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Original Research: Critical Care |

Efficacy and Safety of Early Dexmedetomidine During Noninvasive Ventilation for Patients With Acute Respiratory FailureDexmedetomidine During Noninvasive Ventilation: A Randomized, Double-Blind, Placebo-Controlled Pilot Study FREE TO VIEW

John W. Devlin, PharmD; Nada S. Al-Qadheeb, PharmD, FCCP; Amy Chi, MD; Russel J. Roberts, PharmD; Imrana Qawi, MD; Erik Garpestad, MD, FCCP; Nicholas S. Hill, MD, FCCP
Author and Funding Information

From the School of Pharmacy (Drs Devlin and Al-Qadheeb), Northeastern University; and Division of Pulmonary, Critical Care and Sleep Medicine (Drs Devlin, Chi, Qawi, Garpestad, and Hill) and Department of Pharmacy (Dr Roberts), Tufts Medical Center, Boston, MA.

Correspondence to: John W. Devlin, PharmD, School of Pharmacy, Northeastern University, 360 Huntington Ave, R218 TF, Boston, MA 02115; e-mail: j.devlin@neu.edu


Part of this article has been presented in abstract form at the American Thoracic Society International Conference, May 17-22, 2013, Philadelphia, PA.

Funding/Support: This study was supported by an unrestricted investigator-initiated grant from Hospira, Inc.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;145(6):1204-1212. doi:10.1378/chest.13-1448
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Background:  Successful application of noninvasive ventilation (NIV) for acute respiratory failure (ARF) requires patient cooperation and comfort. The efficacy and safety of early IV dexmedetomidine when added to protocolized, as-needed IV midazolam and fentanyl remain unclear.

Methods:  Adults with ARF and within 8 h of starting NIV were randomized to receive IV dexmedetomidine (0.2 μg/kg/h titrated every 30 min to 0.7 μg/kg/h to maintain a Sedation-Agitation Scale [SAS] score of 3 to 4) or placebo in a double-blind fashion up to 72 h, until NIV was stopped for ≥ 2 h, or until intubation. Patients with agitation (SAS ≥ 5) or pain (visual analog scale ≥ 5 of 10 cm) 15 min after each dexmedetomidine and placebo increase could receive IV midazolam 0.5 to 1.0 mg or IV fentanyl 25 to 50 μg, respectively, at a minimum interval of every 3 h.

Results:  The dexmedetomidine (n = 16) and placebo (n = 17) groups were similar at baseline. Use of early dexmedetomidine did not improve NIV tolerance (score, 1 of 4; OR, 1.44; 95% CI, 0.44-4.70; P = .54) nor, vs placebo, led to a greater median (interquartile range) percent time either tolerating NIV (99% [61%-100%] vs 67% [40%-100%], P = .56) or remaining at the desired sedation level (SAS score = 3 or 4, 100% [86%-100%] vs 100% [100%-100%], P = .28], or fewer intubations (P = .79). Although use of dexmedetomidine was associated with a greater duration of NIV vs placebo (37 [16-72] vs 12 [4-22] h, P = .03), the total ventilation duration (NIV + invasive) was similar (3.3 [2-4] days vs 3.8 [2-5] days, P = .52). More patients receiving dexmedetomidine had one or more episodes of deep sedation vs placebo (SAS ≤ 2, 25% vs 0%, P = .04). Use of midazolam (P = .40) and episodes of either severe bradycardia (heart rate ≤ 50 beats/min, P = .18) or hypotension (systolic BP ≤ 90 mm Hg, P = .64) were similar.

Conclusions:  Initiating dexmedetomidine soon after NIV initiation in patients with ARF neither improves NIV tolerance nor helps to maintain sedation at a desired goal. Randomized, multicenter trials targeting patients with initial intolerance are needed to further elucidate the role for dexmedetomidine in this population.

Trial registry:  ClinicalTrials.gov; No: NCT00871624; URL: www.clinicaltrials.gov

Figures in this Article

Noninvasive positive-pressure ventilation is increasingly being used to manage patients with acute respiratory failure (ARF)1,2 in an effort to avoid the negative sequelae associated with intubation.3 However, noninvasive ventilation (NIV) failure remains a challenging aspect of NIV management, with rates approaching 40% in recent studies.4,5 Patient intolerance and agitation, often related to mask intolerance or claustrophobia, are considered frequent contributors to NIV failure.69 Despite data suggesting that use of sedatives (eg, midazolam, propofol) or opioids may improve patient comfort and tolerance during NIV,1012 clinicians are hesitant to administer these agents because of concerns that they may induce respiratory depression.13,14 Moreover, benzodiazepines and opioids are frequently challenging to titrate their pharmacologic effects because they may accumulate after repeated dosing,15,16 and benzodiazepines are associated with greater delirium.17

Dexmedetomidine is a short-acting IV-administered α2 adrenoreceptor agonist that produces a state of cooperative sedation, facilitating patient-caregiver interaction.18,19 Compared with midazolam and propofol, dexmedetomidine will not affect respiratory drive, has analgesic properties that reduce the need for IV opioid coadministration, has bronchodilator effects, and is less likely to cause delirium.2022 Case series have demonstrated that dexmedetomidine will safely resolve acute agitation that occurs during NIV.2325 One small, randomized trial of patients with acute agitation while receiving NIV reported that continuous IV dexmedetomidine and midazolam are equivalent in their ability to maintain patients at the desired level of sedation, optimize gas exchange, and maintain hemodynamic stability.26 In a more recent randomized trial of 62 patients with cardiogenic pulmonary edema refusing to continue NIV due to discomfort, use of infused dexmedetomidine was associated with a lower intubation rate and shorter stays on mechanical ventilation and in the ICU.27 On the basis of these observations and the favorable pharmacologic profile of dexmedetomidine for use during NIV for ARF, we speculated that compared with as-needed midazolam or fentanyl, routine early use of dexmedetomidine in patients receiving NIV for ARF would be safe, improve NIV tolerance, maintain a more consistent target level of sedation, and avoid NIV failure.

Setting

This prospective, randomized, double-blind, placebo-controlled study was conducted at two medical centers: Tufts Medical Center, a 320-bed academic medical center in Boston, Massachusetts, and Winchester Hospital, a 200-bed community hospital in Winchester, Massachusetts. The institutional review boards at each institution approved the study (IRB #8533 and IRB #5-2008, respectively), and written informed consent was obtained from all patients prior to randomization.

Patients

From September 2008 to October 2012, consecutive adult patients admitted to an ICU with ARF managed with NIV for ≤ 8 h were evaluated for study participation. Study exclusion criteria were age ≥ 85 years, systolic BP ≤ 90 mm Hg, heart rate ≤ 50 beats/min, the presence of acute decompensated heart failure accompanied by a cardiac ejection fraction ≤ 25%, acute alcohol withdrawal or delirium (Intensive Care Delirium Screening Checklist score ≥ 4),28 a history of intubation and mechanical ventilation in the past month, heart block without pacemaker use, end-stage liver failure accompanied by encephalopathy, severe dementia, and treatment with clonidine or dexmedetomidine in the past 30 days.29 At each study site, patients were assigned in blocks of four to one of the two groups in a 1:1 ratio by means of a computer-generated random-number table prepared in advance by the investigational drug service. Treatment allocation was known only to the investigational pharmacist at each site.

