Background
Methods
Data sources and searches
Study selection
Data extraction and quality assessment
Data analysis
Outcomes
Results
Study identification
Study characteristics
Trial | Population | Intervention | Clonidine: adjunctive or stand-alone sedative agent | Comparator(s) | Outcome(s) of interest |
---|---|---|---|---|---|
Duffett et al., 2014 | Mechanically ventilated children 1 month to 18 years old |
n = 25 Clonidine 5 μg/kg enteral (max 200 μg) q6h | Adjunctive (Midazolam, morphine equivalents) | n = 25 Placebo | Level of sedation (COMFORT or State Behavioural scales), dose of sedative agents (midazolam and morphine equivalents), duration of mechanical ventilation, length of PICU/hospital stay, adverse events |
Farasatinasab et a.l, 2015 | Mechanically ventilated adults |
n = 30 Clonidine 0.1–0.2 mg enteral q8h | Adjunctive (Midazolam, morphine equivalents, propofol) |
n = 25 Placebo | Level of sedation (Ramsay Sedation Score), dose of sedative agents (midazolam and morphine equivalents), total amount of sedation used, adverse events |
Hünseler et al., 2014 | Mechanically ventilated newborns and children 0 days to 2 years old. The newborn subgroup was excluded in data analysis |
n = 105 Clonidine 1 μg/kg/hr infusion | Adjunctive (Midazolam, fentanyl, thiopentone prn) |
n = 114 Placebo | Level of sedation (Hartwig and COMFORT scores), dose of sedative agents (fentanyl and midazolam), duration of mechanical ventilation, length of ICU stay, mortality |
Rubino et al., 2009 | Mechanically ventilated adults who had undergone surgical correction of acute type A aortic dissection |
n = 15 Clonidine 0.5 μg/kg intravenous bolus, then 1–2 μg/kg /hr infusion | Adjunctive (Fentanyl, propofol) |
n = 15 Placebo | Incidence of delirium, severity of delirium (Delirium Detection Score), duration of weaning, length of ICU stay |
Spies et al., 1996 | Mechanically ventilated post-trauma surgery adults who were alcohol-dependent |
n = 54 Clonidine 0.3 mg intravenous bolus, then up to 0.88 μg/kg/hr infusion and flunitrazepam 4 mg intravenous bolus, then up to 19 μg/kg/hr infusion | Adjunctive (Flunitrazepam) | (1) n = 50 Chlormethiazole 375 mg intravenous bolus, then up to 8.2 mg/kg/hr infusion and haloperidol 20 mg intravenous, then up to 53 μg/kg/hr infusion. (2) n = 55 Flunitrazepam 6 mg intravenous bolus, then up to 28 μg/kg/hr infusion and haloperidol 20 mg intravenous bolus, then up to 87 μg/kg/hr infusion | Length of ICU stay, incidence of alcohol withdrawal syndrome (revised clinical institute withdrawal assessment for alcohol scale), adverse events |
Srivastava et al., 2014 | Mechanically ventilated adults |
n = 35 Clonidine 1–2 μg/kg/hr infusion | Stand-alone |
n = 35 Dexmedetomidine 0.7 μg/kg intravenous bolus, then 0.2–0.7 μg/kg/hr infusion | Level of sedation (Ramsay sedation score), dose of sedative agents (diazepam, dexmedetomidine, fentanyl), hemodynamic changes, adverse events |
Wolf et al., 2014 | Mechanically ventilated children age 30 days to 15 years |
n = 61 Clonidine 3 μg/kg intravenous bolus, then 0–3 μg /kg/hr infusion | Adjunctive (Midazolam, morphine) |
n = 59 Midazolam 200 μg/kg intravenous bolus, then 0–20 μg/kg/hr infusion | Level of sedation (COMFORT score), time spent adequately sedated, duration of sedation, adverse events, length of ICU/hospital stay, ICU mortality |
Molon et al., 2007 | Mechanically ventilated children (age criteria unspecified) |
n = 31 Clonidine 5 μg/kg intravenous q8h | Adjunctive (Midazolam, morphine) |
n = 38 Placebo | Dose of sedatives (midazolam and morphine), duration of sedation, incidence of withdrawal syndrome (Finnegan score) |
Risk of bias
Certainty of evidence
Quality assessment | № of patients | Effect | Quality | Importance | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
№ of studies | Study design | Risk of bias | Inconsistency | Indirectness | Imprecision | Other considerations | Clonidine | Placebo | Relative (95% CI) | Absolute (95% CI) | ||
Duration of mechanical ventilation (assessed with: days) | ||||||||||||
6 | Randomized trials | Not seriousa
| Seriousb
| Not serious | Not seriousc
| None | 200 | 217 | - | MD 0.05 days more (0.65 fewer to 0.75 more) | ⨁⨁⨁ MODERATE | CRITICAL |
ICU mortality | ||||||||||||
5 | Randomized trials | Seriousd
| Not serious | Not serious | Seriouse
| None | 14/164 (8.5%) | 23/219 (10.5%) | RR 1.00 (0.50 to 2.02) | 0 fewer per 1000(from 53 fewer to 107 more) | ⨁⨁ LOW | CRITICAL |
Dose of benzodiazepines | ||||||||||||
4 | Randomized trials | Not seriousf
| Seriousg
| Not serious | Not seriousc
| None | 130 | 134 | - | SMD 0.02 SD higher (0.34 lower to 0.39 higher) | ⨁⨁⨁ MODERATE | CRITICAL |
Dose of narcotics | ||||||||||||
4 | Randomized trials | Not seriousf
| Not serious | Not serious | Seriouse
| None | 130 | 134 | - | SMD 0.26 SD lower (0.5 lower to 0.02 lower) | ⨁⨁⨁ MODERATE | CRITICAL |
Incidence of withdrawal symptoms from other sedatives | ||||||||||||
3 | Randomized trials | Seriousi
| Not serious | Not serious | Serioush
| None | 40/120 (33.3%) | 49/124 (39.5%) | RR 0.91 (0.67 to 1.23) | 36 fewer per 1000 (from 91 more to 130 fewer) | ⨁⨁ LOW | IMPORTANT |
ICU length of stay | ||||||||||||
6 | Randomized trials | Seriousj
| Not serious | Not serious | Not seriousc
| None | 233 | 240 | - | MD 0.04 days more (0.46 fewer to 0.53 more) | ⨁⨁⨁ MODERATE | CRITICAL |
Incidence of clinically significant hypotension | ||||||||||||
4 | Randomized trials | Not seriousk
| Not serious | Not serious | Seriousl
| None | 31/178 (17.4%) | 12/226 (5.3%) | RR 3.11 (1.64 to 5.87) | 112 more per 1000 (from 34 more to 259 more) | ⨁⨁⨁ MODERATE | CRITICAL |
Incidence of clinically significant bradycardia | ||||||||||||
4 | Randomized trials | Not seriousk
| Not serious | Not serious | Very seriouse
| None | 14/178 (7.9%) | 12/226 (5.3%) | RR 1.34 (0.45 to 3.98) | 18 more per 1000 (from 29 fewer to 158 more) | ⨁⨁ LOW | CRITICAL |