Bolus Dose Research Articles

Compare the Efficacy of Bolus Low Dose Ketamine Versus Bolus plus Infusion Low Dose Ketamine on Pain Management in Emergency Department: A randomized clinical trial.

Ketamine is a promising drug for analgesia in emergency medicine, but a high rate of side effects is a barrier to whispered usage. We hypothesized that ketamine bolus followed by ketamine infusion would provide a more even and longer duration of analgesia and lower rates of side effects in comparison to bolus-only administration. This was a double-blinded, clinical trial. Eligible traumatic patients were randomly allocated with the Numerical Rating Scale (NRS) ≥6 in two study groups. The first group received a dose of 0.3 mg/kg of ketamine over 1 minute, followed by an infusion of saline 0.9% over the next 30 minutes (bolus only group). The second group was given 0.15 mg/kg of ketamine over 1 minute, followed by an infusion of 0.15 mg/kg over the next 30 minutes (bolus and infusion group). The primary outcome was to measure the average reduction in pain scores. 80 patients were recruited. Of these, 77 patients were analyzed. Both groups achieved a statistically significant decrease in pain scores (All p-values<0.001). After 30 minutes, patients in the bolus and infusion group reported lower pain scores in all intervals with lower rates of need for rescue analgesia but this difference was not statistically significant. Vital signs remained stable during the study in both groups. No statistically significant difference was observed between study groups in any side effect (p-value< 0.05). Both administration protocols resulted in significant pain control. No statistically significant difference was observed between study groups in terms of analgesic efficacy and side effects.

Achieving Response With Bolus Dosing of Valproate in Electroconvulsive Therapy (ECT)-Induced Mania: A Case Report

Achieving Response With Bolus Dosing of Valproate in Electroconvulsive Therapy (ECT)-Induced Mania: A Case Report

Primary prevention of post-molar gestational trophoblastic neoplasia in high-risk complete hydatidiform mole: A single-dose prophylactic actinomycin D, associated with uterine evacuation - a long retrospective cohort study.

To evaluate the efficacy of actinomycin D (ActD) as prophylactic chemotherapy (P-chem) in patients with high-risk complete hydatidiform mole (Hr-CHM) on progression to gestational trophoblastic neoplasia (GTN). From 1996 to 2023, 426 Hr-CHMs were selected in a cohort of 1623 patients with gestational trophoblastic disease (GTD). From 1996 to 2023, 290 patients with Hr-CHMs received a single bolus dose of Act-D at the time of uterine evacuation (Hr-CHM P-chem group); 136 with the same risk factors did not receive P-chem (Hr-CHM control group). The variables assessed in post-molar GTN were incidence and morbidity considering hCG serum level at diagnosis, relapse frequency, hysterectomy rates. Post-molar GTN was diagnosed in 19% of the patients with Hr-CHM P-Chem (55/290) and in 39.7% of the patients in the Hr-CHM control group (54/136) (P<0.001). The relative risk of developing post-molar GTN decreased by 52% (RR=0.48; 95% CI: 0.35-0.66; P<0.001), with a number needed to treat (NNT) of 5. Patients in the P-chem group had a lower hCG serum level (P=0.007), lower risk of recurrence (P=0.001) and lower risk of hysterectomy (P=0.04), with no effect on time to GTN diagnosis (P=0.09), first line chemotherapy response (P=0.50) and time to remission (P=0.72). A single bolus dose of Act-D (1.25mg/m2) given as P-chem during uterine evacuation in patients with Hr-CHM may safely prevent the incidence of post-molar GTN and reduce the morbidity associated with GTN. This prophylactic approach can be adopted at any trophoblastic disease center (TDC).

Can Intravenous Lipid Emulsion Reduce Mortality Rate in Cases of Acute Aluminium Phosphide Poisoning? A Systematic Review

