Efficacy and Safety of Dexmedetomidine in Mechanically Ventilated Critically Ill Children: A Systematic Review and Meta-analysis of Randomized Controlled Trials

doi:10.21203/rs.3.rs-4683655/v1

Download PDF

Research Article

Efficacy and Safety of Dexmedetomidine in Mechanically Ventilated Critically Ill Children: A Systematic Review and Meta-analysis of Randomized Controlled Trials

https://doi.org/10.21203/rs.3.rs-4683655/v1

This work is licensed under a CC BY 4.0 License

Version 1

posted

You are reading this latest preprint version

Purpose

Children undergoing mechanical ventilation 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, yet its efficacy and safety 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 efficacy and adverse effects of dexmedetomidine in such patients.

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 efficacy 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 significantly reduced the duration of mechanical ventilation (MD -3.54 h, 95% CI, -6.49 to -0.59), particularly 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 (OR 6.14, 95% CI, 2.20 to 17.12) and hypotension (OR 8.14, 95% CI, 1.37 to 48.31), with no significant difference observed in the incidence of delirium (OR 0.61, 95% CI, 0.16 to 2.31) in comparison to other sedatives.

Conclusion

Although dexmedetomidine notably diminished the duration of mechanical ventilation, 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.

Dexmedetomidine

mechanical ventilation

sedation

pediatric

intensive care unit

Mechanically ventilated children are at a high risk of unplanned extubation, which can lead to airway injuries and life-threatening scenarios like asphyxia (1–3). Effective sedation and analgesia are pivotal 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 (4–7).

The concept of “analgosedation” within the pediatric intensive care unit (PICU) denotes a sedation strategy that combines both analgesia and sedation to enhance the comfort and wellbeing of critically ill patients (8). Despite its critical importance, the management of sedation in the PICU encounters numerous hurdles and limitations, including the need to strike a balance between adequate sedation levels and the prevention of adverse effects, in addition 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 \(\alpha 2\)-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 comparison to midazolam or propofol, dexmedetomidine has been shown to afford advantages such as a diminished time to extubation, 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 (13–15), research concerning its effectiveness and safety in critically ill pediatric patients on MV remains scarce. We performed a systematic review and meta-analysis of RCTs to assess the efficacy and adverse effects of dexmedetomidine in critically ill children on mechanical ventilation.

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).

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 Supplement 1.

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) RCT; (2) involved invasively mechanically ventilated children admitted to the PICU; (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) study type: observational studies, case reports, letters, editorials, or not peer -reviewed; (2) included duplicate samples; (3) participants restricted to neonates or adults; (4) studies that used dexmedetomidine solely during anesthesia or before procedures; (5) studies that administered dexmedetomidine through non-intravenous routes; or (6) studies that used placebo for the control group.

Outcomes

The primary outcome focused on sedation efficacy: duration of MV, length of ICU stays, duration of sedation, and total fentanyl bolus administrations. Secondary outcomes included adverse effects like bradycardia and hypotension.

Quality assessment

The risk of bias in 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.

Statistical analysis

The meta-analysis used R version 4.2.2 (R Foundation for Statistical Computing, Vienna, Austria) to analyze the efficacy and adverse effects of dexmedetomidine in terms of sedation. For continuous outcome data, the mean difference served as the primary measure, with estimates aggregated using the inverse variance method. The Mantel-Haenszel method pooled estimates for binary outcome data, employing odds ratio and risk ratio as main metrics. The choice of either a common or a random effects model was determined by heterogeneity levels, indicated by \({I}^{2}\) exceeding 50%, at which point the random effects model was favored.

Study selection and characteristics

Initially, searches of reference databases identified a total of 348 records. After the screening and eligibility assessment were conducted, eight studies (18–25) satisfied the inclusion criteria and were thus included in the meta-analysis (Fig. 1).

Of the studies selected, five concentrated on post-operative pediatric patients, whereas the others enrolled medical patients. Importantly, children with atrioventricular block were excluded from four of these studies. The detailed characteristics of each study are outlined in Table 1.

