Search

Introduction: Opioid utilization has increased fourfold over the past two decades among developed countries. Previous studies have found that opioid-related adverse drug events (ORADEs) are strongly associated with adverse clinical outcomes in hospitalized patients. The Society of Hospital Medicine in the United States recently published a Consensus Statement regarding opioid safety and suggested that extra caution is needed when using opioids in patients with risk factors for ORADEs. This systematic review aimed to summarize common patient risk factors for ORADEs in hospitalized patients., Methods: Five databases were searched including Medline, Embase, Cochrane Central Register of Controlled Trials, International Pharmaceutical Abstracts, and Scopus. Search themes include opioids, adverse drug events, and acute care settings. Original full-text studies that were published and identified patient risk factors for ORADEs in hospitalized patients were included., Results: A total of 16 observational studies were included, with only two studies considered as poor quality. Seven studies focused on severe ORADEs including over-sedation and respiratory depression. Common patient risk factors for severe ORADEs included comorbidities (eg, sleep apnea and renal diseases), concurrent use of sedatives, and prior opioid exposure. Nine studies focused on a combination of general ORADEs and common patient risk factors included advanced age, male gender, comorbidities (eg, chronic obstructive pulmonary disease and neurologic disorders), concurrent use of sedating medications, and prior opioid exposure., Conclusions: Successful identification of patient risk factors for ORADEs summarized by this systematic review could benefit clinicians when deciding on the appropriateness of opioid therapy in hospital patients. Future studies could focus on developing a validated risk assessment tool based on these risk factors., (© 2022 Pharmacotherapy Publications, Inc.)

Objectives: To conduct a cost analysis of adjunctive hydrocortisone therapy for severe septic shock from the perspective of a third-party payer in the United States., Design: Estimates of outcomes were aggregate data from the Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock and Activated Protein C and Corticosteroids for Human Septic Shock trials. In these trials, the outcomes of interests were ICU length of stay, vasopressor-free days, ventilation-free days, and the proportion of patients receiving blood transfusion. Each outcome was monetized into a set of mutually exclusive components and was aggregated to estimate the cost-per-patient based on each trial. Cost inputs for each outcome were obtained from literature and adjusted based on the medical care consumer price index. To estimate the budget impact using adjunctive hydrocortisone therapy, per-patient avoided cost was multiplied by expected septic shock annual incidence. Deterministic one-way sensitivity analysis evaluated the robustness of the findings, and Monte Carlo simulation estimated 95% CI of the findings., Setting: A total of 103 medical-surgical ICU (69 for Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock and 34 for Activated Protein C and Corticosteroids for Human Septic Shock)., Patients: Adults greater than or equal to 18 years old with septic shock., Interventions: Adjunctive hydrocortisone therapy (hydrocortisone at a dose of 200 mg/d for 7 d for Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock and hydrocortisone at a 50 mg IV bolus every 6 hr and fludrocortisone as a 50 μg tablet once daily)., Measurements and Main Results: Per Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock, adjunctive hydrocortisone therapy showed a 90-day monetized benefit of $8,111 (95% CI, $3,914-$12,307) per patient, driven by improvements in ICU-free days, vasopressor-free days, ventilation-free days, and blood transfusion proportion. The total estimated annual impact of adjunctive hydrocortisone therapy, in 2019 dollars, was $750 million. Per Activated Protein C and Corticosteroids for Human Septic Shock, adjunctive hydrocortisone therapy showed a 90-day monetized benefit of $25,539 per patient (95% CI, $22,853-$28,224), driven by improvements in ICU free-days, vasopressor-free days, and ventilation-free days. The total estimated annual impact of adjunctive hydrocortisone therapy, in 2019 dollars, was $2.3 billion. The deterministic one-way sensitivity analysis showed the cost of ICU stays to be the most influential factor in both analyses. The sensitivity analysis using the reported median showed a greater monetized benefit of $10,658 (Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock) and $30,911 (Activated Protein C and Corticosteroids for Human Septic Shock) per patient., Conclusions: Using adjunctive hydrocortisone therapy yields a significant monetized benefit based on inputs from the Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock and Activated Protein C and Corticosteroids for Human Septic Shock trials.

