Anaphylaxis =========== þ Where to inject epi? - best place is lateral thigh. [Simons, F. E., X. Gu, et al. (2001). "Epinephrine absorption in adults: intramuscular versus subcutaneous injection." The Journal of allergy and clinical immunology 108(5): 871-873.] 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. - Epi-Pen needles aren't long enough for fatter kids [Stecher, D., B. Bulloch, et al. (2009). "Epinephrine auto-injectors: is needle length adequate for delivery of epinephrine intramuscularly?" Pediatrics 124(1): 65-70.] OBJECTIVE: Studies show that intramuscular epinephrine results in peak plasma concentrations of epinephrine faster than the subcutaneous route, and therefore, epinephrine is recommended to be administered intramuscularly. The objective of this study was to determine if the needle length on epinephrine auto-injectors is adequate to deliver epinephrine intramuscularly in children. METHODS: Patients between the ages of 1 and 12 years who presented to a children's hospital were enrolled in the study. Ultrasound was used to determine the depth from the skin to the vastus lateralis muscle. The patient's body mass index was recorded. The data were analyzed using simple descriptive statistics, and logistic regression was used to identify variables that might predict whether or not the needle length was exceeded. RESULTS: A total of 256 children were enrolled. Of these, 158 children weighed less than 30 kilograms and would be prescribed the 0.15 mg epinephrine auto- injector. Nineteen of these children (12%) had a skin to muscle surface distance of >(1/2)'' and would not receive epinephrine intramuscularly from current auto-injectors. There were 98 children weighing >or=30 kilograms who would receive the 0.3 mg epinephrine auto-injector. Of these 98 children, a total of 29 (30%) had a skin to muscle surface distance of >(5/8)'' and would not receive epinephrine intramuscularly. CONCLUSION: The needle on epinephrine auto-injectors is not long enough to reach the muscle in a significant number of children. Increasing the needle length on the auto-injectors would increase the likelihood that more children receive epinephrine by the recommended intramuscular route. þ See also: Angioedema þ See also: Bites and Stings þ Catemenial anaphylaxis - is recurrent, cyclical anaphylaxis in women due to endogenous progesterone secretion. It can be treated with oophorectomy or hormone suppression. Reference: Rosens CD ROM line 16937 þ Epinephrine-resistant anaphylaxis - Patients taking beta blockers may experience epinephrine resistant anaphylaxis. This occurs when the beta effects of epinephrine are suppressed by the beta-blockers. The condition is treated by using glucagon 1 mg IV every 5 minutes PRN. Glucagon acts independently of alpha and beta receptors, and can counteract the systemic effects of anaphylaxis. Reference: Rosens CD Rom p 16989 þ IM or SQ epi better for anaphylaxis? þ Anaphylactoid Reactions to ACE inhibitors: I'm enclosing prepublication text from a Letter to the Editor to be published in an upcoming edition of the Journal of Emergency Medicine on this topic. I don't think many practitioners are aware of the possible therapeutic utility of fresh frozen plasma for ACE-I induced angioedema, to which Dr. Siegelson alludes. James Li **** draft, prepublication **** The Harvard Residency case presentation on angioedema (1) educates emergency physicians on the link between ACE-inhibitor therapy and potentially life-threatening pharyngeal or lingual edema. The patient presented received both H1 and H2 receptor antagonist and steroid intravenous therapy in an attempt to reverse her symptoms while airway equipment was being prepared. Treatment with epinephrine was also considered. Interestingly, none of these therapies have been demonstrated to be efficacious for such presentations (2), though their use is probably justified in cases where anaphylactic shock, rather than angioneurotic edema, is also a likely cause of a patient's symptoms. An alternative therapy which is less known but has ample justification in the literature, is the use of fresh frozen plasma (2-7), which serves to replenish C1 esterase inhibitor, a factor often deficient or depleted in patients with angioedema of uncertain origin. This is worth initiating if emergency airway management is being considered for a patient who presents with oropharyngeal angioedema, and often results in rapid and remarkable recovery. Though most efficacious for the hereditary form of angioneurotic edema, it may be useful in ACE-inhibitor induced edema as well (2,8), and likely is safer than epinephrine or a difficult intubation. As is common in our specialty, while the necessity of urgent therapy is readily apparent in most cases of angioneurotic edema seen by emergency physicians, the cause is not. James Li, M.D. Mount Auburn Hospital Division of Emergency Medicine Harvard Medical School References: 1. Nadel ES, Brown DF. Angioedema. J Emerg Med. 1998;16:477-9. 