Bolus Dose Research Articles

Population pharmacokinetic modeling of the influence of chronic and acute biofilm-forming Pseudomonas aeruginosa lung infection on ciprofloxacin free pulmonary and epithelial lining fluid concentrations

We previously reported that ciprofloxacin (CIP) free lung interstitial concentrations are decreased by biofilm-forming Pseudomonas aeruginosa pulmonary chronic (14 d) infection. To get a better understanding on the influence of infection on CIP lung distribution, in the present study free lung interstitial fluid and epithelial lining fluid (ELF) concentrations were determined by microdialysis in biofilm-forming P. aeruginosa acutely (2 d) and chronically infected (14 d) Wistar rats following CIP 20 mg/kg i.v. bolus dosing. A popPK model was developed, using NONMEM® (version 7.4.3) with FOCE+I, with plasma data described as a three-compartment model with first-order elimination. For lung data inclusion, the model was expanded to four compartments and ELF concentrations were described as a fraction of lung levels estimated as a distribution factor (ƒD). Acute infection had a minor impact on plasma and lung CIP distribution and both infection stages did not alter ELF drug penetration. Probability of target attainment of ƒAUC0–24/MIC ≥ 90 using 20 mg q8h, equivalent to 400 mg q8h in humans, showed that CIP free concentrations in plasma are adequate to successfully treat lung infections. However, lung and ELF free interstitial concentrations might be insufficient to result in efficacious treatment of biofilm-forming P. aeruginosa chronic infection. However, lung and ELF free interstitial concentrations might be insufficient to result in efficacious treatment of biofilm-forming P. aeruginosa chronic infection.

Postoperative infusion of dexmedetomidine via intravenous patient-controlled analgesia for prevention of postoperative delirium in elderly patients undergoing surgery

BackgroundPostoperative delirium (POD) is a common clinical complication in elderly patients after surgery and predicts poor outcomes.AimWe researched whether postoperative infusion of dexmedetomidine (DEX) had prophylactic effect on POD in elderly patients.MethodsA total of 236 patients over the age of 60 years undergoing thoracoabdominal tumor surgery were enrolled in Zhejiang Cancer Hospital from November 2016 to October 2020. The patients were randomly assigned into DEX group (group D) and control group (Group C). DEX was provided via PCIA pump 1–3 days after surgery, which consisted of 3 ug/kg sufentanil and 3 ug/kg DEX in group D, and 3 ug/kg sufentanil without DEX in group C. The PCIA parameters were programmed as follows: total amount 150 ml, 2 ml bolus dose with a lock-out of 10 min and background infusion rate 2 ml/h. The primary endpoint was the incidence of POD, assessed twice daily within 7 days after surgery by Richmond Agitation-Sedation Scale (RASS) and the Confusion Assessment Method–Intensive Care Unit (CAM-ICU). The secondary endpoint was postoperative hospitalization days, ICU stay time, adverse events and non-delirium complications.ResultsThe incidence of POD in all patients was 7%. The incidence of POD in group C was significantly higher than that in group D (10.1% vs 3.4%, P = 0.042). There were no significant differences in length of hospital stay after operation, ICU stay time, the percentage of patients discharged within 7 days after surgery, non-delirium complications, and 30-day all-cause deaths between the two groups. The incidence of hypertension in group D was lower than that in group C (P = 0.003), and there were no differences in other adverse events.ConclusionPatients aged over 60 years received DEX in addition to intravenous patient-controlled analgesia (PCIA) for major thoracoabdominal surgery experienced less delirium.

Safety and efficacy of artesunate treatment in severely injured patients with traumatic hemorrhage. The TOP-ART randomized clinical trial

PurposeThis study aimed at determining whether intravenous artesunate is safe and effective in reducing multiple organ dysfunction syndrome in trauma patients with major hemorrhage.MethodsTOP-ART, a randomized, blinded, placebo-controlled, phase IIa trial, was conducted at a London major trauma center in adult trauma patients who activated the major hemorrhage protocol. Participants received artesunate or placebo (2:1 randomization ratio) as an intravenous bolus dose (2.4 mg/kg or 4.8 mg/kg) within 4 h of injury. The safety outcome was the 28-day serious adverse event (SAE) rate. The primary efficacy outcome was the 48 h sequential organ failure assessment (SOFA) score. The per-protocol recruitment target was 105 patients.ResultsThe trial was terminated after enrolment of 90 patients because of safety concerns. Eighty-three participants received artesunate (n = 54) or placebo (n = 29) and formed the safety population and 75 met per-protocol criteria (48 artesunate, 27 placebo). Admission characteristics were similar between groups (overall 88% male, median age 29 years, median injury severity score 22), except participants who received artesunate were more shocked (median base deficit 9 vs. 4.7, p = 0.042). SAEs occurred in 17 artesunate participants (31%) vs. 5 who received placebo (17%). Venous thromboembolic events (VTE) occurred in 9 artesunate participants (17%) vs. 1 who received placebo (3%). Superiority of artesunate was not supported by the 48 h SOFA score (median 5.5 artesunate vs. 4 placebo, p = 0.303) or any of the trial’s secondary endpoints.ConclusionAmong critically ill trauma patients, artesunate is unlikely to improve organ dysfunction and might be associated with a higher VTE rate.

