Attention-deficit/hyperactivity disorder in pregnancy and the postpartum period.

Attention-deficit/hyperactivity disorder is a childhood-onset neurodevelopmental disorder that frequently persists into adulthood with 3% of adult women having a diagnosis of attention-deficit/hyperactivity disorder. Many women are diagnosed and treated during their reproductive years, which leads to management implications during pregnancy and the postpartum period. We know from clinical practice that attention-deficit/hyperactivity disorder symptoms frequently become challenging to manage during the perinatal period and require additional support and attention. There is often uncertainty among healthcare providers about the management of attention-deficit/hyperactivity disorder in the perinatal period, particularly the safety of pharmacotherapy for the developing fetus. This guideline is focused on best practices in managing attention-deficit/hyperactivity disorder in the perinatal period. We recommend (1) mitigating the risks associated with attention-deficit/hyperactivity disorder that worsen during the perinatal period via individualized treatment planning; (2) providing psychoeducation, self-management strategies or coaching, and psychotherapies; and, for those with moderate or severe attention-deficit/hyperactivity disorder, (3) considering pharmacotherapy for attention-deficit/hyperactivity disorder, which largely has reassuring safety data. Specifically, providers should work collaboratively with patients and their support networks to balance the risks of perinatal attention-deficit/hyperactivity disorder medication with the risks of inadequately treated attention-deficit/hyperactivity disorder during pregnancy. The risks and impacts of attention-deficit/hyperactivity disorder in pregnancy can be successfully managed through preconception counselling and appropriate perinatal planning, management, and support.

Empiric antibiotics for peripartum bacteremia: A chart review from a quaternary Canadian centre.

OBJECTIVE: To evaluate the effectiveness of empiric antibiotic protocols for peripartum bacteremia at a quaternary institution by describing incidence, microbial epidemiology, clinical source of infection, susceptibility patterns, and maternal and neonatal outcomes. METHODS: Retrospective chart review of peripartum patients with positive blood cultures between 2010 and 2018. RESULTS: The incidence of peripartum bacteremia was 0.3%. The most cultured organisms were Escherichia coli (51, 26.7%), Streptococcus spp. (52, 27.2%), and anaerobic spp. (35, 18.3%). Of the E. coli cases, 54.9% (28), 19.6% (10), and 19.6% (10) were resistant to ampicillin, first- and third-generation cephalosporins, respectively. Clinical sources of infection included intra-amniotic infection/endometritis (115, 67.6%), upper and/or lower urinary tract infection (23, 13.5%), and soft tissue infection (8, 4.7%). Appropriate empiric antibiotics were prescribed in 137 (83.0%) cases. There were 7 ICU admissions (4.2%), 18 pregnancy losses (9.9%), 9 neonatal deaths (5.5%), and 6 cases of neonatal bacteremia (3.7%). CONCLUSION: Peripartum bacteremia remains uncommon but associated with maternal morbidity and neonatal morbidity and mortality. Current empiric antimicrobial protocols at our site remain appropriate, but continuous monitoring of antimicrobial resistance patterns is critical given the presence of pathogens resistant to first-line antibiotics.

Perinatal Injectable Opioid Agonist Therapy (iOAT) Administration: A Case Series.

OBJECTIVES: Untreated opioid use disorder (OUD) in pregnancy may lead to adverse outcomes for the individual and fetus. Injectable opioid agonist therapy (iOAT) is the highest intensity treatment for severe refractory OUD currently available; however, research on perinatal administration is limited. We present the first known case series of 13 pregnant or postpartum participants who received intravenous hydromorphone while admitted to the Families in Recovery (FIR) unit, an in-patient perinatal stabilization unit in Canada. METHODS: Patients who received iOAT at FIR between 2019 and 2022 were invited to participate. Prospectively enrolled participants completed a self-report sociodemographics and exposures survey. Medical/social backgrounds of participants at admission, iOAT and other opioid agonist therapy administration, and health/social outcomes of mother and infant at discharge were collected on all participants via retrospective maternal and infant medical chart review. RESULTS: Participants initiated iOAT while pregnant (n = 5) or postpartum (n = 8) and received iOAT for 23 days on average. At discharge, 8 participants underwent planned transition to community with infant in their care and a discharge plan including outpatient prescriptions, housing arrangements, follow-up appointments, and supportive programming. All infants received oral morphine after delivery and were discharged in good health. CONCLUSIONS: This is the first known case series of iOAT administration in the peripartum. The cases illustrate iOAT as an option that can achieve OUD stabilization in perinatal individuals to support patient engagement and retention in care.

