Impact of a Procalcitonin-Based Protocol on Antibiotic Exposure and Costs in Critically Ill Patients.

To examine the impact before and after adoption of a procalcitonin-based protocol to guide sepsis management has on antibiotic use, care costs, and outcomes of critically ill patients. DESIGN: Before-after study. SETTING: ICU of an academic tertiary care center. PATIENTS: Adults over 18 years old admitted to the ICU from January 1, 2017, to January 31, 2020. INTERVENTIONS: In this before-after study, we compared the use of medications, outcomes, and overall cost before and after the introduction of a procalcitonin-based protocol for evaluation and treatment of sepsis. MEASUREMENTS AND MAIN RESULTS: The final study cohort consisted of 1,793 patients admitted to the ICU, 776 patients pre-procalcitonin and 1,017 patients in the post-procalcitonin period. Patients were not different in the pre-procalcitonin adoption period compared with post-procalcitonin adoption with regard to gender, age (62.0 vs 62.6), race, or comorbidities. Patients admitted during the post-procalcitonin adoption period were less likely to receive the examined broad-spectrum antibiotics (odds ratio, -0.58; CI, -0.99 to -0.17; p < 0.01) than patients during the pre-procalcitonin adoption period. The odds of inhospital death did not differ after procalcitonin adoption when compared with before (0.87; CI, 0.70-1.09; p = 0.234). Total charges for each admission were significantly less in the post-procalcitonin adoption period $3,834.99 compared with pre-procalcitonin adoption $4,429.47 (p < 0.05). Patients post-procalcitonin adoption incurred $1,127.18 per patient less in total charges (-1,127.18; CI, -2,014.74 to -239.62; p = 0.013) after controlling for relevant factors. CONCLUSIONS: In critically ill patients in a large U.S. tertiary care hospital, the adoption of a procalcitonin-based protocol for evaluation and treatment of sepsis may be associated with decreased antibiotic use and significant cost savings, with no change in mortality.

The impact of antihypertensive use in the treatment of acute ischemic stroke in patients receiving alteplase.

BACKGROUND: Treatment of acute ischemic stroke (AIS) with intravenous alteplase within 4.5 h of symptom onset is associated with neurologic improvement. High baseline blood pressure (BP) and BP variability during the first 24 h of AIS is associated with increased early adverse events and death. The purpose of this study is to characterize the incidence of poor neurologic outcome in patients treated with alteplase for AIS who received antihypertensive medications prior to and within the first 24 h following alteplase administration compared with patients who did not. METHODS: This was a multicenter, retrospective cohort of patients >18 years diagnosed with AIS from January 1, 2011 through December 31, 2015 who received one or more antihypertensive medication in the first 24 h of AIS in patients receiving alteplase compared to controls. The primary endpoint was poor neurologic outcome at 90 days, according to modified Rankin Scale ≥3. Univariate analysis was conducted using Chi-square, Fisher's exact test, or Mann-Whitney U test. Multivariable logistic regression was conducted to determine independent predictors of poor outcome. RESULTS: Of the 587 patients evaluated, 351 (59.7%) were included, of which 127 (36.2%) received antihypertensive(s). More patients in the antihypertensive treatment group had a history of hypertension (88.2% vs. 69.6%, p < 0.01), diabetes (37% vs. 25.5%, p = 0.03) and chronic kidney disease (19.7% vs. 8.5%, p < 0.01). Intravenous push labetalol was most commonly administered (81.2%), followed by nicardipine (44.1%), and hydralazine (22%). More patients in the antihypertensive treatment group experienced poor neurologic outcome at 90 days (53.5% vs. 38.8%, p < 0.01), however, this finding was not observed after multivariable logistic regression. CONCLUSION: Antihypertensive treatment in the first 24 h of AIS was associated with poor neurologic outcomes at 90 days. However, after controlling for other clinical factors in a multivariable logistic regression, this association was no longer observed.

Major publications in the critical care pharmacotherapy literature: January-December 2017.

