A Comparison of Injectable Diazepam and Lorazepam in the Goal-Directed Management of Severe Alcohol Withdrawal.

BACKGROUND: Benzodiazepines are the gold standard for treatment of alcohol withdrawal, yet the selection of a preferred benzodiazepine is limited due to a lack of comparative studies. OBJECTIVES: The primary objective of this study was to compare the efficacy and safety of injectable lorazepam (LZP) and diazepam (DZP) in the treatment of severe alcohol withdrawal syndrome (AWS). METHODS: Retrospective cohort study of adult patients admitted to an intensive care unit with a primary diagnosis of AWS. Subjects who received at least 12 LZP equivalent units (LEU) of injectable DZP or LZP within 24 hours of initiation of the severe AWS protocol were included. The primary outcome was time with Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) scores at goal over the first 24 hours of treatment. RESULTS: A total of 191 patients were included (DZP n = 89, LZP n = 102). Time with CIWA-Ar scores at goal during the first 24 hours was similar between groups (DZP 12 hours [interquartile range, IQR, = 9-15] vs LZP 14 hours [IQR = 10-17]), P = 0.06). At 24 hours, LEU requirement was similar (DZP 40 [IQR = 22-78] vs LZP 32 [IQR = 18-56], P = 0.05). Drug cost at 24 hours was higher in the DZP group ($204.6 [IQR = 112.53-398.97] vs $8 [IQR = 4.5-14], P < 0.01). CONCLUSION AND RELEVANCE: DZP or LZP are equally efficacious for the treatment of severe AWS. LZP may be preferred due to cost but both medications can be used interchangeably based on availability.

Cefepime Versus Piperacillin-Tazobactam for the Treatment of Intra-Abdominal Infections Secondary to Potential AmpC Beta-Lactamase-Producing Organisms.

Background: Recent studies have established cefepime as an effective treatment option for AmpC beta-lactamase (AmpC) Enterobacterales; however, the efficacy of beta-lactam/beta-lactamase inhibitors is unclear. Objective: The objective of this study was to determine if piperacillintazobactamis an appropriate alternative to cefepime for the treatment of intra-abdominal infections (IAIs) secondary to AmpC-producing organisms. Methods: This multicenter, retrospective cohort study was conducted in hospitalized adults with an IAI caused by an AmpC-producing organism and received either cefepime or piperacillin-tazobactam for definitive treatment after a source control procedure. The primary outcome was a composite of surgical site infections, recurrent IAIs, or in-hospital mortality. Secondary outcomes included the individual components of the composite outcome, hospital length of stay (LOS), microbiologic failure, study antibiotic duration, time to clinical resolution, and incidence of Clostridioides difficile infection (CDI). Results: This study included 119 patients. There was no difference in the primary outcome between the cefepime and piperacillin-tazobactam groups (35% vs 27%, P = 0.14). Microbiological failure was the only secondary outcome with an observed difference between groups (17% vs 0%, P = 0.01): hospital LOS (15 vs 13 days, P = 0.09), days of therapy (7 vs 7 days, P = 0.87), time to clinical resolution (7 vs 4 days, P = 0.30), and CDI (1% vs 2%, P = 0.58) were all similar.

A Comparison of Midazolam and Propofol for Deep Sedation in Patients with Acute Respiratory Distress Syndrome Requiring Neuromuscular Blocking Agents.

Purpose: The optimal agent for deep sedation in patients undergoing continuous infusion (CI) neuromuscular blocking agent (NMBA) use for acute respiratory distress syndrome (ARDS) is unknown. The purpose of this study is to compare the efficacy and safety of propofol and midazolam in ARDS patients requiring CI NMBA. Methods: A multi-center, retrospective study was performed in mechanically ventilated (MV) adult patients requiring CI NMBA for management of ARDS. The primary outcome was to compare the time to liberation from MV in patients sedated with propofol vs midazolam. Results: In the 109 patients included, there was no difference in time to MV liberation with propofol as compared to midazolam (121 hr [Interquartile range (IQR) 67 195] vs 98 hr [IQR 48, 292], P = .72). Median time to sedation emergence after NMBA discontinuation was shorter in patients receiving propofol (12.9 hr [IQR 19.8, 72.5] vs 31.5 hr [IQR 6.4, 34.6], P < .01). There were no significant differences in time to therapeutic sedation, ICU stay, mortality, and adverse events. Conclusion: Propofol may be an effective and safe alternative to midazolam for patients undergoing CI NMBA for ARDS. Additionally, patients receiving propofol may have a quicker return to light sedation after NMBA discontinuation.

