Inadvertent Administration Research Articles

Delirium secondary to inadvertent administration of naltrexone in patient with opioid dependence syndrome: a case report

Delirium secondary to inadvertent administration of naltrexone in patient with opioid dependence syndrome: a case report

Use of Micropipette-Guided Drug Administration as an Alternative Method to Oral Gavage in Rodent Models.

Oral gavage (OG) with the use of a cannula attached to a syringe is one of the most common methods used to deliver precise dosing of compounds to the stomach of research animals. Unfortunately, this method comes with difficulties for both the operator and the research animal. Studies have shown that OG may lead to complications, including esophagitis, perforation of the esophagus, and inadvertent tracheal drug administration. In addition, OG is associated with increased plasma and fecal corticosterone levels (due to stress), altered blood pressure, and increased heart rate, which could negatively influence or bias study results. A previously developed alternative method termed micropipette-guided drug administration (MDA) incentivizes the animal to consume treatments readily in a minimally invasive manner. Herein, we present examples of the use of the MDA technique with treatments reconstituted in different vehicles and demonstrate effective delivery of the varied treatments to multiple different mouse strains. We further demonstrate that MDA is a technique that decreases the timing and invasiveness of drug administration and does not affect the gut microbiome composition as assessed by quantitative analysis of core gut microbial species. Overall, MDA may offer a less stressful and effective alternative to OG.

Pharmacokinetics of isavuconazonium sulfate and its active metabolite isavuconazole in healthy dogs.

Invasive fungal infections (IFIs) are growing in importance in veterinary and human medicine. IFIs such as aspergillosis, blastomycosis, coccidioidomycosis and histoplasmosis remain challenging to treat in dogs. Isavuconazole is a novel antifungal medication that, when compared to currently used azoles, has an expanded spectrum of antifungal activity Rudramurthy (2011), Pfaller (2013), Spec (2018), has more predictable pharmacokinetics in humans Desai (2016), Cojutti (2021) and may cause fewer side effects such as liver and renal toxicity Maertens (2016), DiPippo (2018). The pharmacokinetic profile and safety of isavuconazole in dogs has not yet been characterized. The purpose of this study was to evaluate the pharmacokinetics of isavuconazole in healthy dogs that received a single dose of the prodrug isavuconazonium sulfate. Using full crossover design, six healthy beagle dogs received isavuconazonium sulfate at a mean (+/- SD) dose of 20.6 (+/- 2.8) mg/kg orally and 21.8 (+/- 4.2) mg/kg intravenously. Plasma was collected for batched pharmacokinetic analysis of prodrug and metabolite, isavuconazole, by ultra-high-pressure liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). The median (Q1-Q3) maximum isavuconazole peak plasma concentration was estimated at 3,876.5 (2,811.0-4,800.0) ng/mL following oral administration, with a median (Q1-Q3) peak level at 1.3 (1.0-2.0) hours. Following intravenous administration, the median (Q1-Q3) isavuconazole peak plasma concentration was estimated at 3,221.5 (2,241.5-3,609.0) ng/mL, with a median (Q1-Q3) peak level at 0.4 (0.3-0.6) hours. The median (Q1-Q3) half-life of isavuconazole was 9.4 (7.0-12.2) hours and 14.0 (8.1-21.7) hours for oral and intravenous routes, respectively. One dog received inadvertent subcutaneous drug administration without any apparent adverse effects. Another dog experienced an anaphylactic reaction following accidental rapid drug infusion. No other drug-related adverse events were observed. At dosages used in this study, healthy dogs achieved isavuconazole plasma levels comparable to human therapeutic targets, and when properly administered the drug was well-tolerated.

Diagnosis and Treatment of Presumed Naltrexone-XR-precipitated Opioid Withdrawal in a Patient Chronically Treated With Buprenorphine-XR: A Case Report.

