Association between maxillary sinus floor perforation by dental implants and mucosal thickening: A cone-beam computed tomography study.

OBJECTIVE: To investigate the association of perforation of the maxillary sinus floor by dental implants with mucosal thickening and to describe its characteristics in perforated cases. STUDY DESIGN: One-hundred and twenty-nine maxillary sinuses of 93 patients presenting 202 dental implants in the maxillary posterior region were retrospectively assessed in cone-beam computed tomography scans and classified according to maxillary sinus perforation, bone graft, mucosal thickening, and mucosal appearance. Logistic regression determined the chance of mucosal thickening in perforated maxillary sinuses. The chi-square test compared categorical variables between maxillary sinus perforated or not by implants and maxillary sinus with or without mucosal thickening. The significance level assumed was 5 % (α = 0.05). RESULTS: There was perforation of 60 maxillary sinuses floor (46.5 %) by 74 dental implants. The chance of mucosal thickening was higher when the implant tip was trespassing on the maxillary sinus floor (p < 0.001). There was a significant association between maxillary sinus mucosal thickening and perforation by a dental implant with the tip trespassing the maxillary sinus floor (p < 0.05). CONCLUSION: Maxillary sinus mucosal thickening is associated with sinus floor perforation by dental implants and does not depend on the number of implants perforating it. CLINICAL RELEVANCE: There is an association between dental implants' perforation of the maxillary sinus floor and the thickening of the maxillary sinus. In those cases, the appearance of the mucosa thickening may be irregular, local, or total opacification of the sinus cavity.

Which factors affect the risk of membrane perforation in lateral window maxillary sinus elevation? A prospective cohort study.

It was the aim of this prospective cohort study to assess the various anatomical and other patient-related factors that increase membrane perforation risk. Patients underwent cone-beam computed tomography (CBCT) before surgery. The presence of septa, presence of mucous retention cyst, lateral wall thickness, membrane thickness, and residual bone height were predictive factors. Age, gender, and smoking were covariates for the study. The presence or absence of membrane perforation was the study outcome. In total, 140 subjects were studied. The hazard ratio (HR) for the presence of septa with membrane perforation was 8.07 (2.93-22.29) (p < 0.001). The HR for perforation with a single edentulous area relating to two or more teeth was 68.09 (9.52-49.16). The risk of membrane perforation in smokers was 25 times more than in non-smokers - HR 25 (7.58-82.51) (p < 0.001). The HR for membrane perforation in subjects with mucous retention cysts compared with subjects without retention cysts was 27.75 (8.73-88.23) (p < 0.001). Within the limitations of the study it seems that anatomical, habitual, and pathological factors may increase the risk of Schneiderian membrane perforation when a lateral window approach is used for sinus floor augmentation.

[Impact of sinonasal anatomic changes after endoscopic anterior skull base surgery on nasal airflow and air conditioning: a computational fluid dynamics study].

Objective: To analyze the impact of the sinonasal anatomic changes after endonasal endoscopic anterior skull base surgery on the nasal airflow and heating and humidification by computational fluid dynamics (CFD), and to explore the correlation between the postoperative CFD parameters and the subjective symptoms of the patients. Methods: The clinical data in the Rhinology Department of the First Affiliated Hospital of Zhengzhou University from 2016 to 2021 were retrospectively analyzed. The patients received the endoscopic resection of the anterior skull base tumor were selected as the case group, and the adults whose CT scans had no sinonasal abnormalities were chosen as the control group. The CFD simulation was performed on the sinonasal models after reconstructed from the patients' sinus CT images during the post-surgical follow-up. All the patients were asked to complete the Empty Nose Syndrome 6-Item Questionnaire (ENS6Q) to assess the subjective symptoms. The comparison between two independent groups and the correlation analysis were carried out by using the Mann-Whitney U test and the Spearman correlation test in the SPSS 26.0 software. Results: Nineteen patients (including 8 males and 11 females, from 22 to 67 years old) in the case group and 2 patients (a male of 38 years old and a female of 45 years old) in the control group were enrolled in this study. After the anterior skull base surgery, the high-speed airflow moved to the upper part of the nasal cavity, and the lowest temperature shifted upwards on the choana. Comparing with the control group, the ratio of nasal mucosal surface area to nasal ventilation volume in the case group decreased [0.41 (0.40, 0.41) mm-1 vs 0.32 (0.30, 0.38) mm-1; Z=-2.04, P=0.041], the air flow in the upper and middle part of the nasal cavity increased [61.14 (59.78, 62.51)% vs 78.07 (76.22, 94.43)%; Z=-2.28, P=0.023], the nasal resistance decreased [0.024 (0.022, 0.026) Pa·s/ml vs 0.016 (0.009, 0.018) Pa·s/ml; Z=-2.29, P=0.022], the lowest temperature in the middle of the nasal cavity decreased [28.29 (27.23, 29.35)℃ vs 25.06 (24.07, 25.50)℃; Z=-2.28, P=0.023], the nasal heating efficiency decreased [98.74 (97.95, 99.52)% vs 82.16 (80.24, 86.91)%; Z=-2.28, P=0.023], the lowest relative humidity decreased [(79.62 (76.55, 82.69)% vs 73.28 (71.27, 75.05)%; Z=-2.28, P=0.023], and the nasal humidification efficiency decreased [99.50 (97.69, 101.30)% vs 86.09 (79.33, 87.16)%; Z=-2.28, P=0.023]. The ENS6Q total scores of all patients in the case group were less than 11 points. There was a moderate negative correlation between the proportion of the inferior airflow in the post-surgical nasal cavity negatively and the ENS6Q total scores (rs=-0.50, P=0.029). Conclusions: The sinonasal anatomic changes after the endoscopic anterior skull base surgery alter the nasal airflow patterns, reducing the efficiency of nasal heating and humidification. However, the post-surgical occurrence tendency of the empty nose syndrome is weak.

