Continuous Intravenous Infusion Research Articles

First Seizures, Acute Repetitive Seizures, and Status Epilepticus.

This article provides current evidence on how and when to treat unprovoked first seizures in children and adults, guides intervention with appropriate doses and types of modern and effective therapies for acute repetitive (cluster) seizures, and reviews evidence for the diagnosis and management of established, refractory and super-refractory status epilepticus. Artificial intelligence shows promise as a clinical assistant in decision making after a first seizure. For nonanoxic convulsive refractory status epilepticus third-phase treatment, equipoise exists regarding whether it is better to add a second IV nonsedating antiseizure medication given via loading dose (eg, brivaracetam, lacosamide, levetiracetam, fosphenytoin or valproic acid) or to start an anesthetizing continuous IV infusion antiseizure medication such as ketamine, midazolam, propofol or pentobarbital. After a first seizure, the risk of a second seizure is about 36% at 2 years and 46% after 5 years. The risk is doubled in the presence of EEG epileptiform discharges, a brain imaging abnormality, a nocturnal first seizure, or prior brain trauma. For acute repetitive seizures, providers should give a proper dose of benzodiazepines based on the patient's weight and needs. First-phase treatment for convulsive established status epilepticus is the immediate administration of full doses of benzodiazepines. Second-phase treatment for convulsive established status epilepticus is a full loading dose of IV fosphenytoin, levetiracetam, valproic acid, or if necessary, phenobarbital.

Exploring stress echocardiography in coronary artery disease: insights from a tertiary echocardiography center

Abstract Background/ Introduction Stress echocardiography (SE) is an established functional test with high sensitivity and specificity for diagnosing obstructive coronary artery disease (CAD). Purpose The present study aimed to document the experience of a tertiary hospital’s echocardiography center in using dynamic echocardiography to assess myocardial ischemia. Methods The study was performed retrospectively, including all patients who underwent SE at our center from January 2021 to December 2021. The goal for each test was to reach 85% of the age-predicted maximal heart rate (HR) (220 minus the subject’s age). The adopted Dobutamine stress protocol involved a continuous intravenous infusion of Dobutamine in 3-minute increments, starting at 10μg/kg/min and gradually increasing to 50μg/kg/min. Handgrip exercises were typically used, along with a small dose of intravenous atropine (0.25mg, up to a maximum of 1 mg) if the endpoint was not reached. Parasternal and apical echocardiographic views were obtained at all stages, and a contrast agent was used when appropriate. All tests were conducted under continuous 12-lead electrocardiographic (ECG) monitoring. Results Out of the 323 subjects [mean age 63.5 ± 10.5 years, 221 males (68.4%)], 123 (38.0%) underwent testing due to suspected CAD symptoms, while the remaining subjects (200 / 62.0%) were tested to reassess known CAD (with or without previous intervention). Twenty-one (7.0%) subjects had a left ventricular ejection fraction (LVEF) ≤40% at rest. The maximum dose of dobutamine most commonly administered was 30 μg/kg/min [137 subjects, (43.0%)], and atropine was given in 51 subjects (16.0%). The target HR was achieved in 291 (90.0%) tests. Eighty-seven (27.0%) SEs utilized a contrast agent in all stages, while in 177 (55.0%) a contrast agent was administered only at rest and peak HR. Major complications, such as acute myocardial infarction or persistent ventricular tachycardia, occurred in 6 patients (1.8%). Specifically, 5 (1.5%) experienced transient ST-segment elevation during the test, and one patient had a lateral myocardial infarction with ST-segment elevation after the test. No allergic reactions were reported. In 226 (70.0%) tests, results were classified as "negative for ischemia up to the achieved HR". In the remaining tests, classified as "positive for ischemia" (97/30.0%), the mean wall motion score index (WMSI) at peak HR was 1.3 ± 0.2 with a mean peak-to-rest ΔWMSI of 0.1 ± 0.1 (Table 1). Conclusion Of all the SEs performed at our center with an indication for assessing myocardial ischemia, 30.0% were positive, while major complications occurred in 1.8% of the subjects.

Protein glycation compromises the bioavailability of milk protein-derived lysine in vivo in healthy adult males: a double-blind randomized cross-over trial.

