An Approach to Diversifying the Selection of a Guideline Panel-The Process Utilized for the Updated Adult Critical Care Ultrasound Guidelines.

OBJECTIVES: Clinical practice guidelines are essential for promoting evidence-based healthcare. While diversification of panel members can reduce disparities in care, processes for panel selection lack transparency. We aim to share our approach in forming a diverse expert panel for the updated Adult Critical Care Ultrasound Guidelines. DESIGN: This process evaluation aims to understand whether the implementation of a transparent and intentional approach to guideline panel selection would result in the creation of a diverse expert guideline panel. SETTING: This study was conducted in the setting of creating a guideline panel for the updated Adult Critical Care Ultrasound Guidelines. PATIENTS: Understanding that family/patient advocacy in guideline creations can promote the impact of a clinical practice guideline, patient representation on the expert panel was prioritized. INTERVENTIONS: Interventions included creation of a clear definition of expertise, an open invitation to the Society of Critical Care Medicine membership to apply for the panel, additional panel nomination by guideline leadership, voluntary disclosure of pre-identified diversity criteria by potential candidates, and independent review of applications including diversity criteria. This resulted in an overall score per candidate per reviewer and an open forum for discussion and final consensus. MEASUREMENTS AND MAIN RESULTS: The variables of diversity were collected and analyzed after panel selection. These were compared with historical data on panel composition. The final guideline panel comprised of 33 panelists from six countries: 45% women and 79% historically excluded people and groups. The panel has representation from nonphysician professionals and patients advocates. Of the healthcare professionals, there is representation from early, mid, and late career stages. CONCLUSIONS: Our intentional and transparent approach resulted in a panel with improved gender parity and robust diversity along ethnic, racial, and professional lines. We hope it can serve as a starting point as we strive to become a more inclusive and diverse discipline that creates globally representative guidelines.

Evaluation of an Automated, Pharmacist-Driven, Antimicrobial Patient Acuity Scoring System for Hospitalized Bacteremic Patients.

Purpose: The implementation of an automated, pharmacist-driven, scoring system within the EMR has been shown to improve patient care in patients with Staphylococcus aureus bacteremia by increasing the adherence to disease specific quality-of-care measures. However, there are a lack of studies evaluating the incorporation of blood culture review into standard, non-antimicrobial stewardship pharmacist workflow. Our institution implemented an automated, pharmacist-driven, antimicrobial scoring system in the electronic medical record (EMR) on August 6, 2019. Methods: This was a retrospective, single-center, quasi-experimental study of hospitalized, non-critically ill adult (18-89 years of age) patients with bacteremia between July 6, 2018 and July 5, 2019 (pre-implementation group) and September 6, 2019 and September 5, 2020 (post-implementation group). The primary outcome was time to directed antibiotic therapy in patients with positive blood cultures. Secondary outcomes included hospital length-of-stay, days of therapy (DOT) while inpatient, time to effective therapy, 30-day all-cause mortality, and rates of Clostridioides difficile infections documented within 3 months of positive culture results. Results: Implementation of the antimicrobial scoring system did not result in a significant change in time to directed antibiotic therapy (32.5 hours vs 37.4 hours; P = .757). There was also no difference found for time to effective antibiotic therapy (-12.6 hours vs -14.2 hours; P =.905) and no difference found for all other secondary outcomes. Conclusion: The implementation of the antimicrobial scoring system did not lead to an improvement in clinical outcomes. Further research is needed to better define a patient population that may benefit from this system.

Surgeons, Infectious Diseases, and Twitter Hit a Home Run for Antibiotic Stewardship.

Many infectious diseases (ID) clinicians join Twitter to follow other ID colleagues or "like" people. While there is great value in engaging with people who have similar interests, there is equal value in engaging with "unlike" or non-ID people. Here, we describe how Twitter connected an ID pharmacist with a pediatric surgeon, a vice chair of surgery, a surgeon chief medical officer from Spain, and a surgical intensive care unit pharmacist. This Twitter collaboration resulted in several scholarly activities related to antibiotic resistance and antibiotic stewardship and served as a conduit for global collaboration.

