Abstract

Background:

Dexmedetomidine is increasingly used as an anxiolytic and sedative in pediatric patients with acute respiratory distress for managing anxiety and agitation. However, its effectiveness and safety in the pediatric population remain unclear, and clinical practice is often guided by evidence derived from adults.

Aim:

A systematic review was conducted to examine the evidence on the use of dexmedetomidine in patients undergoing non-invasive respiratory support (NRS) for acute respiratory conditions in both pediatric and adult individuals.

Methods:

A comprehensive literature search was conducted on PubMed, Web of Science and Embase up to September 2025, evaluating dexmedetomidine in patients requiring NRS. The risk of bias was assessed using JBI’s critical appraisal tools, and available comparative studies randomized controlled studies (RCT) were analyzed in a meta-analysis. Certainty was graded according to the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) methodology.

Results:

Ten studies evaluating dexmedetomidine in pediatric NRS were identified. While most studies suggested that dexmedetomidine may improve tolerance to NRS and reduce agitation, the pediatric evidence base consists mainly of observational studies without randomized trials, preventing a quantitative synthesis. Consequently, any direct comparisons with adult results cannot be directly extrapolated and should be considered strictly exploratory. Twenty-four studies (9 RCTs) were conducted in adult patients. The evidence from adult studies was more robust, showing that dexmedetomidine has the potential to reduce agitation, aid NRS acceptance, and decrease the need for intubation, as well as the incidence of delirium.

Conclusion:

Current evidence supporting the use of dexmedetomidine in pediatric patients undergoing NRS is promising but remains insufficient. Findings from adult populations suggest that dexmedetomidine can effectively reduce agitation and may facilitate NRS acceptance in various conditions requiring respiratory support. However, future robust randomized controlled trials in pediatric patients are needed to determine efficacy, optimal dosing and safety in children with acute respiratory distress. These data will enable the development of age-specific guidelines and recommendations, ensuring a safer and more effective use.

1 Introduction

Acute respiratory distress is a life-threatening condition characterized by hypoxemia or hypercapnia resulting from respiratory failure, often requiring respiratory support. Non-invasive respiratory support (NRS) has been increasingly used in the management of respiratory distress in both adults and children, providing a less invasive alternative to endotracheal intubation, which may be associated with complications. However, the effectiveness of NRS depends largely on patient comfort, tolerance and, when using non-invasive ventilation (NIV), synchronization with the ventilator, all of which can be negatively influenced by anxiety, agitation and dyspnea-related distress. Anxiety, fear, and pain have been shown to exacerbate tachypnea, leading to sharp breathing, breath holding, and further oxygen desaturation (1, 2).

Furthermore, in severe cases, in which NIV use might be required, agitation can further reduce mask tolerance, making NIV acceptance and maintenance more challenging, particularly in pediatric patients (3, 4). In these cases, sedative treatment is a pragmatic approach that can be used in both the emergency department and intensive care units. Treatment of agitation and distress in acute respiratory distress has been primarily based on benzodiazepines and opioids (5). Although effective, these agents can adversely affect hemodynamics and breathing drive. For these reasons, the use of dexmedetomidine in this context has been increasingly reported since its introduction in 1999. Indeed, dexmedetomidine, a selective alpha-2-adrenergic agonist, has gained considerable attention in critical care due to its sedative, anxiolytic and analgesic properties, along with minimal respiratory depression, preservation of breathing drive and limited mild hemodynamic effects. These properties stem from its pharmacological profile, selectively acting on alpha-2-adrenergic receptors in the locus coeruleus. Moreover, dexmedetomidine has the advantage of being administered via different routes, with intravenous administration being the most common. However, intranasal administration can also be particularly useful in an acute setting (6).

Despite its increasing off-label use in intensive care settings, the evidence for dexmedetomidine application in the emergency setting - especially in the pediatric population- remains limited and fragmented. Only limited evidence is available in the literature regarding its effectiveness as a supporting agent in acute respiratory distress requiring non-invasive ventilation, with some papers suggesting its effectiveness and others reporting no advantage, with notable differences in outcomes between children and adults (6–9). Clinical practice varies widely, and concerns persist about hemodynamic side effects and optimal dosing strategies. A clearer understanding of dexmedetomidine’s safety, efficacy and impact on NRS outcomes could inform clinical guidelines and enhance care for patients experiencing respiratory distress, ultimately reducing the need for intubation and improving morbidity and mortality.