2. Gaboriau HP, Solomon JW. Angioneurotic edema. J La State Med Soc. 1997;149:50-2. 3. Delfino JJ, Sclaroff A, Gigio JA, Travis M. Management of a patient with hereditary angioneurotic edema. J Oral Surg. 1978;36:890-2. 4. Hamilton AG, Bosley AR, Bowen DJ. Laryngeal oedema due to hereditary angioedema. Anaesthesia. 1977;32:265-7. 5. Koeberle P, Pequenot-Jeannin C, Douge C, Barale F. Angioneurotic edema and anesthesia: preparation and perioperative monitoring. Ann Fr Anesth Reanim. 1994;13:417-20. 6. Hopkinson RB, Sutcliffe AJ. Hereditary angioneurotic oedema. Anaesthesia. 1979;34:183-6. 7. Cohen N, Sharon A, Golik A, Zaidenstein R, Modai D. Hereditary angioneurotic edema with severe hypovolemic shock. J Clin Gastroenterol. 1993;16:237-9. 8. Nussberger J, Cugno M, Amstutz C, Cicardi M, Pellacani A, Agostoni A. Plasma bradykinin in angiooedema. Lancet. 1998;351:1693-7. --------------- It would seem that the majority of you find that although most of the patients who develop angioedema secondary to ACE inhibitors present with massive edema of the tongue (which essentially occludes the oral cavity), that the patients usually do not have any problem with maintaining patentcy of their upper airways and that most patients resolve within 12-48 hours without requiring airway management in terms of intubation or cricothyrotomy. However, a small proportion require emergency airway management - usually in the ICU setting after they leave the ED. Some physicians suggest that a Nutrake or other emergency airway management device (required to perform an emergency cricothyrotomy) should be placed at the patients bedside. However, in my community hospital setting, this precaution would be of little help as the in-house physicians do NOT have the necessary skills required to perform emergency surgical airway techniques and the ENT physician is at home and usually > 30 minutes away from the hospital. I even think that some community-based ENT surgeons do not perform enough emergency cricothyrotomies to be able perform expeditiously when they eventually arrive at the hospital. By the way, I have also read the article in Emergency Medicine News by James Roberts where he shows color photographs of a patient who required an emergency cricothyrotomy - I was very impressed by the amount of anterior neck edema associated with the upper airway swelling in the patient, who had an emergency cricothyrotomy performed. I think that an emergency cricothrotomy in this setting would tax the skill of even the most technically-competent ED physician. Shouldn't we therfore be intubating all these patients prophylactically in the ED (or shortly after arrival by an anesthesiologist in the OR) BEFORE they develop an obstructed airway - on the basis that peforming an emergency surgical airway technique AFTER the patient develops an airway problem will be very difficult and associated with a high morbidity? Jeffrey. --------------------------------------------- >>Saw this same type of patient in the ED this week also. Recently started on >>captopril (two months), presented with angioedema so profound that the tongue >>was protruding from the mouth and occluding most of the oral cavity. No >>respiratory distress, unable to handle secretions. Craig B. Key, MD > >It seems that everybody is reporting tongue involvement in ACE >angioedema. Interestingly, I think all the cases I've seen that seemed >associated with ACE where all off this type, and I just can't remember, >for example, generalized angioedema or any other form of allergic >manifestation. This seems consistent with some litterature reports. >Most of these did response quite slowly to usual treatment, but I can't >remember we needed to intubated >any, since all did finally got better. > >Regards, > >Alain Vadeboncoeur MD > >_________________________________________________ > >DRUG-INDUCED, LIFE-THREATENING ANGIOEDEMA REVISITED > >Thompson, T., et al, Laryngoscope 