Infusion Of Dose Research Articles

Outcome of carbapenem or colistin resistant Klebsiella pneumoniae bacteremia in the intensive care unit

Carbapenem-resistant Klebsiella pneumoniae (CRKp) infections continue to be an important cause of mortality. In this retrospective study, the effect of carbapenem or colistin resistance on mortality in Klebsiella pneumoniae bacteremia and combined meropenem + colistin administration in CRKp bacteremia was evaluated. In addition to that, a mathematical model is applied to explore the relationships between the resistance and mortality. A total of 139 adult patients diagnosed with K. pneumoniae bacteremia(73 carbapenem sensitive and 66 carbapenem resistant) between 01/01/2000 and 31/07/2019 were included in the study. The 30-day mortality in entire cohort were 19.4%. 30-day mortality was significantly higher in the carbapenem resistant-colistin sensitive group and in the carbapenem resistant-colistin resistant group compared to the carbapenem susceptible group. Meropenem + colistin combination was administered to 37 (95%) of carbapenem resistant–colistin sensitive (n = 39) and 25 (93%) of carbapenem resistant–colistin resistant patients(n = 27). Notably, mortality was not significantly affected regardless of whether CRKp was colistin sensitive and whether a high dose and prolonged infusion of meropenem was administered. Mortality is higher in carbapenem resistant Klebsiella pneumoniae bacteremia compared to carbapenem susceptible group. In cases of combined meropenem and colistin administration, high dose and prolonged infusion of meropenem is not superior to standard dose and infusion in both carbapenem resistant–colistin sensitive and carbapenem resistant–colistin resistant K. pneumoniae bacteremia.

SGLT2 inhibitor empagliflozin prevents anthracycline-induced cardiotoxicity in a large-animal model

Abstract Background While the development of cancer therapies has significantly improved the survival of cancer patients, more than 35% of cancer survivors treated with anthracyclines will develop cardiotoxicity. There is currently a lack of preventative therapies against anthracycline-induced cardiotoxicity (AIC). AIC is characterised by a disruption in myocardial metabolism. Sodium-glucose co-transporter (SLGT2) inhibitors represent a potential therapy as they have been shown to modulate myocardial substrate utilisation in other heart-failure contexts. Purpose We developed a highly translational large-animal model to test the ability of SGLT2 inhibitor empagliflozin to prevent AIC at different doses. Methods Female Large-White pigs were randomised (2:1:1) to no treatment (AIC-control group) or empagliflozin at a daily oral dose of 10 mg or 20 mg, beginning at the start of the doxorubicin regimen and continuing to 21 weeks. All pigs received 6 doses of doxorubicin intravenous infusion (25 mg/m2/every 3 weeks) with 2 additional off-dose visits. Pigs were assessed by cardiac magnetic resonance (CMR) and MR spectroscopy (MRS) at baseline and every 3 weeks for 21 weeks. At the end of 21-week follow-up, the LV was collected and processed for analysis by transmission electron microscopy (TEM) and mitochondrial respirometry. Results The primary outcome, final LVEF, was significantly higher in pigs receiving 20 mg empagliflozin than in the AIC-control group (57.5% (IQR=55.5, 60.3) vs 47.0% (40.8, 47.8); p=0.027). Final LVEF in pigs receiving 10 mg empagliflozin was 51% (46.5, 55.5) (p=0.020 vs 20 mg empagliflozin). The 20 mg empagliflozin dose prevented the doxorubicin-induced change in cardiac metabolic substrate utilisation and was associated with preservation of myocardial energetics (ATP/PCr ratio on MRS). TEM revealed disrupted mitochondrial structure and cristae density in AIC-control pigs, while mitochondria respirometry detected deteriorated respiratory function. Both mitochondrial structure and function were preserved in empagliflozin-treated pigs, with the 20 mg dose having the strongest cardioprotective effect. Conclusion The results from our translational large-animal model provide strong evidence that SGLT2 inhibition with empagliflozin prevents AIC by preserving LV systolic function and energetics as well as mitochondrial structural integrity and function. Our results establish the basis for clinical trial testing SGLT2i therapy in patients at high risk of AIC.

