Abstract
Purpose
Children undergoing mechanical ventilation (MV) in the pediatric intensive care unit (PICU) require effective sedation to reduce anxiety and discomfort. Dexmedetomidine, an α2-receptor agonist, presents as a viable sedative alternative. However, its clinical outcomes for critically ill, mechanically ventilated children remain to be fully established. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the clinical outcomes and adverse effects of dexmedetomidine in such patients.
Materials and Methods
A systematic search was conducted up to April 2024. RCTs that compare dexmedetomidine with other sedatives in mechanically ventilated children were included. This analysis focused on both the clinical and safety outcomes through meta-analysis.
Results
Included in the analysis were eight trials, involving a total of 387 mechanically ventilated children. Compared to other sedatives, dexmedetomidine reduced the duration of MV [mean difference -3.54 hours; 95% confidence interval (CI), -6.49 to -0.59], particularly in post-operative patients and when compared to fentanyl. However, dexmedetomidine did not significantly impact the length of ICU stay, duration of sedation, or the necessity for additional sedatives. Dexmedetomidine was associated with a significantly increased risk of bradycardia [odds ratio (OR) 6.14; 95% CI, 2.20 to 17.12] and hypotension (OR 8.14; 95% CI, 1.37 to 48.31) compared to other sedatives.
Conclusion
Although dexmedetomidine notably diminished the duration of MV, the potential for adverse effects necessitates further investigation. Large RCTs are needed to validate our findings and refine sedation management in mechanically ventilated children in PICU.
Keywords: Dexmedetomidine, mechanical ventilation, sedation, pediatric, intensive care unit
Graphical Abstract
INTRODUCTION
Mechanically ventilated children are at a high risk of unplanned extubation, which can lead to airway injuries and life-threatening scenarios like asphyxia.1,2,3 Effective sedation and analgesia are important in managing these patients to not only reduce anxiety and discomfort from endotracheal tubes and intensive care unit (ICU) procedures but also to improve their overall care outcomes.4,5,6,7
The concept of “analgosedation” in the pediatric intensive care unit (PICU) is a sedation strategy that combines both analgesia and sedation to enhance the comfort of critically ill patients.8 Despite its critical importance, the management of sedation in the PICU is challenging due to the absence of standardized protocols specifically designed for pediatric patients. Traditional sedatives such as benzodiazepines and propofol, though commonly administered to mechanically ventilated critically ill children, carry the risk of tolerance, dependency, and withdrawal symptoms.9,10
Dexmedetomidine presents as a favorable alternative sedative, recognized for providing milder sedation levels, decreasing delirium, and possessing analgesic qualities. This highly selective α2-receptor agonist, endorsed by the Food and Drug Administration for use in pediatric patients since 2013, achieves its analgesic effect through the activation of α2-adrenoreceptors in both the spinal and supraspinal areas.11 Extensively employed in surgical anesthesia and ICU sedation, dexmedetomidine is acclaimed for its analgesic, sedative, and anti-sympathetic characteristics. In adults, compared to midazolam or propofol, dexmedetomidine has shown advantages such as shortened duration of mechanical ventilation (MV), enhanced ease of arousal, better patient cooperation, and improved communication.12
Although there is substantial evidence supporting the use of dexmedetomidine in adult populations,13,14,15 research concerning its clinical outcomes in critically ill pediatric patients on MV remains scarce. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the clinical outcomes of dexmedetomidine in critically ill children on MV.
MATERIALS AND METHODS
Study design
A systematic review of RCTs comparing dexmedetomidine with other sedatives in critically ill, mechanically ventilated children was conducted. A meta-analysis was also performed to evaluate the efficacy and safety of dexmedetomidine. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.16
As this study involved the analysis of previously published data, institutional review board (IRB) was not required.
Database and search strategy
A meticulously designed peer-reviewed search strategy was developed by a medical librarian (NJK). Searches were conducted in PubMed, Embase, and the Cochrane Library from their inception up to April 4, 2024, utilizing terms related to dexmedetomidine and pediatric age. The details of this search strategy are provided in Supplementary Table 1 (only online).
Data collection and analysis
Titles and abstracts were screened by two independent reviewers (IKL and KHL) to identify trials potentially eligible for inclusion, with full texts being subsequently evaluated for eligibility. Discrepancies between reviewers were resolved through discussion or by consulting a third reviewer as necessary.