Low-dose versus standard-dose four-factor prothrombin complex concentrate for factor-Xa inhibitor reversal in spontaneous and traumatic intracranial hemorrhage.

STUDY OBJECTIVES: Current neurocritical care guidelines recommend 50 IU/kg four-factor prothrombin complex concentrate (4PCC) for factor Xa inhibitor (FXaI) reversal in intracranial hemorrhage (ICH) based on few clinical studies conducted among non-ICH subjects. Two recent studies suggest that low-dose (25 IU/kg) 4PCC may be similar to 50 IU/kg in reversal of FXaI in ICH, and both 25 and 50 IU/kg doses are used in clinical practice for this indication. To our knowledge, no studies have directly compared 25 IU/kg versus 50 IU/kg 4PCC for FXaI reversal in ICH. The purpose of this study is to determine whether there is a difference in hemostatic efficacy between 25 IU/kg versus 50 IU/kg 4PCC for FXaI reversal in ICH. DESIGN: This multicenter, retrospective cohort study was performed in five hospitals in central Texas from November 2013 to December 2019. DATA SOURCE: Patients were identified with a medication use report of 4PCC and were classified in the low- or standard-dose group based on whether the 25 IU/kg or 50 IU/kg dose was received, respectively. PATIENTS: A total of 93 patients were included (25 IU/kg, n = 62; 50 IU/kg, n = 31). MEASUREMENTS AND MAIN RESULTS: There was no difference in hemostatic efficacy between groups (82.3% low dose vs. 83.9% standard dose, p = 0.846). No differences were identified in-hospital mortality, length of stay, thrombotic events, or the need for surgery or additional blood products between groups. CONCLUSION: For the reversal of FXaI in ICH, a 25 IU/kg dose may be an effective alternative to 50 IU/kg 4PCC dosing.

Rethinking Carbapenems: A Pharmacokinetic Approach for Antimicrobial Selection in Infected Necrotizing Pancreatitis.

OBJECTIVE: To provide an overview of pathophysiological changes to the pancreas during infected necrotizing pancreatitis (INP), optimal drug properties needed to penetrate the pancreas, human and animal studies supporting the use of antimicrobials, and carbapenem-sparing strategies in INP. DATA SOURCES: A literature analysis of PubMed/MEDLINE was performed (from 1960 to September 2020) using the following key terms: infected necrotizing pancreatitis, necrotizing acute pancreatitis, and infected pancreatitis antimicrobial concentration. Individual antimicrobials were investigated with these search terms. STUDY SELECTION AND DATA EXTRACTION: All relevant studies describing the management of INP, and human and animal pharmacokinetic (PK) data supporting antimicrobial use in the pancreas were reviewed for possible inclusion regardless of sample size or study design. DATA SYNTHESIS: Piperacillin/tazobactam and cefepime achieve adequate pancreatic tissue concentrations in INP studies. A majority of the literature supporting carbapenem use in INP involves imipenem, and meropenem Monte Carlo simulations suggest that standard dosing regimens of meropenem may not achieve PK targets to eradicate Pseudomonas aeruginosa. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Carbapenems are often utilized for INP treatment based on guideline recommendations. This review discusses PK data, the history of carbapenem use in INP, and the pathophysiology of pancreatitis to suggest carbapenem-sparing strategies and provides stewardship tactics such as when to start antimicrobials, which empirical antimicrobial to use, and when to discontinue antimicrobials in the INP setting. CONCLUSIONS: Noncarbapenem antipseudomonals, such as piperacillin/tazobactam and cefepime, are appropriate carbapenem-sparing options in INP, based on PK data, spectrum of activity, and risk of collateral damage.

