Evaluation of Goal Phenytoin Levels After an Initial Intravenous Loading Dose at an Academic Medical Center.

BACKGROUND: Phenytoin intravenous loading doses are administered in status epilepticus to rapidly achieve therapeutic levels. Accurately assessing phenytoin levels after the initial load can be challenging because of its complex pharmacokinetic profile and nonstandardized weight-based loading doses. OBJECTIVES: The objectives of this analysis were to determine the incidence of patients achieving goal phenytoin levels after the initial loading dose and characterize factors that contribute to achieving the goal level. METHODS: This single-center, retrospective cohort analysis was approved by our institutional review board and included adult patients who received a phenytoin load from May 2016 to March 2021. Patients were excluded if no total phenytoin level was drawn within 24 hours of the load, if the maintenance dose was given before the first level was drawn, or if the patient was on phenytoin before the load. The major endpoint was the percentage of patients achieving a corrected goal phenytoin level of ≥10 mcg/mL after the initial load. Multivariate regression was used to determine predictors of achieving the goal phenytoin level. RESULTS: Of the 152 patients included, 139 patients (91.4%) achieved a corrected goal level after the first load. Patients at goal received a significantly higher median weight-based loading dose (19.1 mg/kg [15.0-20.0] vs 12.6 mg/kg [10.1-15.0], P < 0.01). The multivariate analysis identified weight-based dosing as a statistically significant predictor of achieving the corrected goal level (odds ratio, 1.30; 95% CI, 1.12-1.53; P < 0.01). CONCLUSION AND RELEVANCE: Most patients achieved a corrected goal phenytoin level after the initial load. A higher median weight-based loading dose was shown to be a predictor of achieving the goal level and should be encouraged for rapid seizure termination. Future studies are warranted to confirm patient-specific factors that affect rapid achievement of the goal phenytoin level.

Naloxone Versus Methylnaltrexone for Opioid-Induced Constipation in Critically Ill Patients.

BACKGROUND: Opioid-induced constipation (OIC) may occur in up to 81% of critically ill patients and can lead to many complications. Opioid antagonists are a reasonable approach and may be used for managing OIC. OBJECTIVE: The purpose of this study was to assess the efficacy of enteral naloxone (NLX) versus subcutaneous methylnaltrexone (MNTX) for the management of OIC in critically ill patients. METHODS: A retrospective analysis was conducted on adult patients who received NLX or MNTX and a continuous opioid infusion for at least 48 hours. The primary end point was time to resolution of constipation, defined as hours to first bowel movement (BM) after the first dose of an opioid antagonist. Reversal of analgesia was assessed by comparing the total number of morphine milligram equivalents (MME) 24 hours preopioid and postopioid antagonist administration. Univariate and multivariate analyses were conducted to assess treatment response within 48 hours. RESULTS: Baseline characteristics were similar between patients receiving NTX (n = 89) and MNTX (n = 71). However, the time to the first BM with NLX was 18 hours compared with 41 hours with MNTX (P = 0.004). There was no difference in MME requirements 24 hours pre/post NLX or MNTX administration. Naloxone administration was identified as a statistically significant predictor of BM within 48 hours (odds ratio [OR] = 2.68 [1.33-5.38]). CONCLUSION AND RELEVANCE: The time to first BM was shorter with enteral NLX. Both NLX and MNTX appear to be effective for the management of OIC without causing reversal of analgesia. Future controlled, prospective trials comparing these agents are warranted.

Evaluation of Dexmedetomidine as an Adjunct to Phenobarbital for Alcohol Withdrawal in Critically Ill Patients.

INTRODUCTION: Dexmedetomidine (DEX) is commonly used with benzodiazepines for the management of alcohol withdrawal syndrome (AWS), but limited data exist regarding its use with phenobarbital (PHB). This analysis evaluated the utility of DEX in addition to PHB for AWS in adult patients admitted to the intensive care unit (ICU). METHODS: This was a single-center, retrospective cohort analysis of critically ill adult patients who received PHB plus either DEX or different adjunctive therapies (NO-DEX) for AWS between 2018 and 2021. Patients were excluded if they had underlying altered mental status or seizure disorder unrelated to AWS or received PHB at outside hospitals. Coarsened exact matching (CEM) was performed to match patients on baseline characteristics in a 1:1 ratio. The primary outcome was ICU length of stay (LOS). A multivariate linear regression analysis was performed to assess the effects of DEX on ICU LOS when accounting for confounders. Secondary outcomes included days with delirium and incidence of mechanical ventilation after PHB administration. RESULTS: Of the 606 encounters evaluated, 197 met criteria for inclusion. After CEM, 56 encounters remained in each group for analysis. The median ICU LOS was 97.2 [50.1:139.5] hours for the DEX group and 47.5 [28.8:88.1] hours for the NO-DEX group (P = .002). The multivariate linear regression analysis showed the use of DEX (P = .008) was independently associated with an increased ICU LOS by 49.8 h. The DEX group had higher rates of total delirium days (208 vs 143 days, P < .001) and a higher incidence of mechanical ventilation after PHB administration (32% vs 9%, P < .001). CONCLUSION: This analysis suggests the use of adjunctive DEX with PHB for AWS was associated with a prolonged ICU LOS. Additional studies are needed to further understand the role of adjunctive DEX in the treatment of AWS in critically ill patients.