Background: Acute pesticide poisoning has remained a significant public health concern for decades. Supportive care has been the mainstay of treatment. Intravenous lipid emulsion (ILE) therapy offers a potential new strategy. Objectives: This systematic review aimed to evaluate the current research on the efficacy of ILE in treating aluminum phosphide (AlP) poisoning. Methods: A comprehensive electronic search was conducted across various databases including PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Campbell Systematic Reviews, Scopus, Web of Science, Springer Nature, Elsevier, Google Scholar, and regional databases encompassing Mansoura, Zagazig, Ain Shams universities, and Indian publications. Studies published in English language were considered for inclusion (from 2015 to 2023). Inclusion criteria focused on human studies evaluating the use of ILE for AlP intoxication. Results: Five studies met the inclusion criteria, three studies were randomized controlled trials, one was observational cross sectional study, and one was case report encompassing a total of 224 patients. Of these, 102 patients received ILE, with all studies utilizing 20% ILE. Three studies administered ILE as a continuous intravenous infusion at a rate of 10 mL/h. Two other studies employed a bolus dose regimen, ranging from 1-3 mL/kg delivered over one minute, followed by continuous infusion. The overall mortality rate was 68.6% in the ILE group compared to 76.2% in the control group and the need for mechanical ventilation was lower in the ILE group with clinical improvement in the ILE group. Conclusion: Intravenous lipid emulsion represents a novel therapeutic approach in toxicology with the potential to improve patient outcomes. This review suggests ILE may reduce mortality associated with AlP poisoning. Additionally, ILE use might be associated with decreased, need for mechanical ventilation, hospital stay and discharge time among survivors.

Evaluation of unfractionated heparin therapy for venous thromboembolism using adjusted body weight in elderly or higher weight patients.

The use of weight-based unfractionated heparin (UFH) infusions is the standard of care in hospital management of venous thromboembolism (VTE). Initial dosing strategies for UFH in older adults and higher body weight patients remain uncertain given differences in pharmacokinetics and concerns for over-anticoagulation. Methods: This was a single-center, retrospective, pre-post study involving older adults aged ≥ 65years and patients weighing ≥ 100kg with suspected or confirmed VTE to determine if the use of adjusted body weight (AdjBW)-based UFH regimens improves time to therapeutic anti-Xa levels compared to total body weight (TBW)-based regimens Patients received weight-based UFH infusions, dosed according to either TBW or AdjBW, to target a therapeutic anti-Xa level. Each cohort consisted of 40 patients, stratified by whether they met age or weight criteria to ensure equal representation of elderly and higher body weight patients between cohorts. The median time to therapeutic anti-Xa levels was shorter in the AdjBW group compared to the TBW group (13.6h versus 20.9h; point estimate 5.3h (95% CI 0.2 to 9.9)). This finding was driven by those aged ≥ 65years and those who received a bolus dose at the start of the infusion. Among older adults and higher weight adults with suspected or confirmed VTE, the use of AdjBW to guide heparin infusion initiation was associated with shorter time to therapeutic anti-Xa levels. This finding driven by the older adult sample and the subgroup analyses did not find a statistically significant difference in time to therapeutic anti-Xa levels in higher body weight patients aged less than 65years.

Pharmacokinetics and brain uptake of sodium selenate and selenium in naïve rats and a lateral fluid percussion injury ratmodel.

Post-traumatic epilepsy (PTE) is a life-long complication of traumatic brain injury (TBI). The development of PTE is associated with neurological morbidity and increases the risk of mortality. An aim of EpiBioS4Rx (Epilepsy Bioinformatics Study for Antiepileptogenic Therapy) was to test potential therapies to prevent the development of PTE in the lateral fluid percussion injury (LFPI) rat model of TBI, in which rats were subjected to injury at the left parietal cortex. Sodium selenate has been reported to be antiepileptogenic post-TBI in rodent models by activating protein phosphatase 2A and reducing phosphorylated tau (p-tau) protein. We aimed to characterize the pharmacokinetics (PK) and brain uptake of sodium selenate using naïve control and LFPI rats. Rats received either a single bolus dose or a single bolus dose followed by a 7-day subcutaneous minipump infusion of sodium selenate. Sodium selenate and selenium concentrations in plasma and brain were analyzed and used for PK estimation and brain exposure assessment. Selenium concentrations rapidly increased after sodium selenate administration, demonstrating biotransformation from sodium selenate to selenium. Sodium selenate and selenium PK parameters were estimated using non-compartmental analysis. Sodium selenate clearance (CL/F) and volume of distribution (Vd/F) varied by dose and route of administration, suggesting differences in bioavailability and nonlinear pharmacokinetics at the doses tested. Brain-to-plasma partition coefficients (AUCbrain/AUCplasma) for sodium selenate and selenium were found to be 0.7-1.3 and 0.1-0.3 following single-dose injection, respectively, indicating active transport of sodium selenate across the blood-brain barrier (BBB).

Effect of Intravenous Lidocaine Infusion on Propofol Dose and Perioperative Pain During Moderate Sedation-Analgesia for Hysteroscopy: A Randomized Controlled Trial.