A Technique Avoiding Cardioplegia Delivery Complications: A Case Using Systemic Hyperkalemia Cardiopulmonary Bypass Combined with Circulatory Arrest

We conducted a high-risk redo mitral valve replacement through a right mini-thoracotomy without rib spreading (redo-MICS MVR) under systemic hyperkalemia combined with circulatory arrest to circumvent complications associated with cardioplegia delivery. The patient, a 75-year-old man, had a predicted mortality rate of 20%. Initial antegrade cardioplegia successfully induced cardiac arrest, which was administered every 30 minutes. However, upon infusion of the second dose of cardioplegia, the aortic root pressure was approximately 20 mmHg. Despite multiple attempts to re-cross clamp, the aortic root pressure did not improve. Consequently, retrograde cardioplegia was considered, but due to significant adhesion of the inferior vena cava, this approach was abandoned. Thus, the procedure was altered to utilize systemic hyperkalemia without aortic cross-clamping. Given the preoperative transesophageal echocardiography (TEE) diagnosis of mild aortic regurgitation, maintaining a clear surgical field was challenging, necessitating the combination of redo-MVR with circulatory arrest. This case exemplifies the successful management of cardioplegia delivery complications using systemic hyperkalemia and circulatory arrest, resulting in a favorable postoperative recovery for the patient.

D-Aspartate Stimulates Growth Hormone Secretion in Wethers.

Growth hormone (GH) is an essential factor in enhancing the productivity of animals. In ruminants, L-aspartate (L-Asp) stimulates the secretion of GH; however, the effect of D-Asp on GH remains unknown. Here, we examined the effect of D-Asp on GH secretion in wethers. Blood GH, insulin, adrenaline, noradrenaline, non-esterified fatty acid (NEFA), and glucose concentrations were evaluated in response to the intravenous infusion of a high-dose (0.1 mmol/kg/min) of D-Asp for 20min. Further, concentrations of these biomolecules were evaluated when a low-dose (0.05 mmol/kg/min) of D-Asp was continuously infused intravenously for 20min. Finally, the direct effect of D-Asp on GH secretion was determined using cultured sections of the anterior pituitary tissue from wethers. Infusion of the high-dose of D-Asp markedly increased blood GH concentrations (P < 0.05), resulting in an increase in the area under the curve (AUC). Plasma GH concentrations and AUC also increased in response to infusion of a low D-Asp dose. Infusion of a high and low D-Asp dose caused a prolonged reduction in plasma insulin concentrations, and the AUC was lower (P < 0.05). Plasma NEFA concentrations gradually increased after the end of D-Asp infusion, with a low D-Asp dose infusion resulting in significantly higher concentrations at 90min (P < 0.05). Plasma adrenaline, noradrenaline, and glucose concentrations did not show significant changes despite differences in the dose of D-Asp. Although D-Asp treatments stimulated GH secretion in the cultured sections of pituitary tissues, the effect was not significant. These results suggest that D-Asp stimulates the secretion of GH in wethers through not only a direct action on the pituitary gland but also through another pathway of GH stimulation.

Collaboration to Remove Barriers to Pump Integration With the Electronic Health Record.

The Institute for Safe Medication Practices and The Joint Commission recommend the implementation of bidirectional smart infusion pump interoperability with the electronic health record (EHR) to improve medication safety. However, there are barriers associated with implementation of this process. The purpose of this process improvement project was to identify, evaluate, and implement improvements in pump integration with the EHR to decrease manual programming and increase the use of the smart pump functions (the dose error reduction system or infusion guardrails). A medication safety task force was formed, and end users were surveyed for barriers. The task force found and implemented solutions to improve the process. Infusion pump integration rates for seven hospitals improved from 79.4% to 91.8% (p < .001), and the use of smart pump programming increased from 84.7% to 93.6%. Including all stakeholders in the project allowed barriers to be identified and solutions to be implemented. As more healthcare systems implement technology-related processes to improve patient safety, this work can guide medication safety teams on how to optimize technology use by removing barriers to the use of pump integration with the EHR.

