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Biomedical subjects

F E Simons

Publications and source records attributed to F E Simons.

At least 19 recordsLinked to original sources
PubMed2001

Income-based drug benefit policy: impact on receipt of inhaled corticosteroid prescriptions by Manitoba children with asthma.

BACKGROUND: Drug benefit policies are an important determinant of a population's use of prescription drugs. This study was undertaken to determine whether a change in a provincial drug benefit policy, from a fixed deductible and copayment system to an income-based deductible system, resulted in changes in receipt of prescriptions for inhaled corticosteroids by Manitoba children with asthma. METHODS: Using Manitoba's health care administrative databases, we identified a population-based cohort of 10,703 school-aged children who met our case definition for asthma treatment before and after the province's drug benefit policy was changed in April 1996. The effects of the program change on the probability of receiving a prescription for an inhaled corticosteroid and on the mean number of inhaled corticosteroid doses dispensed were compared between a group of children insured under other drug programs (the comparison group) and 2 groups of children insured under the deductible program: those living in low-income neighbourhoods and those living in higher-income neighbourhoods. All analyses were adjusted for a measure of asthma severity. RESULTS: For higher-income children with severe asthma who were covered by the deductible program, the probability of receiving an inhaled corticosteroid prescription and the mean annual number of inhaled corticosteroid doses declined after the change to the drug policy. A trend toward a decrease in receipt of prescriptions was also observed for low-income children, but receipt of prescriptions was unaltered in the comparison group. Before the policy change, among children with severe asthma, the mean annual number of inhaled corticosteroid doses was lowest for low-income children, and this pattern persisted after the change. Among children with mild to moderate asthma, those covered by the deductible program (both low income and higher income) were less likely to receive prescriptions for inhaled corticosteroids than those in the comparison group, and this difference was statistically significant for the higher-income children. INTERPRETATION: The change to an income-based drug benefit policy was associated with a decrease in the use of inhaled corticosteroids by higher-income children with severe asthma and did not improve use of these drugs by low-income children.

Administration, Inhalation↗
PubMed2001

Socioeconomic status, drug insurance benefits, and new prescriptions for inhaled corticosteroids in schoolchildren with asthma.

BACKGROUND: Low-income children with asthma are less likely to receive inhaled corticosteroid prescriptions that can prevent asthma morbidity. OBJECTIVE: To determine whether the receipt of inhaled corticosteroids in children with asthma is related to household socioeconomic status and type of drug insurance. DESIGN: Using population-based prescription and health care data from Manitoba, a cohort study of the determinants of receiving new prescriptions for inhaled corticosteroids was conducted in children treated with asthma drugs. PARTICIPANTS: School-aged children (n = 12 481) receiving asthma prescriptions from January 1995 to March 1996 but no inhaled corticosteroid prescriptions in the initial 6-month period. MAIN OUTCOME MEASURES: Household socioeconomic and drug insurance predictors of the probability of receiving a new inhaled corticosteroid prescription from July 1995 to March 1998, following adjustment for disease and health care utilization factors. RESULTS: In comparison with higher-income children insured through a provincial cost-sharing drug plan, the adjusted likelihood ratio for a new inhaled corticosteroid prescription was 0.88 (95% confidence interval, 0.80-0.97) in low-income children insured through the same drug plan and 0.82 (95% confidence interval, 0.76-0.88) in children receiving prescriptions at no charge through provincial income assistance or First Nations benefits programs (Winnipeg, Manitoba). CONCLUSION: Independent of asthma severity, type of drug insurance, or health care utilization patterns, low-income children with asthma are significantly less likely to receive inhaled corticosteroid prescriptions.

Adolescent↗
PubMed2001

In vivo stability of human chemokine and chemokine receptor expression.