Industrial processing and storage of milk products can strongly increase protein glycation level. Previously, we have reported that ingestion of highly glycated milk protein attenuates the post-prandial rise in plasma lysine concentrations when compared to the ingestion of an equivalent amount of milk protein with a low glycation level. Whether the attenuated increase in plasma lysine availability is attributed to compromised protein digestion and subsequent lysine absorption remains to be established. The present study combined stable isotope methodology with the ingestion of, specifically produced, intrinsically labeled protein to assess protein digestion and amino acid absorption following ingestion of milk protein with a high versus low glycation level in vivo in humans. 15 recreationally active, healthy young males participated in this double-blinded, randomized cross-over study. Subjects ingested 40 g intrinsically L-[1-13C]-lysine-labeled milk protein with either a low (3%) or high (50%) glycation level. Continuous intravenous infusion of L-[4,4,5,5-2H4]-lysine was combined with frequent blood sample collection during a 6-h post-prandial period to evaluate dietary protein-derived lysine release into the circulation. Post-prandial plasma lysine concentrations were lower following the ingestion of milk protein with a high versus low glycation level (time*treatment effect: P=0.002; ƞ2=0.214), resulting in a 23 mmol·L-1·360 min-1 [95%-CI:13-32] lower incremental area under the curve (0±12 vs 23±11 mmol·L-1·360 min-1, respectively, P<0.001). The post-prandial release of milk protein-derived lysine into the circulation was attenuated following ingestion of the protein with the high versus low glycation level (time*treatment effect: P<0.001; ƞ2=0.640) and was 31% [95%-CI:26-36] lower over the full 6-h post-prandial period (18±4 vs 49±10% of the ingested lysine, respectively, P<0.001). A high level of milk protein glycation strongly reduces post-prandial plasma lysine availability in vivo in humans. Industrial processing and storage of (milk) protein products can strongly modulate protein bioavailability and, as such, lower the nutritional value of a protein source. This trial was registered at www. gov as NCT05479916: https://clinicaltrials.gov/study/NCT05479916.

Assessing blood flow in uterine fibroids using intravoxel incoherent motion imaging compared with dynamic contrast-enhanced MRI

To assess the utility of IVIM parameters in evaluating uterine fibroid blood flow compared to dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) derived blood flow. Sixteen premenopausal women with uterine fibroids were enrolled in this prospective study. Pelvic MRI scans were obtained for each subject, both with and without continuous intravenous infusion of oxytocin, known to decrease significantly uterine fibroid blood flow, to assess the changes in blood flow of uterine fibroids. IVIM and DCE analyses were conducted using separate dedicated software. The bi-exponential IVIM model was used to estimate perfusion fraction (f), pseudo-diffusion coefficient (D*), and diffusion coefficient (D). DCE blood flow values were derived via T1 perfusion deconvolution arithmetic, utilizing a first pass of an AIF curve. The correlation between the parameters were analyzed by Spearman’s rank correlation analysis due to small sample size. Means of the parameters were compared with a nonparametric Wilcoxon sign rank method for each pair. Statistically significant positive correlations were found between perfusion fraction values and DCE blood flow values with oxytocin (Spearson’s ρ = 0.78, p = 0.0004), and between fD* values and DCE blood flow values with oxytocin (Spearson’s ρ = 0.64, p = 0.0071). Significant differences in blood flow were detected across most IVIM parameters: f, D*, and fD* (p < 0.001, p = 0.0027, and p = 0.0002, respectively) when comparing the values without oxytocin and with oxytocin. IVIM imaging shows promise for assessing blood flow in uterine fibroids.

The Importance of Dose Escalation in the Treatment of Pulmonary Arterial Hypertension with Treprostinil.

Background: Treprostinil, which is administered via continuous subcutaneous or intravenous infusion, is a medication applied in the treatment of pulmonary arterial hypertension (PAH). The dose of treprostinil is adjusted on an individual basis for each patient. A number of factors determine how well patients respond to treatment. Objectives: The aim of this study was to identify factors that may influence the clinical response to the dose of treprostinil at 3 months after the start of therapy. Methods: The factors influencing treatment response were analyzed in consecutive PAH patients who started receiving treprostinil treatment. The treatment efficacy was assessed as improvement in 6 min walk distance (6MWD) and WHO functional class (WHO FC), a reduction in N-terminal prohormone of brain natriuretic peptide (NTproBNP), and the percentage of patients achieving low-risk status after 12 months of treatment. Results: A total of 83 patients were included in this analysis. Classification of patients according to the tertiles of treprostinil dose achieved at 3 months after drug inclusion shows that after 12 months of follow-up, the median WHO FC in the highest dose group was lower than that in the intermediate dose group (WHO FC II vs. WHO FC III, p = 0.005), the median NTproBNP was lower (922 pg/mL, vs. 1686 pg/mL, p = 0.036) and 6MWD was longer (300 m vs. 510 m, p = 0.015). The French Noninvasive Criteria (NIFC) scale score was higher (2 vs. 0, p = 0.008), and the Reveal scale score was lower (5.0 vs. 8.5, p = 0.034). In the group of patients who exceeded a dose of 19.8 ng/kg/min within 3 months, an improvement in 6MWD was observed significantly more often after one year of therapy, and they were more likely to show an increase in NIFC scale scores after one year of therapy than the group of patients who received the lower dose (65% vs. 30%, p = 0.02). In the group of patients younger than 50 years of age, a statistically significant correlation was observed between the dose of treprostinil achieved after three months of treatment and the parameters assessed after 12 months of treatment, including WHO FC, 6MWD, and NIFC prognostic scale scores (all p < 0.05). Conclusions: The clinical effect of treatment is critically dependent on the rapid escalation of the treprostinil dose during the first three months of treatment.