Comparison of the effect of different doses of phenylephrine infusion on the prevention of hypotension in the elderly under spinal anaesthesia in orthopaedic surgery.

Considering the vasopressor drug categories and doses that can be used for elderly patients following hypotension are few, the present trial aimed to compare the effect of different doses of phenylephrine infusion on the prevention of hypotension in elderly patients undergoing orthopaedic lower extremities surgery. This randomised, double-blind prospective clinical trial was conducted by including 60 elderly patients older than 60 years and classified as American Society of Anesthesiology class I and II who were candidates for femur fracture fixation surgery. White and black cards randomly allocated patients to: group A (25µg/kg/h phenylephrine) or group B (35µg/kg/h phenylephrine). At the T3-T7 time points, group A's systolic and diastolic blood pressure was significantly higher than in group B's (p < 0.05). However, after 27 minutes (T0-T7) of phenylephrine infusion, statistical analysis showed no significant difference between the two groups regarding blood pressure (T8-Tend). The frequency of bradycardia and reactive hypertension in group B were significantly higher than in group A (p = 0.02) and (p = 0.03), respectively. There was no significant difference between the bleeding loss, blood transfusion and crystalloid volume in both groups (p > 0.05). Our trial illustrated that high-dose phenylephrine infusion could not assure haemodynamic stability and may cause some side effects.

The Use of Cangrelor in Cardiogenic Shock: Insights from the CAMEO Registry

Little is known about the use of cangrelor in patients with myocardial infarction (MI) presenting with cardiogenic shock (CS). CAMEO (Cangrelor in Acute MI: Effectiveness and Outcomes) is a multicenter observational registry evaluating platelet inhibition in patients with MI. We examined the duration of cangrelor infusion and the amount of time to transition from cangrelor to an oral P2Y12 inhibitor in patients with CS. We also assessed major adverse cardiovascular events (MACEs) and bleeding risks, stratified by dosage duration, time to transition and oral P2Y12 inhibitor potency. Among 2352 cangrelor-treated patients with MI, 249 patients were in CS. Among the patients with CS, 16 (6.4%) received the "bridge" infusion dose, 202 (81.1%) the PCI cangrelor infusion dose, and 30 (12.0%) had a combination of both infusion doses. Patients with CS had a median age of 66 years; 32% were women; 21% were Black patients; 35% had diabetes; 19% received thrombectomy; and 59% received mechanical circulatory support (MCS) (35% intra-aortic balloon pump, 27% Impella). The median duration of infusion was 3.9 (2-21.5 hours) in patients with CS and was 2 (1.6-3.1 hours) for all cangrelor-treated patients. The median duration of transition from cangrelor to oral P2Y12 inhibitor administration was 0.1 (-0.5-21.0 hours) for patients with CS. In multivariable modeling, chronic lung disease and the use of MCS and was associated with longer cangrelor infusions (defined as > 3.9 hours). Among cangrelor-treated patients with CS, 24.1% of these patients had a bleeding event, and 41.8% had a MACE event. After adjustment, a longer cangrelor infusion duration was associated with increased risk of bleeding (P < 0.05). The median duration of cangrelor infusion was longer for patients presenting with CS. Use of MCS was associated with longer cangrelor infusion durations in patients with CS. Further work is needed to understand the pharmacodynamics of antiplatelet agents in patients with CS.

Mass balance and pharmacokinetic characterization ofzavegepant in healthy male subjects.

