Propofol Infusion and Acute Pancreatitis: A Review.

BACKGROUND: Propofol is a short-acting anesthetic used to induce sedation in various ambulatory and inpatient surgical procedures. It is a US Food and Drug Administration approved lipid-based intravenous hypnotic agent, which has been used clinically for the induction and maintenance of anesthesia for over 3 decades. In addition to general anesthesia, it is used to sedate patients undergoing mechanical ventilation or short procedures such as endoscopy, transesophageal echocardiogram, and abscess drainage. An infrequent but serious complication of propofol is acute pancreatitis (AP), with potentially significant morbidity and possible mortality. In this review, we will discuss the proposed mechanisms of AP secondary to propofol, a number of reported cases, studies conducted, and treatment strategies. AREAS OF UNCERTAINTY: There are several case reports in the literature that have shown an association between propofol and pancreatitis. The exact mechanism behind propofol-induced pancreatitis is not fully understood, but proposed mechanisms include hypertriglyceridemia (HTG), hypersensitivity, or direct pancreatic toxicity of the drug. Although the association of propofol and pancreatitis has not been proven conclusively, clinicians should be aware of this possible rare complication to prevent the devastating consequences of AP. DATA SOURCES: We gathered articles on previously documented case reports and up-to-date studies on propofol-induced pancreatitis by searching databases such as PubMed and Google Scholar. RESULTS: Based on previous studies and case reports, we suggest that propofol should be added to a list of drugs having a direct association with AP. CONCLUSIONS: Although, the mechanism of propofol-induced pancreatitis is not fully understood, and the causal relationship of propofol-induced hypertriglyceridemia or idiosyncratic drug reaction has remained unproven. Clinicians should be aware of the association between propofol and pancreatitis, and any patient presenting with abdominal pain after propofol infusion should be evaluated for AP and treated promptly to avoid complications.

Protamine Induced Anaphylactic Shock after Peripheral Vascular Surgery.

Anaphylactic reactions to protamine are quite rare and almost exclusively reported during cardiac surgery. In this report, we illustrate a rare case of protamine reaction after peripheral vascular surgery a couple of months after cardiac surgery and how the patient survived this critical complication.

Hypersensitive adverse drug reactions to glucosamine and chondroitin preparations in Australia between 2000 and 2011.

PURPOSE OF THE STUDY: This study investigates spontaneous adverse drug reactions (ADRs) to glucosamine and chondroitin in the Australian population between 2000 and 2011, with a primary focus on hypersensitivity reactions. STUDY DESIGN: Case reports of ADR to glucosamine and chondroitin sent to the Therapeutic Goods Administration between 2000 and 2011 were obtained and analysed. The demographic information and severity of the ADR were recorded for individual ADR cases. These reactions were classified according to the Brown et al grading system for generalised hypersensitivity reactions. This included mild hypersensitivity reactions (generalised erythema, urticaria and angioedema) through to moderate hypersensitivity reactions (wheeze, nausea, vomiting, dizziness (presyncope), diaphoresis, chest or throat tightness and abdominal pain), and more severe reactions (hypotension, confusion and collapse). RESULTS: In this study of 366 ADRs to glucosamine and chondroitin preparations, 71.85% of cases (n=263) were found to have hypersensitivity reactions. Of these 263 cases, 92 cases were classified as mild (eg, pruritus, urticaria and lip oedema), 128 cases classified as moderate (such as dyspnoea, nausea and abdominal pain), and 43 cases classified as severe (including amnesia, gait disturbance, somnolence and hypotension). It is not clear whether the patients involved had a known shellfish allergy or underlying atopy. CONCLUSION: Results of this investigation support the need for clear labelling on glucosamine and chondroitin preparations to raise awareness of possible adverse events for those predisposed to allergy or atopy in response to shellfish.

Report for the Sixth Meeting of the International Society for Zinc Biology (ISZB-2019).

The sixth meeting of the International Society for Zinc Biology (ISZB-2019) was held on September 9-13, 2019 in Kyoto, Japan. The meeting attracted 215 participants, had four plenary speakers, ten scientific symposia, two oral sessions, and one poster discussion session. In this chapter, we describe the outcomes and events of this very successful meeting.

Molecular mechanisms and pathophysiology of perioperative hypersensitivity and anaphylaxis: a narrative review.