This systematic review aims to synthesizing the current evidence on the use of dexmedetomidine for the management of acute respiratory distress requiring NRS in both children and adults. Specifically, it seeks to evaluate its effects on patient tolerance, intubation rates, sedation quality, respiratory parameters and adverse events. By consolidating existing data, this review aims to clarify the clinical role of dexmedetomidine in this context and identify knowledge gaps warranting further research.

Although the included respiratory conditions have diverse pathophysiologies, they share a common clinical challenge: anxiety, agitation, and interface intolerance often precipitate in non-invasive support failure. Therefore, we included these heterogeneous conditions to pragmatically evaluate dexmedetomidine’s role in targeting this shared pathway—facilitating patient comfort and ventilator synchrony—rather than treating specific disease mechanisms.

2 Methods2.1 Literature search

The systematic review adhered to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines (10).

The study was registered in PROSPERO (n. CRD420251089195).

2.2 Search strategy

Three authors (L.Z., L.W, L.B.) conducted the manual literature search on PubMed,1 Web of Science2 and Embase3 databases up to September 2025, using as key terms, “non-invasive ventilation,” “CPAP,” “high flow cannula,” “dyspnea,” and “acute respiratory distress,” “acute respiratory failure,” “bronchiolitis,” “asthma” and “dexmedetomidine.” Moreover, the ClinicalTrials.gov (for clinical trials) registry and ProQuest (for dissertations and theses) were examined. The full search strategy was reported in Supplementary Table 1.

2.3 Articles selection

Potential study titles and abstracts were manually screened for relevance, followed by full-text evaluation. Studies were independently screened for inclusion by three authors. Duplicates across databases were manually merged. Studies conducted in both the emergency department and the intensive care unit (ICU) were included to capture all indirect evidence.

Inclusion criteria:

Clinical studies on human subjects

Pediatric or adult patients

Use of dexmedetomidine in the context of non-invasive respiratory support, including NIV, Continuous Positive Airway Pressure (CPAP), and high flow nasal cannula in the presence of respiratory conditions, including dyspnea, acute respiratory distress, acute respiratory failure, bronchiolitis, and asthma.

Articles in the English language

Exclusion criteria:

Use of invasive ventilation

Palliative or procedural setting (endoscopy or surgery)

Non-respiratory conditions treated with dexmedetomidine

pre-clinical in vivo, in vitro, or pharmacological studies

articles not in the English language

The discrepancy between the authors regarding study selection was resolved by involving another author.

2.4 Risk of bias assessment

Five authors independently assessed the risk of bias using the Joanna Briggs Institute (JBI)’s critical appraisal tools, tailored to various study designs, including intervention studies, observational cohorts, and case series (11–13). Each checklist item was rated as “Yes,” “No,” “Unclear,” or “Not applicable” in accordance with the official guidelines. Discrepancies were resolved by consensus between authors. The results were visualized using the “robvis” online tool (14).

2.5 Data extraction

The data were manually extracted from the articles by an author (L.Z.), whereas other authors (L.W, L.B. F.P, L.A.D.) checked the correctness of the data, specifically, age, sex, medical condition, and sedation treatment were recorded, as well as outcomes, such as intubation rate, mortality rate, incidence of delirium, NRS duration, and length of stay (LOS) in intensive care unit (ICU).

Intubation rate was defined as the proportion of patients who failed NRS treatment and required intubation, and mortality was defined as the proportion of patients who died. Incidence of delirium indicated the number of delirium cases occurring during NRS therapy. NRS duration referred to the length of time patients received NRS, while LOS in ICU represented the total duration of hospitalization in the ICU.

2.6 Meta-analysis

Only randomized controlled studies (RCT) studies that compared the use of dexmedetomidine to facilitate NRS acceptance to another drug or a placebo were included in the meta-analysis.

The primary outcome was the incidence of intubation, while the mortality rate, incidence of delirium, duration of NRS, and LOS in ICU were considered secondary.

The statistical analysis was performed in R Studio (15, 16) with the “meta” package (17).

