Analgesic/ Anti-inflamm

Question 1

‘Significant’ amount of paracetamol:

Answer 1

ACUTE (within 8 hours):
>10g or >200mg/kg (IR, SR)

REPEATED SUPRATHERAPEUTIC:
- <24hr: same as above
- >24hr: >6g/day or >150mg/kg/day for 48 hours
- >4g or 100mg/kg if liver disease
- 100mg/kg/day if child and >72 hours
OR
- Therapeutic dose for >48 hours with symptoms

Question 2

PARACETAMOL- Acute (IR)

Answer 2

Acute = within 8 hours

R
CRITERIA:
- >10g or 200mg/kg = hepatotoxicity
- ‘Massive’ = >30g or 500mg/kg
- Kids: accidental is benign.

Mx:
Within 8 hours:
–> AC (if within 1 hour)
–> Paracetamol 4+ hours
–> Below line = clear. Above line = NAC. Double the line = High dose NAC
–> Clear post infusion.
(unless massive, rpt level)

Beyond 8 hours:
–> Start NAC
–> Paracetamol + AST/ALT level
–> Both below, cease. Either is up, complete.
- Repeat parac/ALT near end of NAC. If BOTH normal, clear. Otherwise, extend infusion until ALT falling.

E
No

A
NAC will save 100% of peopleif commenced within 8 hours

Question 3

PARACETAMOL OD in children

Answer 3

Additional threshold of >100mg/kg/day for repeated STx exposures beyond 72 hours

NAC dose same, but given in smaller volumes

Question 4

Phases of toxicity in paracetamol OD:

Answer 4

Phase 1 (Day 1):
- Nothing, or mild GI

Phase 2 (Day 2):
Hepatoxicity onset:
- RUQ tenderness
- ALT/AST up (by definition: >1000)
- Coagulopathy
….Need NAC. Most recover

Phase 3 (Day 3):
Established fulminant hepatoxicity
- Coagulopathy, DIC, lactic acidosis, jaundice, encephalopathy, MODS
…..Need transplant

Phase 4 (Day 4 - weeks):
Liver recovery over 1-4 weeks.

Question 5

PARACETAMOL- Modified release

Answer 5

Same threshold as acute (>10g, >200mg/kg 8-24hrs)

AC within 4 hours

Initial paracetamol level at 4+ hours.
- Below line: needs repeat level 4 hours later to account for SR.
- Above line: NAC with rpt level towards end. NAC until level undetectable

Question 6

When might NAC be commenced immediately (ie. pre-biochem):

Answer 6

• At or beyond 8 hours in acute OD
• POSSIBLY beyond 8 hours (eg. unclear)
• Symptoms of liver failure in any setting

Question 7

NAC dose

Answer 7

Adults:
200mg/kg in 500ml N.saline/D5W, over 4 hours
THEN
100mg/kg in 1000ml N.saline/D5W, over 16 hours

• If for extended Tx, repeat second bag
  ** If for high-dose Tx, give second bag at 200mg/kg

Children:
Same dose
Given in smaller volumes (complex regime…)

Question 8

What ALT/ AST level defines established hepatotoxicity:

Answer 8

>1000 IU/ml

Question 9

Criteria for referral to transplant centre in paracetamol OD:

Answer 9

Evidence of fulminant hepatoxicity:

• Hypoglycaemia
• Encephalopathy
• Severe thrombocytopaenia
• Oliguria or Cr >200
• INR >3 at day 2, or >4.5 any time
• pH <7.3 post resus

Question 10

PARACETAMOL OD in pregnancy

Answer 10

No difference.

Crosses placenta, B2
Risk/benefit in favour.

Question 11

PARACETAMOL OD in obese

Answer 11

Threshold worked off ideal body weight

NAC dosing same.

Question 12

PARACETAMOL- Repeated Supratherapeutic

Answer 12

R
Criteria:
- >6g/day or 150mg/kg/day for 48 hours (100/kg if liver disease, or child exposed >72hrs)
OR
SYMPTOMATIC even if therapeutic dose

TESTS:
- Cleared if UNTIMED ALT <50 AND Parac <120.
- NAC if anything else.

D
No

E
No

A
N-ACETYLCYSTEINE

D
Repeat ALT/AST at 8 hours. Can clear if static/falling.

Question 13

NSAIDS OD

Answer 13

R
- Most benign
- Risk of MODS with >300mg/kg ibuprofen
- Kids: accidental is benign
- Exception: Mefamic acid= seizures+- all need ED.

S
ANTICIPATE:
>300:
Seizure, coma
Renal failure
RAGMA- not significant.

-SUPPORT:

I
- 12-lead, BGL, parac (delib)
MODS bloods if Sx/large

D
AC: only if mefamic

E
No

A
No

D
OBSERVE 4 hours

Question 14

SALICYLATES:

Answer 14

Stimulates resp centres, then interferes with oxid. phosphor. in mitochondria (ATP prod.)
____________
R
- >150mg/kg = ‘salicylism’
- >300mg/kg = toxicity
- >500 = pot. fatal
- Beware: ‘Oil of Wintergreen’ (one sip in kids)

S
Initial ‘salicylism’ = Tachypnoea, tinnitus, vomiting –> RESP ALKALOSIS
Then RAGMA
–> By the time actually acidaemic, VERY sick.

I
- 12-lead, BGL, parac (delib)
- Salicylate level - NORMAL = 1.1 - 2.2 (correlates poorly)
- ABG: resp alk + RAGMA

D
AC: Yes, up to 8 hours + repeat if still rising at 12h

Mx
DEFEND pH AGGRESSIVELY- acidaemia allows toxin into CNS. ALOC, reduced RR, vicious ‘death spiral’.

Keep serum AND urine pH 7.5 - 7.55

Intubate and hyperventilate

URINARY ALKALINISATION with SodiBic. Titrate + continue until salicylate level normal (<2.2).

2
- Haemodialysis if:
–> Level >7.2,
–> >4.4 despite treatment
–> Clinically severe (eg. ALOC, acidosis)
–> Can’t do urinary alk

A
Sodi Bic

D
OBSERVE 6 hours (12 enteric)

Question 15

How does chronic salicylate poisoning present?

Answer 15

Often elderly

Very non-specific

Suspect in anyone elderly and dizzy or generally unwell + on aspirin.

Question 16

What are the 2 roles of alkalinisation in salicylate tox:

Answer 16

• Prevent CNS distribution (+subsequent ALOC- resp depression- worse acidosis ‘death spiral’)
• Enhance urinary elimination

Question 17

BACLOFEN

Answer 17

Synthetic GABA.

One pill can kill in kids
>200mg/kg adults

Goes straight to brain, acts as non-selective GABA and causes profound coma and seizures
… APPARENT BRAIN DEATH- fixed, dilated, absent brain stem reflexes!!

Supportive only.

Reinstate any regular baclofen afterwards- or withdrawal is similar to OD!