Martin R. Tramèr Dept Anästhesie, Klinische Pharmakologie & Intensivmedizin
Universitätskliniken & Medizinische Fakultät Genf - Schweiz
Deutscher Anästhesiecongress 2010
PARACETAMOL, DEXAMETHASONE UND NSAR – EINE GEFAHR FÜR DIE KINDER?
2 4 6 8 10 12 14 16 18 20 Number needed to treat
636 Diclofenac 50mg 257 Naproxen 440mg 2898 Ibuprofen 400mg 946 Morphine 10mg IM 816 Paracetamol 650mg/codeine 60mg 963 Paracet 650mg/dextroprop 65mg 5061 Aspirin 650mg 2283 Paracetamol 1000mg 882 Tramadol 100mg 1167 Paracetamol 650mg 440 Dextropropoxyphene 65mg 1305 Codeine 60mg
NTTs for ≥50% pain relief over 4-6h in patients with moderate to severe pain
McQuay & Moore Evidence-Based Resource in Pain Relief, Oxford University Press 1998
Paracetamol
Anesthesiology 2005;103:1296-1304
Paracetamol - Morphine sparing
Morphine consumption in controls: Δ 50 mg/24h
Paracetamol - Pain intensity
Elia et al. Anesthesiology 2005;103:1296-1304
Pain intensity in controls: Δ 4/10 at 24h
Morphine-related adverse effects
Elia et al. Anesthesiology 2005;103:1296-1304
Remy et al. BJA 2005;94:505-13
No impact on the risk of PONV No impact on the risk of sedation No impact on the risk of urinary retention
RCT: 107 young adults undergoing TE under LA (lidocaine + epinephrine)
Prior to surgery: iv single dose of
75 mg diclofenac 3 g paracetamol Placebo
Acta Anaesth Scand 2007;51:1147-54
Silvanto et al. Acta Anaesth Scand 2007;51:1147-54
Plac
Diclo
Para
Plac
Diclo
Para
Plac
Diclo
Para
Silvanto et al. Acta Anaesth Scand 2007;51:1147-54
Aspartate aminotransferase
Alanine aminotransferase
Glutathione transferase
NEJM 1997;337:1112-7
Hepatic coma Death
7 (33%) 4 (19%)
3 (6%) 1 (2%)
0.006 0.04
Acetaminophen ingestion accounted for 12% of all patients hospitalized with overdoses and 40% of patients with acute liver failure
Watkins et al. JAMA 2006;296:87-93
BMJ 2000;321:1460-3
NSAIDs Cox-2 inhibitors
NSAIDs & surgery - PROs
• Analgesic • Multiple routes of administration
- po, pr, iv, sc, im, transcutaneous • Non-opioid
- Opioid sparing effect - Prevention of opioid adverse effects
nausea & vomiting, pruritus, urinary retention, sedation,
respiratory depression - No legal constraints for prescription - No “opioid fear”
NSAIDs & Coxibs - Morphine sparing
Morphine consumption in controls: ± 50 mg/24h
Anesthesiology 2005;103:1296-1304
Anesthesiology 2005;103:1296-1304
Pain intensity in controls: ± 4/10 at 24h
NSAIDs & Coxibs – Decrease in pain intensity
Elia et al. Anesthesiology 2005;103:1296-1304
NNT≈15
Morphine-related adverse effects
• Suppression of cyclooxygenase-mediated thromboxane A2
synthesis
- Block of endogenous prostaglandine synthesis
- Inhibition of platelet aggregation
- Renal dysfunction
- GI
• Allergic reactions
• Hepatic failure
Toxicity with acute NSAID usage
Anesthesiology 2005;103:1296-1304
Anesthesiology 2005;103:1296-1304
NEJM 2005;352:1092-102
NNH 33
BMJ 2006;333:519
Allford et al. Ped Anesth 2009;19:145-52
Cochrane Database Sys Rev 2005;2:CD003591
8/497 (1.6%) 5/458 (1.1%) NNH ± 200 1.46 [0.49, 4.40]
4/40 0/20 4.86 [0.57, 41]
1.88 [0.71, 5.01] 12/522 (2.3%) 5/463 (1.1%) NNH ± 80
“NSAIDs did not cause any increase in bleeding requiring a return to theatre.”
6 RCTs 540 patients 13 bleedings
Anesth & Analg 2003;96:68-77
NNH 60
Reoperation
Anesthesiology 2003;98:1497-502
Reoperation
0.8% ⇒ 4.2% NNH 30
Dexamethasone
Anesth & Analg 2000;90:186-94
BJA 2006;97:593-604
Dose-responsiveness? • for PONV? • for analgesia? Adverse effects?
Otolaryngol Head & Neck Surg 2006;134:181-6
Czarnetzki et al. JAMA 2008;300:2621-30
RCT, dose-finding, placebo-controlled, double-blind
Measurements • During 24 hours hospitalisation • 7 day questionnaire at home • ENT control after 10 days
Eligibility • Age 2-16 years • Elective tonsillectomy (+/- adenotomy) • No bleeding history, no aspirin intake
Intervention • Dexa 0.05, 0.15, or 0.5 mg/kg (max. 20 mg), or placebo IV before surgery • 4 x 80 = 320 children
Trial was stopped early for safety reasons N = 215 children
Czarnetzki et al. JAMA 2008;300:2621-30
Dose-responsiveness for PONV
44%
12% NNT ± 3
Czarnetzki et al. JAMA 2008;300:2621-30
NSAID sparing effect
65%
40% NNT ± 4
Czarnetzki et al. JAMA 2008;300:2621-30
8 children needed a reoperation: PLAC 0 versus DEXA 8
Increased risk of bleeding (despite NSAID sparing)
15 children (68% of those bleeding) had a bleed ≥24h
22 children had a bleed: PLAC 2 versus DEXA 20
ANZ J Surg 2007;77:579-82
Retrospective case note review (n=4,546)
NON-OPIOID ANALGESIA: PARACETAMOL, NSAID, DEXAMETHASONE
Paracetamol
Weak analgesic No opioid-sparing No anti-inflammatory effect CAVE: Hepatotoxicity
NSAIDs
Strong analgesics Some opioid-sparing CAVE: Renal toxicity CAVE: Bleeding tendency
Coxibs Strong analgesics Some opioid-sparing CAVE: Renal toxicity
Dexamethasone
Weak analgesic Some NSAID-sparing Strong antiemetic CAVE: bleeding tendency