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Anaphylactoid reactions to intravenous N-acetylcysteine: a prospective case controlled study Richard Lynch and Robert Robertson A&E Department Hull Royal.

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Presentation on theme: "Anaphylactoid reactions to intravenous N-acetylcysteine: a prospective case controlled study Richard Lynch and Robert Robertson A&E Department Hull Royal."— Presentation transcript:

1 Anaphylactoid reactions to intravenous N-acetylcysteine: a prospective case controlled study Richard Lynch and Robert Robertson A&E Department Hull Royal Infirmary

2 Introduction Paracetamol compounds are the most frequently used substances in DSH in UK 1 Since its introduction in 1977 2 NAC is treatment of choice Fatalities have been reported 3 Anaphylactoid reactions [1] Hawton K, Fagg J. BMJ 1992;304:1409-11. [2] Prescott LF, Park J, Ballantyne A, Lancet 1977;ii:432-4. [3] Mant GK, Tempowski JH, Volans GN, Talbot JCC. BMJ 1984;289:217-19.

3 Objectives To investigate the existence of predictive factors in the likelihood of developing anaphylactoid reactions to NAC Personal observations No published work linking likelihood of reaction with levels, time or risk Case reports 4,5,6 [4] Walton NG, Mann TAN, Shaw KM. Lancet 1979;ii:1298. [5] Ho SW-C, Beilin LJ. BMJ 1983;187:876-7. [6] Chan TY, Critchley JA. Hum Exp Toxicol 1994;13:542-4.

4 Methods Prospective case controlled study Short stay ward at Hull Royal Infirmary between January 1997 and June 1999 Data collected quantity of paracetamol allegedly ingested time to presentation plasma paracetamol concentrations severity and timing of any reaction presence of risk factors whether NAC infusion was commenced before receipt of paracetamol concentrations

5 Results 245 patients with paracetamol overdose 64 (26%) treated with NAC 31 (48.5%) developed reactions

6 Base line characteristics of patient groups _____________________________________________________________________ Non ReactorsReactors (N = 33)(N = 31) _____________________________________________________________________ Sex Female14 (42.4%)18 (58%) Male19 (57.4%)13 (42%) Ageyears (range) Female34.2 (17-91)31.8 (15-78) Male41.2 (20-72)35.4 (20-60) Quantity of paracetamol ingested g (range) Female24.8 (7.5-50)*20.9 (6-97.5) Male26.9 (10-75)25.2 (4.87-40) Quantity of paracetamol ingested mg/kg (range) Female420.1 (94-1041) *365.3 (75-1773) Male361.6 (131-1171)406 (69.6-1403) _____________________________________________________________________ * 2 patients in the non reactors group did not know how much paracetamol they had ingested

7 Time to presentation Non ReactorsReactors (N = 33)(N = 31) ___________________________________________________________________ 8 hours 19 (57.5%)14 (45.2%) > 8 hours 6 (18.2%)13 (41.9%) Staggered 8 (24.3%)4 (12.9%) ___________________________________________________________________ LR = 1.7

8 Clinical features of reactions 71% occurred within 15 minutes (1 st bag) 100% within 60 minutes ____________________________________________________________________ Clinical featuresNumber of patients (n=31) * Rash19 Flushing14 Nausea/vomiting14 Pruritis4 Bronchospasm4 _____________________________________________________________________ * Some patients exhibited more than one of the above clinical features

9 Treatment with N-acetylcysteine _____________________________________________________________________ Non ReactorsReactors _____________________________________________________________________ Commenced before results available 8 hours 04 (28.6%) > 8 hours 4 (66.7%)12 (92.3%) Staggered 4 (50%)3 (75%) Infusion completed 8 hoursYes19 (100%)10 (71.4%) No04 (28.6%) > 8 hoursYes5 (83.3%)7 (53.8%) No1 (16.7%)6 (46.2%) StaggeredYes8 (100%)4 (100%) No00 _____________________________________________________________________ 9/12 high risk

10 Previous / subsequent reactions Two of the reactors presented at a later date, required treatment but did not react First bag given over one hour High risk - levels just below the high-risk treatment line at first presentation and above it on second presentation. Above the normal treatment line for both presentations. One patient received NAC previously

11 At risk patients Non-reactors23.5% (8) Reactors48.4% (15) – Alcohol problem – Malnourished – C-P450 enzyme induction – Previous liver transplant LR = 1.7

12 Discussion NAC reduces the morbidity and mortality following paracetamol overdose 7,8 The frequency of reactions varies considerably from 3% to 23% 3,8 –typically occur within 15-60 minutes –appear to be dose related 9 We have documented substantially higher reaction rate (48.5%) [7] Prescott LF, Illingworth RN, Critchley JAJH, Stewart MJ, Adam RD, Proudfoot AT. BMJ 1979;ii:1097-1100. [8] Bailey B, McGuigan MA. Ann Emerg Med 1998;31(6):710-5. [9] Flanagan RJ, Meredith TJ. Am J Med 1991;91(3C):131-9S.

13 Discussion Only 5 (16%) of reactors above normal line 15 (48.4%) high risk – 2 above normal line 13 (32%) reactions could have been prevented had treatment been delayed until paracetamol levels were available, as recommended by Ho et al 10 [10] Ho SW-C, Beilin LJ. BMJ 1983;187:876-7.

14 Conclusions Patients more likely to react if Low levels/zero levelsLR=1.3 High risk LR=1.7 or if they present late (>8hrs)LR=1.7 Commence NAC before results LR=2.5 Reactions were not severe Giving the loading dose over 60 minutes High-risk Previous reaction 6 [6] Chan TY, Critchley JA. Hum Exp Toxicol 1994;13:542-4.


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