Effects of different grafting materials on volumetric changes in the Schneiderian membrane following lateral maxillary sinus floor elevation: a preliminary study.

OBJECTIVES: To investigate the potential influence of different grafting materials on maxillary sinus membrane dimensions and ostium patency following lateral sinus floor elevation (SFE) as assessed using cone-beam computed tomography (CBCT). MATERIALS AND METHODS: A total of 40 sinuses in 40 patients were included. Twenty sinuses were referred for SFE with deproteinized bovine bone mineral (DBBM), and the remaining 20 sinuses were grafted with calcium phosphate (CP). CBCT was performed prior to and 3 to 4 days after surgery. The dimensions of the Schneiderian membrane volume and ostium patency were evaluated, and potential relationships between volumetric changes and any associated factors were analyzed. RESULTS: The median increase in membrane-whole cavity volume ratios was 43.97% in the DBBM group and 67.58% in the CP group, demonstrating no statistically significant difference (p = 0.17). The rates of increased obstruction after SFE were 11.1% for the DBBM group versus 44.4% for the CP group (p = 0.03). The graft volume was found to be positively correlated with the postoperative membrane-whole cavity volume ratio (r = 0.79; p < 0.01) and the membrane-whole cavity volume ratio increase (r = 0.71; p < 0.01). CONCLUSIONS: The two grafting materials seem to have a similar effect on transient volumetric changes in the sinus mucosa. However, the choice of grafting material should still be made with caution since sinuses grafted using DBBM exhibited less swelling and less ostium obstruction.

Venous networks in the upper airways of bats: A histological and diceCT study.

Our knowledge of nasal cavity anatomy has grown considerably with the advent of micro-computed tomography (CT). More recently, a technique called diffusible iodine-based contrast-enhanced CT (diceCT) has rendered it possible to study nasal soft tissues. Using diceCT and histology, we aim to (a) explore the utility of these techniques for inferring the presence of venous sinuses that typify respiratory mucosa and (b) inquire whether distribution of vascular mucosa may relate to specialization for derived functions of the nasal cavity (i.e., nasal-emission of echolocation sounds) in bats. Matching histology and diceCT data indicate that diceCT can detect venous sinuses as either darkened, "empty" spaces, or radio-opaque islands when blood cells are present. Thus, we show that diceCT provides reliable information on vascular distribution in the mucosa of the nasal airways. Among the bats studied, a nonecholocating pteropodid (Cynopterus sphinx) and an oral-emitter of echolocation sounds (Eptesicus fuscus) possess venous sinus networks that drain into the sphenopalatine vein rostral to the nasopharynx. In contrast, nasopharyngeal passageways of nasal-emitting hipposiderids are notably packed with venous sinuses. The mucosae of the nasopharyngeal passageways are far less vascular in nasal-emitting phyllostomids, in which vascular mucosae are more widely distributed in the nasal cavity, and in some nectar-feeding species, a particularly large venous sinus is adjacent to the vomeronasal organ. Therefore, we do not find a common pattern of venous sinus distribution associated with nasal emission of sounds in phyllostomids and hipposiderids. Instead, vascular mucosa is more likely critical for air-conditioning and sometimes vomeronasal function in all bats.

