Carboxyhemoglobin levels in children with nonspecific flu-like symptoms

CLINICAL AND LABORATORY OBSERVATIONS

Carboxyhemoglobin levels in children with nonspecific flu-like symptoms M. Douglas Baker, MD, Fred M. Henretig, MD, a n d Stephen Ludwig, MD From The Universityof PennsylvaniaSchool of Medicine, Philadelphia

Although carbon monoxide intoxication is thought to account for approximately half of all deaths caused by poisons] the incidence of sublethal toxicity has not been well investigated in a pediatric population. The manifestations of CO poisoning may be severe or subtle. 24 Commo nly, signs and symptoms are gradual and simulate other illnesses.? ,3.5 Flu-like symptoms such as headache, dizziness, weakness, nausea, vomiting, and drowsiness are frequent? The purpose of our study was to determine the possibility of carbon monoxide poisoning as a cause of nonspecific flu-like symptoms in children who had no recognized exposure. METHODS

Children younger than 18 years of age, consecutively seen in The Children's Hospital of Philadelphia Emergency Department for evaluation of flu-like symptoms (headache, dizziness, weakness, nausea, vomiting, altered mental status), were eligible for entry into the study. Excluded were patients with symptoms specifically suggestive of a viral illness, including fever >38.9 ~ C, watery stools, viral exanthem or enanthem, or with a history of smoke inhalation. Enrollees were also required to have one or more exPosure criteria, including the occurrence of symptoms while (1) a motor vehicle passenger; (2) a resident of a home with combustible f u e l heat, including kerosene heaters, wood stoves, fireplaces, natural gas appliances, Sterno units, or central heating systems older than 10 years; or (3) exposed to chemical fumes such as those generated by paint strippers. Presented in part before the American Academy of Pediatrics Section on Emergency Medicine, New Orleans, November 1, 1987. Submitted for publication March 28, 1988; accepted March 28, 1988. Reprint requests: M. Douglas Baker, MD, Emergency Department, The Children's Hospital of Philadelphia, 34th and Civic Center Blvd, Philadelphia, PA 19104.

Patients meeting at least one exposure and one symptom criterion Were enrolled in the study. A 1 ml venous blood sample for cooximetry was obtained as soon as possible after patient registration. Evaluation then proceeded as usual. Patients with carboxyhem0globin levels in excess of 2% were treated with either normobaric or hyperbaric oxygen, as indicated by their individual symptoms and carboxyhemoglobin levels. Additional epidemiologic and demographic data were collected by the managing physician, including type and !ocation of home, cigarette smoke exposure, type of home heat, in-home smoke detector use, and mode of transportation to the hosPital. Venous samples for cooximetry were also collected from contrOl children seen in the Emergency Department for evaluation of non-carbon monoxide-related symptoms and whose blood was drawn for other purposes. The study was conducted from January 5 through March 30, 1987. This period wa s chosen to coincide with the peak use of indoor heaters. The experimental protocol was approved by the hospital Institutional Review Board; informed consent was not required. Statistical significance between data groups was analyzed via chi:square analysis. Significance was defined as p < 0.05, RESULTS Forty-six study patients had 10 control patients were enrolled. Malepatients outnumbered female patients 26:20 within the study group, and 6:4 within the control group. The average age of study patients was 7.1 years, and of Control patients 6.4 years. ThirtY-eight study patients and eight control patients were black; the remainder were white. The average carboxyhemoglobin level of control patients was 1.3 _+ 0.4 (range 0.6 to 1.9). The diagnoses in control patients included asthm a, fever, and upper respiratory tract infection in two patients each, and bronchiolitis, hemophilia, viral enteritis, and cellulitis in one each. None had any history of carbon monoxide exposure. Of the 46 study patients, 22 had carboxyhemoglobin

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Clinical and laboratory observations

The Journal of Pediatrics September 1988

Table I. Environmental factors related to carboxyhemoglobin level (n = 46) Carboxyhemoglobin <2% n

