Intravenous Research Articles

A "suicide" BCG strain provides enhanced immunogenicity and robust protection against Mycobacterium tuberculosis in macaques.

Intravenous (IV) BCG delivery provides robust protection against Mycobacterium tuberculosis (Mtb) in macaques but poses safety challenges. Here, we constructed two BCG strains (BCG-TetON-DL and BCG-TetOFF-DL) in which tetracyclines regulate two phage lysin operons. Once the lysins are expressed, these strains are killed in immunocompetent and immunocompromised mice yet induced similar immune responses and provided similar protection against Mtb challenge as wild type BCG. Lysin induction resulted in release of intracellular BCG antigens and enhanced cytokine production by macrophages. In macaques, cessation of doxycycline administration resulted in rapid elimination of BCG-TetOFF-DL. However, IV BCG-TetOFF-DL induced increased pulmonary CD4 T cell responses compared to WT BCG and provided robust protection against Mtb challenge, with sterilizing immunity in 6 of 8 macaques, compared to 2 of 8 macaques immunized with WT BCG. Thus, a "suicide" BCG strain provides an additional measure of safety when delivered intravenously and robust protection against Mtb infection.

Addressing the Contrast Media Recognition Challenge: A Fully Automated Machine Learning Approach for Predicting Contrast Phases in CT Imaging.

Accurately acquiring and assigning different contrast-enhanced phases in computed tomography (CT) is relevant for clinicians and for artificial intelligence orchestration to select the most appropriate series for analysis. However, this information is commonly extracted from the CT metadata, which is often wrong. This study aimed at developing an automatic pipeline for classifying intravenous (IV) contrast phases and additionally for identifying contrast media in the gastrointestinal tract (GIT). This retrospective study used 1200 CT scans collected at the investigating institution between January 4, 2016 and September 12, 2022, and 240 CT scans from multiple centers from The Cancer Imaging Archive for external validation. The open-source segmentation algorithm TotalSegmentator was used to identify regions of interest (pulmonary artery, aorta, stomach, portal/splenic vein, liver, portal vein/hepatic veins, inferior vena cava, duodenum, small bowel, colon, left/right kidney, urinary bladder), and machine learning classifiers were trained with 5-fold cross-validation to classify IV contrast phases (noncontrast, pulmonary arterial, arterial, venous, and urographic) and GIT contrast enhancement. The performance of the ensembles was evaluated using the receiver operating characteristic area under the curve (AUC) and 95% confidence intervals (CIs). For the IV phase classification task, the following AUC scores were obtained for the internal test set: 99.59% [95% CI, 99.58-99.63] for the noncontrast phase, 99.50% [95% CI, 99.49-99.52] for the pulmonary-arterial phase, 99.13% [95% CI, 99.10-99.15] for the arterial phase, 99.8% [95% CI, 99.79-99.81] for the venous phase, and 99.7% [95% CI, 99.68-99.7] for the urographic phase. For the external dataset, a mean AUC of 97.33% [95% CI, 97.27-97.35] and 97.38% [95% CI, 97.34-97.41] was achieved for all contrast phases for the first and second annotators, respectively. Contrast media in the GIT could be identified with an AUC of 99.90% [95% CI, 99.89-99.9] in the internal dataset, whereas in the external dataset, an AUC of 99.73% [95% CI, 99.71-99.73] and 99.31% [95% CI, 99.27-99.33] was achieved with the first and second annotator, respectively. The integration of open-source segmentation networks and classifiers effectively classified contrast phases and identified GIT contrast enhancement using anatomical landmarks.

Medication errors involving intravenous paracetamol in children: experience from enquiries to the National Poisons Information Service

IntroductionChildren are at higher risk of medication errors due to the complexity of drug prescribing and administration in this patient group. Intravenous (IV) paracetamol overdose differs from overdose by ingestion...

Intravenous administration of ultrasound contrast to critically ill pediatric patients.

