Intravenous Infusion Research Articles

The cell-permeant antioxidant D-thiol ester D-cysteine ethyl ester overcomes physical dependence to morphine in male Sprague Dawley rats.

The ability of morphine to decrease cysteine transport into neurons by inhibition of excitatory amino acid transporter 3 (EAA3) may be a key molecular mechanism underlying the acquisition of physical and psychological dependence to morphine. This study examined whether co-administration of the cell-penetrant antioxidant D-thiol ester, D-cysteine ethyl ester (D-CYSee), with morphine, would diminish the development of physical dependence to morphine in male Sprague Dawley rats. Systemic administration of the opioid receptor antagonist, naloxone (NLX), elicited pronounced withdrawal signs (e.g., wet-dog shakes, jumps, rears, circling) in rats that received a subcutaneous depot of morphine (150mg/kg, SC) for 36h and continuous intravenous infusion of vehicle (20μL/h, IV). The NLX-precipitated withdrawal signs were reduced in rats that received an infusion of D-CYSee, but not D-cysteine, (both at 20.8μmol/kg/h, IV) for the full 36h. NLX elicited pronounced withdrawal signs in rats treated for 48h with morphine (150mg/kg, SC), plus continuous infusion of vehicle (20μL/h, IV) that began at the 36h timepoint of morphine treatment. The NLX-precipitated withdrawal signs were reduced in rats that received a 12h infusion of D-CYSee, but not D-cysteine, (both at 20.8μmol/kg/h, IV) that began at the 36h timepoint of morphine treatment. These findings suggest that D-CYSee may attenuate the development of physical dependence to morphine and reverse established dependence to the opioid in male Sprague Dawley rats. Alternatively, D-CYSee may simply suppress the processes responsible for NLX-precipitated withdrawal. Nonetheless, D-CYSee and analogues may be novel therapeutics for the treatment of opioid use disorders.

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.

Intravenous injection of allogenic canine mesenchymal stem cells in 40 client-owned dogs: a safety assessment in veterinary clinical trials

BackgroundThe aim of this study was to evaluate the adverse effects of allogeneic mesenchymal stem cells (MSCs) transplanted via intravenous infusion in dogs and examine their safety. We performed a retrospective analysis of various clinical assessments, including physical examination, blood tests, and radiographs, and monitored the formation of neoplasms during a 6-month follow-up period in 40 client-owned dogs that received intravenous infusion of adipose tissue-derived MSCs (AT-MSCs) for the treatment of various underlying diseases between 2012 and 2018.ResultsNo significant adverse effects of MSC therapy were detected by clinical assessment, blood tests, or radiographic examination in the 6-month follow-up period after the first MSC treatment. Additionally no new neoplasms were observed during this period.ConclusionsTo our knowledge, this study is the first to evaluate the safety aspects (≥ 6 months) associated with intravenous allogeneic AT-MSC infusion. These results suggest that allogenic AT-MSC infusion could be a useful and relatively safe therapeutic approach in canines.

Impact of Surgical and Anesthetic Procedures after Colorectal Cancer Surgery: A Propensity Score-Matched Cohort Study (The PROCOL Study).

Background: Surgical inflammatory pain decreases the innate and adaptive immune antitumor response and favors residual circulating tumor cells. Objectives: This study investigated whether minimally invasive surgeries (laparoscopic and robotic procedures), which are less painful and inflammatory, improved oncological outcomes after colorectal resection compared to laparotomy. Methods: This research was a single-center propensity score-matched study involving patients who underwent colectomy and rectum resection from July 2017 to December 2019. Results: Seventy-four laparotomies and 211 minimally invasive procedures were included. Minimally invasive procedures were associated with less blood loss (0 mL vs. 75 mL, p < 0.001), shorter length of stay (8 days vs. 12 days, p < 0.001), and fewer complications at 3 months (11.8% vs. 29.4%, p = 0.02) compared to laparotomies. No difference in overall survival (OS) and recurrence-free survival (RFS) at 3 years between groups was observed. Univariate Cox regression analyses demonstrated that age and ASA > 3 can negatively impact OS, while adjuvant chemotherapy can positively influence OS. pT3-T4 stage and postoperative pain could negatively influence RFS. Multivariate Cox regression analyses concluded that age (HR 1.08, p < 0.01) and epidural analgesia (HR 0.12, p = 0.03) were predictors for OS. Lidocaine infusion (HR 0.39, p = 0.04) was a positive predictor for RFS. Conclusions: Minimally invasive procedures reduce postoperative complications and shorten the length of hospital stay compared to major surgeries without improving prognosis. However, the administration of local anesthetics through neuraxial anesthesia or intravenous infusion could improve survival and decrease the occurrence of relapses.