Comparison of trauma-dosed tranexamic acid versus aminocaproic acid in cardiac surgery in the setting of drug shortage.

BACKGROUND: Antifibrinolytic agents, tranexamic acid (TXA) and epsilon-aminocaproic acid (EACA), are often used during cardiac surgery to decrease the number of allogenic blood transfusions and to prevent perioperative bleeding. Weight-based TXA dosing regimens have been compared to fixed-dose regimens of EACA with variable outcomes in perioperative blood product transfusions and chest tube output. Serious adverse events, including seizures, have been reported with higher doses of TXA. Fixed-dose TXA regimens have been evaluated in trauma and orthopedic surgery but there is a paucity of evidence in the cardiac surgery population. AIMS OF THE STUDY: To compare the safety and efficacy of fixed-dose TXA versus EACA in patients undergoing cardiac surgery. METHODS: A single-center, retrospective chart review was conducted at a 793-bed tertiary care academic teaching hospital comparing cardiac surgery patients receiving either fixed-dose TXA 1000 mg followed by a 500-1000 mg infusion or EACA-7.5 g intravenous boluses followed by a 1-1.25 g/h infusion for the duration of the surgery. The major endpoint included chest tube output at 12 h, 24 h, and 7 days postoperatively. Minor endpoints included quantity and incidence of blood product transfusions and reported safety events. RESULTS: There were 1544 patients included. Chest tube output was similar between groups and the TXA group required more intraoperative blood product transfusions (22.7% vs. 18.2%, p = .03). There were no differences in the median quantity of total blood products administered postoperatively at 24 h or at 7 days. Reported safety events were similar between groups. CONCLUSION: Both fixed-dose TXA and EACA may be considered safe and effective options for antifibrinolytic therapy in cardiac surgery patients.

Evaluation of a Phenobarbital-Based Protocol for Severe Alcohol Withdrawal in Critically Ill Patients.

Background: Phenobarbital offers several possible advantages to benzodiazepines including a longer half-life and anti-glutamate activity, and is an alternative for the treatment of alcohol withdrawal. The objective of this analysis was to evaluate the safety and efficacy of a phenobarbital protocol for alcohol withdrawal newly implemented at our institution. Methods: This was a single-center, retrospective analysis of adult patients admitted to the medical/surgical/burn/trauma intensive care unit (ICU) with or at risk of severe alcohol withdrawal. Patients who were admitted prior to guideline implementation and received scheduled benzodiazepines (PRE) were compared to those who received phenobarbital post guideline update (POST). The primary outcome was ICU length of stay (LOS). Results: Upon analysis, 68 patients in the PRE and 64 patients in the POST were identified for inclusion. The median APACHE II score was significantly higher in the POST (4.5 [3:9] vs 10 [5:13], P < 0.001). ICU (2 [1:2] vs 2 [2:5], P = 0.002) and hospital (4.5 [3:6] vs 8 [6:12], P < 0.001) LOS were significantly longer in the POST. There was no difference in mortality or duration of mechanical ventilation. More patients required propofol or dexmedetomidine on day one in the POST (P < 0.001). Conclusion: Patients in the POST had significantly longer ICU and hospital LOS, and had a higher baseline severity of illness. Future research is needed to evaluate the efficacy and safety of phenobarbital compared to benzodiazepines for severe alcohol withdrawal.

Evaluating the incidence of acute kidney injury and gentamicin synergy dosing for endocarditis.