Continuous versus intermittent tacrolimus for graft-versus-host disease prophylaxis in pediatric hematopoietic stem cell transplantation patients (Tic Tac).

Tacrolimus is administered via a continuous or intermittent IV infusion to prevent acute graft versus host disease (aGvHD) in pediatric hematopoietic stem cell transplant (HSCT) recipients. Limited comparison data is available. The primary objective was to compare the proportion of therapeutic tacrolimus trough levels in the first 30 days post-stem cell infusion. Secondary outcomes were prevalence of aGvHD, intra-patient variability (IPV) and safety. This was a retrospective cohort study that included pediatric HSCT recipients between March 1, 2015 and October 31,2021 at BC Childrens Hospital. Adverse events were assessed using the Naranjo scoring tool. Overall, 60 transplants in 59 patients were included; n = 36 intermittent IV and n = 24 continuous IV. Median proportion of blood levels (intermittent and continuous) within 8-12 ug/L was 38% and 56%, respectively (p = 0.04). IPV was 33% and 31% and aGvHD was 39% and 38% in intermittent and continuous respectively. There was a higher proportion of adverse effects in the intermittent group with the exception of hypomagnesemia. Continuous IV tacrolimus provided a higher proportion of levels within therapeutic range. Neither achieved therapeutic trough levels in more than 56% of transplants. However, there was large intra-patient variability in both groups.

Intravenous lidocaine decreased the incidence of SRAEs for ERCP procedures in elderly frailty patients, a randomized controlled trial.

Elderly frailty patients are at particular risk of sedation-related adverse events (SRAEs) during sedation. This study aimed to assess whether intravenous lidocaine could reduce the incidence of SRAEs in elderly frailty patients undergoing endoscopic retrograde cholangiopancreatography (ERCP). A total of 210 elderly frailty patients scheduled for ERCP were randomly divided into two groups: lidocaine and control. Patients in the lidocaine group received intravenous lidocaine (1.0mg/kg) before anesthesia induction, followed by continuous intravenous infusion (2.0mg/kg/h) during ERCP. The control group received an equal volume of saline solution. The primary endpoint was the composite incidence of SRAEs during ERCP. Secondary endpoints were propofol consumption, VAS score, endoscopists' and patients' satisfaction scores and lidocaine-related adverse events and so on. The composite incidence of SRAEs in the lidocaine group was significantly lower than in the control group (41.05% vs. 21.86%, p < 0.05). The propofol requirement (436.11 ± 118.90, 388.54 ± 149.65. p < 0.001) and VAS score of patients (3.02 ± 1.07, 2.54 ± 1.10. p < 0.05) in the lidocaine group were significantly lower than those in the control group. The endoscopists' satisfaction scores (7.77 ± 1.12, 8.23 ± 1.10. p < 0.05) and patients' satisfaction scores (8.53 ± 0.95, 8.98 ± 0.86. p < 0.05) in lidocaine group were significantly higher than those in the control group. Intravenous lidocaine can significantly decrease the incidence of SRAEs for ERCP procedures in elderly frailty patients, with no increase in lidocaine or other related adverse events. Chinese Clinical Trial Registry (Trial ID: ChiCTR2300067796, https://www.chictr.org.cn/showproj.html?proj=185763 ).

Formulas for estimating the initial dosage of tacrolimus for continuous intravenous infusion immediately after pediatric kidney transplantation

Formulas for estimating the initial dosage of tacrolimus for continuous intravenous infusion immediately after pediatric kidney transplantation

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.

