Patama Gomutbutra MD

Case management

Drug induced encephalopathy

Palliative care for pharmacist 14-15th march 2016

Outline

• Case demonstration• Drug induced encephalopathy • Care giver counselling

Case

• Male 68 yo UD DM, HT, Spinal canal stenosis• Consult because alteration of conscious with

occasional jerking movement • Admited to ICU 6 months ago due ruptured

abdominal aorta then off and on infection• later developed ESRD on HD 3 times/weeks

• Current medication (selected) :– Meropenem IV for UTI ESBL– Gabapentin 300 mg PO

Tramadol 1 tab q 8 hrsfor his back pain

– Fluoxetin for his depression– Dilantin 100 mg IV q 8 hrs

because his jerking movement seizure

• Physical exam– Concious: E4VTM5 stuporous , occuasional

spontaneous eye opening but not follow command– Pupil : 3 mm RTLBE– Ocular : roving eyes, no eye deviation, no nystagmus– Movement : equal movement, non-rhythmic jerking

movment of distal hands, stimulus sensitive– Meningeal irritation signs : stiffneck all directions

Kernig’s sing negative– Respiration along ventilator– Reflex : 1+ all, BBK negative both

Goal of care

• “Minimal pain” • Full medication• His family refuse lumbar puncture or any

invasive procedure including CPR

Approach delirum

Appendix 1

D-E-L-I-R-I-U-M nmemonic

• Most of delirium caused by multifactorial– Drugs and dehydration * The most potential reversible – Electrolyte and Endocrine– Low blood flow and Low oxygen (include anemia)– Infection and Inflammation– Retention urine– Impact feces– Uncontroled pain– Mental disorientation

Lawlor PG, Arch Intern Med. 2000 Mar 27;160(6):786.

Drug induced encephalopathy

– Common • Anti-cholinergic (appendix 2)• Dopaminergic • Steroid• Opioid

– Uncommon• Serotoninergic • Antimicrobial• Antiepileptic

Serotoninergic

• serotonin syndrome– limbic : agitation– striatum : tremor , clonus, rigidity : legs> hands– Autonomic instability– GI hypermotility

• Mild anxiety like -> Sever sepsis like• Symptom may develop eariest as 6 hrs• Reverse after 24 hrs discontinue• Antidote:

cyproheptadine via NG 12 mg then 2 mg q 2 hrsmaintanance 8 mg q 6 hrs

Tramadol & Fluoxetinedrug interaction

Antimicrobial drug

• Metronidazole • Cephalosporin *• Carbapenem *• Linezolid• Acyclovir• Isoniazid

* associate with non-convulstive status epilepticus

Antibiotics

• Metronidazole– Dose related : more than 2 g/day– Bilateral symmetrical vasogenic edema

of cerebellar dentate and pons– Reversible : symptom 2 wks to 3 months after

discontinue

Iqbal A. Ann Indian Acad Neurol. 2013 Oct-Dec; 16(4): 569–571.

ReversibleReversible

Antiviral

• Acyclovir– Adjust to renal dose

(Appendix 3)– Reversible symptom after 48-72 hrs after dose

adjusted

Antiepileptic

• Phenytoin– Hypoalbumin

• Valporate– Hypoalbumin– Liver decompensation

• Levetriazetam– Renal impairment

Antiepileptic

• Valporate• Hyperammonia : level >40

– CSF ammonia may high in the normal level serum ammonia

– Inhibit glutamate uptake by astrocyte

• Rx by lactulose to reduce ammonia absorb by intestine.

Care giver advise

• Give them information ‘sens of controllable’– Delirium is not ‘Permanent psychosis’– Tell them basic advise

“D-E-L-I-R-I-U-M”– Reorientation protocol

• Remind patient - time place person• Less confusional environment• Sleep wake adjustment

Take home message

• Drugs and dehydration is the most potential reversible cause of encephalopathy

• Medication involve Ach, DA and Serotonin should be precaution

• Giving information to care giver may be important than medication

Reference

• Comprehensive review with references of drug induce encephalopathy:

http://cdn.intechopen.com/pdfs-wm/35733.pdf

Appendix 1

Appendix 2

PL Detail-Document, Drugs with Anticholinergic Activity. Pharmacist’s Letter/Prescriber’s Letter. December 2011.

Dose adjustment for AcyclovirEncephalitis dose :

CrCl > 50 : 500 mg (10mg/kg) IV q 8 hrs25-50 : 500 mg (10mg/kg) IV q 12 hrs10-25 : 500 mg (10mg/kg) IV q 24 hrs< 10 : 150 mg (5 mg/kg) IV q 24 hrs

give after HD on dialysis dayHD -> 60% decrease dose

Herpes zoster dose:CrCl >25 : 800 mg PO q 4 hrs -5 times a day

10-25 : 800 mg PO q 8 hrs< 10 : 800 mg PO q 12 hrs

Appendix 3