Prophylactic Fixed-Rate Phenylephrine Versus Norepinephrine Infusion in the Prevention of Post-spinal Anesthesia Hypotension During Cesarean Delivery.

Background Maternal hypotension following spinal anesthesia can be actively countered by the use of vasopressors. Prophylactic infusion of vasopressors with a rescue bolus dosing was observed to be more effective for hemodynamic stability when compared to administering a bolus dose alone. Although phenylephrine is the recommended drug to treat spinal hypotension, many recent studies have focussed on the role of norepinephrine infusions during cesarean section. In this study, we compared prophylactic fixed-rate intravenous infusions of phenylephrine and norepinephrine during cesarean delivery under spinal anesthesia and the requirement of intraoperative provider-administered rescue bolus of phenylephrine needed to overcome post-spinal anesthesia hypotension. Methodology A total of 208 patients undergoing elective cesarean section under spinal anesthesia were randomly assigned to two groups (group P and group N). Group N included 104 patients who received norepinephrine infusion at a rate of 2.5 μg/minute (0.04 μg/kg/minute), and group P included 104 patients who received phenylephrine infusion at a rate of 50 μg/minute (0.8 μg/kg/minute)to treat spinal hypotension. The primary outcome of our study was to compare the reduction in the number and total dose of intraoperative provider-administered rescue bolus of phenylephrine needed to maintain systolic blood pressure. The secondary outcome of our study was to compare the neonatal outcome using umbilical venous blood gas sampling and Apgar score at one and five minutes. Results The total number of phenylephrine rescue bolus required to treat hypotension was significantly lower in group N (p = 0.0005) compared to group P. The neonatal outcome was similar between the two groups. Conclusions Prophylactic norepinephrine infusion when compared to prophylactic phenylephrine infusion is associated with a lesser requirement of rescue phenylephrine boluses.

Comparison of Intubating Conditions at 60 Seconds with Cisatracurium 4*ED95 Dose and Cisatracurium 2*ED95 Dose Plus Priming Dose and Low Dose Ketamine.

To compare the intubating conditions at 60 seconds between 4*ED95 dose of cisatracurium and 2*ED95 dose of cisatracurium in combination with priming and low dose ketamine. jaw relaxation for laryngoscopy, vocal cord position on laryngoscopy, and coughing or bucking response to intubation. To compare the hemodynamic changes up 10 minutes after intubation in the two groups. In this prospective study, a total of 68 patients were undergoing general anesthesia for surgery with placement of endotracheal tube placement. Patients will be divided into two groups comprising 34 patients each. The patients were allocated one of the two groups by computerized randomization. *Group A received bolus dose of cisatracurium which is 0.2 mg/kg (4*ED95). **Group B received cisatracurium in dose of 0.1 mg/kg (2*ED95) with priming (which is 10% of the bolus dose) and low dose ketamine of about 0.5 mg/kg. It was possible to achieve acceptable laryngoscopy and intubating condition in both the groups within 90 seconds. When grades of laryngoscopy and ease of intubation were compared, 2*ED95 dose along with priming plus low dose ketamine produced superior results than 4*ED95 group. When the mean arterial pressure and pulse rate were compared between the two groups, it was observed that mean arterial pressure and pulse rate were only slightly higher in the 2*ED95 along with priming and ketamine.

Effectiveness of norepinephrine versus phenylephrine intravenous boluses for the treatment of hypotension in elective lower-segment cesarean section under spinal anesthesia: A randomized controlled, double-blind study

Abstract Background and Aim: Hypotension following spinal anesthesia is a common adverse effect during caesarean sections, with potentially harmful consequences for both the mother and the fetus. While phenylephrine is the current first-line treatment for maternal spinal hypotension during obstetric anesthesia, norepinephrine has been proposed as a possible alternative due to its weaker b-agonist-mediated positive chronotropic action. However, there is a lack of comparative data on the safety and efficacy of these two drugs in obstetric anesthesia. This study aimed to compare the number of bolus doses of phenylephrine and norepinephrine required to treat hypotension after spinal anesthesia in lower segment caesarean sections, as well as to evaluate maternal and fetal outcomes in both groups, including complications. Materials and Method: A prospective double-blinded randomized controlled trial was conducted, The study included 60 term parturients between the ages of 18 and 40, who had singleton pregnancy and were categorized as American Society of Anaesthesiologists (ASA) physical class II, and who were scheduled for elective caesarean section under spinal anesthesia. the parturients were randomized into two groups: Group N and Group P. Group P patients received an intravenous dose of phenylephrine 100 µg, while Group N patients received an intravenous dose of 8 µg whenever the systolic arterial pressure dropped below 20% of the baseline.primary objective was number of intravenous drugs required to treat spinal hypotension, secondary objective were incidence of maternal and foetal Complications. The data was collected on a form and entered into Excel. Statistical analysis was done using Epi Info 7.2.1.0 for Windows. The Kolmogorov-Smirnov test was used to check normality. Mean and standard deviation or median and range were used to present numerical data, while frequency and percentage were used for categorical data. T-tests compared quantitative variables, and Chi-square tests compared categorical data. Two-tailed tests were used, and a P-value of <0.05 was considered significant. Result: The patient’s demographic profile was comparable in both groups.T he number of bolus doses of study drug required to treat spinal hypotension was significantly lower in Group N versus P (1.50 ± 0.57 vs. 2.13 ± 0.73, p =0.001)Incidence of bradycardia was more in group P, but not statistically significant. Other maternal complications like bradycardia, hypertension, nausea, vomiting, shivering were comparable in both groups. Conclusions: According to our study, Intermittent boluses of norepinephrine were effective in the management of spinal-induced hypotension during caesarean section. Norepinephrine boluses can thus be considered as an alternative to phenylephrine boluses.