In China, the majority of hysteroscopic procedures require moderate sedation and analgesia. The efficacy of intravenous lidocaine in reducing the need for sedatives and alleviating perioperative pain during hysteroscopy remains equivocal. This study aims to determine whether the intravenous administration of lidocaine can reduce the required dose of propofol and enhance perioperative pain management. We conducted a prospective, single-center, double-blind randomized controlled trial involving patients with ASA I-II undergoing hysteroscopy. Forty patients were randomly assigned in a 1:1 ratio to either receive an intravenous bolus dose of 1.5 mg/kg lidocaine, followed by a continuous intravenous infusion at 4 mg/kg/h until the conclusion of the procedure, or an equivalent volume of normal saline. Propofol was then titrated to maintain a MOAA/S score of ≤ 2. Compared with the control group, the lidocaine group showed a 13.8% decrease in the total dose of propofol (140.0[120.0, 155.0] mg vs 162.5[140.0, 197.5] mg), which was statistically significant (P = 0.014). The induction dose of propofol was 1.37 (1.29, 1.56) mg/kg in the lidocaine group and 1.61 (1.48, 1.94) mg/kg in the control group, respectively (P = 0.001). However, no significant differences were observed between the groups regarding the supplemental dose of propofol (P = 0.062), the number of involuntary movements during hysteroscopy (P = 0.384), or postoperative pain scores (T0: P = 0.628; T1: P = 0.886; T2: P = 0.711). Additionally, the incidence of intraoperative hypoxia (P = 1.000) and fatigue scores (T0: P = 0.878; T1: P = 0.401; T2: P = 0.056) between the two groups were not statistically significant. Intravenous lidocaine reduces the dose requirements of propofol during the induction phase of anesthesia. However, it does not have a significant influence on alleviating intraoperative and postoperative pain during hysteroscopic procedures.

Can Supplementation with the Cow Start Complete Bolus Result in Elevated Blood Calcium Status in a Group of At-Risk Dairy Cows During the First Four Days of Lactation

The prophylactic supplementation of freshly calved multiparous cows with oral calcium supplements (bolus, drink, drench, paste) has increased in popularity in recent years. Oral calcium supplements are generally only effective for 12 hours, yet the high-risk period for hypocalcaemia in freshly calved multiparous cows is 48 hours post-partum. Therefore, a second application 12 hours post-partum is suggested by manufacturers, yet due to labour shortages on dairy farms, it is very common for the second application to not be carried out. The objectives of this study were to ascertain if a the administration of a single dose of the sustained release bolus (Cow Start Complete, Anchor Life Science, Co. Cork, Ireland) given to the cow at calving, could offer the combined benefits of elevated calcium status over the first 48 hours post-partum from a labour efficient single dose given at calving and also to evaluate if this enhanced calcium status could have a positive effect on daily rumination time and milk production yields in the first three months of lactation. The two groups consisted of an un-supplemented control (CON) group and a Cow Start Complete (CSC) group in which cows were given a single bolus dose at the point of calving. The CON group experienced a clinical milk fever (Blood Ca &amp;lt;1.5mmol/L) incidence rate of 13.3% compared to 0% for the CSC group. Cows given the CSC treatment had significantly (P&amp;lt;0.0001) higher total blood calcium levels (2.14 mmol/L) from the point of calving (0h) to 4 days post-partum (96h) compared to CON (1.98mmol/L), with significant increases at 12h (P&amp;lt;0.01), 24h (P&amp;lt;0.001) and 36h (P&amp;lt;0.01) post-partum. Rumination time for CSC cows (471mins/day) was significantly (P&amp;lt;0.05) higher during the first 14 days post-partum when compared to CON (434mins/day) group. Milk production was also significantly (P&amp;lt;0.01) higher for CSC cows (+1.8kg/day) than in CON cows during the first 90 days of lactation. These findings demonstrate that the convenience of giving a single dose of CSC at calving, can be combined with desired outcomes in a range of key benefits in freshly calved multiparous cows.

Pharmacokinetics of Methadone in Adult Patients Undergoing Cardiac Surgery With Cardiopulmonary Bypass.