Reduction of postoperative pain and opioid consumption by VVZ-149, first-in-class analgesic molecule: A confirmatory phase 3 trial of laparoscopic colectomy.

VVZ-149 is a small molecule that inhibits the glycine transporter type 2 and the serotonin receptor 5-hydroxytryptamine 2A. In this Phase 3 study, we investigated the efficacy and safety of VVZ-149 as a single-use injectable analgesic for treating moderate to severe postoperative pain after laparoscopic colectomy. Randomized, parallel group, double-blind, Phase 3 clinical trial (Trial no. NCT05764525). 5 tertiary referral centers in South Korea. 284 patients undergoing laparoscopic colectomy. A continuous 10-h intravenous infusion of VVZ-149 (n=141) or placebo (n=143) administered after emergence from anesthesia. Pain intensity was assessed using a numeric rating scale (NRS) from the start of infusion for 48h. The primary efficacy measure was the Sum of Pain Intensity Difference (SPID) for the first 12h after the start of drug infusion. Other efficacy measures included SPID at other time points, opioid consumption via on-demand patient-controlled analgesia (PCA) and rescue medication, and proportion of patients who did not require rescue opioids for 48h post-dose. Pain relief as measured by SPID was significantly improved by 35% in the VVZ-149 group compared to the placebo group at 6h (p=0.0193) and 12h (p=0.0047) after the start of infusion. Significantly lower pain intensity scores were observed between 4-10h in the VVZ-149 group compared to the placebo group (p=0.0007), reaching mild pain (mean NRS <4) at 8h. VVZ-149 alleviated pain during the first 12h post-dose with 30.8% less opioid consumption and 60.2% fewer PCA requests when compared with placebo. A higher proportion of patients receiving VVZ-149 were rescue opioid-free during 2-6h (p=0.0026) and 6-12h (p=0.0024) compared with the placebo group. VVZ-149 administration in post-colectomy patients was generally safe and well tolerated. When compared to placebo, VVZ-149 infusion demonstrated a significant reduction of pain within the first 12h after surgery with a substantial decrease in opioid use. VVZ-149 rapidly lowers the pain intensity starting at as early as 4h post-dose, allowing subjects to experience mild pain levels from 8h through 48h. Therefore, the analgesic effect of VVZ-149 was shown to effectively relieve pain and reduce opioid use for treating moderate to severe pain in the early postoperative care setting. Trial Number NCT05764525.

Postoperative Analgesia and Length of Hospital Stay After Surgery for Malignant Pleural Mesothelioma: A Retrospective Observational Study

Background: Pleurectomy/decortication (P/D), a surgical procedure for malignant pleural mesothelioma (MPM), is a highly invasive surgery requiring prolonged hospitalization. Previous studies have reported that postoperative analgesia using regional anesthesia contributes to shorter hospital stays after surgery under general anesthesia by reducing acute postoperative pain. However, the association between postoperative analgesia and the length of hospital stay (LOHS) following P/D has not been evaluated. Objectives: To evaluate the association between postoperative analgesia and postoperative LOHS after P/D. Methods: This single-institution observational study enrolled consecutive adult patients undergoing P/D under general anesthesia, who postoperatively received either intertransverse process block (ITPB) or continuous intravenous (IV) fentanyl infusion as postoperative analgesia between March 2022 and February 2023. Results: Among all enrolled patients with ASA physical status II or III (n = 60), postoperative analgesia was administered using either continuous ITPB (n = 19) or continuous IV fentanyl infusion (n = 41). Multivariable logistic regression analysis revealed that postoperative analgesia with continuous ITPB (P = 0.007), a lower incidence of major complications after surgery (P = 0.034), and female sex (P = 0.033) were significantly associated with a shorter postoperative LOHS. In subgroup analysis, patients who received continuous ITPB had significantly lower postoperative LOHS, lower postoperative serum C-reactive protein levels on postoperative day (POD) 3, and reduced acute postoperative pain on POD3 compared to those who received continuous IV fentanyl infusion. Conclusions: Postoperative analgesia using continuous ITPB appears to be associated with a reduction in LOHS following P/D for MPM under general anesthesia.

Effect of Hematopoietic Stem Cell Transplantation Regimen on Tacrolimus Pharmacokinetics.