Source of exposure Kerosene heater Auto exhaust Oil heater Gas stove/range Wood stove Household smokers Tobacco-packs/day Home smoke detector Total patients

10 0 1 10 1 17 1.2 19 22

level

2-5% %

77 86*

n

3 1 0 7 0 8 0.9 3 11

5-40% %

72 27

n

4 1 2 0 0 6 1.1 3 7

>40% %

86 43

n

1 3 2 0 0 5 1.3 2 6

%

83 40

*p < 0.001.

levels of less than 2% (Table I). Their symptoms Were believed not to be attributed to carbon monoxide toxicity. Exceptions in this group were two siblings (ages 2 and 30 months, respectivelY) who had been removed from a source Of carbon monoxide exposure for approximately 10 hours before carboxyhemoglobin measurement. Both had had significant lethargy and vomiting while sleeping and playing in a kerosene-heated room. The average time of delay from carbon monoxide exposure to carboxyhemoglobin measurement in the other 20 patients in this group was 45 minutes. Of the remaining 24 study patients, 11 had r moglobin levels between 2% and 5%, seven between 5% and 10%, and six greater than t0% (range 2.7% to 27.6%). The average delay from cessation of carbon monoxide exposure to carboxyhemoglobin measurement was 40 minutes. All patients received norm0baric oxygen treatment while in the Emergency Department. Three also required hyperbaric oxygen treatment because of the degree of elevation of carboxyhemoglobin level. No study or control patients received oxygen en route to the hospital. Four sources of carbon monoxide were responsible for elevation of carboxyhemoglobin levels. Auto exhaust and oil heat exhaust exposure were associated with the highest levels. The frequency of household tobacco product use (Table I) did not differ significantly between outcome groups. Similarly~ the type a n d location of principal residence and mode of transportation to the hospital were similar among all groups. Of the 22 study patients with carboxyhemoglobin levels below 2%, 19 (86%) had smoke detectors, whereas only eight (33%) of the 24 patients with higher levels had these units in their homes. The most frequently encountered symptoms (Table II) were headache (63%), lethargy (46%), nausea (33%), and

dizziness (30%). The frequency of symptoms did not significantly differ between study groups. Of the 24 patients with carb0xYhemogl0bin levels greater than 2%, 13 (54%) would not have been suspected to have elevated carboxyhemoglobin levels on the basis of routine history or physical findings alone." For the other 11, history specifically suggestive of carbon monoxide toxicity as a cause of symptoms was available from the onset. The sources of carbon monoxide exposure in the 13 patients with unsuspectedly high carboxyhemoglobin levels were kerosene heaters and gas Stoves in five patients each and oil heaters in three. Six of these patients had documented carboxyhemoglobin levels between 2% and 5%, five between 5% and !0%, and two in excess of 10%. The frequency and distribution of symptoms in this group of patients was similar to that among the others in the study. All patients with carboxyhemoglobin levels in excess of 2.0% noted improvement in symptoms concomitant with normobaric oxygen treatment and reduction of carboxyhemoglobin levels. DISCUSSION Carbon monoxide poisoning has been commonly misdiagnosed in adults as an influenza-like viral illness.6,7 Our data indicate that the same is true in children. More than half (52%) of our patients had measured carboxyhemoglobin levels in excess of the 0% to 2% found in normal nonsmoking subjects. 8,9 Our findings demonstrate that no specific symptom complex could help in distinguishing carbon monoxide poisoning from a presumed viral illness. Indeed, in many of our patients elevated carboxyhemoglobin levels would not have been susPected on the basis of routine history or physical findings alone. Moreover, in our

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Clinical and laboratory observations

503

T a b l e II. Patient symptoms according to carboxyhemoglobin level (n -- 46) Carboxyhemoglobin level <2%