Inclusion criteria
Included were trials that: 1) were RCTs; 2) involved critically ill children, defined as invasively mechanically ventilated children (age ≤18 years) admitted to the ICU; 3) had an intervention group receiving intravenous dexmedetomidine; and 4) had a control group receiving other intravenous sedatives.
Exclusion criteria
Excluded were trials that: 1) were observational studies, case reports, letters, editorials, or were not peer-reviewed; 2) included duplicate samples; 3) had participants restricted to neonates or adults; 4) used dexmedetomidine solely during anesthesia or before procedures; 5) administered dexmedetomidine through non-intravenous routes; or 6) used placebo for the control group.
Outcomes
The primary outcome focused on clinical measures such as duration of MV, length of ICU stays, duration of sedation, and total fentanyl bolus administrations. Secondary outcomes included adverse effects such as bradycardia and hypotension.
Quality assessment
The risk of bias in the included trials was assessed by two reviewers (IKL and KHL) using a modified version of the Cochrane risk of bias tool.17 Each trial was examined for bias across various domains, with each domain assessed as having low, unclear, or high risk of bias. The classification of the overall risk of bias for each trial was as follows: low if the risk of bias was low or possibly low in all domains, unclear if there was an unclear risk of bias in at least one domain with no domain having a high risk of bias, or high if there was a high or possibly high risk of bias in at least one domain. Any discrepancies were resolved through discussion and consensus between the reviewers.
Statistical analysis
The meta-analysis was conducted using R version 4.2.2 (R Foundation for Statistical Computing, Vienna, Austria) with the “meta” and “metafor” packages to analyze the efficacy and adverse effects of dexmedetomidine in terms of sedation. For continuous outcome data, the mean difference (MD) served as the primary measure, with estimates aggregated using the inverse variance method. The Mantel-Haenszel method was used to pool estimates for binary outcome data, employing odds ratio (OR) and risk ratio as the primary metrics. Due to the heterogeneity among the included studies, a random effects model was selected for conducting this meta-analysis.
RESULTS
Study selection and characteristics
Initially, searches of reference databases identified a total of 348 records. After the screening and eligibility assessment were conducted, eight studies18,19,20,21,22,23,24,25 satisfied the inclusion criteria and were thus included in the meta-analysis (Fig. 1).
Fig. 1. Flowchart of study selection process.
Of the studies selected, five concentrated on post-operative pediatric patients, whereas the others enrolled medical patients. The detailed characteristics of each study are outlined in Table 1. Importantly, children with atrioventricular block were excluded from four of these studies (Supplementary Table 2, only online).
Table 1. Characteristics of the Included Studies.
| Author | Primary disease | Inclusion criteria | Number of patients (I/C) | Age of patients (I/C) | Intervention group (dose) | Control group (dose) | Initiation of DEX | Termination of DEX |
|---|---|---|---|---|---|---|---|---|
| Tobias, 200418 | Patients admitted to PICU requiring MV | Children and infants | 30 (20/10) | 39/36 months† | DEX (0.25 mcg/kg/h or 0.5 mcg/kg/h) | Midazolam (0.1 mg/kg/h) | After intubation | After 24 hours on either sedation if MV was still necessary, the patient was switched to the alternative agent |
| Prasad, 201219 | Patients undergoing CHD surgery | 1–14 years, overnight MV was anticipated | 60 (30/30) | 6.07/5.67 years† | DEX (0.5 mcg/kg/h) | Fentanyl (1 mcg/kg/h) | In the post-operative intensive care unit | 6AM on the following day to allow an early extubation trial |
| Aydogan, 201320 | Patients undergoing scoliosis surgery | 12–18 years | 32 (16/16) | 13.6/14.8 years‡ | DEX (0.4 mcg/kg/h) | Midazolam (0.1 mg/kg/h) | After surgery | At the time of extubation Up to 24 hours on either sedation if MV was still necessary |