Zavegepant, a high-affinity, selective, small-molecule calcitonin gene-related peptide receptor antagonist, is approved as a nasal spray for acute treatment of migraine in adults. This phase I, open-label, single-center, single-period, nonrandomized study in six healthy male subjects assessed mass balance recovery after a single 15-min intravenous (IV) infusion dose of carbon-14 ([14C])-zavegepant. Blood, urine, and fecal samples were collected over 192 h for analysis of zavegepant in plasma and urine; total radioactivity (TR) in plasma, whole blood, urine, and feces; and zavegepant metabolite profiling and structural identification in plasma, urine, and feces. An average of 96.6% of radioactivity administered was recovered in excreta. Most TR (mean 84.9%) was recovered in the feces, indicating that biliary/fecal elimination was the main route. Volume of distribution of zavegepant based on the terminal phase (129 L) was higher than total body water (42 L), indicating substantial distribution into tissue. Total plasma clearance of zavegepant (220 mL/min) is identical to whole blood clearance given the blood/plasma partition ratio of 1, lower than typical hepatic blood flow (1450 mL/min). The observed plasma terminal half-life of zavegepant was 6.8 h. Exposure to zavegepant accounted for ~90% of circulating plasma TR, suggesting that very low levels of uncharacterized circulating metabolites were present. Metabolite profiling did not identify any metabolites representing ≥10% of radioactivity in plasma, urine, or feces. A single IV infusion of 5 mg [14C]-zavegepant was well tolerated in healthy male subjects. Disposition findings of IV [14C]-zavegepant are applicable to the disposition of the approved zavegepant nasal spray.

Patient and Physician Perspectives of Treatment Burden in Multiple Sclerosis.

The number of disease-modifying therapies (DMTs) approved for the treatment of multiple sclerosis (MS) has greatly increased in recent decades, leading to higher treatment complexity. DMTs can differ in mode and frequency of administration, benefit-risk profile, and associated costs. Patients with MS contend not only with the burden of their chronic disease but also with the treatment burden of their MS therapy. Adhering to dosing schedules and infusion appointments can be difficult for busy, working-age patients or those with limited access to transportation. Patients and healthcare professionals (HCPs) may have differing priorities, concerns, and preferences when selecting treatment, potentially affecting treatment satisfaction and, importantly, adherence. Additionally, patients face direct and indirect costs related to treatment. These factors can all contribute to a high treatment burden on patients, impacting their quality of life and potentially leading to worse patient outcomes. HCPs, patients, and caregivers must work together to alleviate treatment burden through effective communication, shared decision-making, appreciating each other's perspectives, and additional HCP support. Consideration of treatment burden into clinical guidelines is also warranted. In this review, we examine key factors impacting treatment burden for patients with MS, with a focus on the patient perspective as provided by our patient authors, and provide strategies to minimize treatment burden.

A Retrospective Analysis of Intravenous Push versus Extended Infusion Meropenem in Critically Ill Patients.

Meropenem is a broad-spectrum antibiotic used for the treatment of multi-drug-resistant infections. Due to its pharmacokinetic profile, meropenem's activity is optimized by maintaining a specific time the serum concentration remains above the minimum inhibitory concentration (MIC) via extended infusion (EI), continuous infusion, or intermittent infusion dosing strategies. The available literature varies regarding the superiority of these dosing strategies. This study's primary objective was to determine the difference in time to clinical stabilization between intravenous push (IVP) and EI administration. We performed a retrospective pilot cohort study of 100 critically ill patients who received meropenem by IVP (n = 50) or EI (n = 50) during their intensive care unit (ICU) admission. There was no statistically significant difference in the overall achievement of clinical stabilization between IVP and EI (48% vs. 44%, p = 0.17). However, the median time to clinical stability was shorter for the EI group (20.4 vs. 66.2 h, p = 0.01). EI administration was associated with shorter hospital (13 vs. 17 days; p = 0.05) and ICU (6 vs. 9 days; p = 0.02) lengths of stay. Although we did not find a statistically significant difference in the overall time to clinical stabilization, the results of this pilot study suggest that EI administration may produce quicker clinical resolutions than IVP.

Effect of Continuous Infusion vs Bolus Dose of Hydrocortisone in Septic Shock: A Prospective Randomized Study.

