for efficacy measures. For the adverse event, a number of events were used to determine the risk ratio and its forest plot using RevMan software. Publication bias is visualized using a funnel plot.
RESULTS
A total of 21 randomized control trials evaluating the efficacy and safety of intrathecal dexmedetomidine were included in the meta-analysis. A total of 1382 participants was included in this meta-analysis. The effect estimates for efficacy parameters, i.e. duration of the sensory block having SMD 2.33; CI, 1.83-2.83, motor block with SMD 1.83, CI 1.21, 2.46, and analgesia SMD 2.81; CI, 2.11-3.51. The risk ratio for adverse effects, i.e. nausea/vomiting, bradycardia, hypotension was not significant whereas it was significant for the incidence of shivering with RR 0.38; CI 0.23-0.97. The overall risk of bias among included studies was either of 'some concern' or 'high risk.'
CONCLUSIONS
Intrathecal dexmedetomidine when combined with bupivacaine was found to significantly increase the three efficacy parameters, i.e. duration of sensory block, motor block, and analgesia. It also appears to be safe with no increased risk of bradycardia or hypotension. It is also associated with decreased postoperative shivering.
PubMed: 36644042
DOI: 10.7759/cureus.32425 -
Frontiers in Pediatrics 2023To compare the effects of intranasal dexmedetomidine (Dex) and oral midazolam in the preoperative medication of children by using a method of meta-analysis. (Review)
Review
OBJECTIVE
To compare the effects of intranasal dexmedetomidine (Dex) and oral midazolam in the preoperative medication of children by using a method of meta-analysis.
METHODS
Cochrane Library, Pubmed, Embase, and Web of Science were searched from inception to July 2023. Randomized controlled trials (RCTs) of intranasal Dex vs. oral midazolam in pediatric premedication were collected. Stata 15.0 statistical software was used to analyze the collected data. Relative risk (RR) and 95% confidence interval (CI) were used as effect sizes.
RESULTS
A total of 11 studies with 824 children were included, containing 415 patients in the Dex group and 409 patients in the midazolam group. Compared with the oral midazolam group, the intranasal Dex group had a better preoperative sedation effect at parent-child separation (RR = 1.37, 95% CI: 1.14-1.64) and anesthesia induction (RR = 2.08, 95% CI: 1.03-4.22). In addition, there was no significant difference in the incidence of analgesia remedy (RR = 0.60, 95% CI: 0.36-1.00) the acceptance of anesthesia masks (RR = 0.97, 95% CI: 0.83-1.12), and incidence of adverse events between (RR = 0.25, 95% CI: 0.06-1.13, = 0.072) between the intranasal Dex and oral midazolam groups.
CONCLUSION
Compared with oral midazolam, intranasal Dex has better sedative effects of parent-child separation and anesthesia induction in pediatric premedication, but there was no difference in the incidence of anesthesia remedy, anesthesia mask acceptance, and incidence of adverse events. Therefore, compared with oral midazolam, intranasal Dex is a better choice for premedication in children.
PubMed: 38027288
DOI: 10.3389/fped.2023.1264081 -
Cureus Jun 2022Delirium is defined by the DSM-5 as a fluctuating course of disturbance in attention, cognition, and awareness that develops over a short period without any... (Review)
Review
Delirium is defined by the DSM-5 as a fluctuating course of disturbance in attention, cognition, and awareness that develops over a short period without any pre-existing neurocognitive disorder. As people age, there is an increased risk of complications that may occur following a surgical procedure and one such acute complication is delirium. Studies are emerging to reduce the incidence of postoperative delirium, and one such preventive measures implemented in recent years include the administration of dexmedetomidine, a high selectivity α-2 adrenoceptor agonist. This study aims to review the efficacy of Dexmedetomidine in the prevention of postoperative delirium in randomized controlled trials in patients older than 18 years of age. The literature was explored in three online databases, namely, PubMed, Science Direct, and Scopus. Appropriate keywords and MesH terms were employed to scrutinize relevant articles that demonstrated the effects of dexmedetomidine in the prevention of postoperative delirium. The data was restricted to randomized controlled trials and clinical trials published from 2017 to 2021 in human patients older than >18 years of age undergoing non-cardiac-related procedures. The randomized clinical trials were critically assessed with the Cochrane risk of bias tool. We proceeded to screen 428 records with the assessment of the PRISMA chart and filtered out 420 papers to obtain a total of eight studies where we identified data such as sample size, types of surgeries in which the patients were involved, the delirium assessment tool, the plan of the administration of dexmedetomidine and the outcomes evaluated in each study. The Confusion Assessment Method (CAM) was the prevailing assessment tool used with the sole purpose to evaluate the incidence of postoperative delirium as the primary outcome, and assessment of inflammatory cytokines, sleep quality, and pain scales were considered as secondary outcomes. The dosage of dexmedetomidine varied among studies, and it displayed varying impacts on postoperative delirium and the secondary outcomes as well. Limitations include varying ages and ethnicities of the population. It was concluded that dexmedetomidine prevents the development of postoperative delirium in elderly patients undergoing non-cardiac surgical interventions by modulating important predisposing factors such as neuroinflammation, pain, and sleep quality. No funding was made for this study.
PubMed: 35812638
DOI: 10.7759/cureus.25639 -
Journal of Clinical Pharmacy and... Mar 2022Acute kidney injury (AKI) is a complication following surgery and has been associated with worsened patient outcomes. Providers have used agents that may confer a degree... (Meta-Analysis)
Meta-Analysis Review
WHAT IS KNOWN AND OBJECTIVE
Acute kidney injury (AKI) is a complication following surgery and has been associated with worsened patient outcomes. Providers have used agents that may confer a degree of renal protection in the perioperative stage. Such is the case of dexmedetomidine, a selective alpha-2 adrenergic agonist used in the intensive care unit (ICU) as a sedative agent. The primary objective of this meta-analysis was to characterize the use of dexmedetomidine and to evaluate its impact on renal markers and outcomes in patients after surgery.
METHODS
A systematic review of manuscripts was performed to identify patients who received dexmedetomidine after surgery by searching the PubMed, Embase, and Cochrane databases. The following parameters were captured: blood urea nitrogen (BUN), serum creatinine, creatinine clearance, neutrophil gelatinase-associated lipoprotein (NGAL), cystatin C, urine output, duration of mechanical ventilation, ICU length of stay, AKI, need for dialysis, and mortality.
RESULTS AND DISCUSSION
Nineteen studies with 3,395 patients were included in the analyses. The mean bolus and infusion dose of dexmedetomidine were 0.82 µg/kg and 0.54 mcg/kg/hr, respectively. There was a significant difference in creatinine clearance and NGAL in favour of the dexmedetomidine group. In addition, the dexmedetomidine group had a shorter ICU length of stay, and a lower risk of acute kidney injury and mortality compared to the control. There was no difference in the rest of the parameters.
WHAT IS NEW AND CONCLUSION
Dexmedetomidine appears to have postoperative renal protective effects. This is evidenced by lower NGAL levels and increased creatinine clearance in those who received dexmedetomidine. These effects are associated with decreases in ICU length of stay and risk of AKI and mortality.
Topics: Acute Kidney Injury; Adrenergic alpha-2 Receptor Agonists; Dexmedetomidine; Humans; Hypnotics and Sedatives; Kidney
PubMed: 34510502
DOI: 10.1111/jcpt.13527