| Saleh, 201621 | Patients scheduled for abdominal surgery | 1–10 years, overnight MV was anticipated | 50 (25/25) | 6.12/5.68 years† | DEX (0.3 mcg/kg/h) | Fentanyl (1 mcg/kg/h) | At arrival to the SICU | After 18 hours |
| Garisto, 201822 | Patients undergoing complex CHD surgery | 1–24 months | 48 (22/26) | 4.5/5.5 months‡ | DEX (0.5 mcg/kg/h), midazolam (0.05 mg/kg/h), morphine (10 mcg/kg/h), paracetamol bolus (7.5–15 mg/kg q6 hours) | Midazolam (0.1 mg/kg/h), morphine (20 mcg/kg/h), paracetamol bolus (7.5–15 mg/kg q6 hours) | After CCU admission | Sedative drug weaning proceeded with MV weaning, according to institutional guidelines |
| Erickson, 202023 | Patients admitted to PICU requiring MV | <16 years | 60 (29/31) | 16/3 months‡ | DEX (1.0 mcg/kg/h) | Usual care: propofol, benzodiazepines, chloral hydrate, ketamine, and barbiturates | After randomization | Until sedation was no longer required or to a maximum of 14 days after enrollment |
| Gulla, 202124 | Patients admitted to PICU requiring MV | 1 month–15 years | 47 (23/24) | 8/5.5 months‡ | DEX (0.25–0.75 mcg/kg/h) | Midazolam (1–4 mcg/kg/min) | After randomization | Until 7 days or weaning from MV |
| Attia, 202225 | Patients undergoing CHD surgery | 1 day–15 years | 60 (30/30) | 28.3/25.7 months† | DEX* (0.2–1.5 mcg/kg/h) | Fentanyl (1–3 mcg/kg/h) | During anesthesia | No information available |
I/C, intervention/control; PICU, pediatric intensive care unit; MV, mechanical ventilation; CHD, congenital heart disease; DEX, dexmedetomidine; SICU, surgical intensive care unit; CCU, cardiac intensive care unit.
*Dexmedetomidine was started with a bolus dose; †Mean values; ‡Median values.
Regarding interventions, most of the studies (7/8, 88%) did not implement a dexmedetomidine bolus at the onset of the infusion. Moreover, dexmedetomidine was the exclusive sedative agent employed in most of the studies (7/8, 88%).
With respect to the control groups, the included trials exhibited variability. Namely, three trials (3/8, 38%) used midazolam, the same number employed fentanyl, and the remaining two trials (2/8, 25%) utilized combinations of different sedative medications.
Risk of bias
The risk of bias for the included studies is depicted in Fig. 2.
Fig. 2. Risk of bias of included studies.
Clinical outcomes
MV duration
Data from seven studies were incorporated into the meta-analysis for the duration of MV. One study18 was excluded due to insufficient extractable data for MV duration. Dexmedetomidine was shown to reduce the duration of MV compared to other sedative drugs [MD -3.54 hours, 95% confidence interval (CI), -6.49 to -0.59] (Fig. 3A).
Fig. 3. A forest plot comparing the duration of MV between (A) dexmedetomidine and alternative sedatives, (B) dexmedetomidine and fentanyl, (C) dexmedetomidine and midazolam. MV, mechanical ventilation; IV, inverse variance; MD, mean difference; CI, confidence interval.
The subgroup analysis indicated that dexmedetomidine considerably shortened the MV duration in comparison to fentanyl (MD -1.53 h; 95% CI, -1.92 to -1.13) (Fig. 3B). Nevertheless, no significant disparities in MV duration were found when dexmedetomidine was compared to midazolam (MD -14.58 h; 95% CI, -34.11 to 4.94) (Fig. 3C).
Furthermore, dexmedetomidine significantly decreased MV duration in post-operative patients (MD -4.22 h; 95% CI, -6.15 to -2.28) (Fig. 4A), but not in medical patients (MD -8.18 h; 95% CI, -46.57 to 30.20) (Fig. 4B).
Fig. 4. A forest plot comparing the duration of MV in (A) post-operative children and (B) medical children. MV, mechanical ventilation; IV, inverse variance; MD, mean difference; CI, confidence interval.
ICU length of stay
Eligible data from three studies were included in the meta-analysis concerning the ICU length of stay. Dexmedetomidine, in comparison to other sedative drugs, showed no significant difference in the length of stay in the ICU (MD -0.20; 95% CI, -1.89 to 1.49) (Fig. 5A).