Naltrexone, buprenorphine, and methadone are Food and Drug Administration-approved medications for the treatment of opioid use disorder in the United States. Naltrexone, an opioid antagonist, can precipitate opioid withdrawal if administered too quickly after the use of full or partial opioid agonists for those with either dependence or use disorder. We describe a case of severe precipitated opioid withdrawal syndrome after reported buprenorphine extended-release (XR) administration, despite the patient having been stable on buprenorphine-XR for several years, with no missed doses or recent opioid use. Naltrexone levels were sent and helped to diagnose suspected inadvertent naltrexone-XR administration in this patient, which was likely the etiology of his precipitated opioid withdrawal syndrome. We suggest the use of high-dose buprenorphine, as well as adjunctive medications including benzodiazepines, as a treatment strategy for naltrexone-XR precipitated withdrawal in the setting of chronic buprenorphine-XR treatment.

Safety of methotrexate administration in women with pregnancy of unknown location at high risk of ectopic pregnancy.

To evaluate the safety of current guidelines on methotrexate (MTX) administration in women with pregnancy of unknown location (PUL) who are considered to have a high risk of underlying ectopic pregnancy (EP), and to investigate whether implementation of these guidelines would result in inadvertent exposure to MTX of viable intrauterine pregnancies (IUPs). This was a retrospective observational study of consecutive clinically stable women who were classified with PUL at the early pregnancy unit of Nepean Hospital, Sydney, Australia, between 2007 and 2021. PUL was defined as a positive pregnancy test in the absence of signs of IUP or EP on transvaginal ultrasound. Patients with a PUL that behaved biochemically like an EP, but for which the location of pregnancy was not confirmed on ultrasound, were eligible for MTX to minimize the risk of subsequent tubal rupture. Criteria discussed in the guidelines of the American College of Obstetricians and Gynecologists (ACOG), American Society for Reproductive Medicine (ASRM), Royal College of Obstetricians and Gynaecologists (RCOG) and National Institute for Health and Care Excellence (NICE) were applied to the PUL database. The number of patients eligible to receive MTX and the number with an underlying viable IUP who would be inadvertently prescribed MTX were calculated. A total of 816 women with PUL were reviewed, of whom 724 had complete data and were included in the final analysis. Six patients had persistent PUL and the remaining 718 had a diagnosis of viable IUP, non-viable IUP, EP or failed PUL. According to the ACOG, ASRM, RCOG and NICE guidelines, the rate of MTX administration among patients with PUL would have been 2.76%, 4.56%, 0.41% and 35.36%, respectively. However, no persistent PUL would have received MTX according to the ACOG, ASRM and RCOG protocols (the NICE protocol identified patients with persistent PUL with a sensitivity of 100%), and the majority of MTX treatments were unnecessary because those patients were later classified as having non-viable IUP or failed PUL. Application of ACOG and ASRM guidance could result theoretically in inadvertent MTX administration to women with an underlying viable IUP at a rate of 4.1/1000 (3/724). Current guidelines used to predict high risk of EP in the PUL population lead to inadvertent MTX administration to women with an underlying viable IUP. These guidelines should be used wisely to ensure that no wanted pregnancy is exposed to MTX. Women with PUL should be monitored carefully, and MTX should be used judiciously when the location of pregnancy is yet to be confirmed. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

#2545 Hemodialysis for salbutamol intoxication: patient case report

Abstract Background and Aims Salbutamol/albuterol is a moderately selective beta-2-adrenergic receptor agonist that acts as an airway smooth muscle relaxant. It is used to prevent and treat acute bronchospasm in various respiratory conditions. Due to its large volume of distribution, it is not considered dialysable. Method This is a clinical case report of inadvertent parenteral administration of salbutamol resulting in acute intoxication. Salvage renal replacement therapy was implemented due to the severity of the patient's clinical condition and the large amount of salbutamol administered. Multiple plasma measurements of salbutamol were taken during hemodialysis, allowing for a correlation to be made with the patient's clinical presentation. Results This case report presents an elderly patient with sepsis, Down syndrome, and liver cirrhosis. The patient required non-invasive ventilation due to worsening respiratory failure and was prescribed intravenous methylprednisolone. However, the patient inadvertently received 5mg of parenteral salbutamol (albuterol), which resulted in immediate severe arrhythmic tachycardia followed by hemodynamic collapse. After unsuccessful cardioversion and treatment with landiolol infusion, salvage hemodialysis was initiated to reduce the suspected highly elevated serum salbutamol levels. After 30 minutes, sinus rhythm with normocardia was observed. No rebound tachycardia was noted after the hemodialysis termination. However, due to severe septic shock, hypotension persisted, and vasoactive medications were adjusted. However, the measured levels of plasma salbutamol do not support the view that hemodialysis was the cause of the described improvement. The total amount of the drug cleared was exceedingly small, only 2.8% of the total dose. Data from the literature support our findings, even in the case of the life-threatening intoxication described. Conclusion The results confirm a large volume of distribution for salbutamol. The measured half-life time during hemodialysis (3.1 hours) is comparable to observed half-life times in therapeutic settings. The observed clinical benefit associated with dialysis appears to be fortuitous. This case report highlights the potential bias towards positive clinical outcomes and unproven therapies.

Inadvertent administration of intravenous anaesthesia induction agents via the intracerebroventricular, neuraxial or peripheral nerve route - A narrative review.

Intravenous (IV) medication administration error remains a major concern during the perioperative period. This review examines inadvertent IV anaesthesia induction agent administration via high-risk routes. Using Medline and Google Scholar, the author searched published reports of inadvertent administration via neuraxial (intrathecal, epidural), peripheral nerve or plexus or intracerebroventricular (ICV) route. The author applied the Human Factors Analysis and Classification System (HFACS) framework to identify systemic and human factors. Among 14 patients involved, thiopentone was administered via the epidural route in six patients. Four errors involved the routes of ICV (propofol and etomidate one each) or lumbar intrathecal (propofol infusion and etomidate bolus). Intrathecal thiopentone was associated with cauda equina syndrome in one patient. HFACS identified suboptimal handling of external ventricular and lumbar drains and deficiencies in the transition of care. Organisational policy to improve the handling of neuraxial devices, use of technological tools and improvements in identified deficiencies in preconditions before drug preparation and administration may minimise future risks of inadvertent IV induction agent administration.

Analysis of drug-induced interstitial lung disease caused by herbal medicine using the Japanese Adverse Drug Event Report database

BackgroundDrug-induced interstitial lung disease (DIILD) is a severe adverse event leading to morbidity and mortality. This study evaluated the adverse event indicators of DIILD and time-to-onset profiles following the daily intake of herbal drugs (Scutellariae radix [“ogon” in Japanese], Bupleuri radix [“saiko” in Japanese], and Pinelliae tuber [“hange” in Japanese]) using the Japanese Adverse Drug Event Report database. DIILD was defined in accordance with the Medical Dictionary for Regulatory Activities.MethodsThe Japanese Adverse Drug Event Report database contained 830,079 reports published between April 2004 and April 2023. The association between herbal medicines and DILLD was evaluated using the pharmacovigilance index as the reporting odds ratio (ROR), logistic regression models, propensity score-matching techniques, and Weibull shape parameters.ResultsThe adjusted RORs using multivariate logistic regression models for Scutellariae radix (daily intake), Pinelliae tuber (daily intake), sex (male), age (≥ 60 years), Scutellariae radix (daily intake)*age (≥ 60 years), and Scutellariae radix (daily intake)* Pinelliae tuber (daily intake) were 1.47 (1.36 − 1.59), 1.05 (1.01 − 1.10), 1.45 (1.34 − 1.57), 1.92 (1.74 − 2.11), 3.35 (3.12 − 3.60), and 1.49 (1.46 − 1.53), respectively. DIILD onset profiles were evaluated using the Weibull shape parameter. A logistic plot of daily intake and onset of DIILD was drawn. ROR signals were detected in 32 of 54 herbal medicines, including Scutellariae radix, Bupleuri radix, and Pinelliae tuber. The median duration (days) (interquartile range) to DIILD onset was 36.0 (27.0–63.0) for Saikokaryukotsuboreito, 35.0 (21.0–55.0) for Saireito, and 31.0 (13.5–67.5) for Shosaikoto. The Weibull shape parameter beta (95% confidence interval) values for Saikokaryukotsuboreito, Saireito, and Shosaikoto were 1.36 (1.08–1.67), 1.36 (1.20–1.52), and 1.31 (0.98–1.68), respectively.ConclusionsDIILD demonstrated a dose-dependent to crude drugs. Clinicians should strive for the early detection of DIILD and avoid the inadvertent administration of herbal medicines.

