Laryngeal edema following remimazolam-induced anaphylaxis: a rare clinical manifestation.

BACKGROUND: Remimazolam is an ultra-short-acting intravenous benzodiazepine, which has been used as sedative/anesthetic in procedural sedation and anesthesia. Although peri-operative anaphylaxis due to remimazolam has been reported recently, the spectrum of the allergic reactions is still not fully known. CASE PRESENTATION: We describe a case of anaphylaxis following remimazolam administration in a male patient undergoing colonoscopy under procedural sedation. The patient presented complex clinical signs including airway changes, skin symptoms, gastrointestinal manifestations and hemodynamic fluctuations. Different from other reported cases, laryngeal edema was the initial and main clinical feature of remimiazolam-induced anaphylaxis. CONCLUSIONS: Remimazolam-induced anaphylaxis has a rapid onset and complex clinical features. This case reminds anesthesiologists should be particularly alert to the unknown adverse reactions of new anesthetics.

Exploring the Pathophysiology of Reinke's Edema: The Cellular Impact of Cigarette Smoke and Vibration.

OBJECTIVES: To explore the isolated or combined effects of cigarette smoke extract (CSE) and vibration on human vocal fold fibroblasts (hVFF) in an in vitro setting in order to elucidate their influence in the pathophysiology of Reinke's edema (RE). STUDY DESIGN: Immortalized hVFF were exposed to CSE or control medium under static or vibrational conditions. A phonomimetic bioreactor was used to deliver vibrational patterns to hVFF over a period of 5 days. METHODS: Cytotoxicity was quantified using a lactate dehydrogenase assay. We employed reverse transcription-quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and Magnetic Luminex(R) assays (R&D Systems, Minneapolis, MN) to assess the influence on extracellular matrix production, fibrogenesis, inflammation, and angiogenesis. RESULTS: We observed significant changes induced by CSE alone (hyaluronic acid, matrix metalloproteinase 1, Interleukin-8, cyclooxygenase [COX]1, COX2, vascular endothelial growth factor [VEGF]D), as well as settings in which only the combination of CSE and vibration led to significant changes (transforming growth factor beta 1, VEGFA, VEGFC). Also, CSE-induced levels of COX2 were only significantly reduced when vibration was applied. CONCLUSION: We were able to explore the cellular effects of CSE and vibration on hVFF by employing a phonomimetic bioreactor. Whereas cigarette smoke is generally accepted as a risk factor for RE, the role of vibration remained unclear as it is difficult to study in humans. Our data showed that some genes and proteins in the pathophysiological context of RE were only affected when CSE in combination with vibration was applied. LEVEL OF EVIDENCE: NA Laryngoscope, 131:E547-E554, 2021.

Establishment and validation of the LC-MS/MS method for the determination of lincomycin in human blood: Application to an allergy case in forensic science.

An analytical method to quantify lincomycin in human blood samples by liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed and validated. The selected method was based on a protein precipitation extraction (PPE) with methanol. Instrumental determination was carried out by LC-MS/MS, with quantification based on the internal standard method. Linearity for lincomycin was established in the concentration range of 5-100 ng/mL. The limit of detection (LOD) and limit of quantification (LOQ) were 0.2 and 1 ng/mL, respectively. Analyte recoveries were in the range of 72.70%-84.13% for spiked blood samples. The accuracies ranged between 92.82% and 100.40%, and the intraday and inter-day precisions ranged between 1.19% and 6.40%, respectively. The developed method was applied to an authentic allergy case of lincomycin. By testing the lincomycin content in the venous blood of the deceased and combined with the pathological test results, lincomycin acute allergy appeared to be the most likely cause of death. The acquired results confirm that the developed method is capable of identifying and quantifying lincomycin in human blood and can be suitable for the detection of allergy cases in clinical or forensic science.

A case of late-onset larynx angioedema after ranibizumab intravitreal injection: Ranibizumab-related angioedema.

This case report describes an unusual case of late-onset larynx angioedema after ranibizumab intravitreal injection. A 72-year-old female patient presented to our clinic for decreased vision; right eye (RE) fundoscopy and optical coherence tomography (OCT) revealed mild chorioretinal atrophy and choroidal neovascularization with subretinal fluid. A ranibizumab injection was planned in the RE, with standard pretreatment with daily oral administration of betamethasone, cetirizine, and ranitidine because her medical history revealed two adverse drug reactions (ADRs) to contrast media (CM). Despite the premedication, 2 h after injection, the patient referred throat closing sensation and dyspnea that resolved within few hours by betamethasone 4 mg intramuscular injection, without further reoccurrence. In occasion of the second intravitreal injection, video rhinofibrolaryngoscopy revealed subglottic edema that resolved within few hours by betamethasone 4 mg intramuscular injection. This report suggests that, even in cases of intravitreal injection, patients with history of allergy, despite the anti-allergic treatment, should be hospitalized to detect late onset of such a life-threatening complication.

Acute myocardial infarction in a patient suffering from penicillin-induced laryngeal edema : Kounis syndrome aggravated by adrenaline.

