Clinical study of midazolam sequential with dexmedetomidine for agitated patients undergoing weaning to implement light sedation in intensive care unit

Abstract

PurposeTo evaluate midazolam sequential with dexmedetomidine for agitated patients undergoing weaning to implement light sedation in ICU.MethodsThis randomized, prospective study was conducted in Tianjin Third Central Hospital, China. Using a sealed-envelope method, the patients were randomly divided into 2 groups (40 patients per group). Each patient of group A received an initial loading dose of midazolam at 0.3–3 mg/kg·h 24 h before extubation, followed by an infusion of dexmedetomidine at a rate of 0.2–1 μg/kg·h until extubation. Each patient of group B received midazolam at a dose of 0.3–3 mg/kg·h until extubation. The dose of sedation was regulated according to RASS sedative scores maintaining in the range of -2-1. All patients were continuously monitored for 60 min after extubation. During the course, heart rate (HR), mean artery pressure (MAP), extubation time, adverse reactions, ICU stay, and hospital stay were observed and recorded continuously at the following time points: 24 h before extubation (T1), 12 h before extubation (T2), extubation (T3), 30 min after extubation (T4), 60 min after extubation (T5).ResultsBoth groups reached the goal of sedation needed for ICU patients. Dexmedetomidine was associated with a significant increase in extubation quality compared with midazolam, reflected in the prevalence of delirium after extubation (20% (8/40) vs 45% (18/40)), respectively (p = 0.017). There were no clinically significant decreases in HR and MAP after infusing dexmedetomidine or midazolam. In the group A, HR was not significantly increased after extubation; however, in the group B, HR was significantly increased compared with the preextubation values (p < 0.05). HR was significantly higher in the group B compared with the group A at 30 and 60 min after extubation (both, p < 0.05). Compared with preextubation values, MAP was significantly increased at extubation in the group B (p < 0.05) and MAP was significantly higher at T3, T4, T5 in the group B than group A (p < 0.05). There was a significant difference in extubation time ((3.0 ± 1.5) d vs (4.3 ± 2.2) d, p < 0.05), ICU stay ((5.4 ± 2.1) d vs (8.0 ± 1.4) d, p < 0.05), hospital stay ((10.1 ± 3.0) d vs (15.3 ± 2.6) d, p < 0.05) between group A and B.ConclusionMidazolam sequential with dexmedetomidine can reach the goal of sedation for ICU agitated patients, meanwhile it can maintain the respiratory and circulation parameters and reduce adverse reactions.

A systematic review of interventions to facilitate extubation in patients difficult-to-wean due to delirium, agitation, or anxiety and a meta-analysis of the effect of dexmedetomidine

“…These eight studies were all randomized-controlled trials and regrouped 437 patients. [28][29][30][31][32][33][34][35] One of the studies was only available in abstract form, and the authors were successfully contacted for missing data when needed. 35…”

“…The main characteristics of included studies are shown in the Table. All studies included adult patients, most reporting median ages in the fifties or sixties. Difficultto-wean patients were identified solely based on a clinicians' assessment without objective criteria in four trials, [30][31][32]35 while the others included patients who failed one spontaneous breathing trial 28,29,34 or failed an in-house extubation protocol. 33 Agitation was the reason for DTW in three studies and was measured using the Richmond Agitation Sedation Scale (RASS).…”

“…33 Agitation was the reason for DTW in three studies and was measured using the Richmond Agitation Sedation Scale (RASS). 30,32,34 Agitated delirium was an inclusion criteria in two studies and was assessed using a combination of a positive CAM-ICU and an evaluation with either the RASS 33 or the Mindful Attention Awareness Scale. 32 One study included patients that were DTW due to anxiety and used the State Anxiety Scale.…”

“…Dexmedetomidine was the most frequent pharmacologic intervention evaluated. [28][29][30][31][32][33] Intravenous dexmedetomidine up to a maximum of 1.5 lgÁkg -1 Áhr -1 , was compared with either an infusion of midazolam 0.04-0.2 mgÁkg -1 Áhr -1 , 29,30,33 propofol 0.3-4 mgÁkg -1 Áhr -128 haloperidol 0.5-2 mgÁhr -131 or placebo. 32 Another compared the effects of a single 150 mg dose of oral loxapine with placebo.…”

“…32 Other trials did not mention if cotreatments were permitted or prescribed. 30,35 Weaning protocols were not described in any trial except one where rapid shallow breathing indexes and spontaneous breathing trials were regularly performed. 30,35 Non-pharmacologic measures to alleviate delirium (e.g., early mobilization, sleep promotion, etc.)…”