Cardiopulmonary bypass (CPB) induces profound physiological changes that may alter the pharmacokinetics of methadone. We aimed to describe the pharmacokinetics of an intravenous bolus of methadone racemate in adult patients undergoing heart surgery with CPB. We prospectively studied 29 patients aged 45 to 75 years scheduled for cardiac surgery with CPB who received methadone 0.2 mg/kg after anesthesia induction. Arterial blood samples (n = 10) were taken, before, during, and after CPB. Pharmacokinetic analysis was undertaken using nonlinear mixed effects models. All patients completed the study. The median [interquartile range] methadone concentrations decreased from 34.8 [23.9-48.2] ng/mL (10 minutes before CPB) to 18.2 [9.9-26] ng/mL after 60 minutes of CPB (P < .001). A 3-compartment model adequately described the observed changes in methadone concentrations. The influence of CPB on methadone pharmacokinetics was best described by hemodilution in a fixed volume of 1.5 L (CPB circuit volume) and by sequestration from the CPB components (CLSEQ = 93.4 L/h, 95%CI 59-124, P < .01). The observed effect of CPB in methadone pharmacokinetics can be compensated by giving a supplementary bolus dose of 0.05 mg/kg at the end of CPB. Our results confirmed a decay in methadone concentrations during CPB, which, in our modeling analysis, was attributed to hemodilution and sequestration within the CPB components.

Metabolomic profile of cerebral tissue after acoustically-mediated blood-brain barrier opening in a healthy rat model: a focus on the contralateral side.

Microbubble (MB)-assisted ultrasound (US) is an innovative modality for the non-invasive, targeted, and efficient delivery of therapeutic molecules into the brain. Previously, we reported the first metabolomic signature of blood-brain barrier opening (BBBO) induced by MB-assisted US. In the present study, the neurometabolic consequences of acoustically-mediated BBBO on cerebral tissue were investigated using multimodal metabolomics approaches. Sinusoid US waves (1 MHz, peak negative pressure 0.6 MPa, burst length 10 ms, total treatment time 30 s, MB bolus dose 0.7 × 105 MBs/g) were applied on the rats' right striatum (ipsilateral side). Brain was collected and both striata were then dissected 3 h, 2 days, and 1 week after BBBO. After tissue preparation, the samples were analyzed using nuclear magnetic resonance spectrometry (NMRS) and high-performance liquid chromatography coupled to mass spectrometry (HPLC-MS). Our findings showed a slight disruption of metabolic pathways in contralateral striata of animals. Analyses of metabolic pathways indicated changes in amino acid metabolisms. In addition, tryptophan derivate dosages revealed the perturbation of a central metabolite of the kynurenine pathway (i.e., 3-hydroxy-kynurenine). In conclusion, the acoustically-mediated BBBO of the ipsilateral cerebral hemisphere induced significant change in metabolism of contralateral one.

Effect of Music Therapy on Anxiety, Stress and Sedative Requirements in Patients Undergoing Lower Limb Orthopedic Surgery Under Spinal Anesthesia: A Randomized Controlled Study.

Background Music therapy is a safe, non-pharmacological way to help reduce anxiety, especially before surgery. It helps to calm the nervous system, promotes relaxation, and offers comfort by blocking outside noise and distracting from pain. This can be helpful in managing preoperative anxiety and symptoms like hypertension and tachycardia. While the benefits of music therapy for stress and sedation are well known, its specific effects on patients receiving spinal anesthesia haven't been studied yet. Understanding this could improve care for these patients. Overall, music therapy could be a valuable tool in the surgical process. Objectives Primary objective: The study aimed to compare sedative requirements between two patient groups. Secondary objectives: To compare anxiety levels between two patient groupsusing the State-Trait Anxiety Inventory. It also assessed hemodynamic changes and measured stress levels by analyzing serum cortisol and immunoglobulin A levels in both groups. Materials and methods Ninety-two American Society of Anesthesiologists physical status class I and II patients, aged 18-65 years, with a body mass index of 18-25 kg/m2 undergoing lower limb orthopedic surgery under spinal anesthesia were selected for the study. After spinal anesthesia, the group M (n=46)patients received the music of their choice from headphones connected to mobile phones and patients in group NM (n=46)were attached headphones without any music therapy. After the attachment of headphones, propofol was administered in both the groups for sedation in a bolus dose of 1-2mg/kg iv followed by an infusion dose of 5-50 μg/kg/min. The propofol infusion was titrated based on Bispectral Index (BIS) values kept between 70 and 80 for moderate sedation. Preoperatively, blood samples were collected to measure baseline serum cortisol and IgA levels. Intraoperatively, hemodynamic parameters were measured, and anxiety level was assessed using the State-Trait Anxiety Inventory (STAI) Scale 30 minutes prior to the administration of spinal anesthesia. Postoperatively, anxiety was re-evaluated, and additional blood samples for the assessment of cortisol and IgA were taken at 30 minutes and 12 hours after the administration of spinal anesthesia. Results The mean serum cortisol was lower in Group M as compared to Group NM (15.1±1.2 vs. 17.1±1; p = 0.0001). Mean serum IgA was significantly lower in Group M as compared to Group NM (269.3±54.5 vs. 294.2±49.9; p = 0.024) during the intraoperative period. The mean STAI Score was lower in Group Mcompared to Group NM (34.87±4.53 vs. 34.61±5.06; p = 0.008). The mean propofol requirement (mg) was lower in Group M as compared to Group NM (147.8±11.3 vs. 193±16; p = 0.0001). The hemodynamic parameters were comparable between the groups (p>0.05). Conclusion Patients in the music therapy group experienced lower anxiety, stress, and serum cortisol levels during surgery, with reduced serum IgA levels and decreased propofol requirement for sedation. Overall, music therapy was effective in reducing anxiety, stress, and sedative requirements during surgery under regional anesthesia.

