Sedation

Question 1

Discuss risk assessment of bariturates (pentobarbitone, phenobarbitone, primidone, thupentone)

Answer 1

Ingestion of >8mg/kg of phenobarbitone is expected to produce toxic neurological symptoms in the non tolerant individual. Multiples of this dose are expected to produce profound coma

Self administration of theiopentone or pentobaritone (often by vets) is likley to be lethal unless the mechanics of administration are such that the rapid onset of coma prevents administration of all of the intended dose.

Children - most barbiturate toxicity in children occurs in the context of therapeutic admin. Acute ingestion of >8mg/jg of phenobarb or >40mg/kg of primidone would be expected to produce neurological symptoms

Question 2

Discuss TM and TK of barbiturates

Answer 2

TM: cause CNS depression by enchancing GABA neurotransmission. Bind to GABA receptor complex increses the duration of chloride channel opening. THey also antagonise the effect of the excitatroy neurotransmitter glutamate by causing receptor blockade in the CNS. Ihibition of meduallyar cardioresp centres and hyphtalamic autonomic nuclei results in hypotension, hypothermia and respiratory arrest.

TK- All well absorbed in the GIT, due to rapid redistribution from the CNS and large VD the highly lipid soluble short acting barbs (thiopentone and pentobarbitone) are useful medically only if given IV. THe long acting less lipid soluble barbs such as pehnobarbitone and priidone are distributed more slowly to the CNS and redistrubuted more slowly and are viable oral agents.
All barbs are metabolised by saturable hepatic microsomal pathways. Phenobard undergoes enterohepatic recircualtion

Question 3

Discuss clinical features of barb OD

Answer 3

Toxicity may develop with therapeutic admin of phenobarb or primidone sytmpoms are mild and nuerolgoical in nature and ressolve with cessation

Overdoe is characterised by profound prolonged and potentially fatal depression of the CNS and CVS symtpoms.
Onset is within seconds to minutes of IV overdose and within 1-2 hours of ingestion of phenobarb or primidone
CNS
-ataxia lethargy,slurred speech, drowsiness veritgo and nystagmus are followed by coma hypotnoa hypothermia and respiratory arrest at higher doses.
-profound coma with compelte loss of neurological funciton can develop
-profound resp depression with CHeyne stokes respiration progressing to apnoea

CVS

• Tachycardia frequent
• in very large ingestions hypotension occurs as a result of depression of the medullary vasomotor nuclei as well as peripehral vasodilation and myocardial depression

Other

• Hypothermia
• reduced bowle sounds
• skin bullae

Question 4

Discuss ix of barbs

Answer 4

ECG, BGL and paracetamol

Serum barb levels 
- CNS symptoms correlate well with levels 
15-25mg/lg (therapeutic)
30-80 mg/L increase sedation 
>80mg/L coma requring intubation

Serial levels are essentail in the management of the ccomatose patient – allows monitoring of clinical progress and guides enhanced elimiantion

• Phenobarb >100mg/L prompts consideration for HD
• serum levels are not usually helpful in the absence of coma

Other IX may be needed to exclude other causes of prolonged coma
-EEG in severe barbituate coma will mimic brain death

Question 5

Discuss Management of barbituate overdose

Answer 5

Resus
ABCD
-managed in area equiped for cardiopulmonary monitoring and resus
- Intuabtion is anticipated and performed early in the patient with deterioating GCS

D: Charcoal via NGT once ETT
E: Considered for long acting barbituates - where slow endogenous clearance rates can otherwise result in prolonged ICU
-MDAC
-HD if over >100mg/l or where there is clinical manifestation of severe poisoning in particular persistent hypotension despite inotropes and with evidence of end organ dysfunciton
A: Nil
D: all children susepcted of more than 8mg/kg of phenobarb or 40mg/kg of primidone must be observed in hostpial.
-adults observation for 6 hours if nil CNS can be dishcarged home

Question 6

Discuss risk assessment of benzodiazepines

Answer 6

Are involved in up to 1/3 of all delibrate self poisoning. Excellent prognosis is expected with supportive care of CNS depression. Flumazenil is a useful diagnositc and therapeutic tool in carefully selected cases.

Isolated benzo overdose generally cause only mild sedation irrespective of the dose ingested and can be managed with supportive measures
Alprazolam OD is associated with a greater degree of CNS depression and is more likely to need intubation

Coingestion of other CNS depression (ETOH, opiods, antidepressants) increases the risk of complications length of stay and death

Children: ingestion of one or two benzo tablets usually manigests as mild sedation and ataxia

Question 7

Discuss TM and TK of benzo

Answer 7

TM - enhance GABA mediated neurotransmission via binding of the GABAa complex and increasing frequency of opening
Zolpidem and zopiclone are non benzodiazepine sedative hyponotics that also act at the GABA a receptor complex

TK- Rapidly absorbed orally
Most are highly protein boudn and have VD that vary from 0.5-4LKg ‘
Hepatic metabolism with active metabolits
Duration of effect depends on CNS re-distribution and tolerance rahter than rate of elinination.
Clinical features of intoxication poorly correlate to serum benzo levels

Question 8

Discuss clinical features of benzo

Answer 8

Onset usually within 1-2 hours ataxia, letahrgy slurred speech and drowsiness are followed by decreased responsiveiness. Profound coma is rare except with alprazoloam or mixed ingestion

Question 9

Discuss management

Answer 9

Resus
ABCD

D: actiavted charcoal not indicated because the onset of sedation occursin the first few hours usually ahs good outcome
E: nil
A: flumazenil is a competitive benzodiazepien antagonist with limited role. Its incidcations include
-nmangement of airway and breathing when resources are not aviable for safe intuabtion
- diagnostic tool to avoid further investigation
-reversal of conscious sedation.