Efficacy and Safety of Dexmedetomidine During Non-Invasive Positive Pressure Ventilation

Non-invasive positive-pressure ventilation (NPPV) is increasingly being used to manage
patients with acute respiratory failure (ARF) in an effort to avoid the numerous negative
sequelae associated with intubation and mechanical ventilation. In the USA, it is estimated
that 20-30% of all patients placed on mechanical ventilation are treated with NPPV.
Indications for NPPV include but are not limited to acute or acute-on-chronic hypercapnic
respiratory failure, pulmonary edema, respiratory failure in immunocompromised patients or
that due to chest wall deformity or neuromuscular disease. For NPPV to be successful, it is
critical that the patient be cooperative and comfortable (i.e. no pain) as agitation and
discomfort interfere with the success of NPPV.

Despite the importance of patient comfort during NPPV, physicians infrequently use sedation
or analgesic therapy during NPPV, primarily due to concerns about the respiratory depressant
effects of most of the sedatives (e.g., benzodiazepines) and analgesics (e.g., opioids) that
are currently available. In addition, neither the benzodiazepines nor opioids are easily
titratable, can easily accumulate and can be associated with both the development of delirium
and a withdrawal effect.

Dexmedetomidine is an intravenous rapid-onset, short acting ά 2-receptor agonist that is
approved for short-term sedation in post-operative and critically ill patients. It has been
stated that this drug produces a state of "cooperative sedation" allowing the patient to
interact with health care providers. Dexmedetomidine has been used for its ability to cause
sympatholysis and, because of analgesic properties, to decrease the need for opioids.
Potential advantages include its short half life and intravenous route of administration,
permitting rapid titration to achieve sedation targets and, in patients with respiratory
failure; it can provide both sedation and analgesia without inducing respiratory depression.
Despite these advantages, it is currently used by less than 5% of pulmonologists/
intensivists as the primary sedative option during NPPV and has not been studied in a
controlled fashion in this population. Therefore, dexmedetomidine may prove to be more
efficacious and safe compared to standard sedation/analgesic therapy during NPPV.

Inclusion Criteria:

- Age ≥ 18 years

- Acute respiratory failure requiring the initiation of NPPV

- Admission to the medical ICU service at Tufts Medical Center or Winchester Hospital

Exclusion Criteria:

- Patients with delirium (intensive care delirium screening checklist score ≥ 4) or
disorientation (not oriented to person or place)

- Receiving NPPV for ≥ 8 hours (includes treatment with NPPV at an outside hospital)

- Intubation and mechanical ventilation in the past month based on hospital admission
note

- Age ≥ 85 years

- Inability of the potential subject to give informed consent

- Current treatment with antipsychotic agent based on hospital admission note

- Heart rate ≤ 50 bpm

- Systolic blood pressure ≤ 90 mmHg

- History of heart block without pacemaker use or severe ventricular dysfunction (EF
≤25%) based on hospital admission note

- Acute alcohol withdrawal based on hospital admission note

- History of end stage liver failure (based on presence of ≥ 1 or more of the following:
AST/ALT ≥ 2 times ULN, INR ≥ 2, total bilirubin ≥ 1.5

- Irreversible brain disease consistent with severe dementia based on hospital admission
note

- Pregnancy (all women of child-bearing age will undergo a pregnancy test prior to study
enrollment)

- Treatment with clonidine or dexmedetomidine in the past 30 days based on hospital
admission note

- Known allergy or sensitivity to clonidine or dexmedetomidine