Objectives: The objective of this study was to compare emergency department (ED) length of stay (LOS) between patients treated with opioid analgesia versus non-opioid analgesia for low back pain (LBP) in the ED., Methods: We conducted a secondary analysis of National Hospital Ambulatory Medical Care Survey (NHAMCS) data (2014-2015). Adults (age ≥18 years) who presented to the ED with a reason for visit or primary diagnosis of LBP were included in the final study sample. Patient visits were categorized into two groups based on whether they received opioid analgesia (with or without non-opioid analgesia) or non-opioid analgesia only in the ED. The primary outcome measure was ED LOS, which was log-transformed (as ED LOS was not normally distributed) for analysis. A multivariable linear regression analysis was used to evaluate the association between opioid use and ED LOS., Results: The study sample consisted of a national estimate of approximately 8.6 million ED visits for LBP (during 2014-2015), of which 60.1% received opioids and 39.9% received non-opioids only. The geometric mean ED LOS for patient visits who received opioids was longer than patient visits who received non-opioids (142 versus 92 min, respectively; p < 0.001). After adjusting for confounders in the multivariable analysis, patient visits that received opioids had a significantly longer ED LOS (coefficient 0.25; 95% CI 0.11 to 0.38; p < 0.001)., Conclusions: In a nationally representative sample of patient visits to ED due to LBP in the US, use of opioids in the ED was associated with an increased ED LOS., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: At this time, there are no studies evaluating the risk of delirium or coma with the use of ketamine in mechanically ventilated adult patients, compared to conventional therapies such as propofol or dexmedetomidine., Objective: The objective of this study was to evaluate the number of days alive without delirium or coma in mechanically ventilated patients in the intensive care unit receiving analgosedation infusions with ketamine versus without ketamine., Methods: This was a retrospective cohort study conducted at an academic medical center in the United States. Consecutive mechanically ventilated adult patients between November 2015 and April 2017 were evaluated. Patients were divided into 2 groups based on the sedative regimen used: ketamine based or nonketamine based. The primary outcome was the number of days alive without delirium or coma. The secondary outcomes were incidence of delirium, incidence of coma, and ventilator-free days at day 28., Results: The study cohort consisted of 79 patients, of which 39 received ketamine- and 40 received nonketamine-based sedation. The number of days alive without delirium or coma was 6 days (interquartile range [IQR]: 2-9 days) with ketamine and 4 days (IQR: 3-7 days) with nonketamine ( P = .351). Delirium occurred in 29 (74%) of 39 patients with ketamine and 34 (85%) of 40 patients with nonketamine ( P = .274). Coma occurred in 16 (41%) of 39 patients with ketamine and 6 (15%) of 40 patients with nonketamine ( P = .013). The median ventilator-free days were 13 days (IQR: 0-23 days) with ketamine and 21 days (0-25 days) with nonketamine ( P = .229)., Conclusions: Sustained ketamine-based sedation in mechanically ventilated patients may be associated with a higher rate of observed coma but similar delirium- and coma-free days compared nonketamine-based regimens.

Objective: To quantify the extent and identify predictors of potentially inappropriate antidepressant use among older adults with dementia and newly diagnosed major depressive disorders (MDD)., Methods: This retrospective cohort study included older adults (aged ≥65 years) with dementia and newly diagnosed MDD using Medicare 5% sample claims data (2012-2013). Based on Healthcare Effectiveness Data and Information Set guidelines, intake period for new antidepressant medication use was from May 1, 2012, through April 30, 2013. Index prescription start date was the first date of antidepressant prescription claim during the intake period. Dependent variable of this study was potentially inappropriate antidepressant use as defined by the Beers Criteria and the Screening Tool of Older Persons' potentially inappropriate Prescriptions criteria. The authors conducted multiple logistic regression analysis to identify individual-level predictors of potentially inappropriate antidepressant use., Results: The authors' final study sample consisted of 7,625 older adults with dementia and newly diagnosed MDD, among which 7.59% (N = 579) initiated treatment with a potentially inappropriate antidepressant. Paroxetine (N = 394) was the most commonly initiated potentially inappropriate antidepressant followed by amitriptyline (N = 104), nortriptyline (N = 35), and doxepin (N = 32). Initiation of a potentially inappropriate antidepressant was associated with age and baseline use of anxiolytic medications., Conclusion: More than 7% of older adults in the study sample initiated a potentially inappropriate antidepressant, and the authors identified a few individual-level factors significantly associated with it. Appropriately tailored interventions to address modifiable and nonmodifiable factors significantly associated with potentially inappropriate antidepressant prescribing are required to minimize risks in this vulnerable population., (Copyright © 2019 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objectives: Antimicrobial agents are commonly used in ambulatory care settings. Our objective was to examine national-level patterns of contraindications between oral antibacterial or antifungal agents and patients' other oral medications in the US ambulatory care setting., Methods: This cross-sectional study included multiple year pooled data (2003-2011) from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey (NHAMCS Outpatient Department). Visits by adults (age ≥18 years) in ambulatory settings in the United States who were prescribed oral antibacterial or antifungal agents were evaluated for potential drug-drug interaction (DDI) contraindications. Findings with relative standard error >30% or unweighted sample size <30 were not reported because these were deemed unreliable estimates., Results: From 2003 to 2011, there were 1 235 000 outpatient visits (proportion = 0.52%; 95% confidence interval (CI), 0.29-0.74) in which a patient was prescribed an antimicrobial agent associated with a contraindicated DDI. The most prevalent antimicrobials with contraindicated combination among outpatients were simultaneous use of macrolide-containing products (erythromycin or clarithromycin) with statin medication-containing products (simvastatin or lovastatin) (841 864 visits, proportion = 1.91%; 95% CI, 0.96-2.86). The next most common combination was use of fluoroquinolones with antiarrhythmic agents (amiodarone, sotalol, quinidine or procainamide) (365 622 visits, proportion = 0.19%; 95% CI, 0.06-0.32)., Conclusions: Providers should be aware of potential contraindicated DDIs when prescribing antibiotics, especially macrolides and fluoroquinolones., (Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. All rights reserved.)

Context: The administration of Crotalidae polyvalent immune Fab (FabAV) currently requires close observation, so patients can be monitored for hypersensitivity reactions. The objective of this study was to evaluate the occurrence of hypersensitivity reactions to FabAV., Method: This was a retrospective cohort study utilizing data from a statewide poison center database in the United States. Records of all patients envenomated by a rattlesnake and treated with FabAV between January 2002 and December 2014 were evaluated. Patients with acute hypersensitivity reactions were identified, and reactions were evaluated descriptively., Results: A total of 1340 adult and pediatric patients received FabAV during the study period. Of these, 19 (1.4%) patients had a potential reaction to FabAV, with 10 requiring a reduction in infusion rate, but none requiring discontinuation of the antivenom. Reactions occurred during the loading dose (n = 10), maintenance doses (n = 4), or were delayed reactions (n = 6). Symptoms recorded included pruritus (n = 8), hives (n = 8), rash (n = 7), vomiting (n = 7), nausea (n = 6), dyspnea or wheezing (n = 4), diaphoresis (n = 3), throat irritation (n = 2), and mild hypotension (n = 2). One patient was given a concomitant administration of low dose epinephrine infusion until completion of the antivenom course. However, none of the reactions were considered to be life-threatening., Conclusion: FabAV appears to be associated with a low incidence of acute hypersensitivity reactions. Patients may not require placement in a location capable of detecting and rapidly responding to hemodynamic and/or airway issues for FabAV monitoring alone.