Preventing Neuraxial Administration of Tranexamic Acid

(Can J Anesth/J Can Anesth. (2023) 70:811–816) This editorial refers to a recent case published by Dr Pysyk and Dr Filteau describing an inadvertent administration of tranexamic acid into the epidural space. The authors of the editorial discuss this case involving a medication error and propose mechanisms to prevent similar errors in the future. While the error was recognized and managed without immediate adverse effects, the potential for catastrophic consequences was highlighted.

Fat necrosis following inadvertent subcutaneous administration of influenza vaccination

Fat necrosis following inadvertent subcutaneous administration of influenza vaccination

Tranexamic Acid at Cesarean Delivery: Drug-error Deaths

(Am J Obstet Gynecol. 2023;228:1–4) Tranexamic acid plays an important role in reducing bleeding experienced during postpartum hemorrhage. It is recommended by the World Health Organization that tranexamic acid is administered intravenously, over 10 minutes, within 3 hours of delivery to treat postpartum hemorrhage. However, tranexamic acid, although helpful in cases of postpartum hemorrhage, has caused other problems to arise. It has been found that tranexamic acid is toxic when administered intrathecally (IT). Tranexamic acid has components that are known to lead to neuronal excitation when mistakenly administered in the intrathecal space. This most often leads to generalized convulsions and malignant arrhythmias. This has been occurring more frequently secondary to tranexamic acid being stored in labor and delivery operating rooms on anesthetic drug carts for easy access for hemorrhage during cesarean delivery. Both tranexamic acid and the drugs used for spinal anesthesia are stored in look-alike glass vials making this risk even more likely. A review published in 2019 reported 21 cases of inadvertent intrathecal administration of tranexamic acid, 20 of these cases were life-threatening with ten resulting in patient deaths. The accidental administration of tranexamic acid intrathecally most likely occurs more often than it has been reported. The mistake of replacing spinal anesthesia drugs with tranexamic acid most commonly occurs in small hospitals and low-middle-income countries.

Hidden risk of gadolinium-based contrast agents during interventional pain medicine procedures: a retrospective chart review

IntroductionEpidural steroid injections and epidural blood patches commonly involve the injection of a small amount of radiocontrast media under fluoroscopy to properly identify the target tissue or anatomic space and...

Early neonatal hypoglycemia in exclusively breastfed babies in a developing country - India.

Neonatal hypoglycemia has been a cause for concern due to increasingly frequent reports of long-term sequelae, leading to undue concern and inadvertent administration of formula feeds. Though hypoglycemia is usually encountered only in neonates with classical risk factors, hypoglycemia is also rarely seen even in babies with no known risk factors. These babies may present only with sequelae in later childhood. This is a hospital-based observational, prospective study. We included 299 exclusively breastfed neonates who were shifted to mother's side with no congenital malformation or need for neonatal intensive care unit (NICU) admission. The neonates were studied in two groups: " At Risk" and "No Risk." The "At Risk" group included babies with known risk factors like low birth weight, late preterm (34-36 weeks), small for gestational age (birth weight <10th centile), infant of a diabetic mother, or large for gestational age (birth weight >90th centile). Hypoglycemia was the primary outcome measured independent of feeding time for both groups. For the "At Risk" group, monitoring was done at 0, 1, 2, 3, 4, 12, 24 plus 48 h. For the "Not At Risk" group, it was done at 12 and 24 h of life. The factors associated with both groups were studies as the secondary outcome. Out of 299 exclusively breastfed neonates, 13% were hypoglycemic. 27.06% were hypoglycemic in the "At Risk" group. In the "At Risk" group, low birth weight and primiparity were significant risk factors. The incidence of hypoglycemia in the "No Risk" group was 1.80%. Breast problems and breastfeeding problems, low education status of mother, young age, and primiparity were significant risk factors in the "No Risk" group.

