The epidemiology and burden of gastroparesis: Real-world data from a large healthcare provider in Israel.

BACKGROUND: Gastroparesis is a gastrointestinal motility dysfunction characterized by delayed gastric emptying in the absence of gastric mechanical obstruction. Data on the epidemiology of gastroparesis are sparse even though the condition substantially impairs patients' quality of life. The aim of this study was to describe the epidemiology and estimate the short-term healthcare resource use burden of gastroparesis in a large population. METHODS: This cross-sectional study utilized computerized data from Maccabi Healthcare Services, a 2.5-million member state-mandated health organization in Israel. Data were collected between 2003 and 2018 to assess the prevalence of gastroparesis. Definite gastroparesis was defined by gastroparesis diagnosis and gastric emptying test. Probable gastroparesis was defined by gastroparesis diagnosis only. To compare the healthcare resource utilization (HCRU), data were also collected on controls that were individually matched (1:2) for age, sex, and comorbidities. KEY RESULTS: A total of 522 patients with gastroparesis were identified (21.1 per 100,000 WHO age-standardized), including 204 with definite gastroparesis (8.6 per 100,000 WHO). Male to female ratio was 1:2 and mean ± SD age of 54.7 ± 17.1 years. Diabetes accounted for 25.9% of gastroparesis cases and the rest were idiopathic. Gastroparesis patients were more likely to have cardiovascular diseases (10% vs. 6.9% for controls, p = 0.034) and lower prevalence of obesity (17% vs. 24.4%, p < 0.001). HCRU within the 2 years after index date were higher with more hospitalizations than controls (26.4% vs. 15.4%, p < 0.001), and more emergency room visits (31.6% vs. 24.1%, p = 0.002). CONCLUSIONS & INFERENCES: Gastroparesis is uncommon or under-documented in community care settings. Gastroparesis in general is associated with cardiovascular morbidities, lower BMI, and elevated utilization of healthcare services.

Patients with hereditary angioedema and their treatment patterns in Germany: a Delphi consensus study

Background: Little is known about how many patients with hereditary angioedema due to C1 inhibitor deficiency (HAE-C1-INH) receive on-demand and/or prophylactic treatment and what their clinical features are. Here, we estimated, using Delphi-based consensus, prevalence and treatment patterns in Germany as well as patient features linked to long-term prophylaxis. Materials & Methods: Eight experts, who together treat approximately 75% of all German HAE-C1-INH patients, participated in a classic, two-round Delphi survey. Consensus was defined as agreement between at least 75% of participants. Results: Experts agreed that an estimated 1,350 patients in Germany have HAE-C1-INH, i.e. 1.62 per 100,000. One in four patients was estimated to receive long-term prophylaxis. Patient features linked to the use of prophylactic treatment included reduced quality of life, frequent swellings and swellings that affect the upper airways, and >two attacks per month. Conclusion: The rate of prophylactic treatment in Germany is low, but is expected to increase. The level of disease activity and its impact and control are and should be considered in the choice for prophylactic treatment.

Cytomegalovirus infection and rehospitalization rates after allogeneic hematopoietic stem cell and solid organ transplantation: a retrospective cohort study using German claims data.

PURPOSE: This study aimed to describe the cytomegalovirus (CMV) infection rate, rehospitalizations, and comorbidities following allogeneic hematopoietic stem cell transplantation (allo-HSCT) and solid organ transplantation (SOT). METHODS: Patients who received allo-HSCT or SOT in 01/07/2015-30/06/2018 were identified using anonymized German claims data. The transplantation-related hospital admission date was defined as the index date, and patients were followed for up to 12 months (or death, first event relevant). The frequency of CMV infections (confirmed outpatient/inpatient diagnoses, ICD-10-GM codes: B25.-/B27.1) and the rate, number, and duration of all-cause rehospitalizations in the follow-up period were evaluated. RESULTS: A total of 226 allo-HSCT and 250 SOT patients were identified (mean age 52.8 years, 38.9% female). During the 12 months after transplantation, 29.2% of allo-HSCT patients and 16.8% of SOT patients received a CMV diagnosis. The majority of these diagnoses were given during the initial hospitalization or within the following 3 months. Across transplantation types, CMV patients had more hospital readmission days per patient-year (allo-HSCT 93.3 vs. 49.4, p = 0.001; SOT 42.0 vs. 20.7, p = 0.005), with a longer mean duration of readmissions (allo-HSCT 22.4 vs. 15.4 days, p < 0.001; SOT 11.6 vs. 7.5 days, p = 0.003). Comorbidity burden in transplantation patients was substantial, with several diagnoses being significantly more common among patients with CMV vs. non-CMV. One-year mortality did not differ significantly between patients with/without CMV. CONCLUSION: Burden of transplant recipients with CMV in terms of rehospitalizations and comorbidities is substantial, highlighting the need for improved CMV prevention and treatment.

