Biphasic Anaphylaxis
Biphasic Anaphylaxis
By Richard Harrigan, MD
Associate Professor of Emergency Medicine, Temple University School of Medicine, Philadelphia, PA
Source: Smit de V, et al. Anaphylaxis presentations to an emergency department in Hong Kong: Incidence and predictors of biphasic reactions. J Emerg Med 2005;28:381-388.
Anaphylaxis is one disease entity that has the respect of any emergency physician who has encountered it; multisystem effects and rapid progression make it a true emergency that requires quick diagnosis and treatment. Furthermore, the specter of recurrence after the initial anaphylactic reaction has been terminated successfully termed a "biphasic reaction" is well reported; yet, the expected duration of time between cessation and recurrence has been difficult to characterize. To study this entity is challenging; the nature of the disease does not lend itself to a randomized, placebo-controlled trial. Most of the literature on the subject is in the form of case reports and case series, as well as review papers. This retrospective chart review of a four-year experience in a busy Asian emergency department (ED) with an annual census of approximately 200,000 adds to the current understanding of the presentation and clinical course of anaphylaxis.
Inclusion criteria were based upon capturing patients who were triaged by nursing staff to the resuscitation room with suspected anaphylaxis; a variety of synonyms for the disease and it manifestations were used to select patients from resuscitation room log book records. Patients then were excluded if charts were not available or the physician’s discharge diagnosis was not anaphylaxis. Biphasic reactions were defined as any reaction occurring after initial treatment and resolution of symptoms either in the ED or after admission to the ED observation unit or to the inpatient setting. After only nine exclusions, 282 patients were found to meet study criteria. A variety of clinical and demographic data were then reported. The capricious nature of the syndrome was evidenced in that no clinical feature occurred in more than 80% of the patients—the top four were urticaria (79%), flushing/pruritis (74%), dyspnea (66%), and angioedema (61%). More than 90% were treated with steroids and antihistamines—predominantly H1 blockers—only 4% received H2 blockade. Apparently, this is a hospital-specific phenomenon. Only 67% received epinephrine. Ninety-six percent were admitted: more than half to the observation unit (planned stay 12-24 hours) and 8% to the intensive care unit. Astonishingly, the median ED length-of-stay was 42 minutes. (That is most assuredly not happening in my ED!)
Fifteen patients (5.3%) experienced a biphasic reaction. The mean time from ED presentation to onset of the biphasic reaction was slightly more than 8 hours (SD 5.46, range 1.4-23 hours), and the mean time from initiation of treatment to biphasic reaction was approximately 7½ hours (SD 5.46, range 1.2-22.5 hours). In those patients who developed a biphasic reaction, cutaneous manifestations were more common and respiratory features less common—but this finding maybe only incidental. The majority of biphasic reactions were mild, and the symptoms of recurrence were similar to those on initial presentation. In the 15 patients who had a biphasic reaction, the onset was more than 8 hours after presentation in eight patients. Had all patients been observed for 24 hours after presentation, no one would have been discharged before developing his biphasic reaction. There were no fatalities in this study.
Commentary
This was the largest case series to date reporting on biphasic reactions in anaphylaxis. Previous reports (See Table) described similarly low rates of 3-6%—close to that seen in this study (5.3%).1-3 Other studies have reported higher rates: 18% 4 and 20%.5 These studies had lower enrollment numbers (34 and 25, respectively); thus, if one fewer case were included in each, the incidence would have dropped to about 15%. Therefore, what can we take away from this observational study about the nature of biphasic reactions? As in previous studies, they seem to be hard to predict, generally well tolerated, and seem to mimic the initial presentation in terms of clinical features. The time to onset of the second phase seen in this study and others includes some fairly late presentations. It appears that observing people for 24 hours is safest, but is not always feasible or necessary. Knowledge of the potential for biphasic reactions emphasizes the point that all patients discharged after treatment for anaphylaxis should be given a prescription for injectable epinephrine, along with instructions on how and when to use the drug.
This study suffered some of the usual limitations of most retrospective studies (e.g., the incidence of the various clinical features depends upon the clinicians’ documentation of those features). Follow-up seemed fairly tight in this study. All Hong Kong residents have unique identification numbers that allowed the authors to search for their reappearance at the study hospital as well as other institutions; therefore, it is likely that the reported incidence of biphasic reactions is valid. Perhaps the term anaphylaxis was applied a little too broadly in patient recruitment—only 94% of patients had more than one organ system affected—yet, the definition of anaphylaxis includes the term "multisystem." Nonetheless, this study is a valuable addition to the anaphylaxis literature.
References
1. Douglas DM, et al. Biphasic systemic anaphylaxis: an inpatients and outpatient study. J Allergy Clin Immunol 1994; 93:977-985.
2. Lee JM, et al. Biphasic anaphylactic reactions in pediatrics. Pediatrics 2000; 106:762-766.
3. Brady WJ Jr, et al. Multiphasic anaphylaxis: An uncommon event in the emergency department. Acad Emerg Med 1997; 4:193-197.
4. Stark BJ, et al. Biphasic and protracted anaphylaxis. J Allergy Clin Immunol 1986;78:76-83.
5. Brazil E, et al. "Not so immediate" hypersensitivity the danger of biphasic anaphylactic reactions. J Accid Emerg Med 1998; 15:252-253.
Anaphylaxis is one disease entity that has the respect of any emergency physician who has encountered it; multisystem effects and rapid progression make it a true emergency that requires quick diagnosis and treatment.Subscribe Now for Access
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