Perioperative hypersensitivity reactions (POH) constitute a clinical and diagnostic challenge, a consequence of heterogeneous clinical presentations, and multiple underlying pathomechanisms. POH do not necessarily involve an allergen-specific immune response with cross-linking of specific immunoglobulin E (sIgE) antibodies on mast cells and basophils. POH can also result from alternative specific and non-specific effector cell activation/degranulation such as complement-derived anaphylatoxins and off-target occupancy of mast cell, basophil, or both surface receptors. Moreover, POH and anaphylaxis can occur independent from mast cell and basophil degranulation. The manifestations of POH primarily affect the cardiovascular, respiratory, and integumentary systems. POH present within the context of surgical or procedural pathology and the effects of surgical and anaesthetic techniques on pre-existing physiological reserve. The majority of cases of appropriately-treated intraoperative anaphylaxis can be considered a compensated cardiovascular anaphylaxis. With increasing severity of anaphylaxis, maldistribution and hypovolaemia lead to reduced venous return and circulatory failure. Treatment with a combination of epinephrine and i.v. fluid is critical for successful resuscitation, although the excessive use of epinephrine without adequate volume expansion may be deleterious. Neural control of the airways is important in the pathophysiology of bronchospasm. Anticholinergic drug premedication is beneficial in patients with hyperreactive airways. Pulmonary oedema can result from a combination of pulmonary capillary hypertension, incompetence of the alveolocapillary membrane, or both. Angioedema can be distinguished mechanistically into histaminergic and non-histaminergic (e.g. bradykinin-mediated). An understanding of the molecular mechanisms and pathophysiology of POH are essential for the immediate management and subsequent investigation of these cases.

Differential diagnosis of late-type reactions to injected local anaesthetics: Inflammation at the injection site is the only indicator of allergic hypersensitivity.

BACKGROUND: Anaphylaxis-like reactions developing within a few minutes are the most frequent complications of subcutaneous or submucosal injections of local anaesthetics (LAs), and topically applied LAs are potential contact allergens. In addition, injected LAs have been reported to induce delayed reactions, including local inflammation at the injection site, and various general symptoms. OBJECTIVES: To assess the frequency and symptoms of late-type hypersensitivity occurring several hours after LA injections. METHODS: We retrospectively evaluated clinical data and test results from all patients referred to our allergy clinic in a period of 20 years for diagnostic work-up of LA-associated late-type reactions. RESULTS: Of 202 patients reporting symptoms with onset at least 1 hour after LA injection, 40 had cutaneous inflammation confined to the injection site, and 162 reported various systemic symptoms. LA hypersensitivity could be excluded in all patients with systemic complaints by means of skin testing and subsequent subcutaneous provocation. In 8 of the 40 patients (20%) with local inflammatory reactions, late-type allergic LA hypersensitivity was confirmed. CONCLUSIONS: Late-type LA allergy commonly causes inflammatory skin reactions confined to the injection site. Conversely, LAs are highly unlikely to trigger delayed systemic symptoms such as urticarial or exanthematous skin eruptions.

Acute generalized exanthematous pustulosis due to ceftriaxone: Report of a pediatric case with recurrence after positive patch test.

Acute generalized exanthematous pustulosis (AGEP) is seen uncommonly in children and sometimes shows atypical clinical features in this population. Patch testing can be used effectively in children for the confirmation of the culprit drug in cases of multiple drug use. Here, we report a rare, pediatric case of ceftriaxone-induced AGEP confirmed by patch testing with subsequent recurrence of the skin eruption.

Beyond Penicillin: Rapid Desensitization for Specific Flucloxacillin Hypersensitivity.

Beta-lactam therapy for severe staphylococcal infections is associated with superior outcomes, compared to non-beta-lactam therapy. For patients with immediate hypersensitivity to beta-lactams, desensitization has been widely employed to allow beta-lactam therapy, but published protocols for antistaphylococcal beta-lactams such as flucloxacillin are lacking. Here, we report a case and describe the desensitization protocol successfully used for a patient with isolated flucloxacillin immediate hypersensitivity, for whom a penicillin desensitization protocol would likely have resulted in an adverse drug reaction.

Anaesthesia, surgery, and life-threatening allergic reactions: epidemiology and clinical features of perioperative anaphylaxis in the 6th National Audit Project (NAP6).

