Incidence Of Anaphylactic Reactions Research Articles

Lidocaine-induced anaphylactic shock – A case report

IgE-mediated hypersensitivity reactions (HRs) to local anaesthetics are extremely uncommon. One of the most widely used local anaesthetics for minor dental and other surgical procedures is lidocaine. The incidence of anaphylactic reaction by Inj. Lidocaine among global population is <1%. The first anaphylactic reaction reported in 1902. A 69-year-old female patient shifted to community hospital emergency department. She presented with complaints of vertigo, anxiety, tachypnoea, hypoxia, and sudden onset of breathlessness. History revealed on administration of Inj. Lidocaine a local anaesthesia to her before knee surgery developed above-mentioned symptoms after 15 minutes. After receiving her from OT patient vitals observed as pulse rate-97bpm, GRBS-140mg/dl, blood pressure-170/70mmHg, spo95% with 0. On emergency basis treated her with anti-histamines (Inj. Chlorpheniramine), steroids (Inj. Hydrocortisone-400mg, Inj.solumedrol-1gm), oxygen support of 7 to 8 lit/min, after 4 days she recovered completely and discharged. We used a scale (Naranjo scale) to evaluate the severity of the adverse drug reaction as per scale, score was five that indicates probability of happening adverse reaction. We conclude the case as anaphylactic reaction to lidocaine could have been cause of the event. It is important to collect patients complete past medical history and their allergic history. Also by giving importance to drug sensitivity testing at least to the list of drugs that are reported to show allergic reactions or anaphylactic reactions in post marketing surveillance. Optimised management protocols can save both the patient life and dilemma faced by physicians.

Food-induced anaphylaxis in children up to 3-years-old— preliminary study

The aim of the study was to determine the frequency of food-induced anaphylaxis, analyze the symptoms, and the trigger factors in the group of the youngest children. The additional aim of the study is to estimate the frequency of anaphylaxis episodes in the population of children in the Kuyavian-Pomeranian Voivodeship. Retrospective analysis of medical records of 29 children aged 0-3 years that presented symptoms of food-induced anaphylaxis. Medical charts were reviewed using a collection of documents with the clinical data. The frequency of anaphylaxis was determined to be 0.3% of all hospitalized children aged 0-3 years and 1.9% of children suspected of food allergy. The mean age of an anaphylactic reaction was 12 ± 9 months. The most common symptom was mild-moderate urticaria. The respiratory symptoms were significantly more prevalent in toddlers than in infants (p = 0.148). Cardiac symptoms occurred only in the infant group, that is, in two (11%) infants. As a possible cause of the symptoms, in 18 (62%) cases, parents most often indicated the consumption of milk or milk-rice porridge. Anaphylaxis as the first manifestation of food-allergy was significantly more prevalent in infants than in older children (p = 0.0002). The incidence of anaphylactic reactions rated at 0.3% of all children hospitalized at this age. The most common symptoms of anaphylactic reaction were skin lesions. The primary cause of allergic reactions was cow's milk after first exposure at home. Anaphylaxis has different patterns of symptoms depending on the age of the child.

Perioperative anaphylaxis in children: A report from the Wake-Up Safe collaborative.

Anaphylactic reactions to antigens in the perioperative environment are uncommon, but they have a potential to lead to serious morbidity and/or mortality. The incidence of anaphylactic reactions is 1:37000 pediatric anesthetics, and substantially less than the 1:10000 to 1:20000 incidence in the adult population. Neuromuscular blocking agents, latex, and antibiotics are the most frequently cited triggers. To date, there is no comprehensive report on perioperative anaphylactic reactions in children in the United States. Using the Wake-up Safe database, we examined the incidence and consequences of reported perioperative anaphylaxis events. We reviewed the Wake-up Safe database from 2010 to 2017 and identified all reported instances of anaphylaxis. The triggering agent, timing, and location of the registered event, severity of patient harm, and preventability were identified. Narrative review of free-text comments entered by reporting centers was performed to determine presenting symptoms, and interventions required. Type of case was identified from procedure codes provided in mandatory fields. Among 2261749 cases reported to the Wake-up Safe database during the study period, perioperative anaphylactic reactions occurred in 1:36479 (0.003%). Antibiotics, neuromuscular blocking agents, and opioid analgesics were the main triggers. Forty-nine cases (79%) occurred in the operating room, and 13 cases (21%) occurred in off-site locations. Seven (11%) patients required cardiopulmonary resuscitation following the onset of symptoms. Thirty-five (57%) patients were treated with epinephrine or epinephrine plus other medications, whereas 5% were managed only with phenylephrine. Most cases (97%) required escalation of care after the event. Regarding case preventability, 91% of cases were marked as either "likely could not have been prevented" or "almost certainly could not have been prevented." The estimated incidence of anaphylaxis and inciting agents among the pediatric population in this study were consistent with the most recent published studies outside of the United States; however, new findings included need for cardiopulmonary resuscitation in 11% of cases, and estimated fatality of 1.6%. The management of perioperative anaphylaxis could be improved for some cases as epinephrine was not administered, or its administration was delayed. Fewer than half of reported cases had additional investigation to formally identify the responsible agent.

