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EVIDENCE BASED MEDICINE Carbon Monoxide (CO) and Hyperbaric oxygen therapy (HBOT) Najim Mohammady MS7 (PGY-2) 09-30-15 Slide 2 CO is one of the leading causes of poisoning in the United States Nearly 500 deaths annually in US Slide 3 Incomplete combustion of hydrocarbons Endogenous source: Heme degradation into bile pigments Slide 4 C=O binds Hb with 210x affinity than O 2 Slide 5 MYOGLOBIN CYTOCHROME C HYPOXIA Slide 6 C=O causes nonspecific symptoms Slide 7 Have a high level of suspicion Vague symptoms CarboxyHb levels do not correlate well with toxicity Ambient air measurements of C=O DO NOT trust pulse Ox Slide 8 100% Oxygen is the mainstay of therapy C=O (carboxyHb) half-life is ~5 hours 100% O2 via NRB reduces this to ~1-1.5hour Hyperbaric 100% O2 reduces this to ~20-30 min Slide 9 HBOT increases dissolved O 2 Increases dissolved oxygen in blood stream and tissues side effects: reversible myopia, cataract, tracheobronchial symptoms, self-limited seizures and barotraumas to the middle ear, cranial sinuses, rarely teeth or lungs Undersea and Hyperbaric Medicine Society recommend HBOT: LOC Abnormal neurologic signs Cardiovascular dysfunction Severe acidosis Age over 36 years CO exposure of 24 hours Carboxyhemoglobin level 25% Slide 10 Slide 11 Slide 12 Evidence Based Medicine Tools: PICO Defining a clinical question in terms of the specific patient problem Slide 13 What are the indications for use of HBOT in adults with CO2 poisoning? Do patients who receive HBOT have better neurological outcomes than patients with conventional therapy? Slide 14 ACEP makes recommendations based on review of the literature Level A reflect a high degree of clinical certainty Level B reflect moderate clinical certainty Level C recommendations represent other patient management strategies that are based on preliminary, inconclusive, or conflicting evidence, or based on committee consensus. Slide 15 Should HBO2 therapy be used for the treatment of patients with acute CO poisoning? LEVEL C: HBO2 is a therapeutic option for CO-poisoned patients; however, its use cannot be mandated. Slide 16 The primary outcome was the incidence of cognitive sequela six weeks. Slide 17 Randomized into HBOT or sham HBOT Randomized, double blinded placebo controlled 152 patients total Included sick patients (1/2 LOC, 8% intubated) Randomly with 3 sessions of HBOT vs. 1 normobaric + 2 sham Defined neurological problems as cognitive and neurological exam i.e. cerebellar function (finger to nose) Mental exams; trail making, digit span, etc Measured immediately after tx, @2 weeks, 6 weeks, 6 months and 12 months Slide 18 Cognitive sequelae at six weeks were less frequent in the hyperbaric oxygen group (19 of 76 [25.0%]) than in the normobaric oxygen group (35 of 76 [46.1 %], P=0.007) Slide 19 Slide 20 Slide 21 Problems with the Weaver et al study Concern for observer bias Groups were not really the same Their definition of neurological sequela changed 3 times Primary outcome was actually a secondary outcome initially Intention to treat analysis No actual differences in functional outcomes i.e. ADLs Slide 22 T score in a normal population was 5010 for each sub- test. Maybe the tests they used arent really that good to begin with Slide 23 Slide 24 Outcome: self reported symptoms of neurological sequela and deterioration in at least 1 of the 6 tests occurring anytime after treatment Slide 25 Randomized to single HBOT vs. oxygen mask HBO at a pressure of 2.8 ATA for 30 minutes, followed by 2.0 ATA for 90 minutes; Normobaric with 100% oxygen through a NRB mask until all symptoms resolved. Sick patients excluded (no LOC or cardiac) Delayed neurological sequalae defined as: recurrence of original symptoms or development of new symptoms considered to be typical of the DNS syndrome, plus a deterioration in one or more subtest scores on the neuropsychometric tests Slide 26 Slide 27 Initial test scores were the same for the both groups right after therapy 0% in the HBOT group (95% CI 0 -12%) had delayed sxs vs. 23% in only mask (95% CI 10-42%) all the neurological problems resolved by 77 days Slide 28 Thom et al study problems Not blinded Low sample size No Sham chamber Sick patients were not included (LOC, cardiac) Self reported data Trial stopped at 65 patients when their initial interim analysis at 58 patients showed no statistical significance (i.e. only 7 patients were added to the study) Not powered Slide 29 Outcome: self reported symptoms of neurological sequela and deterioration in at least 1 of the 6 tests occurring anytime after treatment Slide 30 Hyperbaric or normobaric oxygen for acute carbon monoxide poisoning: a randomised controlled clinical trial. Scheinkestel CD, Bailey M, Myles PS, Jones