Fig. 5. A forest plot comparing (A) ICU length of stay, (B) duration of sedation, and (C) the number of fentanyl boluses between dexmedetomidine and other sedatives. ICU, intensive care unit; IV, inverse variance; MD, mean difference; CI, confidence interval.
Duration of sedation
Analysis of data from four studies on sedation duration revealed no significant reduction when compared to other sedatives (MD 0.16; 95% CI, -0.82 to 1.13) (Fig. 5B).
Number of fentanyl bolus doses
Data on the requirement for additional fentanyl boluses were available from three trials. No significant reduction in the need for fentanyl boluses was observed when compared to other sedatives (MD -0.66; 95% CI, -2.73 to 1.40) (Fig. 5C).
Safety outcomes
Four trials contributed data for the analysis of bradycardia incidence, while two trials provided data for the analysis of hypotension incidence. Compared to other sedatives, dexmedetomidine was significantly associated with a higher risk of bradycardia (OR 4.55; 95% CI, 1.51 to 13.69) (Fig. 6A) and hypotension (OR 6.20; 95% CI, 1.01 to 38.07) (Fig. 6B).
Fig. 6. A forest plot comparing (A) bradycardia events and (B) hypotension events between dexmedetomidine and other sedatives. MH, mantel-haenszel; OR, odds ratio; CI, confidence interval.
Publication bias
The funnel plot for MV duration suggests potential publication bias and study heterogeneity due to its asymmetry (Supplementary Fig. 1, only online).
DISCUSSION
This systematic review and meta-analysis, encompassing eight trials with 387 mechanically ventilated children, provides evidence that dexmedetomidine reduces MV duration in this population, particularly in post-operative children and when compared to fentanyl. However, dexmedetomidine did not demonstrate significant effects on the length of ICU stays, duration of sedation, or the need for additional sedatives. Moreover, dexmedetomidine was associated with a significantly higher risk of bradycardia and hypotension compared to other sedatives.
Several hypotheses offer explanations for how dexmedetomidine may improve MV duration. Firstly, dexmedetomidine has been found to enhance compliance, reduce resistance, and improve oxygenation during ongoing MV, potentially leading to a quicker extubation time.26 Secondly, dexmedetomidine’s unique pharmacologic profile, including easy arousability and minimal respiratory depression, may facilitate effective sedation while minimizing complications associated with respiratory suppression.27 Furthermore, dexmedetomidine has been linked to a reduced risk of adverse events like delirium in adults,13 possibly aiding in a smoother extubation process.
Our study builds upon previous meta-analyses in various important aspects. Prior meta-analyses have mainly concentrated on the efficacy of dexmedetomidine in specific pediatric cohorts, such as those undergoing cardiac surgery.28 Our investigation, conversely, broadens this scope to include both post-operative and medical pediatric populations, although dexmedetomidine only reduced MV duration in post-operative children. Unlike the previous meta-analysis that limited its focus to post-operative children,28 we excluded studies that administered dexmedetomidine only during anesthesia to evaluate its clinical effects in the context of MV in PICU settings. Furthermore, our meta-analysis assesses both the sedation clinical outcomes and the adverse effects of dexmedetomidine, unlike previous analyses that concentrated primarily on the safety profile of dexmedetomidine.29
In subgroup analysis, dexmedetomidine significantly decreased MV duration in post-operative children for 4.22 hours. Conversely, no significant impact was observed in medical patients, suggesting that the benefits of dexmedetomidine may be limited to post-operative settings. The clinical relevance of a 4.22-hour reduction may be debatable. However, in post-operative patients, the 4.22-hour reduction could potentially impact clinical practice. Furthermore, dexmedetomidine significantly decreased MV duration when compared to fentanyl, a commonly used opioid in pediatric critical care. This suggests that dexmedetomidine could be a viable alternative to opioid-based sedation strategies, potentially reducing opioid use in the PICU. Further research is needed to determine its efficacy across different patient populations and clinical scenarios.
Additionally, our analysis distinctly focused on trials comparing dexmedetomidine with other sedatives, deliberately excluding those comparisons with placebo. This decision was made under the rationale that placebo-controlled trials might not reflect the practical clinical conditions where dexmedetomidine is usually compared against active sedatives. While placebo-controlled trials are informative regarding dexmedetomidine’s specific effects, our intentional exclusion stems from our objective to evaluate dexmedetomidine’s relative effectiveness against common clinical interventions.