Inflammatory Bowel Disease Patients' Treatment Preferences Using a Discrete Choice Experiment Technique: The InPuT Study.

INTRODUCTION: The aim of this study was to investigate patients' preferences regarding the evolving treatment landscape in Crohn's disease (CD) and ulcerative colitis (UC) based on a discrete choice experiment. METHODS: Eligible patients (aged 18 years or older) had a confirmed diagnosis of CD or UC and were willing and able to participate in telephone interviews. The survey design is based on a prior literature review, a pilot study, and clinical expert discussions. Preferences related to clinical and practical features of advanced therapies, like tumor necrosis factor alpha inhibitors, anti-integrins, anti-interleukins, and Janus kinase inhibitors, were assessed. Patients were asked to choose between two different hypothetical treatment alternatives visualized in up to 11 choice scenarios. Based on these choices, the relative importance of treatment characteristics was derived from regression coefficients estimated by a conditional logit model. RESULTS: Of the 291 patients included, 219 (75%) were eligible for this analysis. Among the evaluated attributes in CD, 1-year remission rate was ranked highest, with 42.3% relevance for the overall decision. The second most important attribute was the frequency of serious adverse events (AE) (25.1%), followed by sustained remission over 2 years (17.8%). Lower importance was assigned to the administration mode (14.6%) and none to the frequency of non-serious AE (0.1%). In UC, preferences were driven by efficacy (25.3% for mucosal healing; 23.4% for corticosteroid-free remission) and the frequency of serious AE (18.3%), followed by the administration mode (18.1%). Also, non-serious AE were classified as relevant factors for decision-making (10.7%), while maintaining remission for at least 2 years showed no significant impact (4.4%). CONCLUSION: For both indications, efficacy outcomes were rated most important, followed by the frequency of serious AE. Variations were mainly found in the evaluation of non-serious AE and sustained remission. Considering patient preferences may improve the effectiveness of available therapies for moderate to severe CD and UC.

Novel Approaches Identifying Relevant Patient-Reported Outcomes in Patients With Inflammatory Bowel Diseases-LISTEN 1.

Background: Several patient-reported outcomes (PROs) have been established and are widely used in the assessment of patients with inflammatory bowel disease (IBD). However, it has never been investigated which PRO items are experienced by and are considered most relevant for IBD patients. Methods: A review of IBD-related disease scores by a steering committee led to the identification of relevant PRO questions and assignment to 16 different PRO categories (9 symptoms and 7 impacts) that characterize patient's disease burden. In a cross-sectional study, a digital patient survey was carried out to determine the self-reported experience by multiple response, the relevance of these PRO categories by pairwise comparison and the suitability of the respective questions and answer possibilities by yes-or-no-question. Results: Sixty patients with Crohn's disease (CD) (56.7% women; mean age 40.6 years; mean disease duration 12.4 years) and 60 patients with ulcerative colitis (UC) (51.7% women; mean age 37.3 years; mean disease duration 9.0 years) participated in the patient survey. All predefined symptoms and impacts, with the exception of nausea, were experienced by at least 50% of patients. Stool urgency and pain were rated the 2 most important symptoms in CD patients with similar ratings for relevance. Stool urgency was also the most important symptom in patients with UC, followed by stool frequency. Differences in self-reported experience between CD and UC patients were seen for the symptoms of rectal bleeding, pain, and nausea. Most important impact of symptoms in both patient groups were general wellbeing followed by social activities, while sexual activity was the least relevant impact category. Conclusions: Stool urgency was the most relevant and most self-reported symptom for both CD and UC. Relevance and self-reported experience of pain and rectal bleeding differed between the 2 diseases. Therefore, the future collection of PROs should take these disease specificities into consideration.

