Carbon Monoxide Carbon Monoxide PoisoningPoisoning

Joshua Rocker, MDJoshua Rocker, MD

Pediatric Emergency MedicinePediatric Emergency Medicine

Schneider Children’s HospitalSchneider Children’s Hospital

The BasicsThe Basics

• CO is an odorless, tasteless, colorless, non-irritating CO is an odorless, tasteless, colorless, non-irritating gas formed by organic (hydrocarbon) combustiongas formed by organic (hydrocarbon) combustion

The BasicsThe Basics

• CO binds hemoglobin with a much greater affinity CO binds hemoglobin with a much greater affinity then O2 (200-250x) forming carboxyhemoglobin then O2 (200-250x) forming carboxyhemoglobin (COHb)(COHb)

SourcesSources

• Motor Vehicle ExhaustMotor Vehicle Exhaust• Smoke from firesSmoke from fires• Gas powered equipmentGas powered equipment• Non-electric heaters (kerosene, gas water)Non-electric heaters (kerosene, gas water)• Charcoal or Hibachi grillsCharcoal or Hibachi grills• Spray paint, solvents, methylene chloride, Spray paint, solvents, methylene chloride,

degreasers and paint removersdegreasers and paint removers

Risks for exposureRisks for exposure

• Riding in back of pickup trucksRiding in back of pickup trucks• Swimming behind motor boatSwimming behind motor boat• Industrial workers where combustion occursIndustrial workers where combustion occurs• Personnel at fire scenesPersonnel at fire scenes• Using combustion engines indoorsUsing combustion engines indoors• Using non-electric heating devices without proper Using non-electric heating devices without proper

ventilationventilation

EpidemiologyEpidemiology

• 40,000 ER visits per year40,000 ER visits per year

• 5,000-6,000 deaths per year5,000-6,000 deaths per year

• Accidental CO poisoning only responsible for Accidental CO poisoning only responsible for approximately 500 deaths annually approximately 500 deaths annually

• Leading cause of accidental poisoning deaths in Leading cause of accidental poisoning deaths in AmericaAmerica

Recent TrendRecent Trend

Data from the CDC

All U.S.A. Deaths from CO All U.S.A. Deaths from CO Poisoning, 1979 – 1988Poisoning, 1979 – 1988

• Highest death rates among: males, blacks, the Highest death rates among: males, blacks, the elderly, and residents of northern states elderly, and residents of northern states

• Motor vehicle exhaust caused 57% of Motor vehicle exhaust caused 57% of unintentional deathsunintentional deaths

• 83% of deaths associated with stationary 83% of deaths associated with stationary

automobiles automobiles

Cobb, N. & R.A. Etzel. (1991) Unintentional carbon monoxide-related deaths in the United States, 1979 through 1988. JAMA, 266, 659-663.

Age Distribution of casesAge Distribution of cases

• <6 y/o- approximately 14%<6 y/o- approximately 14%

• 6-19 y/o- approximately 16%6-19 y/o- approximately 16%

• >19 y/o- approximately 70%>19 y/o- approximately 70%

Data for 1996 and 1997 from the Annual Report of the Am. Assoc. of Poison Control Centers, Toxic Exposure

Surveillance System (published in the American J. Emergency Medicine).

SymptomsSymptoms

SymptomsSymptoms

• Variable and nonspecificVariable and nonspecific

• Cherry red lips or skinCherry red lips or skin

• associated with high COHb, but rare associated with high COHb, but rare (2-3%) and insensitive(2-3%) and insensitive

SymptomsSymptoms Frequency (%)Frequency (%)

FatigueFatigue 9292

HeadacheHeadache 8787

DizzinessDizziness 6969

Sleep DisturbancesSleep Disturbances 6666

Cardiac SymptomsCardiac Symptoms 6262

ApathyApathy 5454

Nausea, vomitingNausea, vomiting 4242

Memory LossMemory Loss 4040

Decreased LibidoDecreased Libido 2222

Loss of AppetiteLoss of Appetite 1212

SymptomsSymptoms

• Older child and adult symptoms are similarOlder child and adult symptoms are similar

• Symptoms of infant or young child may be more Symptoms of infant or young child may be more vague and difficult to clarifyvague and difficult to clarify

• Irritability, poor feedingIrritability, poor feeding

Symptoms loosely Symptoms loosely associated with COHb levelassociated with COHb level