Study Outcomes

Tolerance of NIV was evaluated as the main outcome variable using a four-point NIV intolerance score adapted from previously published four- and five-point NIV tolerance scores.3032 A score of 1 indicated a comfortable and relaxed patient tolerating NIV; 2, mild intolerance with some discomfort and occasional grabbing at the NIV mask; 3, moderate intolerance and discomfort with the NIV mask most of the time with frequent grabbing at the mask (sometimes pulling it off); and 4, severe NIV intolerance with agitation with an inability to leave the NIV mask in place. This NIV intolerance score was based on the following constructs: (1) degree of NIV intolerance was more important to differentiate in patients than degree of tolerance; (2) specific patient-related descriptors of intolerance (eg, occasional grabbing at the mask) were preferable to general terms like “poor”; and (3) a four-point score was preferable to a five-point score when comparing tolerance scores between two groups. NIV tolerance was evaluated at baseline; after 30 min; after 1, 3, 6, and 12 h of NIV; and thereafter every 12 h until the dexmedetomidine (or placebo) was discontinued. NIV failure was defined as need for intubation or death while NIV was still applied.

The Sedation-Agitation Scale (SAS) score was used to evaluate level of sedation every 4 h, with an SAS score ≥ 5 representing agitation and an SAS score ≤ 2 deep sedation.33 A 10-cm visual analog scale (VAS) was used to evaluate pain every 6 h, with a score of 0 cm indicating no pain and a score of 10 cm indicating severe pain.3436 In situations where the patient was not able to complete the VAS (eg, sedated, visually impaired), the bedside nurse documented the patient’s self-reported pain score on the VAS form. Patients were screened for delirium every 12 h using the Intensive Care Delirium Screening Checklist.28 All sedation, pain, and delirium assessments were conducted by the bedside nurse, who had received prior education regarding each assessment.37 Hypotension was defined as a systolic BP ≤ 90 mm Hg, bradycardia as a heart rate ≤ 50 beats/min, and bradypnea as a respiratory rate ≤ 12 breaths/min.

In an effort to evaluate the influence of dexmedetomidine on other clinically relevant NIV-related domains, the bedside nurse and on-duty respiratory therapist independently evaluated each patient’s level of communication (1 = not communicating; 10 = fully communicating), cooperation with care (1 = not cooperating; 10 = fully cooperating), and NIV tolerance (1 = not tolerating; 10 = fully tolerating) on three different scales every 12 h. The bedside nurse also administered a satisfaction assessment to each patient every 12 h where the patient was asked to self-rate on a 10-point scale his or her current breathing status (1 = cannot breathe; 10 = breathing well), level of pain (1 = no pain; 10 = worst pain ever), and level of anxiety (1 = no anxiety; 10 = extreme anxiety). These patient-specific domains were derived from a careful assessment of the NIV literature.1,2,58,2327,3032,38 At the time of randomization and at predetermined follow-up intervals, where appropriate,8 data on patient demographics, location, and pertinent physiologic parameters were collected.8,3840

Intervention

Dexmedetomidine (or placebo) was initiated as an IV infusion without an initial bolus at a rate of 0.2 μg/kg/h and then titrated by 0.1 μg/kg/h every 30 min (up to a maximum rate of 0.7 μg/kg/h) to maintain an SAS score of 3 to 4. Fifteen minutes after any dexmedetomidine (or placebo) dose increase, a single dose of midazolam 0.5 to 1.0 mg IV could be administered as needed if the patient was agitated (SAS score ≥ 5), and a single dose of fentanyl 25 to 50 μg IV could be administered as needed if the patient reported pain (VAS score ≥ 5 of 10 cm) as long as 3 h had elapsed since the last midazolam or fentanyl dose. In any patient in whom delirium developed, haloperidol 0.5 to 1 mg IV q6h could be administered as needed. The study sedation protocol was posted at the patient’s bedside, and the bedside nurse managing a study patient received education about the protocol (and related procedures) at the beginning of each shift.

Patients meeting criteria for clinical stability on NIV40 were weaned by removing the mask and starting oxygen supplementation to maintain an arterial oxygen saturation of ≥ 92%. NIV was resumed without delay when one or more of the following developed: respiratory rate increase of ≥ 24 breaths/min, accessory muscle use or respiratory distress increase, or arterial oxygen saturation of 89% on a steady level of oxygen supplementation.40 The dexmedetomidine (or placebo) infusion was discontinued when the patient remained stable for ≥ 2 h after NIV mask removal. Other defined end points for dexmedetomidine (or placebo) discontinuation were 72 h of administration, requirement for intubation, or development of a serious adverse event warranting dexmedetomidine (or placebo) discontinuation.