Position Paper on Critical Care Pharmacy Services (Executive Summary): 2020 Update.

OBJECTIVES: Provide a multiorganizational statement to update the statement from a paper in 2000 about critical care pharmacy practice and makes recommendations for future practice. DESIGN: The Society of Critical Care Medicine, American College of Clinical Pharmacy Critical Care Practice and Research Network, and the American Society of Health-Systems Pharmacists convened a joint task force of 15 pharmacists representing a broad cross-section of critical care pharmacy practice and pharmacy administration, inclusive of geography, critical care practice setting, and roles. The Task Force chairs reviewed and organized primary literature, outlined topic domains, and prepared the methodology for group review and consensus. A modified Delphi method was used until consensus (> 66% agreement) was reached for each practice recommendation. Previous position statement recommendations were reviewed and voted to either retain, revise, or retire. Recommendations were categorized by level of ICU service to be applicable by setting, and grouped into five domains: patient care, quality improvement, research and scholarship, training and education, and professional development. MAIN RESULTS: There are 82 recommendation statements: forty-four original recommendations and 38 new recommendation statements. Thirty-four recommendations were made for patient care, primarily relating to critical care pharmacist duties and pharmacy services. In the quality improvement domain, 21 recommendations address the role of the critical care pharmacist in patient and medication safety, clinical quality programs, and analytics. Nine recommendations were made in the domain of research and scholarship. Ten recommendations are in the domain of training and education and eight recommendations regarding professional development. CONCLUSIONS: The statements recommended by this taskforce delineate the activities of a critical care pharmacist and the scope of pharmacy services within the ICU. Effort should be made from all stakeholders to implement the recommendations provided, with continuous effort toward improving the delivery of care for critically ill patients.

Position Paper on Critical Care Pharmacy Services: 2020 Update.

OBJECTIVES: To provide a multiorganizational statement to update recommendations for critical care pharmacy practice and make recommendations for future practice. A position paper outlining critical care pharmacist activities was last published in 2000. Since that time, significant changes in healthcare and critical care have occurred. DESIGN: The Society of Critical Care Medicine, American College of Clinical Pharmacy Critical Care Practice and Research Network, and the American Society of Health-Systems Pharmacists convened a joint task force of 15 pharmacists representing a broad cross-section of critical care pharmacy practice and pharmacy administration, inclusive of geography, critical care practice setting, and roles. The Task Force chairs reviewed and organized primary literature, outlined topic domains, and prepared the methodology for group review and consensus. A modified Delphi method was used until consensus (> 66% agreement) was reached for each practice recommendation. Previous position statement recommendations were reviewed and voted to either retain, revise, or retire. Recommendations were categorized by level of ICU service to be applicable by setting and grouped into five domains: patient care, quality improvement, research and scholarship, training and education, and professional development. MAIN RESULTS: There are 82 recommendation statements: 44 original recommendations and 38 new recommendation statements. Thirty-four recommendations represent the domain of patient care, primarily relating to critical care pharmacist duties and pharmacy services. In the quality improvement domain, 21 recommendations address the role of the critical care pharmacist in patient and medication safety, clinical quality programs, and analytics. Nine recommendations were made in the domain of research and scholarship. Ten recommendations were made in the domain of training and education and eight recommendations regarding professional development. CONCLUSIONS: Critical care pharmacists are essential members of the multiprofessional critical care team. The statements recommended by this taskforce delineate the activities of a critical care pharmacist and the scope of pharmacy services within the ICU. Effort should be made from all stakeholders to implement the recommendations provided, with continuous effort toward improving the delivery of care for critically ill patients.

Position Paper on Critical Care Pharmacy Services (Executive Summary): 2020 Update.