Objectives: Current infective endocarditis guidelines recommend two different gentamicin synergy dosing strategies for selected Gram-positive organisms. The purpose of this analysis was to evaluate the incidence of acute kidney injury (AKI) with gentamicin synergy dosing, comparing divided-daily and once-daily dosing strategies for infective endocarditis (IE). Methods: Groups were split into patients who received gentamicin divided-daily dosing and once-daily (3 mg/kg) dosing for Gram-positive IE. The primary outcome was the incidence of AKI defined by RIFLE (risk, injury, failure, loss, end-stage renal disease) criteria after starting gentamicin. A multivariable logistic regression analysis was performed to identify possible independent predictors of developing AKI. Notable secondary outcomes included hospital length of stay, need for gentamicin dose adjustments based on therapeutic drug monitoring, and assessment of each case of AKI using the Naranjo algorithm. Results: The incidence of AKI was significantly higher in the divided-daily group compared with the once-daily group (52.5% versus 13%, P < 0.01). The divided-dosing group had significantly longer median [IQR] hospital length of stay (19 days [12:29] versus 13.5 days [9:22], P < 0.01) and a greater number of patients who required dose adjustments (76.2% versus 21.7%, P < 0.01). The multivariable regression analysis showed that the divided-dosing strategy, duration and institution were independently associated with incidence of AKI. Conclusions: This analysis suggests a lower incidence of AKI in the treatment of endocarditis with gentamicin synergy dosed once-daily compared with a divided-daily dosing. Further studies are warranted to assess if there is a difference in efficacy between gentamicin synergy dosing strategies and in gentamicin compared with no gentamicin regimens for IE.

Managing Clinical Programs in Pharmacy at an Academic Medical Center in the United States.

Managing clinical pharmacy programs requires communication, coordination, and organization to provide the best possible care to patients and to support staff members. While different areas of pharmacy have slight variations in management style, there are core concepts that all clinical managers should address. These include training, staff evaluation and  support, assessment and improvement of policies and processes and research. Standardized training performed by high performing members of  staff is essential in providing the framework for strong employees and clinical  pharmacists. Routine communication, evaluation, and discussion of reward and promotion will provide support to staff and recognition of high-quality  work. Continued evaluation and improvement of policies and processes will  bring attention to areas of improvement and how the change can be agreed  upon and implemented. Research is necessary to advance the healthcare  practice and improve patient outcomes. Managers and administrators should tailor their approach based on what is best for their practice setting,  institution, and staff to promote strong and capable pharmacists, policies, and workflow to provide the best possible care to patients.

La gestión de los programas de Farmacia Clínica requiere comunicación, coordinación y organización para brindar la mejor atención  posible a los pacientes y apoyar a los profesionales de los servicios de  farmacia. Si bien existen ligeras variaciones entre los estilos de gestión de los  diferentes ámbitos de la farmacia hospitalaria, existen algunos conceptos  básicos que todos los gestores clínicos deben abordar. Estos incluyen  formación, evaluación y apoyo al personal, evaluación y mejora de políticas y  procesos, e investigación y docencia. La formación reglada impartida por  personal cualificado es esencial para proporcionar un marco de actuación sólido encaminado a fortalecer las competencias del personal en general y de  los farmacéuticos clínicos en particular. La comunicación, evaluación y  discusión continuas sobre recompensas y promociones sirven para intensificar el apoyo al personal y reconocer la excelencia profesional. La  evaluación y mejora continuas de políticas y procesos ayudan a identificar  posibles áreas de mejora y a consensuar e implementar los cambios  necesarios. La investigación es necesaria para optimizar la atención sanitaria y  mejorar los resultados en salud. Los gerentes y responsables hospitalarios  deben adaptar sus métodos de trabajo en función de las necesidades de su  práctica asistencial, de las características de la institución en la que trabajan y  de los profesionales que ejercen sus funciones en ella. De este modo, podrá  promoverse el desarrollo de profesionales farmacéuticos, políticas y rutinas de  trabajo que permitan ofrecer a los pacientes la más alta calidad asistencial.

Evaluation of the safety of 500 mg intravenous push thiamine at a tertiary academic medical center.

Background: Thiamine, also known as vitamin B1, is an essential water-soluble micronutrient. Although thiamine has minimal safety concerns, parenteral administration has been associated with rare cases of anaphylactic shock, cardiac arrest, and injection site reaction. The objective of this analysis is to evaluate the incidence of anaphylaxis and injection site reactions associated with the administration of thiamine 500 mg as an intravenous (IV) push in adult patients. Method: This single-center, retrospective analysis was performed at Brigham and Women's Hospital in Boston, Massachusetts. Electronic health records were used to identify all adult patients who were ordered for thiamine 500 mg IV push between July 1, 2020, and December 31, 2020. For the major and minor endpoints, anaphylaxis and injection site reactions were assessed, respectively. Descriptive statistics were used as appropriate. Results: A total of 463 doses of thiamine in 69 patients were evaluated. Thiamine was administered peripherally for 392 (84.7%) doses and centrally for 68 (14.7) doses. No anaphylactic reactions were observed. A total of 4 injection site reactions (0.86%) were noted with 4 unique doses. All reactions were classified as low-grade based on our institutional grading system. All injection site reactions were classified as "possible" (Naranjo score of 1-4). Conclusion: Administration of IV push 500 mg thiamine was not associated with anaphylactic events and was associated with a low rate of injection site reactions.