Treatment with tacrolimus requires strict control of the whole-blood concentration in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). In patients undergoing cord blood transplantation (CBT), there is a negative correlation between volume of distribution of tacrolimus and hemoglobin levels, which reflect the red blood cell (RBC) count. In this study, we evaluated the influence of the conditioning regimen (myeloablative and reduced-intensity conditioning) or donor source (cord blood, bone marrow, and peripheral blood stem cells) on the pharmacokinetics of tacrolimus in patients undergoing HSCT, including those undergoing CBT. We also examined applicability of dosing strategy of tacrolimus considering the RBC count. We retrospectively analyzed clinical data-including whole-blood tacrolimus concentrations-from patients with HSCT. The observation period spanned from first continuous intravenous infusions until switch to oral medication, transfer to another hospital, relapse, or death. Population pharmacokinetic analysis was performed on whole-blood tacrolimus concentrations obtained from therapeutic drug monitoring during the observation period. Patient characteristics and laboratory data were evaluated as covariates. We enrolled 91 patients undergoing HSCT (CBT: n = 56; bone marrow transplantation: n = 22; and peripheral blood stem cell transplantation: n = 13); 58 and 33 patients received myeloablative conditioning and reduced-intensity conditioning, respectively. Whole-blood tacrolimus concentrations were accurately captured (n = 1,658 measurements) using a one-compartment and additive error model. The conditioning regimen and donor source did not have an impact on the pharmacokinetics of tacrolimus. Therefore, these factors were not considered when forming the dosing strategy. Nevertheless, a negative correlation between volume of distribution and hemoglobin level was confirmed, indicating that monitoring the RBC count is useful in assessing the dosing strategy. A tacrolimus dosing strategy that considers the variability in hemoglobin levels applies to all patients undergoing HSCT.

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.

Short-Course Blinatumomab Treatment as a Bridge to Further Salvage Therapy for Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia: A Retrospective Single-Center Study.

The high cost of blinatumomab in full doses of full treatments has led to dose reduction and fewer treatment cycles for most patients in China. With current needs for cost-efficiency and resource management in health care, we retrospectively evaluated the clinical effects of short-course blinatumomab treatment for R/R Ph- B-ALL at our center. Blinatumomab was administered with 24-h continuous intravenous infusion (9 μg/day for the first 3 days and 28 μg/day for 6-10 days). The clinical data of 30 R/R B-ALL patients were collected and analyzed. A total of 25 patients (83.3%) including 13 (43.3%) with a high leukemic load (> 50%) achieved morphological CR. Twelve patients (40%) were MRD-negative. The estimated 2-year OS rate was 82.62%. The 2-year PFS rate was 78.35%. The estimated 2-year OS and PFS were significantly better in patients receiving further treatment. Our findings provide novel insights into the optimization of blinatumomab therapy, proposing a viable treatment alternative that aligns with current needs for cost-efficiency and resource management in health care.

Retrospective comparison of the effects of remimazolam and dexmedetomidine on postoperative delirium in elderly patients undergoing orthopedic surgery of the lower extremities under spinal anesthesia.

Remimazolam is often used for perioperative sedation due to its rapid onset and offset. However, the possible association between remimazolam and postoperative delirium (POD) remains undetermined. The present study evaluated whether remimazolam increased the incidence of POD compared with dexmedetomidine in elderly patients undergoing orthopedic surgery of the lower extremities. This retrospective study included patients aged ≥ 65years who had undergone orthopedic surgery of the lower extremities under spinal anesthesia from January 2020 to November 2022 and were sedated with continuous intravenous infusion of dexmedetomidine or remimazolam. The incidence of POD was assessed through a validated comprehensive review process of each patient's medical records. The effect of remimazolam on the occurrence of POD compared with dexmedetomidine was evaluated by propensity score weighted multivariable logistic models. A total of 447 patients were included in the final analysis. The crude incidence of POD within 3days after surgery was 7.5% (17/226) in the dexmedetomidine group and 11.8% (26/221) in the remimazolam group, increasing to 9.7% (22/226) and 15.8% (35/221), respectively (p = 0.073), within 5days. The multivariable models showed that, compared with dexmedetomidine, intraoperative sedation with remimazolam significantly increased the occurrence of POD within 3days (odds ratio [OR] 2.21, 95% confidence interval [CI] 1.31 to 3.82, p = 0.003) and 5days (OR 2.10, 95% CI 1.32 to 3.40, p = 0.002). Compared with dexmedetomidine, remimazolam infusion may be associated with a higher risk of POD in elderly patients undergoing orthopedic surgery of the lower extremities under spinal anesthesia.

Midazolam Boosting With Cobicistat in a Patient With Drug-Resistant Epilepsy and Focal Status Epilepticus.