OBJECTIVES: Provide a multiorganizational statement to update the statement from a paper in 2000 about critical care pharmacy practice and make recommendations for future practice. DESIGN: The Society of Critical Care Medicine, American College of Clinical Pharmacy Critical Care Practice and Research Network, and the American Society of Health-System Pharmacists convened a joint task force of 15 pharmacists representing a broad cross-section of critical care pharmacy practice and pharmacy administration, inclusive of geography, critical care practice setting, and roles. The Task Force chairs reviewed and organized primary literature, outlined topic domains, and prepared the methodology for group review and consensus. A modified Delphi method was used until consensus (>66% agreement) was reached for each practice recommendation. Previous position statement recommendations were reviewed and voted to either retain, revise, or retire. Recommendations were categorized by level of ICU service to be applicable by setting, and grouped into five domains: patient care, quality improvement, research and scholarship, training and education, and professional development. MAIN RESULTS: There are 82 recommendation statements: forty-four original recommendations and 38 new recommendation statements. Thirty-four recommendations were made for patient care, primarily relating to critical care pharmacist duties and pharmacy services. In the quality improvement domain, 21 recommendations address the role of the critical care pharmacist in patient and medication safety, clinical quality programs, and analytics. Nine recommendations were made in the domain of research and scholarship. Ten recommendations are in the domain of training and education and eight recommendations regarding professional development. CONCLUSIONS: The statements recommended by this taskforce delineate the activities of a critical care pharmacist and the scope of pharmacy services within the ICU. Effort should be made from all stakeholders to implement the recommendations provided, with continuous effort toward improving the delivery of care for critically ill patients.

Antithrombotic therapy for postinterventional management of peripheral arterial disease.

PURPOSE: Evidence on the use of antithrombotic pharmacotherapy in patients undergoing revascularization of lower extremities for symptomatic peripheral arterial disease (PAD) is reviewed. SUMMARY: Individuals with PAD can experience leg pain, intermittent claudication, critical limb ischemia, and acute limb ischemia. In such patients, revascularization may be indicated to improve the quality of life and to prevent amputations. Antithrombotic therapy is often intensified in the postrevascularization period to prevent restenosis of the index artery and to counteract the prothrombotic state induced by the intervention. Therapeutic modalities include dual antiplatelet therapy (DAPT), anticoagulation, a combination of antiplatelet and anticoagulation therapy, and addition of cilostazol to single antiplatelet therapy. Subgroup analyses of data from randomized clinical trials provided low-quality evidence for the use of DAPT in patients with a below-knee prosthetic bypass graft and anticoagulation for those with a venous bypass graft. Cilostazol, when added to aspirin therapy, has been shown to prevent index vessel reocclusion after an endovascular intervention in patients at low risk for thrombosis in several small randomized trials. CONCLUSION: There is a considerable paucity of high-quality evidence on the optimal antithrombotic regimen for patients undergoing lower extremity revascularization, with no particular therapy shown to consistently improve patient outcomes. The decision to initiate intensified antithrombotic therapy should include a close examination of its risk-benefit profile. The demonstrated benefit of such treatment is restricted to the prevention of index artery reocclusion, while an increased risk of bleeding may lead to significant morbidity and mortality.

A Multicenter, Prospective, Observational Study to Determine Predictive Factors for Multidrug-Resistant Pneumonia in Critically Ill Adults: The DEFINE Study.