Corticosteroids are recommended for use in adult patients with septic shock requiring vasopressors for blood pressure maintenance. However, this predisposes them to hyperglycemia, which is associated with a poor outcome. This prospective randomized study compares the effect of continuous infusion with bolus hydrocortisone on blood glucose levels in septic shock. Forty adult patients with sepsis and septic shock requiring vasopressor support were randomly allocated to either group C (continuous infusion of hydrocortisone 200 mg/day) or group B (intermittent bolus dose of hydrocortisone 50 mg IV 6 hourly). Blood glucose level (primary objective), number of hyperglycemic and hypoglycemic episodes, daily insulin requirement, shock reversal incidence, time to shock reversal, and nursing workload required to maintain blood glucose within the target range (82-180 mg/dL) were compared. The mean blood glucose level was comparable in the two groups (136.5 ± 22.08 mg/dL in group C vs 135.85 ± 19.06 mg/dL in group B; p = 0.921). The number of hyperglycemic and hypoglycemic episodes (p = 1.000 each), insulin requirement/day (p = 1.000), and nursing workload (p = 0.751) were also comparable among groups. Shock reversal was seen in 7/20 (35%) patients in continuous group and 12/20 (60%) patients in bolus group (p = 0.113). Time to shock reversal (p = 0.917) and duration of ICU stay (p = 0.751) were also statistically comparable. Both the regimes of hydrocortisone, continuous infusion, and bolus dose, have comparable effects on blood glucose levels in patients with septic shock.The study was registered prospectively with ctri.nic.in (Ref. No. CTRI/2021/01/030342; registered on 8/1/2021). Salhotra R, Sharahudeen A, Tyagi A, Rautela RS, Kemprai R. Effect of Continuous Infusion vs Bolus Dose of Hydrocortisone in Septic Shock: A Prospective Randomized Study. Indian J Crit Care Med 2024;28(9):837-841.

LBA61 Conventional oral morphine vs. IV patient-controlled analgesia (IPCA) with either hydromorphone (HM) continuous infusion plus rescue dose (CIRD) or HM bolus-only (BO) for severe cancer pain: A randomized phase III study

LBA61 Conventional oral morphine vs. IV patient-controlled analgesia (IPCA) with either hydromorphone (HM) continuous infusion plus rescue dose (CIRD) or HM bolus-only (BO) for severe cancer pain: A randomized phase III study

Low-Intensity Heparin Infusion Compared With High-Intensity Heparin Infusion Dosing in Patients With Mechanical Mitral Valves: A Retrospective Cohort Study.

Patients with a mechanical mitral valve have an increased risk of thrombosis, and guidelines recommend a higher international normalized ratio goal for vitamin K antagonists-based anticoagulation. Guidelines provide recommendations for bridging with unfractionated heparin; however, there is no clear guidance on the heparin infusion intensity that should be used. This study was a retrospective, single-center, cohort study of patients aged ≥18 years or older with a mechanical mitral valve admitted from June 2019 to September 2022 who were maintained on a singular heparin infusion intensity nomogram for at least 48 hours. The patients were stratified into either a low- or a high-intensity heparin infusion nomogram. The exclusion criteria included non-nomogram heparin infusions and patients within 30 days of valve implantation. The primary outcome of this study was a composite of all bleeding events (major, clinically significant nonmajor, and minor bleeding). The secondary outcomes included bleeding events, analyzed individually, and thrombotic events. Seven total bleeding events were observed between the 2 groups, with 1 minor bleeding event in the low-intensity group and 6 bleeding events in the high-intensity group. One thrombotic event occurred in the high-intensity group. No statistically significant differences were found between the primary and secondary outcomes. Future studies are necessary to guide heparin infusion intensity selection in patients with mechanical mitral valves.

Critical norepinephrine dose to predict early mortality during circulatory shock in intensive care: a retrospective study in 3423 ICU patients over 4-year period.