Duration of Antibiotic Therapy for General Medicine and General Surgery Patients Throughout Transitions of Care: An Antibiotic Stewardship Opportunity for Noninfectious Disease Pharmacists.

BACKGROUND: Overuse of antibiotics from the inpatient to outpatient setting is an antibiotic stewardship initiative where noninfectious disease (ID) pharmacists can have a large impact. Our purpose was to evaluate antibiotic durations across transitions of care from the inpatient to outpatient setting. METHODS: This is a single-center, retrospective cohort analysis evaluating antibiotic durations from the inpatient and outpatient setting in adult patients admitted to general surgery and medicine services at an academic medical center between January 1, 2017 and September 20, 2017. The primary outcome was to assess total antibiotic duration for patients with uncomplicated and complicated urinary tract infections (UTI, cUTI), community-acquired pneumonia (CAP), and hospital-acquired pneumonia (HAP). Outpatient electronic discharge prescriptions were used to calculate intended antibiotic duration upon transitions of care. Excessive duration of therapy was defined as >3 days-UTI, >5 days-CAP, and >7 days-cUTI or HAP. RESULTS: One hundred and one patients met inclusion criteria. Overall, most of the patients (81%) had antibiotics longer than recommended with only 3% receiving less than the recommended duration. Median total duration of therapy compared with recommended duration specified in national guidelines was UTI: 10 days [7 -10], cUTI: 12 days [7.5-12.5], CAP: 7 days [7 -9], HAP: 10 days [8 -12]. The median antibiotic duration was shorter in patients with no cultures or culture negative results compared with patients with positive cultures for all indications (UTI: 10.3 vs 10.8 days, cUTI: 9 vs 12 days, CAP: 8 vs 9.1 days, HAP: 10.5 vs 19.8 days). Overall, the recommended duration of antibiotics was completed while inpatient in 34.7%, but varied by infection. More patients with UTI or cUTI completed recommended duration of therapy while inpatient vs for CAP or HAP (53.8% vs 28%, P = .03). Eighty percent of those with UTI, 18.2% with cUTI, 25.6% with CAP, and 31.2% with HAP had already received the recommended duration of treatment, or more, on day of hospital discharge. CONCLUSIONS: The median duration of antibiotic therapy for all indications evaluated was longer than recommended in national guidelines. Opportunities for stewardship by non-ID pharmacists to impact postdischarge antimicrobial use at transitions of care have been identified.

Ceftolozane/Tazobactam vs Polymyxin or Aminoglycoside-based Regimens for the Treatment of Drug-resistant Pseudomonas aeruginosa.

BACKGROUND: Ceftolozane/tazobactam is a novel cephalosporin/beta-lactamase inhibitor combination that often retains activity against resistant Pseudomonas aeruginosa. The comparative safety and efficacy vs polymyxins or aminoglycosides in this setting remains unknown. METHODS: A retrospective, multicenter, observational cohort study was performed. Patients who received ceftolozane/tazobactam were compared with those treated with either polymyxin or aminoglycoside-based regimens for infections due to drug-resistant P. aeruginosa. Multivariate logistic regression was performed controlling for factors associated with treatment to assess the independent impact of ceftolozane/tazobactam on clinical cure, acute kidney injury (AKI), and in-hospital mortality. RESULTS: A total of 200 patients were included (100 in each treatment arm). The cohort represented an ill population with 69% in the intensive care unit, 63% mechanically ventilated, and 42% in severe sepsis or septic shock at infection onset. The most common infection type was ventilator-associated pneumonia (52%); 7% of patients were bacteremic. Combination therapy was more commonly used in polymyxin/aminoglycoside patients than those who received ceftolozane/tazobactam (72% vs 15%, P < .001). After adjusting for differences between groups, receipt of ceftolozane/tazobactam was independently associated with clinical cure (adjusted odds ratio [aOR], 2.63; 95% confidence interval [CI], 1.31-5.30) and protective against AKI (aOR, 0.08; 95% CI, 0.03-0.22). There was no difference in in-hospital mortality. The number needed to treat for a clinical cure with ceftolozane/tazobactam was 5, and the number needed to harm with AKI with a polymyxin/aminoglycoside was 4. CONCLUSIONS: These data support the preferential use of ceftolozane/tazobactam over polymyxins or aminoglycosides for drug-resistant P. aeruginosa infections.