PURPOSE: To summarize selected meta-analyses and trials related to critical care pharmacotherapy published in 2017. The Critical Care Pharmacotherapy Literature Update (CCPLU) Group screened 32 journals monthly for impactful articles and reviewed 115 during 2017. Two meta-analyses and eight original research trials were reviewed here from those included in the monthly CCPLU. Meta-analyses on early, goal-directed therapy for septic shock and statin therapy for acute respiratory distress syndrome were summarized. Original research trials that were included evaluate thrombolytic therapy in severe stroke, hyperoxia and hypertonic saline in septic shock, intraoperative ketamine for prevention of post-operative delirium, intravenous ketorolac dosing regimens for acute pain, angiotensin II for vasodilatory shock, dabigatran reversal with idarucizumab, bivalirudin versus heparin monotherapy for myocardial infarction, and balanced crystalloids versus saline fluid resuscitation. CONCLUSION: This clinical review provides perspectives on impactful critical care pharmacotherapy publications in 2017.

Pharmacist Participation in Acute Ischemic Stroke Decreases Door-to-Needle Time to Recombinant Tissue Plasminogen Activator.

BACKGROUND: Pharmacists are an important member of the stroke team and aid in obtaining medication and medical history, providing education, managing blood pressure, reviewing exclusion criteria for recombinant tissue plasminogen activator (rtPA), and facilitating reconstitution and administration of rtPA. OBJECTIVE: To determine if pharmacist presence at bedside during acute ischemic stroke resulted in a reduction in door-to-needle (DTN) times. METHODS: This was a retrospective cohort study between January 1, 2011 and December 31, 2015 of patients who received rtPA for acute ischemic stroke in either the emergency department or hospital. RESULTS: Of the 125 included patients, 45 patients (36%) had a pharmacist present (PharmD group) and 80 patients (64%) did not (no PharmD group). Median DTN time was significantly shorter in the PharmD group: 48 minutes versus 73 minutes in the no PharmD group ( P < 0.01). The goal of DTN ≤60 minutes was met in 71% of patients in the PharmD group compared to 29% ( P < 0.01). Pharmacist at the bedside was the only factor found to be independently associated with reduction DTN time (ßcoefficient -23.5 minutes, 95% confidence interval [95% CI] -38.6 to -8.50 minutes). CONCLUSION: A pharmacist at the bedside of emergency department or in-patient stroke codes reduced DTN time by a median of 23.5 minutes after adjusting for confounding factors and increased the percentage of patients meeting DTN goal time of ≤60 minutes by 49%. These findings support the inclusion of a stroke-competent pharmacist in the bedside response team for acute ischemic stroke patients.

Multidrug-Resistant Organism Infections in Patients with Left Ventricular Assist Devices.

Left ventricular assist devices improve survival prospects in patients with end-stage heart failure; however, infection complicates up to 59% of implantation cases. How many of these infections are caused by multidrug-resistant organisms is unknown. We sought to identify the incidence, risk factors, and outcomes of multidrug-resistant organism infection in patients who have left ventricular assist devices. We retrospectively evaluated the incidence of multidrug-resistant organisms and the independent risk factors associated with them in 57 patients who had permanent left ventricular assist devices implanted at our institution from May 2007 through October 2011. Outcomes included death, transplantation, device explantation, number of subsequent hospital admissions, and number of subsequent admissions related to infection. Infections were categorized in accordance with criteria from the Infectious Diseases Council of the International Society for Heart and Lung Transplantation. Multidrug-resistant organism infections developed in 18 of 57 patients (31.6%)-a high incidence. We found 3 independent risk factors: therapeutic goal (destination therapy vs bridging), P=0.01; body mass index, P=0.04; and exposed velour at driveline exit sites, P=0.004. We found no significant differences in mortality, transplantation, or device explantation rates; however, there was a statistically significant increase in postimplantation hospital admissions in patients with multidrug-resistant organism infection. To our knowledge, this is the first report in the medical literature concerning multidrug-resistant organism infection in patients who have permanent left ventricular assist devices.

Early administration of therapeutic anticoagulation following intravenous thrombolysis for acute cardiogenic embolic stroke caused by left ventricular thrombus: case report and topic review.