Abstract 4144517: Feasibility of Deep Sedation for Catheter Ablation of Atrial Fibrillation Using Pulsed Field Ablation

Introduction: General anesthesia is commonly utilized during catheter ablation of atrial fibrillation (AF) in the United States, providing patient immobility and permitting esophageal temperature management for radiofrequency ablation. Pulsed field ablation (PFA) is associated with shorter procedure time, less risk of esophageal injury, and less dependence on catheter stability compared with radiofrequency ablation. There are limited data available on performing the procedure with deep sedation as an alternative to general anesthesia with endotracheal intubation. Methods: Consecutive patients who underwent catheter ablation of AF at Endeavor Health (Chicago, IL) using pulsed field ablation (Farapulse, Boston Scientific, Marlborough, MA or PulseSelect, Medtronic, Minneapolis, MN) and deep sedation between March and May 2024 were retrospectively included in this study. Deep sedation (monitored anesthesia care) was administered by a certified registered nurse anesthetist and attending anesthesiologist, consisting of bolus and infusion dosing of propofol, dexmedetomidine, fentanyl, and midazolam at the discretion of the practitioner with continuous monitoring of vital signs and end-tidal CO2. The primary endpoint was the rate of airway complications or requirement for conversion to general anesthesia. Secondary endpoints were the rate of acute procedural success (all pulmonary veins isolated), total time in the EP lab, procedure time (from lidocaine to removal of sheaths), and non-procedure time (difference between total time in lab and procedure time). Results: A total of 40 patients (mean age 70.4 ± 13.6 years, BMI 30.2 ± 7.4, 60% females) were included in the analysis. There were no instances of airway complications or conversion from deep sedation to general anesthesia. There was a 100% rate of acute isolation of pulmonary veins. The average total time in the lab was 156.6 ± 41.5 minutes; consisting of a mean procedure time of 107.1 ± 39.7 minutes and non-procedure time 49.5 ± 10.3 minutes. Conclusions: In this initial experience at a single center, deep sedation (monitored anesthesia care) for PFA was associated with no instances of airway complications. The findings may not apply to patients with moderate or severe obstructive sleep apnea or other pulmonary diseases. Although patients generally were amnestic to the procedure, larger studies incorporating patient-reported outcomes are needed, as well as data regarding long-term clinical outcomes and cost.

Abstract 4136654: Urine Output Response to a Furosemide Infusion is Associated with Acute Kidney Injury in Infants Following Cardiac Surgery