Impact of Extended Duty Hours on Perceptions of Care and Objective Patient Outcomes.

OBJECTIVE: In 2017, interns were permitted to work continuously for up to 28 hours at a time, a reversal from the previously mandated 16-hour limit. Our objective was to evaluate perceptions of care and patient outcomes on an extended (28-hour) compared with a limited (16-hour) duty-hour system on identical interdisciplinary teams. METHODS: Sixty-two interns, 27 residents, 28 attendings, and 449 patients participated. Patients completed surveys assessing their satisfaction. Anonymous weekly surveys were obtained from interns, residents, and attendings evaluating perceptions of intern tiredness, overall satisfaction, and performance. Nursing surveys evaluated intern and medical team performance. Objective outcome measures, including intensive care unit transfers, length of stay, readmissions, mortality, and complications, were assessed through a retrospective, blinded chart review. RESULTS: Patients reported similar satisfaction in care. Extended duty-hour interns reported significantly decreased familiarity with their patients, decreased ability to conduct physical exams on new patients, increased tiredness, and decreased overall satisfaction. Residents overseeing extended-duty interns reported significantly decreased quality in intern presentations and overall quality of teaching, and increased perception of intern tiredness and increased incorrect orders. Attending physicians reported significantly improved quality of new patient presentations by extended duty-hour interns. No significant differences in patient objective outcome measures were noted. CONCLUSIONS: Extended intern duty hours do not affect patient's satisfaction with their care. Although interns in the extended duty-hour system reported significantly increased fatigue and decreased overall satisfaction and residents' perceived increases in incorrect intern orders in the extended duty-hour system, there were no detrimental effects on patient safety.

Review of Pharmacologic Sleep Agents for Critically Ill Patients.

Sleep is a dynamic restorative process that is frequently disrupted in critically ill patients. Inadequate sleep can contribute to delirium and impaired healing. The etiology is multifactorial and practitioners often use a combination of nonpharmacologic and pharmacologic therapies to promote a healthy sleep cycle. There are many pharmacologic agents that may be used to promote sleep, and they display varying degrees of efficacy and safety. The selection of agent(s) should be based on patient- and disease-specific factors. All members of the treatment team can aid in assessing and optimizing sleep for critically ill patients.

Gestión de programas clínicos en farmacia en un hospital docente de los Estados Unidos / Managing Clinical Programs in Pharmacy at an Academic Medical Center in the United States

La gestión de los programas de Farmacia Clínica requiere comunicación,coordinación y organización para brindar la mejor atención posiblea los pacientes y apoyar a los profesionales de los servicios de farmacia. Sibien existen ligeras variaciones entre los estilos de gestión de los diferentesámbitos de la farmacia hospitalaria, existen algunos conceptos básicos quetodos los gestores clínicos deben abordar. Estos incluyen formación, evaluacióny apoyo al personal, evaluación y mejora de políticas y procesos,e investigación y docencia. La formación reglada impartida por personalcualificado es esencial para proporcionar un marco de actuación sólidoencaminado a fortalecer las competencias del personal en general y delos farmacéuticos clínicos en particular. La comunicación, evaluación y discusióncontinuas sobre recompensas y promociones sirven para intensificarel apoyo al personal y reconocer la excelencia profesional. La evaluacióny mejora continuas de políticas y procesos ayudan a identificar posiblesáreas de mejora y a consensuar e implementar los cambios necesarios. Lainvestigación es necesaria para optimizar la atención sanitaria y mejorarlos resultados en salud. Los gerentes y responsables hospitalarios debenadaptar sus métodos de trabajo en función de las necesidades de su prácticaasistencial, de las características de la institución en la que trabajany de los profesionales que ejercen sus funciones en ella. De este modo,podrá promoverse el desarrollo de profesionales farmacéuticos, políticas yrutinas de trabajo que permitan ofrecer a los pacientes la más alta calidadasistencial.

Managing clinical pharmacy programs requires communication, coordination,and organization to provide the best possible care to patients andto support staff members. While different areas of pharmacy have slightvariations in management style, there are core concepts that all clinicalmanagers should address. These include training, staff evaluation and support,assessment and improvement of policies and processes and research.Standardized training performed by high performing members of staff isessential in providing the framework for strong employees and clinical pharmacists.Routine communication, evaluation, and discussion of reward andpromotion will provide support to staff and recognition of high-quality work.Continued evaluation and improvement of policies and processes will bringattention to areas of improvement and how the change can be agreed uponand implemented. Research is necessary to advance the healthcare practiceand improve patient outcomes. Managers and administrators shouldtailor their approach based on what is best for their practice setting, institution,and staff to promote strong and capable pharmacists, policies, andworkflow to provide the best possible care to patients.