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Meta-Analysis
. 2015 Jan 6;1(1):CD010269.
doi: 10.1002/14651858.CD010269.pub2.

Alpha-2 agonists for long-term sedation during mechanical ventilation in critically ill patients

Ken Chen  1 , Zhijun Lu, Yi Chun Xin, Yong Cai, Yi Chen, Shu Ming Pan
Affiliations
Meta-Analysis

Alpha-2 agonists for long-term sedation during mechanical ventilation in critically ill patients

Ken Chen et al. Cochrane Database Syst Rev. .

Abstract

Background: Sedation reduces patient levels of anxiety and stress, facilitates the delivery of care and ensures safety. Alpha-2 agonists have a range of effects including sedation, analgesia and antianxiety. They sedate, but allow staff to interact with patients and do not suppress respiration. They are attractive alternatives for long-term sedation during mechanical ventilation in critically ill patients.

Objectives: To assess the safety and efficacy of alpha-2 agonists for sedation of more than 24 hours, compared with traditional sedatives, in mechanically-ventilated critically ill patients.

Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 10, 2014), MEDLINE (1946 to 9 October 2014), EMBASE (1980 to 9 October 2014), CINAHL (1982 to 9 October 2014), Latin American and Caribbean Health Sciences Literature (1982 to 9 October 2014), ISI Web of Science (1987 to 9 October 2014), Chinese Biological Medical Database (1978 to 9 October 2014) and China National Knowledge Infrastructure (1979 to 9 October 2014), the World Health Organization international clinical trials registry platform (to 9 October 2014), Current Controlled Trials metaRegister of controlled trials active registers (to 9 October 2014), the ClinicalTrials.gov database (to 9 October 2014), the conference proceedings citation index (to 9 October 2014) and the reference lists of included studies and previously published meta-analyses and systematic reviews for relevant studies. We imposed no language restriction.

Selection criteria: We included all randomized and quasi-randomized controlled trials comparing alpha-2 agonists (clonidine or dexmedetomidine) versus alternative sedatives for long-term sedation (more than 24 hours) during mechanical ventilation in critically ill patients.

Data collection and analysis: Two review authors independently assessed study quality and extracted data. We contacted study authors for additional information. We performed meta-analyses when more than three studies were included, and selected a random-effects model due to expected clinical heterogeneity. We calculated the geometric mean difference for continuous outcomes and the risk ratio for dichotomous outcomes. We described the effects by values and 95% confidence intervals (CIs). We considered two-sided P < 0.05 to be statistically significant.

Main results: Seven studies, covering 1624 participants, met the inclusion criteria. All included studies investigated adults and compared dexmedetomidine with traditional sedatives, including propofol, midazolam and lorazepam. Compared with traditional sedatives, dexmedetomidine reduced the geometric mean duration of mechanical ventilation by 22% (95% CI 10% to 33%; four studies, 1120 participants, low quality evidence), and consequently the length of stay in the intensive care unit (ICU) by 14% (95% CI 1% to 24%; five studies, 1223 participants, very low quality evidence). There was no evidence that dexmedetomidine decreased the risk of delirium (RR 0.85; 95% CI 0.63 to 1.14; seven studies, 1624 participants, very low quality evidence) as results were consistent with both no effect and appreciable benefit. Only one study assessed the risk of coma, but lacked methodological reliability (RR 0.69; 95% CI 0.55 to 0.86, very low quality evidence). Of all the adverse events included, the most commonly reported one was bradycardia, and we observed a doubled (111%) increase in the incidence of bradycardia (RR 2.11; 95% CI 1.39 to 3.20; six studies, 1587 participants, very low quality evidence). Our meta-analysis provided no evidence that dexmedetomidine had any impact on mortality (RR 0.99; 95% CI 0.79 to 1.24; six studies, 1584 participants, very low quality evidence). We observed high levels of heterogeneity in risk of delirium (I² = 70%), but due to the limited number of studies we were unable to determine the source of heterogeneity through subgroup analyses or meta-regression. We judged six of the seven studies to be at high risk of bias.