Penicillin de-labelling in vancouver, British Columbia, Canada: comparison of approaches, outcomes and future directions.

BACKGROUND: Inaccurate penicillin allergy labels lead to inappropriate antibiotic prescriptions and harmful patient consequences. System-wide efforts are needed to remove incorrect penicillin allergy labels, but more health services research is required on how to best deliver these services. METHODS: Data was extracted from five hospitals in Vancouver, British Columbia, Canada from October 2018-May 2022. The primary outcomes of this study were to outline de-labelling protocol designs, identify the roles of various healthcare professionals in de-labelling protocols and identify rates of de-labelling penicillin allergies and associated adverse events at various institutions. Our secondary outcome was to describe de-labelling rates for special populations, including pediatric, obstetric and immunocompromised subpopulations. To achieve these outcomes, participating institutions provided their de-labelling protocol designs and data on program participants. Protocols were then compared to find common themes and differences. Furthermore, adverse events were reviewed and percentages of patients de-labelled at each institution and in total were calculated. RESULTS: Protocols demonstrated a high level of variability, including different methods of participant identification, risk-stratification and roles of providers. All protocols used oral and direct oral challenges, heavily involved pharmacists and had physician oversight. Despite the differences, of the 711 patients enrolled in all programs, 697 (98.0%) were de-labelled. There were 9 adverse events (1.3%) with oral challenges with mainly minor symptoms. CONCLUSIONS: Our data demonstrates that de-labelling programs effectively and safely remove penicillin allergy labels, including pediatric, obstetric and immunocompromised patients. Consistent with current literature, most patients with a penicillin allergy label are not allergic. De-labelling programs could benefit from increasing clinician engagement by increasing accessibility of resources to providers, including guidance for de-labelling of special populations.

Effectiveness of a neonatal intensive care unit-specific antimicrobial stewardship program: A ten-year review.

OBJECTIVE: To evaluate the change in consumption of specific antibiotics in a neonatal intensive care unit after the implementation of an antimicrobial stewardship program (ASP). DESIGN: Retrospective cohort study between January 1, 2010, and December 31,2019. SETTING: The neonatal intensive care unit at British Columbia Women's Hospital (Vancouver Canada), a tertiary-care center. PATIENTS: Admitted neonates prescribed antibiotics. METHODS: We implemented an ASP with an early implementation phase starting in January 2014 (period 2) and a later phase starting in January 2017 (period 3). Patient demographics were collected, including birth weight, gestational age, history of necrotizing enterocolitis (NEC), and surgical operations from existing databases. Interrupted time-series analysis was used, and comparison of antibiotic days of therapy (DOT) averages were conducted across the preimplementation period (period 1), period 2, and period 3 regarding total patients and subgroups. RESULTS: We identified 4,512 infants. There was a significant decrease in DOT from 472 (95% confidence interval [CI], 431-517) in period 1 to 405 (95% CI, 367-446) in period 2 to 313 (95% CI, 280-350) in period 3. We detected a significant decrease in the use of ampicillin, aminoglycosides, cloxacillin, and linezolid but not in vancomycin or cefotaxime. Subgroup analyses of infants <1,500 g and those without NEC or surgery showed decreases in the use of cloxacillin, aminoglycosides, and linezolid. CONCLUSIONS: The implementation of an ASP was associated with a significant decrease in the overall DOT and use of certain antibiotics. This study presents important targets for ongoing ASP work.

Breastfeeding on Injectable Opioid Agonist Therapy: A Case Report.

