16A24: Exam Report

Describe the ideal sedative agent for an Intensive Care patient (50% of marks). How does midazolam compare to this (50% of marks)?

60% of candidates passed this question.

Candidates who had a structured approach (i.e. pharmaceutical, pharmacokinetic, pharmacodynamic) provided more content and scored higher. Candidates who also approached pharmacodynamic effects in an organ system based approach scored higher. Relating a pharmacokinetic property of midazolam (e.g. volume of distribution or half-life) to a un/desirable attribute e.g. offset of action and accumulation displayed a greater understanding of the question. For many candidates, the description of an ideal drug contained more detail and candidates were not able to adequately state how midazolam compares.

K2i / 16A24: Describe the ideal sedative for an ICU patient (50 marks) + How does midazolam compare to this (50 marks)

Physical

Ideal

Midazolam

Stable in H2O

H2O soluble

Stable in solution

pH solution 3.5

pH <4 = imidazole

ring open (H2O soluble)

pH > 4 = imidazole ring closed (lipid soluble)

No reconstitution before use

None required

Stable in air & light

Yes

Long shelf

Yes

Stored room temp

Yes

Doesn’t support bacterial growth

Does not

Compatible with drugs & fluids

Incompatible with some drugs

No additives

Cheap. But only more cost effective than PPF if using it for prolonged sedation in ICU

PK

Ideal

Midazolam

Onset

Ideal

Rapid onset

Midazolam

~10 mins

Wide individual variability

VD

Ideal

High oiL/H2O solubility

Midazolam

At physiological pH, highly lipophilic with small VD 1.5L/kg

C5HT

Ideal

Short

Midazolam

Not ideal

360 min after 9hrs

Metabolism

Ideal

Completely metabolised

Organ independent

Active & inactive metabolites

Midazolam

Liver 3A4

Hydroxylation & then glucuronidation

5% to OXAZEPAM = active metabolite

Elimination

Ideal

Rapid clearance with short DoA

Midazolam

Short DoA 2° redistribution (highly lipophilic)

Metabolites excreted in urine, renal impairment has little effect

Clearance 7mL/kg/min → lasts ~60mins

PD

Ideal

Midazolam

MoA

Ideal

Known with antagonist

↓CMRO2, ↓CBF, ↓ICP

Midazolam

Binds B2D receptor

Potentiates GABA

↑frequency Clchannel opening

Flumazenil = antagonist

Yes

CNS

Ideal

Anxiolysis

Amnesia

Analgesia

Ability to progress to GA

Midazolam

Yes

Anterograde

None

Large dose required

CVS

Ideal

Minimal CVS depression

Midazolam

Small ↓SVR

Blunts CVS response to intubation

Resp

Ideal

Minimal resp depression

Midazolam

Apnoea

↓response to ↑PaCO2

GI

Ideal

No N&V

Midazolam

↓PONV

Pain on Injection

Ideal

None

Midazolam

Occasional discomfort

Histamine Release

Ideal

None

Midazolam

None

Allergy/ Anaphylaxis

Ideal

None

Midazolam

Rare