H a n n a h W u n s c h , M D M S cH e r b e r t I r v i n g A s s i s t a n t P r o f e s s o r o f A n e s t h e s i o l o g y &

E p i d e m i o l o g y

D e p a r t m e n t o f A n e s t h e s i o l o g y , C o l l e g e o f P h y s i c i a n s & S u r g e o n sD e p a r t m e n t o f E p i d e m i o l o g y , M a i l m a n S c h o o l o f P u b l i c H e a l t h

C o l u m b i a U n i v e r s i t y

Targeting patients for use of dexmedetomidine

Conflicts

• None

• Talking about off-label uses of dexmedetomidine

Dexmedetomidine

Alpha-2 agonist

7 times more selective than clonidine for the receptor

Infusion only

0.2 to 1.5 μg/kg/hr PER HOUR

Loading dose of 1 mcg/kg over 10 min

Distribution half-life of 6 minutes

Terminal elimination half-life of 2 hours

Hepatic clearance, renal excretion of metabolites

US FDA approval

1999/2000

Mechanically ventilated patients in the intensive care setting up to 24 hrs

0.2 to 0.7 μg/kg/hr

2008

Non-intubated patients requiring sedation prior to and/or during surgical and other procedures

Canada

Sedation of initially intubated and mechanically ventilated postsurgical patients during treatment in an intensive care setting by continuous intravenous infusion (must not exceed 24 hours).

Sedation of non-intubated patients prior to and/or during surgical and other procedures: Monitored Anesthesia Care (MAC)

Awake Fiberoptic Intubation (AFI)

Clinical profile

Anxiolysis

Some analgesia

No respiratory depression Can keep it going during extubation

No amnesia

Bradycardia

hypotension

Does it help with delirium?

Delirium

• 4 large RCTs recently in JAMA• MENDS

• (vs lorazepam)

• SEDCOM

• (vs midazolam)

• MIDEX/PRODEX

• (vs midazolam and vs propofol)

Coma

PRODEX/MIDEX

Jakob et al

? Proxy for delirium

Question of doses…

MIDEX

0.2 μg/kg/hr dex = 2.1 mg/hr midaz (0.03 mg/kg)

My version

0.2 μg/kg/hr dex = 0.5 mg/hr midazolam

Goal RASS -3 to 0

Dexmed Midazolam Dexmed Propofol

RASS Score during study period

-0.9

(-1.9 to -0.1)

-1.5

(-2.5 to -0.5)

-1.0

(-1.9 to -0.2)

-1.7

(-2.5 to -0.7)

Sedation stop performed

89.7% 93.3% 89.0% 90.1%

Jakob et al JAMA 2012

Which patients get dexmedetomidine?

Medical/Surgical Patients – use over time

Wunsch et al Anesthesiology 2010

Cardiac surgery patients – use over time

Wunsch et al Anesthesiology 2010

Why cardiac surgery patients?

Prelim studies in cardiac surgery patients

Generally <24 hrs on ventilator

Low analgesia requirements (for surgical patients)

?More likely to be cared for by anesthesiologists

Our own experience

Patients who have received dexmedetomidine

Post cardiac surgery

Post general surgery

Transplants (heart, lung, liver, kidney)

ARDS

Septic shock

Etoh withdrawal

Pancreatitis

Etc…

We do not have IV clonidine

Potential problems

Barriers

Dosing error (mcg/kg/HR)

Staff anxiety regarding its sedative effects

‘Wrong’ patients

Bradycardia

Need for deeper sedation

Need for long period of sedation Rebound (a la clonidine) after many days

Planning to transfer a patient out of the ICU

Deep sedation

> 200 μg/hr fentanyl

Pandharipande JAMA 2007

Economics

Midazolam patients were generally more sedated

SEDCOM data

Costs of drugs

$58.31 per 200-microgm vial, and the midazolam cost was $1.56 per 5-mg vial

0.7 mcg/kg/hr = 49 mcg/hr = 1,176 mcg/day

6 vials (at 200 mcgs) = $350.00

Dosing of 1.5 mcg/kg/hr = $700.00

Areas for potential use

That patient who is agitated and/or delirious every time you try to wake them up

Anxious patient not receiving mechanical ventilation

Neurological ICU: shivering

?Alcohol withdrawal

?Sleep deprived

So who are those ‘ideal’patients?

Example #1

Slightly hemodynamically unstable (but not so much that they can’t be awake)

Trying to wean

Emerging agitated from other sedation

Oversedated when given antipsychotics

Example #2

Elderly/fragile – (you know they are a setup for delirium)

Mild respiratory distress but not needing intubation Trying to tolerate BIPAP

Moderately anxious, starting to get sleep deprived

Shivering

Etoh withdrawal

• Adjunct to benzodiazepines• Case reports only

“In mechanically ventilated patients, nighttime infusions of dexmedetomidine preserved the day-night cycle of sleep but induced severely disturbed sleep

architecture without evidence of [slow wave sleep] or REM sleep”

Other options…

No sedation

Opiate-based sedation

Antipsychotic medications Haloperidol

Atypicals

Ketamine infusion

(Inhaled anesthetic)

(New formulation of etomidate)

Summary

Dexmedetomidine is another tool

Greatest benefits

Lack of respiratory depression

Hard(er) to over-sedate

May help with delirium

Downsides

Cost

Bradycardia

Lack of deep sedation

hw2125@columbia.edu