BACKGROUND: Injectable opioid agonist therapy (iOAT) is the highest-intensity treatment currently available in Canada for individuals with severe opioid use disorder. However, there is limited data on iOAT administration in the perinatal period, with no research, practice guidelines, or known reports of breastfeeding on iOAT. This article presents the first known case of an individual breastfeeding on iOAT. CASE SUMMARY: We present a case of a pregnant 32-year-old woman from Canada with severe opioid use disorder, who stabilized with iOAT and chose to breastfeed her infant. She presented to hospital at 38 + 6 gestation in labor, unstable in her substance use disorder despite multiple interventions and was initiated on iOAT (intravenous hydromorphone) shortly after delivery. Before initiation of breastfeeding the infant was admitted to the neonatal intensive care unit for monitoring. On day 9 of life the infant received breastmilk for the first time, and was discharged from neonatal intensive care unit on day 12 of life with no clinical evidence of sedation or respiratory depression. The infant maintained mixed feeding and at 58 days of life was discharged in the mother and father's care, a healthy infant with stable vitals. DISCUSSION: This case suggests positive infant and maternal health and social outcomes for breastfeeding on iOAT. Further research on perinatal iOAT use and the pharmacokinetics of high-dose hydromorphone in breastmilk is required to inform clinical practice guidelines to safely support individuals and their infants who are impacted by substance use.

Establishing obstetrics-specific metrics and interventions for antimicrobial stewardship.

Background: To describe baseline antimicrobial stewardship (AMS) metrics and apply AMS interventions in an inpatient obstetrical population. Methods: From October 2018 to October 2019, our tertiary-care obstetrical center reviewed components of our AMS program, which included: (1) antimicrobial consumption data, (2) point prevalence surveys (PPS), and (3) prospective audit and feedback. We reviewed institutional data for antimicrobial consumption from the pharmacy database. Detailed point prevalence surveys were conducted for all antimicrobial prescriptions on two predefined dates each month. Daily audits and feedback assessed the appropriateness of all non-protocolized antimicrobials. Results: Our average antimicrobial length of therapy (LOT) was 12 days per 100 patient-days, where erythromycin (2.33), amoxicillin (2.28), and ampicillin (1.81) were the greatest contributors. Point prevalence surveys revealed that 28.8% of obstetrical inpatients were on antimicrobials, of which 11.2% were inappropriate. Protocolized antimicrobials were 62% less likely (p = 0.027) to be inappropriate. From 565 audited prescriptions, 110 (19.5%) resulted in feedback, where 90% of recommendations were accepted and implemented. The most common reasons for interventions include incorrect dosage, recommending a diagnostic test before continuing antimicrobials, and changing antimicrobials based on specific culture and sensitivity. Conclusions: Antimicrobial use in obstetrics is unique compared to general inpatients. We provide a baseline set of metrics for AMS at our obstetrical center intending to lay the groundwork for AMS programming in our discipline. Antimicrobial protocolization, as well as audit and feedback, are feasible interventions to improve antimicrobial prescribing patterns.

Historique: Décrire les mesures de gouvernance antimicrobienne (GAM) fondamentales et utiliser les interventions de GAM dans une population obstétricale hospitalisée. Méthodologie: D'octobre 2018 à octobre 2019, le centre obstétrical de soins tertiaires a révisé les éléments du programme de GAM, qui incluait : 1) les données sur la consommation d'antimicrobiens, 2) les enquêtes de prévalence ponctuelles (EPP) et 3) la vérification et la rétroaction prospectives. Les chercheurs ont examiné les données institutionnelles relatives à la consommation d'antimicrobiens dans la base de données de la pharmacie. Ils ont effectué des enquêtes de prévalence ponctuelles détaillées sur toutes les prescriptions d'antimicrobiens à deux dates déterminées chaque mois. Les vérifications et les rétroactions quotidiennes ont permis d'évaluer la pertinence de tous les antimicrobiens non protocolisés. Résultats: La durée du traitement antimicrobien moyen était de 12 jours sur 100 jours-patients, et l'érythromycine (2,33), l'amoxicilline (2,28) et l'ampicilline (1,81) étaient les plus utilisées. Les enquêtes de prévalence ponctuelles ont révélé que 28,8 % des patientes obstétricales hospitalisées prenaient des antimicrobiens, dont 11,2 % étaient inappropriés. Les antimicrobiens protocolisés étaient 62 % moins susceptibles d'être inappropriés (p = 0,027). Des 565 prescriptions vérifiées, 110 (19,5 %) ont donné lieu à des rétroactions, et 90 % des recommandations ont été acceptées et mises en œuvre. Les principales raisons d'intervenir incluaient une posologie inexacte, la recommandation d'un test diagnostique avant de poursuivre l'antimicrobien, ainsi que le changement d'antimicrobien d'après la culture et sensibilité spécifiques. Conclusions: L'utilisation d'antimicrobiens est unique en obstétrique par rapport aux autres patients hospitalisés. Les chercheurs fournissent la série de mesures de GAM de référence utilisée à leur centre obstétrical pour jeter les bases de la programmation de la GAM dans la discipline. La protocolisation des antimicrobiens, de même que la vérification et la rétroaction, est une intervention faisable pour améliorer les profils de prescription d'antimicrobiens.