Data Analysis

A difference in the mean four-point NIV intolerance score of 1 over the course of the study or between two groups was considered through investigator consensus to be clinically meaningful. Assuming that the SD of the NIV intolerance scores was 1 and that an α of 0.05 would be used for testing, it was determined that 18 subjects were needed in each group to achieve 80% power.

Patients were analyzed in the groups to which they were randomized using an intention-to-treat principle. Upon reviewing the data across all patients for all time points, < 5% of intolerance scores were > 2, so for the analysis, we dichotomized the NIV intolerance scores as either NIV tolerant (intolerance score = 1) or NIV intolerant (intolerance score = 2, 3, or 4). A generalized estimating equation approach was used to analyze changes in the dichotomized intolerance score over time between the two groups. For the other outcomes, means were compared using the Student t test, and proportions were compared using the χ2 test with two-tailed P values. For variables with skewed distributions, including lengths of mechanical ventilation and ICU stay, results were reported as median and interquartile range (IQR) and compared between groups using a Mann-Whitney U test. P ≤ .05 was considered significant.

Sixty-one patients were evaluated for participation in the study; 25 were excluded, and 36 were randomized (Fig 1). Three patients were withdrawn from the study before dexmedetomidine (or placebo) could be administered because of consent withdrawal (n = 1), emergent intubation (n = 1), and the accidental administration of nonblinded, nonstudy dexmedetomidine (n = 1). Thirty-three patients were, therefore, included in the final intention-to-treat analysis.

Figure Jump LinkFigure 1. Description of patients who were screened, enrolled, and randomized into the study. EF = ejection fraction.Grahic Jump Location

Baseline characteristics were similar between the two groups (Table 1). Dexmedetomidine, initiated on average 4 h after NIV application, was not associated with a significantly greater odds of tolerating NIV (OR, 1.44; 95% CI, 0.44-4.7; P = .54) (Fig 2) or in patients spending a greater percentage of time tolerating NIV vs placebo (OR, 99 [95% CI, 61-100] vs 67 [95% CI, 40-100]; P = .56) (Table 2). Among the six patients (38%) receiving dexmedetomidine and five (29%) receiving placebo who were intolerant of NIV at baseline, dexmedetomidine was not associated with a significant increase in the likelihood of tolerating NIV (OR, 2.71; 95% CI, 0.49-15.07; P = .25). Among this same baseline intolerant group, the percentage of time spent tolerant of NIV also was not significantly different between the dexmedetomidine (median, 73%; IQR, 0%-97%) and placebo (median, 40%; IQR, 17%-50%; P = .46) groups.

Table Graphic Jump Location
Table 1 —Baseline Characteristics

Data are presented as mean ± SD, %, or median (interquartile range). APACHE = Acute Physiology and Chronic Health Evaluation; ARF = acute respiratory failure; ICDSC = Intensive Care Delirium Screening Checklist; NIV = noninvasive ventilation; SAS = Sedation-Agitation Scale.

Figure Jump LinkFigure 2. Proportion of patients deemed to be NIV tolerant (tolerance score = 1 of 4) across each assessment period during dexmedetomidine or placebo administration. The table shows the number of patients still receiving dexmedetomidine or placebo at each assessment period. NIV = noninvasive ventilation.Grahic Jump Location
Table Graphic Jump Location
Table 2 —Clinical Outcomes

Data are presented as median (interquartile range) or %. TS = tolerance score. See Table 1 legend for expansion of other abbreviation.