A comparison of severe hemodynamic disturbances between dexmedetomidine and propofol for sedation in neurocritical care patients.

OBJECTIVE: Dexmedetomidine and propofol are commonly used sedatives in neurocritical care as they allow for frequent neurologic examinations. However, both agents are associated with significant hemodynamic side effects. The primary objective of this study is to compare the prevalence of severe hemodynamic effects in neurocritical care patients receiving dexmedetomidine and propofol. DESIGN: Multicenter, retrospective, propensity-matched cohort study. SETTING: Neurocritical care units at two academic medical centers with dedicated neurocritical care teams and board-certified neurointensivists. PATIENTS: Neurocritical care patients admitted between July 2009 and September 2012 were evaluated and then matched 1:1 based on propensity scoring of baseline characteristics. INTERVENTIONS: Continuous sedation with dexmedetomidine or propofol. MEASUREMENTS AND MAIN RESULTS: A total of 342 patients (105 dexmedetomidine and 237 propofol) were included in the analysis, with 190 matched (95 in each group) by propensity score. The primary outcome of this study was a composite of severe hypotension (mean arterial pressure < 60 mm Hg) and bradycardia (heart rate < 50 beats/min) during sedative infusion. No difference in the primary composite outcome in both the unmatched (30% vs 30%, p = 0.94) or matched cohorts (28% vs 34%, p = 0.35) could be found. When analyzed separately, no differences could be found in the prevalence of severe hypotension or bradycardia in either the unmatched or matched cohorts. CONCLUSIONS: Severe hypotension and bradycardia occur at similar prevalence in neurocritical care patients who receive dexmedetomidine or propofol. Providers should similarly consider the likelihood of hypotension or bradycardia before starting either sedative.

Comorbidity-polypharmacy score: a novel adjunct in post-emergency department trauma triage.

OBJECTIVE: Post-emergency department triage of older trauma patients continues to be challenging, as morbidity and mortality for any given level of injury severity tend to increase with age. The comorbidity-polypharmacy score (CPS) combines the number of pre-injury medications with the number of comorbidities to estimate the severity of comorbid conditions. This retrospective study examines the relationship between CPS and triage accuracy for older (≥45y) patients admitted for traumatic injury. METHODS: Patients aged 45y and older presenting to level 1 trauma center from 2005 to 2008 were included. Basic data included patient demographics, injury severity score, morbidity and mortality, and functional outcome measures. CPS was calculated by adding total numbers of comorbid conditions and pre-injury medications. Patients were divided into three triage groups: undertriage (UT), appropriate triage (AT), and overtriage (OT). UT criteria included initial admission to the floor or step-down unit followed by an unplanned transfer to intensive care unit (ICU) within 24h of admission. OT was defined as initial ICU admission for <1d without stated need for ICU level of care (i.e., lack of evidence for tracheal intubation or mechanical ventilation, injury-related hemorrhage, or other traditional ICU indications, such as intracranial bleeding). All other patients were presumed to be correctly triaged. The three triage groups were then analyzed looking for contributors to mistriage. RESULTS: Charts for 711 patients were evaluated (mean age, 63.5y; 55.7% male; mean ISS, 9.02). Of those, 11 (1.55%) met criteria for UT and 14 (1.97%) for OT. The remaining 686 patients had no evidence of mistriage. The three groups were similar in terms of injury severity and GCS. The groups were significantly different with respect to CPS, with UT CPSs (14.9±6.80) being nearly three times higher than OT CPSs (5.14±3.48). There were more similarities between AT and OT groups, with the UT group being characterized by greater number of complications and lower functional outcomes at discharge (all, P<0.05). The UT group had significantly higher mortality (27%) than the AT and OT groups (6% and 0%, respectively). CONCLUSIONS: In the era of medication reconciliation, CPS is easy to obtain and calculate in patients who are not critically injured. This study suggests that CPS may be a promising adjunct in identifying older trauma patients who are more likely to be undertriaged. The significance of our findings is especially important when considering that injury severity in the UT group was similar to that in the other groups. Further evaluation of CPS as a triage tool in acute trauma is warranted.