Injection ranitidine induced death

Ranitidine is a histamine-2-receptor antagonist. It was a commonly used drug. It holds excellent safety record. Anaphylactic reactions to ranitidine is uncommonly encountered. Death due to ranitidine is extremely a rare event and very few cases are reported world-wide. Clinical history, Lab investigations and histological data of a 43-Years old woman with negative history of allergic events, who died suddenly after the intra-venous administration of 50mg of intravenous ranitidine which was prescribed as a routine pre medication prior hysterectomy is presented below. Though the incidence of anaphylactic reactions is less with ranitidine, precautions to be taken prior administration of the drug and when such an event is encountered it should be promptly managed.

Anaphylactic Reaction to a Change in the Route of Administration of Abatacept: A Case Study

The incidence of anaphylactic reaction after the long-term use of abatacept has not been reported until now. Herein, we present a case of rheumatoid arthritis (RA) in which the patient experienced an anaphylactic reaction one year after initiation of treatment with abatacept. A 75-year-old woman visited our hospital with symptoms of bilateral knee pain and swelling. She was initially treated with methotrexate (6 mg/week increased to 8 mg/week). Two months later, because of inadequate response, self-injections of abatacept (subcutaneous; 125 mg every two weeks) were prescribed. However, 6 months later, because of frequent stomatitis, the methotrexate dose was decreased to 6 mg/week, which resulted in worsening of RA. We changed the route of abatacept administration from subcutaneous injection to intravenous infusion (500 mg/month as a drip). After 30 min of starting the drip, the patient experienced itchiness and drop in vital signs, which were managed using methylprednisolone (2 doses, 125 mg each), dopamine hydrochloride (8 mg/h), and oxygen therapy (flow decreased from 3 L/min to 1 L/min). Wheals and redness were treated with oral antihistamines. Six hours after the onset of the anaphylactic reaction, the vital signs were stabilized. On the subsequent day, the patient’s general state was confirmed to be normal. One month later, etanercept (25 mg) treatment was initiated. The patient is currently in remission. We recommend caution when changing the route of administration and dosage of abatacept in anti-cyclic citrullinated peptide antibody-positive patients or those with a history of mild infusion-related reaction.

Anaphylaxis

Anaphylaxis, a serious allergic reaction, is rapid in onset and marked by flushing, urticaria, angioedema, pruritus, bronchospasm, and abdominal cramping with nausea, vomiting, and diarrhea. It is not uncommon; approximate lifetime prevalence of anaphylaxis was estimated to be 0.5 to 2% or possibly higher due to the common academic belief that the incidence of anaphylactic reactions is underreported. Rarely, anaphylaxis may cause death, most commonly from drugs, foods, and insect stings. This review covers the epidemiology, etiology, pathogenesis, diagnosis, clinical manifestations, treatment, and prognosis. Figures show inflammatory pathways in allergic inflammation and mast cell degranulation and pathways of activation. This review contains 2 figures, 5 tables, and 72 references. Keywords: Anaphylaxis, allergy, shock, auto-injector epinephrine, inflammation, mast cell, venom

A 6 months retrospective observational study to assess the rationality and effectiveness of snake bite management in a tertiary care teaching hospital of rural Bengal, India