The number of patients remaining in the study dropped off sharply after the 12-h assessment period (Fig 2). Over the first 12 h, dexmedetomidine was associated with a greater, but still nonsignificant, odds of tolerating NIV (OR, 4.20; 95% CI, 0.82-21.48; P = .08). Although the duration of NIV was longer in the dexmedetomidine group (median, 37 h; IQR 16-72 h) than in the placebo group (median, 12 h; IQR, 4-22 h; P = .03), the intubation rate (31% vs 29%, dexmedetomidine vs placebo, respectively; P = .80) and the duration of invasive ventilation for patients requiring intubation (P = .12) were similar (Table 2). No patient died during NIV therapy, so the rate of NIV failure was the same as the intubation rate. Duration of ICU stay (P = .71) and the proportion of patients discharged from the hospital either to home or to a rehabilitation center (P = .90) were similar between the two groups.

The time spent at the desired sedation goal (SAS score = 3 or 4) and free of pain (VAS score < 5 cm) was similar and nearly 100% in both the dexmedetomidine and the placebo groups (Table 2). More patients in the dexmedetomidine-treated group had one or more episodes of deep sedation (25% vs 0%, P = .04). No patient in either group required restraints.

Neither total nurse, respiratory therapist, nor patient satisfaction evaluations, or any of the individual domains in each, were different between the dexmedetomidine and placebo groups (Table 3). Dexmedetomidine and placebo infusions were titrated in a similar fashion, with 25% of patients in each group administered a dexmedetomidine (or placebo) infusion at a rate of ≥ 0.5 μg/kg/h (Table 4). The use of as-needed IV midazolam, fentanyl, and haloperidol was similar between the two groups.

Table Graphic Jump Location
Table 3 —Nursing, Respiratory Therapist, and Patient Satisfaction

Data are presented as mean ± SD. See Table 1 legend for expansion of abbreviation.

a 

Average of the three satisfaction domains.

Table Graphic Jump Location
Table 4 —Medication Use During Period of Dexmedetomidine (or Placebo) Administration

Data presented as median (interquartile range) or %.

Only one study patient (placebo arm) had to have the study drug discontinued because of a serious adverse event. This patient experienced a run of supraventricular tachycardia that was accompanied by hypotension that resolved after cardioversion. Severe bradycardia or hypotension did not develop in any patient in either group. The average heart rate was lower in the dexmedetomidine group than in the placebo group (81 ± 15 beats/min vs 98 ± 24 beats/min, P = .02). The two other reasons for stopping dexmedetomidine (or placebo) therapy were intubation (five patients in each group) or the successful withdrawal of NIV therapy (11 patients in each group).

Unlike other reports that have focused solely on either evaluating the role of dexmedetomidine as treatment of acute agitation during NIV2326 or in patients refusing to continue NIV,27 the present randomized, double-blind study sought to determine whether the routine early initiation of dexmedetomidine after the application of NIV would improve NIV tolerance. In a population of patients of which only one-third was intolerant of NIV at baseline, we found that the addition of low-dose IV dexmedetomidine to a pain and sedation protocol of as-needed IV intermittent midazolam and fentanyl did not significantly improve NIV tolerability or help to maintain patients at the desired sedation goal, although it was associated with a longer duration of NIV. Compared with standard use of intermittent midazolam and fentanyl, dexmedetomidine, as used in this study, did not prevent agitation, reduce pain or delirium, prevent intubation, or improve nurse, respiratory therapist, and patient satisfaction and was associated with more episodes of deep sedation.

This investigation has a number of strengths. With the exception of the investigational drug pharmacists who had no input in clinical management, neither investigators nor clinicians were aware of the patient’s treatment allocation given the double-blind study design. Dexmedetomidine (or placebo) was started early (within 8 h of NIV therapy), averaging 4 to 4.5 h after initiation. The use of a formal dexmedetomidine (or placebo) titration protocol that incorporated a standardized approach to the use of as-needed IV midazolam and fentanyl, and was accompanied by substantial education regarding its use, resulted in an average administered volume of study drug that was nearly identical in both study groups. A study investigator evaluated intolerance to NIV at regular intervals using a descriptive 4-point intolerance score, and a similar protocolized approach to NIV weaning and intubation was used in all patients.