Population Pharmacokinetic Modeling of Free Plasma and Free Brain Concentrations of Ceftaroline in Healthy and Methicillin-Resistant Staphylococcus aureus-Infected Wistar Rats.

A population pharmacokinetic model was developed to describe alterations in ceftaroline brain disposition caused by meningitis in healthy and methicillin-resistant Staphylococcus aureus (MRSA)-infected rats. Blood and brain microdialysate samples were obtained after a single bolus dose of ceftaroline fosamil (20 mg/kg) administered intravenously. Plasma data were modeled as one compartment, and brain data were added to the model as a second compartment, with bidirectional drug transport between plasma and brain (Qin and Qout). The cardiac output (CO) of the animals showed a significant correlation with the relative recovery (RR) of plasma microdialysis probes, with animals with greater CO presenting lower RR values. The Qin was approximately 60% higher in infected animals, leading to greater brain exposure to ceftaroline. Ceftaroline brain penetration was influenced by MRSA infection, increasing from 17% (Qin/Qout) in healthy animals to 27% in infected animals. Simulations of a 2-h intravenous infusion of 50 mg/kg every 8 h achieved >90% probability of target attainment (PTA) in plasma and brain for the modal MRSA MIC (0.25 mg/L), suggesting that the drug should be considered an option for treating central nervous system infections.

The Effectiveness of Intravenous lidocaine in Burn Pain Relief: A Randomized Double-Blind Controlled Trial

Objectives: Poor pain control in burn patients as a great public health problem disrupts the healing and rehabilitation process and results in several adverse outcomes. The aim of this study was to investigate the efficacy and safety of intravenous lidocaine in reducing the pain of burn injuries. Materials and Methods: From August 2014 to March 2015, 66 eligible burn patients participated in the study and were randomly divided into two groups of lidocaine (L) and placebo (P). In group L, lidocaine 2% was injected at a bolus dose of 1.5 mg/kg followed by infusion at the dosage of 1.5 mg/kg/h, and in group P, saline was administrated. Pain severity was measured during 24 hours at baseline and 1, 2, 4, 8, 12, 16, 20, 24 hours after intervention based on Numerical Rating Scale (NRS-11). Morphine consumption, Ramsay score, and side effects were also documented. Results: Finally the data from 60 patients were analyzed. Comparing baseline with 24 hours after intervention, NRS-11 scores decreased from 7.12±1.42 to 3.33±0.76 (P<0.001) in group P and from 6.45±1.02 to 2.50±0.72 (P<0.001) in group L. Moreover, the mean of NRS scores during 24 hours in the lidocaine group was significantly lower compared to the placebo group, 3.93±0.72 vs 4.73 ±1.14, (P=0.03). The mean amounts of morphine consumption in group L were significantly lower compared to group P, 14.41 ± 4.86 vs 21.07±6.86, (P=0.001). The mean of Ramsay score in group L was significantly lower compared to group P, 1.38±0.59 vs 1.45±0.6, (P=0.014). Conclusions: This study revealed that intravenous lidocaine was an effective and safe drug for pain reduction in burn patients.

Theory and Practice of Glucocorticoids in COVID-19: Getting to the Heart of the Matter-A Critical Review and Viewpoints.

Prolonged, low-dose glucocorticoids (GCs) have shown the highest efficacy among pharmacological and non-pharmacological treatments for COVID-19. Despite the World Health Organization's recommendation against their use at the beginning of the pandemic, GCs at a dose equivalent to dexamethasone 6 mg/day for 10 days are now indicated in all COVID-19 cases who require respiratory support. However, the efficacy of the intervention depends on the timing of initiation, the dose, and other individual factors. Indeed, patients treated with similar GC protocols often experience different outcomes, which do not always correlate with the presence of comorbidities or with the severity of respiratory involvement at baseline. This prompted us to critically review the literature on the rationale, pharmacological principles, and clinical evidence that should guide GC treatment. Based on these data, the best treatment protocol probably involves an initial bolus dose to saturate the glucocorticoid receptors, followed by a continuous infusion to maintain constant plasma levels, and eventually a slow tapering to interruption. Methylprednisolone has shown the highest efficacy among different GC molecules, most likely thanks to its higher ability to penetrate the lung. Decreased tissue sensitivity to glucocorticoids is thought to be the main mechanism accounting for the lower response to the treatment in some individuals. We do not have a readily available test to identify GC resistance; therefore, to address inter-individual variability, future research should aim at investigating clinical, physiological, and laboratory markers to guide a personalized GC treatment approach.

