MDO september B. J. Snel AIOS anesthesiologie

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1 MDO september 2014 B. J. Snel AIOS anesthesiologie

2 Casus Man, 1955 RvO: SAB obv PICA dissectie embolisatie PICA, EVD Problemen Wisselend EMV / hoge druk Hikken bij (verdenking) Wallenbergsyndroom waarvoor gabapetine, Koorts e.c.i., geen antibiotica bij negatieve kweken. koelen, paracetamol

3 Casus

4 Navarro VJ, Senior JR. Drug-related hepatotoxicity. N Eng J Med 2006; 354:

5 Nieuwe vraag: paracetamolspiegel = 0 Heeft het zin om acetylcysteine te geven? Naast remmen formatie van toxische (niet-meetbare) metabolieten: hepatoprotectief effect

6 Hodgman MJ, Garrard AR. A review of acetaminophen poisoining. Crit Care Clin 2012; 28:

7 Acetylcysteine - mechanisme Naast remming van aanmaak toxische metabolieten: Schade aan levercellen wordt beperkt: Acetylcysteine verbetert hepatische perfusie en zuurstofdelevery Scavenging van zuurstof- en stikstofradicalen Verbeterde mitochondriale energieproductie Saito C, Zwingmann C, et al. Novel mechanisms of protection against acetaminophen hepatotoxicity in mice by glutathione and N-acetylcysteine. Hepatology 2010; 51:

8 Timing Casus late leverenzymstijgingen: Bebarta VS, Shiner DC, et al. A case of moderate liver enzyme elevation after acute acetaminophen Overdose despite undetectable acetaminophen level and normal initial liver enzymes. Am J Ther 2014; 21: e82-e84.

9 Timing Casus late leverenzymstijgingen: Our patient also responded to a short course (16 hours) of N- acetylcysteine before the liver enzymes decreased significantly. Bebarta VS, Shiner DC, et al. A case of moderate liver enzyme elevation after acute acetaminophen Overdose despite undetectable acetaminophen level and normal initial liver enzymes. Am J Ther 2014; 21: e82-e84.

10 Nieuwe vraag: paracetamolspiegel = 0 Heeft acetylcysteine zin, wanneer leverenzymen gestegen zijn?

11 late treatment Harrison: 100 patienten (1990) niets: n=57 overleden=33 progressie 75% < 10 uur n=2 overleden=0 progressie 0 > 10 uur n=41 overleden=15 progressie 51% Discussie: [voorheen:] if a patient developed fulminant hepatic failure, the antidote was assumed to have failed Late acetylcysteine treatment reduced progression to encephalopathy ( ) and the beneficial effect on survival was shown even in patients with poor prognostic criteria Harrison PM, Keays R, et al. Improved outcome of paracetamol-induced fulminant hepatic failure by late administration af acetylcysteine. Lancet 1990; 335:

12 late treatment Jones: review van medische literatuur (1998) there is a trend suggesting beneficial effect beyond 15 hours, further research is necessary candidate mechanisms are improved liver blood flow, glutathione replenishment, modification of cytokine production, or free radical scavenging. Jones AL. Mechanism of action and value of N-acetylcysteine in the treatment of early and late acetaminophen poisoning: a critical review. J Toxicol Clin Toxicol 1998; 36:

13 Casus late treatment Casus uit Iran: 18 jarige patient, 105 tabletten 325mg paracetamol bewusteloosheid, mechanische ventilatie, INR = 6 72 uur later (paracetamolspiegel 0) start behandeling met acetylcysteine Daarna langzaam (10 dagen) normaliseren kliniek Conclusie: draagt bij aan de behandeling men zou de acetylcysteine langer dan normale 72 uur moeten geven tot er herstel optreedt Mehrpour O, Shadnia S, et al. Late extensive intravenous administration of N-acetylcysteine can reverse Hepatic failure in acetaminophen overdose. Hum Exp Toxicol 2011; 30: 51-54

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15 Niet-paracetamol leverfalen beneficial effect in acute non-acetaminophen liver failure in children Retrospectief, 170 kinderen Kortsalioudaki C, Taylor RM, et al. Safety and efficacy of N-acetylcysteine in children with nonacetaminophen- Induced acute liver failure. Liver Transpl 2008; 14:

16 Niet-paracetamol leverfalen The data suggest marginal benefit of acetylcysteine in nonacetaminophen-induced acute liver failure Meta-analyse met daarin 11 artikelen waarvan 8 case reports en 1 prospectieve studie Sales I, Dzierba AL, et al. Use of acetaminophen for non-acetaminophen-induced acute liver failure. Ann Hepatol 2013; 12: 6-10.

17 Niet-paracetamol leverfalen did not improve 1-year survival in children with nonacetaminophen acute liver failure 184 kinderen, prospectief, multi-center, placebo-controlled Squires RH, Dhawan A, et al. Intravenous N-acetylcysteine in pediatric patients with nonacetaminophen acute liver failure: a placebo-controlled clinical trail. Hepatology 2013; 57: