Adrian Wong

Evaluation of Adjunctive Ketamine to Benzodiazepines for Management of Alcohol Withdrawal Syndrome

Background: Adjunctive medications to manage alcohol withdrawal syndrome (AWS) in patients not adequately responding to escalating doses of benzodiazepines (BZDs) are limited. The use of the N-methyl-d-aspartate antagonist ketamine, may serve as an effective adjunct agent; however, no published data currently exist for this practice. Objective: To determine the safety and efficacy of adjunct ketamine for management of AWS. Methods: The study was a retrospective review of adult patients from April 2011 to March 2014 who were administered ketamine specifically for management of AWS. Outcomes included changes in BZD requirements and ketamine-related adverse reactions. Results: Of 235 patients screened, 23 patients met study eligibility. Ketamine was initiated primarily with toxicology consultation for significant BZD requirements or delirium tremens. The mean time to initiation of ketamine from first treatment of AWS, and total duration of therapy were 33.6 and 55.8 hours, respectively. Mean initial infusion dose and median total infusion rate during therapy were 0.21 and 0.20 mg/kg/h, respectively. There was no change in sedation or alcohol withdrawal scores in patients within 6 hours of ketamine initiation. The median change in BZD requirements at 12 and 24 hours post–ketamine initiation were −40.0 and −13.3 mg, respectively. The mean time to AWS resolution was 5.6 days. There was one documented adverse reaction of oversedation, requiring dose reduction. Conclusions: Ketamine appears to reduce BZD requirements and is well tolerated at low doses. Prospective dose range evaluations in the management of AWS would be helpful in determining its place as an adjunctive agent.

Management of benzodiazepine-resistant alcohol withdrawal across a healthcare system: Benzodiazepine dose-escalation with or without propofol☆

BACKGROUND Severe cases of alcohol withdrawal syndrome (AWS) may not resolve despite escalating doses of benzodiazepines (BZDs). Benzodiazepine-resistant alcohol withdrawal (RAW) is a subset of severe alcohol withdrawal defined by the requirement of ≥40mg of diazepam administered within one hour. Use of adjunct agents, such as propofol, may be beneficial to minimize BZD adverse effects and improve symptom control. While limited evidence suggests propofol as an effective adjunct in AWS through improved sedation, evidence is currently lacking for the addition of only propofol to BZDs for management of RAW. METHODS Retrospective review of adult patients from January, 2009 to March, 2012 with RAW. Patients were categorized into BZD dose-escalation only or BZD plus propofol. The primary endpoint was time to resolution of AWS. Secondary endpoints included safety outcomes associated with medication use. RESULTS Of 1083 patients with severe AWS, 66 RAW patients (n=33 BZD only, n=33 BZD plus propofol) met inclusion. Median time to AWS resolution was 5.0 and 7.0 days for BZD only vs. BZD plus propofol (p=0.025). Duration of mechanical ventilation, ICU and hospital length of stay were significantly higher with propofol (p=0.017, <0.001 and <0.001, respectively). Ten patients required intervention for management of propofol-induced adverse reactions. CONCLUSIONS The addition of propofol for RAW treatment is associated with significant increases in clinical care. While randomized, prospective evaluations are necessary to determine the cause of this association, our data suggests use of adjunctive propofol therapy in RAW is associated with longer and more complicated hospital admissions.