OBJECTIVE: This study was conducted to describe the prevalence, epidemiology, and clinical outcomes of multidrug-resistant (MDR) organism (MDRO) pneumonia in critically ill patients. METHODS: A multicenter, prospective, observational study of patients admitted to 60 intensive care units (ICUs), from 34 hospitals, in the United States from November to December 2016. Adults (> 18 yrs) receiving antimicrobial therapy at least 5 days for pneumonia were included. Patients were classified into two categories, with or without MDRO, and subcategorized by pneumonia type. MEASUREMENTS AND MAIN RESULTS: Demographics, medication histories, and health care exposure were collected during ICU admission and compared using t test and chi-square tests. Multivariate logistic regression was used to determine predictive factors for MDRO pneumonia and hospital mortality. Of 652 patients, 92 patients (14.1%) developed MDR pneumonia. Predictors of MDRO pneumonia were acid suppression therapy within the previous 90 days (odds ratio [OR] 1.88 [1.14-3.09]; p=0.013), mechanical ventilation (OR 1.96 [1.14-3.35]; p<0.001), and history of MDRO infection (OR 4.74 [2.21-10.18]; p<0.001). Appropriate initial antimicrobial selection occurred in 58 patients (63%) with MDRO pneumonia compared to 464 patients (82.7%) in patients without MDRO pneumonia (p<0.001). MDRO pneumonia was not associated with hospital mortality (18.5% vs 17.6%, p=0.087). CONCLUSIONS: In a broad cohort of critically ill patients, MDRO pneumonia is infrequent, and associated with factors describing the intensity of health care provided. Presence of MDRO pneumonia is not associated with hospital mortality. Further study is needed to clarify risk factors for multidrug-resistant pneumonia in critically ill patients.

Perceptions regarding vasopressin use and practices in septic shock, and cost containment strategies.

Background: Clinician preferences and practices regarding appropriate vasopressin use in light of its increased acquisition cost secondary to rebranding has not been evaluated or described since the most recent iteration of the Surviving Sepsis Campaign Guideline was published. Objective: To assess vasopressin cost containment initiatives and pharmacists' opinions regarding appropriate vasopressin use. Methods: A scenario-based survey was distributed to critical care and emergency medicine pharmacists. Responses were characterized using frequency and descriptive statistics. Categorical variables between those who implemented changes (Vasopressin Cost Consideration) and those who did not (Usual Care) were compared using chi-square or Fisher's exact tests. McNemar's test was used to compare responses in clinical scenarios between Vasopressin Cost Consideration and Usual Care groups. Results: Among 1757 pharmacists surveyed, 200 (11.3%) responded. When respondents considered vasopressin cost and evidence (vs evidence alone), fewer respondents would use vasopressin adjunctively with norepinephrine (21% vs 26.6%, P = 0.031), to raise mean arterial pressure compared with epinephrine (65.2% vs 72.3%, P = 0.012), or to reduce norepinephrine infusion rates (71.4% vs 81.4%, P < 0.001), but would use with steroids (62.4% vs 28.3%, P < 0.001). Most (72%) respondents had implemented vasopressin cost containment and/or education initiatives. The Vasopressin Cost Consideration group respondents were more likely to initiate vasopressin at 0.03 units/minute without titrating (47.9% vs 33.9%, P = 0.045). Conclusion: Since vasopressin was generically rebranded, most institutions have implemented at least one initiative to reduce vasopressin use and/or educate clinicians about its appropriate use. When vasopressin acquisition costs were considered, pharmacists recommended its use less frequently, particularly in clinical scenarios where its use is controversial.

Clinical Utility of Methicillin-Resistant Staphylococcus aureus Nasal Screening for Antimicrobial Stewardship: A Review of Current Literature.

Significant clinical and financial consequences are associated with both inadequate and unnecessary exposure to broad-spectrum antibiotics. As such, antimicrobial stewardship programs seek objective, reliable, and cost-effective tests to identify patients at highest or lowest risk for drug-resistant organisms to guide empirical antimicrobial selection. Use of methicillin-resistant Staphylococcus aureus (MRSA) nasal screening to rule out MRSA in lower respiratory tract infections has led to significant reductions in duration of vancomycin therapy. The clinical utility of MRSA nasal screening in other types of infection remains less clear. This review describes the performance of MRSA nasal screening in predicting MRSA infection, highlights practical considerations for use of MRSA nasal screening, and provides guidance for incorporating MRSA nasal screening into clinical practice. With a high negative predictive value when the prevalence of MRSA is low, MRSA nasal screening is a valuable antimicrobial stewardship tool with potential applications beyond lower respiratory tract infections. In appropriately selected patients, negative MRSA nasal screening can prevent initiation or guide discontinuation of anti-MRSA therapy. Antimicrobial stewardship programs should develop institutional guidelines to promote proper use of MRSA nasal screening. Pharmacists are well positioned to assist with education, interpretation, and application of MRSA nasal screening results.