Effect of ridge preservation at molar extraction sites with severe periodontitis on the Schneiderian membrane thickness changes: a pilot study.

BACKGROUND: Information regarding the reaction of bone augmentation in terms to sinus mucosa thickness of periodontally compromised molar extraction sites is limited. This retrospective study aimed to analyze the effect of ridge preservation procedures following the extraction of molars with severe periodontitis on the healing pattern of adjacent maxillary sinus mucosal membranes. METHODS: Thirty-one periodontally compromised maxillary molar teeth either receiving ridge preservation (test group, n = 20) or undergoing spontaneous healing (control group, n = 11) were investigated. Cone-beam computed tomography (CBCT) scanning was performed before the extraction procedure and repeated 6 months later. The mucosa thickness (MT) of the adjacent periodontally compromised molar tooth was measured from CBCT images before tooth extraction and after 6 months of healing at nine assigned measurement points. The data were analyzed at α = 0.05. RESULTS: The prevalence of pre-extraction maxillary sinus mucosal thickening was 60.0% and 63.6% in the test and control groups, respectively. The average MT of the thickened sinus mucosa before tooth extraction was 3.78 ± 2.36 mm in the test group and 4.63 ± 3.20 mm in the control group (P = 0.063). The mean mucosal thickening reductions in the thickened MT subjects after 6 months of healing were 2.20 ± 2.05 mm (test group) and 2.64 ± 2.70 mm (control group), P = 0.289. The differences of MT between the time prior to extraction and after 6 months of healing were statistically significant within both groups (P < 0.05). CONCLUSIONS: Following extraction of molars with severe periodontitis, a reduction in swelling of the Schneiderian membrane has been observed regardless of the addition of a DBBM socket graft. However, a mucosal thickness > 2 mm was still frequently observed.

Composite Chondromucosal Nasoseptal Flap for Reconstruction of Suprasellar Defects.

BACKGROUND: The pedicled nasoseptal flap (NSF) is the mainstay for endoscopic skull base reconstruction. We present a novel technique using a semirigid chondromucosal NSF that improves the reinforcement and protection of intracranial structures. METHODS: Composite NSFs were performed to repair intraoperative high-flow cerebrospinal fluid leaks in 2 patients who had undergone endoscopic endonasal resection of a suprasellar mass. The surgical technique and postoperative outcomes are described. RESULTS: The flaps were sufficient for defect coverage, and the patients did not experience any cerebrospinal fluid leak in the immediate and delayed postoperative periods. No complications related to the composite flap had developed. CONCLUSIONS: The composite chondromucosal NSF is a reliable reconstruction option for select ventral cranial base reconstruction cases with the potential to improve the protection of intracranial structures. Additional surgical cases and longer follow-up are required for a better assessment of long-term outcomes.

Adult-onset Woakes' syndrome: a rare entity.

Woakes' syndrome (WS) is a rare entity, defined as severe recalcitrant nasal polyposis with consecutive deformity of the nasal pyramid. WS occurs mainly in childhood and its aetiology remains unclear. We report a case of a 68-year old woman, with aspirin-exacerbated respiratory disease, who presented with recurrent nasal polyposis and progressive broadening of the nasal dorsum. CT scan revealed extensive bilateral nasal polyposis and diffuse osteitis, with anterior ethmoidal calcified lesions. The patient underwent revision endoscopic sinus surgery and nasal pyramid deformity was successfully managed without osteotomies.

Management of FDG avid Benign Sinonasal Schneiderian Papilloma: A Case Report and Review of the Literature.

BACKGROUND: The inverted and oncocytic subtypes of sinonasal Schneiderian papillomas are benign tumors with possible rare malignant transformation and are typically managed with complete surgical resection and close follow-up. While computed tomography (CT) and magnetic resonance imaging (MRI) are mainstays in preoperative evaluation of bony invasion and soft tissue extension of the lesion, their imaging characteristics by 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) is less well characterized. OBJECTIVE: To describe the clinical presentation and management of a PET positive sinonasal lesion. To conduct a literature review of FDG uptake in benign sinonasal papillomas. METHODS: Case report (n = 1) and literature review of similar cases (n = 32). RESULTS: We report the case of a 69-year-old man presenting with an isolated left maxillary sinus mass with avid FDG uptake, discovered on PET/CT imaging. An endoscopic left maxillary mega-antrostomy provided successful definitive treatment for final pathologic diagnosis of oncocytic papilloma. Literature review of cases of sinonasal papillomas with avid FDG uptake found that oncocytic papillomas, on average, exhibit greater uptake than inverted papillomas and both may be mistaken as malignancies on PET. CONCLUSION: While PET imaging demonstrating avid FDG uptake is associated with an increased risk of malignancy, it does not rule out the possibility of a benign sinonasal papilloma nor other benign inflammatory lesions. Particularly, oncocytic papillomas may have very high FDG uptake and mimic malignant lesions.

