Dr Tiffany Fan

ST6 Paediatric Nephrology

Southampton Children’s Hospital

The Wee Is Not Enough

Paracetamol Overdose

and Acute Renal

Failure

• 15 year old girl S

• No past medical history of note

• No known mental health issue

Background

• Mother and father history of cocaine use, physical violence

• Moved around the country, changing schools

• Now lives with mum, stepfather, brother

• Poor relationship with family

• Alleged sexual + physical assault by ex-boyfriend

• Bullying at school and physical assaults

Social History

• Presented to ED at local hospital

• Abdominal pain and feeling unwell

• Abdomen tender

• Admits taking 32 paracetamol tablets the evening before

• Took to help her sleep, denies intention to kill herself

• Went to school next day, felt unwell

• Disclosure to friend and teacher

• Admitted and commenced IV N-acetylcysteine

• Paracetamol level 26

4/5/17

4/5/17

12:20

5/5/17

13:20

5/5/17

19:30

6/5/17

03:54

7/5/17

15:20

8/5/17

05:40

9/5/17

06:00

Na 136 137 137 137 142 139 140

K 3.8 4.1 3.9 3.7 3.7 3.9 4.2

Urea 4.9 3.3 5.1 7.2 8.9 5.7 1.7

Creat 56 46 73 135 365 271 169

ALT 332 5581 15770 10015 3736 2660

ALP 108 6437 115 83 76

AST 6437 17620

Bili 10 31 27 18 14 14

INR 1.2 1.2 2.7 2.1 1.3 1.2

APTR 1.22 1.05 1.78 1.71

4/5/17

12:20

5/5/17

13:20

5/5/17

19:30

6/5/17

03:54

7/5/17

15:20

8/5/17

05:40

9/5/17

06:00

Na 136 137 137 137 142 139 140

K 3.8 4.1 3.9 3.7 3.7 3.9 4.2

Urea 4.9 3.3 5.1 7.2 8.9 5.7 1.7

Creat 56 46 73 135 365 271 169

ALT 332 5581 15770 10015 3736 2660

ALP 108 6437 115 83 76

AST 6437 17620

Bili 10 31 27 18 14 14

INR 1.2 1.2 2.7 2.1 1.3 1.2

APTR 1.22 1.05 1.78 1.71

4/5/17

12:20

5/5/17

13:20

5/5/17

19:30

6/5/17

03:54

7/5/17

15:20

8/5/17

05:40

9/5/17

06:00

Na 136 137 137 137 142 139 140

K 3.8 4.1 3.9 3.7 3.7 3.9 4.2

Urea 4.9 3.3 5.1 7.2 8.9 5.7 1.7

Creat 56 46 73 135 365 271 169

ALT 332 5581 15770 10015 3736 2660

ALP 108 6437 115 83 76

AST 6437 17620

Bili 10 31 27 18 14 14

INR 1.2 1.2 2.7 2.1 1.3 1.2

APTR 1.22 1.05 1.78 1.71

4/5/17

12:20

5/5/17

13:20

5/5/17

19:30

6/5/17

03:54

7/5/17

15:20

8/5/17

05:40

9/5/17

06:00

Na 136 137 137 137 142 139 140

K 3.8 4.1 3.9 3.7 3.7 3.9 4.2

Urea 4.9 3.3 5.1 7.2 8.9 5.7 1.7

Creat 56 46 73 135 365 271 169

ALT 332 5581 15770 10015 3736 2660

ALP 108 6437 115 83 76

AST 6437 17620

Bili 10 31 27 18 14 14

INR 1.2 1.2 2.7 2.1 1.3 1.2

APTR 1.22 1.05 1.78 1.71

4/5/17

12:20

5/5/17

13:20

5/5/17

19:30

6/5/17

03:54

7/5/17

15:20

8/5/17

05:40

9/5/17

06:00

Na 136 137 137 137 142 139 140

K 3.8 4.1 3.9 3.7 3.7 3.9 4.2

Urea 4.9 3.3 5.1 7.2 8.9 5.7 1.7

Creat 56 46 73 135 365 271 169

ALT 332 5581 15770 10015 3736 2660

ALP 108 6437 115 83 76

AST 6437 17620

Bili 10 31 27 18 14 14

INR 1.2 1.2 2.7 2.1 1.3 1.2

APTR 1.22 1.05 1.78 1.71

4/5/17

12:20

5/5/17

13:20

5/5/17

19:30

6/5/17

03:54

7/5/17

15:20

8/5/17

05:40

9/5/17

06:00

Na 136 137 137 137 142 139 140

K 3.8 4.1 3.9 3.7 3.7 3.9 4.2

Urea 4.9 3.3 5.1 7.2 8.9 5.7 1.7

Creat 56 46 73 135 365 271 169

ALT 332 5581 15770 10015 3736 2660