Effectiveness of a bundled approach to reduce urinary catheters and infection rates in trauma patients.

BACKGROUND: Catheter-associated urinary tract infections (CAUTIs) are common nosocomial infections. In 2015, the Centers for Medicare and Medicaid Services began imposing financial penalties for institutions where CAUTI rates are higher than predicted. However, the surveillance definition for CAUTI is not a clinical diagnosis and may represent asymptomatic bacteriuria. The objective of this study was to compare rates of urinary catheterization and CAUTI before and after the implementation of a bundled intervention. METHODS: This retrospective review evaluated trauma patients from January 2013-January 2015. The bundled intervention optimized the urinary catheterization process and culturing practices to reduce false positives. The CAUTI rate was defined as a positive surveillance CAUTI divided by total catheter days multiplied by 1,000 days. RESULTS: A total of 6,236 patients were included (pre: n = 5,003; post: n = 1,233). Fewer patients in the post bundle group received a urinary catheter (pre: 25% vs post: 16%; P < .001). After bundle implementation, the CAUTI rate reduced over one third (pre: 4.07 vs post: 2.56; incidence rate ratio, 0.63; 95% confidence interval, 0.19-2.07). CONCLUSIONS: Although the number of patients exposed to urinary catheters and catheter days was decreased, optimization of culturing practices was essential to prevent the CAUTI rate from increasing from a reduced denominator. Implementation of a CAUTI prevention bundle works synergistically to improve patient safety and hospital performance.

Optimization of intelligent infusion pump technology to minimize vasopressor pump programming errors.

BACKGROUND: There is a lack of data evaluating the impact of hard limit implementation into intelligent infusion pump technology (IIPT). The purpose of this study was to determine if incorporation of vasopressor upper hard limits (UHL) into IIPT increases efficacy of alerts by preventing pump programming errors. METHODS: Retrospective review from five hospitals within a single healthcare network between April 1, 2013 and May 31, 2014. A total of 65,680 vasopressor data entries were evaluated; 19,377 prior to hard limit implementation and 46,303 after hard limit implementation. The primary outcome was the percent of effective alerts. The secondary outcome was the proportional dose increase from the soft limit provided. RESULTS: A reduction in alert rate occurred after incorporation of hard limits to the IIPT drug library (pre-UHL 4.7% vs. post-UHL 4.0%) with a subsequent increase in the number of errors prevented as represented by a higher effective alert rate (pre-UHL 23.0% vs. post-UHL 37.3%; p < 0.001). The proportional dose increase was significantly reduced (pre-UHL 188% ± 380%] vs. post-UHL 95% ± 128%; p < 0.001). CONCLUSIONS: Incorporation of UHLs into IIPT in a multi-site health system with varying intensive care unit and emergency department acuity increases alert effectiveness, reduces dosing errors, and reduces the magnitude of dosing errors that reach the patient.

Thromboelastogram does not detect pre-injury anticoagulation in acute trauma patients.

PURPOSE: Thromboelastography (TEG) has been recommended to characterize post-traumatic coagulopathy, yet no study has evaluated the impact of pre-injury anticoagulation (AC) on TEG variables. We hypothesized patients on pre-injury AC have a greater incidence of coagulopathy on TEG compared to those without AC. METHODS: This retrospective chart review evaluated all trauma patients admitted to an urban, level one trauma center from February 2011 to September 2014 who received a TEG within the first 24h. Patients were classified as receiving pre-injury AC or no AC if their documented medications prior to admission included warfarin, dabigatran, or anti-Xa (aXa) inhibitors (apixaban or rivaroxaban). The presence of coagulopathy on TEG or conventional assays was defined by exceeding local laboratory reference standards. RESULTS: A total of 54 patients were included (AC, n=27 [warfarin n=13, dabigatran n=6, aXa inhibitor n=8] vs. no AC, n=27). Baseline characteristics were similar between groups, including age (72±13years vs. 72±15; p=0.85), male gender (70% vs. 74%; p=0.76) and blunt mechanism of injury (100% vs. 100%; p=1). There was no difference in the number of patients determined to have coagulopathy on TEG (no AC 11% vs. AC 15%; p=0.99). Conventional tests, including the international normalized ratio (INR) and activated partial thromboplastin time (aPTT), identified coagulopathy in a high proportion of anti-coagulated patients (no AC 22% vs. AC 85%; p<0.01). CONCLUSION: TEG has limited clinical utility to evaluate the presence of pre-injury AC. Traditional markers of drug induced coagulopathy should guide reversal decisions.