For dichotomous outcomes (incidence of intubation, mortality rate, and incidence of delirium), pooled risk ratios (RRs) with 95% confidence intervals were calculated using random-effects models (REM). For continuous outcomes (duration of NRS and LOS in ICU), inverse variance weighting was employed to compute mean differences (MD). Heterogeneity across studies was assessed using the I2 statistic and τ2. Influence diagnostics were conducted to identify outlier studies that may disproportionately affect the pooled estimates.

The Grade of Evidence was assessed according to the guidelines of the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework (18). Specifically, GRADE was used to ensure confidence in the evidence and the strengths (or weaknesses) of our recommendations. The rating was based on the risk of bias (assessed by JBI’s critical appraisal tools), effect estimates (derived from the meta-analysis using REM), inconsistency (variation of the results across the studies, as measured by I2), indirectness (determining if the evidence directly addressed the research question), imprecision (degree of uncertainty evaluated by 95% CI), publication bias. The final rating was determined by consensus among all the authors.

3 Results

The flowchart of the literature search strategy is shown in Figure 1. A total of 199 studies were initially identified in PubMed, 310 in Web of Science and 265 in Embase. After removing 296 duplicates, 478 articles (title and abstract) were screened for eligibility. Moreover, CENTRAL, clinicaltrial.gov and Proquest were searched (n = 274), but no additional studies were identified. Overall, 57 articles were retrieved for full-text assessment. Finally, 33 articles were included in the review, 10 conducted in pediatric patients and 24 in adults (Tables 1, 2).

Flowchart of the study.