Background: Snake envenomation is a common life-threatening problem encountered all-over West Bengal particularly in the rural areas. There are a large number of patients attending the Emergency unit and being admitted to the Medicine ward, some in the intensive care unit (ICU) and intensive therapy unit (ITU) of the tertiary health care facilities. The objective of this study was to assess rationality and effectiveness of management of venomous snake bite following standard protocol – Standard treatment guidelines of Government of West Bengal and National snakebite management protocol of Government of India.Methods: This was a retrospective observational study of six months (May - October 2017) duration. Data were collected from the treatment records of patients admitted with history of snake bite in the Medicine ward, ICU and ITU of tertiary care teaching hospital of rural Bengal.Results: Of the 63 venomous bite patients, most (82.5 %) were diagnosed to have features of neurotoxic envenomation. All of them (100%) received anti-snake venom (ASV). There was no incidence of anaphylactic reaction as well as any serious adverse drug reaction following ASV administration. Two patients developed acute renal failure, needed haemodialysis. Overall percentage of mortality was 3.2%.Conclusions: The survival rate in venomous snake bite is found to be high in this institution. The practice of snake bite management is found to be adherent with standard protocol. A multicentric study of longer duration is suggested to draw a firm conclusion.

Incidence of anaphylactic reactions after propofol administration in dogs.

Propofol is an anesthetic agent suspended in an emulsion system that includes egg yolk lecithin and soybean oil, because of which, there is concern about the use of propofol in patients allergic to these substances. We examined the association between propofol administration and incidence of adverse events in dogs with allergy to egg yolk lecithin and soybean oil. On the basis of the findings of an allergen-specific immunoglobulin E (IgE) test, 14 dogs with high levels (high-IgE group) and 7 dogs with low levels (normal-IgE group) of IgE were selected. Following intravenous administration of propofol, the incidence of anaphylactic reactions and plasma histamine concentrations under general anesthesia maintained with isoflurane throughout surgery were compared between the two groups. The frequency of anaphylactic reactions and plasma histamine concentrations were compared by the chi-square test and Student t-test, respectively. The statistical significance for both tests was set at P<0.05. In the high- and normal-IgE groups, the average frequencies of anaphylactic reactions after propofol administration were 21.4 and 14.3%, and the mean plasma histamine concentrations were 167.9 ± 94.5 nM and 65.7 ± 40.3 nM, respectively. Animals of neither groups experienced shock-like symptoms. These results revealed that propofol might be relatively safe, although careful perioperative anesthesia monitoring and standby protocols are required when using propofol in dogs with a history of allergic diseases or high chicken- or soybean-specific IgE levels.

Epidemiology of perioperative anaphylaxis

Anaphylactic reactions may be either of immune (allergy, usually IgE-mediated, sometimes IgG-mediated) or non-immune origin. The incidence of anaphylactic reactions during anaesthesia varies between countries ranging from 1/1250 to 1/18,600 per procedure. In France, the estimated incidence of allergic reactions is 100.6 [76.2-125.3]/million procedure with a high female predominance (male: 55.4 [42.0-69.0], female: 154.9 [117.2-193.1]). The proportion of IgE-mediated allergic reactions seems to be relatively similar between countries, ranging from 50 to 60%. Substantial geographical variability regarding the different drugs or substances involved is reported. Reactions involving neuromuscular blocking agents are a major cause in several countries but are less frequently reported in the United States or Denmark. Reactions involving antibiotics, dyes or chlorhexidine are reported with a high and sometimes increasing frequency in most series. Reactions to latex are rapidly decreasing as a result of primary and secondary prevention policy. Regional differences are a strong incentive for repeated epidemiological surveys in different countries.

The allergic emergency – management of severe allergic reactions

Anaphylaxis is characterized by the sudden onset of acute allergic symptoms involving two or more organ systems. An acute allergic emergency is a challenge for physicians due to its life-threatening potential. The incidence of anaphylactic reactions has increased in recent years. Most frequent elicitors of mast cell and primarily histamine dependent anaphylactic reactions are food, insect venom or drugs. Allergic -reactions are graded into four groups according to the classification by Ring and Messmer; grade I is defined by the onset of cutaneous symptoms only whereas grade IV is characterized by cardiovascular shock as well as cardiac and/or respiratory arrest. The treatment of allergic reactions should be guided by the severity of the reaction. Initially an intramuscular epinephrine injection into the lateral thigh should be given if cutaneous, mucosal and cardiovascular/respiratory symptoms occur. Additionally, the patient should receive intravenous antihistamines and corticosteroids. For self-treatment in the case of an allergic emergency, oral antihistamines and corticosteroids should be prescribed to the patient.