Impact of Norepinephrine Weight-Based Dosing Compared With Non-Weight-Based Dosing in Achieving Time to Goal Mean Arterial Pressure in Obese Patients With Septic Shock.

BACKGROUND: Currently, a lack of standardization exists in norepinephrine dosing units, the first-line vasopressor for septic shock. Timely achievement of goal mean arterial pressure (MAP) is dependent on optimal vasopressor dosing. OBJECTIVE: To determine if weight-based dosing (WBD) of norepinephrine leads to earlier time to goal MAP compared with non-WBD in obese patients with septic shock. METHODS: This was a retrospective, multicenter cohort study. Patients had a body mass index (BMI) ≥30 kg/m2 and received norepinephrine for septic shock with either a non-WBD strategy (between December 2009 and January 2013) or WBD strategy (between January 2013 and December 2015). The primary outcome was time to goal MAP. Secondary outcomes were norepinephrine duration, dose requirements, and development of treatment-related complications. RESULTS: A total of 287 patients were included (WBD 144; non-WBD 143). There was no difference in median time to goal MAP (WBD 58 minutes, interquartile range [IQR] = 16.8-118.5, vs non-WBD 60 minutes, IQR = 17.5-193.5; P = 0.28). However, there was a difference in median cumulative norepinephrine dose (WBD 12.6 mg, IQR = 4.9-45.9, vs non-WBD 10.5 mg, IQR = 3.9-25.6; P = 0.04) and time to norepinephrine discontinuation (WBD 33 hours, IQR = 15-69, vs non-WBD 27 hours, IQR = 12-51; P = 0.03). There was no difference in rates of atrial fibrillation (WBD 15.3% vs non-WBD 23.7%; P = 0.07) or mortality (WBD 23.6% vs non-WBD 23.1%; P = 0.92). CONCLUSION: WBD of norepinephrine does not achieve time to goal MAP earlier in obese patients with septic shock. However, WBD may lead to higher norepinephrine cumulative dose requirements and prolonged time until norepinephrine discontinuation.

Are first-generation cephalosporins obsolete? A retrospective, non-inferiority, cohort study comparing empirical therapy with cefazolin versus ceftriaxone for acute pyelonephritis in hospitalized patients.

OBJECTIVES: Literature is lacking regarding the utilization of first-generation cephalosporins for the treatment of acute pyelonephritis. The aim of this study was to determine whether cefazolin is non-inferior to ceftriaxone for the empirical treatment of acute pyelonephritis in hospitalized patients. The primary outcome included a composite of symptomatic resolution plus either defervescence at 72 h or normalization of serum white blood cell count at 72 h (non-inferiority margin 15%). Secondary outcomes included length of stay and 30 day readmission. A subgroup analysis of the composite outcome was also conducted for imaging-confirmed pyelonephritis. METHODS: This was a retrospective, non-inferiority, multicentre, cohort study comparing cefazolin versus ceftriaxone for the empirical treatment of acute pyelonephritis in hospitalized patients. RESULTS: Overall, 184 patients received one of the two treatments between July 2009 and March 2015. The composite outcome was achieved in 80/92 (87.0%) in the cefazolin group versus 79/92 (85.9%) in the ceftriaxone group (absolute difference 1.1%, 95% CI -11.1% to 8.9%, P = 0.83), meeting the pre-defined criteria for non-inferiority. The composite outcome for patients with imaging-confirmed pyelonephritis was achieved in 46/56 (82.1%) versus 42/50 (84.0%) for the cefazolin group and the ceftriaxone group, respectively (absolute difference 1.9%, 95% CI -12.8% to 16.5%, P = 0.80). Additionally, there were no statistically significant differences in length of stay or 30 day readmission for cystitis or pyelonephritis. CONCLUSIONS: Cefazolin was non-inferior to ceftriaxone with regard to clinical response for the treatment of hospitalized patients with acute pyelonephritis in this study. No difference was observed for length of stay or 30 day readmission.