Objectives: The use of etomidate and rocuronium for rapid sequence intubation (RSI) results in a duration of paralysis that exceeds the duration of sedation. The primary objective of this study was to compare the number of analgosedative (AGS) interventions early versus late post-RSI, with this drug combination. The secondary objective was to descriptively assess time to first AGS intervention., Methods: This was a retrospective cohort study conducted in an academic ED in the United States between January 2015 and June 2016. The study was conducted after a pharmacy-led education program. Consecutive adult patients who received the combination of etomidate and rocuronium for RSI were included. The primary outcome measure was the number of AGS interventions post-RSI. An AGS intervention was defined as initiation of an opioid or sedative, or a dose increase of an infusion rate. Interventions were categorized as early (0-30min post-RSI) or late (60-90min post-RSI)., Results: The sample (n=108) had a mean age of 58±19years, and the majority was male (n=62, 57%). The mean rocuronium dose was 1.1±0.3mg/kg. There was a median of 2 interventions (IQR 1-3) that occurred early versus 0 interventions (IQR 0 to 1) that occurred late post-RSI (p<0.001). The median time to first AGS intervention was 7min (IQR 3 to 13min)., Conclusions: When rocuronium was used for RSI in the ED there was no delay in provision of post-intubation sedation or analgesia, after a pharmacy-led educational program., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The transition of patients from the intensive care unit (ICU) to the ward is a complicated process and patients may be at risk of increased levels of pain., Objectives: The primary objective was to identify predictors of pain during the transition from the surgical ICU to the surgical ward. The secondary objective was to describe the patient pain experience during this transition., Methods: This was a cross-sectional study conducted at an academic medical centre in the United States. Patients who were discharged from the ICU were interviewed regarding their pain during transition from ICU to the ward using the Revised American Pain Society Patient Outcome Questionnaire (APS-POQ-R). The primary outcome measures were the total score of this validated instrument (0-180 points) and score of the pain severity and sleep interference subscale (0-50 points). Predictors of pain control during this 24-h transition period were identified using linear regression analysis., Results: A total of 50 patients were included. After transition from the ICU, the median score on the APS-POQ-R was 45 (Q1 29 to Q3 74), and the median score on the pain severity and sleep interference subscale was 23 (Q1 15 to Q3 30). After adjusting for sex in a multivariate model, mean pain score in the preceding 24 h of ICU stay explained 31% of the variation in total APS-POQ-R score and 39% of variation in the pain severity and sleep interference subscale. Age, sex, race, type of surgery, number of surgeries, and opioid dose in the 24-h period before transfer were not significantly associated with either outcome measure. The worst pain experienced by patients during transfer was severe (i.e. score ≥7 on 0 to 10 scale) in 90% (n = 45) of patients. For 70% (n = 35) of patients, severe pain persisted for more than 50% of the time during the transition period., Conclusion: Pain scores in the last 24 h of ICU stay is a predictor of total APS-POQ-R score and pain severity and sleep interference subscale score., (Copyright © 2018 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Patients who present to the emergency department (ED) with mild skin and soft tissue infections (SSTIs) are often given a single dose of an antibiotic before being discharged home on oral antibiotics. The objective of this study was to determine if administration of antibiotics in the ED increases length of stay., Methods: This was cross-sectional study using data from the National Hospital Ambulatory Medical Care Survey. Patients with SSTIs who were discharged home with antibiotics were included. Patients were categorized into 2 groups based on whether any antibiotics were administered in the ED. The ED length of stay was compared between the groups. A multivariate analysis was conducted to adjust for pertinent confounders., Results: There were 3000895 cases of patients with SSTIs who presented to the ED and directly discharged home on antibiotic therapy from 2008 to 2010. Of these, 46.8% (n = 1403710) involved the administration of an antibiotic in the ED, whereas the others only received antibiotic prescriptions upon discharge. The mean ED length of stay was 83.8 ± 160.6 minutes with no antibiotics vs 112.2 ± 193.6 minutes for antibiotic use in the ED (P < .05). After adjusting for confounders, there was a 43% increase in ED length of stay associated with administration of first dose of antibiotics in the ED (exp[b] = 1.43; 95% confidence interval, 1.19-1.70; P < .001)., Conclusion: The administration of an antibiotic in the ED before discharge is associated with an increased ED length of stay in patients with SSTIs., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: The primary objective of this study was to compare the analgesic response to morphine in non-obese, obese and morbidly obese patients for acute pain., Methods: This was a retrospective cohort study conducted in a tertiary care emergency department in the USA. Consecutive adults who received intravenous morphine 4 mg for pain were included. Patients were categorised into three groups based on body mass index (BMI): non-obese (18.5-29.9 kg/m(2)); obese (30.0-39.9 kg/m(2)); and morbidly obese (≥40 kg/m(2)). Baseline and post-dose pain scores were recorded. Pain was measured on a 0-10 numerical rating scale (0=no pain; 10=worst possible pain). Analgesic response was defined as the difference between the initial pain score and post-dose pain score., Results: 300 patients were included in the study (100 in each group). The median baseline pain scores were 8.5, 8 and 8.5 in the non-obese, obese and morbidly obese groups, respectively (p=0.464). The median analgesic response after morphine administration was 2, 3 and 2 in the non-obese, obese and morbidly obese groups, respectively (p=0.160). In the linear regression analysis (R(2)=0.006), BMI was not predictive of analgesic response (coefficient -0.020; p=0.199)., Conclusions: Obesity status did not influence analgesic response to a fixed dose of morphine. This suggests that obese and morbidly obese patients do not require a higher dose of morphine for acute pain reduction compared to non-obese patients.