Study (reference)Study typePatients (age, sex)Clinical conditionInterventionOutcomesKey resultsAdverse effect if anyObservational studiesBermúdez-Barrezueta (19)Prospective, multicenter, observational trial457 patients (median age 3.3 months, IQR 1.3–16.1) M 54.7%, F 45.3%Children with acute respiratory failure (ARF) Bronchiolitis Bronchospasm Pneumonia Cardiogenic pulmonary edema SepsisNIV 213 (46.6%) children required sedation with various sedative agents Dexmedetomidine used in 23.5% of cases (median initial dose of 0.5 μg/kg/h and median cumulative dose of 16.5 μg/kg)NIV success in 95.6% of patients, intubation 6.1% in sedation group and 2.9% in non sedation groupSedation can help in improving the physiological parameters and comfort status during NIV of children < 5 years with ARFAdverse effects associated with sedations were recorded in 8% of patients: 11 cases of bradycardia in those who received dexmedetomidine (n = 33), 2 cases of bradycardia and 1 case of respiratory depression in those who received benzodiazepines (n = 102), 1 case of respiratory depression in a patient who received propofol (n = 13)Cousin (26)Retrospective study49 patients. Median age was 61 days (IQR 44–73) sex NRSevere bronchiolitis failing initial NIV supportNon-invasive neurally adjusted ventilatory assist ventilation (NIV-NAVA) with a total face mask interface (TFM) IV dexmedetomidine (0.3–1 mcg/kg/h)No patients required intubation and no patient experienced intoleranceRespiratory support with TFM-NIV-NAVA is a feasible rescue therapy in bronchiolitisNot reportedChristian (20)Retrospective study43 patients 14 no delirium median 0, (0–10), 79% F, 21% M, 29 delirium 1, (0–17). F 48%, M 52%Pediatric ICU patients with respiratory insufficiency (viral bronchiolitis, pneumonia, influenza A infection, and status asthmaticus.) requiring NIV.NIV: BiPAP-bilevel positive airway pressure; 26, CPAP 2, high-flow nasal cannula- HFNC 27 Various drugs among them dexmedetomidineAll patients weaned off NIV and experienced NIV discontinuation delirium in 29 of 43 patients.Delirium is common in patients requiring NIV due to sedative agent, (mainly benzodiazepine).Delirium was observed in 28 of the 36 patients who received dexmedetomidine; 19 of these patients also received benzodiazepinesEidman (6)Retrospective cohort study137 no sedation (mean age 96 months range 3–237), F 47%, M 53%;
68 sedation (40 months 3–193), F 46%, M 54%Asthma, Bronchiolitis, Pneumonia, viral respiratory infection, Aspiration pneumonia, Chronic lung disease exacerbationNIV dexmedetomidine (range 0.2–1 mg/kg/h)Dexmedetomidine patients experienced an intubation rate of 13.09% while no sedated patients of 12.41%Dexmedetomidine may improve NIV tolerance in patients with acute respiratory failure without increasing risk for intubationIn the sedation group (n = 68) 10 patients developed bradycardia, which was transient and improved spontaneously, and 8 patients experienced hypotension, although the authors attributed it to other causesShutes (23)Retrospective chart review0–18, (1–24 months 76%) F 41%, M 59%382 PICU patients Bronchiolitis Asthma Pneumonia Viral pneumonia Aspiration pneumoniaPositive Pressure ventilation dexmedetomidine infusion (starting dose 0.4 μg/kg/h range 0.4–0.5, median peak dose of 1 μg/kg/h range 0.6–1.2)336 patients (88%) experienced dexmedetomidine discontinuation, and 19 patients (5%) withdrawal.Dexmedetomidine use for noninvasive positive pressure ventilation sedation presented hemodynamic alterations. Withdrawal was associated with higher dosesThe hemodynamic alterations observed 4 h after reaching the peak dose included bradycardia in 28% of patients, hypertension in 33%, and hypotension in 2%; during the dose escalation phase, bradycardia was observed in 75% of patients and hypotension in 30%Venkatraman (24)Observational cohort study.202 patients Age, median (IQR) 2.0 (1.0–4.0), F 52%, M 48%Status asthmaticus, Acute bronchiolitis oncologic diagnosis Croup Septic shockNIV CPAP, BiPAP, or high-flow nasal cannula Dexmedetomidine infusion (0.61 μg/kg/h) (range 0.4–0.8)168 patients (83%) achieved target sedation level for at least 80% of the NIV duration. 96% the outcome of NIV was successfulDexmedetomidine was effective as continuous sedative infusion during NIVBradycardia was observed in 26 patients (13%), hypotension in 41 patients (20%), and hypopnea in 11 patients (5%). Endotracheal intubation was required in 5 patients (2.5%), including 1 patient (0.5%) who experienced cardiorespiratory arrest.Case seriesMusolino (25)Retrospective, observational, consecutive case series26 patients 72 months median range (16–345), F 42%, M 58%Moderate-to severe bronchiolitisHelmet Continuous Positive Airway Pressure one-time bolus dose of dexmedetomidine (0.25 mcg/kg/dose)Pharmacological sedation with a single dose of dexmedetomidine was required in 15/26 patients (57%) 22 patients tolerated the interfaceIn non-intensive settings H-CPAP for infants with bronchiolitis may be feasible2 patients developed relative bradycardiaPiastra (22)Retrospective case series40 patients Median age was 16 months (IQR 6,5; 33.50), F 25% M 75%Acute respiratory failure Bronchiolitis ARDS Chest trauma Burn-associated Respiratory Failure Status Asthmaticus Neurological illness Pneumonia Bronchopulmonary Dysplasia Post-operative patientsNIV Helmet 12, Total Face Mask 11, Nasal Mask 17 dexmedetomidine IV (start 0.5–0.7 mcg/kg/h until 1.0–1.4 mcg/kg/h)No NIV discontinuation due to NIV intoleranceDexmedetomidine should be considered safe and help in improving NIV and reduced+G8 agitation statusThe authors report a significant decrease in heart rate and mean arterial pressure 2 h after the introduction of dexmedetomidine; however, no patient developed severe bradycardia or hypotension requiring interruption of the infusion or administration of rescue medications.Case reportCozzi 2017 (9)Case report2 patients 15 months (F) and 4 years old (F)2 patients with acute asthma exacerbationOxygen supplementation with high-flow nasal cannula albuterol IV dexmedetomidine intranasal at 3 mcg/kgOxygen saturation from 88 to 93%, 90–94%Dexmedetomidine allowed to rest and improved tolerance to therapyNot reportedLichtsinn (21)Case report2 pediatric patients 8 week old (M), 27 month old (M)Acute hypoxemic respiratory failure due to RSV bronchiolitis, pulmonary hypertension secondary to pulmonary hypoplasiaBiPAP dexmedetomidine infusion was started at 0.2 mcg/kg/h up to 0.7 endotracheal intubation 0.3 mcg/kg/h 1.1 mcg/kg/h, up to 1.2Dexmedetomidine discontinuationDexmedetomidine increased vagal tone episodes resulting in asystoleIn the first case, the patient experienced bradycardia with episodes of asystole lasting up to 6 s
In the second case, the patient exhibited a 15-s period of asystole requiring cardiopulmonary resuscitation, followed by bradycardia

Characteristics of studies conducted on pediatric patients.