The off-label use of contrast-enhanced ultrasound has been increasingly used for pediatric patients. The purpose of this retrospective study is to report any observed clinical changes associated with the intravenous (IV) administration of ultrasound contrast to critically ill neonates, infants, children, and adolescents. All critically ill patients who had 1 or more contrast-enhanced ultrasound scans while being closely monitored in the neonatal, pediatric, or pediatric cardiac intensive care units were identified. Subjective and objective data concerning cardiopulmonary, neurological, and hemodynamic monitoring were extracted from the patient's electronic medical records. Vital signs and laboratory values before, during, and after administration of ultrasound contrast were obtained. Statistical analyses were performed using JMP Pro, version 15. Results were accepted as statistically significant for P-value<0.05. Forty-seven contrast-enhanced ultrasound scans were performed on 38 critically ill patients, 2 days to 17 years old, 19 of which were female (50%), and 19 had history of prematurity (50%). At the time of the contrast-enhanced ultrasound scans, 15 patients had cardiac shunts or a patent ductus arteriosus, 25 had respiratory failure requiring invasive mechanical oxygenation and ventilation, 19 were hemodynamically unstable requiring continual vasoactive infusions, and 8 were receiving inhaled nitric oxide. In all cases, no significant respiratory, neurologic, cardiac, perfusion, or vital sign changes associated with IV ultrasound contrast were identified. This study did not retrospectively identify any adverse clinical effects associated with the IV administration of ultrasound contrast to critically ill neonates, infants, children, and adolescents.

Iron-carbohydrate complexes treating iron anaemia: Understanding the nano-structure and interactions with proteins through orthogonal characterisation

Intravenous (IV) iron-carbohydrate complexes are widely used nanoparticles (NPs) to treat iron deficiency anaemia, often associated with medical conditions such as chronic kidney disease, heart failure and various inflammatory conditions. Even though a plethora of physicochemical characterisation data and clinical studies are available for these products, evidence-based correlation between physicochemical properties of iron-carbohydrate complexes and clinical outcome has not fully been elucidated yet. Studies on other metal oxide NPs suggest that early interactions between NPs and blood upon IV injection are key to understanding how differences in physicochemical characteristics of iron-carbohydrate complexes cause variance in clinical outcomes. We therefore investigated the core-ligand structure of two clinically relevant iron-carbohydrate complexes, iron sucrose (IS) and ferric carboxymaltose (FCM), and their interactions with two structurally different human plasma proteins, human serum albumin (HSA) and fibrinogen, using a combination of cryo-scanning transmission electron microscopy (cryo-STEM), x-ray diffraction (XRD), small-angle x-ray scattering (SAXS) and small-angle neutron scattering (SANS). Using this orthogonal approach, we defined the nano-structure, individual building blocks and surface morphology for IS and FCM. Importantly, we revealed significant differences in the surface morphology of the iron-carbohydrate complexes. FCM shows a localised carbohydrate shell around its core, in contrast to IS, which is characterised by a diffuse and dynamic layer of carbohydrate ligand surrounding its core. We hypothesised that such differences in carbohydrate morphology determine the interaction between iron-carbohydrate complexes and proteins and therefore investigated the NPs in the presence of HSA and fibrinogen. Intriguingly, IS showed significant interaction with HSA and fibrinogen, forming NP-protein clusters, while FCM only showed significant interaction with fibrinogen. We postulate that these differences could influence bio-response of the two formulations and their clinical outcome. In conclusion, our study provides orthogonal characterisation of two clinically relevant iron-carbohydrate complexes and first hints at their interaction behaviour with proteins in the human bloodstream, setting a prerequisite towards complete understanding of the correlation between physicochemical properties and clinical outcome.