EFFECT OF REMIFENTANIL BOLUS VS FENTANYL IN ATTENUATING HEMODYNAMIC RESPONSE IN VIDEOLARYNGOSCOPIC ENDOTRACHEAL INTUBATION

Background Elevation of blood pressure and pulse rate are hemodynamic changes that occur during general anesthesia as a consequence of laryngoscopy and endotracheal intubation ETI, different laryngoscopies and many drugs have been tried to reduce these changes.
 Objectives To evaluate and compare the efficacy of minimum dose of fentanyl and comparable remifentanil bolus dose during videolaryngoscopic ETI. 
 Patients and MethodsA triple blind randomized clinical trial implemented on 224 patients of age group between 16-65 years of either sex (ASA I and ASA II) scheduled for elective operation under general anesthesia with endotracheal intubation, they are randomly assigned into two groups, group A and group B representing both fentanyl and remifentanil as the drug preparation was unknown neither by the patient nor by the researcher and nor by the data analyser, in addition propofol two mg/kg and rocuronium 0.8 mg/kg were given then systolic blood pressure SBP, diastolic blood pressure DBP, mean arterial blood pressure MAP and heart rate HR were recorded in five different occasions as (T0) for baseline preinduction, (T1) one minute before ETI, (T2) one minute after ETI, (T3) three minutes after ETI and (T4) five minutes after ETI.
 ResultsThere was a significant difference in the mean value of HR, SBP, DBP, MAP in both groups before, one, three and five minutes after endotracheal intubation with King vision videolaryngoscope KVVL and one μg/kg remifentanil bolus administration (group B) effectively showed substantial reduction in all hemodynamic parameters with significant statistical result (P < 0.05) when compared to intravenous IV fentanyl one μg/kg (group A). 
 ConclusionRemifentanil bolus of one μg/kg is better than intravenous fentanyl one μg/kg in attenuating hemodynamic response to ETI when KVVL used.

Effects of Whey Protein Combined with Amylopectin/Chromium on the Muscle Protein Synthesis and mTOR Phosphorylation in Exercised Rats.

This study aimed to examine the impact of varying doses of whey protein (WP) and amylopectin/chromium complex (ACr) supplementation on muscle protein synthesis (MPS), amino acid and insulin levels, and the rapamycin (mTOR) signaling pathways in exercised rats. A total of 72 rats were randomly divided into nine groups: (1) Exercise (Ex), (2) Ex + WPI to (5) Ex + WPIV with various oral doses of whey protein (0.465, 1.55, 2.33, and 3.1g/kg) and (6) Ex + WPI + ACr to (9) Ex + WPIV + ACr with various doses of whey protein combined with 0.155g/kg ACr. On the day of single-dose administration, the products were given by oral gavage after exercise. To measure the protein fractional synthesis rate (FSR), a bolus dose of deuterium-labeled phenylalanine was given, and its effects were evaluated 1h after supplementation. Rats that received 3.1g/kg of whey protein (WP) combined with ACr exhibited the most significant increase in muscle protein synthesis (MPS) compared to the Ex group (115.7%, p < 0.0001). In comparison to rats that received the same dose of WP alone, those given the combination of WP and ACr at the same dosage showed a 14.3% increase in MPS (p < 0.0001). Furthermore, the WP (3.1g/kg) + ACr group exhibited the highest elevation in serum insulin levels when compared to the Ex group (111.9%, p < 0.0001). Among the different groups, the WP (2.33g/kg) + ACr group demonstrated the greatest increase in mTOR levels (224.2%, p < 0.0001). Additionally, the combination of WP (2.33g/kg) and ACr resulted in a 169.8% increase in 4E-BP1 levels (p < 0.0001), while S6K1 levels rose by 141.2% in the WP (2.33g/kg) + ACr group (p < 0.0001). Overall, supplementation with various doses of WP combined with ACr increased MPS and enhanced the mTOR signaling pathway compared to WP alone and the Ex group.