Authors' conclusions: In this review, we found no eligible studies for children or for clonidine. Compared with traditional sedatives, long-term sedation using dexmedetomidine in critically ill adults reduced the duration of mechanical ventilation and ICU length of stay. There was no evidence for a beneficial effect on risk of delirium and the heterogeneity was high. The evidence for risk of coma was inadequate. The most common adverse event was bradycardia. No evidence indicated that dexmedetomidine changed mortality. The general quality of evidence ranged from very low to low, due to high risks of bias, serious inconsistency and imprecision, and strongly suspected publication bias. Future studies could pay more attention to children and to using clonidine

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Conflict of interest statement

Ken Chen: none known Zhijun Lu: none known Yi Chun Xin: none known Yong Cai: none known Yi Chen: none known Shu Ming Pan: none known

Figures

1
1
Selection process for studies included in data synthesis.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 Dexmedetomidine versus traditional sedative agents, Outcome 1 Duration of mechanical ventilation (subgroup: class of alternative agents).
1.2
1.2. Analysis
Comparison 1 Dexmedetomidine versus traditional sedative agents, Outcome 2 Duration of mechanical ventilation (sensitivity analysis using data from 'time to extubation'").
1.3
1.3. Analysis
Comparison 1 Dexmedetomidine versus traditional sedative agents, Outcome 3 Risk of delirium (subgroup: class of alternative agents).
1.4
1.4. Analysis
Comparison 1 Dexmedetomidine versus traditional sedative agents, Outcome 4 Risk of delirium (sensitivity analysis for observed data only).
1.5
1.5. Analysis
Comparison 1 Dexmedetomidine versus traditional sedative agents, Outcome 5 Incidence of bradycardia (subgroup: class of alternative agents).
1.6
1.6. Analysis
Comparison 1 Dexmedetomidine versus traditional sedative agents, Outcome 6 Incidence of bradycardia (subgroup: dosing regimens).
1.7
1.7. Analysis
Comparison 1 Dexmedetomidine versus traditional sedative agents, Outcome 7 Incidence of bradycardia (sensitivity analysis for observed data only).
1.8
1.8. Analysis
Comparison 1 Dexmedetomidine versus traditional sedative agents, Outcome 8 Incidence of hypotension (subgroup: class of alternative agents).
1.9
1.9. Analysis
Comparison 1 Dexmedetomidine versus traditional sedative agents, Outcome 9 Incidence of hypotension (subgroup: dosing regimens).
1.10
1.10. Analysis
Comparison 1 Dexmedetomidine versus traditional sedative agents, Outcome 10 Incidence of hypotension (sensitivity analysis for observed data only).
1.12
1.12. Analysis
Comparison 1 Dexmedetomidine versus traditional sedative agents, Outcome 12 ICU length of stay (LOS) (subgroup: class of alternative agents).
1.13
1.13. Analysis
Comparison 1 Dexmedetomidine versus traditional sedative agents, Outcome 13 Mortality (subgroup: class of alternative agents).
1.14
1.14. Analysis
Comparison 1 Dexmedetomidine versus traditional sedative agents, Outcome 14 Mortality (sensitivity analysis for observed data only).
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Comment in

References

References to studies included in this review

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Ruokonen 2009 {published data only}
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References to studies excluded from this review

