Front-loaded diazepam versus lorazepam for treatment of alcohol withdrawal agitated delirium.

BACKGROUND: Front-loaded diazepam is used to rapidly control agitation in patients with severe alcohol withdrawal syndrome (AWS). Our institution began using front-loaded lorazepam in August 2017 secondary to a nation-wide shortage of intravenous (IV) diazepam. Currently, there are no studies comparing lorazepam to diazepam for frontloading in severe AWS. METHOD: Retrospective cohort study of all adults presenting to the emergency department with a diagnosis of AWS and prescribed the institution's alcohol withdrawal agitated delirium protocol 8 months pre and post shortage of IV diazepam were eligible inclusion for the study. Of these, 106 patients were front-loaded with diazepam and 70 patients were front-loaded with lorazepam. RESULTS: There was no difference in the mean change in Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised scores 24 h pre and post front-loading in the two groups (-13.9 ± -8.08 vs. -13.1 ± -8.91, p = 0.534). Patients who received front-loaded lorazepam had an increased incidence of ICU-delirium (positive for the Confusion Assessment Method in the ICU: 75% with lorazepam vs. 52.6% with diazepam, p = 0.009) and a higher risk of over-sedation, but this did not reach statistical significance (Richmond Agitation-Sedation Scale score < -1: 32.1% with lorazepam vs. 18.2% with diazepam, p = 0.063). CONCLUSION: Front-loaded lorazepam was similar to front-loaded diazepam in controlling AWS symptoms. Lorazepam's delayed onset of action should be considered when determining how quickly repeat doses are administered to avoid the potential for adverse drug events.

Phenobarbital for Acute Alcohol Withdrawal Management in Surgical Trauma Patients-A Retrospective Comparison Study.

BACKGROUND: Alcohol withdrawal syndrome (AWS) in surgical trauma patients is associated with significant morbidity and mortality. Benzodiazepines, commonly used for withdrawal management, pose unique challenges in this population given the high prevalence of head trauma and delirium. Phenobarbital is an antiepileptic drug that offers a viable alternative to benzodiazepines for AWS treatment. METHODS: This is a retrospective chart review of patients with active alcohol use disorder who presented to a level 1 trauma center over a 4-year period and required medication-assisted management for AWS. The primary outcome variable examined was the development of AWS and associated complications. Additional outcomes measured included hospital length of stay, mortality, and medication-related adverse events. RESULTS: Of the 85 patients in the study sample, 52 received a fixed-dose benzodiazepine-based protocol and 33 received phenobarbital-based protocol. In the benzodiazepine-based protocol group, 25 patients (48.2%) developed AWD and 38 (73.1%) developed uncomplicated AWS, as compared to 0 patients in the phenobarbital-based protocol (P = 0.0001). There were 10 (19.2%) patients with medication adverse side effects in the benzodiazepine-based protocol group versus 0 patients in the phenobarbital-based protocol group. There were no statically significant differences between the 2 groups as pertains to rates of other AWS-related complications, patient mortality, or length of stay. CONCLUSION: The use of a phenobarbital-based protocol in trauma patients with underlying active alcohol use disorder resulted in a statistically significant decrease in the incidence of AWD and uncomplicated AWS secondary to AWS when compared to patients treated with a fixed-dose benzodiazepine-based protocol.

High-Dose Gabapentin for the Treatment of Severe Alcohol Withdrawal Syndrome: A Retrospective Cohort Analysis.