Our study also showed a heightened risk of bradycardia and hypotension linked to dexmedetomidine, consistent with findings from previous research. Acting through α-2a receptor agonism, dexmedetomidine induces sedation by decreasing plasma norepinephrine levels, potentially causing bradycardia and hypotension.30 Despite noting these adverse effects, it is still ambiguous whether they were reversible with non-invasive interventions or required vasoactive agents for management. Additionally, the dose-dependency of these adverse events deserves further exploration. Previous studies have indicated that bradycardia and hypotension are infrequent in critically ill children treated with dexmedetomidine for extended periods and are typically reversible with minimal interventions.29
Challenges emerged in evaluating delirium within our meta-analysis due to scarce data on this outcome. Among the included studies, only two explored the assessment of delirium,20,23 with a single study focusing primarily on adolescent participants.20 Although meta-analyses involving adults have underscored dexmedetomidine’s role in reducing delirium compared to other sedatives,13,31 the lack of pediatric-specific data complicates the interpretation of these findings.
Notwithstanding the valuable insights derived from our study, it presents several limitations that merit acknowledgment. Firstly, evaluating time in adequate sedation was impractical due to the disparate sedation assessment tools used in the studies. Secondly, assessing delirium and withdrawal syndrome in pediatric patients presents intrinsic challenges. Thirdly, the variable definitions of bradycardia across studies undermine the reliability of the results. Fourthly, the inconsistent definitions of bradycardia across studies complicate the reliability of our findings. Furthermore, assessing publication bias was not feasible due to limited number of studies. Lastly, the high heterogeneity and significant risk of bias necessitate caution in interpreting our results.
In summary, our study highlights the potential advantages of dexmedetomidine in shortening MV duration in critically ill children, while also underscoring the importance of further research to delineate its safety profile, harmonize sedation protocols, and refine dosing approaches. Consequently, comprehensive RCTs and multicenter studies are necessary to corroborate our findings and establish evidence-based sedation protocols that cater to the specific demands of PICU patients. Incorporating the knowledge obtained from our study into clinical practice will enable healthcare professionals to enhance sedation management and improve outcomes for mechanically ventilated children.
Footnotes
The authors have no potential conflicts of interest to disclose.
- Conceptualization: In Kyung Lee and Kyunghoon Kim.
- Data curation: In Kyung Lee and Kyeong Hun Lee.
- Formal analysis: In Young Choi.
- Investigation: In Kyung Lee and Kyeong Hun Lee.
- Methodology: In Kyung Lee and Kyeong Hun Lee.
- Project administration: Kyunghoon Kim.
- Resources: Na Jin Kim.
- Software: In Young Choi.
- Supervision: Kyunghoon Kim.
- Validation: In Kyung Lee and Kyunghoon Kim.
- Visualization: Hye-ji Han.
- Writing—original draft: In Kyung Lee and Kyeong Hun Lee.
- Writing—review & editing: Kyunghoon Kim.
- Approval of final manuscript: all authors.
AVAILABILITY OF DATA AND MATERIALS
The datasets used in the current study are available from the corresponding author on reasonable request.
SUPPLEMENTARY MATERIALS
Details of the Search Strategy
Exclusion Criteria of the Included Studies
A funnel plot for mechanical ventilation duration.