Background: Acute kidney injury (AKI) following cardiac surgery in infants is common and associated with longer mechanical ventilation times and length of stay. Prior studies have shown that a lack of responsiveness to bolus dose furosemide has been associated with increased incidence of AKI. However, these studies have excluded patients on continuous furosemide infusions who are often younger, more hemodynamically unstable, and at higher risk for AKI. Hypothesis: Decreased urine output after initiation of a furosemide infusion predicts development of AKI. Methods: A retrospective cohort study of infants (&lt;1 year of age) was conducted who underwent cardiac surgery requiring cardiopulmonary bypass from 2020-2023 and were on a furosemide infusion post-operatively. The primary outcome was post-operative AKI as defined using KDIGO (Kidney Disease: Improving Global Outcomes) guidelines. A furosemide response score (FRS) was calculated using the total urine output divided by the total dose of furosemide administered over a given time. Univariate and multivariate analyses were performed, and receiver operating characteristic curves used to determine the discriminatory ability of the FRS with regards to the primary outcome. Results: A total of 155 infants (median age at surgery 9 days) were included. Overall, 77% of infants met definition for the primary outcome of AKI; 32% stage 1, 30% stage 2, and 15% stage 3. Lower FRS at 4, 10, and 24 hours after infusion initiation were associated with AKI development (p&lt;0.0001). Younger age, smaller weight at surgery, lack of pre-operative feedings, pre-operative inotropic use and higher surgical complexity were also associated with a higher risk of AKI. An FRS (mL/mg/kg) cutoff of &lt;11.3 at 4 hours, &lt;25.5 at 10 hours, and &lt;55.3 at 24 hours had good discriminatory ability (area under the curve 0.7-0.75) in predicting AKI stage 2 or 3 (p&lt;0.001). Controlling for the significant univariate variables listed above, the FRS cutoffs remained an independent risk factor for the development of AKI stage 2 or 3, (p&lt;0.01) and were significantly associated with longer mechanical ventilation days and length of stay. Conclusion: Lack of responsiveness to a furosemide infusion (as measured by urine output corrected for dose of furosemide) is associated with the development of AKI in a high-risk cohort of infants. These novel findings may be helpful to predict those at risk and allow for further investigations for modifiable risk factors.

The Effects of Intra-Operative Lidocaine Infusion on Post Operative Pain and Morphine Consumption Following Major Gynaecological Surgeries Under General Anaesthesia

&amp;lt;i&amp;gt;Introduction&amp;lt;/i&amp;gt;: Major gynaecological surgeries are associated with considerable postoperative pain, which remains a challenge for many practitioners. Multimodal forms of analgesia significantly reduce the requirement of opioids for pain management. Despite its local anaesthetic effects, lidocaine infusion improves postoperative pain and morphine consumption following gynaecological surgeries. &amp;lt;i&amp;gt;Materials and methods&amp;lt;/i&amp;gt;: Sixty patients were assigned randomly into 2 groups (A and B) with 30 patients per group. Group A received intravenous lidocaine 1.5 mg/kg at induction via a bolus injection and 1.5 mg/kg/hr in normal saline infusion from onset of surgery to the end of surgery, while the control group (Group B) received equal volume of normal saline at the same timelines. Pain scores were assessed postoperatively using the numerical rating scale and the cumulative morphine consumed postoperatively were also measured. &amp;lt;i&amp;gt;Results&amp;lt;/i&amp;gt;: The mean pain scores were significantly higher in the Saline Group than in the Lidocaine group. The cumulative morphine consumption after 48 hours was significantly reduced in the study group 4.87 ± 1.80 mg vs 14.13 ± 4.10 mg (P&amp;lt;0.0001). Conclusion: The administration of a bolus dose (1.5 mg/kg) of intravenous lidocaine at induction and a continuous intravenous infusion of 1.5 mg/kg/hr from onset of surgery till skin closure reduced the postoperative pain intensity and morphine consumption in patients undergoing major gynaecological surgeries under general anaesthesia.

CTNI-79. ASSESSING SYSTEMIC AND LOCAL LEVELS OF LIDOCAINE DURING SURGERY FOR GLIOBLASTOMA

Abstract The objective of this study is to assess the pharmacokinetics of lidocaine penetration into tumor tissue during glioblastoma surgery. In-vitro studies of glioblastoma have demonstrated co-culture with lidocaine inhibits glioblastoma proliferation via inhibition of TRPM7 channels. TRPM7 is a transmembrane ion channel that modulates proliferation and migration in several human cancers. Scalp block with lidocaine during glioblastoma surgery has been associated with improved survival in human studies. Twelve patients were enrolled in this study. The study group received an intravenous bolus dose of 1.5 mg/kg IBW of lidocaine at induction of anesthesia followed by 2 mg/kg IBW/hr infusion of lidocaine. Craniotomy was performed in the standard fashion. A total of 3 fresh tumor specimens were collected hourly from each patient after confirmation of glioblastoma diagnosis by frozen section. Plasma samples were simultaneously collected for analysis. Lidocaine concentration was measured using mass spectroscopy. The maximum concentration of lidocaine (Cmax), time from bolus to maximum concentration (Tmax), and area under curve from 0-3 hours (AUC) were calculated for each patient. Patients were followed for survival and adverse events. The median tumor specimen Cmax, Tmax, and AUC values were 333 ng/dL (range 226-555), 179 min (range 126-211), and 20665 ng*min/dL (range 8003-55,426), respectively. Peak lidocaine concentration was reached in 6 of 12 cases. Median Cmax and Tmax for plasma samples were 1195 ng/dL (range 951-1475) and 191 min (range 156-211), respectively. Median overall survival was 308 days (range 74-413). Two grade 3 adverse events occurred which were deemed to be unlikely to be related to the study intervention. In conclusion, lidocaine infiltrates tumor tissue when administered intravenously during glioblastoma surgery. Concentrations do not reach levels previously demonstrated to inhibit tumor growth in in vitro studies (roughly 2*108 ng/dL lidocaine). Alternative mechanisms may explain previously observed improved outcomes with lidocaine administration in human studies.