ALP 108 6437 115 83 76

AST 6437 17620

Bili 10 31 27 18 14 14

INR 1.2 1.2 2.7 2.1 1.3 1.2

APTR 1.22 1.05 1.78 1.71

4/5/17

12:20

5/5/17

13:20

5/5/17

19:30

6/5/17

03:54

7/5/17

15:20

8/5/17

05:40

9/5/17

06:00

Na 136 137 137 137 142 139 140

K 3.8 4.1 3.9 3.7 3.7 3.9 4.2

Urea 4.9 3.3 5.1 7.2 8.9 5.7 1.7

Creat 56 46 73 135 365 271 169

ALT 332 5581 15770 10015 3736 2660

ALP 108 6437 115 83 76

AST 6437 17620

Bili 10 31 27 18 14 14

INR 1.2 1.2 2.7 2.1 1.3 1.2

APTR 1.22 1.05 1.78 1.71

• Transferred to PICU

• CVVHDF not restarted – transfer to ward

• On admission to G4N ward

• Ongoing abdominal pain, headache, blurred vision

• Swelling and pain in right arm

• Toothache, especially after tazocin

• Poor oral intake

• UO 0.9ml/kg/hr

PICU / G4N ward

• Doppler of veins in right arm – thrombosis in segments of basilic vein and

cephalic vein

• Nutrition – started fortini and polycal added to water

• Lactulose prescribed as NBO

• NAC continued

• 11/5 Tazocin course completed

• D/w Kings – INR normalised, stop NAC

• UO continued 0.9-1ml/kg/hr. Weight 90Kg

10/5 – 11/5

Progress on ward

• UO continue to improve

• Rebound rise creatinine

• Pain improving

• Reviewed by CAMHS team on ward

• Regrets OD, didn’t realise how toxic drug was

• “no chance of her doing this again”

• No ongoing suicidal thoughts

• 16/6

• Creatinine improving

• CP conference in community planned

• Discharge with plan for repeat bloods in 1 week

9/5 11/5 13/5 16/5 24/5

Na 140 139 140 141 139

K 4.4 4.4 4.6 4.5 4.3

Urea 1.9 9.0 10.8 12.9 8.0

Creat 207 535 660 446 99

ALT 1566 766 416 173 55

INR 1.2 1.0

Paracetamol overdose and

renal failure

• Incidence of acute kidney injury1

• Between 1-2%

• 12-18 year olds requiring NAC for severe paracetamol overdose2

• 8.9% nephrotoxicity (n=4)

• 1 developed nephrotoxicity without elevated hepatic transaminases

• 10-18 year old presenting with paracetamol overdose3

• 3.4% acute renal failure

Paracetamol poisoning and renal

impairment

1. Mayzer. J Med Tox 2008 2. Boutis K. J Toxicol Clin Toxicol 2001 3. Le Vaillant J et al. Arch Pediatr 2016

Paracetamol

glucuronidation sulfation Cytochrome

P450

N-acetyl-p-benzo-quinoneimine

(NAPQI) - Toxic

• Risk factors for nephrotoxicity

• Starvation / fasting

• Chronic alcoholism

• CYP-450 inducers

• Adolescents and young adults may be at higher risk

• Confounding factors – ingestion of other nephrotoxic drugs, dehydration, pre-existing renal

dysfunction, multiorgan failure

• Relationship to dose ingested unclear

• Case reports / case series of renal insufficiency in absence of significant

hepatotoxicity

Risk factors

• Onset of renal insufficiency day 1-8 after ingestion

• Most cases reported between day 2-5

• Serum creatinine peak on average on day 7 (range 3-16)

• Majority return to baseline within 1 month

• 1% require dialysis (less likely in isolated renal dysfunction)

• NAC

• not proven to be harmful to kidneys

• No benefit demonstrated in nephrotoxicity alone

• Dosing adjustment if dialysis used

Clinical course and management

Current guidelines