Cross-sectional analyses of human PBMC, plasma, and tissue have reported altered chemokine and/or chemokine receptor expression in several inflammatory diseases. Interpretation of such studies is difficult without data on the in vivo stability of such parameters. Using four color flow cytometry, we longitudinally followed CXCR3, CCR5 (Th1-associated), and CCR3 (Th2-associated) expression within CD4+/CD45RO+ and CD8+/CD45RO+ T cell populations in peripheral blood of healthy individuals over a 21 day period. In parallel, we quantified plasma levels of IP-10, Mig, eotaxin and TARC. Chemokine and receptor expression differed markedly between subjects but was highly stable, varying by <5% within individuals. Differences in chemokine receptor expression between subjects were markedly altered when quantified as absolute cell numbers rather than frequencies. Finally, CCR3 expression by CD4+/CD45RO+ T cells was positively correlated with plasma levels of its ligand, eotaxin, whereas strong negative correlations were evident between CXCR3 expression and IP-10 or Mig. These data demonstrate longitudinal stability of chemokine receptor and ligand expression among healthy individuals; reveal that both frequency and absolute cell count analysis is essential for accurate assessment of chemokine receptor expression; and identify inverse relationships between type 1 and type 2 immunity-associated receptors and their ligands in vivo.

Adult↗
PubMed2001

Epinephrine dispensing for the out-of-hospital treatment of anaphylaxis in infants and children: a population-based study.

BACKGROUND: Epinephrine is life-saving in the treatment of anaphylaxis. A limited number of fixed-dose epinephrine formulations are available for out-of-hospital treatment of this disorder. OBJECTIVE: To examine dispensing patterns for epinephrine formulations over 4 consecutive years in a population of 279,638 infants, children, and adolescents (from birth up to but not including the 17th birthday). METHODS: We used the Drug Programs Information Network, an administrative claims database for prescriptions dispensed in ambulatory care settings, developed from real-time computer links with retail pharmacies in the province of Manitoba, Canada. We studied the specific epinephrine formulation dispensed and the precise age of the infant or child at the time it was dispensed. RESULTS: Epinephrine formulations were dispensed for 1.2% of the pediatric population (3,340 children). Boys comprised 59.5% of the recipients. Of all epinephrine formulations, 38.6% were dispensed as EpiPen Jr (0.15 mg), and 57.4% were dispensed as EpiPen (0.3 mg). EpiPen Jr was dispensed for patients ranging in age from 2 months to 16 years, 10 months, inclusive. EpiPen was dispensed for patients ranging in age from 1 year, 8 months to 16 years, 11 months, inclusive. During the 4 years studied, a subgroup of children transitioned from EpiPen Jr to EpiPen auto-injectors at a mean age of 6 years, 6 months +/- 2 years, 8 months (range 1 year, 10 months to 16 years, 11 months). CONCLUSIONS: Both EpiPen Jr and EpiPen auto-injectors were dispensed over almost the entire age range of the pediatric population. Physicians should consider a child's age more carefully when prescribing these auto-injectors. Additional concentrations of epinephrine are needed in these fixed-dose formulations.

Adolescent↗
PubMed2001

Suppression of the early and late cutaneous allergic responses using fexofenadine and montelukast.

BACKGROUND: The relative contribution of histamine and the cysteinyl leukotrienes to the early and late cutaneous allergic responses (ECAR and LCAR) can be studied using antagonists of these mediators. OBJECTIVE: To determine the relative suppression of the ECARs and LCARs using standard doses of an H1-receptor antagonist, a cysteinyl leukotriene1-receptor antagonist, and the two antagonists administered concurrently. METHODS: We carried out a prospective, randomized, double-blind, placebo-controlled, four-way crossover study in 12 highly allergic participants. Intradermal tests with standardized allergen, and with histamine phosphate, LTD4, and saline controls were performed on 5 different test days as follows: pretreatment baseline and at steady state immediately after the seventh and last dose of a 1-week course of treatment with once-daily fexofenadine, 120 mg; montelukast, 10 mg; fexofenadine and montelukast administered concurrently; or placebo. On each test day, the skin test results were read at intervals from 0.25 to 24 hours after the intradermal injections were performed. RESULTS: After allergen injection, compared with baseline, all treatment regimens significantly decreased the ECAR and LCAR. After allergen injection, compared with placebo, fexofenadine significantly decreased the ECAR and the LCAR from 0.25 to 2 hours and at 8 hours. Montelukast did not significantly decrease the ECAR or LCAR. Fexofenadine and montelukast administered concurrently were not more effective than fexofenadine alone at any time. In the control skin tests, compared with placebo, fexofenadine, but not montelukast, significantly decreased the histamine-induced response, and montelukast, but not fexofenadine, significantly decreased the LTD4-induced response. CONCLUSIONS: Fexofenadine and montelukast administered concurrently were not significantly more effective than fexofenadine alone in decreasing the ECAR and LCAR. Montelukast does not need to be discontinued before allergen skin testing. Further studies of the effect of concurrent treatment with higher doses of a histamine antagonist and a leukotriene modifier on the allergic response in the skin are needed.