Children SpecificChildren Specific

• In theory children at higher risk of toxicity In theory children at higher risk of toxicity • higher metabolic rate higher metabolic rate • higher tissue oxygen demandhigher tissue oxygen demand

• Infants with high F-Hgb or other forms of anemias Infants with high F-Hgb or other forms of anemias may be at higher risk of deleterious effectsmay be at higher risk of deleterious effects

• Higher rate of lethargy and syncopy in children at Higher rate of lethargy and syncopy in children at lower levels of COHb than expected lower levels of COHb than expected (Crocker,William: (Crocker,William: J Emerg MedJ Emerg Med, 1985.) , 1985.)

Be careful: MisdiagnosesBe careful: Misdiagnoses

• Flu, viral syndromeFlu, viral syndrome• AGEAGE• MigraineMigraine• StrokeStroke• Alcohol Related BehaviorAlcohol Related Behavior• Psychiatric DisorderPsychiatric Disorder• CADCAD

Delayed Neuropsychiatric Delayed Neuropsychiatric Syndrome (DNS)Syndrome (DNS)

• Seen in up to 40% of those with significant exposureSeen in up to 40% of those with significant exposure

• Onset- 3-240 days after exposureOnset- 3-240 days after exposure

• Variable degrees of cognitive deficits, personality Variable degrees of cognitive deficits, personality changes, movement disorders or focal neurological changes, movement disorders or focal neurological deficitsdeficits• In children may b/w difficulty in schoolIn children may b/w difficulty in school

• May persist for yearsMay persist for years

DNSDNS

• Cannot be reliably predictedCannot be reliably predicted• Increased risk if patient presented with Increased risk if patient presented with

LOC during acute phaseLOC during acute phase

PathophysiologyPathophysiology

PathophysiologyPathophysiology

• EffectsEffects• Oxygen deliveryOxygen delivery

• Total oxygen delivery diminishedTotal oxygen delivery diminished

• Oxygen utilizationOxygen utilization• AsphyxiaAsphyxia

PathophysiologyPathophysiology

• CO rapidly diffuses across pulmonary CO rapidly diffuses across pulmonary capillary membrane and binds hemoglobin capillary membrane and binds hemoglobin forming COHbforming COHb

• Once COHb is formed an allosteric change Once COHb is formed an allosteric change occurs and the hemoglobin protein’s ability to occurs and the hemoglobin protein’s ability to off-load the other 3 O2 is greatly diminishedoff-load the other 3 O2 is greatly diminished

TOTAL OXYGEN CONTENT DIMINSHED

Oxyhemoglobin Oxyhemoglobin dissociation curve:dissociation curve:

Left shiftLeft shift

Left shift- ↓ P50 ↑ affinity

(↑ pH, ↓DPG, ↓temp, CO, met-hgb,F-hgb)

Right shift- ↑ P50 ↓ affinity

PathophysiologyPathophysiology

• CO also interferes with peripheral O2 CO also interferes with peripheral O2 utilization by impairing oxidative utilization by impairing oxidative phosphorylation in the mitochondriaphosphorylation in the mitochondria

ASPHYXIA

But…But…

• neither the transient hypoxemia nor the neither the transient hypoxemia nor the transient asphyxia explains the symptoms in transient asphyxia explains the symptoms in full- especially the DNS.full- especially the DNS.

NeuropathopysiologyNeuropathopysiology

• CO binds to cytochrome oxidase which CO binds to cytochrome oxidase which caused oxidative stress caused oxidative stress

• NO is released from platelets and endothelial NO is released from platelets and endothelial cellscells

• Form free radical peroxynitriteForm free radical peroxynitrite• Damages the neural vascular endotheliumDamages the neural vascular endothelium

• END RESULT: lipid peroxidation of the brain END RESULT: lipid peroxidation of the brain occurs during recoveryoccurs during recovery

Lipid PeroxidationLipid Peroxidation

• With perfusion of brain- leukocytes adhesion With perfusion of brain- leukocytes adhesion and subsequent release of destructive and subsequent release of destructive enzymesenzymes

• Excitatory AA exacerbation oxidative injuryExcitatory AA exacerbation oxidative injury

NeuropathophysiologyNeuropathophysiology

• CO has predilection for the basal gangliaCO has predilection for the basal ganglia• Explain movement abnormalitiesExplain movement abnormalities