Safety of a Novel Continuous Glucose Monitoring–Informed Insulin Bolus Calculator Mobile Application for People With Type 1 or Type 2 Diabetes

BACKGROUND Managing bolus insulin dosing can be a significant burden for people with diabetes, many of whom have limited numeracy skills. Insulin bolus calculators (IBCs) may improve glycemia as well as treatment satisfaction. OBJECTIVE The purpose of this study was to demonstrate the safety of a novel, continuous glucose monitoring (CGM)-informed IBC mobile device app that applies trend arrow adjustments to bolus insulin dose recommendations. RESEARCH DESIGN AND METHODS This clinical trial was an open-label, industry-sponsored single-arm study conducted at two sites. Fifty-four participants with type 1 or type 2 diabetes were enrolled and used the IBC app on their mobile device for 30 days. Study participants were adults who were already using CGM and dosing bolus insulin. The analysis examined both noninferiority and superiority of time in range (TIR) during the study period compared with baseline. Other important end points included hypoglycemia, glucose variability, nocturnal and diurnal TIR, and diabetes distress. The per-protocol (PP) group was defined as participants who used the IBC &amp;gt;30 times during the study. RESULTS Mean TIR improved by 3.8% (95% CI 0.7–6.9%) from 69.2 to 73.0% (P = 0.017) in the PP group. This TIR corresponds to a mean of 0.9 more hours per day spent in range, and the improvement was driven by those with type 2 diabetes. There was no increase in measures of hypoglycemia or diabetes distress. Exploratory analysis revealed a reduction in measures of glucose variability. In addition, individuals with type 1 diabetes had greater improvements in diurnal TIR than in nocturnal TIR. CONCLUSION A CGM-informed IBC app that applies trend arrow adjustments to bolus insulin dose recommendations improved TIR without increasing hypoglycemia or diabetes distress in individuals with type 1 or type 2 diabetes.

Can distinct Gram-negative biofilm-forming bacteria have different impacts on ciprofloxacin lung penetration?

Literature have shown that Gram-negative bacteria release endotoxins which alter drug membrane transporters and could potentially influence antimicrobials distribution to the infection site depending on the infecting bacteria. Previously, a population pharmacokinetic (popPK) model describing ciprofloxacin (CIP) concentrations in healthy, and Pseudomonas aeruginosa pneumonic rats showed that the chronic stage of the infection significantly reduced the drug lung penetration. In this study, CIP lung penetration in Klebsiella pneumoniae chronically (14 d) infected rats following CIP 20 mg/kg i.v. bolus dosing was investigated and the popPK model developed previously was used to evaluate CIP lung exposure. Drug plasma exposure was similar for both bacteria and higher than observed in healthy animals. Probability of target attainment analysis using plasma data following current dosing regimen (20 mg q8h equivalent to 400 mg q8h in humans) showed that CIP PK/PD index (ƒAUC0-24/MIC ≥90) is achieved for the most prevalent MIC's of both bacteria. However, CIP free lung concentrations were reduced in infected animals by 46.8 % (P. aeruginosa) and 68.4 % (K. pneumoniae) in comparison to healthy animals. The higher lung clearance observed (0.306 L/h/kg) in K. pneumoniae infected animals lead to a lower free CIP lung exposure in comparison to the P. aeruginosa group (0.105 L/h/kg). In summary, although plasma PK/PD index is achieved by the current regimen, chronic pneumonia by biofilm-forming bacteria decreases lung exposure to CIP and this decrease is dependent on the infecting bacteria. The clinical relevance of this finding needs to be determined.

Intraoperative bleeding model for swine gastric endoscopic submucosal dissection via heparinization.