BACKGROUND: Anaphylaxis during anaesthesia is a serious complication for patients and anaesthetists. METHODS: The 6th National Audit Project (NAP6) on perioperative anaphylaxis collected and reviewed 266 reports of Grades 3-5 anaphylaxis over 1 yr from all NHS hospitals in the UK. RESULTS: The estimated incidence was ≈1:10 000 anaesthetics. Case exclusion because of reporting delays or incomplete data means true incidence might be ≈70% higher. The distribution of 199 identified culprit agents included antibiotics (94), neuromuscular blocking agents (65), chlorhexidine (18), and Patent Blue dye (9). Teicoplanin comprised 12% of antibiotic exposures, but caused 38% of antibiotic-induced anaphylaxis. Eighteen patients reacted to an antibiotic test dose. Succinylcholine-induced anaphylaxis, mainly presenting with bronchospasm, was two-fold more likely than other neuromuscular blocking agents. Atracurium-induced anaphylaxis mainly presented with hypotension. Non-depolarising neuromuscular blocking agents had similar incidences to each other. There were no reports of local anaesthetic or latex-induced anaphylaxis. The commonest presenting features were hypotension (46%), bronchospasm (18%), tachycardia (9.8%), oxygen desaturation (4.7%), bradycardia (3%), and reduced/absent capnography trace (2.3%). All patients were hypotensive during the episode. Onset was rapid for neuromuscular blocking agents and antibiotics, but delayed with chlorhexidine and Patent Blue dye. There were 10 deaths and 40 cardiac arrests. Pulseless electrical activity was the usual type of cardiac arrest, often with bradycardia. Poor outcomes were associated with increased ASA, obesity, beta blocker, and angiotensin-converting enzyme inhibitor medication. Seventy per cent of cases were reported to the hospital incident reporting system, and only 24% to Medicines and Healthcare products Regulatory Agency via the Yellow Card Scheme. CONCLUSIONS: The overall incidence of perioperative anaphylaxis was estimated to be 1 in 10 000 anaesthetics.

Cross-reactivity between halogenated platinum salts in an immediate-type respiratory hypersensitivity model.

Halogenated platinum salts can trigger the development of occupational asthma. Until recently, laboratory research into the development and manifestation of platinum hypersensitivity responses were hindered by the lack of an animal model suitable for assessing the functional consequences of allergic sensitization. We employed a newly developed mouse model to assess the potential allergenicity of ammonium tetrachloroplatinate (ATCP), compare the relative potency of ATCP and another platinum salt, ammonium hexachloroplatinate (AHCP) and assess potential cross-reactivity. Mice were topically sensitized with ATCP before being challenged by intratracheal aspiration (IA) with ATCP. Ventilatory responses were assessed using whole-body plethysmography (WBP). An immediate response (IR) was observed in ATCP-sensitized and challenged mice. Two days later, responsiveness to the nonspecific stimuli methacholine (Mch) was detected in ATCP-sensitized mice using WBP. Bronchoalveolar lavage fluid collected from sensitized mice contained an average of 3.3% eosinophils compared to less than 0.5% in non-sensitized mice (p<.05). Serum harvested from sensitized mice also contained increased total serum immunoglobulin E (p<.05). These data are the first to demonstrate that topical exposure to ATCP is sufficient to develop immediate type hypersensitivity and that a single intra-airway challenge is capable of triggering pulmonary responses. To investigate potential cross-reactivity, mice were sensitized to AHCP and, challenged by a single IA with a second platinum compound, ATCP. Compared to non-sensitized mice challenged with ATCP, these mice exhibited an IR, responsiveness to Mch, and eosinophilic infiltration in the lungs similar to that achieved with AHCP challenge, thus demonstrating cross-reactivity.

Evaluation of periprocedural hypersensitivity reactions.

BACKGROUND: Identifying the cause of periprocedural hypersensitivity reactions (HSRs) remains challenging because of the multitude of medications involved. Antibiotics are the most common cause in the United States, whereas neuromuscular blocking agents are most common in Europe. OBJECTIVE: To identify causative agents for periprocedural HSRs. METHODS: This study was a 7-year retrospective medical record review of patients evaluated between December 2009 and January 2017 at a drug allergy center in Bronx, New York for periprocedural HSRs, defined as occurring soon before, during, or soon after a medical procedure or operation with or without general anesthesia. Demographics, description of historical HSRs, results of testing to potential causative medications, and tolerance of subsequent anesthesia were reviewed. RESULTS: Thirty-four patients completed a comprehensive evaluation. Skin testing identified an IgE-mediated cause in 22 patients (64.7%). The most common causative class of medications was induction agents (n = 9 [36%]), with midazolam being the most frequently implicated (n = 6 [3 positive skin test results, 3 equivocal skin test results]). Cefazolin was the most common agent identified (n = 8 [32%]) followed by ondansetron (n = 3 [12%]). Sixteen of 22 contacted patients were exposed to subsequent anesthesia, including 3 patients with negative evaluations. One patient experienced a mild urticarial HSR. CONCLUSION: Induction agents were the most common causative agents in our patients, which differs from other studies. Given the variability in evaluations of periprocedural HSRs across the United States with data published on small sample sizes, there is a need to establish national guidelines to standardize evaluations and to create a national registry to allow for data sharing.