Safety of vedolizumab in the treatment of pregnant women with inflammatory bowel disease: a targeted literature review.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) commonly affect women in their childbearing years. Vedolizumab (VDZ) is approved for treatment of moderate-to-severe CD and UC, but there is a knowledge gap regarding its use during pregnancy. This targeted literature review describes available evidence on safety of VDZ in pregnant patients in order to offer physicians a detailed and balanced view on persistent data during their decision-making process for an individualized treatment concept. METHODS: The search included literature from the MEDLINE database and abstracts of five gastroenterological conferences published until November 2019. Publications were included if pregnancy outcomes in women receiving VDZ or neonatal outcomes in newborns of women previously exposed to VDZ were reported. RESULTS: Out of 196 initially identified records, 18 publications reporting results of five different studies were identified. In total, for 213 of 284 VDZ-exposed documented pregnancies the following pregnancy outcomes were reported: 167 live births (172 infants due to twin births), 1 stillbirth, 35 miscarriages, 10 elective terminations (1 due to detected Down syndrome). Furthermore, during pregnancy, the following complications were observed: seven cases of (pre) eclampsia, three cases of premature rupture of membranes and one case each of placenta previa, chorioamnionitis, pneumonia, first-trimester bleeding, cholestasis, sepsis, or neonatal intraventricular hemorrhage. Based on 172 infants, 30 preterm deliveries (17.4%), 9 cases of low birth weight (5.2%), 5 infections (2.9%), and 6 cases (3.8%) with congenital anomalies were reported. CONCLUSION: There was no evidence for safety concerns regarding pregnancy outcomes associated with VDZ therapy. Due to the limited scope of included records, further research is needed to understand the safety profile regarding the use of VDZ during pregnancy.

Real-world clinical effectiveness and safety of vedolizumab and anti-tumor necrosis factor alpha treatment in ulcerative colitis and Crohn's disease patients: a German retrospective chart review.

BACKGROUND: Real-world comparisons of biologic treatment outcomes for ulcerative colitis (UC) or Crohn's disease (CD) patients are limited. We sought to evaluate the real-world effectiveness of vedolizumab (VDZ) and anti-tumor necrosis factor alpha (anti-TNFα) in UC and CD patients in Germany. METHODS: A retrospective chart review (15 sites) investigated UC and CD patients who were biologic-treatment naïve (biologic-naïve) or had received no more than one prior anti-TNFα before initiating treatment with VDZ or anti-TNFα between 15 July 2014 and 20 October 2015. Kaplan-Meier analyses assessed time to first chart-documented clinical remission (CR) and symptom resolution (UC: rectal bleeding [RB], stool frequency [SF]; CD: abdominal pain [AP], liquid stools [LS]) and outcome duration. RESULTS: A total of 133 UC (76 VDZ; 57 anti-TNFα) and 174 CD (69 VDZ; 105 anti-TNFα) patients were included. By Week 26, estimated cumulative rates of patients achieving CR or symptom resolution with VDZ vs anti-TNFα treatment were for UC: CR, 53.7% vs 31.7%; RB, 66.8% vs 55.8%; and SF, 59.8% vs 50.7%, respectively; and for CD: CR, 14.4% vs 32.8%; AP, 62.5% vs 56.0%; and LS, 29.9% vs 50.3%, respectively. Outcomes were sustained similarly between treatments, except RB (VDZ vs anti-TNFα: median 38.1 vs 15.1 weeks, P = 0.03). Treatment-related adverse events occurred in 5.3% vs 7.0% (UC) and 8.7% vs 19.0% (CD) of VDZ vs anti-TNFα patients, respectively. CONCLUSIONS: Although there were differences in CR, symptom resolution, and safety profiles, real-world data support both VDZ and anti-TNFα as effective treatment options in UC and CD.

The Nonmetabolized ß-Blocker Nadolol Is a Substrate of OCT1, OCT2, MATE1, MATE2-K, and P-Glycoprotein, but Not of OATP1B1 and OATP1B3.

Nadolol is a nonmetabolized ß-adrenoceptor antagonist and is a substrate of OATP1A2, but not of OATP2B1. However, other drug transporters involved in translocation of nadolol have not been characterized in detail. We therefore investigated nadolol as a potential substrate of the hepatic uptake transporters OATP1B1, OATP1B3, and OCT1 and of the renal transporters OCT2, MATE1, and MATE2-K expressed in HEK cells. Moreover, the importance of P-glycoprotein (P-gp) for nadolol transport was studied using double transfected MDCK-OCT1-P-gp cells. Nadolol was not transported by OATP1B1 and OATP1B3. In contrast, a significantly higher nadolol accumulation (at 1 and 10 µM) was found in OCT1, OCT2, MATE1, and MATE2-K cells compared to control cells (P < 0.01). Km values for OCT2-, MATE1-, and MATE2-K-mediated nadolol uptake were 122, 531, and 372 µM, respectively. Cimetidine (100 µM, P < 0.01) and trimethoprim (100 µM, P < 0.001) significantly inhibited OCT1-, OCT2-, MATE1-, and MATE2-K-mediated nadolol transport. The P-gp inhibitor zosuquidar significantly reduced basal to apical nadolol transport in monolayers of MDCK-OCT1-P-gp cells. In summary, nadolol is a substrate of the cation transporters OCT1, OCT2, MATE1, MATE2-K, and of P-gp. These data will aid future in vivo studies on potential transporter-mediated drug-drug or drug-food interactions with involvement of nadolol.