An in vitro study for reducing the cytotoxicity and dose dumping risk of remdesivir via entrapment in nanostructured lipid carriers

The aim of this study was to synthesize and evaluate nanostructured lipid carriers (NLCs) loaded with Remdesivir (RDV) to control its side effects in COVID-19 patients. Due to the low solubility and short half-life of RDV in the blood, an injectable formulation was prepared using sulphobutylether-beta-cyclodextrin. However, it can accumulate in the kidney and cause renal impairment. NLCs improve the parenteral delivery of hydrophobic drugs such as RDV by increasing drug solubility and bioavailability. For the synthesis of RDV-NLCs, the aqueous phase containing Tween 80 was injected into the lipid phase under rapid stirring and was sonicated. The experimental conditions were optimized using Box-Behnken design and Design Expert software. The optimum formulation contained a total lipid of 2.13%, a total surfactant of 1%, and a hot bath time of 71 min. The optimum formulation showed particle size, polydispersity index, zeta potential, and entrapment efficiency values of 151.0 ± 1.7 nm (from 149.1 to 152.1), 0.4 ± 0.1 (from 0.3 to 0.5), −43.8 ± 1.2 mV (from −42.4 to −44.7), and 81.34 ± 1.57% (from 79.52 to 82.33%), respectively. RDV-NLCs showed acceptable stability for 30 days at 25 ℃ and were compatible with commonly used intravenous infusion fluids for 48 h. FE-SEM images of RDV-NLC showed spherical particles with a mean diameter of 207 nm. The NLC-RDV formulation showed a sustained release of RDV with a low risk of dose-dumping, minimizing potential side effects. In addition, RDV in the form of RDV-NLC causes less cytotoxicity to healthy normal kidney cells, which is expected to reduce renal impairment in COVID-19 patients.

Diagnosis of Brugada Syndrome With a Sodium-Channel-Blocker Test: Who Should Be Tested? Who Should Not?

Intravenous infusion of sodium-channel blockers (SCB) with either ajmaline, flecainide, procainamide, or pilsicainide to unmask the ECG of Brugada syndrome is the drug challenge most commonly used for diagnostic purposes when investigating cases possibly related to inherited arrhythmia syndromes. For a patient undergoing an SCB challenge, the impact of a positive result goes well beyond its diagnostic implications. It is, therefore, appropriate to question who should undergo a SCB test to diagnose or exclude Brugada syndrome and, perhaps more importantly, who should not. We present a critical review of the benefits and drawbacks of the SCB challenge when performed in cardiac arrest survivors, patients presenting with syncope, family members of probands with confirmed Brugada syndrome, and asymptomatic patients with suspicious ECG.

Intravenous infusions of mesenchymal stromal cells have cumulative beneficial effects in a porcine model of chronic ischemic cardiomyopathy.

The development of cell therapy as a widely-available clinical option for ischemic cardiomyopathy is hindered by the invasive nature of current cell delivery methods. Furthermore, the rapid disappearance of cells after transplantation provides a cogent rationale for using repeated cell doses, which, however, has not been done thus far in clinical trials because it is not feasible with invasive approaches. The goal of this translational study was to test the therapeutic utility of the intravenous route for cell delivery. Pigs with chronic ischemic cardiomyopathy induced by myocardial infarction received one or three intravenous doses of allogeneic bone marrow mesenchymal stromal cells (MSCs) or placebo 35 days apart. Rigor guidelines, including blinding and randomization, were strictly followed. A comprehensive assessment of LV function was conducted with three independent methods (echocardiography, magnetic resonance imaging, and hemodynamic studies). The results demonstrate that three doses of MSCs improved both load-dependent and independent indices of left ventricular (LV) function and reduced myocardial hypertrophy and fibrosis; in contrast, one dose failed to produce most of these benefits. To our knowledge, this is the first study to show that intravenous infusion of a cell product improves LV function and structure in a large animal model of chronic ischemic cardiomyopathy and that repeated infusions are necessary to produce robust effects. This study, conducted in a clinically-relevant model, supports a new therapeutic strategy based on repeated intravenous infusions of allogeneic MSCs and provides a foundation for a first-in-human trial testing this strategy in patients with chronic ischemic cardiomyopathy.