Drug Hypersensitivity and Desensitizations: Mechanisms and New Approaches.

Drug hypersensitivity reactions (HSRs) are increasing in the 21st Century with the ever expanding availability of new therapeutic agents. Patients with cancer, chronic inflammatory diseases, cystic fibrosis, or diabetes can become allergic to their first line therapy after repeated exposures or through cross reactivity with environmental allergens. Avoidance of the offending allergenic drug may impact disease management, quality of life, and life expectancy. Precision medicine provides new tools for the understanding and management of hypersensitivity reactions (HSRs), as well as a personalized treatment approach for IgE (Immunoglobuline E) and non-IgE mediated HSRs with drug desensitization (DS). DS induces a temporary hyporesponsive state by incremental escalation of sub-optimal doses of the offending drug. In vitro models have shown evidence that IgE desensitization is an antigen-specific process which blocks calcium flux, impacts antigen/IgE/FcεRI complex internalization and prevents the acute and late phase reactions as well as mast cell mediator release. Through a "bench to bedside" approach, in vitro desensitization models help elucidate the molecular pathways involved in DS, providing new insights to improved desensitization protocols for all patients. The aim of this review is to summarize up to date information on the drug HSRs, the IgE mediated mechanisms of desensitization, and their clinical applications.

Sulfasalazine-Related Hypersensitivity Reactions in Patients With Rheumatic Diseases.

BACKGROUND: Sulfasalazine (SSZ), which has an arylamine sulfonamide structure, is an anti-inflammatory drug used in the treatment of many rheumatic diseases. Various adverse effects have been reported related to SSZ. In the present study, we aimed to define the frequency of SSZ-related hypersensitivity reaction in patients with rheumatoid arthritis and ankylosing spondylitis. METHODS: A total of 136 patients were included in this study. During follow-ups, reaction type, reaction duration, and drug doses were recorded in patients who developed hypersensitivity reactions. Drugs were discontinued in patients who developed reactions, and they were treated with antihistaminics and/or corticosteroids, according to requirements. Drug provocation tests with the drugs and aminosalicylic acid were performed in patients with negative skin prick test individually. RESULTS: A total of 136 patients, with ages ranging from 19 to 71 years (mean, 41.97 [SD, 12.04] years), were included in the study. Hypersensitivity reactions according to the drug provocation test were found against SSZ in 12 patients (8.8%). The SSZ-related hypersensitivity reaction types were urticaria in 7 patients, urticaria and angioedema in 4 patients, and pruritus in 1 patient. CONCLUSIONS: Sulfasalazine is widely used by rheumatologists in the treatment of rheumatic diseases. Whereas the frequency of sulfonamide-related hypersensitivity reactions was reported as 3.0% in the population, we detected hypersensitivity reactions to be 8.8% with SSZ usage in rheumatic diseases.

Association of HLA genotypes with phenobarbital hypersensitivity in children.