2-5%

5.'10%

>10%

Symptom

n

%

n

%

n

%

n

%

Headache Lethargy/abnormal sensorium Nausea Dizziness Vomiting Irritability Weakness

13 9 8 5 6 5 2

59 41 36 23 27 23 9

8 5 4 4 4 0 0

73 45 36 36 36 0 0

4 4 2 3 2 1 0

57 57 29 43 29 14 0

4 3 1 2 1 1 1

67 50 17 33 17 17 17

patients specifically identified on the basis of likely exposure to carbon monoxide sources, almost half had carboxyhemoglobin levels within the normal range. Nevertheless, our data demonstrate the importance of obtaining an exact clinical history and of maintaining a high level of suspicion. Four carbon monoxide sources accounted for all of the elevated carboxyhemoglobin levels. The two most commonsources were kerosene heaters and natural gas stoves improperly used as heating sources. Kerosene heaters have been documented as a source of carbon monoxide toxicity in both the clinicall~ and laboratory setting. H Although natural gas does not contain carbon monoxide, it yields carbon monoxide if incompletely burned, 2 as when natural gas appliances, such as gas stoves, are defective and their exhausts are improperly vented. Tobacco use is another documented source of carbon monoxide. Cigarette smoking produces levels of 5% to 9%.9.12 None of our study or control patients were primary tobacco users, and the number of household smokers and packs per day smoked in each household did not significantly differ between study groups. More patients whose carboxyhemoglobin levels were below 2% used home smoke detectors than did those whose levels were above 2%. That none of our patients was alerted to the presence of smoke by these detectors discounts any preventive influence they might have exerted. However, it is reasonable to hypothesize t h a t smoke detector users might, in general, be more safety conscious or in a higher economic group, and less likely to create and inhabit an improperly ventilated living environment. Some previous investigators have correlated symptoms with carboxyhemoglobin levels, denoting complete absence of associated symptoms when (in the acute setting) patient levels were below 10%.2,13'14 Others have noted mild symptoms and objective evidence for psychomotor impairment at carboxyhemoglobin levels below 10%.15 Our data

support the latter findings. All patients whose initial carboxyhemoglobin levels were between 2% and 10% noted improvement in symptoms concomitant with treatment with oxygen and lowering of carboxyhemoglobin levels. This discrepancy in symptom manifestation between adults and children has been previously observed, l~ It has been hypothesized that increased metabolic demands on oxygen delivery make infants more susceptible than adults to carbon monoxide poisoning.15 It might be argued that children with carboxyhemoglobin levels in the 2% to 5% range have minimal symptoms and that their ill effects would likely be self-limited. We contend that the crucial importance of accurate diagnosis in this group is not the opportunity provided for prompt treatment to reduce carboxyhemoglobin levels so much as the prompt recognition of a hazardous environment. These same children (and their families) are potentially at risk for serious and possibly life-threatening injury if exposure were to continue. Our data illustrate the importance of obtaining a careful environmental history in all children with afebrile flu-like symptoms during cold weather months. We recognize that our study population is not representative of the urban pediatric population as a whole. We specifically eliminated patients with fever, diarrhea, and viral exanthems from our study population in order to (theoretically) minimize sampling in children presumed to have carboxyhemoglobin levels in the nontoxic range. In doing so, we may have eliminated some patients with elevated levels, but we believe that our exposure criteria were broad enough to eliminate few. In fact, no potential study enrollees were eliminated on the basis of lack of exposure criteria alone. Given the almost ubiquitous presence of potential sources of exposure to carbon monoxide for inner city children in temperate climates during the winter, it will be important to study this population with less restrictive eligibiiity criteria to get a more precise