The ability of patients to cooperate during NIV is an important predictor of NIV success.6 Although the present study suggests that the early, routine use of dexmedetomidine does not lead to a benefit for all patients who are initiated on NIV for ARF, it does suggest that dexmedetomidine may be beneficial in patients identified to be intolerant of NIV and where nonpharmacologic maneuvers to resolve intolerance are not effective.79 In this respect, the study by Huang et al,27 which showed reductions in intubation rate and length of ICU stay after initiation of dexmedetomidine in a group of patients refusing to continue NIV, is illustrative. Although the present trial was underpowered to investigate outcomes in specific patient subgroups, there was a trend for the one-third of patients in the study who were not tolerant to NIV at baseline to become tolerant when administered dexmedetomidine. With the intubation rate being similar between the two groups, it remains unclear whether the longer duration of NIV use in the dexmedetomidine group was a result of improved NIV tolerance leading to continued NIV therapy or a reduced ability to remove patients from NIV due to oversedation. The fact that the proportion of patients in the placebo group who received a dose of midazolam and fentanyl was each less than one-half implies that dexmedetomidine was not actually needed in many patients. The role for dexmedetomidine as a strategy to treat NIV intolerance when other nonpharmacologic strategies fail requires further investigation.

Limitations of this study must also be acknowledged. Although our pilot investigation was powered to detect a one-point difference in NIV intolerance between groups, the large proportion of study patients who were tolerant of NIV at baseline may have diminished our ability to demonstrate a significant improvement (or even trend) in this outcome. The small proportion of patients with more severe intolerance may be related to intubation before these patients could be considered for study participation and the exclusion of patients with conditions (eg, delirium) that might have led to greater intolerance. In addition, our pilot investigation had small numbers, which exposes the study to possible β-error and limits the analysis of pertinent subgroups, such as those less tolerant of NIV at its initiation. Furthermore, we used no initial bolus dose and raised the infusion rate slowly. A more aggressive dosing regimen could have yielded different results. The method by which dexmedetomidine was titrated in this study may be different than in settings where dexmedetomidine use is not blinded or clinician experience with its use in the NIV population is greater. Although blinded to study allocation, clinicians and investigators may have been able to guess which patients were receiving dexmedetomidine given the greater occurrence of deep sedation observed in this group.

Education on study assessments was provided to all bedside nurses and respiratory therapists, but we did not assess interrater reliability. Although the comfort of all patients was managed with a formalized as-needed IV fentanyl and midazolam protocol, variability in the pain and sedation assessments documented and the decision of the bedside nurse to administer or not administer one of these agents may have influenced the NIV intolerance scores observed. Factors other than the amount of dexmedetomidine or as-needed midazolam or fentanyl administered may have also influenced NIV tolerance. The study did not allow conclusions to be made about the safety or efficacy of dexmedetomidine in very elderly patients, long-term users of NIV at home, patients with underlying cardiomyopathy, or patients with delirium or hemodynamic instability because these patients were all excluded.

We conclude that the routine early use of low-dose dexmedetomidine during NIV does not improve overall tolerance of NIV, but dexmedetomidine may have beneficial effects for patients who are initially less tolerant. Dexmedetomidine also appears to be safe, although its use was associated with the greater occurrence of deep sedation compared with standard intermittent administration of benzodiazepines and narcotics.

Author contributions: Dr Devlin had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Dr Devlin: contributed to the study concept, data acquisition and interpretation, and manuscript preparation and final approval.

Dr Al-Qadheeb: contributed to the data acquisition and interpretation and manuscript preparation and final approval.

Dr Chi: contributed to the data acquisition and interpretation and manuscript preparation and final approval.

Dr Roberts: contributed to the data acquisition and interpretation and manuscript preparation and final approval.

Dr Qawi: contributed to the data acquisition and interpretation and manuscript preparation and final approval.