807-P: Patient and Health Care Provider Experiences of Suboptimal Insulin Dosing in the United States

Objectives: This study described the frequency of suboptimal insulin dosing (missed and mistimed doses) and the factors underlying this behavior from the perspective of people with diabetes (PwD) and healthcare professionals (HCPs.) Methods: For this cross-sectional, multinational non-interventional study, 640 HCPs and 1150 PwD (300 with type 1 diabetes, 850 with type 2 diabetes) completed an online survey. A research vendor recruited adult PwD currently using a non-connected insulin pen (400 from US) and eligible HCPs (160 from US) via validated panels, referrals, list acquisition, and custom methods. Results are presented for US data. Results: Overall, 42% and 61% of PwD reported missing basal and bolus insulin doses in the past 30 days. The average number of missed basal and bolus doses were 3.1 (SD=3.81) and 5.0 (SD=10.30), respectively. PwD reported forgetting, being too busy/distracted, and out of my normal routine as key reasons for missed doses. Overall, 37% and 49% of PwD reported mistiming basal and bolus doses, respectively, in the past 30 days. This corresponded to an average of 3.1 (SD=3.29) mistimed basal and 4.9 (SD=6.28) mistimed bolus doses. Key reasons PwD reported for mistimed doses included being too busy/distracted, forgot or having an unexpected or earlier/later-than-expected meal. Conversely, the majority of HCPs reported ≤20% of their PwD missed/skipped a dose in the past 30 days. HCPs reported dosing reminders (90%), automatically recorded insulin doses and timing (92%) and having insulin and glucose data in one place (94%) as identified solutions. Conclusions: PwD are missing, skipping, or delaying their insulin doses, largely for preventable reasons. HCPs perceive PwD dosing adherence greater than PwD self-reported behaviors. Digital health solutions, such as connected insulin pens, may help PwD reduce missed and mistimed doses as well as help close the perception gap to further optimize insulin management. Disclosure M.B.Davidson: Employee; Eli Lilly and Company. F.Gelsey: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. J.Bower: None. E.Artime: None. E.Spaepen: Consultant; Eli Lilly and Company. R.Newson: Employee; Eli Lilly and Company. Funding Eli Lilly and Company

928-P: The Use of a Novel CGM-Informed Insulin Bolus Calculator Mobile Application by People with Type 1 and Type 2 Diabetes Improves Time in Range

Background and Aims: People with diabetes on basal-bolus insulin regimens face challenges calculating bolus doses. Continuous glucose monitoring (CGM) systems can assist users with bolus dosing optimization through trend arrows. The purpose of this study was to demonstrate the safety and effectiveness of a CGM-informed insulin bolus calculator (IBC, Welldoc, Inc., Columbia, MD, U.S.A.) integrated into a mobile application that applies trend arrow and exercise adjustments to the bolus insulin dose recommendation. This investigational software also provided real-time coaching on CGM data to assist users in improving their time in range (TIR). Methods: Fifty-four participants with diabetes using CGM (Dexcom G6, San Diego, CA, U.S.A.) were enrolled in a 30-day prospective study conducted at two research sites. Participants were asked to use the mobile application to monitor their CGM data and calculate their insulin doses. TIR during the prospective 30-day period was compared to that from 30 days of baseline data. Three populations were defined: 1) the intention-to-treat (ITT) group consisted of all enrolled subjects; 2) the complete cases (CC) group had ≥90% sensor wear time; and 3) the per-protocol (PP) group used the IBC at least 30 times during the study period. Results: In the ITT group, the TIR improved from 68.4% to 71.8% (N=54, P=0.013). In the CC group, the TIR improved from 69.1% to 73.0% (N=49, P=0.005). In the PP group, the TIR improved from 69.2% to 73.0% (N=39, P=0.017). There was no increase in time with low glucose (&amp;lt;70 mg/dL) in all three populations. In a subgroup analysis, TIR increased from 74.7% to 81.4% in those with type 2 diabetes and from 64.4% to 65.2% in those with type 1 diabetes. Conclusions: Use of a novel CGM-informed insulin bolus calculator with trend arrow and exercise dose adjustment by individuals with type 1 and type 2 diabetes was associated with significant improvement in TIR. Disclosure M.Shomali: Employee; WellDoc. C.Kelly: Consultant; WellDoc, Caladrius Biosciences, Inc., Epigenomics AG, Luna, Nevro Corp., Presidio Medical, Hitachi, Ltd., Resmed, Inc., Seaspine Hldgs, Inc., ViaCyte, Inc. A.K.Iyer: Employee; WellDoc. J.Y.Park: None. G.Aleppo: Advisory Panel; Medscape, Consultant; Bayer Inc., Insulet Corporation, Research Support; Dexcom, Inc., Eli Lilly and Company, Emmes, Insulet Corporation, Fractyl Health, Inc., WellDoc, Speaker's Bureau; Dexcom, Inc. Funding Welldoc Inc.

275-OR: Association between Treatment Adherence and CGM Outcomes in People with T1D Using Smart Insulin Pens in a Real-World Setting