ARDS, Acute Respiratory Distress Syndrome; BiPAP, Bilevel Positive Airway Pressure; CPAP, Continuous Positive Airway Pressure; H-CPAP, Helmet Continuous Positive Airway Pressure; HFNC, High-Flow Nasal Cannula; IQR, Interquartile Range; IV, Intravenous; NIV, Non-Invasive Ventilation; NIV-NAVA, Non-Invasive Neurally Adjusted Ventilatory Assist; PICU, Pediatric Intensive Care Unit; RF, Acute Respiratory Failure; RSV, Respiratory Syncytial Virus; TFM, Total Face Mask (ventilation interface).

Study (reference)Study typePatients (age, sex)Clinical conditionInterventionOutcomesKey resultsAdverse effect if anyObservational studies/RCTsAbdelgalel (28)Randomized, double blinded controlled study90 patients 30 dexmedetomidine mean 51.1 ± 8.4 (F 2 0%, M 80%) 30 haloperidol mean 51.0 ± 8.8 SD (M 73%, F 27%) 30 placebo mean 49.1 ± 8.0 SD (M 70%, F 30%)Acute exacerbation of acute respiratory failure in COPD, acute hypoxemic cardiogenic pulmonary edema, postoperative respiratory failure patientsNIV dexmedetomidine loading dose of 1.0 lg/kg, then 0.2–0.7 lg/kg/h haloperidol loading dose 2.5 mg, then, 0.5–2 mg/h placebo group saline infusionIncidence of delirium, NIV duration, length of ICU and in hospital, were reduced in dexmedetomidine treated patients respect to haloperidol and placebo groups Mortality rate was inferior in dexmedetomidine, and haloperidol patients respect to placebo.Dexmedetomidine is more effective in preventing delirium during NIV compared to haloperidol. Furthermore, there was a lower incidence of endotracheal intubation, NIV failure and shorter stay on ICU in patients that received dexmedetomidine compared to patients that received haloperidol.Bradycardia: dexmedetomidine group n.8, haloperidol n.2, placebo n.1. prolonged QTc-interval (>500 ms): haloperidol n.2 arrhythmia: dexmedetomidine group n.2, haloperidol n.3, placebo n.2 Hypotension: dexmedetomidine group n.4, haloperidol n.3, placebo n.3 vomiting: dexmedetomidine group n.3, haloperidol n.5, placebo n.3.Altınkaya Çavuş (33)Prospective randomized cohort study227 patients dexmedetomidine low L dose median 66 (IQR 60–82) F 61%, M 39% dexmedetomidine high H dose 74 (59–80) F 39%, M 61% remifentanil low dose 71 (67–77) F 61% M39% remifentanil high dose 72 (62–76) F 26%, M 74% propofol PROP 71.5 (64.5–76) F 36%, M 64%NIV intolerance, acute respiratory acidosis, a diagnosis of COPD, and respiratory distressNIV dexmedetomidine IV loading 1 μg/kg, then 0.2 μg/kg/h in the DEXL group and at 0.6 μg/kg/h in the DEXH group. Remifentanil: initial at 1 μg/kg, then 0.03 μg/kg/h in the REML group, and at 0.06 μg/kg/h in the REMH group. propofol: IV initial at 0.3 mg/kg/h, then, any increases and/or decreases 0.1 mg/kg/h.NIV failure: 2 (8.7%) DEXL, 3 (13%) DEXH, 7 (30.4%) REML, 13 (56.5%) REMH, and 20 (71.4%) PROP Mortality: 1 (4.3) DEXL, 2 (8.7) DEXH, 5 (21.7) REML, 5 (21.7) REMH, 10 (35.7) PROP NIV duration, ICU and hospital length of stay were lower in DEXH and DEXL groupsNIV failure, mortality, ICU LOS, IMV time, and hospital LOS were found to be lower with dexmedetomidine.Side effects: 1 DEXL, 3 DEXH, 1 REML, 8 REMH, 8 PROP Apnea: 0 in DEXL; DEXH; REML, 1 REMH, 7 PROP higher incidence of bradycardia in the DEXL (4.3%) and DEXH (8.7%) groups than in the other groups (0%), (not statistically Significant) Not other side effectsBasilim (37)Multicenter, retrospective cohort study291 patients mean age SD 59.6 (15.46) M 61.4%, F 38.6% 259 control 32 dexmedetomidineCOVID-19 in the ICUsNoninvasive mechanical ventilation dexmedetomidine does not reportedNIV failure is higher in control group Time to invasive mechanical ventilation was longer in control. Longer ICU LOS but shorter hospital LOS ICU length of stay in dexmedetomidine group. However, all these comparison were not significantly different between the 2 groups. In hospital mortality was similarDexmedetomidine did not lower the risk of respiratory failure requiring invasive ventilation. Though the mean time on invasive ventilation was lower in the dexmedetomidine group.No significant difference in ICU related complications between both group such as kidney failure, shock, liver injury or delirium.Deletombe (29)RCT19 patients with chest trauma