The maximal norepinephrine (NE) dose >1 μg/kg/min during circulatory shock apparently is associated with higher mortality, but this threshold needs confirmation. This study aimed at investigating whether NE infusion at a dose >1 μg/kg/min could predict early intensive care unit (ICU) mortality (first 5 days). The secondary objective was to assess the day-by-day relationship between NE dose during the first four days of ICU stay and subsequent mortality. We conducted a retrospective analysis of data from ICU patients receiving NE for circulatory shock at the Nimes University Hospital (France) from January/2016 to December/2019. 5,735 patients were admitted, 3,693 were screened and 3,423 were analyzed. NE infusion at a dose >1 μg/kg/min was associated with day-5 mortality (Hazard Ratio: 7.40, p < 0.0001). The area under the receiver operating characteristic was 0.79 to predict day-5 mortality in ICU for maximal NE > 1 μg/kg/min. The calculated threshold of 1.13 μg/kg/min for maximal NE was the best prognostic value (Sensitivity: 67%, Specificity: 80%, positive predictive value: 45%). When the 1.2 μg/kg/min threshold was crossed either on the first, second, third or fourth day of ICU stay, the probability of subsequent death was 47%, 49%, 60% and 40%, respectively. Along the first four days of ICU stay, the risk of death increased with increasing NE infusion dose. A NE infusion rate > 1.13 μg/kg/min predicts day-5 mortality in ICU patients with circulatory shock. The time to reach maximal NE infusion rate was shorter in survivors than in non-survivors.

Prostatic Pharmacokinetic and Pharmacodynamic Analysis of Ceftazidime: Dosing Strategy for Bacterial Prostatitis.

This study aimed to develop a prostatic pharmacokinetic model of ceftazidime and suggest more effective dosing strategy for the bacterial prostatitis, based on a site-specific pharmacokinetic and pharmacodynamic perspective. Subjects were prostatic hyperplasia patients prophylactically receiving a 0.5-h infusion of 1.0 g or 2.0 g ceftazidime before transurethral resection of the prostate. Plasma and prostate samples were premeditatedly collected after the administration and the concentrations were measured by high-performance liquid chromatography. The prostate tissue/plasma ratio in area under the drug concentration-time curve was approximately 0.476. The prostatic population pharmacokinetic model incorporated creatinine clearance (CLcr) into ceftazidime clearance was developed, and adequately predicted prostate tissue concentrations by diagnostic scatter plots and visual predictive checks. Aiming for a bactericidal target of 70% of time above minimum inhibitory concentration (T > MIC) in prostate tissue, 2.0 g twice daily achieved ≥90% expected probability against main pathogens like Escherichia coli and Proteus species in patients regardless of renal function (CLcr = 60 and 90 mL/min). However, since the expected probability of attaining the bactericidal target of 0.5-h infusion dosing regimen did not achieve 90% against Pseudomonas aeruginosa in patients with CLcr = 60 and 90 mL/min, 4-h infusion dosing regimen of 2.0 g three times daily (6 g/day) might be required for empirical treatment. Based on site-specific simulations, the present study provides more effective dosing strategy for bacterial prostatitis.

Toward Model-Informed Precision Dosing for Remimazolam: A Population Pharmacokinetic-Pharmacodynamic Analysis.

Remimazolam, widely used for procedural sedation and general anesthesia, is a new ultra short-acting benzodiazepine for intravenous sedation and anesthesia. We aim to characterize the pharmacokinetics/pharmacodynamics (PK/PD) of remimazolam and its metabolite CNS 7054 in healthy Chinese volunteers using population analysis and suggest an optimal dosing regimen for sedation therapy. Data were collected from a single-center, placebo-controlled, randomized, and dose-escalation clinical pharmacology study. Forty-six healthy volunteers received a single infusion dose of remimazolam, while nine healthy subjects received a continuous infusion of remimazolam. A population PK/PD model was established and RxODE and Shiny in R were used to design the remimazolam dosing regimens. A three-compartment model best described the PK of remimazolam and a two-compartment model with one transit compartment was adopted for CNS 7054. The relationship between exposure and the bispectral index was best described using an effect compartment model with an inhibitory sigmoid model. Additionally, a web-based dashboard was developed to provide individualized dosing regimens, complemented by a graphical illustration of the PK/PD profiles of the proposed dosing regimen. The established population PK/PD model characterized the dose-exposure-response relationship of remimazolam well, which could be applied to optimize individual dosing regimens.