Acetates↗
PubMed2001

Skin concentrations of H1-receptor antagonists.

BACKGROUND: H1-receptor antagonists are widely used in the treatment of allergic skin disorders. OBJECTIVE: We sought to evaluate the extent of fexofenadine and diphenhydramine distribution into the skin concomitantly with their peripheral H1-receptor antagonist activity. METHODS: In a prospective, randomized, double-blind, parallel-group study, 7 men received 120 mg of fexofenadine, and 7 received 50 mg of diphenhydramine. Before dosing; at 1, 3, 6, 9, and 24 hours after the first dose; and at 168 hours (steady-state), 12 hours after the seventh and last daily dose, blood samples and skin punch biopsy specimens were obtained, and epicutaneous tests with histamine phosphate, 1 mg/mL, were performed. RESULTS: Fexofenadine penetrated the skin to a significantly greater extent than diphenhydramine at 6, 9, 24, and 168 hours (P < or = .05). Maximum skin/plasma ratios of both the H1-antagonists (41.3 +/- 7.8 for fexofenadine and 8.1 +/- 4.4 for diphenhydramine) were obtained at 24 hours. Fexofenadine also produced significantly greater suppression of wheals at 3, 6, and 9 hours and of flares at 3, 6, 9, and 168 hours compared with diphenhydramine (P < or = .05). CONCLUSION: In disorders in which the presence and the effects of H1-receptor antagonists in the skin are clinically relevant, our results support the use of fexofenadine and indicate the need to re-examine the role of diphenhydramine.

Adult↗
PubMed2001

Prevention of acute urticaria in young children with atopic dermatitis.

BACKGROUND: There are no published prospective, randomized, double-blind, placebo-controlled studies of urticaria prevention in children. OBJECTIVE: Our objective was to study the effect of long-term treatment with the H(1)-receptor antagonist cetirizine in the prevention of urticaria in young children with atopic dermatitis. METHODS: In the prospective, double-blind, parallel-group Early Treatment of the Atopic Child study, 817 children with atopic dermatitis who were 12 to 24 months of age at study entry were randomized to receive either cetirizine, 0.25 mg/kg, or matching placebo twice daily for 18 months and to be followed up for an additional 6 months, during which time the study medication code remained unbroken. During both these double-blind phases of the study, for a total of 24 months, caregivers prospectively recorded all symptoms and events, including hives, in a diary on a weekly basis when the child was well and on a daily basis when a symptom or event was observed. The diaries were reviewed and validated with the investigators at each regularly scheduled study visit. RESULTS: Acute urticaria occurred in 16.2% of the placebo-treated children and in 5.8% of the children treated with cetirizine (P <.001). The protective effect of cetirizine disappeared when treatment was stopped. In the study population as a whole, urticaria episodes were most commonly associated with intercurrent infection or with food ingestion or direct skin contact. CONCLUSION: Acute urticaria is common in toddlers with atopic dermatitis and can be prevented with cetirizine in this high-risk population.

Acute Disease↗
PubMed2001

Epinephrine absorption in adults: intramuscular versus subcutaneous injection.

We report a prospective, randomized, blinded, placebo-controlled, 6-way crossover study of intramuscular versus subcutaneous injection of epinephrine in young men. Peak plasma epinephrine concentrations were significantly higher (P < .01) after epinephrine was injected intramuscularly into the thigh than after epinephrine was injected intramuscularly or subcutaneously into the upper arm. We recommend intramuscular injection of epinephrine into the thigh as the preferred route and site of injection of this life-saving medication in the initial treatment of anaphylaxis.