Evaluation of a novel, low-cost, 3D printed video laryngoscope with borescope in anesthetized Beagle dogs

ObjectiveTo develop and evaluate a low-cost three-dimensional (3D)-printed video laryngoscope (VLVET) for use with a commercial borescope. Study designInstrument development and pilot study. AnimalsA total of six adult male Beagle dogs. MethodsThe VLVET consisted of a laryngoscope handle and a Miller-type blade, and a detachable camera holder that attached to various locations along the blade. The laryngoscope and camera holder were 3D-printed using black polylactic acid filament. Dogs were premedicated with intravenous (IV) medetomidine (15 μg kg−1) and anesthesia induced with IV alfaxalone (1.5 mg kg−1). The VLVET, combined with a borescope, was used for laryngeal visualization and intubation. Performance was evaluated by comparing direct and video-assisted views in sternal recumbency. The borescope camera was sequentially positioned at 2, 4, 6, 8 and 10 cm from the blade tip (distanceLARYNX-CAM), which was placed on the epiglottis during intubation or laryngoscopy. At the 10 cm distanceLARYNX-CAM, laryngeal visualization was sequentially scored at inter-incisor gaps of 10, 8, 6, 4 and 2 cm. Laryngeal visualization scores (0–3 range, with 0 = obstructed and 3 = unobstructed views) were statistically analyzed using the Friedman’s test. ResultsUnder direct visualization, the 2 cm distanceLARYNX-CAM had a significantly lower score compared with all other distanceLARYNX-CAM (all p = 0.014) because the view was obstructed by the camera holder and borescope camera. With both direct and camera-assisted views, visualization scores were higher at inter-incisor gaps ≥ 4 cm compared with 2 cm (all p < 0.05). Conclusions and clinical relevanceDuring laryngoscopy and intubation, the VLVET and borescope facilitated both direct and video laryngoscopy at distanceLARYNX-CAM in Beagle dogs when inter-incisor gaps were ≥ 4 cm.

Pseudomonas aeruginosa ventricular assist device infections: findings from ineffective phage therapies in five cases.

Left ventricular assist devices (LVAD) are increasingly used for management of heart failure; infection remains a frequent complication. Phage therapy has been successful in a variety of antibiotic refractory infections and is of interest in treating LVAD infections. We performed a retrospective review of four patients that underwent five separate courses of intravenous (IV) phage therapy with concomitant antibiotic for treatment of endovascular Pseudomonas aeruginosa LVAD infection. We assessed phage susceptibility, bacterial strain sequencing, serum neutralization, biofilm activity, and shelf-life of phage preparations. Five treatments of one to four wild-type virulent phage(s) were administered for 14-51 days after informed consent and regulatory approval. There was no successful outcome. Breakthrough bacteremia occurred in four of five treatments. Two patients died from the underlying infection. We noted a variable decline in phage susceptibility following three of five treatments, four of four tested developed serum neutralization, and prophage presence was confirmed in isolates of two tested patients. Two phage preparations showed an initial titer drop. Phage biofilm activity was confirmed in two. Phage susceptibility alone was not predictive of clinical efficacy in P. aeruginosa endovascular LVAD infection. IV phage was associated with serum neutralization in most cases though lack of clinical effect may be multifactorial including presence of multiple bacterial isolates with varying phage susceptibility, presence of prophages, decline in phage titers, and possible lack of biofilm activity. Breakthrough bacteremia occurred frequently (while the organism remained susceptible to administered phage) and is an important safety consideration.

Improved Postoperative Pain Management Outcomes After Implementation of Enhanced Recovery After Surgery (ERAS) Protocol for Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS-HIPEC).

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for patients with peritoneal carcinomatosis is promising but has potential for significant morbidity and prolonged hospitalization. Enhanced Recovery After Surgery (ERAS) is a standardized protocol designed to optimize perioperative care. This study describes trends in epidural and opioid use after implementing ERAS for CRS-HIPEC at a tertiary academic center. A retrospective analysis of patients undergoing CRS-HIPEC from January 2020 to September 2023 was conducted. ERAS was implemented in February 2022. Medication and outcomes data were compared before and after ERAS initiation. All opioids were converted to morphine milligram equivalents (MMEs). A total of 136 patients underwent CRS-HIPEC: 73 (54%) pre- and 63 (46%) post-ERAS. Epidural usage increased from 63% pre-ERAS to 87% post-ERAS (p = 0.001). Compared with those without epidurals, patients with epidurals had decreased total 7-day oral and intravenous (IV) opioid requirements (45 MME vs. 316 MME; p < 0.001). There was no difference in 7-day opioid totals between pre- and post-ERAS groups. After ERAS, more patients achieved early ambulation (83% vs. 53%; p < 0.001), early diet initiation (81% vs. 25%; p < 0.001), and early return of bowel function (86% vs. 67%; p = 0.012). ERAS implementation for CRS-HIPEC was associated with increased epidural use, decreased oral and IV opioid use, and earlier bowel function return. Our study demonstrates that epidural analgesia provides adequate pain control while significantly decreasing oral and IV opioid use, which may promote gastrointestinal recovery postoperatively. These findings support the implementation of an ERAS protocol for effective pain management in patients undergoing CRS-HIPEC.