Dr Garpestad: contributed to the data acquisition and interpretation and manuscript preparation and final approval.

Dr Hill: contributed to the study concept, data acquisition and interpretation, and manuscript preparation and final approval.

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Devlin has received research funding and continuing medical education speaker honoraria from Hospira, Inc. Dr Hill has received research funding from Hospira, Inc. Drs Al-Qadheeb, Chi, Roberts, Qawi, and Garpestad have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Role of sponsors: The funder had no influence in the study design, conduct, and analysis or in the preparation of this article.

Other contributions: The authors thank Robin Ruthazer, MPH, for the statistical analysis and the nurses and respiratory therapists for patient management and data collection.

ARF

acute respiratory failure

IQR

interquartile range

NIV

noninvasive ventilation

SAS

Sedation-Agitation Scale

VAS

visual analog scale

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Bergeron N, Dubois MJ, Dumont M, Dial S, Skrobik Y. Intensive Care Delirium Screening Checklist: evaluation of a new screening tool. Intensive Care Med. 2001;27(5):859-864. [CrossRef]
 
Charlesworth M, Elliott MW, Holmes JD. Noninvasive positive pressure ventilation for acute respiratory failure in delirious patients: understudied, underreported, or underappreciated? A systematic review and meta-analysis. Lung. 2012;190(6):597-603. [CrossRef]
 
Nava S, Ambrosino N, Bruschi C, Confalonieri M, Rampulla C. Physiological effects of flow and pressure triggering during non-invasive mechanical ventilation in patients with chronic obstructive pulmonary disease. Thorax. 1997;52(3):249-254. [CrossRef]
 
Vitacca M, Rubini F, Foglio K, Scalvini S, Nava S, Ambrosino N. Non-invasive modalities of positive pressure ventilation improve the outcome of acute exacerbations in COLD patients. Intensive Care Med. 1993;19(8):450-455. [CrossRef]
 
Carlucci A, Pisani L, Ceriana P, Malovini A, Nava S. Patient-ventilator asynchronies: may the respiratory mechanics play a role? Crit Care. 2013;17(2):R54. [CrossRef]
 
Riker RR, Picard JT, Fraser GL. Prospective evaluation of the Sedation-Agitation Scale for adult critically ill patients. Crit Care Med. 1999;27(7):1325-1329. [CrossRef]
 
Ho K, Spence J, Murphy MF. Review of pain-measurement tools. Ann Emerg Med. 1996;27(4):427-432.
 
Huskisson E. Visual analogue scales.. In:Melzack R., ed. Pain Measurement and Assessment. New York, NY: Raven Press; 1983:33-37.
 
Jensen MP, Karoly P, Braver S. The measurement of clinical pain intensity: a comparison of six methods. Pain. 1986;27(1):117-126. [CrossRef]
 
Devlin JW, Marquis F, Riker RR, et al. Combined didactic and scenario-based education improves the ability of intensive care unit staff to recognize delirium at the bedside. Crit Care. 2008;12(1):R19. [CrossRef]
 
Schneider E, Dualé C, Vaille JL, et al. Comparison of tolerance of facemask vs. mouthpiece for non-invasive ventilation. Anaesthesia. 2006;61(1):20-23. [CrossRef]
 
Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med. 1985;13(10):818-829. [CrossRef]
 
Mehta S, Jay GD, Woolard RH, et al. Randomized, prospective trial of bilevel versus continuous positive airway pressure in acute pulmonary edema. Crit Care Med. 1997;25(4):620-628. [CrossRef]
 

Figures

Figure Jump LinkFigure 1. Description of patients who were screened, enrolled, and randomized into the study. EF = ejection fraction.Grahic Jump Location
Figure Jump LinkFigure 2. Proportion of patients deemed to be NIV tolerant (tolerance score = 1 of 4) across each assessment period during dexmedetomidine or placebo administration. The table shows the number of patients still receiving dexmedetomidine or placebo at each assessment period. NIV = noninvasive ventilation.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1 —Baseline Characteristics

Data are presented as mean ± SD, %, or median (interquartile range). APACHE = Acute Physiology and Chronic Health Evaluation; ARF = acute respiratory failure; ICDSC = Intensive Care Delirium Screening Checklist; NIV = noninvasive ventilation; SAS = Sedation-Agitation Scale.