Inhibitory Effects of Green Tea and (-)-Epigallocatechin Gallate on Transport by OATP1B1, OATP1B3, OCT1, OCT2, MATE1, MATE2-K and P-Glycoprotein.

Green tea catechins inhibit the function of organic anion transporting polypeptides (OATPs) that mediate the uptake of a diverse group of drugs and endogenous compounds into cells. The present study was aimed at investigating the effect of green tea and its most abundant catechin epigallocatechin gallate (EGCG) on the transport activity of several drug transporters expressed in enterocytes, hepatocytes and renal proximal tubular cells such as OATPs, organic cation transporters (OCTs), multidrug and toxin extrusion proteins (MATEs), and P-glycoprotein (P-gp). Uptake of the typical substrates metformin for OCTs and MATEs and bromosulphophthalein (BSP) and atorvastatin for OATPs was measured in the absence and presence of a commercially available green tea and EGCG. Transcellular transport of digoxin, a typical substrate of P-gp, was measured over 4 hours in the absence and presence of green tea or EGCG in Caco-2 cell monolayers. OCT1-, OCT2-, MATE1- and MATE2-K-mediated metformin uptake was significantly reduced in the presence of green tea and EGCG (P < 0.05). BSP net uptake by OATP1B1 and OATP1B3 was inhibited by green tea [IC50 2.6% (v/v) and 0.39% (v/v), respectively]. Green tea also inhibited OATP1B1- and OATP1B3-mediated atorvastatin net uptake with IC50 values of 1.9% (v/v) and 1.0% (v/v), respectively. Basolateral to apical transport of digoxin was significantly decreased in the presence of green tea and EGCG. These findings indicate that green tea and EGCG inhibit multiple drug transporters in vitro. Further studies are necessary to investigate the effects of green tea on prototoypical substrates of these transporters in humans, in particular on substrates of hepatic uptake transporters (e.g. statins) as well as on P-glycoprotein substrates.

Renal tubular secretion of pramipexole.

The dopamine agonist pramipexole is cleared predominantly by the kidney with a major contribution of active renal secretion. Previously the organic cation transporter 2 (OCT2) was shown to be involved in the uptake of pramipexole by renal tubular cells, while the mechanism underlying efflux into tubular lumen remains unclear. Cimetidine, a potent inhibitor of multidrug and toxin extrusion proteins 1 (MATE1) and 2-K (MATE2-K), decreases renal pramipexole clearance in humans. We hypothesized that, in addition to OCT2, pramipexole may be a substrate of MATE-mediated transport. Pramipexole uptake was investigated using MDCK or HEK cells overexpressing OCT2, MATE1 or MATE2-K and the respective vector controls (Co). Transcellular pramipexole transport was investigated in MDCK cells single- or double-transfected with OCT2 and/or MATE1 and in Co cells, separating a basal from an apical compartment in a model for renal tubular secretion. Pramipexole uptake was 1.6-, 1.1-, or 1.6-folds in cells overexpressing OCT2, MATE1 or MATE2-K, respectively as compared to Co cells (p<0.05). In transcellular transport experiments, intracellular pramipexole accumulation was 1.7-folds in MDCK-OCT2 (p<0.001), and transcellular pramipexole transport was 2.2- and 4.0-folds in MDCK-MATE1 and MDCK-OCT2-MATE1 cells as compared to Co cells (p<0.001). Transcellular pramipexole transport was pH dependent and inhibited by cimetidine with IC50 values of 12µM and 5.5µM in MATE1 and OCT2-MATE1 cells, respectively. Taken together, coordinate activity of OCT2-mediated uptake and MATE-mediated efflux determines pramipexole renal secretion. Reduced OCT2 or MATE transport activity due to genetic variation or drug-drug interactions may affect pramipexole renal secretion.

Identification of PDGF-BB binding to thymosin ß4 by chemical cross-linking.

INTRODUCTION: The purpose of our work was to identify unknown interaction partners of thymosin ß4 (Tß4). It was suggested that Tß4 could be an antifibrotic drug for treatment of liver fibrogenesis, because Tß4 prevents the platelet-derived growth factor-BB (PDGF-BB)-induced activation of hepatic stellate cells (HSCs). Very little information is available how Tß4 counteracts the PDGF-BB-induced activation of HSCs. We propose the hypothesis that Tß4 could bind directly to PDGF-BB and thereby reduce the concentration of free PDGF-BB available for binding to the PDGF-ß receptor. METHODS: To prove our suggestion of a direct interaction between Tß4 and PDGF-BB, we carried out chemical as well as photochemical cross-linking experiments between the two pure proteins in vitro. RESULTS: We identified an interaction between Tß4 and PDGF-BB by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) cross-linking as well as through biotin label transfer using a bifunctional photoactivatable derivative of Tß4. In an in vitro system, PDGF-BB was identified as the first extracellular partner interacting with Tß4. This interaction could influence PDGF-BB binding to its receptor and abolish PDGF-BB-related effects. CONCLUSION: Direct interaction of Tß4 with extracellular factors should be considered as a potential mechanism to explain the pleiotropic effects of ß-thymosins.

Peptide labeling with photoactivatable trifunctional cadaverine derivative and identification of interacting partners by biotin transfer.

A new photoactivatable trifunctional cross-linker, cBED (cadaverine-2-[6-(biotinamido)-2-(p-azidobenzamido) hexanoamido]ethyl-1,3'-dithiopropionate), was synthesized by chemical conversion of sulfo-SBED (sulfosuccinimidyl-2-[6-(biotinamido)-2-(p-azidobenzamido) hexanoamido]ethyl-1,3'-dithiopropionate) with cadaverine. This cross-linker was purified by reversed-phase high-performance liquid chromatography (RP-HPLC) and characterized using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) analysis. cBED is based on sulfo-SBED that has a photoactivatable azido group, a cleavable disulfide bond for label transfer methods, and a biotin moiety for highly sensitive biotin/avidin detection. By ultraviolet (UV) light, the azido group is converted to a reactive nitrene, transforming transient bindings of interacting structures to covalent bonds. In contrast to the sulfo-N-hydroxysuccinimide (sulfo-NHS) moiety of sulfo-SBED, which attaches quite unspecifically to amino groups, cBED includes a cadaverine moiety that can be attached by transglutaminase more specifically to certain glutamine residues. For instance, thymosin ß4 can be labeled with cBED using tissue transglutaminase. By high-resolution HPLC/ESI-MS (electrospray ionization-mass spectrometry) and tandem MS (MS/MS) of the trypsin digest, it was established that glutamine residues at positions 23 and 36 were labeled, whereas Q39 showed no reactivity. The covalent binding of cBED to thymosin ß4 did not influence its G-actin sequestering activity, and the complex could be used to identify new interaction partners. Therefore, cBED can be used to better understand the multifunctional role of thymosin ß4 as well as of other proteins and peptides.

Thymosin ß4 and tissue transglutaminase. Molecular characterization of cyclic thymosin ß4.

Thymosin ß4 is the prototype of ß-thymosins and is present in almost every mammalian cell. It is regarded to be the main intracellular G-actin sequestering peptide. Thymosin ß4 serves as a specific glutaminyl substrate for guinea pig transglutaminase. In the absence of an appropriate additional aminyl donor an ε-amino group of thymosin ß4 serves also as an aminyl substrate and an intramolecular bond is formed concomitantly NH3 (17 Da) is lost. The molecular mass of the product is 4,949.6 Da. This is 16.3 Da less than the molecular mass of thymosin ß4 (4,965.9 Da). Digestion with endopeptidases and Edman degradation of the fragments identified the exact position of the ring forming isopeptide bond. In spite of 3 glutaminyl and 9 lysyl residues of thymosin ß4 only one isopeptide bond between Lys16 and Gln36 was formed (cyclic thymosin ß4). These two amino acid residues are conserved in all ß-thymosins. Cyclic thymosin ß4 still forms a complex with G-actin albeit the stability of the complex is about one fiftieth of the stability of the thymosin ß4 × G-actin complex.

High-resolution HPLC-ESI-MS characterization of the contact sites of the actin-thymosin ß(4) complex by chemical and enzymatic cross-linking.

