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

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

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

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

Normal Observations in 14 yr old Male Respiratory Rate 12-15 breaths/min Systolic BP 100-120mmHg Heart Rate 60-100bpm

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˚

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

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

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

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

References Blackman J, Patrick P, Buck M et al. Paroxysmal autonomic instability with dystonia after brain injury. Arch Neurol 2004; 61: 321-328 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