Performance of different body weights in the Cockcroft-Gault equation in critically ill patients with and without augmented renal clearance: A multicenter cohort.

STUDY OBJECTIVE: The primary objective was to evaluate the performance of the Cockcroft-Gault (CG) equation with different body weights (BWs) compared to a measured creatinine clearance (mCrCl) in an intensive care unit (ICU) population with and without augmented renal clearance (ARC). DESIGN: Multicenter, retrospective cohort. SETTING: Two ICUs in the United States and four ICUs from a previous international observational analysis. PATIENTS: Adult ICU patients admitted from January 1, 2010 to July 30, 2020 with at least one mCrCl collected within the initial 10 days of hospitalization were eligible for inclusion. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the performance of the CG equation in ARC (mCrCl≥130 ml/min/1.73 m2 ) and non-ARC (mCrCl<130 ml/min/1.73 m2 ) patients. Correlation was analyzed by Pearson's correlation coefficient, bias by mean difference, and accuracy by the percentage of patients within 30% of the mCrCl. A total of 383 patients were included, which provided 1708 mCrCl values. The majority were male (n = 239, 62%), median age of 55 years [IQR 40-65] with a surgical diagnosis (n = 239, 77%). ARC was identified in 229 (60%) patients. The ARC group had lower Scr values (0.6 [0.5-0.7] vs. 0.7 [0.6-0.9] mg/dl, p < 0.001) and higher mCrCl (172.8 (SD 39.1) vs. 89.9 mL/min/1.73 m2 (SD 25.4), p < 0.001) compared with the non-ARC group, respectively. Among non-ARC patients there was a moderate correlation (r = 0.33-0.39), moderate accuracy (range 48-58%), and low bias (range of -12.9 to 17.1) among the different BW estimations with the adjusted BW having the better performance. Among ARC patients there was low correlation (r = 0.24-0.28), low to moderate accuracy (range 38-70%), and high bias (range of -58.5 to -21.6). CONCLUSIONS: The CG-adjusted BW had the best performance in the non-ARC patients, while CG performed poorly with any BW in ARC patients. Although the CG equation remains the standard equation for estimating CrCl in the ICU setting, a new, validated equation is needed for patients with ARC.

Bleeding risk factors associated with argatroban therapy in the critically ill.

Argatroban is a parenteral direct thrombin inhibitor labeled for anticoagulation in patients with confirmed or suspected heparin-induced thrombocytopenia in the United States. Currently there are no studies evaluating bleeding risk factors in Intensive Care Unit patients.To determine bleeding risk factors associated with argatroban therapy in the critically ill. Critically ill patients admitted between July 2007-June 2008 who received argatroban were included in this retrospective cohort study. The primary endpoint was the incidence of bleeding complications associated with argatroban. Major bleeding was defined as a hemoglobin reduction ≥2 g/dL plus a transfusion of ≥2 units of blood in a 24 h period, or a retroperitoneal, intracranial, prosthetic joint, or other life-threatening bleed. Minor bleeding was any overt bleeding not fitting the major bleeding definition. Secondary outcomes included identifying risk factors for bleeding. Seventy-three patients were included with 16 (21.9%) total bleeding complications, 7 (9.6%) major and 9 (12.3%) minor bleeds. Four risk factors for bleeding were identified by univariate analysis: major surgery prior to or during argatroban therapy (OR = 8.4, 95% CI: 2.3-30.1, p = 0.001), dosing weight >90 kg (OR = 4.8, 95% CI: 1.4-15.8, p = 0.01), total bilirubin >3 mg/dL (OR = 8.1, 95% CI: 2.1-31.1, p = 0.002), and baseline platelets ≤70 K/µL (OR = 4.2, 95 % CI: 1.1-16.3, p = 0.039).Risks and benefits of argatroban should be weighed in patients with major surgery prior to or during argatroban, dosing weight ≥90 kg, total bilirubin ≥3 mg/dL, and baseline platelets ≤70 K/µL.

Evaluation of Dexmedetomidine's Effect on Temperature in Obese Critically Ill Patients.