K, Cooper DJ, Millar IL, Tuxen DV Alfred Hospital, Melbourne, VIC. cdsch@ozemail.com.au Medical Journal of Australia 1999 Outcome: Neuropsychological performance at completion of treatment, and at one month where possible. Slide 31 Hyperbaric vs sham N= 191 patients Randomized into HBOT or sham continuous O2 by face mask for 3 days after CO with daily trips to HBOT chamber Sham chamber used for normobaric group to maintain blinding Pts with severe poisoning included >1/2 comatose Slide 32 Results and Problems with the study 74% in HBOT and 68% of controls had bad outcomes (reported OR 1.7; 95% CI 0.8 to 4.0; P0.19 ) 73% of patients enrolled were very sick, severe poisoning endpoints measured at completion of therapy and at 1 month (1 month data actually never made it) only stat significant result was better for normobaric group verbal learning 54% of patients lost to follow up (high attrition rate) used greater O2 doses than conventional therapy (3 days of face mask regardless of HBOT or sham (not generalizable) Slide 33 Hyperbaric or normobaric oxygen for acute carbon monoxide poisoning: a randomised controlled clinical trial. Scheinkestel CD, Bailey M, Myles PS, Jones K, Cooper DJ, Millar IL, Tuxen DV Alfred Hospital, Melbourne, VIC. cdsch@ozemail.com.au Medical Journal of Australia 1999 Outcome: Neuropsychological performance at completion of treatment, and at one month where possible. Slide 34 primary outcome was self reported symptoms, PE and Neurological exam Slide 35 Prospective, randomized, unblinded 343 CO poisoning without LOC within 12 hours of CO2 exposure Randomized to 1 HBOT or mask 1 month after tx 32.1% of patients with HBO2 and 33.8% of control reported neurological symptoms (P=0.75 X2) 97% of patients resumed their daily lives Slide 36 primary outcome was self reported symptoms, PE and Neurological exam Slide 37 Since the ACEP policy 2 parallel clinical trials in France using HBOT in LOC and comatose patients Hyperbaric oxygen therapy for acute domestic carbon monoxide poisoning: two randomized controlled trials n=385 In patients with transient loss of consciousness, there was no evidence of superiority of HBO over NBO. In comatose patients, two HBO sessions were associated with worse outcomes than one HBO session. Slide 38 Slide 39 Cochrane review Studies extremely heterogenous severity of CO poisoning, the treatment regimens, and outcome assessment varied significantly among trials. High risk of bias (incomplete blinding, allocation Many of studies published by hyperbaric experts More research is needed Slide 40 What I would do NRB 100% O2 to start things off Send off carboxyHb but dont hang my hat Good neurological exam For my critically ill patients; consider HBOT if available, transport is not an issue, and family understands risks Slide 41 Q /A Slide 42 References Annane, D., et al. (2011). "Hyperbaric oxygen therapy for acute domestic carbon monoxide poisoning: two randomized controlled trials." Intensive care medicine 37(3): 486-492. Guzman, J. A. (2012). "Carbon monoxide poisoning." Critical care clinics 28(4): 537-548. Juurlink, D., et al. (2005). "Hyperbaric oxygen for carbon monoxide poisoning (Review). Prockop, L. D. and R. I. Chichkova (2007). "Carbon monoxide intoxication: an updated review." Journal of the neurological sciences 262(1): 122-130 Raphael, J.-C., et al. (1989). "Trial of normobaric and hyperbaric oxygen for acute carbon monoxide intoxication." The Lancet 334(8660): 414-419. Scheinkestel, C. D., et al. (1999). "Hyperbaric or normobaric oxygen for acute carbon monoxide poisoning: a randomised controlled clinical trial." The Medical journal of Australia 170(5): 203-210. Slide 43 References continued Silver, S., et al. (2006). "Should hyperbaric oxygen be used for carbon monoxide poisoning?" Cjem 8(01): 43-46. Sykes, O. T. and E. Walker (2015). "The neurotoxicology of carbon monoxide Historical perspective and review." Cortex. Thom, S. R., et al. (1995). "Delayed neuropsychologic sequelae after carbon monoxide poisoning: prevention by treatment with hyperbaric oxygen." Annals of emergency medicine 25(4): 474-480. Weaver, L. K. (2009). "Carbon monoxide poisoning." New England Journal of Medicine 360(12): 1217-1225. Weaver, L. K., et al. (2002). "Hyperbaric oxygen for acute carbon monoxide poisoning." New England Journal of Medicine 347(14): 1057-1067. Weaver, L. K., et al. (2007). "Carbon monoxide poisoning: risk factors for cognitive sequelae and the role of hyperbaric oxygen." American Journal of Respiratory and Critical Care Medicine 176(5): 491-497. Wolf, S. J., et al. (2008). "Clinical policy: critical issues in the management of adult patients presenting to the emergency department with acute carbon monoxide poisoning." Journal of Emergency Nursing 34(2): e19-e32.