103(1, Part 1):10, January 1993 > >BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors can produce >potentially life- threatening angioedema. At the same time, given their >therapeutic efficacy, and their relatively low incidence of side effects and >low cost, these agents are being used with increasing frequency. > >METHODS: The authors, from the Medical College of Virginia, report on 36 >patients with ACE inhibitor-induced angioedema involving structures of >the head and neck. The incidence of cases increased with time, from one >per year >between 1984 and 1987, to 14 in 1990. > >RESULTS: Although the interval between onset of ACE inhibitor therapy >(with enalapril, captopril, or lisinopril) and development of angioedema >ranged from a few hours to three years, most cases (26, or 72%) occurred >within the >first week of treatment (as has been similarly reported in other series). >Medical therapy used on these patients included IV diphenhydramine >hydrochloride (25mg every six hours until the edema had resolved), IV >Decadron for patients with laryngeal edema, and subcutaneous epinephrine >or nebulized racemic epinephrine in patients with airway obstruction. Immediate >airway intervention was used in six cases (17%). None of the patients >resumed ACE inhibitor therapy, and there were no recurrences. > >CONCLUSIONS: The frequency of ACE inhibitor-induced angioedema may >increase with increasing use of these agents. The authors also point out >that this potentially life-threatening reaction is most likely not IgE >mediated, and that airway compromise may not be corrected with standard >therapies such as anti-histamines, steroids, or epinephrine. > >15 references > >Copyright 1993 by Emergency Medical Abstracts - All Rights Reserved 06/93 >- #1 > > LIFE-THREATENING ANGIOEDEMA > >Barna, J.S., et al, Otolaryngol Head Neck Surg 103(5, Part 1):795, >November 1990 > >The ACE inhibitors enalapril and captopril have been associated with the >production of angioedema, which has been reported in 0.02% of patients >taking enalapril and 0.01% of those taking captopril. The authors, from >the Medical College of Virginia Hospitals in Richmond, report on ten >patients presenting to the ED with potentially life-threatening >angioedema that was related to treatment with enalapril (eight cases) or >captopril (two cases). The patients typically presented with edema of the >tongue, with or without complaints of dysphagia, and clinical evidence of >spread of the edema to include the floor of the mouth and supraglottic >structures. Two of the patients required intubation for airway >inadequacy. The patients reported initiation of enalapril or captopril >therapy from one day to one year prior to presentation. Treatment >included discontinuation of ACE inhibitor therapy, and administration of >epinephrine, Benadryl, and Decadron, and was associated with resolution >of signs and symptoms after 24-48 hours. A possible mechanism of >production of angioedema by ACE inhibitors is potentiation of bradykinin, >which is a vasopressor that contributes to the inflammatory response. The >authors suggest that a prolonged interval between >initiation of ACE inhibitor therapy and the onset of angioedema may >confuse the diagnosis, and that this condition may therefore be more >common than has >previously been appreciated. They note that clinicians should advise >patients on ACE inhibitor therapy of this rare but potentially fatal >complication. They further observe that conventional therapy may not be >effective, since ACE inhibitor-induced angioedema may not be mediated by >IgE, and cite the possible need for early surgical intervention. > >13 references > ------------------------------ I found abstract of article 2 and 8 in Jim's reference on treating ACE inhibitor angiooedema with FFP. . Alan Gaboriau HP - J La State Med Soc - 1997 Feb; 149(2): 50-2 >From NIH/NLM MEDLINE Number of References: 16 Abstract: Angioneurotic edema can involve the face and mucous membranes and can progress toward laryngeal obstruction and death. ACE inhibitors are the main etiology, followed by the hereditary forms and the acquired forms. Quantitative and qualitative measurements of C1 inhibitors are important to differentiate the common form of HAE from the variant form. Long-term therapy is based upon antifibrinolytics and androgen therapy. Fresh frozen plasma can be given for short-term therapy. Treatment of the acute attack is mainly supportive