OBJECTIVE: Phenobarbital hypersensitivity is one of the common drug hypersensitivity syndromes in children. Clinical symptoms of phenobarbital hypersensitivity vary from maculopapular rashes (MPs) to severe cutaneous adverse drug reactions (SCARs) including drug reactions with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Drug hypersensitivity has been demonstrated to be associated with variations in the HLA genotypes. This study was to investigate the association between the variations of HLA genotypes and phenobarbital hypersensitivity in Thai children. METHODS: The cases were Thai children, between 0 and 18 years of age, who were diagnosed with phenobarbital hypersensitivity, which included SCARs and MPs. The control patients were Thai children of a corresponding age who had taken phenobarbital for at least 12 weeks without any hypersensitivity reaction. Blood samples were collected for HLA genotyping by using a reverse-sequence-specific oligonucleotide (SSO) probes method. The carrier rates of HLA alleles were compared between 47 cases (27 SCARs and 20 MPs) and 54 controls. RESULTS: The carrier rates of HLA-A*01:01 and HLA-B*13:01 were significantly higher in the phenobarbital-induced SCARs than in the tolerant controls (18.5% vs. 1.85%, p = 0.01, odds ratio [OR] 11.66, 95% confidence interval [CI] 1.21-578.19; 37.04% vs. 11.11%, p = 0.009, OR 4.60, 95%CI 1.29-17.98). There was a trend of a higher carrier rate of HLA-C*06:02 in the phenobarbital-induced SCARs when compared with those in the tolerant controls (29.63% vs. 11.11%, p = 0.059, OR 3.31, 95% CI 0.88-13.31). In contrast to the phenobarbital-induced SCARs, only the HLA-A*01:01 carrier rate in the phenobarbital-induced MPs was significantly higher than those in the tolerant controls (20% vs. 1.85%, p = 0.017, OR 12.69, 95% CI 1.15-661.62). SIGNIFICANCE: An association between phenobarbital hypersensitivity and HLA-A*01:01 and HLA-B*13:01 has been demonstrated in Thai children.

Toxicity profile of repeated doses of PEG-asparaginase incorporated into a pediatric-type regimen for adult acute lymphoblastic leukemia.

Despite having been long regarded as too toxic for adult patients, pediatric-like regimens containing L-asparaginase have resulted in improved outcomes for adults with acute lymphoblastic leukemia (ALL). To characterize the spectrum of toxicity of repeated doses of polyethylene glycolated-asparaginase (PEG-asp) in adults, we reviewed all doses (2000 IU/m(2) ) administered as part of a pediatric-inspired regimen in adult ALL at our center. Subjects aged 18-60 yr with ALL (n = 152, 69.1% male) contributed 522 dose cycles to the study. Hepatotoxicity was the most common adverse event: grades 3-4 transaminitis and hyperbilirubinemia occurred in 53.9% and 23.7% of subjects, respectively. Hepatotoxicity was reversible; no cases of fulminate hepatic failure were observed. Other toxicities affecting at least 5% of subjects were grades 3-4 triglyceridemia in 50.9%, hypofibrinogenemia (<100 mg/dL) in 47.9%, clinical pancreatitis in 12.6%, venous thromboembolism in 11.2%, allergic reaction in 7.2%, and any grade bleeding in 5.3%. PEG-asp was always discontinued after grades 3-4 pancreatitis or allergic reaction. Otherwise, toxicities did not preclude administration of additional cycles of the drug. Our results suggest that repeated PEG-asp dosing is safe in adults aged 18-60 yr, even after occurrence of a drug-related toxicity.

Phenotypical characterization of children with hypersensitivity reactions to NSAIDs.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are the main cause of drug-induced hypersensitivity in children. Many classifications have been proposed, focusing on adults. So far, no large study has deeply investigated a pediatric cohort. The aim of the present study was to describe a population of NSAID hypersensitive patients reporting a reaction during their childhood and to verify whether it is possible to classify pediatric patients, following the EAACI/ENDA classification. METHODS: We conducted a historical prospective study including patients evaluated from 1996 to 2015 in the allergy unit of the Montpellier University Hospital. We included 635 patients. For each patient, we recorded clinical manifestations and possible comorbidities and tried to identify possible risk factors. RESULTS: NSAID hypersensitivity was diagnosed in 107 of 635 patients (16.9%). In this group, 43 patients (40.2%) could not be classified following the ENDA recommendations. The main discrepancies were on the patients' clinical manifestations and on their possible underlying diseases. We identified, on a multivariate analysis, some risk factors for NSAID hypersensitivity: chronic urticaria (OR 7.737, 3.375-18.296 95%CI), atopic status (OR 2.514, 1.504-4.364 95%CI), and allergic rhinoconjunctivitis (OR 1.799, 1.138-2.837 95%CI). On the basis of our results, we are proposing an adapted classification for NSAID hypersensitivity in children. CONCLUSIONS: The current ENDA classification does not seem to be adapted for pediatric patients; a modified version does. Our study could help allergists better understand the differences between adults and children in developing hypersensitivity reactions to NSAIDs, but further large-scale prospective longitudinal analyses are required to validate this new classification.

Low incidence of anti-drug antibodies in patients with type 2 diabetes treated with once-weekly glucagon-like peptide-1 receptor agonist dulaglutide.