Age median 56 (IQR 29, 67), F 11%, M 89%Patients with Chest trauma who needed NIVInfusion of DEX (0.7 mcg/kg/h) vs. placebo to improve NIV toleranceDexmedetomidine prolonged the duration of NIV compared to placebo: 280 min versus 120 min Dex associated to lower score for RASS and respiratory discomfortDexmedetomidine could facilitate the acceptance of the first session of non-invasive ventilation for patients with chest traumaBradycardia 1 arterial hypotension 5Devlin (8)RCTAdults, 16 received DEX, 17 received placebo, dexmedetomidine mean age 68 (SD 6), F 31% M 69%
Placebo mean age 62 (SD 17), F 65% M 35%ARF and NIVRandomization: IV dexmedetomidine (0.2 m g/kg/h and then titrated by 0.1 m g/kg/h every 30 min) or placebo up to 72 h, until NIV was stopped for 2 h, or until intubationUse of dexmedetomidine did not impact on NIV tolerance, sedation level, intubation rate or duration of invasive ventilation. Dex incremented NIV durationDexmedetomidine did not improve NIV tolerance nor time tolerating NIV or remaining at the desired level of sedationSevere bradycardia or hypotension did not develop in any patient in either groupDumbar (39)Observational multicenter cohort retrospective433,357 patients on NIV who received sedation or analgesia, mean age 67 (SD 14) F 52%, M 48%Patients with ARF and NIV26.7/f the patients received sedation or analgesia. 11%received opioids only, 9% benzodiazepines only, 5% opioids and benzodiazepines, 0.4% dexmedetomidine only, 0.6% dexmedetomidine + opioids/benzodiazepinesExposure to medications was associated with significantly increased odds of need for invasive ventilation or mortality use of dexmedetomidine was associated with greatest risk of intubation or mortality.The use of sedation during NIV for ARF is potentially harmfulNo reportedGhazaly (35)RCT45 patients, 15 dexmedetomidine, 15 ketamin3, 15 placebo, age median 36 (IQR 24.5–47.5) M 95.6%, F 4.4%Blunt chest traumaDexmedetomidine infusions initial 0.7 μg/kg/h, up to a maximum dose of 1.3 μg/kg/h. Ketamine infusion initial 0.20 mg/kg/h, up to a maximum dose of 0.5 mg/kg/hNIV duration longer in patients receiving dexmedetomidine or ketamine respect to placebo
RASS lower in dexmedetomidine group than ketamine or placeboThe use of dexmedetomidine improved NIV toleranceNot reportedHao (30)RCT179 patients, 89 remifentanil, 90 dexmedetomidine age 63 years (56–70 IQR), F 31% M 69%NIV and ARF in cardiac surgery patientsRemifentanil IV an initial dosage of 0.05 μg/kg/min, dexmedetomidine an initial dosage of 0.5 μg/kg/min increment of 0.01 μg/kg/min for remifentanil and 0.1 μg/kg/h for DEX.Initially the mitigation of NIV intolerance was better when using remifentanil, as well as the cumulative effect over time, however after 6 h the mitigation rate was similar. No differences between the two groups for NIV failure, reintubation, tracheostomy, ICU LOS, and mortalityNo differences between remifentanil ad dexmedetomidine to achieve mitigationRemifentanil group, no adverse effect dexmedetomidine 3 bradycardia and 6 severe hypotensionHuang (34)RCT62 patients (29 treated with midazolam, 33 with DEX)