Anaphylaxis in an emergency setting – elicitors, therapy and incidence of severe allergic reactions

Anaphylaxis is a severe potentially life-threatening hypersensitivity reaction with an estimated lifetime prevalence of 0.5-2.0%. The prevalence and incidence of anaphylactic reactions in Germany are unknown. We therefore assessed anaphylactic patients seen by emergency physicians in the Berlin area covering 4million people. A standardised questionnaire was filled from 2008 to 2010 by the emergency physicians. A total of 333 cases of anaphylaxis were reported. 295 of these met the inclusion criteria for severity and were analysed. 13.9% (n=41) were reactions with respiratory symptoms, 25.4% (n=75) with cardiovascular, and in 60.7% (n=179) of cases, respiratory and cardiovascular symptoms were reported. Two reactions were fatal. The most common elicitors were food products (32.2%), drugs (29.2%) and insect venom (19.3%). The most frequently given drugs were corticoids and antihistamines, but not adrenaline. For 2008, the calculated incidence was 4.5 per 100000. Our data show that food products are frequent elicitors of severe allergic reactions in the general population including children and adults. It unravels a strong underuse of adrenaline by emergency physicians, not reflecting treatment protocols according to the current guidelines. As data obtained from allergists reveal a different rank order of elicitors, this study suggests that food-allergic adult patients may present a risk population and should receive more attention by allergists.

Risque allergique en anesthésie

Anaphylactic reactions may be either of immune(allergy, usually IgE-mediated, sometimes IgG-mediated) or non-immune origin. The incidence of anaphylactic reactions during anaesthesia varies between countries ranging from 1/1250 to 1/13,000 per procedure. In France, the estimated incidence of allergic reactions is 100.6 [76.2-125.3]/million procedures with a high female predominance (male: 55.4 [42.0-69.0], female: 154.9 [117.2-193.1]). This predominance is not observed in children. In adults, the most frequently incriminated substances are neuromuscular blocking agents, followed by latex and antibiotics. The estimated incidence of allergic reactions to neuromuscular blocking agents is 184.0 [139.3-229.7]/million procedure. In most cases there is a close reaction between clinical symptoms and drug administration. When the reaction is delayed, occurring during the surgical procedure, a reaction involving latex, a vital dye, an antiseptic or a volume expanding fluid should be suspected. Reaction severity may vary. The most frequently reported initial symptoms are pulselessness, erythema, increased airway pressure, desaturation or decreased end-tidal CO2. Clinical symptoms may occur as an isolated condition, making proper diagnosis difficult. In some cases a cardiovascular arrest can be observed. Reaction mechanism identification relies on mediators (tryptase, histamine) measurement at the time of the reaction. In case of allergic reaction, the responsible drug can be identified by the detection of specific IgE using immunoassays or by skin tests performed 6 weeks after the reaction. Predictive allergy investigation to latex or anaesthetics in the absence of history of reaction should be restricted to at-risk patients. Premedication cannot prevent the onset of an allergic reaction. Providing a latex-free environment can be used for primary or secondary prevention. Treatment is based on allergen administration interruption, epinephrine administration in a titrated manner based on symptoms severity, and on volume expansion.

Photochemical Degradation of Glaphenine Solution

The aim of this work was to study the effect of light on glaphenine stability in solutions. Glaphenine solutions in various solvents, including alcohols, acidic alcohols, water and acidic aqueous media, were exposed to both artificial light source and solar radiation. The photodegradation was followed using different techniques including UV-visible spectrophotometry, spectrofluorometry, mass spectrometry, HPLC and TLC. Studying the effect of solvents on the stability showed that glaphenine is completely stable towards light in water and in acidic media. In neutral alcohols, the rate of photodecomposition was found to increase in the order methanol < ethanol < pentanol < butanol < propanol, which may be explained by solvent-solute interaction and viscous properties of the solvent. Two photodegraded products were separated and identified as a-glycerylanthranilate and 7-chloroquinoline. Drug molecules having particular structures may undergo photodegradation when irradiated with light. This necessitates the testing for photodecomposition in the preformulation stage to safeguard against such deterioration. Factors affecting photodecomposition differ between solid and liquid forms. Consequently, photodecomposed species need to be identified when possible, in solid and solution states. Glaphenine, a-glyceryl N-(7-chloro4-quinolyl) anthranilate, is an analgesic that has been used for the relief of all types of pain. Recently, its use has been limited by the high incidence of anaphylactic reactions. Glaphenine comprises anthranilic and quinoline nuclei, which show instability towards UV or visible radiation in solution (Fujishiro 1960; Stermitz et a1 1970). Glaphenine powder is stable against heat and moisture but undergoes photodegradation when exposed to UV-visible or solar radiation. The decomposition products are similar regardless of the method of radiation used. Two main photodecomposed products were identified as N(7-chloro-4-quinolyl) anthranilic acid and methyl N-(7-chloro-4-quinolyl) anthranilate; intramolecular abstraction leads to the formation of these photodegraded products (Badwan et a1 1992). It is of prime interest to compare the degradation products produced from solid state and those obtained Correspondence: A. A. Badwan, The Jordanian Pharmaceutical Manufacturing Co., PO Box 94, NAOR 11710, Jordan.