Patient preferences regarding pharmacologic venous thromboembolism prophylaxis

BACKGROUND The 2012 American College of Chest Physicians venous thromboembolism prevention guidelines emphasized the importance of considering patient preferences when ordering venous thromboembolism prophylaxis. OBJECTIVE Determine patient preferences regarding pharmacologic venous thromboembolism prophylaxis. DESIGN Single-center, mixed-methods survey. SETTING Academic medical center. PATIENTS Consecutive hospitalized patients on surgical and medical units. MEASUREMENTS Patients were asked about their preferences regarding the route of administration for pharmacologic venous thromboembolism prophylaxis and the rationale for their preference. Qualitative analyses of themes were determined from patient rationale. RESULTS Of the 227 patients, a majority (60.4%) preferred an oral medication, if equally effective to subcutaneous options. Dislike of needles (30.0%) and pain from injection (27.7%) were identified as rationales for their preference. Patients favoring subcutaneous administration (27.5%) identified a presumed faster onset of action (40.3%) as the primary reason for their preference. Patients with a preference for subcutaneous injections were less likely to refuse prophylaxis than patients who preferred an oral route of administration (37.5% vs 51.3%, P < 0.0001). LIMITATION Only medical and surgical patients participated. CONCLUSION In a sample of consecutive medical and surgical patients, a majority preferred an oral route of administration for prophylaxis. Patients preferring subcutaneous injections were less likely to refuse doses of ordered pharmacologic prophylaxis. These results indicate use of an oral agent for venous thromboembolism prophylaxis may improve adherence and that integrating patient preferences into care may increase delivery of effective prophylaxis and reduce the incidence of venous thromboembolism.

Multicenter evaluation of pharmacologic management and outcomes associated with severe resistant alcohol withdrawal

INTRODUCTION A subset of patients with alcohol withdrawal syndrome does not respond to benzodiazepine treatment despite escalating doses. Resistant alcohol withdrawal (RAW) is associated with higher incidences of mechanical ventilation and nosocomial pneumonia and longer intensive care unit (ICU) stay. The objective of this study is to characterize pharmacologic management of RAW and outcomes. METHODS Adult patients were identified retrospectively via International Classification of Diseases, Ninth Revision codes for severe alcohol withdrawal from 2009 to 2012 at 3 hospitals. Data collected included pharmacologic management and clinical outcomes. RESULTS A total of 184 patients met inclusion criteria. Sixteen medications and 74 combinations of medications were used for management. Propofol was the most common adjunct agent, with dexmedetomidine and antipsychotics also used. One hundred seventy-five patients (96.2%) were admitted to the ICU, with 149 patients (81.9%) requiring ventilator support. Median time to resolution of alcohol withdrawal syndrome from RAW designation was 6.0 days. Median ICU and hospital length of stay were 9.0 and 12.7 days, respectively. CONCLUSION Diverse patterns exist in the management of patients meeting RAW criteria, indicating lack of refined approach to treatment. High doses of sedatives used for these patients may result in a high level of care, illustrating a need for evidence-based clinical guidelines to optimize outcomes.

Evaluation of medication-related clinical decision support alert overrides in the intensive care unit

Purpose: Medication‐related clinical decision support (CDS) has been identified as a method to improve patient outcomes but is historically frequently overridden and may be inappropriately so. Patients in the intensive care unit (ICU) are at a higher risk of harm from adverse drug events (ADEs) and these overrides may increase patient harm. The objective of this study is to determine appropriateness of overridden medication‐related CDS overrides in the ICU. Materials and methods: We evaluated overridden medication‐related alerts of four alert categories from January 2009 to December 2011. The primary outcome was the appropriateness of a random sample of overrides based on predetermined criteria. Secondary outcomes included the incidence of adverse drug events (ADEs) that resulted from the overridden alert. Results: A total of 47,449 overridden alerts were included for evaluation. The appropriateness rate for overridden alerts varied by alert category (allergy: 94%, drug‐drug interaction: 84%, geriatric: 57%, renal: 27%). A total of seven actual ADEs were identified in the random sample and where the medication(s) was administered (n = 366), with an increased risk of ADEs associated with inappropriately overridden alerts (p = 0.0078). Conclusions: The appropriateness of medication‐related clinical decision support overrides in the ICU varied substantially by the type of alert. Inappropriately overridden alerts were associated with an increased risk of ADEs compared to appropriately overridden alerts. HighlightsMedication‐related clinical decision support has been shown to improve patient safety, but is frequently overriddenThis study evaluated the appropriateness of overrides that exhibits an increased risk for adverse events.Alert categories evaluated were drug‐allergy, drug‐drug interaction, geriatric and renalOverall, weighted appropriateness of the evaluated overrides was 92.3%, with significant variance by alert type (p < 0.001)Inappropriately overridden alerts were associated with an increased risk of adverse drug events (p < 0.0078)

Review of adjunctive dexmedetomidine in the management of severe acute alcohol withdrawal syndrome

Abstract Background: The primary management of alcohol withdrawal involves the administration of a γ-aminobutyric acid agonist, such as benzodiazepines, for management of symptoms and to prevent further progression to seizure or delirium tremens. Despite escalating doses of benzodiazepines, published literature indicates that some patient’s alcohol withdrawal syndrome symptoms do not respond, and that the use of adjunctive agents may be beneficial in these patients. Dexmedetomidine, an α2-agonist, serves as a potential adjunctive agent through management of associated autonomic symptoms. Understanding of recent literature evaluating its use is necessary for appropriate selection. Objective: To review available literature supporting the use of adjunctive dexmedetomidine for management of severe alcohol withdrawal syndrome. Methods: A total of 13 published articles evaluating the efficacy and safety of dexmedetomidine as an adjunctive agent for the treatment of alcohol withdrawal in adult patients were identified from a MEDLINE search using the key words alcohol withdrawal, delirium tremens and dexmedetomidine. Results: Evaluation of the literature indicates that dexmedetomidine is associated with a decrease in short-term benzodiazepine requirements after initiation, and improvement in hemodynamic parameters in relation to the adrenergic drive present in alcohol withdrawal. Conclusion: The use of dexmedetomidine in the management of severe alcohol withdrawal should be considered as an adjunctive agent. Dexmedetomidine appears to be well tolerated, with an expected decrease in blood pressure and heart rate. Seizures have occurred in patients with alcohol withdrawal despite the use of dexmedetomidine, with and without benzodiazepines, due to lack of γ-aminobutyric acid agonist administration.

Drug Class Combination–Associated Acute Kidney Injury

Objective: To evaluate the quality of available evidence of drug class combinations and their association with the development of acute kidney injury (AKI). Data Sources: A search of MEDLINE and Embase databases was completed using the following terms: “risk factor AND (acute kidney injury or acute kidney failure) AND (drug or medication).” Study Selection and Data Extraction: Inclusion criteria were the following: English language, full-text availability, and at least 1 drug-combination. Each citation was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria. The literature was evaluated using the quality of evidence component of GRADE. No standardized definition of AKI was applied throughout.. Data Synthesis: Out of 2139 total citations, 151 were assessed for full-text review, with 121 citations (6%) meeting inclusion criteria, producing76 unique drug class combinations. Overall, 56 combinations (73.7%) were considered very low quality; 12 (15.8%) were considered low quality. There were 8 (10.5%) of moderate quality, and no combination was considered high quality. 58 (76%) combinations that had a single citation,with a mean of 1.6 citations per drug class combination. The combination of nonsteroidal anti-inflammatory drugs (NSAIDs) and diuretics was reported in 10 citations, the largest number of citations. Conclusions: Our study demonstrates a lack of well-designed studies addressing drug class combination–associated AKI. The combination of NSAIDs and diuretics with or without additional renin-angiotensin aldosterone agents had the strongest level of evidence. Despite limitations, the information included in this review may result in additional scrutiny about combining certain individual nephrotoxic drugs.

Natural Language Processing and Its Implications for the Future of Medication Safety: A Narrative Review of Recent Advances and Challenges

The safety of medication use has been a priority in the United States since the late 1930s. Recently, it has gained prominence due to the increasing amount of data suggesting that a large amount of patient harm is preventable and can be mitigated with effective risk strategies that have not been sufficiently adopted. Adverse events from medications are part of clinical practice, but the ability to identify a patients risk and to minimize that risk must be a priority. The ability to identify adverse events has been a challenge due to limitations of available data sources, which are often free text. The use of natural language processing (NLP) may help to address these limitations. NLP is the artificial intelligence domain of computer science that uses computers to manipulate unstructured data (i.e., narrative text or speech data) in the context of a specific task. In this narrative review, we illustrate the fundamentals of NLP and discuss NLPs application to medication safety in four data sources: electronic health records, Internet‐based data, published literature, and reporting systems. Given the magnitude of available data from these sources, a growing area is the use of computer algorithms to help automatically detect associations between medications and adverse effects. The main benefit of NLP is in the time savings associated with automation of various medication safety tasks such as the medication reconciliation process facilitated by computers, as well as the potential for near–real‐time identification of adverse events for postmarketing surveillance such as those posted on social media that would otherwise go unanalyzed. NLP is limited by a lack of data sharing between health care organizations due to insufficient interoperability capabilities, inhibiting large‐scale adverse event monitoring across populations. We anticipate that future work in this area will focus on the integration of data sources from different domains to improve the ability to identify potential adverse events more quickly and to improve clinical decision support with regard to a patients estimated risk for specific adverse events at the time of medication prescription or review.

Prospective evaluation of medication-related clinical decision support over-rides in the intensive care unit

Background Clinical decision support (CDS) displayed in electronic health records has been found to reduce the incidence of medication errors and adverse drug events (ADE). Recent data suggested that medication-related CDS alerts were frequently over-ridden, often inappropriately. Patients in the intensive care unit (ICU) are at an increased risk of ADEs; however, limited data exist on the benefits of CDS in the ICU. This study aims to evaluate potential harm associated with medication-related CDS over-rides in the ICU. Methods This was a prospective observational study of adults admitted to any of six ICUs between July 2016 and April 2017 at our institution. Patients with provider-overridden CDS for dose (orders for scheduled frequency and not pro re nata), drug allergy, drug–drug interaction, geriatric and renal alerts (contraindicated medications for renal function or renal dosing) were included. The primary outcome was the appropriateness of over-rides, which were evaluated by two independent reviewers. Secondary outcomes included incidence of ADEs following alert over-ride and risk of ADEs based on over-ride appropriateness. Results A total of 2448 over-ridden alerts from 712 unique patient encounters met inclusion criteria. The overall appropriateness rate for over-rides was 81.6% and varied by alert type. More ADEs (potential and definite) were identified following inappropriate over-rides compared with appropriate over-rides (16.5 vs 2.74 per 100 over-ridden alerts, Fisher’s exact test P<0.001). An adjusted logistic regression model showed that inappropriate over-rides were associated with an increased risk of ADEs (OR 6.14, 95% CI 4.63 to 7.71, P<0.001). Conclusions Approximately four of five identified CDS over-rides were appropriately over-ridden, with the rate varying by alert type. However, inappropriate over-rides were six times as likely to be associated with potential and definite ADEs, compared with appropriate over-rides. Further efforts should be targeted at improving the positive predictive value of CDS such as by suppressing alerts that are appropriately over-ridden.

Major publications in the critical care pharmacotherapy literature in 2015

Purpose. Recently published practice guidelines and research reports on pharmacotherapy in critical care patient populations are summarized. Summary. The Critical Care Pharmacotherapy Literature Update (CCPLU) Group is composed of over 50 experienced critical care pharmacists who evaluate 31 peer‐reviewed journals monthly to identify literature pertaining to pharmacotherapy in critical care populations. Articles are chosen for summarization in a monthly CCPLU Group publication on the basis of applicability and relevance to clinical practice and strength of study design. From January to December 2015, a total of 121 articles were summarized; of these, 3 articles presenting clinical practice guidelines and 12 articles presenting original research findings were objectively selected for inclusion in this review based on their potential to change or reinforce current evidence‐based practice. The reviewed guidelines address the management of intracranial hemorrhage (ICH), adult advanced cardiac life support (ACLS) and post‐cardiac arrest care, and the management of supraventricular tachycardia (SVT). The reviewed research reports address topics such as nutrition in critically ill adults, administration of β‐lactams for severe sepsis, anticoagulant selection in the context of continuous renal replacement therapy, early goal‐directed therapy in septic shock, magnesium use for neuroprotection in acute stroke, and progesterone use in patients with traumatic brain injury. Conclusion. Important recent additions to the critical care pharmacy literature include updated joint clinical practice guidelines on the management of spontaneous ICH, ACLS, and SVT.