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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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case 1
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
case 2
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
case 21
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
slide6
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
pharmacokinetics
Pharmacokinetics
  • Absorption : rapidly via alveolar membranes
  • Binds Hb with ~ 250 X > affinity than O2
  • Elimination – depend on O2
pathophysiology
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

pathophysiology1
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
slide10
CO + heme containing plt proteins

NO + CO platelets

affects βintegrins

PMNs adhere to vascular endothelium

Xanthine dehydrogenase → Xanthine oxidase

Free radicals

Lipid peroxidation

slide11
CO + heme containing plt proteins

NO + CO platelets

affects βintegrins

PMNs adhere to vascular endothelium

Xanthine dehydrogenase → Xanthine oxidase

Free radicals

Lipid peroxidation

clinical presentation
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
management

Management

Hyperbaric Oxygen (HBO)

hyperbaric oxygen
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
slide16
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
slide17
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.
slide18
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.
slide19
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%
slide20
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
slide21
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.
discussion
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
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