• Autopsy results show involvement of: Autopsy results show involvement of: cerebral cortex, hippocampus, cerebellum cerebral cortex, hippocampus, cerebellum and substantia nigraand substantia nigra• Explain the diverse neurological Explain the diverse neurological

abnormalitiesabnormalities

Laboratory evaluationLaboratory evaluation

• VBG/ABG, COHb, CPK, CBC, lytes and EKGVBG/ABG, COHb, CPK, CBC, lytes and EKG

• Consider: tox screen, EtOH level and cardiac Consider: tox screen, EtOH level and cardiac enzymes enzymes

COHbCOHb

• Normal levelsNormal levels• Non-smokers: 0-3Non-smokers: 0-3• Smokers: 3-5 (can be up to 10)Smokers: 3-5 (can be up to 10)

• Elevation does not always directly translate to Elevation does not always directly translate to more symptoms or worse prognosis more symptoms or worse prognosis

ManagementManagement

ManagementManagement

#1- GET OUT!!!!!!

ManagementManagement

• 1- Remove oneself from source of CO1- Remove oneself from source of CO• 2- Seek medical attention2- Seek medical attention

• In ambulance- 100% non-rebreather (NRB)In ambulance- 100% non-rebreather (NRB)• In hospital- always …ABCsIn hospital- always …ABCs

ManagementManagement

• 3. 100% NRB3. 100% NRB• Half-life of COHb is 4-5 hours at RAHalf-life of COHb is 4-5 hours at RA• Half-life is 40-80 minutes with NRBHalf-life is 40-80 minutes with NRB

• (Normobaric oxygen therapy- NBO)(Normobaric oxygen therapy- NBO)

ManagementManagement

• 4. Hyperbaric Therapy4. Hyperbaric Therapy• Delivery 100% O2 at 2.5-3 atms of Delivery 100% O2 at 2.5-3 atms of

pressurepressure• Alters the half life of COHb to less than 30 Alters the half life of COHb to less than 30

minutes.minutes.

Hyperbaric Therapy:Hyperbaric Therapy:

• Henry’s Law Henry’s Law • amount of an ideal gas dissolved in a solution is amount of an ideal gas dissolved in a solution is

directly proportional to its partial pressure.directly proportional to its partial pressure.

• Dissolved Plasma Oxygen Content:Dissolved Plasma Oxygen Content:• RA @ 1 atm- 0.3 ml/dl RA @ 1 atm- 0.3 ml/dl • 100% O2 @ 1 atm- 1.5 ml/dl100% O2 @ 1 atm- 1.5 ml/dl• 100% O2 @ 3 atm- 6 ml/dl100% O2 @ 3 atm- 6 ml/dl

• Sufficient to meet resting O2 demands Sufficient to meet resting O2 demands regardless of hgb-O2 supplyregardless of hgb-O2 supply

HBOHBO

• Single place vs multi-place chambersSingle place vs multi-place chambers• Raise pressure to 2.5-3 atmsRaise pressure to 2.5-3 atms• Length of tx- 45-300 minutesLength of tx- 45-300 minutes

• Concerns:Concerns:• Can child tolerate alone- if singleCan child tolerate alone- if single• Deterioration in chamber- can’t open Deterioration in chamber- can’t open

immediatelyimmediately

HBOHBO

• Complications:Complications:• 20%- reversible myopia20%- reversible myopia• 3-20%- otic barotrauma3-20%- otic barotrauma• pulmonary barotrauma pulmonary barotrauma • pulmonary oxygen toxicity pulmonary oxygen toxicity • seizuresseizures

HBOHBO

• Absolute contraindications:Absolute contraindications:• Untreated pneumothoraxUntreated pneumothorax

• Relative contraindicationsRelative contraindications• URI, sinus disease, claustrophobiaURI, sinus disease, claustrophobia• Hx of seizure d/o, pneumothorax or chest Hx of seizure d/o, pneumothorax or chest

surgerysurgery

HBO: how does it work??HBO: how does it work??

• Decreasing the occurrence of DNS does not Decreasing the occurrence of DNS does not seem to be solely based on the COHb seem to be solely based on the COHb elimination but rather on the reduction of free elimination but rather on the reduction of free radical production and lipid peroxidation.radical production and lipid peroxidation.