Silent delayed middle cerebral artery occlusion post-mechanical thrombectomy: A case report

Mechanical thrombectomy (MT) for atherothrombotic lesions entails significant risks, including reocclusion and the possibility of worsening stenotic changes through endothelial injury. We treated a 45-year-old male admitted to our hospital with the sudden onset of left hemiparesis. Magnetic resonance imaging (MRI) revealed an occlusion of the right middle cerebral artery (MCA). Immediate intravenous tissue plasminogen activator infusion followed by MT successfully reperfused the MCA, although residual stenosis persisted in the distal portion of the M1 segment. Following the procedure, the patient&amp;rsquo;s symptoms resolved, and he was discharged. Three months later, follow-up MRI showed reocclusion of the right MCA and hemodynamic changes indicating reduced cerebral blood flow and cerebrovascular reactivity in the MCA territory. Subsequently, extracranial&amp;ndash;intracranial bypass surgery was performed, and the patient did not develop any new symptoms postoperatively. While the patient in this case did not develop permanent symptoms, diligent observation is imperative following MT due to the potential for delayed progressive stenosis or occlusion.

The Infusion of Piperacillin/Tazobactam with an Elastomeric Device: A Combined 24-H Stability Study and Drug Solution Flow Rate Analysis.

Bacterial respiratory tract infections (e.g., in patients with cystic fibrosis) may be treated with the intravenous infusion of a piperacillin/tazobactam (P/T) solution through an elastomeric device. In the present work, we combined a 24-h drug stability study with an assessment of the drug solution flow rate during an in vitro simulated infusion. Experiments were performed in triplicate with two excipient-free generic P/T solutions and an excipient-containing proprietary P/T solution in saline (all 50/6.25 mg/mL) released from an elastomeric infusion device at 32 °C. The P/T solutions' stability was assessed by an HPLC-UV assay, pH and osmolality measurements, a visual assessment, and particle counting. Before these analyses, a forced degradation study was performed. To assess the flow rate, a precision scale was used to weigh the solution collected at the infusion line outlet. The stability criteria were <10% degradation and a flow rate within ± 15% of the nominal value over the 24-h infusion period: all three P/T solutions were found to be stable. The actual flow rate was lower than the expected flow rate; this difference was probably due to the drug solution's high viscosity and must be taken into account in clinical use.

Material-driven immunomodulation and ECM remodeling reverse pulmonary fibrosis by local delivery of stem cell-laden microcapsules

Recent progress in stem cell therapy has demonstrated the therapeutic potential of intravenous stem cell infusions for treating the life-threatening lung disease of pulmonary fibrosis (PF). However, it is confronted with limitations, such as a lack of control over cellular function and rapid clearance by the host after implantation. In this study, we developed an innovative PF therapy through tracheal administration of microfluidic-templated stem cell-laden microcapsules, which effectively reversed the progression of inflammation and fibrotic injury. Our findings highlight that hydrogel microencapsulation can enhance the persistence of donor mesenchymal stem cells (MSCs) in the host while driving MSCs to substantially augment their therapeutic functions, including immunoregulation and matrix metalloproteinase (MMP)-mediated extracellular matrix (ECM) remodeling. We revealed that microencapsulation activates the MAPK signaling pathway in MSCs to increase MMP expression, thereby degrading overexpressed collagen accumulated in fibrotic lungs. Our research demonstrates the potential of hydrogel microcapsules to enhance the therapeutic efficacy of MSCs through cell-material interactions, presenting a promising yet straightforward strategy for designing advanced stem cell therapies for fibrotic diseases.

Management and Treatment Outcomes of Hemolytic Disease of the Fetus and Newborn (HDFN)-A Retrospective Cohort Study.

Background: Hemolytic disease of the fetus and newborn (HDFN) is caused by maternal antibodies attacking fetal blood cell antigens. Despite routine antenatal anti-D prophylaxis, intrauterine transfusions (IUTs) are still needed in some HDFN cases. Methods: We conducted a retrospective cohort study on newborns with HDFN born in the 1st Department of Obstetrics and Gynecology of the Medical University of Warsaw. We analyzed 274 neonates with HDFN, identifying 46 who required IUT due to fetal anemia and 228 who did not. The laboratory results, management, and outcomes were compared between these groups. Results: Comparative analysis showed that newborns treated with IUT were more likely to have significant anemia, hyperbilirubinemia, and iron overload, indicated by a high ferritin concentration. These neonates more often required top-up transfusions, phototherapy, intravenous immunoglobulin infusions, and exchange transfusions. The length of stay was longer for newborns who received IUT. Conclusions: HDFN requiring IUT is associated with a greater number of complications in the neonatal period and more often requires additional treatment compared to HDFN not requiring IUT.

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.

Efficacy and safety of trimodulin in patients with severe COVID-19: results from a randomised, placebo-controlled, double-blind, multicentre, phase II trial (ESsCOVID)

BackgroundTrimodulin (human polyvalent immunoglobulin [Ig] M ~ 23%, IgA ~ 21%, IgG ~ 56% preparation) has previously been associated with a lower mortality rate in a subpopulation of patients with severe community-acquired pneumonia on invasive mechanical ventilation (IMV) and with clear signs of inflammation. The hypothesis for the ESsCOVID trial was that trimodulin may prevent inflammation-driven progression of severe coronavirus disease 2019 (COVID-19) to critical disease or even death.MethodsAdults with severe COVID-19 were randomised to receive intravenous infusions of trimodulin or placebo for 5 consecutive days in addition to standard of care. The primary efficacy endpoint was a composite of clinical deterioration (Days 6–29) and 28-day all-cause mortality (Days 1–29).ResultsOne-hundred-and-sixty-six patients received trimodulin (n = 84) or placebo (n = 82). Thirty-three patients died, nine during the treatment phase. Overall, 84.9% and 76.5% of patients completed treatment and follow-up, respectively. The primary efficacy endpoint was reported in 33.3% of patients on trimodulin and 34.1% of patients on placebo (P = 0.912). No differences were observed in the proportion of patients recovered on Day 29, days of invasive mechanical ventilation, or intensive care unit-free days. Rates of treatment-emergent adverse events were comparable.A post hoc analysis was conducted in patients with early systemic inflammation by excluding those with high CRP (> 150 mg/L) and/or D-dimer (≥ 3 mg/L) and/or low platelet counts (< 130 × 109/L) at baseline. Forty-seven patients in the trimodulin group and 49 in the placebo group met these criteria. A difference of 15.5 percentage points in clinical deterioration and mortality was observed in favour of trimodulin (95% confidence interval: −4.46, 34.78; P = 0.096).ConclusionAlthough there was no difference in the primary outcome in the overall population, observations in a subgroup of patients with early systemic inflammation suggest that trimodulin may have potential in this setting that warrants further investigation.ESsCOVID was registered prospectively at ClinicalTrials.gov on October 6, 2020.NCT04576728

Flow Rate Sensor inside Infusion Tube

Infusion systems are widely used in clinical medicine. Intravenous infusion therapy must be monitored to ensure patient safety. We proposed a compact flow rate sensor device based on the time-of-flight method. This device included one ceramic heater and two infrared sensors. Practical sensor prototypes were fabricated and characterized. The response time was 30 s. The sensor range was estimated to be 33 dB from μL/min to tens of mL/min, covering almost the entire usage range This flow rate sensor can be applied to common infusion tubes. Through the use of a mobile phone app, detailed information can be presented in real time.

