1. Clonidine for the treatment of Paroxysmal Autonomic Instability with Dystonia (PAID) following traumatic brain injury
Sarah Dunne
Associate Care Group Pharmacist for Child Health, Southampton University Hospitals NHS Trust

3. Dysfunction of the autonomic centres
Many theories: 1. cortically provoked release of adrenomedullary catecholamines during PAID episode may contribute to increase in BP as well as tachycardia and tachypnea.
2. Temp dysfunction may be linked with hypermetabolic state that accompanies sustained muscular contractions.
3. Loss of cortical and subcortical control of vegetative functions inc regulation of BP and Temp

4. The syndrome, PAID Other terms May be mistaken for…
Diencephalic seizures
Midbrain dysregulatory syndrome
Sympathetic storming
May be mistaken for…
Seizures
Sepsis
Side-effects of drugs
Withdrawal from drugs
Pain
Other terms for this syndrome: diencephalic seizures or midbrain dysregulatory syndrome
Syndrome remains poorly understood and recognised despite distinct characteristic features
Literature is limited
Common syndrome after traumatic or hypoxic brain injury other causes; tumour, intracranial haemorrhage or hydrocephalus

5. Two Cases Presented 14yr male Near drowning 20mins under water
Out of hospital arrest
CT Head –severe hypoxic ischaemic insult
Despite Tx with SNP, Nifedipine, Amlodipine, & Enalapril
BP remained high
Excessive sweating
Agitation
↑HR
↑Temp
14yr male
Cyclist (no helmet) Vs Car (50mph)
Decompressive craniectomy to control ICP
Traumatic subarachnoid haemorrhage
Despite Tx with GTN & Atenolol
BP remained high
Excessive sweating
Agitation
↑HR
↑Temp

6. Normal Observations in 14 yr old Male
Respiratory Rate breaths/min
Systolic BP mmHg
Heart Rate bpm

7. Observations recorded during NC inpatient stay, highlighting episodes of PAID
200micrograms 4˚
800micrograms 2˚
IV clonidine started
200micrograms 4˚
400micrograms 4˚
800micrograms 4˚
150micrograms 4˚
600micrograms 4˚

8. Observations recorded during GL inpatient stay, highlighting episodes of PAID
500micrograms 4˚
Clonidine Started
250micrograms 4˚

9. Clonidine α2- adrenergic agonist Well absorbed orally
Located pre & postsynaptically on neurons in the brain
↓ release of NA
Well absorbed orally
Peak plasma concn reached in 3-5hrs
T1/2 8hrs in children
Works by..
↓ sympathetic outflow from CNS; decreasing BP
Behaviour stabilising effect
Sedation
Other agents used: morphine, bromocriptine, propranolol, lorazepam and dantrolene

10. Supply Tablets (if whole dose) Suspension made in house Cardinal
100microgram tab disperse within 2mins when in 10ml water
Flushes via 8Fr NG tube without blockage
25microgram tab (film coated) can be crushed but does not disperse readily
Suspension made in house
100micrograms/ml and 300micrograms/ml (not available at the same time)
7 day expiry
Cardinal

11. Take home message Manifestations of PAID can lead to…
Hypertensive or hyperthermic encephalopathy and even death
Rational approach to management
Rule out other causes
If diagnosis of PAID treat early with clonidine

12. References
Blackman J, Patrick P, Buck M et al. Paroxysmal autonomic instability with dystonia after brain injury. Arch Neurol 2004; 61:
White R. & Bradman V. Handbook of drug administration via enteral feeding tubes. Pharm Press 2007
With special thanks to my colleagues at Southampton General Hospital