Background and study aims: Live swine have a high degree of coagulation and aggregation and using them for training about how to manage intraoperative bleeding during endoscopic submucosal dissection (ESD) is unsatisfactory. This study aimed to identify the appropriate heparin dose in an intraoperative bleeding model and validate its applicability. Methods: First, we explored the dose of heparin required for a swine bleeding model in which the activated clotting time reached and maintained the upper limit of measurement (1500 s) after 10 minutes. Second, we compared intraoperative bleeding and hematoma frequency during ESD for 2-cm lesions between the heparinized bleeding model and control groups. Intraoperative bleeding was classified according to the Forrest classification. Results: The combination of a bolus (300 U/kg), continuous infusion (300 U/kg/h), and a bolus dose (150 U/kg) of heparin 10 minutes after the first infusion was identified as the dose for the bleeding model. Five ESDs were performed in each heparinized bleeding model and the control group. The median number of intraoperative bleeds was significantly higher in the heparinized model than in the control group (5 interquartile range [IQR] 4-7 vs. 3 [IQR 0-4, P = 0.028). All of the intraoperative bleeding events oozing (Forrest Ib) rather than spurting (Forrest Ia). The median number of hematomas was significantly higher in the heparinized model group than in the control group (3 [IQR 1-4] vs. 0 [IQR 0-1], P = 0.023). Conclusions: High doses of heparin significantly increased intraoperative bleeding and hematoma during swine ESD.

Comparing the Effects of Infusion and Bolus Doses of Bupivacaine Applied with Infraclavicular Catheter on the Duration and Need of Postoperative Analgesia

Objective: This study aimed to evaluate postoperative analgesia duration, analgesic requirements, and patient satisfaction between continuous infusion and bolus injection techniques using an infraclavicular catheter in patients undergoing forearm surgery. Material and Method: We examined 100 patients which were divided into 2 groups to evaluate the data retrospectively. Bolus Injection Group (B): Patients who received 4 mL of bupivacaine (0.5%) from the catheter if the VAS value was &gt; 3. Continuous Infusion Group (C): Patients who received 20 mg bupivacaine (0.02%) infusion via catheter using an infusion pump in 24 hours. Demographic data, American Society of Anesthesiologists (ASA) score, intraoperative and postoperative hemodynamic data, sensory and motor block onset times, postoperative Visual Analogue Scale (VAS) (1-2-6-12-24th hour), postoperative 24th and 48th hour satisfaction score, obtained from anesthesia and algology follow-up forms, were evaluated. Results: When both groups were compared, VAS6 and VAS24 values of Group C were found to be statistically significantly lower than Group B. Satisfaction scores revealed that significantly more patients in Group C reported being very satisfied compared to Group B. Conclusion: Our findings suggest that continuous local anesthetic infusion via catheter offers more sustainable analgesia compared to bolus administration.

Outcomes of Bolus Dose Furosemide Versus Continuous Infusion in Patients With Acute Decompensated Left Ventricular Failure and Atrial Fibrillation.

This prospective, randomized trial aimed to compare the efficacy and safety of different intravenous diuretic regimens in acute decompensated heart failure (ADHF) patients. ADHF patients were enrolled and randomized into three groups: continuous intravenous furosemide infusion (cIV), bolus furosemide injection (bI), and furosemide plus hypertonic saline solution (HSS). Clinical outcomes were assessed over 48 h. In a study involving 1276 patients admitted for ADHF, three therapeutic regimens (T × 1, T × 2, and T × 3) were compared. T × 1 administered an 80 mg furosemide intravenous bolus infusion twice daily to 479 patients, while T × 2 involved a continuous 16-h infusion of 160 mg furosemide daily to 420 patients. T × 3 treated 377 patients with 160 mg furosemide combined with 150 mL of HSS containing 1.95% NaCl over 30 min. Yet, overall changes in renal markers such as BUN, Na, K, and serum creatinine did not differ significantly. Analysis of prespecified study endpoints revealed notable variations in hospitalization length among the treatment arms. T × 1 demonstrated a significantly shorter hospital stay (3.7 days) compared to T × 2 (6.6 days) and T × 3 (7.9 days). Conversely, alterations in serum creatinine at 48 h, overall changes in serum creatinine, body weight loss, and serum potassium levels did not significantly differ among the treatment groups. While intravenous bolus of furosemide showed potential benefits in reducing hospitalization duration, limitations such as a small sample size and short-term observation emphasize the need for larger studies to validate these outcomes further.