Combined treatment with vitamin C, hydrocortisone and thiamine does not attenuate morbidity and mortality of septic sheep

BackgroundSepsis is associated with a highest mortality rate in the ICU. Present study tests the efficacy of combined therapy with vitamin C, hydrocortisone and thiamine (combined therapy) in the ovine model of sepsis induced by Pseudomonas aeruginosa. In this study, sepsis was induced in sheep by instillation of Pseudomonas aeruginosa (1 × 1011 CFU) into the lungs via bronchoscope, under anesthesia. Nine hours after injury, intravenous infusion of vitamin C (0.75 g every 6 h), hydrocortisone (25 mg every 6 h), and thiamine (100 mg every 12 h) or saline was given to the treatment and control groups. Cardiopulmonary variables were recorded.ResultsThe survival rate was 16.7% in control and 33.3% in treatment groups. In the control group, mean arterial pressure dropped from 93.6 ± 8.6 to 75.5 ± 9.7 mmHg by 9 h, which was not affected by the combined therapy. Pulmonary dysfunction was not attenuated by the combined therapy either. The combined therapy had no effect on increased extravascular lung water content and fluid effusion into thoracic cavity. The bacterial number in the bronchoalveolar lavage fluid was significantly increased in the treatment group than the control group. The blood bacterial number remained comparable between groups.ConclusionsCombined vitamin C, hydrocortisone, and thiamine did not attenuate severity of ovine sepsis.

In-use stability of Rituximab and IVIG during intravenous infusion: Impact of peristaltic pump, IV bags, flow rate, and plastic syringes

This study investigates the impact of intravenous (IV) infusion protocols on the stability of Intravenous Immunoglobulin G (IVIG) and Rituximab, with a particular focus on subvisible particle generation. Infusion set based on peristaltic movement (Medifusion DI-2000 pump) was compared to a gravity-based infusion system (Accu-Drip) at different flow rates. The impacts of different diluents (0.9 % saline and 5.0 % dextrose) and plastic syringes with or without silicone oil (SO) were also investigated. The results from the aforementioned particular case demonstrated that peristaltic pumps generated high levels of subvisible particles (prominently < 25 µm), exacerbated by increasing flow rates, specifically in formulations lacking surfactants. Other factors, such as diluent type and syringe composition, also increased the number of subvisible particles. Strategies that can help overcome these complications include surfactant addition as well as the use of SO-free syringes and a gravity infusion system, which aid in reducing particle formation and preserving antibody monomer during administration. Altogether, these findings highlight the importance of the careful selection of formulations and infusion protocols to minimize particle generation during IV infusion both for patients’ safety and treatment efficacy.

Accuracy of gravity based automatic infusion system applied to chemoport for intravenous infusion.

191 Background: When a vesicant drug is administered to the peripheral vein, a gravity drip method rather than an peristaltic infusion pump is recommended. In addition, it is reported that the gravity based pump has less particle generation than the peristaltic pump that injects fluid through constant peristaltic movement. However, it is pointed out that the disadvantage of gravity based pump is that the rate of administration can easily change according to the change in the location of the injection site. We evaluate the accuracy of new gravity based pump (pressure-sensitive speed control fluid injection device, Accudrip made by Hanvit MD ) at various injection rates and hanging heights common to hospital settings. Methods: The accuracy and safety of the intravenous (IV) flow controller were evaluated for patients receiving IV chemotherapy in the oncology department. It was verified whether the accurate injection rate could be maintained even in various fluid heights, fluid amounts, and types of anticancer drugs that could affect the injection rate. Various anticancer drugs, including immune checkpoint inhibitor, were mixed with 250 ml/500 ml of normal saline and administered for 30 min/60 min, and glucose 500 ml/1000 ml was administered for 60 min/120 min to measure accuracy, each progressed 25 times. Medical staff were surveyed on the ease and limitations of medical practice for each peristaltic infusion pump and new gravity based pump. In addition, side effects occurring in patients during fluid administration were recorded. Results: The mean degree of error in the estimated end time of gravity based automatic infusion system was 3.09% (2.09 ~ 4.10). The error of the gravity based automatic infusion system was statistically significant depending on the patient age (p=.001) and the infusion time (p=.016), but the degree of error according to the type of fluids (p=.302) and fluid concentration (p=.844) was not statistically significant. Among the subjects of the study, nurses' satisfaction with the application of gravity based pump was 4.10 (±0.62) out of 5, and among the general characteristics of nurses, age ( p&lt;.078), and working department (p&lt;.91) did not show a statistically significant difference, but work experience ( p &lt;.021) showed a statistically significant difference. Conclusions: The accuracy of Gravity based automatic infusion system was determined because the degree of error in the expected end time of infusion was not significant according to the infusion variable. In a survey of nurses who have used gravity based pump directly, it was found that the ease of use and satisfaction were similar to those of the conventional peristaltic pump. These findings will contribute greatly to the precise drug administration (over or under-administration) and minimization of adverse events in real-world hospital settings.