Kounis syndrome or allergic angina is defined as the coincidental occurrence of chest pain and allergic reactions accompanied by clinical and laboratory findings of classical angina pectoris. It is triggered by the action of potent vasoactive and inflammatory mediators, which are released from the mast cells during the allergic reaction. Epinephrine is a life-saving medication in anaphylaxis; however, it can aggravate ischemia and induce coronary vasospasm and arrhythmias. Here, we present a patient with Kounis syndrome that was caused by intramuscular injection of procaine penicillin G, and in whom epinephrine administration for treatment of laryngeal edema had provoked severe myocardial ischemia.

Recurrent angioedema associated with pharmacological inhibition of dipeptidyl peptidase IV.

Angioedema (AE) of the upper airways is a severe and potentially life-threatening condition. The incidence has been increasing in the past two decades, primarily due to increased use of medications inhibiting the degradation of vasoactive peptides. Acquired angioedema related to angiotensin-converting enzyme inhibitors (ACEI-AAE) is well known, but other pharmaceutical agents also affect the degradation of bradykinin and substance P. We present a middle-aged man with recurrent episodes of severe AE of the oral cavity, hypopharynx and larynx due to pharmacological inhibition of dipeptidyl peptidase IV.

Laryngeal Side Effects of Tyrosine Kinase Inhibitors.

OBJECTIVES: Tyrosine kinase inhibitors (TKIs) are common targeted drugs, used in the treatment of hematological and solid malignancies. These drugs present a multitude of potential adverse effects. Laryngeal manifestations, including laryngeal edema, secondary to TKIs treatment have not been well studied, despite their potential lethality. METHODS: This cross-sectional study included adult patients (>18 years) treated with TKIs who were followed in a secondary medical center and underwent a voluntary otolaryngological examination, which included laryngeal fiber-optic laryngoscopy (FOL). FOL was independently performed by two senior otolaryngologists, and results were recorded and evaluated by two grading systems, to assess the degree of laryngeal edema. In addition, medical files were reviewed, and data collected included past medical history, signs and symptoms, physical examination, laboratory results, treatment type, and duration. RESULTS: Sixteen patients, aged 68.2 ± 13.6 years, were examined during October 2014 to December 2014. Of them, three (19%) were males. Eleven (68%) patients presented with varying degrees of laryngeal edema. A significant correlation was found between gastroesophageal reflux symptoms and laryngeal edema (P = 0.02). TKI treatment was stopped in one patient, because of symptomatic laryngeal edema, which completely resolved within 2 weeks. CONCLUSIONS: Laryngeal edema was common in our study group. This edema was most often not life threatening. Yet, because of the potential severity of this side effect, we propose a routine FOL examination of patients before commencing TKI treatment and a reevaluation performed during treatment.

The role of icatibant-the B2 bradykinin receptor antagonist-in life-threatening laryngeal angioedema in the ED.

Angioedema is a localized, sudden, transient, and often recurrent swelling of the deeper layers of the skin or mucosa with no epidermal component. It is caused by vasoactive substances that produce a transient increase in endothelial permeability. Angioedema involving the laryngeal components is a life-threatening situation for the patient,and it is a challenge for the emergency medicine physician to rapidly achieve a safety airway. Most cases of laryngeal angioedema are induced by histamine release; but 10% are bradykinin induced, which does not respond to the conventional algorithm of treating allergic induced angioedema. We present a case report of an angiotensin converting enzyme (ACE) inhibitor­induced laryngeal angioedema alleviated only after treatment with the new bradykinin receptor inhibitor medication icatibant which was licensed only for use in hereditary angioedema. We reviewed the literature for the use of icatibant in acquired drug-induced angioedema; and because of the similar pathogenesis between the hereditary angioedema and the ACE inhibitor­induced angioedema,we propose an algorithm for careful use of icatibantin life-threatening angioedema in the emergency department.

Nickel dental alloys can induce laryngeal edema attacks: a case report.

Nickel is a strong immunological sensitizer and may result in contact hypersensitivity. Case reports of allergic reactions to intraoral nickel have occasionally been reported in the published work and these allergic reactions are generally of a delayed type (type IV). Here, we present a case of a nickel allergic patient displaying frequent laryngeal edema attacks which required treatment with epinephrine injections followed by parenteral corticosteroid doses. Her complaints ceased after the removal of the dental bridge and the foods containing nickel. In summary, we propose that in the case of recurrent laryngeal edema attacks without any explainable cause, an allergic reaction due to nickel exposure should be taken into consideration.

[Case of iodism complicated with severe airway stenosis due to pharyngolaryngeal edema].

A 22-year-old man was admitted to our hospital with dilute iodine tincture poisoning. He had ingested 150 mL in a suicide attempt. On arrival, he was in need of urgent airway management as he was repeatedly vomiting. Although we had difficulty with endotracheal intubation because of remarkable pharyngolaryngeal mucosal edema induced by dilute iodine tincture, we managed to secure the airway. On the 2nd day, laryngoscope showed severe mucosal erosion from the upper to middle pharynx and epiglottis. On the 4th day, we performed a tracheoctomy in anticipation of prolonged airway management. On the 16th day, laryngoscopy showed improvement in each of the 2nd day findings. On the 30th day, the patient was transferred to a psychiatric hospital. Generally, iodine poisoning induces multiple organ disorders and there have been several reports describing iatrogenic iodine poisoning. However, cases of severe airway stenosis due to ingestion of iodine are very rare. Presently, members of the public can easily purchase dilute iodine tincture in Japan, therefore emergency medical personnel should be aware of iodine poisoning as a method of suicide attempt.