Bilateral pericapsular end nerve blocks for steroid-induced avascular necrosis following COVID-19 infection requiring bilateral total hip replacement

BACKGROUND Osteonecrosis or avascular necrosis (AVN) of the hip was one of the dreaded complications of coronavirus disease 2019 (COVID-19), which emerged in patients who received steroid therapy. Corticosteroids have been a mainstay in the treatment protocol of COVID-19 patients. Popular corticosteroid drugs used in patients suffering from COVID-19 were intravenous (IV) or oral dexamethasone, methylprednisolone or hydrocortisone. The use of such high doses of corticosteroids has shown very positive results and has been lifesaving in many cases. Still, long-term consequences were drug-induced diabetes, osteoporosis, Cushing syndrome, muscle wasting, peripheral fat mobilization, AVN, hirsutism, sleep disturbances and poor wound healing. A significant number of young patients were admitted for bilateral total hip replacements (THR) secondary to AVN following steroid use for COVID-19 treatment. AIM To assess the efficacy of bilateral pericapsular end nerve group (PENG) blocks in patients posted for bilateral THR post-steroid therapy after COVID-19 infection and assess the time taken to first ambulate after surgery. METHODS This prospective observational study was conducted between January 2023 and August 2023 at Care Hospitals, Hyderabad, India. Twenty young patients 30-35 years of age who underwent bilateral THR were studied after due consent over 8 months. All the patients received spinal anaesthesia for surgery and bilateral PENG blocks for postoperative analgesia. RESULTS The duration of surgery was 2.5 h on average. Seventeen out of twenty patients (85%) had a Visual Analog Score (VAS) of less than 2 and did not require any supplementation. One patient was removed from the study, as he required re-exploration. The remaining two patients had a VAS of more than 8 and received IV morphine post-operatively as a rescue analgesic drug. Fifteen out of seventeen patients (88.2%) could be mobilized 12 h after the procedure. CONCLUSION Osteonecrosis or AVN of the hip was one of the dreaded complications of COVID-19, which surfaced in patients who received steroid therapy requiring surgical intervention. Bilateral PENG block is an effective technique to provide post-operative analgesia resulting in early mobilization and enhanced recovery after surgery.

Cost evaluation of continuation of therapy with dalbavancin compared to standard-of-care antibiotics alone in hospitalized persons who inject drugs with severe gram-positive infections.

Persons who inject drugs (PWID) are at risk for severe gram-positive infections and may require prolonged hospitalization and intravenous (IV) antibiotic therapy. Dalbavancin (DBV) is a long-acting lipoglycopeptide that may reduce costs and provide effective treatment in this population. This was a retrospective review of PWID with severe gram-positive infections. Patients admitted from January 1, 2017, to November 1, 2019 (standard-of-care [SOC] group) and from November 15, 2019, to March 31, 2022 (DBV group) were included. The primary outcome was the total cost to the healthcare system. Secondary outcomes included hospital days saved and treatment failure. A total of 87 patients were included (37 in the DBV group and 50 in the SOC group). Patients were a median of 34 years old and were predominantly Caucasian (82%). Staphylococcus aureus (82%) was the most common organism, and bacteremia (71%) was the most common type of infection. Compared to the SOC group, the DBV group would have had a median of 14 additional days of hospitalization if they had stayed to complete their therapy (P = 0.014). The median total cost to the healthcare system was significantly lower in the DBV group than in the SOC group ($31,698.00 vs $45,093.50; P = 0.035). The rate of treatment failure was similar between the groups (32.4% in the DBV group vs 36% in the SOC group; P = 0.729). DBV is a cost-saving alternative to SOC IV antibiotics for severe gram-positive infections in PWID, with similar treatment outcomes. Larger prospective studies, including other patient populations, may demonstrate additional benefit.