INTRODUCTION: Previous literature showed an association between hyperthermia and dexmedetomidine (DEX) use for ongoing sedation in non-obese patients. The purpose of this study is to evaluate DEX's effect on temperature in obese critically ill patients. METHODS: This single center, retrospective, cohort study included patients ≥18 years, admitted to a surgical or medical ICU, received DEX for ≥8 hours as a single continuous infusion sedative, and weighed ≥120% of ideal body weight. Patients were excluded if they had a fever (≥38°C) and positive cultures within 48 hours of DEX initiation. The primary endpoint was a fever (Tmax of ≥38°C) within 48 hours of DEX initiation. RESULTS: A total of 186 patients were included for evaluation. Forty-two patients (22.5%) had a fever during the first 48 hours of DEX initiation. Median weight was not different between the febrile and afebrile groups (99.4 [90.6-122.4] vs 97.6 [81.6-114.2] kg, P = .6). Median change from baseline temperature for all patients within 48 hours was an increase of .5 (.1-.8) °C, P < .001. In multiple regression analysis, duration of DEX and baseline temperature were the only significant predictors of fever development with an adjusted odds ratio of 1.041 (95% CI 1.009-1.074, P = .012) and 7.058 (95% CI 3.307-15.064, P < .001), respectively. CONCLUSIONS: This study suggests that there is a significant increase in body temperature from baseline for obese patients on DEX. Duration of DEX and baseline temperature were found to be risk factors for fever development in this population. Further studies are warranted.

High-dose dexmedetomidine for sedation in the intensive care unit: an evaluation of clinical efficacy and safety.

BACKGROUND: Dexmedetomidine is an α(2)-receptor agonist used for sedation in the intensive care unit (ICU). Although dexmedetomidine is labeled for sedation in critically ill patients at doses up to 0.7 µg/kg/h, recent studies have used more liberal dosing regimens. However, to our knowledge, no study has assessed the clinical impact of doses greater than 0.7 µg/kg/h when compared to doses within the Food and Drug Administration--approved labeling. OBJECTIVE: To compare the clinical efficacy and safety of high (HD) and low (LD) doses of dexmedetomidine for sedation in the ICU. METHODS: This retrospective study included a sample of patients who received dexmedetomidine in medical, surgical, medical/surgical, and cardiothoracic ICUs between January 1, 2008, and December 1, 2009. Patients were included in the LD group if their maximum dose was less than 0.7 µg/kg/h or in the HD group if any dose was more than 0.7 µg/kg/h. Efficacy was determined by the percentage of Richmond Agitation and Sedation Scale (RASS) scores for each patient maintained at goal sedation (-1 to +1), and safety was determined by the incidence of hypotension and bradycardia. RESULTS: Forty-three of 133 patients received HD dexmedetomidine. Patients in the LD group had a significantly higher percentage of RASS scores at goal (60.0% vs 48.6%; p = 0.03), while those in the HD group experienced a higher percentage of RASS scores classified as undersedated (19.2% vs 4.9%; p = 0.001). There was no significant difference in the incidence of hypotension or bradycardia between groups. CONCLUSIONS: Patients treated with HD dexmedetomidine had fewer RASS scores at goal. Our data suggest that increasing the dose of dexmedetomidine may not enhance sedation efficacy or lead to an increased incidence of adverse effects. Patients who have not achieved goal sedation at doses of 0.7 µg/kg/h or less may not respond further to increased doses.

Discordance of renal drug dosing using estimated creatinine clearance and measured urine creatinine clearance in hospitalized adults: A retrospective cohort study.