Thymosin ß4 sequesters actin by formation of a 1:1 complex. This transient binding in the complex was stabilized by formation of covalent bonds using the cross-linking agents 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and a microbial transglutaminase. The localization of cross-linking sites was determined after separating the products using SDS-PAGE by tryptic in-gel digestion and high-resolution HPLC-ESI-MS. Three cross-linked fragments were identified after chemical cross-linking, indicating three contact sites. Because the cross-linked fragments were detected simultaneously with the corresponding non-cross-linked fragments, the three contact sites were not formed in parallel. K3 of thymosin ß4 was cross-linked to E167 of actin, K18 or K19 of thymosin ß4 to one of the first three amino acids of actin (DDE), and S43 of thymosin ß4 to H40 of actin. The imidazole ring of histidine was proven to be an acyl acceptor for carbodiimide-mediated cross-linking. Molecular modeling proved an extended conformation of thymosin ß4 along the subdomains 1 to 3 of actin. The enzymatic cross-linking using a microbial transglutaminase led to the formation of three cross-linking sites. Q41 of actin was cross-linked to K19 of thymosin ß4, and K61 of actin to Q39 of thymosin ß4. The third cross-linking site was identified between Q41 of actin and Q39 of thymosin ß4, which are simultaneously cross-linked to K16, K18, or K19 of thymosin ß4. When both cross-linking reactions are taken together, the complex formation of actin by thymosin ß4 is more likely to be flexible than rigid and is localized along the subdomains 1 to 3 of actin.

Identification of interaction partners of ß-thymosins: application of thymosin ß4 labeled by transglutaminase.

In this review, we identify potential interaction partners of the ß-thymosin family. The proteins of this family are highly conserved peptides in mammals and yet only one intracellular (G-actin) and one cell-surface protein (ß subunit of F(1) -F(0) ATP synthase) were identified as interaction partners of thymosin ß4. Cross-linking experiments may be a possible approach to discover additional proteins that interact with the ß-thymosin family. It has previously been shown that thymosin ß4 can be labeled at its glutaminyl residues with various cadaverines using tissue transglutaminase. Here, we illuminate recent results and give an outlook on upcoming work in the field.

Antibodies in research of thymosin ß4: investigation of cross-reactivity and influence of fixatives.

Antibodies against thymosin ß4 are available from various sources and have been used in immunohistochemistry, ELISA, and Western blot analyses. None of these antibodies have been fully characterized for specificity and influence of fixation techniques. This presents a difficulty because many tissues express more than one member of the ß-thymosin family; in addition, highly homologous sequences are typical elements of ß-thymosins. It is also important to scrutinize the influence of fixatives on the antibody-binding capability. Fixatives such as formaldehyde are well known as cross-linking reagents. Chemical modifications within the thymosin ß4 molecule might change the putative epitope recognized by the antibody. These considerations suggest that investigations on thymosin ß4 antibodies available to the scientific community are important and necessary before any experiment can be performed to exclude cross-reactivity with other ß-thymosins that are coexistent in the examined tissue and to prove antibody binding after fixation steps.

Role of ultrasound compared to age-related formulas for uncuffed endotracheal intubation in a pediatric population.

BACKGROUND: It is often difficult to determine the correct size of endotracheal tubes (ETT) needed for intubating pediatric patients. Therefore, we evaluated the role of ultrasound in pediatric patients to compare the correct size of an uncuffed (ETT) with the minimal transverse diameter of the subglottic airway (MTDSA) measured by ultrasound and with tube size predicted by different age-related formulas. METHODS: A total of 50 pediatric patients ≤ 5 years were enrolled. As a standard, we defined the adequate ETT size with no audible leakage below a ventilation pressure of 15 mbar and with an audible leakage above 25 mbar. The maximum allowed difference between the prediction method result and the ETT that fit was defined as 0.3 mm. Ultrasound was performed before the intubation procedure; the intubating anesthesiologists were blinded to the results of the ultrasound measurement. Agreement between the two age-based formulas most commonly used at our department and MTDSA with the correct ETT size (standard) was analyzed using a Bland-Altman plot. Correlation and regression analyses were performed and the numbers of correct intubation trials recorded. RESULTS: The frequency of bias ≤ 0.3 mm between each method and the correct ETT in the first attempt was <50% and the mean number of reintubations 1.6 ± 1.3. In contrast to age-related formulas, however, the ultrasonographically determined MTDSA was not significantly different from the correct ETT. MTDSA was highly associated with the outer diameter of the ETT (r = 0.869, R(2) = 0.754). CONCLUSIONS: Measuring MTDSA by ultrasound facilitates selection of the appropriate ETT in pediatric patients and may reduce the number of reintubations.