Iatrogenic myelodysplastic syndrome complicating multiple sclerosis: A case report.

After 1.5 years of treatment with dimethyl fumarate (DMF) for multiple sclerosis, preceded 8 years earlier by intravenous (IV) cladribine and 1 year earlier by natalizumab, our patient developed myelodysplastic syndrome (MDS). The initial manifestation was a severe drop in absolute neutrophil and lymphocyte counts. Repeat bone marrow biopsy demonstrated a new unbalanced translocation (between the chromosome 1 long arm and chromosome 7 short arm). This case report, to our knowledge, is the first linking iatrogenic MDS to DMF and cladribine, while also suggesting caution with immunosuppressants in multiple sclerosis patients.

Intravenous Ketamine for Suicidal Behavior in Severe Depression with Psychotic Features

Abstract Depression is the leading cause of suicide, and antidepressants and modified electroconvulsive therapy (mECT) are the preferred treatment modalities. Ketamine is an established anesthetic agent and evidence for its use in depression is evolving. Here, we discuss the experience of treating severe depression with intravenous (IV) ketamine. A patient in his mid-forties presented with a 2-month history of pervasive low mood, altered biological functions, decreased interest, and suspiciousness and was diagnosed with severe depression with psychotic features and suicidal ideas. As per the guidelines, started on antidepressants and planned for mECT. As the patient and family members were not willing for mECT, based on evidence, IV ketamine was discussed and started. Over six sessions of IV ketamine, there was significant improvement in both objective rating scores and clinically. IV ketamine can be a good adjunctive in the treatment of severe depression with suicidal ideas but needs to be backed up by robust studies.

Perceptions and experiences of intravenous iron treatment for anaemia in pregnancy in Malawi: a formative qualitative study

Background The study objective was to explore opinions, identify experiences, and describe perspectives on the acceptability of intravenous (IV) iron to treat anaemia in pregnancy and identify potential barriers and facilitators of introducing IV iron in the Malawian healthcare system. Methods We conducted 15 in-depth interviews and two focus group discussions with pregnant women, and seven in-depth interviews with health workers at a community-based health centre in Blantyre and a tertiary hospital in Zomba. Results Most women who used IV iron treatment during the second trimester of pregnancy reported feeling better and stronger after receiving the intervention. Women perceived that IV iron treatment worked faster than oral iron tablets and increased their haemoglobin count. However, cultural beliefs that IV iron treatment will cause miscarriage and the perception that study procedures involved Satanism and vampirism practices were barriers to acceptability. Health workers found IV iron treatment easy to administer because it is a single-dose treatment, simultaneously reducing the burden for pregnant women taking daily oral iron tablets. However, health workers expressed concerns about the costs and the need to train health workers before the large-scale implementation and integration of IV iron treatment into Malawi’s routine care. Conclusions Despite the perceived concerns and challenges experienced in participating in the first IV iron infusion trial in Malawi, participants’ reflections suggest that IV iron infusion is acceptable for treating iron-deficiency anaemia in pregnancy. Participant advocate groups can offer a peer-to-peer education approach to sensitize and engage community members on the benefits of treatment and dispel concerns when the country contemplates integrating IV iron infusion for treating anaemia in pregnancy in Malawi.