STUDY OBJECTIVE: Gabapentin has been proved to be beneficial in promoting abstinence, decreasing alcohol cravings, and improving mood and sleep quality when given at higher doses; however, data are limited regarding the efficacy and safety of using high-dose gabapentin as part of the treatment of alcohol withdrawal syndrome (AWS). The aim of this study was to evaluate the impact of high-dose gabapentin on benzodiazepine requirements, alcohol withdrawal symptoms, and hospital length of stay in patients hospitalized with AWS. DESIGN: Retrospective cohort study. SETTING: Large academic medical center. PATIENTS: All adults presenting to the emergency department between January 2015 and April 2018 with a diagnosis of severe AWS (Clinical Institute Withdrawal Assessment for Alcohol Scale, Revised [CIWA-Ar] score ≥ 15) and prescribed the institution's alcohol withdrawal agitated delirium protocol were eligible for inclusion in the study. Of these, 50 patients who received high-dose gabapentin (≥ 1800 mg/day) in the first 48 hours of hospital admission (treatment group) were propensity score-matched to 50 patients who did not receive gabapentin (control group). MEASUREMENTS AND MAIN RESULTS: Patients who received high-dose gabapentin required a significantly lower overall amount of benzodiazepines (mean ± SD 109.5 ± 53.4 mg vs 88.5 ± 35.6 mg [lorazepam equivalents], p=0.023) and had a significantly lower mean CIWA-Ar score (10.1 ± 4.7 vs 7.7 ± 3.9, p=0.010) and maximum CIWA-Ar score (16.0 ± 7.0 vs 12.6 ± 6.1, p=0.016) on day 3 of hospitalization. The high-dose gabapentin regimen was well tolerated, without an increased risk of oversedation, compared with the control group (Richmond Agitation-Sedation Scale score < -1: 34% in the treatment group vs 20% in the control group, p=0.115). Patients receiving high-dose gabapentin had a shorter length of hospital stay (7.4 ± 4.0 days vs 6.0 ± 2.6 days, p=0.034) and increased likelihood of being discharged home (66% vs 88%, p=0.009) compared with the control group. CONCLUSION: Early initiation of high-dose gabapentin was associated with a significant reduction in benzodiazepine exposure, faster stabilization of alcohol withdrawal-related symptoms, and shorter hospital length of stay. Future studies evaluating gabapentin's effect on long-term safety and hospital readmission are warranted.

Antibiotic use and duration in association with Clostridioides difficile infection in a tertiary academic medical center: A retrospective case-control study.

Previous literature has attributed the use of certain antibiotics to Clostridioides difficile infection (CDI); however, the time from administration to CDI onset is not adequately evaluated. We aimed to determine the type of antibiotics and duration of therapy associated with the highest CDI incidence at a tertiary academic medical center. This was a retrospective, case-control study of adult inpatients who received at least one course of antibiotic treatment. Patients were divided into either cases or controls. For cases, their first episode of CDI was a determining factor. Primary outcome were the types of antibiotics associated with risk of CDI development and the median time of antibiotic usage defining this risk. Of 601 patients who developed CDI, 313 were included as cases while 150 of 291 who received antibiotics but did not develop CDI were included as controls. Cefepime and cefazolin were significantly associated with increased risk for CDI with odds ratios of 3.01 (95% CI, 1.96-4.65; P < 0.001) and 1.71 (95% CI, 1.02-2.95; P < 0.05), respectively. Cefepime was associated with CDI after a median time of 8 days while CDI may have occurred after 6 days of therapy with cefazolin. Use of antineoplastic agents was significantly associated with CDI (odds ratio, 2.32; 95% CI, 1.35-4.13; P < 0.01). Antibiotic use increased the risk of CDI, particularly with cefepime and cefazolin with a median time to incidence of 8 and 6 days, respectively. CDI risk was also increased with the use of antineoplastic agents.

Low-dose corticosteroids in septic shock: Has the pendulum shifted?

PURPOSE: The utility of low-dose corticosteroids in septic shock is reviewed. SUMMARY: Low-dose corticosteroids are suggested as treatment for septic shock patients who remain hemodynamically unstable despite adequate fluid resuscitation and vasopressor therapy. However, the risks and benefits of corticosteroids are unclear in this patient population. Previous multicenter trials have yielded conflicting results on the survival benefits of corticosteroids. The recently published Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock (ADRENAL) and Activated Protein C and Corticosteroids for Human Septic Shock (APROCCHSS) trials provide valuable but opposing insight into this ongoing debate. Discordant findings related to mortality in these trials are likely related to differences in study design, corticosteroid regimen, and baseline characteristics among enrolled patients. The utility of adding fludrocortisone to hydrocortisone compared with using hydrocortisone alone is unclear. There does not appear to be an advantage to administering corticosteroids as a continuous infusion to reduce the rate of hyperglycemia or providing a taper to prevent rebound hypotension. CONCLUSION: The mortality benefit of corticosteroids appears to be greatest in septic shock patients with high vasopressor requirements, evidence of multiorgan failure, and primary lung infections. Corticosteroids consistently lead to a faster reversal of shock and may shorten the duration of mechanical ventilation. Corticosteroids do not seem to increase the risk of superinfection at low doses but frequently lead to a higher frequency of hyperglycemia. We recommend the administration of corticosteroids to septic shock patients with escalating doses of vasopressors and evidence of multiorgan dysfunction.

Utility of initial procalcitonin values to predict urinary tract infection.