Cardiogenic cerebral embolism represents 20% of all acute ischemic strokes (AISs) with one-third of these being caused by left ventricular thrombus (LVT). LVT is not a contraindication for treatment with intravenous recombinant tissue plasminogen activator (IV rtPA) for AIS. However, the subsequent treatment of a potentially unstable LVT is contraindicated for 24 h following the use of IV rtPA according to current guidelines. We present a 66-year-old man with AIS treated with IV rtPA. Echocardiogram shortly after treatment demonstrated both a large apical and septal thrombus in the left ventricle and at 12 h post IV rtPA infusion, therapeutic anticoagulation with heparin was started without complication. In practice, the action of IV rtPA outlasts its apparent half-life because of thrombin-binding and the prolonged effects and longer half-life of its product, plasmin; however, the pharmacokinetics do not warrant prolonged avoidance of therapeutic anticoagulation when clinically indicated. Our case demonstrates that anticoagulation for potentially unstable LVT can be safely initiated at 12 h following IV rtPA treatment for AIS.

Major publications in the critical care pharmacotherapy literature: January-December 2013.

PURPOSE: Ten recently published articles with important implications for critical care pharmacotherapy are summarized. SUMMARY: The Critical Care Pharmacotherapy Literature Update (CCPLU) group is a national assembly of experienced intensive care unit (ICU) pharmacists across the United States. Group members monitor 25 peer-reviewed journals on an ongoing basis to identify literature relevant to pharmacy practice in the critical care setting. After evaluation by CCPLU group members, selected articles are chosen for summarization and distribution to group members nationwide based on (1) applicability to critical care practice, (2) relevance to pharmacy practitioners, and (3) quality of evidence or research methodology. Hundreds of relevant articles were evaluated by the group during the period January-December 2013, of which 98 were summarized and disseminated nationally to CCPLU group members. Among those 98 publications, 10 deemed to be of particularly high utility to critical care practitioners were included in this review. The 10 articles address topics such as rapid lowering of blood pressure in patients with intracranial hemorrhage, adjunctive therapy to prevent renal injury due to acute heart failure, triple-drug therapy to improve neurologic outcomes after cardiac arrest, and continuous versus intermittent infusion of ß-lactam antibiotics in severe sepsis. CONCLUSION: There were many important additions to the critical care pharmacotherapy literature in 2013, including an updated guideline on the management of myocardial infarction and reports on advances in research focused on improving outcomes in patients with stroke or cardiac arrest and preventing the spread of drug-resistant pathogens in the ICU.

New drugs of abuse.

Drug abuse is a common problem and growing concern in the United States, and over the past decade, novel or atypical drugs have emerged and have become increasingly popular. Recognition and treatment of new drugs of abuse pose many challenges for health care providers due to lack of quantitative reporting and routine surveillance, and the difficulty of detection in routine blood and urine analyses. Furthermore, street manufacturers are able to rapidly adapt and develop new synthetic isolates of older drugs as soon as law enforcement agencies render them illegal. In this article, we describe the clinical and adverse effects and purported pharmacology of several new classes of drugs of abuse including synthetic cannabinoids, synthetic cathinones, salvia, desomorphine, and kratom. Because many of these substances can have severe or life-threatening adverse effects, knowledge of general toxicology is key in recognizing acute intoxication and overdose; however, typical toxidromes (e.g., cholinergic, sympathomimetic, opioid, etc.) are not precipitated by many of these agents. Medical management of patients who abuse or overdose on these drugs largely consists of supportive care, although naloxone may be used as an antidote for desomorphine overdose. Symptoms of aggression and psychosis may be treated with sedation (benzodiazepines, propofol) and antipsychotics (haloperidol or atypical agents such as quetiapine or ziprasidone). Other facets of management to consider include treatment for withdrawal or addiction, nutrition support, and potential for transmission of infectious diseases.

Management of diabetic ketoacidosis.

Diabetes, a chronic medical condition, continues to increase in prevalence. One of the most severe complications of diabetes, diabetic ketoacidosis (DKA), results from insulin deficiency and is a medical emergency that is frequently encountered in the emergency department. Prompt diagnosis, assessment of key laboratory values, appropriate treatment, and close monitoring are important to the successful treatment of this complex metabolic disorder. Fluid repletion and insulin administration are mainstays of DKA treatment and serve to restore normal hemodynamic status while decreasing the metabolic acidosis. Careful monitoring of glucose concentrations, vital signs, and electrolytes is essential to prevent complications arising from the treatment of DKA. This article provides an overview of the pathophysiology, presentation, diagnosis, treatment, monitoring, and complications of DKA.