Exposure–efficacy relationship of vedolizumab subcutaneous and intravenous formulations in Crohn’s disease and ulcerative colitis

ABSTRACT Background and aims This posthoc analysis of the GEMINI and VISIBLE studies in ulcerative colitis (UC) and Crohn's Disease (CD) assessed exposure−efficacy of vedolizumab intravenous (IV) and subcutaneous (SC). Methods A previously described population pharmacokinetic model was used to predict average serum and trough concentrations at steady state (Cav,ss, Ctrough,ss) and simulate the transition from vedolizumab IV to SC. Efficacy was defined as clinical remission at week 52: complete Mayo score ≤ 2 points and no individual subscore > 1 point (UC), and CD activity index score ≤ 150 points (CD). Results Data were from 1968 patients (GEMINI 1 [n = 334], VISIBLE 1 [n = 216], GEMINI 2 [n = 1009], VISIBLE 2 [n = 409]) who received maintenance treatment with vedolizumab IV-Q8W, IV-Q4W, SC-Q2W, or placebo. Model-predicted Cav,ss for IV-Q8W and SC-Q2W was similar in UC and CD. Cav,ss was higher for IV-Q4W than IV-Q8W and SC-Q2W. Ctrough,ss values from IV and SC aligned well with pooled observed Ctrough by treatment group in UC and CD. Cav,ss was equivalent for SC and IV. For UC and CD, efficacy rates were greater in patients in the highest quartiles of vedolizumab exposure for both formulations. Conclusion Exposure−efficacy relationships for IV and SC vedolizumab administration were comparable, confirming that both are equally effective during maintenance treatment.

Intraventricular or intrathecal polymyxin B for treatment of post-neurosurgical intracranial infection caused by carbapenem-resistant gram-negative bacteria: a 8-year retrospective study.

Post-neurosurgical intracranial infection caused by carbapenem-resistant gram-negative bacteria (CRGNB) is a life-threatening complication. This study aimed to assess the current practices and clinical outcomes of intravenous (IV) combined with intraventricular (IVT)/intrathecal (ITH) polymyxin B in treating CRGNB intracranial infection. A retrospective study was conducted on patients with post-neurosurgical intracranial infection due to CRGNB from January 2013 to December 2020. Clinical characteristics and treatment outcomes were collected and described. Kaplan-Meier survival and multivariate logistic regression analyses were performed. The study included 114 patients, of which 72 received systemic antimicrobial therapy combined with IVT/ITH polymyxin B, and 42 received IV administration alone. Most infections were caused by carbapenem-resistant Acinetobacter baumannii (CRAB, 63.2%), followed by carbapenem-resistant Klebsiella pneumoniae (CRKP, 31.6%). Compared with the IV group, the IVT/ITH group had a higher cerebrospinal fluid (CSF) sterilization rate in 7 days (p < 0.001) and lower 30-day mortality (p = 0.032). In the IVT/ITH group, patients with CRKP infection had a higher initial fever (p = 0.014), higher incidence of bloodstream infection (p = 0.040), lower CSF sterilization in 7 days (p < 0.001), and higher 30-day mortality (p = 0.005) than those with CRAB infection. Multivariate logistic regression analysis revealed that the duration of IVT/ITH polymyxin B (p = 0.021) was independently associated with 30-day mortality. Intravenous combined with IVT/ITH polymyxin B increased CSF microbiological eradication and improved clinical outcomes. CRKP intracranial infections may lead to more difficult treatment and thus warrant attention and further optimized treatment.

Investigation of Antibody Pharmacokinetics in the Brain Following Intra-CNS Administration and Development of PBPK Model to Characterize the Data.

