Treatment of anaphylaxis with parenteral unfractionated heparin in a porcine model

Study objectives: Heparin binds mast cell mediators and has been proposed as a treatment for systemic anaphylaxis. It is used for this purpose in some otolaryngologic practices. No current evidence exists for the efficacy of heparin as a treatment for anaphylaxis. This study compares heparin with placebo and standard therapy in an experimental model of anaphylaxis. Methods: The study design was a controlled study comparing unfractionated heparin with placebo and standard therapy with epinephrine and diphenhydramine. The setting was a university animal laboratory. Subjects were 9 anesthetized pigs weighing 11 to 16 kg. Arterial lines were placed to monitor mean arterial blood pressure (MAP) and for phlebotomy. Cardiac rhythm was monitored continuously. Serum histamine levels were measured before and after injection using an enzyme-linked immunosorbent assay technique. Calcium ionophore A23187 was obtained (Sigma-Aldrich, St. Louis, MO) and resuspended in dimethyl sulfoxide at a concentration of 50 mg/mL. A23187 was administered intravenously at a dose of 0.5 mg/kg. At the onset of shock, defined as a greater than 20% decrease in MAP, 3 pigs received intravenous heparin at a dose of 100 U/kg, 3 pigs received a saline placebo injection of equal volume, and 3 pigs received epinephrine 0.01 mg/kg with diphenhydramine 1.0 mg/kg. Data were analyzed using Wilcoxon rank sum and analysis of variance as appropriate. Results: Before administration of A23187, there were no differences between the groups in terms of MAP and pulse rate. All 9 pigs developed generalized flushing. Hypotension developed in all pigs, with MAP decreasing from 73±9.6 mm Hg to 28±16 mm Hg. Mean histamine increased from 712±731 μmol/dL to 1154±799 μmol/dL. Treatment with heparin increased MAP from a low of 27.6±5.26 to 106±16.5 mm Hg. Treatment with epinephrine plus diphenhydramine increased MAP from a low of 35.3±8.7 to 134.3±8.6 mm Hg. The mean time from administration of heparin to reversal of hypotension was 5.667±1.453 minutes versus 3.667±0.883 minutes for epinephrine and diphenhydramine ( P =.3046). In the placebo group, MAP decreased from 20.0±23.5 to 5.3±9.2 after saline injection. Both heparin and standard therapy were superior to placebo in improving MAP, with P values of .0007 and .0002, respectively. Standard therapy improved MAP more than heparin, although this trend was not statistically different ( P =.124). Administration of placebo had no effect on hypotension, and 2 of 3 pigs receiving placebo died. One of 3 pigs in the standard therapy group arrested but was successfully resuscitated with treatment. Conclusion: In this experimental model, heparin reversed anaphylactic shock and was superior to placebo. Compared with that of standard therapy, the onset of action of heparin was delayed, although this preliminary investigation did not have the power to detect a difference. According to this study, epinephrine and diphenhydramine remain the treatments of choice for anaphylactic shock. Further investigation is needed to determine what, if any, is the role of heparin in clinical practice.