Subjective and Objective Measurements of Sinonasal Manifestations in Patients With Autoimmune Disorders.

OBJECTIVES/HYPOTHESIS: A number of autoimmune disorders (ADs) are associated with a spectrum of sinonasal manifestations comparable to chronic rhinosinusitis (CRS). Our objective was to study the subjective and objective measurements of sinonasal manifestations of ADs. STUDY DESIGN: Retrospective cohort study. METHODS: All patients with ADs referred to our tertiary care rhinology clinic from 2008 to 2019 with sinonasal symptoms were compared to randomly selected cohorts of noneosinophilic CRS without nasal polyps (neCRSsNP) and eosinophilic CRSsNP (eCRSsNP). Demographic data, along with the 22-item Sino-Nasal Outcome Test (SNOT-22), Lund-Kennedy (LK) endoscopy score, Lund-Mackay (LM) computed tomography (CT) score, nasal crusting, and epistaxis were reviewed at presentation. RESULTS: Fifty-three patients with an AD (26 with sarcoidosis, 14 with systemic lupus erythematosus, 10 with granulomatosis with polyangiitis [GPA], and three with pemphigoid vulgaris) were identified, and compared to 75 randomly selected neCRSsNP patients and 75 eCRSsNP patients. Patients with an AD had an average SNOT-22 score of 44.4 (confidence interval [CI]: 34.6-51.2) compared to 25 (CI: 24.4-25.1) and 29.7 (CI: 20.3-29.7) for neCRSsNP and eCRSsNP patients, respectively (P < .0001), and an average LK endoscopy score of 5.3 (CI: 4.3-6.3), compared to 3.4 (P = .005, CI: 2.7-4) in neCRSsNP and 4.4 in eCRSsNP (P = .2, CI: 3.7-5). There was no significant difference in the CT score compared to both groups. Patients with an AD also scored significantly worse on all four SNOT-33 subdomains, nasal obstruction, nasal crusting, and epistaxis. Additionally, patients with GPA had the worst symptomatic and endoscopy scores. CONCLUSIONS: Patients with ADs presenting with sinonasal symptoms have a more severe subjective and objective presentation than patients with CRS without nasal polyps. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:255-259, 2021.

Anterior Pedicled Lateral Nasal Wall Flap for Endonasal Lining: A Radiologic and Anatomical Study.

OBJECTIVES/HYPOTHESIS: The objective of this radiological/anatomical study was to evaluate the feasibility of a new endoscopic technique that uses the anterior pedicled lateral nasal flap (APLNW) for the endonasal lining in complex nasal reconstructions. STUDY DESIGN: An anatomical study was performed on 20 nasal fossae of cadaverous specimens to measure the area and lengths of the anterior pedicled nasal lateral wall flap. In addition, a radiological analysis with computed tomography was performed in 150 nostrils to determine the potential donor of the simple and extended flap in the nasal fossa floor. Complex nasal reconstruction with nasofrontal flap and internal lining using the lateral wall pedicled flap was performed in 3 patients. RESULTS: Complete reconstruction for the inner lining of the nasal tip and lateral nasal wall was achieved in the cadaveric study (10 specimens). The surface areas of the simple and extended APLNW flaps were 7.53 (standard deviation [SD] 1.25) cm2 and 24.6 (SD 3.14) cm2 , respectively. Using computed tomography scans, we determined that to reconstruct defects secondary to full-thickness nasal defects, the APLNW flap surface for the simple and extended versions was 7.90 (SD 1.68) cm2 and 23.64 (SD 4.7) cm2 . We present one case were the APLNW flap was used. CONCLUSIONS: The simple or expanded APLNW flap represents a feasible option to reconstruct the internal lining in complex nasal reconstruction. LEVEL OF EVIDENCE: NA Laryngoscope, 131:E1462-E1467, 2021.