Pharmacokinetics of Efmoroctocog alfa by Two-Compartment Model Highlights Hemophilia A Patients with Biphasic Decay, Long Mean Residence Time, and Beta Half-Life.

Background/Objectives: A compartmental pharmacokinetics (PK) analysis of new extended half-life FVIII concentrates has never been performed in a large cohort of hemophilia patients. An improved PK analysis of individual outcomes may help to tailor hemophilia replacement treatment. Methods: PK outcomes after the infusion of a standard single dose of Efmoroctocog alfa were collected from 173 patients with severe/moderately severe hemophilia A in 11 Italian hemophilia centers. Factor VIII clotting activity (FVIII:C) was measured by one-stage clotting assay (OSA) in all patients, and chromogenic substrate assay (CSA) in a subgroup (n = 52). Fifty patients underwent a comparative PK assessment with standard half-life (SHL) recombinant FVIII (rFVIII) products. Non-compartmental analysis (NCA), one compartment model (OCM), and TCM were used to analyze the decay curves of all patients, and one-way paired ANOVA to compare the PK outcomes. Results: All 173 PKs conformed to the NCA and OCM, but only 106 (61%) conformed to the TCM based on the biphasic features of their decay curves. According to the TCM, the Beta HL and MRT of rFVIIIFc were 20.42 ± 7.73 and 25.64 ± 7.61 h, respectively. ANOVA analysis of the outcomes from the three PK models showed significant differences in clearance, half-life (HL), and mean residence time (MRT) (p < 0.001 for all parameters). As anticipated, the HL and MRT of rFVIIIFc were longer than those of SHL rFVIII. Comparing OSA with CSA outcomes, Cmax resulted higher when measured by CSA (p = 0.05) and, according to TCM, Beta HL resulted longer when measured by OSA (p = 0.03). FVIII:C trough levels obtained with SHL concentrates were significantly lower than those obtained with rFVIIIFc at each post-infusion time point. Conclusions: In a large group of hemophilia A (HA) patients, three different PK models confirmed the improved pharmacokinetic (PK) characteristics of rFVIIIFc, compared with standard half-life rFVIII concentrates. The TCM only fits two-thirds of the PKs, highlighting their biphasic decay and a long Beta half-life. In these patients, the TCM would be preferable to properly evaluate individual PK features.

Assessment of effect of two different doses of dexmedetomidine infusion on emergence agitation and quality of recovery after nasal surgery

: To evaluate two different doses of dexmedetomidine infusion on emergence agitation and measurement of hemodynamics, bispectral index, cortisol levels, and quality of recovery in patients who underwent nasal surgery under general anaesthesia.94 individuals of either sex between the ages of 18 and 65 who experienced nasal surgery under general anesthesia were split into two groups for this randomized experimental study. Before induction, each group received loading doses of dexmedetomidine (DEX) infusion at a rate of 1 µg/kg over a period of 10 minutes. Group B underwent a standard induction and then received an infusion of 0.4μg/kg/h of dexmedetomidine every hour until they were extubated, while group A received an infusion of 0.8μg/kg/h. Sevoflurane was employed for maintenance. During emergence, the frequency of agitation, cough hemodynamic parameters, and recovery traits were assessed. Patients received the Quality of Recovery (QoR-40) questionnaire 24 hours following surgery.The hemodynamic reaction to laryngoscopy and intubation was blunted and the intubating circumstances were improved by both doses equally well. Group A's intraoperative mean PR and MAP were significantly (P&amp;#60;0.05) lower than group B's. Coughing was more common among the subjects in group A. A statistically significant difference was found between groups in comparing emergence agitation. Cortisol levels were significantly higher postoperatively in the 0.4µg/kg dose of dexmedetomidine 0.8µg/kg/ group (p=0.001). Global QoR-40 score at 24 h after surgery showed a better global recovery profile in group A. :Although a greater dose of DEX may have more hemodynamic adverse effects, it may also reduce the incidence of emergent agitation, the surgical stress response, and a smoother recovery profile.