Objective: The objective of this study was to determine if patients who weigh ≥100 kg are more likely to receive under-dosing of etomidate compared to those who weigh <100 kg for rapid sequence intubation in the emergency department (ED)., Methods: This was a retrospective cohort study conducted in an academic ED in the United States. Adult patients who received etomidate for rapid sequence intubation were evaluated and categorized into two groups based on weight: 1) <100 kg or 2) ≥100 kg. The mean dose of etomidate (mg/kg) was compared between the groups using an unpaired Student's t-test. The percentage of patients who received under-dosing (less than 0.2 mg/kg) was compared between groups using the Chi-squared test., Results: A total of 200 patients were included in the final analyses (100 patients in the <100 kg group and 100 patients in the ≥100 kg group). There were no baseline differences in age, sex, paralytic used, or trauma status between the treatment groups. The mean etomidate dose (mg/kg ± standard deviation) was significantly lower in the ≥100 kg group compared to the <100 kg group (0.18 ± 0.03 vs. 0.28 ± 0.07, respectively; p<0.001). There were significantly more patients in the ≥100 kg group who received under-dosing of etomidate compared to the <100 kg group (68% vs. 2%, respectively; p<0.001)., Conclusions: Patients who weigh ≥100 kg are more likely to receive under-dosing of etomidate compared to those who weigh <100 kg for rapid sequence intubation in the ED.

Background: The purpose of this study was to evaluate the effect of epidural analgesia use on postoperative complications in patients undergoing pancreaticoduodenectomy., Methods: This retrospective cohort study used the 2009 Nationwide Inpatient Sample from the Agency for Healthcare Research and Quality. Patients who underwent pancreaticoduodenectomy were grouped on the basis of whether they received epidural analgesia. The effect of epidural use on the composite end point of major complications including death was investigated using a generalized linear model., Results: Overall, 8,610 cases of pancreaticoduodenectomy occurred within the United States in 2009, and 11.0% of these patients received epidural analgesia. After controlling for various potential confounders, results of the multivariate regression indicated that epidural analgesia use was associated with lower odds of composite complications including death (odds ratio, .61; 95% confidence interval, .37-.99; P = .044)., Conclusions: In patients who underwent pancreaticoduodenectomy, epidural analgesia was associated with significantly lower postoperative composite complications., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Study Objective: The primary objective of this study is to determine the activities of pharmacists that lead to medication error interception in the emergency department (ED)., Methods: This was a prospective, multicenter cohort study conducted in 4 geographically diverse academic and community EDs in the United States. Each site had clinical pharmacy services. Pharmacists at each site recorded their medication error interceptions for 250 hours of cumulative time when present in the ED (1,000 hours total for all 4 sites). Items recorded included the activities of the pharmacist that led to medication error interception, type of orders, phase of medication use process, and type of error. Independent evaluators reviewed all medication errors. Descriptive analyses were performed for all variables., Results: A total of 16,446 patients presented to the EDs during the study, resulting in 364 confirmed medication error interceptions by pharmacists. The pharmacists' activities that led to medication error interception were as follows: involvement in consultative activities (n=187; 51.4%), review of medication orders (n=127; 34.9%), and other (n=50; 13.7%). The types of orders resulting in medication error interceptions were written or computerized orders (n=198; 54.4%), verbal orders (n=119; 32.7%), and other (n=47; 12.9%). Most medication error interceptions occurred during the prescribing phase of the medication use process (n=300; 82.4%) and the most common type of error was wrong dose (n=161; 44.2%)., Conclusion: Pharmacists' review of written or computerized medication orders accounts for only a third of medication error interceptions. Most medication error interceptions occur during consultative activities., (Copyright © 2011. Published by Mosby, Inc.)