Level of sex hormones and their association with acetylsalicylic acid intolerance and nasal polyposis.

BACKGROUND: Chronic rhinosinusitis may be associated with nasal polyposis. Recurrence of disease is often observed and may be due to an intolerance of acetylsalicylic acid. Sex hormones are known to modulate allergic reactions and inflammation. Whether they may be involved in the development and progression of nasal polyposis has not been investigated yet. AIM: Examine the relationship between levels of sex hormones and nasal polyposis. METHODS: Hormonal levels (estradiol, testosterone and progesterone) in patients with nasal polyposis (n = 26) with or without acetylsalicylic acid-intolerance were determined and compared to hormonal levels in patients with septal deviation (n = 35). Cone-beam computed tomography scans were analysed by using scores as defined by Lund and Mackay and by Kennedy. RESULTS: Our results show a 5 times greater odds (p = 0.01) for developing nasal polyposis in the presence of lowered estradiol plasma levels than in the presence of normal / elevated levels. When analyzing females and males separately, a 6 times greater odds for females to develop nasal polyposis in the presence of lowered estradiol plasma levels was calculated (p = 0.02). Thus, females are more likely to develop nasal polyposis when they have lowered estradiol levels than males. In addition, female patients showed an increased risk for developing ASA intolerance (p = 0.01). CONCLUSION: Variation of sex hormones may be involved in nasal polyposis. Further studies including more patients to validate the presented results are required. SIGNIFICANCE: Retrospective clinical investigation suggesting a correlation between varying sex hormones and nasal polyposis.

Nasal Brushing Sampling and Processing using Digital High Speed Ciliary Videomicroscopy - Adaptation for the COVID-19 Pandemic.

Primary Ciliary Dyskinesia (PCD) is a genetic motile ciliopathy, leading to significant otosinopulmonary disease. PCD diagnosis is often missed or delayed due to challenges with different diagnostic modalities. Ciliary videomicroscopy, using Digital High-Speed Videomicroscopy (DHSV), one of the diagnostic tools for PCD, is considered the optimal method to perform ciliary functional analysis (CFA), comprising of ciliary beat frequency (CBF) and beat pattern (CBP) analysis. However, DHSV lacks standardized, published operating procedure for processing and analyzing samples. It also uses living respiratory epithelium, a significant infection control issue during the COVID-19 pandemic. To continue providing a diagnostic service during this health crisis, the ciliary videomicroscopy protocol has been adapted to include adequate infection control measures. Here, we describe a revised protocol for sampling and laboratory processing of ciliated respiratory samples, highlighting adaptations made to comply with COVID-19 infection control measures. Representative results of CFA from nasal brushing samples obtained from 16 healthy subjects, processed and analyzed according to this protocol, are described. We also illustrate the importance of obtaining and processing optimal quality epithelial ciliated strips, as samples not meeting quality selection criteria do now allow for CFA, potentially decreasing the diagnostic reliability and the efficiency of this technique.

In vivo assessment of cerebrospinal fluid efflux to nasal mucosa in humans.

Extra-vascular molecular clearance routes from the brain and cerebrospinal fluid (CSF) remain insufficiently characterized in humans. Animal studies consistently suggest that the cribriform plate and nasal lymphatic vessels are crucial for molecular clearance from CSF. In this study, we aimed to examine human in vivo transport of a CSF tracer from CSF to nasal mucosa. We hypothesised a CSF tracer would enrich in nasal mucosa provided that nasal lymphatic drainage has a significant role in CSF molecular clearance. Consecutive magnetic resonance imaging during 48 h after intrathecal administration of a tracer (gadobutrol) was performed in 24 patients. Despite a strong enrichment of CSF tracer in CSF spaces nearby the cribriform plate, there was no significant enrichment of CSF tracer in nasal mucosa, as measured in superior, medial and inferior turbinates, or in the nasal septum. Therefore, this in vivo study questions the importance of CSF drainage to the human nasal mucosa and emphasizes the need of further human studies.

Radiological changes in maxillary sinus morphology after lateral sinus floor augmentation.