BACKGROUND: Assessment of kidney function is fundamental to optimize drug dosing. The Cockcroft-Gault (CG) equation is widely used but has questionable validity for females, changing renal function, and the critical ill. Eight-hour urine collections (U8h) offer direct measurement of creatinine clearance (CrCl) but lack the data for drug dosing. The primary objective of this study was to determine if there was a difference in renal drug dosing based on the estimation of CG CrCl (CrClCG) versus 8-h CrCl (CrCl8h). METHODS: This was an observational, retrospective cohort study of adult patients admitted between March 2018 and September 2018 with a collection U8h during hospitalization. The primary outcome was discordance of renal drug dosing defined as the percentage of U8h for which at least one different active medication CrCl dosing cutoff would result using the CrClCG versus CrCl8h. The secondary outcomes were correlation between CrClCG and CrCl8h and percentage of CrClCG values outside ± 20% of the CrCl8h. RESULTS: One hundred collections drawn from 85 unique patients (50.6% male, median age 55 [41-70] years, intensive care unit 88%) were included in the analysis. Median serum creatinine was 0.76 (0.52-1.06) mg/dL and blood urea nitrogen was 20 (14-28) mg/dL at time of collection8h. Median CrCl8h was 86.2 (43.5-140.3) mL/min versus 99.7 (56.5-166.9) mL/min CrClCG(P < 0.001) and discordance was 25%. The correlation between CrCl8h and CrClCG was 0.76 (P < 0.001). Only 31% of CrClCG values were within ± 20% of the CrCl8h value. CONCLUSION: We found 25% discordance for drug dosing between CrCl8h and CrClCG. Further studies are needed to determine the impact on clinical outcomes.

COVID-19 pandemic: Challenges and solutions from the cardiology pharmacist's perspective.

The recent coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenges pharmacists worldwide. Alongside other specialized pharmacists, we re-evaluated daily processes and therapies used to treat COVID-19 patients within our institutions from a cardiovascular perspective and share what we have learned. To develop a collaborative approach for cardiology issues and concerns in the care of confirmed or suspected COVID-19 patients by drawing on the experiences of cardiology pharmacists across the country. On March 26, 2020, a conference call was convened composed of 24 cardiology residency-trained pharmacists (23 actively practicing in cardiology and 1 in critical care) from 16 institutions across the United States to discuss cardiology issues each have encountered with COVID-19 patients. Discussion centered around providing optimal pharmaceutical care while limiting staff exposure. The collaborative of pharmacists found for the ST-elevation myocardial infarction patient, many institutions were diverting COVID-19 rule-out patients to their Emergency Department (ED). Thrombolytics are an alternative to percutaneous coronary intervention (PCI) allowing for timely treatment of patients and decreased staff exposure. An emergency response grab and go kit includes initial drugs and airway equipment so the patient can be treated and the cart can be left outside the room. Cardiology pharmacists have developed policies and procedures to address monitoring of QT prolonging medications, the use of inhaled prostacyclins, and national drug shortages. Technology has allowed us to practice social distancing, while staying in close contact with our teams, patients, and colleagues and continuing to teach. Residents are engaged in unique decision-making processes with their preceptors and assist as pharmacist extenders. Cardiology pharmacists are in a unique position to work with other pharmacists and health care professionals to implement safe and effective practice changes during the COVID-19 pandemic. Ongoing monitoring and adjustments are necessary in rapidly changing times.

Antibiotic Stewardship in the Intensive Care Unit. An Official American Thoracic Society Workshop Report in Collaboration with the AACN, CHEST, CDC, and SCCM.

Intensive care units (ICUs) are an appropriate focus of antibiotic stewardship program efforts because a large proportion of any hospital's use of parenteral antibiotics, especially broad-spectrum, occurs in the ICU. Given the importance of antibiotic stewardship for critically ill patients and the importance of critical care practitioners as the front line for antibiotic stewardship, a workshop was convened to specifically address barriers to antibiotic stewardship in the ICU and discuss tactics to overcome these. The working definition of antibiotic stewardship is "the right drug at the right time and the right dose for the right bug for the right duration." A major emphasis was that antibiotic stewardship should be a core competency of critical care clinicians. Fear of pathogens that are not covered by empirical antibiotics is a major driver of excessively broad-spectrum therapy in critically ill patients. Better diagnostics and outcome data can address this fear and expand efforts to narrow or shorten therapy. Greater awareness of the substantial adverse effects of antibiotics should be emphasized and is an important counterargument to broad-spectrum therapy in individual low-risk patients. Optimal antibiotic stewardship should not focus solely on reducing antibiotic use or ensuring compliance with guidelines. Instead, it should enhance care both for individual patients (by improving and individualizing their choice of antibiotic) and for the ICU population as a whole. Opportunities for antibiotic stewardship in common ICU infections, including community- and hospital-acquired pneumonia and sepsis, are discussed. Intensivists can partner with antibiotic stewardship programs to address barriers and improve patient care.