Anaphylactic Reactions Presented to the Emergency Department: Managment and Outcomes

The incidence of Anaphylactic Reactions (AR) in Israel is unknown at the present time. We decided to assess the clinical course, management, incidence, presumed causes, recommendations upon discharge and frequency of referrals to an allergy specialist in a central hospital's emergency department (ED). Management of AR in the ED was assessed retrospectively by reviewing file records from January 2004 to December 2005 based on a detailed questionnaire. All admissions with the primary diagnosis of AR, using international codes, were reviewed. Data included: age, sex, clinical management, presumed causes, discharge recommendations, including follow up care. Data was statistically analyzed to show the prevalence of AR in this patient group. Out of 173,864 admissions to SMC's ED during the years 2004-2005, diagnosis of AR was established in 46 cases. The rate of AR in this patient population was estimated at 26.45 per 100,000 admissions. 20 patients (43.4%) were treated by adrenalin at the ED. Surprisingly, only 13% of AR were coded as such at the ED and 24% after discharge from the hospital. 19 patients (42.2%) were referred to allergy specialist for further evaluation. The rate of AR presented to ED in a central hospital was similar to reported rates universally. Charts with the diagnosis of AR was frequently missed due of inappropriate coding by the present ICD system. Dispensing of Epi-pen was rarely made. Increased awareness and prompt diagnosis of AR will improve treatment of patients presented to the ED and further referrals to allergy specialists.

Anaphylaxis during anesthesia - role of skin prick testing in diagnosing multiple sensitivities.

The true incidence of anaphylactic reactions and their associated morbidity and mortality remain poorly defined. This is due to uncertainties in reporting accuracy and exhaustivity. A 23 years old male developed severe anaphylaxis under general anesthesia with cardiovascular collapse, bronchospasm and angio-edema. He was promptly managed with intravenous Adrenaline, Hydrocortisone, colloid solutions and Promethazine. The temporal relation suggested Atracurium to be the cause. However, skin prick test, performed 8 weeks later, showed a very strong (+++) positive test for Atracurium and mild sensitivity (+) with Suxamethonium. No sensitivity to Nalbuphine, Thiopentone or Pancuronium was noted. The relevant information was endorsed in patient's medical record sheet for his future exposure.

Vaccine adverse events reported in post-marketing study of the Kitasato Institute from 1994 to 2004

General physicians, pediatricians and parents realize that serious adverse events occur with an extremely rare incidence, but have no information on the incidences of vaccine-associated adverse events. A proper understanding of vaccine adverse events would be helpful in promoting an immunization strategy. Causal association can rarely be determined in adverse events through laboratory examinations. We examined the cases reported in the post-marketing surveillance of the Kitasato Institute, categorizing them into two groups: allergic reactions and severe systemic illnesses. Anaphylactic patients with gelatin allergy after immunization with live measles, rubella and mumps monovalent vaccines have been reported since 1993, but the number of reported cases with anaphylaxis dramatically decreased after 1999 when gelatin was removed from all brands of DPT. The incidence of anaphylactic reaction was estimated to be 0.63 per million for Japanese encephalitis virus (JEV) vaccine, 0.95 for DPT and 0.68 for Influenza vaccine, but the causative component has not yet been specified. Among 67.2 million immunization practices, 6 cases with encephalitis or encephalopathy, 7 with acute disseminated encephalomyelitis (ADEM), 10 with Guillain–Barré syndrome and 12 with idiopathic thrombocytopenic purpura (ITP) were reported. The wild-type measles virus genome was detected in a patient with encephalitis and in two of four bone marrow aspirates obtained from ITP after measles vaccination. Enterovirus infection was identified in two patients after mumps vaccination (one each with encephalitis and ADEM), one patient with encephalitis after immunization with JEV vaccine, and one with aseptic meningitis after immunization with influenza vaccine. The total estimated incidence of serious neurological illness after vaccination was 0.1–0.2 per million immunization practices. We found that enterovirus or wild-type measles virus infection was coincidentally associated with vaccination in several cases suspected of being vaccine adverse events.