Despite the promising potential of direct central nervous system (CNS) antibody administration to enhance brain exposure, there remains a significant gap in understanding the disposition of antibodies following different intra-CNS injection routes. To bridge this knowledge gap, this study quantitatively investigated the brain pharmacokinetics (PK) of antibodies following intra-CNS administration. The microdialysis samples from the striatum (ST), cerebrospinal fluid (CSF) samples through cisterna magna (CM) puncture, plasma, and brain homogenate samples were collected to characterize the pharmacokinetics (PK) profiles of a non-targeting antibody, trastuzumab, following intracerebroventricular (ICV), intracisternal (ICM), and intrastriatal (IST) administration. For a comprehensive analysis, these intra-CNS injection datasets were juxtaposed against our previously acquired intravenous (IV) injection data obtained under analogous experimental conditions. Our findings highlighted that direct CSF injections, either through ICV or ICM, resulted in ~ 5-6-fold higher interstitial fluid (ISF) drug exposure than IV administration. Additionally, the low bioavailability observed following IST administration indicates the existence of a local degradation process for antibody elimination in the brain ISF along with the ISF bulk flow. The study further refined a physiologically based pharmacokinetic (PBPK) model based on new observations by adding the perivascular compartments, oscillated CSF flow, and the nonspecific uptake and degradation of antibodies by brain parenchymal cells. The updated model can well characterize the antibody PK following systemic and intra-CNS administration. Thus, our research offers quantitative insight into antibody brain disposition pathways and paves the way for determining optimal dosing and administration strategies for antibodies targeting CNS disorders.

Effects of Endotracheal Epinephrine on Pharmacokinetics and Survival in a Swine Pediatric Cardiac Arrest Model.

The aim of this study was to compare the endotracheal tube (ET) and intravenous (IV) administration of epinephrine relative to concentration maximum, time to maximum concentration, mean concentration over time (MC), area under the curve, odds, and time to return of spontaneous circulation (ROSC) in a normovolemic pediatric cardiac arrest model. Male swine weighing 24-37 kg were assigned to 4 groups: ET (n = 8), IV (n = 7), cardiopulmonary resuscitation (CPR) + defibrillation (CPR + Defib) (n = 5), and CPR only (n = 3). Swine were placed arrest for 2 minutes, and then CPR was initiated for 2 minutes. Epinephrine (0.1 mg/kg) for the ET group or 0.01 mg/kg for the IV was administered every 4 minutes or until ROSC. Defibrillation started at 3 minutes and continued every 2 minutes for 30 minutes or until ROSC for all groups except the CPR-only group. Blood samples were collected over a period of 5 minutes. The MC of plasma epinephrine for the IV group was significantly higher at the 30- and 60-second time points (P = 0.001). The ET group had a significantly higher MC of epinephrine at the 180- and 240-second time points (P < 0.05). The concentration maximum of plasma epinephrine was significantly lower for the ET group (195 ± 32 ng/mL) than for the IV group (428 ± 38 ng/mL) (P = 0.01). The time to maximum concentration was significantly longer for the ET group (145 ± 26 seconds) than for the IV group (42 ± 16 seconds) (P = 0.01). No significant difference existed in area under the curve between the 2 groups (P = 0.62). The odds of ROSC were 7.7 times greater for the ET versus IV group. Time to ROSC was not significantly different among the IV, ET, and CPR + Defib groups (P = 0.31). Based on the results of this study, the ET route of administration should be considered a first-line intervention.

Long-Term Satisfaction of Oral Sedation versus Standard-of-Care Intravenous Sedation for Ocular Surgery.

Long-term patient satisfaction may influence patients' perspectives of the quality of care and their relationship with their providers. This is a follow up to a comparative effectiveness study investigating oral to intravenous sedation (OIV study). The OIV study found that oral sedation was noninferior in patient satisfaction to standard intravenous (IV) sedation for anterior segment and vitreoretinal surgeries. This study aims to determine if patient satisfaction with oral sedation remained noninferior long term. Patients were re-interviewed using the same satisfaction survey given during the OIV study. Statistical analysis involved t-tests for noninferiority of the long-term mean satisfaction score of oral and IV sedation. We also compared the original mean satisfaction score and the follow-up mean satisfaction score for each type of sedation and for both groups combined. Participants were interviewed at a median of 1225.5 days (range 754-1675 days) from their surgery. The original mean satisfaction score was 5.26 ± 0.79 for the oral treatment group (n = 52) and 5.27 ± 0.64 for the intravenous treatment group (n = 46), demonstrating noninferiority with a difference in mean satisfaction score of 0.015 (p < 0.0001). The follow-up mean satisfaction score was 5.23 ± 0.90 for oral sedation and 5.60 ± 0.61 for IV sedation, with a difference in the mean satisfaction score of 0.371 (p = 0.2071). Satisfaction scores did not differ between the original mean satisfaction score and the follow-up mean satisfaction score for the oral treatment group alone (p = 0.8367), but scores in the intravenous treatment group increased longitudinally (p = 0.0004). In this study, long-term patient satisfaction with oral sedation was not noninferior to satisfaction with IV sedation, unlike our findings with short-term patient satisfaction in our original study. Patient satisfaction also remained unchanged over time for the oral treatment group, but patients in the intravenous treatment group reported higher long-term satisfaction with their anesthesia experience compared to the immediate post-operative period.