directed toward airway protection. Epinephrine, steroids, and antihistamine have not been proven to be efficacious. Anaesthesist 1996 Dec;45(12):1268-9 Abstract: Angio-oedema is a recognised complication of angiotensin converting enzyme (ACE) inhibitor therapy, occurring in 0.1% to 0.5% of patients taking captopril, enalapril, or lisinopril. This is the first report of severe angio-oedema complicating therapy with quinapril, a new, long-acting drug. CASE REPORT. A 74-year-old female had been taking quinapril (10 mg/day) nd diuretics (fixed combination of triamterene and hydrochlorothiazide) for arterial hypertension for 18 months without any complication. After a fracture of the ankle, the patient received spinal anaesthesia uneventfully for an osteosynthesis. Ten days postoperatively, she noted swelling of the lips and the left half of the tongue. Following intravenous injection of antihistamines and prednisolone, these symptoms regressed. However, a relapse occurred on the 16th postoperative day with rapidly increasing oedema of the lips, face, ventral collar area, and entire tongue. Despite high-dose steroids, dyspnoea developed within 2 h. Direct laryngoscopy was impossible, and a flexible bronchoscope was used for nasotracheal intubation. At this point, the diagnosis of ACE inhibitor-induced angio-oedema was made and quinapril was withdrawn. The patient recovered, tracheal extubation was performed after 48 h, and the later course was uneventful. DISCUSSION. This is the second report of angio-oedema as a postoperative complication in a patient on long-term and previously unremarkable ACE inhibitor therapy. The first reported case occurred immediately after oral intubation and was perhaps precipitated by mechanical irritation. In this case, it is likely that postoperative deterioration of renal function due to dehydration and diuretic therapy was the precipitant, as has been reported in patients on lisinopril without surgery. Despite a significant increase in angio-oedema associated with the use of long-acting ACE-inhibitors, there appears to be a lack of familiarity among anaesthesiologist and other emergency physicians concerning this adverse effect. Withdrawal of the drug is the only effective treatment. High-dose steroids may be helpful, but if there is beginning dyspnoea or stridor, early endoscopically controlled intubation or emergency tracheostomy is essential to avoid hypoxaemia and death, as has occurred in the past. Waldfahrer F - HNO - 1995 Jan; 43(1): 35-8 Abstract: Inhibitors of angiotensin converting enzyme (ACE) are suspected of inducing angioedemas in up to 0.2% of all patients. These angioedemas are mainly localized in the upper airways and therefore can cause severe airway obstruction and even death due to suffocation. We report the case of a 64-year-old man, who underwent emergency tracheotomy because of severe angioedema of the larynx, which was refractory to pharmacological treatment. We conclude that patients with ACE inhibitor-induced angioedemas should be observed by monitoring in an intensive care unit to ensure the possibility of early intubation, because conventional antiallergic-antiedematous therapy by histamine-receptor antagonists and corticosteroids is an insufficient, unreliable form of therapy in severe cases. Especially otolaryngologists should know about this uncommon potentially life-threatening side-effect of ACE inhibitors. Brandes A - Mund Kiefer Gesichtschir - 1997 Feb; 1(1): 68-70 Abstract: Although generally showing a low incidence of side effects, inhibitors of angiotensin-converting enzyme (ACE) may in rare cases induce angioedemas, mainly located in the oro-facial area and larynx. The interval between the beginning of the ACE inhibitor therapy and the occurrence of such angioedemas may range from a few hours to a few years. Here, the case of a 53-year-old man with massive swelling of the tongue after dental surgery is presented who had started with ACE inhibitor therapy only 24 h before. At admission to the clinic, obstruction of the upper airway due to the tongue swelling had already progressed so far that fiberoptic intubation was necessary. Additionally, the patient was treated with corticosteroids, antihistaminics and epinephrine, avoiding any further administration of the ACE inhibitor. The swelling resolved within 48-72 h. Dentists and physicians should take into consideration this potential side effect in patients treated with ACE inhibitors.