Arenas 2004 {published data only}
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Kadoi 2008 {published data only}
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Kaneko 2008 {published data only}
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Li 2011 {published data only}
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Li 2012 {published data only}
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Li 2013 {published data only}
    1. Li ZY. The influence of dexmedetomidine on patients' renal function [右美托咪定用于计划镇静时对病人肾脏功能的影响]. Chinese Selected Doctoral Dissertations and Master's Theses Full‐Text Databases 2013; Vol. 2.
Linj 2012 {published data only}
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Liu 2013a {published data only}
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Liu 2013b {published data only}
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Luo 2012a {published data only}
    1. Luo J, Tan XF, Deng XK, Wu HB. The use of dexmedetomidine hydrochloride in mechanical ventilated patients [盐酸右美托咪定在机械通气患者中的应用]. Hebei Medical Journal 2012;34:989‐90.
Luo 2012b {published data only}
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Luo 2012c {published data only}
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Peng 2011 {published data only}
    1. Peng M, Fang WQ, Yu XT, Cai JY. Clinical application of dexmedetomidine in intensive care unit [右美托咪定在重症监护病房镇静中的临床应用]. Chinese Journal of Critical Care Medicine 2011;31(3):197‐9.
Pu 2012 {published data only}
    1. Pu N, Wu Y, Cao QT. Clinical observation of sedate treatment of dexmedetomidine on ICU patients [右美托咪定在重症监护患者镇静中的临床观察]. Guide of China Medicine 2012;10:24‐5.
Qu 2011 {published data only}
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Su 2014 {published data only}
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Tasdogan 2009 {published data only}
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Tian 2010 {published data only}
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Tobias 2004 {published data only}
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Venn 2001 {published data only}
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Wan 2011 {published data only}
    1. Wan LJ, Huang QQ, Yue JX, Lin L, Li SH. Comparison of sedative effect of dexmedetomidine and midazolam for post‐operative patients undergoing mechanical ventilation in surgical intensive care unit [右美托咪啶与咪达唑仑用于外科重症监护病房术后机械通气患者镇静的比较研究]. Chinese Critical Care Medicine 2011;23:543‐6. [PUBMED: 21944176] - PubMed
Wang 2011a {published data only}
    1. Wang CY, Shang M, Cheng L, Zhou QS. Dexmedetomidine vs midazolam for sedation in critically ill patients [右美托咪啶和咪达唑仑用于危重症患者镇静效应的比较]. Journal of Hainan Medical University 2011;17(96):695‐7.
Wang 2011b {published data only}
    1. Wang HL, Liu HT, Yu KJ. Comparison of dexmedetomidine and propofol for sedation of eclampsia patients in intensive care unit [右美托咪定与丙泊酚用于重症监护病房子痫患者镇静的效果比较]. Shanghai Medical Journal 2011;34(8):613‐5.
Wang 2011c {published data only}
    1. Wang KM, Sun YH, Hou YQ. Clinical observation of dexmedetomidine hydrochloride on sedation and analgesia of ICU patients [盐酸右美托咪定用于重症监护患者镇静及镇痛的临床观察]. Journal of Henan University of Science & Technology (Medical Science) 2011;29(4):267‐8, 271.
Wang 2012a {published data only}
    1. Wang HB, Li KP, Deng ZB. The sedation effect comparison of dexmedetomidine and midazolam to treat patients with flail chest complicated with pulmonary injury in ICU [右美托咪定与咪达唑仑用于重症监护病房连枷胸并肺损伤患者镇静的效果比较]. Journal of Heze Medical College 2012;24(90):4‐5, 60.
Wang 2012b {published data only}
    1. Wang H. Curative effect observation of dexmedetomidine in ICU sedation [右美托嘧啶在ICU中镇静的疗效观察]. Guide of China Medicine 2012;10:153‐4.
Wang 2014 {published data only}
    1. Wang S, Zhu L. Efficacy of dexmedetomidine and midazolam combined with fentanyl on sedation of postoperative and mechanically ventilated ICU patients [右美托咪定和咪达唑仑复合芬太尼对ICU术后机械通气患者镇静的影响]. Practical Pharmacy and Clinical Remedies 2014;3:308‐10.
Xiao 2013 {published data only}
    1. Xiao Y, Wang Y, Wu Y. Evaluation on sedation effect of dexmedetomidine used in ICU [右美托咪啶用于重症监护病房镇静的效果评价]. China Pharmaceuticals 2013;20:37‐9.
Yang 2013 {published data only}
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Yao 2010 {published data only}
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Yuan 2014 {published data only}
    1. Yuan L, Ma HY. Comparasion of dexmedetomidine and midazolam for ICU patients with mechanical ventilation [右美托咪定与咪达唑仑用于ICU机械通气患者镇静疗效比较]. Jilin Medical Journal 2014;12:2555.
Zhang 2012a {published data only}
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Zhang 2012b {published data only}
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Zhang 2013 {published data only}
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Zhang 2014a {published data only}
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Zhang 2014b {published data only}
    1. Zhang W, Tan J, Guan R, Xie S. Clinical study of dexmedetomidine hydrochloride in mechanical ventilation for critical patients [盐酸右美托咪定在危重症患者机械通气的临床研究]. China Medicine and Pharmacy 2014;12:82‐3.
Zheng 2012 {published data only}
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Zhou 2012a {published data only}
    1. Zhou J. Clinical research of sedation with dexmedetomidine for surgical patients requiring mechanical ventilation [右美托咪定用于外科手术后需机械通气患者镇静治疗的临床观察]. Chinese Selected Doctoral Dissertations and Master's Theses Full‐Text Databases 2012; Vol. 11.
Zhou 2012b {published data only}
    1. Zhou LX, Yang TF. The sedative effect of dexmedetomidine in ICU patients receiving mechanical ventilation [右美托咪定用于ICU机械通气患者的镇静效果及护理]. Strait Pharmaceutical Journal 2012;24(150):187‐8.

References to studies awaiting assessment

Tao 2011 {published data only}
    1. Tao SY, Li WX, Qi XF. Sedative effects of dexmedetomidine on patients in intensive care unit [右美托咪定在ICU患者镇静中的疗效分析]. Chinese Journal of Critical Care Medicine 2011;31(12):1103‐5.

References to ongoing studies

NCT01059929 {published data only}
    1. NCT01059929. Dexmedetomidine Versus Propofol in the Medical Intensive Care Unit (MICU). clinicaltrials.gov/ct2/show/NCT01059929 accessed 10 December 2014.
NCT01760967 {published data only}
    1. NCT01760967. Dexmedetomidine for Sepsis in ICU Randomized Evaluation Trial (DESIRE). clinicaltrials.gov/ct2/show/NCT01760967 accessed 10 December 2014.

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