Absorption↗
PubMed2001

Epinephrine for the out-of-hospital (first-aid) treatment of anaphylaxis in infants: is the ampule/syringe/needle method practical?

BACKGROUND: Little information is available about administration of an accurate epinephrine dose to infants experiencing anaphylaxis outside the hospital setting. OBJECTIVE: Our purpose was to perform a prospective, controlled study of (1) the time needed by parents to draw up an infant epinephrine dose from an ampule and (2) the dose accuracy. METHODS: We gave 18 parents written instructions and asked them to draw up epinephrine 0.09 mL. We timed them by means of a stopwatch and measured the epinephrine content (in micrograms) in each dose by using HPLC-UV. Eighteen resident physicians, 18 general duty nurses, and 18 emergency department nurses served as controls. RESULTS: The parents took significantly longer (P < .05) than the controls to draw up the dose; the mean (+/- SEM) times were 142 +/- 13 seconds (range, 83-248) for the parents, 52 +/- 3 seconds (range, 30-83) for the physicians, 40 +/- 2 seconds (range, 26-71) for the general duty nurses, and 29 +/- 0.09 seconds (range, 27-33) for the emergency department nurses. The control groups did not differ significantly from each other in speed (P > .05). The epinephrine content of the doses drawn up by the parents ranged 40-fold in contrast to the physicians' doses (7- to 8-fold), general duty nurses' doses (3-fold), and emergency department nurses' doses (2-fold). The mean epinephrine content did not differ significantly (P > .05) among the 4 groups. CONCLUSIONS: Most parents were unable to draw up an infant epinephrine dose rapidly or accurately. Most health care professionals drew up the dose rapidly; however, their accuracy was compromised by inherent variations of epinephrine concentrations in the ampules (United States Pharmacopeia compendial limits, 90% to 115%) and the inherent difficulty of measuring low volumes (<0.1 mL) of epinephrine. User-friendly premeasured epinephrine doses suitable for infants should be developed.

Anaphylaxis↗
PubMed2001

Montelukast added to budesonide in children with persistent asthma: a randomized, double-blind, crossover study.

OBJECTIVE: We tested the hypothesis that adding montelukast to budesonide would improve asthma control in children with inhaled glucocorticoid-dependent persistent asthma. STUDY DESIGN: In a multicenter, randomized, double-blind, crossover study, we compared the benefit of adding montelukast, 5 mg, or placebo once daily to budesonide, 200 microg, twice daily. RESULTS: After a 1-month run-in with budesonide, 200 microg, twice daily, 279 children were randomized to montelukast or placebo. The mean +/- SD age was 10.4 +/- 2.2 years, the mean forced expiratory volume in 1 second (FEV(1)) was 77.7% +/- 10.6% predicted, and reversibility was 18.1% +/- 12.9%. Compared with adding placebo to budesonide, adding montelukast produced significant improvements in mean percent change from baseline FEV(1) (P =.062 [P =.010 for per-protocol analysis]), mean absolute change from baseline FEV(1) (P =.040), mean increase from baseline in morning (P =.023) and evening (P =.012) peak expiratory flows, decrease in exacerbation days by approximately 23% (P <.001), decreased beta2-agonist use (P =.013), and reduced blood eosinophil counts (P <.001). The treatments did not differ significantly with regard to safety. CONCLUSIONS: Montelukast, 5 mg, added to budesonide improved asthma control significantly, indicated by a small additive effect on lung function and a clinically relevant decrease in asthma exacerbation days.

Acetates↗
PubMed2001

CpG oligodeoxynucleotide vaccination suppresses IgE induction but may fail to down-regulate ongoing IgE responses in mice.