Use of subcutaneous lepirudin in an obese surgical intensive care unit patient with heparin resistance.

OBJECTIVE: To report the use of subcutaneous lepirudin in an obese patient with heparin resistance. CASE SUMMARY: A 34-year-old morbidly obese male (weight 145 kg) presented with hypoxia on postoperative day 1 following a sigmoid colectomy. A continuous unfractionated heparin infusion was started for a suspected pulmonary embolism. Doses were escalated without therapeutic activated partial thromboplastin time (aPTT) response and an antithrombin (AT) level was obtained. The AT level was reported as 78% (reference range 85-120%). Computed tomography angiography ruled out pulmonary embolism and lepirudin 50 mg administered subcutaneously twice daily was started (serum creatinine 1.3 mg/dL) for prevention of venous thromboembolism. The resulting aPTT values were therapeutic (63 and 60 sec, reference range 24-34, therapeutic heparin range 55-85). The dose was adjusted to 25 mg twice daily. aPTT values were 35 and 48 seconds. His serum creatinine increased to 1.6 mg/dL and minor bleeding was noted. The dose was decreased to 25 mg once daily, with resulting aPTT values of 31, 39, and 41 seconds. The patient was discharged to home without development of venous thromboembolism, as confirmed by duplex ultrasonography. DISCUSSION: Commonly administered anticoagulants, such as unfractionated heparin, low-molecular-weight heparins, and fondaparinux, exert their effect by complexing with AT and thrombin (Factor IIa), activating AT and preventing thrombin from exerting coagulation effect. Without AT present, these drugs have little effect on inhibiting the coagulation cascade. Lepirudin is a synthetic irreversible direct thrombin inhibitor and does not rely on AT to exert its anticoagulation action. It can be given subcutaneously and is eliminated primarily by the kidneys. Dosage adjustments for both renal function and obesity need to be considered and aPTT should be monitored. CONCLUSIONS: In obese patients or those with heparin resistance, subcutaneous lepirudin can be monitored and the regimen adjusted based on aPTT values. Further studies are warranted to maximize efficacy and define dosing.

An updated focused review of dexmedetomidine in adults.

OBJECTIVE: To evaluate recent comparative studies regarding the safety and efficacy of dexmedetomidine in adults. DATA SOURCES: Articles evaluating safety and efficacy of dexmedetomidine were identified from an English-language MEDLINE search (1996-July 2009), with a focus on data published since our previous review in 2007 to the present. MeSH terms included dexmedetomidine, medetomidine, alpha2-agonist, and sedation. References from selected articles were also reviewed for additional material. STUDY SELECTION AND DATA EXTRACTION: Experimental and observational English-language studies that focused on the efficacy, safety, and pharmacoeconomics of dexmedetomidine in humans were selected. DATA SYNTHESIS: Dexmedetomidine is an 2-agonist used for sedation during procedures and in critical illness. Compared with placebo, use of dexmedetomidine during procedures was associated with decreased use of rescue midazolam and a similar degree of sedation compared with various agents used during surgery or for procedures. Use of long-term (>24 h) dexmedetomidine sedation is comparable to sedation with benzodiazepines in critically ill patients. In a Phase 4 study, dexmedetomidine was safe in dosages up to 1.4 microg/kg/hour for greater than 24 hours and did not produce rebound tachycardia or hypertension when abruptly discontinued. One small randomized controlled trial demonstrated decreased incidence of delirium, the primary endpoint, with dexmedetomidine compared with midazolam or propofol for sedation after cardiac valve surgery. Many, but not all, studies suggest that dexmedetomidine has a promising role in prevention and treatment of delirium in critically ill patients when delirium was studied as a secondary endpoint. CONCLUSIONS: Dexmedetomidine is an alternative for procedural sedation and can be used long-term (>24 h) in critically ill patients, in dosages up to 1.5 microg/kg/hour. More studies are needed to better define the role of dexmedetomidine in preventing and treating delirium.