Prolonged magnesium sulfate infusion as adjuvant analgesia in postoperative transplant patients in the pediatric ICU: Preliminary results of a feasibility study

AbstractThe opioid crisis has emphasized identification of opioid‐sparing analgesics. This study was designed as a prospective trial with retrospective control group to determine feasibility for implementing a high‐dose prolonged magnesium sulfate infusion for adjuvant analgesia in the pediatric intensive care unit. Approval was granted for study of children receiving total pancreatectomy with islet cell autotransplantation and liver transplantation ages 3–18 years. Study exclusions were pregnancy, neuromuscular disease, hypersensitivity, preoperative creatinine &gt;1.5 times upper limit normal, arrhythmia or pacemaker presence, and clinician concern. Eleven patients were enrolled between January 2020 and December 2022. Magnesium sulfate bolus (50 mg/kg) followed by intravenous infusion (15 mg/kg/h) was initiated in the operating room and extended postoperatively (maximum 48 h). Serum magnesium levels were monitored serially. To prioritize safety, infusion dose was decreased by 5 mg/kg/h for levels greater than 3.5 mg/dL. Clinical team otherwise followed standard multimodal pain practice. Primary outcome was oral morphine equivalent per kg per day during intensive care course (maximum 7 days). Secondary outcomes focused primarily on magnesium safety, including hemodynamic variables, electrolyte variables, respiratory support, and opioid‐related side effects. There were no serious adverse events. Treatment group trended toward slightly higher intravenous fluid requirement (~1 bolus), however no increase in blood product. Treatment and control groups were otherwise comparable in targeted outcomes and overall adverse event profile. Use of a high‐dose magnesium sulfate infusion protocol for analgesic postoperative use in select transplant recipients appears feasible for continued optimization of study in the PICU.

Perioperative dexmedetomidine-induced delirium in a patient with schizophrenia: a case report

BackgroundDexmedetomidine is a selective α2 receptor agonist with sedative, analgesic, anxiolytic, and anti-sympathetic effects. Dexmedetomidine is widely used for various surgical procedures performed under general anaesthesia and sedation in the intensive care unit. Dexmedetomidine was known to relieve or improve the symptoms of delirium. Schizophrenia is a common psychiatric disease, and the number of surgical patients with schizophrenia is increasing gradually. Dexmedetomidine-induced delirium in patients with schizophrenia is a particular case.Case presentationThis patient was a 75-year-old woman (height: 156 cm; weight: 60 kg) with a 5-year history of schizophrenia. Her schizophrenia was well controlled with medications. She was scheduled for open reduction and internal fixation for a patellar fracture. Spinal anaesthesia was administered for surgery, and dexmedetomidine was administered intravenously to maintain sedation. The patient became delirious half an hour after the surgery began. The intravenous infusion of dexmedetomidine was discontinued immediately, intravenous propofol was subsequently administered, and the patient stopped experiencing dysphoria and fell asleep. After surgery, the patient stopped using propofol and recovered smoothly. She was transferred back to the general ward and was discharged from the hospital without any abnormal conditions on the 9th day after surgery.ConclusionsTo the best of our knowledge, this is the first report of a patient with schizophrenia who developed delirium during the infusion of a normal dose of dexmedetomidine without an intravenous injection of any other sedative. The exact mechanism causing dexmedetomidine-induced delirium remains unclear, and this adverse reaction is rare and easy to ignore. Clinicians and pharmacists should be vigilant in identifying this condition.