From disinfectants to antibiotics: Enhanced biosafety of quaternary ammonium compounds by chemical modification

The excessive use of quaternary ammonium compounds (QACs) following the COVID-19 pandemic has raised substantial concerns regarding their biosafety. Overuse of QACs has been associated with chronic biological adverse effects, including genotoxicity or carcinogenicity. In particular, inadvertent intravascular administration or oral ingestion of QACs can lead to fatal acute toxicity. To enhance the biosafety and antimicrobial efficacy of QACs, this study reports a new series of QACs, termed as PACs, with the alkyl chain of benzalkonium substituted by a phthalocyanine moiety. Firstly, the rigid phthalocyanine moiety enhances the selectivity of QACs to bacteria over human cells and reduces alkyl chain’s entropic penalty of binding to bacterial membranes. Furthermore, phthalocyanine neutralizes hemolysis and cytotoxicity of QACs by binding with albumin in plasma. Our experimental results demonstrate that PACs inherit the optical properties of phthalocyanine and validate the broad-spectrum antibacterial activity of PACs in vitro. Moreover, the intravascular administration of the most potent PAC, PAC1a, significantly reduced bacterial burden and ameliorated inflammation level in a bacteria-induced septic mouse model. This study presents a new strategy to improve the antimicrobial efficacy and biosafety of QACs, thus expanding their range of applications to the treatment of systemic infections.

Inadvertent Sodium Administration from Medicines, Intravenous Fluid Therapy, and Diluents in Patients with Heart Failure with Reduced Ejection Fraction Admitted to Cardiac and Non-Cardiac Units in a Tertiary Hospital Network

Inadvertent Sodium Administration from Medicines, Intravenous Fluid Therapy, and Diluents in Patients with Heart Failure with Reduced Ejection Fraction Admitted to Cardiac and Non-Cardiac Units in a Tertiary Hospital Network

Sugammadex Use for Reversal in Nonobstetric Surgery During Pregnancy: A Reexamination of the Evidence.

Sugammadex Use for Reversal in Nonobstetric Surgery During Pregnancy: A Reexamination of the Evidence.

Disseminated varicella zoster virus infection following live attenuated herpes zoster vaccine: descriptive analysis of reports to Australia’s spontaneous vaccine pharmacovigilance system, 2016–2020

ObjectivesTo examine the reported incidence and features of disseminated varicella zoster virus (VZV) infection following live attenuated herpes zoster vaccine live (ZVL: Zostavax, Merck) in immunocompromised people in Australia.Design and...

Imaging of Umbilical Venous Catheter-Related Hepatic Complications in Neonates.

An umbilical venous catheter (UVC) is commonly placed for central venous access in preterm or critically ill full-term neonates to provide total parenteral nutrition (TPN) and medication. However, UVCs can result in complications, including infection, portal vein thrombosis, and hepatic tissue injury. The inadvertent administration of hypertonic fluid through a malpositioned UVC can also cause hepatic parenchymal damage with mass-like fluid collection that simulates a tumorous condition during imaging. Ultrasonography and radiographic examinations play an essential role in detecting UVC-related complications. This pictorial essay aims to present the imaging findings of UVC-related hepatic complications in neonates.

Mass Casualty Incident Involving Rapid Acting Insulin

We report on an unusual prehospital incident involving the inadvertent administration of short-acting insulin among a group of high school students. Sixteen students iatrogenically received 10 units of insulin lispro intradermally instead of tuberculin purified protein derivative (PPD), resulting in several students experiencing symptomatic hypoglycemia. A mass casualty incident was declared and the local poison center consulted. An incident command system, with the support of on-scene EMS physicians, was established to track, treat, and transport the involved patients.

Peripheral venous extravasation injury

Extravasation is the inadvertent administration or leakage of blood, lymph or other fluid (including medication) into the subcutaneous or subdermal tissues, instead of the intended vascular or lymphatic pathways.1,2