BACKGROUND: Urinary tract infections (UTIs) are one of the most common reasons women seek treatment in the emergency department (ED). The biomarker procalcitonin (PCT) has gained popularity over the last decade to improve the diagnosis of bacterial infections and reduce unnecessary exposure to antibiotics. PCT has been extensively studied in patients with pneumonia and sepsis and may have additional role in UTI. METHODS: A retrospective study of patients who presented to the ED in which a urinalysis test and a PCT level was obtained within the first 24h of presentation. Signs and symptoms of UTI and urine cultures were reviewed to determine a positive diagnosis of UTI. The area under the receiver operating curve was used to calculate the test characteristics of PCT. Different breakpoints were analyzed to determine which PCT level corresponded to the highest sensitivity and specificity. RESULTS: 293 patients were included in this single center, retrospective study. The AUC of PCT to predict UTI was 0.717; 95% CI: 0.643-0.791 (p<0.001). A PCT threshold of 0.25ng/ml corresponded to the best combination of sensitivity (67%) and specificity (63%), with a positive predictive value and negative predictive value of 26% and 91%, respectively. CONCLUSIONS: A PCT threshold <0.25ng/ml was a strong predictor of the absence of UTI. The high negative predictive value of PCT may be useful as an adjunct to urinalysis results to rule out UTI and facilitate noninitiation or earlier discontinuation of empiric antibiotics.

A Collaborative Approach to Improve Consistent Use of Procalcitonin in Lower Respiratory Tract Infections.

BACKGROUND: Procalcitonin (PCT) is a biomarker that can help differentiate bacterial from viral infections and has been extensively studied in patients with sepsis and pneumonia to guide antibiotic therapy. However, there is poor adherence to prescribed algorithms when used to discontinue antibiotics in the real world. A quality improvement project was implemented to increase consistent use of PCT. OBJECTIVE: To evaluate use of PCT and impact on antibiotic length of therapy (LOT) preimplementation and postimplementation of a quality improvement initiative. METHODS: This was a single-center retrospective cohort study in patients with lower respiratory tract infections (LRTIs). RESULTS: In all, 330 patients were included in this study. Following implementation of the quality improvement initiative, ordering PCT in the first 24 hours increased from 59.6% to 75.5% ( P = 0.011). Documentation to discontinue antibiotics in patients with low initial PCT values increased from 13.2% to 28.6% ( P = 0.100). Increased PCT use correlated with an overall mean reduction of 1.05 antibiotic days between cohorts (6.82 ± 3.88 vs 5.77 ± 3.43, P = 0.028). There was no difference in incidence of antibiotic-associated adverse effects or 30-day hospital readmission rates attributed to pneumonia. CONCLUSIONS: Consistent use of PCT was achieved through a collaborative effort with the clinical pharmacy and hospitalist staff. Increased use of PCT was associated with a significant reduction in antibiotic LOT among patients with LRTIs. When controlling for other factors, low initial PCT values had the strongest influence on discontinuing antibiotics within 72 hours in the intervention group.

Impact of a Multidisciplinary Bundle on Time to Antibiotic Administration in Septic SICU Patients.

PURPOSE: The goal of this study was to investigate barriers to timely antibiotic administration in septic surgical intensive care unit (SICU) patients and examine the impact of a multidisciplinary bundle on the time from prescription to antibiotic administration. METHODS: This was a pre- and postintervention study that consisted of 3 phases: (1) preintervention phase, retrospective evaluation of data, (2) intervention implementation, and (3) a postintervention phase. A nurse survey was conducted to identify barriers to rapid antibiotic administration during phase 1. Based on this survey, multidisciplinary interventions included adding antibiotics to the automatic dispensing cabinet, educating monthly staff, and providing an antibiotic dosing table to all prescribers, which is attached to the computer workstations. Our multidisciplinary team consisted of the ICU medical directors, nurse managers, nurses, a critical care fellow, and ICU pharmacists. RESULTS: The percentage of antibiotics that were received within 60 minutes was 26.3% in the pregroup versus 84.0% in the postgroup ( P < .001). The mean total prescriber to patient time was 110 minutes in the pregroup versus 58.4 minutes in the postgroup ( P < .001). CONCLUSION: We achieved a higher rate of timely antibiotic administration among septic SICU patients by implementing process changes based on barriers identified by the nurses.

Daily vancomycin dose requirements as a continuous infusion in obese versus non-obese SICU patients.