Antigen-specific IgE plays an important role in the pathogenesis of allergic disorders. Immunostimulatory CpG motifs (CpG) in bacterial DNA or synthesized oligodeoxynucleotides (ODN) are gaining recognition as potential immunomodulators for switching on protectiveT(h)1-mediated immunity and preventing or potentially inhibiting T(h)2-dependent allergic responses. To date, allergic models used in CpG ODN studies have been established by immunization of mice with allergen in the presence of adjuvant. This, in addition to failure to assess specific IgE production in most of the studies, has limited understanding of the role of CpG ODN vaccination in allergic responses. Here, we examine the effects of synthesized CpG ODN on both developing and ongoing IgE responses in mice sensitized using a recombinant mosquito salivary antigen (rAed a 2) without adjuvant. Pretreatment of mice with CpG ODN mixed with rAed a 2 successfully inhibited subsequent induction of serum rAed a 2-specific IgE (but not IgG1) and antigen-induced IL-4 and IL-5 production in spleen cells. This was associated with an increase of serum IgG2a and IL-12, and increased IFN-gamma and IL-12 production by spleen cells. In this model, however, co-administration of CpG ODN with rAed a 2 to presensitized mice failed to down-regulate ongoing IgE responses despite significant up-regulation of serum IL-12 and specific IgG2a. Strikingly, a transient skin delayed-type hypersensitivity reaction occurred in CpG ODN-treated mice. These observations provide a new insight into the potential therapeutic application of CpG ODN to allergic disorders.

Adjuvants, Immunologic↗
PubMed2001

Expression, purification, characterization and clinical relevance of rAed a 1--a 68-kDa recombinant mosquito Aedes aegypti salivary allergen.

Accurate diagnosis of mosquito allergy has been precluded by the difficulty of obtaining salivary allergens. In this study, we expressed, purified, characterized and investigated the clinical relevance of a recombinant Aedes aegypti salivary allergen, rAed a 1. Two cDNA segments were ligated together to form the full-length Aed a 1 gene. rAed a 1 was expressed using a baculovirus/insect cell system, and purified using a combination of anion-exchange and gel-filtration chromatography. The purified rAed a 1 bound to human IgE, as detected by ELISA, ELISA inhibition tests and immunoblot analyses. Epicutaneous tests with rAed a 1 and a commercial whole-body AE: aegypti extract, and AE: aegypti bite tests were performed in 48 subjects. Nine of 31 (29%) of the subjects with positive immediate bite tests also had a positive rAed a 1 immediate skin reaction and 32% had an positive immediate test to the commercial extract. Six of 33 (18%) of the subjects with positive delayed bite tests also had a positive rAed a 1 delayed skin reaction and 6% had a positive delayed test to the commercial extract. Furthermore, rAed a 1-induced flare sizes significantly correlated with mosquito bite-induced flare sizes. None of the subjects with negative bite tests had a positive skin test to rAed a 1 or to commercial extract. We conclude that the rAed a 1 has identical antigenicity and biological activity to native Aed a 1, can be used in the in vitro and in vivo diagnosis of mosquito allergy, and is more sensitive than mosquito whole-body extract for detecting delayed skin reactions.

Aedes↗
PubMed2000

Experimental approaches to analysis of immune dysregulation in human allergic disease.

Over the last 40 years, much attention has been directed towards identification of the immunologic, genetic and environmental factors that predispose towards development of allergic disease. An implicit assumption in many such studies is that clinical tolerance reflects from immunologic tolerance. Here we critically review the conceptual background and experimental data arguing for the alternative hypothesis that failure to develop atopic disease reflects the success of type 1 dominated immunity that constitutively impedes development of type 2 responses to environmental antigens, hence, clinical immediate hypersensitivity. We report that endogenous production of type 1 chemokines such as IP-10 by non-atopic individuals may play a substantive role in maintaining this putatively protective type 1 bias in non-atopic subjects. Polyclonal activators (superantigen TSST-1, anti-CD3, PHA) were used to activate distinct intracellular signaling pathways, inducing quantitatively different IFNgamma:IL-4 ratios in primary culture of human PBMC. In parallel, physiologic stimuli such as grass pollen or cat antigen were used to evaluate the impact of IP-10 on CD4 T cell dependant, chloroquine-sensitive cytokine synthesis. IFNgamma responses by non-atopic subjects were markedly increased in the presence of nM concentrations of rhIP-10 while type 2 cytokine synthesis remained unaffected. Optimal rIP-10 concentrations for promoting expression and maintenance of type 1 cytokine synthesis in vitro (0.1 to 10 ng/ml) were at or well below those generally used for chemotaxis (5 to 100 ng/ml). Collectively, our findings suggest a potential role for this T cell focused chemokine in maintaining the default type 1 responses usually caused to environmental antigens in non-atopic subjects. These may play a role in determining the relative susceptibility of individuals to develop atopic disease. Taken together with recent reports of other roles played by chemokines in shaping the nature of immune responses, the data suggest that constitutive, endogenous type 1 chemokine synthesis may play a homeostatic role in inhibiting development of atopic disease.