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Clinical and laboratory observations

measure of the actual incidence of carbon monoxide toxicity. REFERENCES

1. Accident facts. Chicago: National Safety Council, 1982:804. 2. Zimmerman SS, Truxal B. Carbon monoxide poisoning. Pediatrics 1981;68:215-24. 3. Haldane J. The relation of the action of carbonic oxide to oxygen tension. J Physiol 1985;18:201-17. 4. Myers R, Snyder SK, Majerus TC, et al. Cutaneous blisters and carbon monoxide poisoning. Ann Emerg Med 1985; 14:603-6. 5. Burney RE, Wu SC, Nemiroff MJ. Mass monoxide poisoning: Clinical effects and results of treatment in 184 victims. Ann Emerg Med 1982;11:394-9. 6. Dolan MC, Haltom TL, Barrows GH, et al. Carboxyhemoglobin levels in patients with flu-like symptoms [Abst]. Ann Emerg Med 1986;15:653. 7. Grace TW, Platt FW. Subacute carbon monoxide poisoning. JAMA 1981;246:1698-1700.

The Journal of Pediatrics September 1988

8. Coburn RF. Endogenous carbon monoxide production. N Engl J Med 1970;282:207-9. 9. Steward RD, Baretta ED, Plate LR, et al. Carboxyhemoglobin levels in American blood donors. JAMA 1974;229:118795. 10. O'Sullivan BP. Carbon monoxide poisoning in an infant exposed to a kerosene heater. J PEDIATR 1983;103:249-51. 11. Traynod GW, Allen JR, Apte MG, et al. Pollutant emissions from portable kerosene-fired space heaters. Environ Sci Technol 1983;17:369-71. 12. Russel MAH. Blood carboxyhemoglobin changes during tobacco smoking. Postgrad Med J 1973;49:684-7. 13. Lacey DJ. Neurologic sequelae of acute carbon monoxide intoxication. Am J Dis Child 19281;135:145-7. 14. Winter PM, Miller JN. Carbon monoxide poisoning. JAMA 1976;236:1502-4. 15. Kassen CD. Nonmetallic environmental toxicants: Air pollutants, solvents, and vapors, and pesticides. In: Gilman AG, Goodman L, Gilman A, eds. The pharmacologic basis of therapeutics, 6th ed. New York: Macmillan, 1980:1641.

Safe administration of mumps-measles-rubella vaccine in egg-allergic children M a r k A. G r e e n b e r g , MAJ, MC, a n d D e b o r a h L. Birx, MAJ, MC From the Allergy/Immunization Clinic, Womack Army Community Hospital, Fort Bragg, North Carolina, and the Allergy/Immunology Service, Walter Reed Army Medical Center, Washington, D.C.

Egg allergy is the most common IgE-mediated food hypersensitivity during the first i2 months of life) The attenuated mumps and measles viruses in the mumpsmeasles-rubella vaccine are grown in avian embryos and contain minute amounts of egg products. 2 H e r m a n et a l ) reported on two children with anaphylactic sensitivity to eggs who experienced urticaria, angioedema, and respiratory difficulties after M M R injection. The manufacturer of the M M R vaccine recommends that children with a prior history of anaphylactie or other immediate reactions not be given the vaccine.* However,

The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense. Submitted for publication April 13, 1988; accepted April 26, 1988. No reprints available. *Package insert for MMR vaccine. West Point, Pa.: Merck Sharpe & Dohme, 1985.

others have advocated the use of vaccine skin tests in egg-sensitive patients to predict the likelihood of a systemic reaction to a vaccine containing viruses grown in avian embryos or whole eggs) -5 The combined M M R vaccine was not evaluated in any of these studies. The American Academy of Pediatrics currently recommends a compreI

MMR

Mumps-measles-rubella

hensive, time-intensive screening protocol using a series of three vaccine skin tests to determine the safety of immunization with such vaccines in egg-allergic children: The objective of this study was to assess the reliability of a negative intradermal skin test in which a 1:100 dilution of M M R vaccine is used in predicting the safety of M M R immunization in egg-allergic children. METHODS The patient population consisted of 17 children, 15 to 36 months of age, referred from family practice or pediatric