Incidence of propofol-related infusion syndrome in critically ill adults: a prospective, multicenter study.

INTRODUCTION: While propofol is associated with an infusion syndrome (PRIS) that may cause death, the incidence of PRIS is unknown. Determining the incidence of PRIS and the frequency of PRIS-related clinical manifestations are key steps prior to the completion of any controlled studies investigating PRIS. This prospective, multicenter study sought to determine the incidence of PRIS and PRIS-related clinical manifestations in a large cohort of critically ill adults prescribed propofol. METHODS: Critically ill adults from 11 academic medical centers administered an infusion of propofol for [>or=] 24 hours were monitored at baseline and then on a daily basis until propofol was discontinued for the presence of 11 different PRIS-associated clinical manifestations and risk factors derived from 83 published case reports of PRIS. RESULTS: Among 1017 patients [medical (35%), neurosurgical (25%)], PRIS (defined as metabolic acidosis plus cardiac dysfunction and [>or=] 1 of: rhabdomyolysis, hypertriglyceridemia or renal failure occurring after the start of propofol therapy) developed in 11 (1.1%) patients an average of 3 (1-6) [median (range)] days after the start of propofol. While most (91%) of the patients who developed PRIS were receiving a vasopressor (80% initiated after the start of propofol therapy), few received a propofol dose >83 mcg/kg/min (18%) or died (18%). Compared to the 1006 patients who did not develop PRIS, the APACHE II score (25 +/- 6 vs 20 +/- 7, P = 0.01) was greater in patients with PRIS but both the duration of propofol use (P = 0.43) and ICU length of stay (P = 0.82) were similar. CONCLUSIONS: Despite using a conservative definition for PRIS, and only considering new-onset PRIS clinical manifestations, the incidence of PRIS slightly exceeds 1%. Future controlled studies focusing on evaluating whether propofol manifests the derangements of critical illness more frequently than other sedatives will need to be large. These studies should also investigate the mechanism(s) and risk factors for PRIS.

Pharmacokinetic/pharmacodynamic predictions and clinical outcomes of patients with augmented renal clearance and Pseudomonas aeruginosa bacteremia and/or pneumonia treated with extended infusion cefepime versus extended infusion piperacillin/tazobactam.

AIM: We sought to correlate pharmacokinetic (PK)/pharmacodynamic (PD) predictions of antibacterial efficacy and clinical outcomes in patients with augmented renal clearance (ARC) and Pseudomonas aeruginosa bacteremia or pneumonia treated with extended infusion cefepime or piperacillin/tazobactam. MATERIALS AND METHODS: Cefepime (2 g every 8 h) and piperacillin/tazobactam (4.5 g every 8 h) were administered over 4 h after a loading dose infused over 30 min, and minimum inhibitory concentration was determined by E-test. Published population PK evaluations in critically ill patients were used, and PD analyses were conducted using estimated patient-specific PK parameters and known minimum inhibitory concentration values for P. aeruginosa. Concentration-time profiles were generated every 6 min using first-dose drug exposure estimates including a loading infusion, and free concentration above the minimum inhibitory concentration (fT> MIC) was estimated. Clinical cure was defined as resolution of signs and symptoms attributable to P. aeruginosa infection without need for escalation of antimicrobial. RESULTS: One hundred and two patients were included (36 cefepime and 66 piperacillin/tazobactam). The two groups of patients had similar age, serum creatinine, weight, and creatinine clearance. The majority of patients required intensive care unit care (63.9% vs. 63.6%) and most had pneumonia (61%). The fT>MIC (93.6 [69.9-100] vs. 57.2 [47.6-72.4], P < 0.001) and clinical cure (91.7% vs. 74.2%, P = 0.039) were significantly higher in cefepime group, whereas mortality (8.3% vs. 22.7%, P = 0.1) and infection-related mortality (0% vs. 2%, P = 0.54) were similar. CONCLUSIONS: Patients with ARC and P. aeruginosa pneumonia and/or bacteremia who received extended-infusion cefepime achieved higher fT>MIC and clinical cure than those receiving extended infusion piperacillin/tazobactam.