HBO: how does it workHBO: how does it work

• Thom, SR: Antagonism of CO-mediated brain Thom, SR: Antagonism of CO-mediated brain lipid peroxidation by HBO. Toxicol Appl lipid peroxidation by HBO. Toxicol Appl Pharmacol, 1990, 105: 340-344.Pharmacol, 1990, 105: 340-344.• Animal study which revealed that HBOT Animal study which revealed that HBOT

accelerated the elimination of CO from accelerated the elimination of CO from bound cytochrome oxidase, therefore bound cytochrome oxidase, therefore preventing oxidative brain injury.preventing oxidative brain injury.

HBO: how about in kids?HBO: how about in kids?

• Rudge: CO poisoning in infants. Rudge: CO poisoning in infants. South Med JSouth Med J 1993, 86: 334-337 1993, 86: 334-337

• Complete neurological recovery in 13 of 14 Complete neurological recovery in 13 of 14 children < 2 y/o receiving HBOchildren < 2 y/o receiving HBO

• Crocker and Walker: Pediatric CO toxicity. Crocker and Walker: Pediatric CO toxicity. J Emerg MedJ Emerg Med 1985, 1985, 3: 443-448.3: 443-448.

• No m and m among 16 children who No m and m among 16 children who received HBO vs 25% developed DNS in received HBO vs 25% developed DNS in those receiving NBO.those receiving NBO.

• Kim and Coe: Clinical study on CO intoxication in children. Kim and Coe: Clinical study on CO intoxication in children. Yonsei Med JYonsei Med J 1987, 28:266-273. 1987, 28:266-273.

• 29.4% vs 19.4% (NBO vs HBO) with 29.4% vs 19.4% (NBO vs HBO) with neurological sequelaeneurological sequelae

•BUT…BUT…

HBO: controversyHBO: controversy

• Tibbles and Perrotta: Treatment of Carbon Tibbles and Perrotta: Treatment of Carbon Monoxide poisoning: a critical review of Monoxide poisoning: a critical review of human outcome studies comparing NBO with human outcome studies comparing NBO with HBO. HBO. Ann Emerg MedAnn Emerg Med, 1994., 1994.

• "no randomized, controlled, blinded clinical "no randomized, controlled, blinded clinical trial demonstrated a clear advantage of trial demonstrated a clear advantage of HBO over NBO in reducing morbidity and HBO over NBO in reducing morbidity and mortality in carbon monoxide poisoning."mortality in carbon monoxide poisoning."

Tibbles PM, Edelsberg JS. Hyperbaric-oxygen therapy. N Engl J Med 1996;334:1642-1648 a

Criteria for HBO:Criteria for HBO: Although controversial, these are general Although controversial, these are general

acceptedaccepted

• SyncopySyncopy• Acutely severe neurological symptomsAcutely severe neurological symptoms• MIMI• Cardiac DysrhythmiasCardiac Dysrhythmias• Persistent neuro symptomsPersistent neuro symptoms• Pregnancy if >COHb15Pregnancy if >COHb15• Severe acidemiaSevere acidemia

Criteria to Criteria to considerconsider HBO HBO

• COHb >20-25%COHb >20-25%• <6 months with symptoms<6 months with symptoms• Children with underlying disease for whom Children with underlying disease for whom

hypoxia may be deleterioushypoxia may be deleterious• > 60 y/o> 60 y/o

Further ManagementFurther Management

• Treat other issues…Treat other issues…• Hypotension- 2Hypotension- 2º to º to myocardial damagemyocardial damage• HypoglycemiaHypoglycemia• Cardiac IschemiaCardiac Ischemia• Smoke inhalation injuriesSmoke inhalation injuries• BurnsBurns• SeizuresSeizures• RhabdomyolysisRhabdomyolysis

PreventionPrevention

• Careful behaviorCareful behavior• Proper ventilationProper ventilation• CO monitorsCO monitors

• ““To protect against carbon monoxide-To protect against carbon monoxide-related deaths, New York State related deaths, New York State implemented a new law requiring carbon implemented a new law requiring carbon monoxide detectors in all one- and two-monoxide detectors in all one- and two-family houses, condominiums and co-ops family houses, condominiums and co-ops built on or after December 1, 2002.”built on or after December 1, 2002.”