BACKGROUND: Limited data are available assessing vancomycin concentrations in obese critically ill patients. Currently, there are no studies evaluating dosing requirements in this population who receive vancomycin administered as a continuous infusion (CI). The aim of this study was to assess whether there was a difference in the weight-based maintenance dose required to reach a therapeutic vancomycin concentration at 24 hours when given as a CI in obese versus non-obese critically ill patients. METHODS: A retrospective cohort study of adult obese patients admitted to the SICU between 2013 and 2015 receiving a vancomycin CI (CIV), and with 24-hour serum measurements were included. Obese patients (body mass index (BMI) ≥35 kg/m(2)) were matched with non-obese patients (BMI <30 kg/m(2)) based on renal function, age and acute physiology and chronic health evaluation (APACHE)-II score at admission. All patients in this study received a loading dose of 25 mg/kg then a maintenance dose based on renal function according to the protocol. The study was approved by the Institutional Review Board. The primary outcome was the weight-based total daily maintenance dose required to achieve a vancomycin level of 20 mg/L. The secondary endpoints included the achievement of a therapeutic level at 24 hours. RESULTS: Twenty-six matched pairs of patients met the inclusion criteria. Of these, 17 pairs had preserved renal function and 9 pairs required continuous venovenous hemofiltration. Mean BMI was 40.9 kg/m(2) in obese and 24.8 kg/m(2) in non-obese patients. To achieve a vancomycin concentration of 20 mg/L, the weight-based daily maintenance dose in obese patients was 25.6 mg/kg versus 43.8 mg/kg in non-obese patients (p <0.01). Therapeutic 24-hour levels were achieved in 24/26 obese versus 23/26 no-obese patients (p = 0.63). Mean 24-hour vancomycin level was 20.3 ± 3.81 mcg/ml in obese compared to 20.03 ± 3.79 mcg/ml in non-obese patients (p = 0.77). Mean daily maintenance doses required to achieve a level of 20 mcg/ml were 2961 ± 1670 mg in obese compared to 3189 ± 1600.69 mg in non-obese (p = 0.61). CONCLUSIONS: The results of our study suggest that critically ill obese patients treated with CIV required a significantly lower maintenance dose per unit of body weight than non-obese patients to achieve the same target level.

Noise Levels in Surgical ICUs Are Consistently Above Recommended Standards.

OBJECTIVE: The equipment, monitor alarms, and acuity of patients in ICUs make it one of the loudest patient care areas in a hospital. Increased sound levels may contribute to worsened outcomes in these particularly vulnerable patients. Our objective was to determine whether ambient sound levels in surgical ICUs comply with recommendations established by the World Health Organization and Environmental Protection Agency, and whether implementation of an overnight "quiet time" intervention is associated with lower ambient sound levels. DESIGN: Prospective, observational cohort study. SETTING: Two comparable 18-bed, surgical ICUs in a large, teaching hospital. Only one ICU had a formal overnight quiet time policy at the start of the study period. MEASUREMENTS AND MAIN RESULTS: Sound levels were measured in 30-second blocks at preselected locations during the day and night over a period of 6 weeks using a simple, hand-held sound meter. All sound measurements in both units at all times exceeded recommended standards. Median minimum sound levels were lower at night in both units (50.8 and 50.3 vs 53.1 and 51.0 dB, p = 0.0003 and p = 0.009) and were similar between the two units (p = 0.52). The maximum overnight sound levels were statistically lower in the unit with the quiet time intervention implemented (62.5 vs 59.6 dB; p = 0.0040) and decreased overnight immediately after implementation of quiet time in the other unit (62.5 vs 56.1 dB; p < 0.0001). Maximum sound levels were lower inside patient rooms (52.2 vs 55.3 dB; p = 0.004), but minimum sound levels were similar (49.1 vs 49.2 dB; p = 0.23). Linear regression analysis showed that ICU census did not significantly influence sound levels. CONCLUSIONS: Ambient sound levels in the surgical ICUs were consistently above levels recommended by the World Health Organization and Environmental Protection Agency at all times. The use of a formal quiet time intervention was associated with a significant, but clinically irrelevant reduction in the median maximum sound level at night. Our results suggest that excessive ambient noise in the ICU is largely attributable to environmental factors, and behavior modifications are unlikely to have a meaningful impact. Future investigations, as well as hospital designs, should target interventions toward ubiquitous noise sources such as ventilation systems, which may not traditionally be associated with patient care.

Weight based heparin dosing for thromboembolic disease is associated with earlier anticoagulation in surgical patients.