Vancomycin Three Ways: Multimodal Utilization of Intraoperative Antibiosis in Complex Foot and Ankle Infection

Osteomyelitis of the foot and ankle is an unfortunate, albeit pervasive, complication faced by orthopedic surgeons and their patients. Chronic osteomyelitis confers a great risk of amputation and protracted hospital admission in patients with diabetes, existing orthopedic hardware, and/or compromised tissue perfusion. The current standard of practice in the treatment of osteomyelitis is the initiation of broad antibiotic coverage followed by subsequent narrowing informed by culture data and sensitivities. While mild to moderate infections are treated with oral antibiotics, more severe infections are often treated using intravenous (IV) antibiotics. Vancomycin, in its IV form, is frequently administered intraoperatively for patients with osteomyelitis as it confers adequate coverage of common causative organisms, including staphylococcus aureus. However, given the diminished blood flow to distal extremities commonly seen in patients experiencing this complication, inadequate distribution of oral or IV antibiotics may occur. This is especially problematic, as it leads to an increased risk of recurrent infection and the ultimate need for amputation. Here, we present an alternate method of intraoperative vancomycin administration for patients with chronic osteomyelitis in the form of paste, powder, and injectable slurry. Postoperatively, oral or IV antibiotics are continued based on OR culture susceptibility. We found this to be an effective way to administer intraoperative antibiotics to ensure adequate osseous and soft tissue penetration in patients with complicated osteomyelitis of the foot and ankle. Level of Evidence: III.

Intravenous Versus Locally Injected Tranexamic Acid in a Fragility Hip Fracture Population: A Retrospective Review.

Evaluate differences between blood transfusion and complication rates among fragility hip fracture patients treated with locally injected (Local) versus intravenous (IV) tranexamic acid (TXA). Design: Retrospective comparative cohort. Tertiary referral orthopaedic specialty hospital; Level I trauma center. Patients aged 50 years and over who underwent surgical treatment for a proximal femur fragility fracture (Orthopedic Trauma Association/Arbeitsgemeinschaft für Osteosynthesefragen 31A and 31B). Between March 2018 and April 2022 with or without the use of local TXA during wound closure or IV TXA. Postoperative blood transfusion, venous thromboembolism, surgical site infections, and 30-day readmissions compared between those who received IV TXA, Local TXA, and controls that did not receive any TXA. Seven hundred forty-six patients (258 received IV TXA, 252 received Local TXA, and 236 controls that did not receive any TXA) were studied. Both Local and IV TXA groups received fewer blood transfusion versus controls. IV TXA was associated with a transfusion rate reduction of 12% compared with Local TXA ( P < 0.001). Regression analysis indicated that IV TXA reduced the odds of a postoperative blood transfusion by 48% compared with Local TXA ( P = 0.017). There were no differences in complication rates among the groups; however, patients receiving IV TXA had a significantly lower 30-day readmission rate (5%) than the control (13.9%) or Local (13.8%) TXA groups ( P = 0.001). IV TXA significantly reduced the risk of postoperative transfusion compared with controls and patients receiving Local TXA. There was no increased risk of complications, and a lower 30-day readmission was observed for the IV TXA group. IV TXA seems to be a safe and effective way to reduce postoperative blood transfusion in patients with fragility hip fractures. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.