New York City Department of Health and Mental HygieneNew York City Department of Health and Mental Hygiene

MiscellaneousMiscellaneous

• Pulse oximetry may read normal or even Pulse oximetry may read normal or even over-estimate the arterial hemoglobin oxygen over-estimate the arterial hemoglobin oxygen saturationsaturation

Hampson, NB. Pulse oximetry in severe carbon monoxide poisoning. Chest, 1998; 114:1036-1041

QuestionsQuestions

A family of 5 presents to the ER. The 5 and 7 years old A family of 5 presents to the ER. The 5 and 7 years old children present with headaches and abdominal pain. The 6 children present with headaches and abdominal pain. The 6 month old is refusing feeds and is having diarrhea. Their month old is refusing feeds and is having diarrhea. Their vitals are WNL. The mother passed out at home. What vitals are WNL. The mother passed out at home. What should you do first? should you do first?

• A. Call Jacobi and see if they will receive these A. Call Jacobi and see if they will receive these patientspatients

• B. Call 1-800-POISONSB. Call 1-800-POISONS• C. Obtain COHb levels on all the childrenC. Obtain COHb levels on all the children• D. Put 100% NRB on the older children and give D. Put 100% NRB on the older children and give

20cc/kg NS bolus to the youngest20cc/kg NS bolus to the youngest• E. Place all the children on 100% NRB E. Place all the children on 100% NRB

• ABCsABCs• 100% NRB to all100% NRB to all• Secondary survey may reveal a dehydrated Secondary survey may reveal a dehydrated

child which can be addressed but it is child which can be addressed but it is secondary.secondary.

• HBO may be necessary but institute first line HBO may be necessary but institute first line therapy first.therapy first.

• Yes, draw the levels- after O2.Yes, draw the levels- after O2.

A 9 yr old girl is brought to the ER because she is lethargic. A 9 yr old girl is brought to the ER because she is lethargic. The mother returned home to find her minimally responsive. The mother returned home to find her minimally responsive. The mother suffers from chronic lower back pain and has The mother suffers from chronic lower back pain and has medications in the home. The child is on winter vacation from medications in the home. The child is on winter vacation from school. There home is heated with an old coal furnace. On school. There home is heated with an old coal furnace. On exam she is obtunded. Her vitals are: 36.8 C, HR 100, RR-8, exam she is obtunded. Her vitals are: 36.8 C, HR 100, RR-8, BP- 80/40. O2 sat is- 95%. With 100% NRB her sats increase BP- 80/40. O2 sat is- 95%. With 100% NRB her sats increase to 100%. Her skin is normal color. Her lungs are clear. Her to 100%. Her skin is normal color. Her lungs are clear. Her pupils are miotic. What is the most likely confirmatory study?pupils are miotic. What is the most likely confirmatory study?

• A. CXRA. CXR• B. Methemoglobin levelB. Methemoglobin level• C. COHb levelC. COHb level• D. Urine toxD. Urine tox• E. LPE. LP

• CXRCXR• no respiratory distress only depressionno respiratory distress only depression

• MethgbMethgb• toxin-induced from ingestion or dermal exposure toxin-induced from ingestion or dermal exposure

to an oxidizing agent to an oxidizing agent • anilineaniline• dapsone,dapsone,• local anestheticslocal anesthetics• phenazopyridinephenazopyridine• nitrates/nitritesnitrates/nitrites• naphthalenenaphthalene

• GeneticGenetic• dietary (eg, well water nitrates), dietary (eg, well water nitrates), • idiopathic causes (acidosis).idiopathic causes (acidosis).• Patients usually present with cyanosis not Patients usually present with cyanosis not

responsive to oxygen administration.responsive to oxygen administration.

• COHbCOHb• Right seasonRight season• right risk factors- indoor furnaceright risk factors- indoor furnace• right symptom- obtunded, but… miotic, right symptom- obtunded, but… miotic,

hypotensive and experiencing respiratory hypotensive and experiencing respiratory depression. Still treat and w/u.depression. Still treat and w/u.

• Urine toxUrine tox• Where the money is. Mom with meds at Where the money is. Mom with meds at

home and patient with signs of opiate tox.home and patient with signs of opiate tox.• LPLP

• No fever, respiratory and BP involved. No fever, respiratory and BP involved. Unlikely, but if else negative encephilitis is Unlikely, but if else negative encephilitis is possiblity.possiblity.

QUESTIONS???QUESTIONS???