<b>Background:</b> Restoration of the masticatory function in patients with edentulous posterior maxilla is often challenging due to the severe atrophy of the alveolar ridges and proximity of the maxillary sinus, resulting in insufficient bone quantity for implant-supported dentures. <br><b>Aim:</b> The purpose of this study was to analyze the changes in Schneiderian membrane thickness after lateral sinus floor augmentation (LSFA) using cone beam computed tomography (CBCT). <br><b>Material and methods:</b> WLSFA procedures using different bone grafting materials were performed in 87 patients, operated on in two clinical institutions from 2016 to 2018. CBCT examination was performed in all patients before the LSFA procedure, at 1 month after surgery, and after 6 months, before implant placement or loading. <br><b>Results: </b>Minor r adiological changes in mucous membrane morphology were observed preoperatively in 17.1% of patients. Postoperative CBCT in the early postsurgical period demonstrated that the number of intact non-specific sinuses decreased significantly, i.e. from 86.7% to 26.7%. The number of cases with local hypertrophia of the mucous membrane increased from 20.3% to 26.7%. Mucosal thickening was observed in 41.7% vs 7.5%. The number of intact sinuses increased to 57.8%. The number of cases with local membrane hypertrophia also increased - to 37.4%. The number of cases with mucosal thickening or fluid accumulation decreased significantly to 11.8 and 5.3% respectively. In 2 cases the development of chronic sinusitis required secondary surgeries. <br><b>Conclusion:</b> The present retrospective study revealed that minor radiological changes in the morphology of the maxillary sinus mucosa were observed preoperatively in 17.1% of patients who underwent LSFA procedures. In the early and late postoperative period their frequency increased to 68.5% and 47.1%, respectively. However, the clinical signs of sinusitis developed only in 19.26% of patients. No significant correlations were found between the frequency and severity of postoperative radiological changes and residual bone height, sinus anatomy, initial state of the mucous membrane and type of the grafting material.

Schneiderian membrane thickness variation following endodontic procedures: a retrospective cone beam computed tomography study.

BACKGROUND: To assess the change of the Schneider membrane thickness measured by CBCT before and after root canal treatment, retreatment and pulp capping procedures. METHODS: This retrospective study was conducted on CBCT scans of a patient population of Guy's Hospital NHS Foundation Trust, London. Three groups of patients were studied: Group 1 consisted of patients referred for primary endodontic treatment; Group 2 for endodontic retreatment; Group 3 for indirect pulp capping procedures (serving as a control group). Follow up scans were carried out 1 year after treatment. Measurements were carried out on CBCT scans and data were analysed statistically by Wilcoxon Signed Rank Test. Linear regression was used to assess predictive parameters for membrane thickness. RESULTS: A statistically significant reduction of the Schneider membrane thickness was observed one year after endodontic treatment and retreatment (P < 0.05) but no significant reduction was observed after pulp capping procedures. Linear regression showed that age and gender were significant predictors influencing the Schneider membrane thickness. CONCLUSIONS: Within the limitations of this retrospective study, following root canal treatment and re-treatment a Schneiderian membrane thickness reduction occurred at 1-year follow-up. The removal of odontogenic infection following endodontic treatment may help reducing the thickness of the Schneider membrane.

Effects of Intranasal Epinephrine on Cerebrospinal Fluid Epinephrine Pharmacokinetics, Nasal Mucosa, Plasma Epinephrine Pharmacokinetics, and Cardiovascular Changes.

PURPOSE: We aimed to assess intranasal (IN) epinephrine effects on cerebrospinal fluid (CSF) absorption, nasal mucosa quality, plasma epinephrine pharmacokinetics (PK), and cardiovascular changes in dogs. METHODS: CSF epinephrine concentration was measured and nasal mucosa quality was evaluated after IN epinephrine 4 mg and one or two 4 mg doses (21 min apart), respectively. Maximum plasma concentration [Cmax], time to Cmax [Tmax], area under the curve from 0 to 120 min [AUC0-120], and cardiovascular effects were evaluated after epinephrine IN (4 and 5 mg) and intramuscular (IM; 0.3 mg). Clinical observations were assessed. RESULTS: After epinephrine IN, there were no changes in CSF epinephrine or nasal mucosa. Cmax, Tmax, and AUC1-120 were similar following epinephrine IN and IM. Epinephrine IN versus IM increased plasma epinephrine at 1 min (mean ± SEM, 1.15 ± 0.48 for 4 mg IN and 1.7 ± 0.72 for 5 mg IN versus 0.47 ± 0.11 ng/mL for 0.3 mg IM). Epinephrine IN and IM produced similar heart rate and ECG results. Clinical observations included salivation and vomiting. CONCLUSIONS: Epinephrine IN did not alter CSF epinephrine or nasal tissue and had similar cardiovascular effects as epinephrine IM. Epinephrine IN rapidly increased plasma epinephrine concentration versus epinephrine IM.