Table Graphic Jump Location
Table 2 —Clinical Outcomes

Data are presented as median (interquartile range) or %. TS = tolerance score. See Table 1 legend for expansion of other abbreviation.

Table Graphic Jump Location
Table 3 —Nursing, Respiratory Therapist, and Patient Satisfaction

Data are presented as mean ± SD. See Table 1 legend for expansion of abbreviation.

a 

Average of the three satisfaction domains.

Table Graphic Jump Location
Table 4 —Medication Use During Period of Dexmedetomidine (or Placebo) Administration

Data presented as median (interquartile range) or %.

References

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Senoglu N, Oksuz H, Dogan Z, Yildiz H, Demirkiran H, Ekerbicer H. Sedation during noninvasive mechanical ventilation with dexmedetomidine or midazolam: a randomized. double-blind, prospective study. Curr Ther Res Clin Exp. 2010;71(3):141-153. [CrossRef]
 
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Bergeron N, Dubois MJ, Dumont M, Dial S, Skrobik Y. Intensive Care Delirium Screening Checklist: evaluation of a new screening tool. Intensive Care Med. 2001;27(5):859-864. [CrossRef]
 
Charlesworth M, Elliott MW, Holmes JD. Noninvasive positive pressure ventilation for acute respiratory failure in delirious patients: understudied, underreported, or underappreciated? A systematic review and meta-analysis. Lung. 2012;190(6):597-603. [CrossRef]
 
Nava S, Ambrosino N, Bruschi C, Confalonieri M, Rampulla C. Physiological effects of flow and pressure triggering during non-invasive mechanical ventilation in patients with chronic obstructive pulmonary disease. Thorax. 1997;52(3):249-254. [CrossRef]
 
Vitacca M, Rubini F, Foglio K, Scalvini S, Nava S, Ambrosino N. Non-invasive modalities of positive pressure ventilation improve the outcome of acute exacerbations in COLD patients. Intensive Care Med. 1993;19(8):450-455. [CrossRef]
 
Carlucci A, Pisani L, Ceriana P, Malovini A, Nava S. Patient-ventilator asynchronies: may the respiratory mechanics play a role? Crit Care. 2013;17(2):R54. [CrossRef]
 
Riker RR, Picard JT, Fraser GL. Prospective evaluation of the Sedation-Agitation Scale for adult critically ill patients. Crit Care Med. 1999;27(7):1325-1329. [CrossRef]
 
Ho K, Spence J, Murphy MF. Review of pain-measurement tools. Ann Emerg Med. 1996;27(4):427-432.
 
Huskisson E. Visual analogue scales.. In:Melzack R., ed. Pain Measurement and Assessment. New York, NY: Raven Press; 1983:33-37.
 
Jensen MP, Karoly P, Braver S. The measurement of clinical pain intensity: a comparison of six methods. Pain. 1986;27(1):117-126. [CrossRef]
 
Devlin JW, Marquis F, Riker RR, et al. Combined didactic and scenario-based education improves the ability of intensive care unit staff to recognize delirium at the bedside. Crit Care. 2008;12(1):R19. [CrossRef]
 
Schneider E, Dualé C, Vaille JL, et al. Comparison of tolerance of facemask vs. mouthpiece for non-invasive ventilation. Anaesthesia. 2006;61(1):20-23. [CrossRef]
 
Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med. 1985;13(10):818-829. [CrossRef]
 
Mehta S, Jay GD, Woolard RH, et al. Randomized, prospective trial of bilevel versus continuous positive airway pressure in acute pulmonary edema. Crit Care Med. 1997;25(4):620-628. [CrossRef]
 
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