Table 1

Characteristics of included studies.
Author, year	Primary disease	Study period	Inclusion criteria	Exclusion criteria	Number of patients (I/C)	Intervention group (dose)	Control group (dose)	Initiation of DEX	Duration of DEX
Tobias, 2004 [18]	Patients admitted to PICU requiring MV	No information available	Children and infants	CNS dysfunction	30 (20/10)	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, 2012 [19]	Patients undergoing CHD surgery	No information available	1–14 years, overnight MV was anticipated	< 1 year, undergoing re-operation, surgeries done under deep hypothermia, patients with severe liver dysfunction, second and third degree heart block, patients requiring MV > 24h	60 (30/30)	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, 2013 [20]	Patients undergoing scoliosis surgery	No information available	12–18 years	History of midazolam and/or DEX, delirium, developmental delay, mental retardation, an American Society of Anesthesiologists classification greater than III, known previous reactions to anesthesia, a history of asthma or an anticipated difficult airway, a history of hypertension, chronic opioid, sedative, analgesic, antihypertensive agents or digoxin prior to the procedure, concomitant disease	32 (16/16)	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, 2016 [21]	Patients scheduled for abdominal surgery	Sep 2013 ~ Dec 2014	1–10 years, overnight MV was anticipated	< 1 year, emergency surgeries, severe liver dysfunction, patients requiring MV more than 24 h	50 (25/25)	DEX (0.3 mcg/kg/h)	Fentanyl (1 mcg/kg/h)	At arrival to the SICU	After 18 h
Garisto, 2018 [22]	Patients undergoing complex CHD surgery	July 2012 – Dec 2015	1 month – 24 months	Newborns, brain or bone malformations, neuromuscular disease, post-surgical delayed sternal closure, post-operative neurological or pulmonary complications, ECMO requirement, AV block, VIS > 30, hepatic failure, renal impairment	48 (22/26)	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, 2020 [23]	Patients admitted to PICU requiring MV	Jan 2015 – July 2016	− 16 years	Acute brain injury, neurologic injury, requirement for continuous neuromuscular blockade, cardiovascular instability	60 (29/31)	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, 2020 [24]	Patients admitted to PICU requiring MV	August 2016 – April 2018	1 month – 15 years	Catecholamine resistant shock, already on sedative drug infusion, bradycardia, AV block, primary CNS involvement, hepatic impairment, infusion of muscle relaxants, previous participation in the study	47 (23/24)	DEX (0.25–0.75 mcg/kg/h)	Midazolam (1–4 mcg/kg/min)	After randomization	Until 7 days or weaning from MV
Attia, 2022 [25]	Patients undergoing CHD surgery	April 2020 – Dec 2021	1 day – 15 years	Neuromuscular disorders, demyelinating illness, cerebral palsy, developmental and behavioral issues, inborn metabolic errors, acute severe neurological condition, decompensated heart failure, acute hemodynamic instability, septic shock, HR 60 beats/min, grade II or III AV block	60 (30/30)	DEX* (0.2–1.5 mcg/kg/h)	Fentanyl (1–3 mcg/kg/h)	During anesthesia	No information available
Abbreviations: I/C, intervention/control; PICU, pediatric intensive care unit; MV, mechanical ventilation; CHD, congenital heart disease; DEX, dexmedetomidine; CNS, central nervous system; SICU, surgical intensive care unit; ECMO, extracorporeal membrane oxygenation; VIS, vasoactive inotropic score; AV, atrioventricular; PAH, pulmonary hypertension; CCU, cardiac intensive care unit * Dexmedetomidine was started with a bolus dose.

Regarding interventions, the majority of the studies (7/8, 88%) did not implement a dexmedetomidine bolus at the onset of the infusion. Moreover, in most studies (7/8, 88%) dexmedetomidine was the exclusive sedative agent employed.

With respect to the control groups, the included trials exhibited variability. Namely, three trials (3/8, 38%) used midazolam, an equivalent number applied fentanyl, and the two remaining trials (2/8, 25%) utilized combinations of different sedative medications.

