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Toxicology Meeting

Toxicology Meeting. Dr. V. Ng. 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

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Toxicology Meeting

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

  7. Pharmacokinetics • Absorption : rapidly via alveolar membranes • Binds Hb with ~ 250 X > affinity than O2 • Elimination – depend on O2

  8. Pathophysiology • CO + Hb → CO Hb • Displaces O2 from Hb • Shifts O2 dissociation curve • Thus , decrease O2 delivery to tissue • CO + Myoglobin → COMb • Inhibits O2 delivery to myocyte • → Myocardial & skeletal muscle hypoxia • CO + cytochrome oxidase • →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 • 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. • ↓ conversion of X.D. to X. oxidase • Improved neurologic outcome

  15. RCT for Hyperbaric Oxygen

  16. Trial of normobaric & hyperbaric O2 for acute CO intoxicationRaphael 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 HBOStephen 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 trialCarlos 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 trialCarlos D Scheinkestel et al Med J Aust 1999; 170:203-210 • Limitations • 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 • Patient are predominantly suicidal • Follow up was only 46%

  20. Hyperbaric Oxygen for acute carbon monoxide poisoningWeaver 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

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