Adherence to insulin therapy can be challenging for individuals with T1D. This analysis explored how adherence to basal and bolus insulin injections influences glycemic outcomes. Data were collected from adults (≥18 years) administering basal insulin (degludec) and bolus insulin (aspart or faster aspart) using smart insulin pens with CGM; data were aggregated in 14-day periods. Treatment adherence was defined as the number of missed basal insulin doses (&amp;gt;40 hrs between doses), flex basal insulin doses (dosing time deviated &amp;gt;±6 hrs from previous day) and missed bolus insulin doses (meals with no bolus dose within -15 to +60 mins from meal onset). Glycemic outcomes included time in range (TIR), time below range, glucose management index (GMI), and coefficient of variation. Multinational data from 403 adults who had 3588 14-day periods with ≥70% CGM coverage were analyzed. Individuals with one missed basal dose per 14-days had a lower TIR (-4.04% [95% CI: -6.83; -1.26]) and higher GMI (0.20% [95% CI: 0.02; 0.38]) than individuals without missed basal doses; flex basal doses were not associated with TIR changes. Missed bolus insulin doses were also associated with lower TIR (Table). These real-world data confirm associations between missed basal and bolus insulin doses and impaired TIR, highlighting a need for digital tools such as smart insulin pens to help individuals manage their diabetes. Disclosure T.Danne: Research Support; Abbott Diabetes, AstraZeneca, Bayer Inc., Boehringer-Ingelheim, Dexcom, Inc., Eli Lilly and Company, Novo Nordisk A/S, Sanofi, Medtronic, Stock/Shareholder; DreaMed Diabetes, Ltd. N.V.Hartvig: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. A.Kaas: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. N.N.Knudsen: Employee; Novo Nordisk. J.K.Mader: Advisory Panel; Novo Nordisk A/S, Abbott Diabetes, Roche Diabetes Care, Eli Lilly and Company, Sanofi, Medtronic, Becton, Dickinson and Company, Pharmasense, embecta, Research Support; A. Menarini Diagnostics, Abbott Diabetes, Roche Diabetes Care, Dexcom, Inc., Profusa, Inc., Speaker's Bureau; Novo Nordisk A/S, A. Menarini Diagnostics, Abbott Diabetes, Roche Diabetes Care, Eli Lilly and Company, Sanofi, Boehringer Ingelheim Inc., Becton, Dickinson and Company, Ypsomed AG, Viatris Inc., Servier Laboratories, Medtrust, Stock/Shareholder; Decide Clinical Software GmbH. Funding Novo Nordisk A/S

805-P: Double-Blind Crossover Study of Ultra-Rapid AT247 Compared with NovoLog and Fiasp during Continuous Subcutaneous Infusion (CSII) Assessed by a Hyperinsulinemic Euglycemic Clamp

Background: AT247 is a novel insulin aspart formulation designed for ultra rapid absorption following subcutaneous injection to achieve optimal postprandial glycemic control. Method: Adults (29) with T1DM were randomized to 6 treatment sequences of AT247, Novolog (N), and Fiasp (F). Bolus (0.15 U/kg) and basal (0.02 U/kg/h) doses of insulin were administered via CSII for 3 days. PK and PD were assessed using euglycemic clamps on days (D) 1 and 3. Results: A higher early insulin exposure (AUCIns 0-30min mU/L/h) was observed for AT247 (16.7) vs N (6.3*) or F (13.0**) on D1, Fig 1A. The difference for AT247 was maintained on D3 (20.8) vs N (10.5*) but not vs F (19.2). A higher early glucose lowering effect (AUCGIR 0-60 mins mg/kg) was observed for AT247 (144.4) vs N (70.4*) but not vs F (145.8) on D1 only, Fig 1B. Time to early 50% Cmax insulin (h) occurred earlier for AT247 (0.18) compared to N (0.43*) and F (0.28**) on D1 and D3 (AT247 0.17; N 0.33**; F 0.22**). Statistical significance was p&amp;lt;0.05* or p&amp;lt;0.01**. AT247 was well tolerated with no significant adverse effects. Conclusions: The faster absorption of AT247 resulted in higher early insulin exposure than for F or N following bolus dose delivery during CSII. The demonstrated PK profile of AT247 supports further investigation into its potential to further improve automated insulin delivery. Disclosure M.Hompesch: Board Member; ProSciento, Consultant; Wiley-Blackwell, Employee; ProSciento, Stock/Shareholder; ProSciento. F.J.Lawrence: None. J.Jezek: None. D.J.Gerring: Employee; Arecor. T.Pieber: Advisory Panel; Arecor, Novo Nordisk A/S, Consultant; Lilly, Research Support; AstraZeneca, Novo Nordisk A/S, Sanofi, Speaker's Bureau; Roche Diagnostics.

925-P: Postprandial Glucose Control Using an Extended Bolus for High Fat High Protein (HFHP) Meals during Closed-Loop (CL) in Patients with Type 1 Diabetes (T1D)