Severe anaphylactic shock without exanthema in a case of unknown latex allergy and review of the literature

We describe a case of severe anaphylactic shock without exanthema in an 8-year-old boy who was undergoing elective surgery for an ileostomy. The boy had a history of four anorectal operations in the newborn period, but no history of allergies. Sudden, profound bronchospasm and cardiorespiratory collapse occurred 30 min after the beginning of the operation. No signs of exanthema or urticaria were seen. The patient was resuscitated successfully and remained ventilated for 25 h. During this time, he needed epinephrine in dosages of 0.3-0.05 microg.kg-1.min-1. Radioallergosorbent (RAST) tests for the patient were positive Cap Class 3 and 4, and specific immunoglobulin E was highly positive, suggesting a natural rubber latex allergy as the cause of the anaphylactic shock. Ethylene oxide was negative. Eleven days later, a further operation was performed with a strict latex-free protocol in the presence of histamine 1 and 2 receptor antagonists. On this occasion, the intraoperative course was uneventful. Incidence of anaphylactic reactions, prevalence of latex sensitization, special risk groups and management are discussed.

Incidence of anaphylaxis in the emergency department of a general hospital in Milan

Objective: To evaluate incidence and causes of anaphylactic reactions in the emergency room (E.R.) of a general hospital in Milan during a 2-year period. Methods: We retrospectively studied the computerized records of patients discharged from an E.R. with a diagnosis of anaphylactic reaction. Anaphylaxis was established on the presence of at least two cutaneous, respiratory, gastrointestinal or cardiovascular system symptoms. Results: During 1997 and 1998, out of 38 685 patients referred to the E.R., 13 had severe anaphylaxis with loss of consciousness (LOC) and 127 had anaphylactic symptoms, without LOC. Of the 13 patients with LOC, a possible cause was identified in 12 (five foods, six drugs, one hair dye). In the other 127 patients anaphylaxis was related to foods in 49 cases (38.5%), drugs in 44 (34.6%), unknown causes in 29 (22.8%), hymenoptera stings in two (1.5%), and other causes in three (2.3%). Conclusion: The incidence of anaphylactic reactions was 0.4% and mainly affected females and atopic subjects. Foods, particularly fruits and vegetables, appeared to be the most important cause; other important causes were non steroidal antiinflammatory drugs and β-lactam antibiotics.

Anaphylactic Shock to Neuromuscular Blocking Agent

THE incidence of anaphylactic reactions during anesthesia is estimated in France to be approximately 1/3,500 general anesthesia, 1-3 Muscle relaxants are the most common cause of anaphylactic reactions during anesthesia We report two cases of anaphylactic shock in relation to the administration of nondepolarizing neuromuscular blocking agents that occurred in the members of a family, which suggests that there may be a familial predisposing factor to anaphylactic reactions induced by muscle relaxants.

Hydroxyethyl starch antibodies in humans: incidence and clinical relevance.

Hydroxyethyl starch (HES) is a plasma expander used for perioperative i.v. fluid management, as well as for resuscitation from trauma and shock. HES is very well tolerated, and the incidence of anaphylactic reactions is lower than with dextran or gelatin. Dextran anaphylaxis is caused by circulating dextran-reactive antibodies (ABs) of the immunoglobin G (IgG) class found in most adults. Histamine release from mast cells induces adverse reactions after gelatin infusion. The cause of adverse reactions due to HES is not yet clear. To investigate AB formation due to HES, we collected sera of 1004 patients at least 14 days after starch administration. Using a highly sensitive enzyme-linked immunoabsorbent assay technique, we found one patient with a low 1:10 titer of HES-reactive ABs (immunoglobin M [IgM] class). Despite repeated HES infusions, no clinical reaction could be detected in this patient. On the basis of a binomial distribution, a one-tailed confidence interval (99%) was used to calculate the percentage of the occurrence of ABs in general with maximum of 33 in 10,000 persons (IgM) and 23 in 10,000 persons (IgG). We suggest that HES-reactive ABs are extremely rare and that they do not necessarily induce anaphylaxis. Other mechanisms may be responsible for adverse reactions due to HES. The frequency of antibody formation due to hydroxyethyl starch, a commonly used plasma expander, was prospectively investigated in 1004 patients. Only one patient showed transient antibody formation, which was not harmful to the patient. This low antigenicity could explain the excellent tolerance of hydroxyethyl starch compared with other plasma expanders.