Midazolam, age 61.5 ± 7.3, F 59%, M 41% dexmedetomidine age 67.4 ± 8.2, F 58%, M 42%Acute pulmonary edema and hypoxemia in NIV failure due to discomfortLoading dose up to 1 μg/kg dexmedetomidine or 0.05 mg/kg midazolam. Maintenance infusion dose 0.2–0.7 μg/kg/h dexmedetomidine and 0.05–0.1 mg/kg/h midazolam.Sedative scores in both groups. NIV failure was lower when using dexmedetomidine. Duration of mechanical ventilation and the ICU duration was decrease in dexmedetomidine group.Dexmedetomidine performed better than midazolam in achieving sedation and awaking sedation, it decreased duration of mechanical ventilation and the ICU LOSBradycardia without medical intervention dexmedetomidine-18.2% midazolam 0%.
Hypotension 12.1% (mid 17)
Hypotension with intervention 3%(mid 3.4%)
Delirium 3% (mid 13)
Vomit 6.1% (mid 31)
Gastric aspiration 6% (mid 10)
Respiratory infections 9% (mid31)Kim (40)Observational prospective multi-center155 patients treated with NIV, 26 received sedation 71.7 ± 11.4, F 34.6%, M 65.4%
129 control no sedation age 71.7 ± 11.5 years, F 39.5%, M 60.5%ARF due mainly to exacerbation of COPD or pneumonia26 patients who received analgo-sedation (15 remifentanil, 8dex, 1 fentanyl, 1 midazolam, 1 morphine)Sedation group experienced higher NIV failure and intubation mainly due to inadequate efficacy and less to discomfort (13–14%). LOS was similar in the two groups as well as mortality rateSedation can be used for pain control in some patients and may be not unsafeSedation group 9 complications mainly skin erythema control group 45 complication, mainly skin erythema, large leakMatsumoto (41)Observation cohort120 patients analyzed. 83 received sedation, adultsAcute respiratory distress syndrome/acute lung injury/severe pneumonia or acute exacerbation of interstitial pneumonia.Sedation (risperidone, haloperidol, dexmedetomidine, midazolam, propofol, morphine, fentanyl) was performed only intermittently in 72 (60%) patients, was switched to continuously in 37 (31%) and was applied only continuously in 11 (9%) dexmedetomidine IV initial dose 0.2 μg/kg/h, increasing dose 0.1 μg/kg/hIn group non DNI (do not intubate), mortality and intubation rate did not differ between continuous or intermittent sedation. Among the DNI patients’ mortality higher in continuous use.Sedation may be used at avoid NIV failure in agitated patients, however, a continuous use may lead to increased hypercapnic state and the possibility of increased mortality.Midazolam 1 hypotension 1 delirium, 1 ileus, 3 hypercapnia pre-sedation progress and exhibited drowsiness
Not side effects of DEX reportedRiccardi (42)Observational retrospective66 patients who underwent sedation for NIV
Ketamine-dexmedetomidine 78.33 ± 8.72, F 59.1%, M 40.9%, ketamine 79.41 ± 10.76, F 59.1%, M 40.9%, dexmedetomidine 77.21 ± 12.33, F 55.5%, M 44.5%Acute respiratory distress due to COVID19 pneumoniaNIV CPAP 22 patients ketamine (1 mg/kg, followed by 1 mg/kg/h) and dexmedetomidine (0.7 mcg/kg, followed by 0.7 mcg/kg/h). 22 patients DEX (0.7 mcg/kg in 10 min, followed by 0.7 mcg/kg/h up to 2 mcg/kg/h) 22 patients ketamine (1 mg/kg, followed by 1 mg/kg/h)The combination of ketamine- dexmedetomidine resulted in faster sedation rates and better hemodynamic profiles than dexmedetomidine aloneThe combination of ketamine- dexmedetomidine is beneficial and effective for NIV adherence particularly in ICUDexmedetomidine: 10 hypotension ketamine: 10 hypotension ketamine dexmedetomidine: Hypotension in 10 out of 12 patients treated with DEX onlySenoglu (32)RCT40 patients in NIV dexmedetomidine median 58 (range 28–80) F 55%, M 45% midazolam median 60 (range 30–81), F 50%, M 50%Acute respiratory failure due to acute exacerbations or COPDNIV dexmedetomidine: loading dose 1 μg/kg IV r 0.05, maintenance i0.5 μg/kg/h midazolam: loading dose 0.05 mg/kg, maintenance 0.1 mg/kg/hLow level of RSS at 4 h in dexmedetomidine group respect to midazolam High level of RSAS at 8 h in dexmedetomidine group respect to midazolam high BIS in dexmedetomidine group respect to midazolam.Similar effectiveness for Dexmedetomidine and midazolam in NIV patients. Dexmedetomidine respect to midazolam required fewer dose adjustmentsNo patient experienced adverse cardiovascular effects midazolam 1 oversedation 2 excluded for agitationSimioli (43)Retrospective cohort study170 patients median age 71 (IQR 61–80), F 29%, M 71%Interstitial pneumonia with critical extension compatible with severe COVID-19, acute respiratory failure and moderate ARDSNon-invasive ventilation (NIV) and high-flow nasal cannula (HFNC). dexmedetomidine initial dose of 0.3 mcg/kg/h, maintenance dose between 0.2 and 0.8 mcg/kg/hIncreased pO2/FiO2 ratio. Reduction of NIV duration and reduction of endotracheal intubation in DEX group compared to the controls.The adjunctive therapy with dexmedetomidine is associated with a higher pO2/FiO2, lower duration of NIV, and a lower risk of NIV failureA higher incidence of sinus bradycardia was observed in the DEX group
Hypotension and delirium as controls
Bradycardia 30% (vs 18% controls)Sinnot (44)Cohort retrospective103 patients in emergency department, age median 54 (IQR 37–65), F 32.2%, M 67.8%ARF, dexmedetomidine for mechanical ventilation and NIV facilitation0.4 micrograms/kilogram/h (mcg/kg/h) in non-intubated patients. Mechanically ventilated patients starting dose 0.7 mcg/kg/h, titration of 0.1 mcg/kg/h every 45 minNo differences was observed between the groups with/without adverse effects for ventilator-free days, ICU-free days, and hospital-free days and mortality. Duration of DEX treatment in the ED correlated with increased risk of hypotension or bradycardiaWhile adverse events are relatively common, they are of questionable clinical significance.Hypotension (39%) bradycardia <60 bpm (17.5%). Dexmedetomidine interruption due to adverse event (7.8%)
Non bradycardia under 40 bpm
18% of hypotensions were over 30% from baselineUeno (31)RCT24 patients 12 dexmedetomidine 12 not treated median age 76 (IQR 70, 78) F 37.5%, M 62.5%Critical ill patients with ARF, at admission diagnosis was cardiovascular surgery, Acute respiratory failure, congestive heart failure, acute myocardial infarctionHigh-flow nasal cannula oxygen therapy (HFNC) dexmedetomidine initially at 0.4 μg / kg / h, then 0.2 to 0.7 μg / kg / hIncrement of Total Sleep Time and sleep efficiency in patients treated with dexmedetomidineDexmedetomidine improved sleep quantity without any side events in critically ill patientsSimilar frequency of respiratory depression and hemodynamic instability in the two groups hypotension 1/12 in dex, 0/12 in non dex; bradycardia 0/12 For each groupYildirim (45)Retrospective cohort study60 patients mean age 68 ± 11 SD, F 30% M 70%Patients underwent major abdominal surgery gastrectomy, colorectal surgery, liver surgery, and pancreatectomyDexmedetomidine IV loading dose of 0.2 mcg/kg for 10 min, maintained at 0.2–0.7 mcg/kg/hRASS score improved 92.5% of patients. Achieved the targeted sedation level. 7 patients experienced NIV failure and required intubation for worsening 56 patients improved and were discharged from ICUDexmedetomidine demonstrates effective sedation in patients with postoperative ARF during NIMV application after abdominal surgery. Dexmedetomidine can be considered safe and capable of improving NIMV success.6 bradycardia and 5 hypotension
10%bradycardia (No one Needed intervention); 8.3% hypotension, (No one Needed intervention)Baumgartner (38)Prospective observational cohort study