We investigated the impact of an extended bolus (EB) for a HFHP breakfast on postprandial glycemia in adolescents with T1D using the Control IQ (CIQ) system. In a randomized cross-over trial, following optimization, the participants with CIQ were asked to have identical standardized HFHP breakfasts (carbohydrate:51 g, fat:40 g, protein:54 g). Meal insulin bolus infusion began within 0.25 hrs of meal consumption (time 0). Eight adolescents (mean age 15.2 ± 1.7 yrs) were randomly assigned in blocks of two to the order in which they received the extended and standard insulin bolus (SB). Postprandial sensor glucose (SG) was measured for 5 hrs. The 5-hr incremental area under the curves (AUC) for SG was comparable for EB and SB (8913 and 10305 mg/dl/min, respectively). Peak SG value, time to peak SG, time in range SG (69.75% for SB vs. 71.7% for EB) and percent time &amp;gt;180 mg/dl were similar in both groups; however, the AUC for SG 2 hrs post meal onset and the rise in SG was significantly higher with EB (p= 0.02 and 0.03 respectively). Insulin use was not significantly different between arms. CL cannot fully compensate for a HFHP meal. However, SB appears to achieve better glycemic control than EB during the two hour postprandial period. Further studies with a larger sample size and larger and longer extended meal boluses may be needed to optimize pre-meal bolus dosing for HFHP meals. Disclosure L.Ekhlaspour: Consultant; Ypsomed AG, Tandem Diabetes Care, Inc., Other Relationship; NIH - National Institutes of Health, Research Support; MannKind Corporation, Tandem Diabetes Care, Inc., JDRF, Speaker's Bureau; Insulet Corporation. Y.J.Hosseinipour: None. B.A.Buckingham: Advisory Panel; Medtronic, Novo Nordisk, Consultant; Lilly, Research Support; Medtronic, Insulet Corporation, Tandem Diabetes Care, Inc. E.Cengiz: Advisory Panel; Eli Lilly and Company, Adocia, Novo Nordisk, Arecor. Funding National Institutes of Health (1K23DK121942)

984-P: Importance and Use of Smart Insulin Pens with Connectivity for Diabetes Management

Smart insulin pens have the potential to fulfill some of the unmet needs of people with diabetes through the accurate administration of bolus doses, the simplification of documentation relating to diabetes therapy, the improvement of communication and the quality of advice given to patients. 305 (2021) and 336 diabetologists in Germany (2022; 38% female, average age 55.2 years) were asked via an online survey about the importance and use of smart insulin pens. In 2022, only 4.8% of all people with type 1 diabetes and 1.5% of all people with type 2 diabetes used a smart pen. The total estimated utilization in 5 years is 18.3% (2021: 23.9%). The importance of smart pens is currently estimated by diabetologists at 8.0%, which is not very high and lower than in 2021 (15.5%). This also applies to the estimated relevance in 5 years (2022: 24.7 %; 2021: 37.9 %). However, 29.7% of all people with type 1 diabetes are considered to have an indication for a smart pen, 30.8% of people with type 2 diabetes and basal insulin therapy, and 37.6% with multiple injection therapy. The main barriers to smart pens identified were patient preference for prefabricated pens (54.6% agreement), low added benefit (49.4%), lack of interoperability with glucose analysis software (44.3%), lack of interoperability with apps (35.6%), too little choice (need to change insulin), and too high cost (33.9%). Despite a very positive attitude towards digitization of diabetes therapy among physicians (2021: 81.9%; 2022: 86.3%), smart pens are currently used only very rarely and their importance for diabetes therapy is considered rather low. Better, simpler, and patient-friendly solutions are needed so that all types of smart insulin devices can be read easily by glucose management software and users experience perceivable benefits. Disclosure L.Heinemann: Consultant; 9am.health. D.Ehrmann: Advisory Panel; Roche Diabetes Care, mySugr, Dexcom, Inc., Speaker's Bureau; Berlin-Chemie AG, Dexcom, Inc. N.Hermanns: Advisory Panel; Insulet Corporation, Research Support; Sanofi-Aventis Deutschland GmbH, Roche Diagnostics, Becton, Dickinson and Company, Speaker's Bureau; Dexcom, Inc., Berlin-Chemie AG. T.Roos: None. B.Kulzer: Advisory Panel; Berlin-Chemie AG, Abbott Diabetes, Bayer Inc., Dexcom, Inc., Novo Nordisk, Insulet Corporation, embecta, Research Support; Sanofi, Roche Diabetes Care.

Systemic transit time correlates with renal cortical perfusion: a preliminary study