INTRODUCTION: Achievement of early therapeutic anticoagulation with unfractionated heparin (UFH) is associated with improved outcomes in thromboembolic disease. Weight based UFH expedites time to therapeutic anticoagulation. Treatment with UFH is challenging in surgical patients due to their high propensity for bleeding. We sought to test the hypothesis that an initial weight based UFH infusion in surgical patients increases the percentage of patients who achieve early therapeutic anticoagulation without increasing the risk of hemorrhagic events. METHODS: Using a non-concurrent retrospective cohort study design, adult surgical patients receiving UFH for venous thromboembolism (VTE) at a tertiary care center were included. Two groups were identified: the weight based (WB) and the under-dosed (UD) heparin groups. For our primary outcome, we compared percentage of patients in each group that achieved a therapeutic PTT within 24 h. Secondary outcomes included the incidence of supratherapeutic PTT levels, hemorrhagic events, and complications associated with VTE. RESULTS: 73 subjects met study criteria, which included 8 subjects in the WB group and 65 in the UD group. The demographic, baseline laboratory, admitting service and type of VTE were similar between the 2 groups. The percentages of WB and UD subjects who achieved a therapeutic PTT within 24 h were 75% and 28%, respectively (p < 0.01). There was no difference in the incidence of supratherapeutic PTT or hemorrhagic events. CONCLUSION: Surgical patients who received an initial weight based UFH infusion achieved earlier therapeutic anticoagulation compared to under-dosed UFH without increasing the occurrence of supratherapeutic PTT levels or hemorrhagic events.

Oral midodrine treatment accelerates the liberation of intensive care unit patients from intravenous vasopressor infusions.

PURPOSE: Persistent low-level hypotension represents a barrier to discharging patients from the intensive care unit (ICU). Midodrine may be an effective adjunct to wean intravenous (IV) vasopressors and permit ICU discharge. We tested the hypothesis that midodrine, given to patients on IV vasopressors who otherwise met ICU discharge criteria, increased the magnitude of change in IV vasopressor rate. MATERIALS AND METHODS: This was a prospective, observational study in 20 adult surgical ICU patients who met ICU discharge criteria except for an IV vasopressor requirement. We compared the change in phenylephrine equivalent rates during the day before midodrine to the change in phenylephrine equivalent rates after midodrine initiation and analyzed changes in total body fluid balance, heart rate, mean arterial pressure, and white blood cell count during this period. RESULTS: Patients received 41.0±33.4 µg/min of phenylephrine equivalents and the change in IV vasopressor rate (slope) decreased significantly from -0.62 µg/min per hour of phenylephrine equivalents before midodrine to -2.20 µg/min per hour following the initiation of midodrine treatment (P=.012). Change in total body fluid balance, heart rate, mean arterial pressure, and white blood cell count did not correlate with change in IV vasopressor rate. CONCLUSION: Midodrine treatment was associated with an increase in the magnitude of decline of the IV vasopressor rate. Oral midodrine may facilitate liberation of surgical ICU patients from an IV vasopressor infusion, and this may affect discharge readiness of patients from the ICU.

Evaluation of a vancomycin dosing nomogram based on the Modification of Diet in Renal Disease equation in intensive care unit patients.

PURPOSE: The purpose of the study is to evaluate the effectiveness of a vancomycin nomogram using actual body weight and the Modification of Diet in Renal Disease equation to estimate renal function in intensive care unit patients. METHODS: Retrospective evaluation (preimplementation group, n=57) was conducted from March 2011 to April 2011. Prospective evaluation was conducted after nomogram implementation (postimplementation group, n=60) from December 2011 to February 2012. RESULTS: The percentage of patients with an initial vancomycin trough concentration 15 µg/mL or higher increased in the postimplementation group as compared with the preimplementation group (72% vs 39%, P=.0004). The postimplementation group also demonstrated an increase in the percentage of patients with initial trough concentration between 15 and 20 µg/mL (42% vs 19%, P=.0099), and no statistical difference in the percentage of patients with an initial trough greater than 20 µg/mL (30% vs 19%, P=.2041). There was no difference in nephrotoxicity in the postimplementation group compared with the preimplementation group (18% vs 17.5%, P=1.0). CONCLUSION: Use of a vancomycin nomogram increased the percentage of initial vancomycin trough concentrations 15 µg/mL or higher in intensive care unit patients and was not associated with an increased occurrence of nephrotoxicity.