Risk of bias

The risk of bias within the included studies is depicted in Fig. 2.

Efficacy outcomes

1. Mechanical ventilation duration

Data from seven studies were incorporated into the meta-analysis for the duration of MV. Dexmedetomidine was shown to significantly reduce the duration of MV when compared to other sedative drugs(MD -3.54 h, 95% CI, -6.49 to -0.59, Fig. 3A).

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).

2. 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, Supplement 2A).

3. Duration of sedation

Analysis of four studies’ data on sedation duration revealed no significant reduction when compared to other sedatives (MD 0.16, 95% CI, -0.82 to 1.13, Supplement 2B).

4. 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, Supplement 2C).

Safety outcomes

Four trials contributed data to the analysis of bradycardia incidence, while two trials did so for the analysis of hypotension incidence. Compared to other sedatives, dexmedetomidine was significantly associated with a higher risk of bradycardia (OR 6.14, 95% CI, 2.20 to 17.12, Fig. 3A) and hypotension (OR 8.14, 95% CI, 1.37 to 48.31, Fig. 3B).

Moreover, no significant difference in delirium incidence was demonstrated when compared to alternative sedatives across two trials (OR 0.61, 95% CI, 0.16 to 2.31, Fig. 3C).

This systematic review and meta-analysis, encompassing eight trials with 387 mechanically ventilated children, provides evidence that dexmedetomidine significantly reduces MV duration in this population, particularly 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 but did not impact the incidence of delirium.

Several hypotheses offer explanations for how dexmedetomidine may improve MV duration. First, dexmedetomidine has been found to enhance compliance, reduce resistance, and improve oxygenation during ongoing MV, potentially leading to a quicker extubation time(26). Second, 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). The meta-analysis addressing children undergoing cardiac surgery concluded that perioperative dexmedetomidine administration might reduce MV duration, as well as the lengths of ICU and hospital stays. Our investigation, conversely, broadens this scope to include both post-operative and medical pediatric populations. Unlike the earlier meta-analysis that limited its focus to post-operative children (28), we excluded studies that administered dexmedetomidine solely during anesthesia to evaluate its efficacy in the context of MV in PICU settings. Furthermore, our meta-analysis assesses both the sedation efficacy and the adverse effects of dexmedetomidine, unlike previous analyses that concentrated primarily on the safety profile of dexmedetomidine (29). This dual focus offers vital insights for pediatric intensive care, providing a more comprehensive perspective on the application of dexmedetomidine in critically ill children.

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.

However, our study also uncovered a heightened risk of bradycardia and hypotension linked to dexmedetomidine. 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 because of scarce data on this outcome. Among the included studies, only two explored the assessment of delirium, 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, our study’s observed high heterogeneity and significant risk of bias advise caution in interpreting these results. Lastly, the variation in weaning protocols among the studies introduces additional complexity to our analysis.

In summation, 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 enables healthcare professionals to enhance sedation management and improve outcomes for mechanically ventilated children.

Disclosure statement

The authors have no conflicts of interest to declare.

Funding sources

No funding sources.