Therapeutic administration of peptides may result in anti-drug antibody (ADA) formation, hypersensitivity adverse events (AEs) and reduced efficacy. As a large peptide, the immunogenicity of once-weekly glucagon-like peptide-1 (GLP-1) receptor agonist dulaglutide is of considerable interest. The present study assessed the incidence of treatment-emergent dulaglutide ADAs, hypersensitivity AEs, injection site reactions (ISRs), and glycaemic control in ADA-positive patients in nine phase II and phase III trials (dulaglutide, N = 4006; exenatide, N = 276; non-GLP-1 comparators, N = 1141). Treatment-emergent dulaglutide ADAs were detected using a solid-phase extraction acid dissociation binding assay. Neutralizing ADAs were detected using a cell-based assay derived from human endothelial kidney cells (HEK293). A total of 64 dulaglutide-treated patients (1.6% of the population) tested ADA-positive versus eight (0.7%) from the non-GLP-1 comparator group. Of these 64 patients, 34 (0.9%) had dulaglutide-neutralizing ADAs, 36 (0.9%) had native-sequence GLP-1 (nsGLP-1) cross-reactive ADAs and four (0.1%) had nsGLP-1 neutralization ADAs. The incidence of hypersensitivity AEs and ISRs was similar in the dulaglutide versus placebo groups. No dulaglutide ADA-positive patient reported hypersensitivity AEs. Because of the low incidence of ADAs, it was not possible to establish their effect on glycaemic control.

Clindamycin-induced hypersensitivity reaction.

Drug-induced anaphylaxis is an unpredictable adverse reaction. Although it may occur with any medication, antibiotics induce more cases of anaphylaxis than any other medication class with most cases being induced by ß-lactam antibiotics. Clindamycin is an antibiotic with good gram-positive and anaerobe coverage which is often used in patients with ß-lactam allergies. We report the case of a 46-year-old female who experienced anaphylaxis after a dose of intravenous (IV) clindamycin. Following treatment with methylprednisolone, epinephrine, diphenhydramine, and albuterol, the patient stabilized. The patient's score on the Naranjo's algorithm was 8 (probable); a score of 9 (definite) limited only by absence of drug re-challenge. To our knowledge, this is the first report of a clindamycin-induced anaphylaxis where the patient was not exposed to any other agent that may have triggered the response, the first case in the United States, and only the third documented case in the literature. Clinicians should be aware of the potential for drug-induced anaphylaxis in all medications.

The Effectiveness and Stability of a 20% Emulsified Sevoflurane Formulation for Intravenous Use in Rats.

BACKGROUND: Halogenated volatile anesthetics can be safely and rapidly administered to animals and humans using emulsion formulations. However, they must be administered simultaneously with a high dose of lipids. Increasing the concentration of volatile anesthetics may solve this clinical issue. Moreover, careful observation is needed when the emulsion is injected because anaphylactic reactions have been reported. METHODS: We prepared a 20% sevoflurane lipid emulsion and administered it to 69 male Sprague-Dawley rats via the tail vein. The median effective dose (ED50) for the loss of righting reflex and the median lethal dose (LD50) were determined. ED50 and LD50 values were calculated using nonlinear regression, and data were fitted with a cumulative Gaussian model using GraphPad Prism. Measurements of vital signs and evaluation of the presence of adverse effects associated with continuous infusion of emulsions were verified. Stability of the emulsion was assessed by measuring particle size at 365 days and sevoflurane concentrations after opening the vial at 180 minutes. RESULTS: The ED50 and LD50 were 0.47 mL/kg (95% confidence interval [CI], 0.46-0.48) and 1.13 mL/kg (95% CI, 1.07-1.18), respectively. The therapeutic index (LD50/ED50) was 2.41 (95 CI%, 2.23-2.59), which compares favorably with therapeutic index of a fluoropolymer-based emulsion of sevoflurane, propofol, and thiopental. There were no adverse effects associated with the continuous infusion of emulsions. Particle size of the emulsion at 365 days after preparation was 78.9 ± 3.8 nm (±SD), and sevoflurane concentration at 180 minutes after opening the vial was 19.0% ± 0.6% (±SD). CONCLUSIONS: We prepared a 20% sevoflurane lipid emulsion using caprylic triglyceride (i.e., medium-chain triglyceride). In rats, this emulsion was an effective anesthetic and was not associated with adverse events. The emulsion was stable after consecutive evaluation for 365 days and for 180 minutes after the vial was opened.