References
- 1.Klugman D, Melton K, Maynord PO, Dawson A, Madhavan G, Montgomery VL, et al. Assessment of an unplanned extubation bundle to reduce unplanned extubations in critically ill neonates, infants, and children. JAMA Pediatr. 2020;174:e200268. doi: 10.1001/jamapediatrics.2020.0268. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Lucchini A, Bambi S, Galazzi A, Elli S, Negrini C, Vaccino S, et al. Unplanned extubations in general intensive care unit: a nine-year retrospective analysis. Acta Biomed. 2018;89(7-S):25–31. doi: 10.23750/abm.v89i7-S.7815. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Morris HF, Schuller L, Archer J, Niesen A, Ellsworth S, Egan J, et al. Decreasing unplanned extubation in the neonatal ICU with a focus on endotracheal tube tip position. Respir Care. 2020;65:1648–1654. doi: 10.4187/respcare.07446. [DOI] [PubMed] [Google Scholar]
- 4.Kress JP, Hall JB. Sedation in the mechanically ventilated patient. Crit Care Med. 2006;34:2541–2546. doi: 10.1097/01.CCM.0000239117.39890.E3. [DOI] [PubMed] [Google Scholar]
- 5.Shehabi Y, Nakae H, Hammond N, Bass F, Nicholson L, Chen J. The effect of dexmedetomidine on agitation during weaning of mechanical ventilation in critically ill patients. Anaesth Intensive Care. 2010;38:82–90. doi: 10.1177/0310057X1003800115. [DOI] [PubMed] [Google Scholar]
- 6.Gerlach AT, Dasta JF, Steinberg S, Martin LC, Cook CH. A new dosing protocol reduces dexmedetomidine-associated hypotension in critically ill surgical patients. J Crit Care. 2009;24:568–574. doi: 10.1016/j.jcrc.2009.05.015. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Iirola T, Aantaa R, Laitio R, Kentala E, Lahtinen M, Wighton A, et al. Pharmacokinetics of prolonged infusion of high-dose dexmedetomidine in critically ill patients. Crit Care. 2011;15:R257. doi: 10.1186/cc10518. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Egbuta C, Mason KP. Current state of analgesia and sedation in the pediatric intensive care unit. J Clin Med. 2021;10:1847. doi: 10.3390/jcm10091847. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Fonsmark L, Rasmussen YH, Carl P. Occurrence of withdrawal in critically ill sedated children. Crit Care Med. 1999;27:196–199. doi: 10.1097/00003246-199901000-00052. [DOI] [PubMed] [Google Scholar]
- 10.Ista E, van Dijk M, Gamel C, Tibboel D, de Hoog M. Withdrawal symptoms in critically ill children after long-term administration of sedatives and/or analgesics: a first evaluation. Crit Care Med. 2008;36:2427–2432. doi: 10.1097/CCM.0b013e318181600d. [DOI] [PubMed] [Google Scholar]
- 11.Kaye AD, Urman RD, Rappaport Y, Siddaiah H, Cornett EM, Belani K, et al. Multimodal analgesia as an essential part of enhanced recovery protocols in the ambulatory settings. J Anaesthesiol Clin Pharmacol. 2019;35(Suppl 1):S40–S45. doi: 10.4103/joacp.JOACP_51_18. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Keating GM. Dexmedetomidine: a review of its use for sedation in the intensive care setting. Drugs. 2015;75:1119–1130. doi: 10.1007/s40265-015-0419-5. [DOI] [PubMed] [Google Scholar]
- 13.Lewis K, Alshamsi F, Carayannopoulos KL, Granholm A, Piticaru J, Al Duhailib Z, et al. Dexmedetomidine vs other sedatives in critically ill mechanically ventilated adults: a systematic review and meta-analysis of randomized trials. Intensive Care Med. 2022;48:811–840. doi: 10.1007/s00134-022-06712-2. [DOI] [PubMed] [Google Scholar]
- 14.Zhou WJ, Liu M, Fan XP. Differences in efficacy and safety of midazolam vs. dexmedetomidine in critically ill patients: a meta-analysis of randomized controlled trial. Exp Ther Med. 2021;21:156. doi: 10.3892/etm.2020.9297. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Heybati K, Zhou F, Ali S, Deng J, Mohananey D, Villablanca P, et al. Outcomes of dexmedetomidine versus propofol sedation in critically ill adults requiring mechanical ventilation: a systematic review and meta-analysis of randomised controlled trials. Br J Anaesth. 2022;129:515–526. doi: 10.1016/j.bja.2022.06.020. [DOI] [PubMed] [Google Scholar]
- 16.Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Ann Intern Med. 2009;151:W65–W94. doi: 10.7326/0003-4819-151-4-200908180-00136. [DOI] [PubMed] [Google Scholar]