Klugman D, Melton K, Maynord PON, 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(6):e200268-e.
Alberto L, Stefano B, Alessandro G, Stefano E, Cristina N, Stefania V, et al. Unplanned extubations in general intensive care unit: A nine-year retrospective analysis. Acta Bio Medica: Atenei Parmensis. 2018;89(Suppl 7):25.
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. Resp Care. 2020;65(11):1648-54.
Kress JP, Hall JB. Sedation in the mechanically ventilated patient. Critical care medicine. 2006;34(10):2541-6.
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 Intens Care. 2010;38(1):82-90.
Gerlach AT, Dasta JF, Steinberg S, Martin LC, Cook CH. A new dosing protocol reduces dexmedetomidine-associated hypotension in critically ill surgical patients. Journal of critical care. 2009;24(4):568-74.
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. Critical care. 2011;15(5):1-10.
Egbuta C, Mason KP. Current State of Analgesia and Sedation in the Pediatric Intensive Care Unit. J Clin Med. 2021;10(9).
Fonsmark L, Rasmussen YH, Carl P. Occurrence of withdrawal in critically ill sedated children. Critical care medicine. 1999;27(1):196-9.
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. Critical care medicine. 2008;36(8):2427-32.
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. Journal of Anaesthesiology Clinical Pharmacology. 2019;35(Suppl 1):S40-S5.
Keating GM. Dexmedetomidine: a review of its use for sedation in the intensive care setting. Drugs. 2015;75:1119-30.
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(7):811-40.
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(2):156.
Heybati K, Zhou F, Ali S, Deng J, Mohananey D, Villablanca P, Ramakrishna H. 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(4):515-26.
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. Annals of internal medicine. 2009;151(4):W-65-W-94.
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.
Tobias JD, Berkenbosch JW. Sedation during mechanical ventilation in infants and children: dexmedetomidine versus midazolam. South Med J. 2004;97(5):451-5.
Prasad S, Simha PP, Jagadeesh A. Comparative study between dexmedetomidine and fentanyl for sedation during mechanical ventilation in post-operative paediatric cardiac surgical patients. Indian journal of anaesthesia. 2012;56(6):547-52.
Aydogan MS, Korkmaz MF, Ozgul 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(5):446-52.
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. Egyptian Journal of Anaesthesia. 2016;32(1):137-42.
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 anestesiologica. 2018;84(9):1053-62.
Erickson SJ, Millar J, Anderson BJ, Festa MS, Straney L, Shehabi Y, Long DA. Dexmedetomidine sedation in mechanically ventilated critically ill children: a pilot randomized controlled trial. Pediatric Critical Care Medicine. 2020;21(9):e731-e9.
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(2):117-22.
Attia WA, Aziz OMA, Reheem AMA, Sayed OME-e, Mahmoud MM. Comparison Between Sedative And Analgesic Effects Of Dexmedetomidine Versus Fentanyl For Pediatric Patients Following Cardiac Surgery In Intensive Care Unit. Journal of Pharmaceutical Negative Results. 2022:1058-64.
Senoglu N, Oksuz H, Dogan Z, Yildiz H, Kamaz A, Ugur N. Effects of Dexmedetomidine on respiratory mechanics during mechanical ventilation. Journal of Anaesthesiology Clinical Pharmacology. 2009;25(3):273-6.
Gupta S, Singh D, Sood D, Kathuria S. Role of dexmedetomidine in early extubation of the intensive care unit patients. Journal of Anaesthesiology Clinical Pharmacology. 2015;31(1):92-8.
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(5):852-8.
Daverio M, Sperotto F, Zanetto L, Coscini N, Frigo AC, Mondardini MC, Amigoni A. Dexmedetomidine for Prolonged Sedation in the PICU: A Systematic Review and Meta-Analysis. Pediatr Crit Care Med. 2020;21(7):e467-e74.
Gerlach AT, Blais DM, Jones GM, Burcham PK, Stawicki SP, Cook CH, Murphy CV. Predictors of dexmedetomidine-associated hypotension in critically ill patients. International Journal of Critical Illness and Injury Science. 2016;6(3):109-14.
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 Cardiothor Vasc An. 2014;28(6):1459-66.

No competing interests reported.

Supplement1.docx
Supplement 1. Details of the search strategy
Supplement2.jpg
Supplement 2. 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. MD stands for mean difference, and CI denotes confidence interval.

Download PDF

Version 1

posted

You are reading this latest preprint version

Efficacy and Safety of Dexmedetomidine in Mechanically Ventilated Critically Ill Children: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Status:

Version 1

Abstract

Figures

Introduction

Methods

Study Design

Database and search strategy

Data collection and analysis

Inclusion criteria

Exclusion criteria

Outcomes

Quality assessment

Statistical analysis

Results

Study selection and characteristics

Risk of bias

1. Mechanical ventilation duration

2. ICU length of stay

3. Duration of sedation

4. Number of fentanyl bolus doses

Safety outcomes

Discussion

Declarations

References

Additional Declarations

Supplementary Files

Status:

Version 1