This report presents the case of a patient with drug-resistant epilepsy. Despite treatment with 4 antiepileptic drugs, the patient experienced an increasing frequency of focal seizures, necessitating hospitalization, and continuous intravenous midazolam infusion. Cobicistat was introduced as a pharmacokinetic booster to decrease the metabolic clearance of midazolam, leading to increased exposure and an extended half-life. Cobicistat boosting allowed the switch from intravenous to oral midazolam, and the patient was discharged on an oral midazolam regimen. Cobicistat can be effectively used to boost midazolam exposure pharmacokinetically in patients with drug-resistant epilepsy who require stable midazolam blood concentrations.

Co-administration of dexmedetomidine with total intravenous anaesthesia in carotid endarterectomy reduces requirements for propofol and improves haemodynamic stability: A single-centre, prospective, randomised controlled trial.

Total intravenous anaesthesia guided by electroencephalography and neurophysiological monitoring may be used for carotid endarterectomy. Reduction of brain metabolic demand during cross-clamping of the internal carotid artery with propofol titrated to burst suppression requires effect-site concentrations that may delay emergence and interfere with intraoperative neurophysiological monitoring. To test the hypothesis that dexmedetomidine decreases the effect-site concentration of propofol required for burst-suppression in patients undergoing carotid endarterectomy. Randomised controlled trial. Patients undergoing carotid endarterectomy. University Hospital of Berne, Switzerland, from October 2018 to September 2024. Patients were randomised into a control (n = 23) and a dexmedetomidine groups (n = 22). Total intravenous anaesthesia was administered to both groups. Patients in the dexmedetomidine group received an intravenous bolus of dexmedetomidine (0.4 μg kg-1 over 10 min) before induction, followed by a continuous intravenous infusion (0.4 μg kg-1 h-1). The effect-site concentrations of propofol were titrated against frontal electroencephalography parameters. Burst suppression was induced with propofol during cross-clamping of the internal carotid artery. The primary outcome was the effect-site concentration of propofol required for burst-suppression. The secondary outcomes were the requirement for vasoactive substances, neurophysiological monitoring parameters, and postoperative delirium. The effect-site concentration of propofol required for burst suppression was 4.0 μg ml-1 [3.50 to 4.90] (median [interquartile range]) in the dexmedetomidine group compared with 6.0 μg ml-1 [5.5 to 7.3] in the control group (P < 0.001). Less norepinephrine was required in the dexmedetomidine group (total 454 μg [246 to 818] compared with 1000 μg [444 to 1326] (P = 0.015) in the control group). Dexmedetomidine did not affect intraoperative neurophysiological monitoring. Co-administration of dexmedetomidine to total intravenous anaesthesia for carotid endarterectomy decreased the effect-site concentrations of propofol required for burst suppression by 33%. The propofol-sparing effect and peripheral alpha-agonism of dexmedetomidine may explain the reduced requirement for vasopressors. Clinicaltrials.gov identifier: NCT04662177.

Selenoprotein P as a prognostic biomarker of burn sepsis: A prospective cohort study

IntroductionSeverely burned patients exhibit increased nutritional requirements and are at high risk of developing sepsis. Selenium is an essential trace element supporting antioxidant and anti-inflammatory pathways, mediated by incorporation into selenoproteins. The selenium status may affect sepsis risk in burn injury. MethodsThis prospective cohort study included 90 adult patients admitted to Zurich Burn Center, Switzerland. All patients received a continuous intravenous infusion of 1000 μg sodium selenite per day during the first week as part of local standard of care. Three complementary biomarkers of serum selenium status were determined at nine time-points up to six months postburn, namely total selenium, selenoprotein P, and glutathione peroxidase 3. The resulting data were correlated to clinical parameters and outcomes, with sepsis as the primary end point. ResultsA high fraction of the patients displayed selenium deficiency already at admission, and developed sepsis during hospitalization (n = 55; 61 %). Selenium status at admission was inversely related to burn severity. Low baseline selenoprotein P was associated with sepsis incidence, irrespective of trauma severity (adjusted HR, 1.94; 95 % CI, 1.05–3.63; p = 0.035). Burn severity and baseline concentrations of selenoprotein P and white blood cells together predicted sepsis with an area under the curve of 0.84 (95 % CI, 0.75–0.93; p < 0.0001). Supplemental selenium was associated with a transient normalization of selenium status. ConclusionConsidering its rapid decline following severe burn injury, the assessment of serum selenoprotein P upon admission may contribute to an early prediction of sepsis risk.

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.

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.