Management of angiotensin-converting enzyme inhibitor-induced angioedema.

OBJECTIVES/HYPOTHESIS: To develop and validate a clinical algorithm for management of patients with angiotensin-converting enzyme inhibitor-induced angioedema (AIIA). STUDY DESIGN: Prospective cohort observational study. METHODS: Over 1 year, 40 patients with AIIA were evaluated by otolaryngology, underwent laryngoscopy, and were followed until disease resolution. The need for airway intervention, disposition for appropriate level of care, and other parameters were analyzed. RESULTS: Treatment started within 61.5 minutes of presentation to the emergency department (ED). Mean duration until resolution of edema was 29 hours. Twenty (50%) patients required intensive care unit (ICU) admission, and six (15%) required intubation. Seventeen (42.5%) were monitored and discharged from the ED. Floor-of-mouth edema was present in 19 (47.5%), and massive tongue edema was found in four (10%) patients. The aryepiglottic fold was involved in 20 (50%) patients on laryngoscopy. Older patients (P = .048) with subjective dyspnea (P = .003) and dysphonia (P = .001) were most likely to require ICU admission. Upper lip swelling had a negative correlation with airway edema identifiable on laryngoscopy alone (P = .008). Dysphonia (n = 16) predicted airway edema upon laryngoscopy (P = .001). All 40 patients were triaged successfully without the need for readmission or escalation of level of care. CONCLUSIONS: The management protocol was successful in 40 consecutive patients to the appropriate level of care. History and physical examination may predict airway findings identified on laryngoscopy and help guide management when treatment by otolaryngology is not immediately available. A subset of patients will require acute airway intervention and can be identified at initial presentation.

[Case of upper airway stenosis after accidental ingestion of neutral detergent containing cationic surfactant (HDQ Neutral)].

We had a case of upper airway stenosis after accidental ingestion of neutral detergent containing cationic surfactant (HDQ Neutral). An 85-year-old man was transported to our hospital by ambulance after ingesting 50 mL of HDQ Neutral. On arrival, he had an edematous buccopharyngeal membrane with bleeding. Laryngeal edema was observed by laryngoscopy, and severe upper airway stenosis occurred. He also had hypoxemia and was therefore intubated and put on mechanical ventilation. After admission, his respiratory condition was stable. On day 3, upper airway edema had improved and extubation was performed. He was cured without other complications. Surfactants generally have low toxicity but can cause damage to the mucous membrane of the respiratory tract and gastrointestinal tract. Therefore, immediate evaluation and treatment are needed for intoxication with them. They can also cause harm to circulation dynamics or the central nerve system, and careful follow-up is therefore needed.

A review of the pathophysiology, diagnosis, and management of allergic reactions in the dental office.

Since more than 50 million people in the United States have allergies, knowledge of the management of allergic reactions in the dental office is extremely important. Appropriate care may range from a simple referral to a primary care physician to lifesaving measures implemented during acute anaphylactic reactions. The authors present a basic review of the pathophysiology of allergic reactions and provide information detailing the diagnosis and management of allergic reactions that may be encountered in the dental office. Utilizing this information, the dental practitioner and ancillary staff will have a thorough understanding of allergic reactions and be prepared to successfully identify and treat these reactions.

A severe laryngeal angioedema reaction from cefadroxil in a patient with no known allergies to penicillins.

We report a life-threatening anaphylactic reaction to cefadroxil in a 60-year old female with no previous history of allergies to penicillins. Cefadroxil is a first-generation cephalosporin and anaphylactic reactions to it in patients with no previous history of penicillin allergy are very rare. Since cefadroxil is a commonly prescribed antibiotic for both adults and children in the Caribbean, an appropriate level of caution should be exercised in its use even with no reported history of previous allergies to the penicillin class of medications.

Clinical profile of acute paraphenylenediamine intoxication in Egypt.

Orientation to paraphenylenediamine (PPD) acute systemic intoxication in Egypt has been increased over the last decade. The aim of this study was to provide more insight into the clinical profile of acute PPD intoxication with reviewing the possible underlying mechanisms. Our study was retrospective. It was conducted over 7 years (2001-2008) on 25 cases with acute PPD intoxication admitted to the Poison Control Center Ain Shams University Hospitals, Cairo, Egypt. The mean age of the cases was 35.34 +/- 10.5 years; the male to female ratio was 18:7. Cervicofacial and laryngeal edema was the dominating presenting manifestation in 72% of the cases, 100% of the cases developed rhabdomyolysis, 80% had impaired renal functions, elevated liver transaminases were detected in 76% of cases, 75% showed hyperkalemia and 16% died due to ventricular arrhythmia. In conclusion, PPD causes serious multisystem toxicity and its selling to the public should be officially restricted.