Allergens↗
PubMed2000

Clinical pharmacology of the H1-receptor antagonists cetirizine and loratadine in children.

H1-receptor antagonists are widely used in children but are not as well-studied in children as they are in adults. Our objective was to determine the onset and duration of action and the relative potency of the H1-receptor antagonists cetirizine and loratadine in children. We performed a prospective, randomized, placebo-controlled, double-blind, crossover, single-dose study of cetirizine and loratadine using suppression of the histamine-induced wheal and flare as the primary outcome. In 15 allergic children, mean age 9 years, compared with baseline, cetirizine (10 mg) suppressed the wheals and flares significantly from 0.25 to 24 h, achieving nearly 100% of flare suppression from 2 to 24 h, inclusive, and loratadine (10 mg) suppressed the wheals and flares significantly from 0.75 to 24 h, inclusive. Cetirizine suppressed the wheals and flares significantly more than loratadine from 0.25 to 1 h, inclusive, and at 0.5, 1, 2, 3, 5, 6, 7, and 24 h, respectively. Placebo also suppressed the wheal and flare significantly at some assessment times. Cetirizine and loratadine both have excellent antihistaminic activity in children, with a rapid onset of action and a 24-h duration of action in this population.

Anti-Allergic Agents↗
PubMed2000

Outdated EpiPen and EpiPen Jr autoinjectors: past their prime?

BACKGROUND: EpiPen and EpiPen Jr autoinjectors are often recommended for prehospital treatment of anaphylaxis. When these units become outdated, there may be a delay in replacing them. OBJECTIVES: Our purpose was to evaluate unused, outdated EpiPen and EpiPen Jr autoinjectors, obtained from patients at risk for anaphylaxis, for epinephrine bioavailability and epinephrine content. METHODS: We conducted a prospective, randomized, cross-over study of epinephrine bioavailability after injection from outdated autoinjectors in rabbits; controls included EpiPen and EpiPen Jr autoinjectors that had not expired ("in-date" autoinjectors) and intramuscular injection of 0.9% saline solution. In addition, the epinephrine content of the outdated EpiPen and EpiPen Jr autoinjectors was measured by a spectrophotometric method and an HPLC-UV method. RESULTS: Twenty-eight EpiPen and 6EpiPen Jr autoinjectors were studied 1 to 90 months after the stated expiration date. Most were not discolored and did not contain precipitates. Epinephrine bioavailability from the outdated EpiPen autoinjectors was significantly reduced (P <.05) compared with epinephrine bioavailability from the in-date autoinjectors. The inverse correlation between the decreased epinephrine content of the outdated autoinjectors, assessed with an HPLC-UV method, and the number of months past the expiration date was 0.63. CONCLUSIONS: For prehospital treatment of anaphylaxis, we recommend the use of EpiPen and EpiPen Jr autoinjectors that are not outdated. If, however, the only autoinjector available is an outdated one, it could be used as long as no discoloration or precipitates are apparent because the potential benefit of using it is greater than the potential risk of a suboptimal epinephrine dose or of no epinephrine treatment at all.

Anaphylaxis↗
PubMed2000

Can epinephrine inhalations be substituted for epinephrine injection in children at risk for systemic anaphylaxis?

