1. Toxicology Meeting Dr. V. Ng

2. Case 1 M/26 Suicidal attempt, burning charcoal 11 am + 8 tabs of sleeping pills Wake up at 6 pm, headache and nausea Presented to AED at 6:41pm Fully conscious and alert,GCS 15/15 COHb at AED 19.4 Repeated COHb 0.4 after 24hr of 100% O2 Discharged on day 4, FU psy & medical

3. Case 2 M/67, COPD, recent dx CA rectum Suicidal attempt,burning charcoal (not sealed) + 10 tab sleeping pill Found LOC at home by friend, ? Duration GCS 3/15 in AED, spontaneous breathing 100% O2 + nasal airway given urine BZ + Transfer to ICU for further Mx

4. Case 2 1 st COHb 19% GCS gradually improving 100% O2 and AC given Psychi consulted Mild cognitive impairment Other Cx : COAD exacerbation / chest infection/ rhabdomyolysis

5. Carbon Monoxide Poisoning

6. Data Oversea TESS 2003 TESS 2003 2,395,582 records 2,395,582 records 16,151 CO exposure (0.6%) 16,151 CO exposure (0.6%) 5.963 treated in hospital 5.963 treated in hospital 46 death 46 death Local UCH 00’ to 04’ 1,883 records 53 CO exposure (2.8%) 2 death ?

7. Pharmacokinetics Absorption : rapidly via alveolar membranes Binds Hb with ~ 250 X > affinity than O2 Elimination – depend on O2 Fi O2 Room air 21% 100% at 1 ATM 100% at 3 ATM CoHb T1/2 2-7 hrs 90 mins 23 mins

8. Pathophysiology CO + Hb → CO Hb Displaces O2 from Hb Displaces O2 from Hb Shifts O2 dissociation curve Shifts O2 dissociation curve Thus, decrease O2 delivery to tissue Thus, decrease O2 delivery to tissue CO + Myoglobin → COMb Inhibits O2 delivery to myocyte Inhibits O2 delivery to myocyte → Myocardial & skeletal muscle hypoxia → Myocardial & skeletal muscle hypoxia CO + cytochrome oxidase →inhibit electron transport →inhibit electron transport →impaired mitochondrial utilization of O2 &ATP

9. Pathophysiology CO induces lipid peroxidation in CNS → neurological sequelae Ischiropoulos H et al : Nitric oxide production and perivascular nitration in brain after CO poisoning in the rat. J Clin Invest 1996 May 15;97 (100: 2260-7 Thom SR : CO mediated brain lipid peroxidation in the rat. J Appl Physio 1990;68:997-1003 Thom SR,et al : Nitric oxide release by platelets inhibits neutophil B2 integrin function following acute CO posioning. Toxicol Appl Pharmacol 1994;128: 105-110

10. CO + heme containing plt proteins NO + CO platelets affects βintegrins PMNs adhere to vascular endothelium Xanthine dehydrogenase → Xanthine oxidase Free radicals Lipid peroxidation

11. CO + heme containing plt proteins NO + CO platelets affects βintegrins PMNs adhere to vascular endothelium Xanthine dehydrogenase → Xanthine oxidase Free radicals Lipid peroxidation

12. Clinical Presentation Acute S/S are due to tissue hypoxia Heart and brain most Heart and brain most CoHb levels are poorly correlate with symptoms and do not predict neuropyschiatric sequelae Acute S/S vs Delayed S/S

13. Management Hyperbaric Oxygen (HBO)

14. Hyperbaric Oxygen Decrease t ½ of CO Hb Displaces CO from myoglobin and cytochrome oxidase in tissues Increases O2 content of blood to improve delivery O2 Decrease lipid peroxidation ↓binding of leukocytes to CNS microvascul. ↓binding of leukocytes to CNS microvascul. ↓ conversion of X.D. to X. oxidase ↓ conversion of X.D. to X. oxidase Improved neurologic outcome

15. RCT for Hyperbaric Oxygen

16. Trial of normobaric & hyperbaric O2 for acute CO intoxication Raphael JC et al. Lancet 1989 Aug 19;2(8660): 414-9 Design : RCT in 629 adults who had been poisoned with CO at home in the 12 hr before admission. Intervention: Incidence of recovery was compared between groups treated with normobaric O2 or HBO. Patients with and without LOC was compared. Conclusion: HBO was not useful in patients who did not LOC during CO intoxication,irrespective of their COHb levels

17. Delayed Neuropsychologic Sequelae after CO poisoning: prevention by treatment with HBO Stephen R Thom et al. Annals of Emerg Med Apr 1995 Vol 25 No 4  Design : RCT in patients with mild to moderate CO poisoning who presented within 6 hrs. Patients had no hx of LOC or cardiac instability  Intervention : Incidence of DNS was compared between groups treated with ambient pressure 100% O2 or HBO  Conclusion: HBO treatment decreased the incidence of DNS after CO poisoning. Neither hx nor CO Hb levels can predict DNS.

18. Hyperbaric or normobaric oxygen for acute CO poisoning: randomized controlled clinical trial Carlos D Scheinkestel et al Med J Aust 1999; 170:203-210 Design: RCT to assess neurological sequelae in patients with all grades of CO poisoning after tx with HBO and NBO Intervention : Daily 60mins at 2.8 atm for HBO gp and at 1.0 atm for NBO gp for 6 days + 100% O2 between tx. Neuropsychological performance was then assessed. Conclusion: HBO therapy did not benefit, and may have worsened, the outcome.

19. Hyperbaric or normobaric oxygen for acute CO poisoning: randomized controlled clinical trial Carlos D Scheinkestel et al Med J Aust 1999; 170:203-210 Limitations Unconventional tx modality in the HBO arm vs control arm Unconventional tx modality in the HBO arm vs control arm Average delay to tx with HBO was 7.1 hr, which is longer than optimal Average delay to tx with HBO was 7.1 hr, which is longer than optimal Patient are predominantly suicidal Patient are predominantly suicidal Follow up was only 46% Follow up was only 46%

20. Hyperbaric Oxygen for acute carbon monoxide poisoning Weaver LK et al. N Engl J Med. 2002 Oct 3;347(14):1057-67. Design : RCT to evaluate the effect of HBO treatment on cognitive sequelae Intervention: Randomly assigned acute CO poisoned patients to 3-chamber sessions within 24 hr, consisting of either 3 HBO treatment OR 1 NBO + 2 NBRm. Conclusion: 3 HBO tx within 24-hr appeared to reduce the risk of congnitive sequelae 6 wks & 12mths after acute CO posioning

21. Hyperbaric oxygen for CO poisoning (cochrane Review) Juurlink DN et al.The Cochrane Library, Issue 1, 2005 Objectives : To examine randomized trials of the effectiveness of HBO compared to NBO for the prevention of neurological sequelae in patients with acute CO poisoning Main results: 7 RCT of varying quality were identified Conclusions: Existing RCT do not establish whether the HBO to patients with CO poisoning reduces the incidence of adverse neurological outcomes. Additional research is needed.

22. Discussion The positive effect of HBO on cognitive sequelae after CO poisoning has important implications for patients and physicians Since facilities for HBO are only available at specialized centers, a boarder indication for the use of it would lead to increase in time- consuming and costly transportation of patients, which is not without risk It is important to indicate which subgroup of patients will benefit most from HBO

23. Thank You