Development of a national neonatal intensive care unit-specific antimicrobial stewardship programme in Canada: protocol for a cohort study.

INTRODUCTION: Early empiric treatment with broad-spectrum antimicrobials is common in neonatal intensive care units (NICU) due to the non-specific clinical presentation of infection. However, excessive and inappropriate antimicrobial use can lead to the emergence of drug-resistant organisms and adverse neonatal outcomes. This study aims to develop and implement a nationwide NICU-specific antimicrobial stewardship programme (ASP) to promote judicious antimicrobial use and control the emergence of multidrug-resistant organisms (MDROs) in Canada. METHODS AND ANALYSIS: Our study population will include all very low-birth-weight neonates admitted to participating tertiary NICU in Canada. Based on the existing limited literature, we will develop consensus on NICU antimicrobial stewardship interventions to enhance best practices. Using an expanded Canadian Neonatal Network (CNN) platform, we will collect data on antimicrobial use and the susceptibility of organisms identified in clinical samples from blood and cerebrospinal fluid over a period of 2 years. These data will be used to provide all NICU stakeholders with benchmarked centre-adjusted antimicrobial use and MDRO prevalence reports. An ASP plan will be developed at both individual unit and national levels in the subsequent years. Knowledge translation strategies will be implemented through the well-established Evidence-based Practice for Improving Quality methodology. ETHICS AND DISSEMINATION: Ethics for the study has been granted by the University of British Columbia Children's & Women's Research Ethics Board (H19-02490) and supported by CNN Executive Committee. The study results will be disseminated through national organisations and open access peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT04388293.

Does probiotic bacteremia in premature infants impact clinically relevant outcomes? A case report and updated review of literature.

Prophylactic use of probiotics decreases the incidence of necrotizing enterocolitis (NEC) in premature infants. However, there are ongoing concerns related to the routine use of probiotics including inconsistent literature regarding optimal dose and strain, lack of regulatory standards in production and reports regarding potential side effects. There is limited data regarding the incidence of probiotic bacteremia and its impact on relevant clinical outcomes in the premature population. We report the first case of Bifidobacterium longum bacteremia in our center since the routine introduction of probiotics. The neonate had NEC with perforation on day of life 7, which likely led to translocation of the probiotic strain to the blood stream. The neonate did not have any hemodynamic instability and the repeat blood culture was negative after starting antibiotic therapy. We also conducted a literature review and found 13 other cases of probiotic bacteremia in premature or very low birth weight neonates. Although the incidence of probiotic bacteremia is low, it can impact several clinical outcomes including prolonged exposure to antibiotics, removal of central lines and additional laboratory testing such as lumbar puncture. There has been no mortality attributable to probiotic bacteremia and there is no data regarding long term neurodevelopmental outcomes.

Neonatal and Neurodevelopmental Outcomes Following Linezolid for Coagulase-negative Staphylococcal Infection: Real World Evidence.

BACKGROUND: Coagulase-negative staphylococci (CoNS) frequently causes late-onset sepsis in preterm infants. Vancomycin is the first-line therapy, but the emergence of reduced vancomycin-susceptibility strains has resulted in linezolid use, of which long-term safety in preterm infants is unknown. OBJECTIVE: Evaluate the association between linezolid exposure and neurodevelopmental impairment (NDI) or death at 18-21 months of corrected age, in preterm infants with CoNS sepsis. METHODS: Multicentric retrospective cohort study comparing long-term outcomes of preterm infants exposed to linezolid versus other antistaphylococcal antimicrobials. We included infants ≤28 weeks' gestational age (GA), with CoNS sepsis, admitted between January 2011 and June 2015 in 3 level-3 Canadian NICUs. Primary outcome was a composite of death or significant NDI (sNDI) at 18-21 months of corrected age. Secondary outcomes included NDI and individual components of the primary outcome. We assessed the relationship between linezolid exposure and outcomes using a multivariable logistic regression. RESULTS: Of 274 infants included, 67 (24.4%) were exposed to linezolid. Median GA was 26 weeks and clinical characteristics were similar between groups. There was no difference in composite outcome of death or sNDI among the infants of both groups, but significantly more death by 18-21 months in the linezolid group (29.9% vs. 17.6%; P = 0.01). CONCLUSIONS: Linezolid exposure was not associated with composite outcome of death or sNDI at 18-21 months. The association between linezolid and death may be due to indication bias. Further studies are warranted.