- 17.Higgins JP, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928. doi: 10.1136/bmj.d5928. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Tobias JD, Berkenbosch JW. Sedation during mechanical ventilation in infants and children: dexmedetomidine versus midazolam. South Med J. 2004;97:451–455. doi: 10.1097/00007611-200405000-00007. [DOI] [PubMed] [Google Scholar]
- 19.Prasad SR, Simha PP, Jagadeesh AM. Comparative study between dexmedetomidine and fentanyl for sedation during mechanical ventilation in post-operative paediatric cardiac surgical patients. Indian J Anaesth. 2012;56:547–552. doi: 10.4103/0019-5049.104572. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Aydogan MS, Korkmaz MF, Ozgül U, Erdogan MA, Yucel A, Karaman A, et al. Pain, fentanyl consumption, and delirium in adolescents after scoliosis surgery: dexmedetomidine vs midazolam. Paediatr Anaesth. 2013;23:446–452. doi: 10.1111/pan.12128. [DOI] [PubMed] [Google Scholar]
- 21.Saleh RH. Randomized controlled comparative trial between low dose dexmedetomidine sedation and that of fentanyl in children after surgical procedures in surgical pediatric intensive care unit. Egypt J Anaesth. 2016;32:137–142. [Google Scholar]
- 22.Garisto C, Ricci Z, Tofani L, Benegni S, Pezzella C, Cogo P. Use of low-dose dexmedetomidine in combination with opioids and midazolam in pediatric cardiac surgical patients: randomized controlled trial. Minerva Anestesiol. 2018;84:1053–1062. doi: 10.23736/S0375-9393.18.12213-9. [DOI] [PubMed] [Google Scholar]
- 23.Erickson SJ, Millar J, Anderson BJ, Festa MS, Straney L, Shehabi Y, et al. Dexmedetomidine sedation in mechanically ventilated critically ill children: a pilot randomized controlled trial. Pediatr Crit Care Med. 2020;21:e731–e739. doi: 10.1097/PCC.0000000000002483. [DOI] [PubMed] [Google Scholar]
- 24.Gulla KM, Sankar J, Jat KR, Kabra SK, Lodha R. Dexmedetomidine vs midazolam for sedation in mechanically ventilated children: a randomized controlled trial. Indian Pediatr. 2021;58:117–122. [PubMed] [Google Scholar]
- 25.Attia WA, Aziz OMA, Reheem AMA, Sayed OMEE, Mahmoud MM. Comparison between sedative and analgesic effects of dexmedetomidine versus fentanyl for pediatric patients following cardiac surgery in intensive care unit. J Pharm Negat Results. 2022;13:1058–1064. [Google Scholar]
- 26.Senoglu N, Oksuz H, Dogan Z, Yildiz H, Kamaz A, Ugur N. Effects of dexmedetomidine on respiratory mechanics during mechanical ventilation. J Anaesthesiol Clin Pharmacol. 2009;25:273–276. [Google Scholar]
- 27.Gupta S, Singh D, Sood D, Kathuria S. Role of dexmedetomidine in early extubation of the intensive care unit patients. J Anaesthesiol Clin Pharmacol. 2015;31:92–98. doi: 10.4103/0970-9185.150554. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Liu Y, Bian W, Liu P, Zang X, Gu X, Chen W. Dexmedetomidine improves the outcomes in paediatric cardiac surgery: a meta-analysis of randomized controlled trials. Interact Cardiovasc Thorac Surg. 2018;26:852–858. doi: 10.1093/icvts/ivy043. [DOI] [PubMed] [Google Scholar]
- 29.Daverio M, Sperotto F, Zanetto L, Coscini N, Frigo AC, Mondardini MC, et al. Dexmedetomidine for prolonged sedation in the PICU: a systematic review and meta-analysis. Pediatr Crit Care Med. 2020;21:e467–e474. doi: 10.1097/PCC.0000000000002325. [DOI] [PubMed] [Google Scholar]
- 30.Gerlach AT, Blais DM, Jones GM, Burcham PK, Stawicki SP, Cook CH, et al. Predictors of dexmedetomidine-associated hypotension in critically ill patients. Int J Crit Illn Inj Sci. 2016;6:109–114. doi: 10.4103/2229-5151.190656. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Pasin L, Landoni G, Nardelli P, Belletti A, Di Prima AL, Taddeo D, et al. Dexmedetomidine reduces the risk of delirium, agitation and confusion in critically Ill patients: a meta-analysis of randomized controlled trials. J Cardiothorac Vasc Anesth. 2014;28:1459–1466. doi: 10.1053/j.jvca.2014.03.010. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Details of the Search Strategy
Exclusion Criteria of the Included Studies
A funnel plot for mechanical ventilation duration.
Data Availability Statement
The datasets used in the current study are available from the corresponding author on reasonable request.