BACKGROUND: For out-of-hospital treatment of anaphylaxis, inhalation of epinephrine from a pressurized metered-dose inhaler is sometimes recommended as a noninvasive, user-friendly alternative to an epinephrine injection. OBJECTIVE: To determine the feasibility of administering an adequate epinephrine dose from a metered-dose inhaler in children at risk for anaphylaxis by assessing the rate and extent of epinephrine absorption after inhalation. METHODS: We performed a prospective, randomized, observer-blind, placebo-controlled, parallel-group study in 19 asymptomatic children with a history of anaphylaxis. Based on the child's weight, 10, 15, or 20 carefully supervised epinephrine or placebo inhalations were attempted. Before dosing, and at intervals from 5 to 180 minutes after dosing, we monitored plasma epinephrine concentrations, blood glucose, heart rate, blood pressure, and adverse effects. RESULTS: Eleven children (mean +/- standard error of the mean: 9 +/- 1 years and 33 +/- 3 kg) in the epinephrine group were able to inhale 11 +/- 2 (range: 3-20) puffs, equivalent to 74% +/- 7% of the precalculated dose or 0.078 +/- 0.009 mg/kg. They achieved a mean peak plasma epinephrine concentration of 1822 +/- 413 (range: 230-4518) pg/mL at 32.7 +/- 6.2 minutes. Eight children (10 +/- 1 years of age and 33 +/- 5 kg) in the placebo group were able to inhale 12 +/- 2 (range: 8-20) puffs, 89% +/- 3% of the precalculated dose, and had a peak endogenous plasma epinephrine concentration of 1316 +/- 247 (range: 522-2687) pg/mL at 44.4 +/- 16.7 minutes. In the children receiving epinephrine compared with those receiving placebo, mean plasma epinephrine concentrations were not significantly higher at any time, mean blood glucose concentrations were significantly higher from 10 to 30 minutes, mean heart rate was not significantly different at any time, and mean systolic and diastolic blood pressures were not significantly increased at most times. After the inhalations of epinephrine or placebo, the children complained of bad taste and many experienced cough or dizziness. After inhaling epinephrine, 1 child developed nausea, pallor, and muscle twitching. CONCLUSIONS: Despite expert coaching, because of the number of epinephrine inhalations required and the bad taste of the inhalations, most children were unable to inhale sufficient epinephrine to increase their plasma epinephrine concentrations promptly and significantly. Therefore, we urge caution in recommending epinephrine inhalation as a substitute for epinephrine injection for out-of-hospital treatment of anaphylaxis symptoms in children.

Administration, Inhalation↗
PubMed1999

Epinephrine absorption after different routes of administration in an animal model.

BACKGROUND: The administration of epinephrine is the most important initial treatment in systemic anaphylaxis. PURPOSE: We wanted to determine the relationship between the route of epinephrine administration and the rate and extent of epinephrine absorption. METHODS: In a prospective, randomized, five-way crossover study in rabbits, we measured plasma epinephrine concentrations before, and at intervals up to 180 min after epinephrine administration by intramuscular or subcutaneous injection, or by inhalation, with intravenous epinephrine and intramuscular saline as the positive and negative controls, respectively. RESULTS: Maximum plasma epinephrine concentrations were higher, and occurred more rapidly, after intramuscular injection than after subcutaneous injection or inhalation, and were 7719+/-3943 (S.E.M.) pg/mL at 32.5+/-6.6 min, 2692+/-863 pg/mL at 111.7+/-30.8 min and 1196+/-369 pg/mL at 45. 8+/-19.2 min, respectively. Intravenous injection of epinephrine resulted in a plasma concentration of 3544+/-422 pg/mL at 5 min, and an elimination half-life (t(1/2)) of 11.0+/-2.5 min. In the saline control study, the endogenous epinephrine concentration peaked at 518+/-142 pg/mL. CONCLUSION: In this model, absorption of epinephrine was significantly faster after intramuscular injection than after subcutaneous injection or inhalation. The extent of absorption was satisfactory after both intramuscular and subcutaneous injections. Neither the rate nor the extent of absorption was satisfactory after administration by inhalation.

Absorption↗