Reduction of Inappropriate Antimicrobial Prescriptions in a Tertiary Neonatal Intensive Care Unit After Antimicrobial Stewardship Care Bundle Implementation.

BACKGROUND: Our objective was to evaluate the appropriateness of antibiotic prescriptions in the neonatal intensive care unit using standardized criteria and determine the effects of an antimicrobial stewardship program (ASP) on patterns of antibiotic usage. METHODS: A retrospective audit of antibiotic use from July 2010 to June 2013 was conducted, focusing on prescriptions of vancomycin, cefotaxime, meropenem and linezolid for >3 calendar-days. We evaluated the appropriateness of each course of antibiotic treatment based on the Centers for Disease Control and Prevention 12-Step Guidelines to Prevent Antimicrobial Resistance (steps 4, 6 and 9). An ASP was introduced in August 2014, and the same audit criteria were applied to review antimicrobial use in the subsequent 12 months. RESULTS: In the pre-ASP era, 26.3%, 12.1%, 11.4% and 0% of meropenem, cefotaxime, vancomycin and linezolid courses, respectively, were inappropriate. The most common instance of inappropriate utilization included failure to use narrow-spectrum antimicrobials when appropriate. After the introduction of ASP program, 22.2%, 7.5%, 5.4% and 0% of meropenem, cefotaxime, vancomycin and linezolid courses, respectively, were inappropriate. The numbers of inappropriate antibiotic-days/1000 days of therapy with meropenem, cefotaxime and vancomycin changed from 1.89 to 1.96 [rate ratio (RR), 1.04 (0.70-1.52)], 3.56 to 1.73 [RR, 0.49 (0.33-0.71)] and 2.70 to 1.01 [RR, 0.37 (0.22-0.60)], respectively. In subgroup analysis, very low birth weight infants (birth weight, <1500 g) showed no improvement in the rates of inappropriate antibiotic prescriptions. CONCLUSIONS: In this study, we found that ASP initiatives can be applied in neonatal populations to reduce inappropriate antimicrobial prescriptions, though a different approach may be needed among very low birth weight infants.

Levetiracetam Clinical Pharmacokinetic Monitoring in Pediatric Patients with Epilepsy.

Levetiracetam is a broad-spectrum antiepileptic drug (AED) with a unique mechanism of action. Older AEDs can cause serious short- and long-term adverse drug reactions and complications, rendering them undesirable to use in pediatric patients. Characteristics that make levetiracetam a near-ideal AED include its broad spectrum of activity, good tolerability profile, and minimal drug-drug interactions. Clinical pharmacokinetic monitoring (CPM) is often recommended in pediatric patients for certain AEDs due to large interindividual pharmacokinetic differences and unpredictable drug disposition. Our objective was to determine whether monitoring levetiracetam concentrations is warranted for pediatric patients with epilepsy, using a previously published 9-step decision-making algorithm. A literature search of the MEDLINE (1946-August 2016), EMBASE (1974-August 2016), CENTRAL, and Google Scholar databases was performed to identify relevant English-language articles and answer the questions posed in the algorithm for levetiracetam CPM in pediatric epilepsies. Additional articles were identified from a manual bibliographic review of the relevant literature. We found that levetiracetam CPM met some criteria of the algorithm: levetiracetam is an appropriate adjunctive or monotherapy for pediatric patients with either focal or generalized seizures; it is readily measurable in plasma, with an appropriate degree of sensitivity, accuracy, and precision; it exhibits interindividual variation in pharmacokinetics; often, its pharmacologic effect cannot be easily measured; and the duration of therapy is expected to be long-term. However, important criteria not met include the following: there is no clear evidence for a concentration-response relationship for efficacy or toxicity; the proposed therapeutic range of 12-46 µg/mL is not well-defined and is generally considered as wide. Thus, clinical decision making is unlikely to be affected as a result of routine levetiracetam CPM. In general, routine CPM of levetiracetam cannot be recommended for pediatric patients with epilepsy. However, CPM may be beneficial in select cases, such as patients in whom noncompliance is suspected, those who have severe overdoses, those switching between product brands, or patients for whom an 'individual therapeutic concentration' is documented. Nonetheless, in the majority of pediatric patients with epilepsy, measurement of levetiracetam concentrations is not expected to yield a therapeutic benefit. Thus, clinical assessment and judgment, without measuring drug concentrations, remain the monitoring strategy of choice for levetiracetam therapy.