Abstract Funding Acknowledgements Type of funding sources: None. Introduction We sought to measure systemic transit time (STT) on MRI dynamic sequences of images in patients based on the recirculation time. In a subset of patients, using the same images, when the abdominal aorta and at least part of one kidney was available, we used a 2-compartment filtration model to approximate renal cortical plasma perfusion (RCPF). Methods This is a retrospective study in a single site MR unit. 218 patients underwent a standard myocardial MR imaging protocol on a 1.5 Tesla MRI system including a pulse-gated, free breathing, dynamic first-pass perfusion scan of 100 phases using a saturation recovery turbo-FLASH pulse sequence (TR = 172 ms / TE = 1.1 ms / flip angle = 5°). Motion correction was applied. All patients were injected intravenously with a bolus dose of gadoteratemeglumine followed by a 20 ml saline flush. On the 218 patients studied, 20 patients were excluded due to shunts:n=5, inadequate first pass perfusion signal:n=8, fitting script did not converge on a solution:n=7. Circular ROIs were placed in the RV (Right Ventricle) and LV (Left Ventricle)cavities. The time curves for each cavity’s signals were fitted to a time-sliding 3 component-LogNormal function using an in-house python script based on the lmfit package (Levenberg-Marquardt method) to determine systemic (STT) and pulmonary transit times (PTT). In a subset of 61 patients, an attempt to measure RCPF was undertaken. An elliptic ROI was drawn in the aorta to follow arterial input. A spline polygon ROI was placed on the visible renal cortical tissue. 14 sets of images were rejected for plasma perfusion analysis for different reasons (absence of suitable abdominal aorta image, absence of suitable renal cortical image, motion artifact, …). Plasma perfusion measurements were made using a 2-compartment filtration model. Results We studied 198 sets of MRI dynamic perfusion images. Our population consists of 65,7% men aged 53,0±16,9 (mean± SD) and 34,3% women aged 55,9 ± 14,1 (mean ± SD). Fitting of the experimental data was very good in most cases (mean R² for RV:0.981, max:0.997, min: 0.907, SD:0.014) (mean R² for LV: 0.994, max:0.999, min: 0.975, SD: 0.004). An example of experimental data fitting can be seen in fig. 1. STT values were as follows: mean = 14.3 s, SD = 3.0s, max = 27.1 s, min = 8.7 s. Measures of recirculation time were highly correlated on the RV and LV side (Pearson’s R =0,975; p &amp;lt; 0,001). We found a significant correlation between STT and PTT (Pearson’s R = 0,521; p &amp;lt; 0,001). In the 47 patients where RCPF could be calculated, a significant negative correlation was found between STT and RCPF (Pearson’s R = -0,578; p &amp;lt; 0,001) (fig. 2). Conclusions Systemic transit time can be accurately measured on standard MRI perfusion scans and is negatively correlated with cortical renal plasma perfusion. Assessing systemic transit time using MRI dynamic perfusion imaging of the heart could be a usable surrogate for end-organ perfusion.

Opioid requirement and pain intensity after mandibular surgeries with dexmedetomidine administration in two ways: intraoperative infusion versus bolus injection.

The purpose of this study is to compare the opioid requirement and pain intensity after surgeries of mandibular fractures with administration of dexmedetomidine by two approaches of infusion and single bolus. In this double-blind clinical trial, the participants were randomized and matched in terms of age and gender in two groups (infusion and bolus). In both groups, the amount of narcotic used, hemodynamic indices, oxygen saturation, and pain intensity were collected based on the ten-point Visual Analogue Scale (VAS) at 7 time points for 24 h. SPSS version 24 software was used for data analysis. A significance level of less than 5% was considered. A total of 40 patients were included in the study. There was no significant difference between the two groups in terms of gender, age, ASA class, and duration of surgery (P>0.05). There was no significant difference between the two groups in terms of nausea and vomiting and subsequently receiving anti-nausea medication (P>0.05). The need for opioid consumption after surgery was not different in two groups (P>0.05). Infusion of dexmedetomidine reduced postoperative pain more rapidly than its single bolus dose (P<0.05). However, over time, there was no significant difference between the two groups in terms of changes in oxygen saturation variables (P>0.05). Homodynamic indices including heart rate, systolic blood pressure, and diastolic blood pressure in the bolus group were significantly lower than the infusion group (P<0.05). Administration of dexmedetomidine in the form of infusion can reduce postoperative pain better than bolus injection, with less probability of hypotension and bradycardia.

Role of Dexmedetomidine in Attenuation of Hemodynamic Response to Laryngoscopy - A Dose-Finding Study

Aim: Determining efficacy of pre-operative bolus dose of dexmedetomidine 0.75 and 0.5µg/kg as an infusion and compare it with placebo in attenuation of hemodynamic response to laryngoscopy and tracheal intubation (LTI). Design: Double-blind randomized control. Place &amp; duration: Sindh Institute of Urology &amp; Transplantation, Karachi, Pakistan, from August 2019 to August 2021. Methodology: Patients were stratified into three groups. Group A received normal saline (NS), Group B received dexmedetomidine 0.5 μ/kg and Group C received dexmedetomidine 0.75 μ/kg as an infusion over 10 minutes followed by standardized general anaesthesia. Primary outcome measures were hemodynamic variables at 1, 3, 5 and 10 minutes post LTI. Secondary outcome measures were adverse effects related to dexmedetomidine. Results: Both dexmedetomidine groups showed better attenuation of hemodynamic response to LTI thansaline group. Dexmedetomidine 0.75 µg/kg attenuated hemodynamic response to LTIsignificantly better thandexmedetomidine 0.5 μ/kgand placebo without causing any statistically significant adverse effects. Practical implication: The function of dexmedetomidine in attenuating hemodynamic response to laryngoscopy has several practical implications, including improved patient safety, optimal dosing, reduced anaesthetic requirements, cost-effective treatment, and enhanced patient comfort. Conclusion: Dexmedetomidine 0.75 µg/kg efficient than 0.5 µg/kg and placebo in attenuating hemodynamic response to LTI when given as a pre-induction bolus. Keywords: Anesthesia; Dexmedetomidine, Laryngoscopy, Intubation, Stress Response.