Thromboelastography Does Not Detect Preinjury Antiplatelet Therapy in Acute Trauma Patients.

Thromboelastography (TEG) with platelet mapping has been proposed as an assay to detect the presence of antiplatelet agents (APA), yet no study has evaluated TEG markers of platelet dysfunction in acute trauma patients stratified by the use of preinjury APA. We hypothesized that patients on preinjury APA would demonstrate prolonged TEG markers of platelet dysfunction compared with those not on preinjury APA. This retrospective review evaluated all trauma patients admitted to a Level I trauma center from February 2011 to April 2013 who received a TEG within the first 24 hours of admission. Patients were classified as receiving preinjury APA or no APA if their documented medications included either aspirin or adenosine diphosphate (ADP) antagonists, including clopidogrel, prasugrel, and ticagrelor. A total of 129 patients were included (APA, n = 35; no APA n = 94) in the study. The time from admission to the first TEG was similar (APA 175 ± 289 minutes versus no APA 216 ± 321 minutes, P = 0.5). There was no significant difference in TEG markers of platelet dysfunction, including per cent ADP inhibition (APA 61.7 ± 25.8% versus no APA 62.3 ± 28.8%; P = 0.91) or per cent arachidonic acid inhibition (APA 58.2 ± 31% versus no APA 53.8 ± 34%; P = 0.54). Both groups had similar proportion of severe platelet dysfunction, defined as ADP inhibition greater than 70 per cent (APA 40% versus no APA 40%; P = 0.8) and arachidonic acid inhibition greater than 70 per cent (APA 40% versus no APA 39%; P = 0.89). In conclusion, platelet dysfunction after major trauma is common. Therefore, TEG alone should not be used to evaluate for the presence of APA due to apparent lack of specificity.

Implications of Augmented Renal Clearance on Drug Dosing in Critically Ill Patients: A Focus on Antibiotics.

Augmented renal clearance (ARC) has been reported in approximately 30-65% of patients in the intensive care unit (ICU) despite the presence of a normal serum creatinine concentration. In certain ICU patient populations (e.g., patients with sepsis or trauma), the incidence increases to roughly 50-85%. Risk factors for ARC include the following: age younger than 50-55 years, male sex, higher diastolic blood pressure, fewer comorbidities, and a lower Acute Physiology and Chronic Health Evaluation II (APACHE II) or modified Sequential Organ Failure Assessment (SOFA) score at ICU admission. In addition, patient populations with the highest reported incidence of ARC include those with major trauma, sepsis, traumatic brain injury, subarachnoid hemorrhage, and central nervous system infection. Due to the high incidence of ARC in patients with a normal serum creatinine concentration, clinicians should consider screening ICU patients deemed high risk by using the ARC scoring system or the identification and assessment algorithm provided in this review. In addition, an 8-hour continuous urine collection should be considered to assess a measured creatinine clearance for evaluating the necessity of medication dosage adjustments. There is a clear association between ARC and subtherapeutic antibiotic concentrations as well as literature suggesting worse clinical outcomes; thus, the risk of underdosing antibiotics in a patient with ARC could increase the risk of treatment failure. This review examines strategies to overcome ARC and summarizes current pharmacokinetic and pharmacodynamic literature in patients with ARC in an effort to provide dosing guidance for this patient population.