Lacosamide as adjunctive therapy in refractory epilepsy in adults: a systematic review.

PURPOSE: To review the evidence for efficacy and safety of lacosamide in adult patients with refractory epilepsy and refractory status epilepticus (RSE). METHODS: A systematic literature search of MEDLINE, PubMed, EMBASE, IPA, Google and Google Scholar (through October 2014) was performed. RESULTS: Fourteen studies assessing lacosamide in 3509 refractory epilepsy patients were included. In 3 RCTs, more patients had at least 50% reduction in seizure frequency with lacosamide compared to placebo with 38.3-41.1%, 38.1-41.2%, and 18.3-25.8%, in the 400 mg/day, 600 mg/day, and placebo groups, respectively. In non-comparative trials, 18-69% of patients achieved at least 50% reduction in seizure frequency, and 1.7-26.2% achieved seizure freedom. Non-responders were documented in two trials, with 26.2-34% having no response. Thirteen studies assessing lacosamide in 390 RSE patients were included. When assessing lacosamide's ability to terminate RSE, one comparative cohort study found no improvement in SE duration or seizure control with addition of lacosamide. Another study documented no difference compared to use of phenytoin. Eleven descriptive studies using lacosamide as add-on RSE therapy revealed seizure termination rates of 0-100% (median 64.7%). In all patients receiving lacosamide, dizziness (21.8%), vision disturbances (10.4%), drowsiness (7.4%), headache (7.0%), nausea (6.5%), and coordination problems (5.8%) were the most common adverse effects. CONCLUSION: Based on evidence to date, adjunctive lacosamide is a treatment option to reduce seizure frequency in patients with refractory epilepsy and terminate seizures in patients with RSE. The safety information summary can be used to advise patients of potential adverse effects.

Describing Intravenous Extravasation in Children (DIVE Study).

BACKGROUND: Extravasation, the inadvertent leakage of intravenous (IV) medication from the vein into the surrounding tissue, is a iatrogenic cause of patient injury. Extravasation has been reported to occur in 0.1% to 6.5% of hospital inpatients. The incidence may be higher among children because they have multiple risk factors, including small and fragile veins, decreased peripheral circulation, capillary leakage, and flexible subcutaneous tissue. OBJECTIVES: To describe the incidence of extravasation at a pediatric tertiary care hospital, to identify the agents causing extravasation, and to describe the use of antidotes to manage identified cases. A secondary objective was to describe adverse drug effects associated with the antidotes administered. METHODS: The medical records of pediatric patients with documented extravasation of an IV medication between January 1, 2006, and August 31, 2008, were analyzed retrospectively. The appropriateness of antidote use was determined in terms of adherence to the institution's protocol for treatment of extravasation. RESULTS: A total of 42 patients had documented extravasation, for an overall incidence of 0.04% per patient-day. Of the 40 cases in which location was documented, 12 (30%) occurred on the general pediatric wards, 10 (25%) on the surgical ward, 9 (22%) in the neonatal intensive care unit, 5 (12%) in the pediatric intensive care unit, 3 (8%) in day care, and 1 (2%) in the emergency department. The most common medications involved were fluids for IV administration (18 [43%]), potassium chloride (11 [26%]), antibiotics (8 [19%]), total parenteral nutrition (8 [19%]), calcium chloride (2 [5%]), and epinephrine (2 [5%]). Multiple drugs were involved in some cases of extravasation. The decision to administer an antidote and the choice of antidote (if required) were appropriate in 50% of the cases. No adverse drug effects were reported with use of antidotes. CONCLUSIONS: The incidence of extravasation was low. The medications most commonly involved were similar to those reported in the literature. Antidotes were well tolerated but were appropriately used in only half of the events. Prospective trials are needed to determine the clinical severity of injury and to assess the effectiveness and safety of antidotes.