Fetal bradycardia and acidosis during maternal parenteral iron: Case reports and literature review.

Iron deficiency anemia is an important problem among pregnant women, and intravenous (IV) iron infusions have been increasingly used. Whether fetal monitoring is required during infusion has been debated, with a recent guideline by Hematologists recommending against such. We report two cases of fetal bradycardia after iron isomaltoside (IIM), in women with otherwise good maternal and fetal health. Both developed dyspnea with desaturation minutes from infusion, followed by persistent fetal bradycardia. Both underwent category 1 CS, with cord arterial pH of 7.08 and 6.94 respectively. Upon literature review, only three case reports on fetal bradycardia in IV iron were identified. For older IV iron formulations, a case was reported after IV dextran test dose, while two cases after ferric gluconate were reported. For the new formulation IIM, only one case was reported so far, but in a woman with Crohn's disease and intrauterine growth restriction. IV iron in pregnancy carries risk of anaphylactic or hypersensitivity reactions, even with the newest formulations and in women with good maternal and fetal health. While rarely reported so far, fetal bradycardia is a possible consequence, commonly preceded by respiratory symptoms. Fetal monitoring should therefore be considered during infusion.

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.

Drug Combination Nanoparticles Containing Gemcitabine and Paclitaxel Enable Orthotopic 4T1 Breast Tumor Regression.

Early diagnosis, intervention, and therapeutic advancements have extended the lives of breast cancer patients; however, even with molecularly targeted therapies, many patients eventually progress to metastatic cancer. Recent data suggest that residual breast cancer cells often reside in the lymphatic system before rapidly spreading through the bloodstream. To address this challenge, an effective drug combination composed of gemcitabine (G) and paclitaxel (T) is administered intravenously in sequence at the metastatic stage, but intravenous GT infusion may limit lymphatic GT drug accessibility and asynchronous drug exposure in cancer cells within the lymph. To determine whether co-localization of intracellular gemcitabine and paclitaxel (referred to as GT) could overcome these limitations and enhance the efficacy of GT, we have evaluated a previously reported GT drug-combination formulated in nanoparticle (referred to as GT-in-DcNP) evaluated in an orthotopic breast tumor model. Previously, with indocyanine green-labeled nanoparticles, we reported that GT-in-DcNP particles after subcutaneous dosing were taken up rapidly and preferentially into the lymph instead of blood vessels. The pharmacokinetic study showed enhanced co-localization of GT within the tumors and likely through lymphatic access, before drug apparency in the plasma leading to apparent long-acting plasma time-course. The mechanisms may be related to significantly greater inhibitions of tumor growth-by 100 to 140 times-in both sub-iliac and axillary regions compared to the equivalent dosing with free-and-soluble GT formulation. Furthermore, GT-in-DcNP exhibited dose-dependent effects with significant tumor regression. In contrast, even at the highest dose of free GT combination, only a modest tumor growth reduction was notable. Preliminary studies with MDA-231-HM human breast cancer in an orthotopic xenograft model indicated that GT-in-DcNP may be effective in suppressing human breast tumor growth. Taken together, the synchronized delivery of GT-in-DcNP to mammary tumors through the lymphatic system offers enhanced cellular retention and greater efficacy.