Sufentanil Sublingual Tablet: A New Option for Acute Pain Management.

Objective: The purpose of this article is to review the safety and efficacy of sufentanil sublingual tablet (SST) and suggest its place in therapy for managing acute pain in patients requiring intravenous (IV) opioids. Data Sources: A MEDLINE/PubMed search was performed (2010 to April 2019) using the following keywords: sufentanil sublingual tablet, sufentanil, opioid, moderate to severe acute pain. Study Selection and Data Extraction Quantification: We included English language articles evaluating SST pharmacology, pharmacokinetics, efficacy, and safety in humans for the treatment of acute pain. Data Synthesis: SST is Food and Drug Administration approved and considered safe and effective for the treatment of acute pain in Risk Evaluation and Mitigation Strategy-certified and medically supervised health care settings. Phase III clinical trials showed a statistically significant decrease in summed pain intensity score when SST was compared with placebo. Relevance to Patient Care and Clinical Practice: SST can be a useful option in patients requiring a parenteral opioid who do not have IV access, or it may be unnecessary or difficult to obtain. Because of its quick onset and sustained analgesia, SST may also be useful for procedural pain in the critically ill, to expedite discharges for outpatient procedures, in emergency departments (EDs), and in the battlefield. Conclusions: SST can satisfy an unmet need in patients with acute pain, who require parenteral opioids, and either have no IV access or require prolonged time to achieve IV access such as patients in outpatient surgical centers, EDs, and the battlefield. During periods of parenteral opioid shortage, SST may provide another option for adequate analgesia.

The Impact of Mortality on Total Costs Within the ICU.

OBJECTIVES: The high cost of critical care has engendered research into identifying influential factors. However, existing studies have not considered patient vital status at ICU discharge. This study sought to determine the effect of mortality upon the total cost of an ICU stay. DESIGN: Retrospective cohort study. SETTING: Twenty-six ICUs at 13 hospitals in the United States. PATIENTS: 58,344 admissions from January 1, 2012, to June 30, 2016, obtained from a commercial ICU database. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The median observed cost of a unit stay was $9,619 (mean = $16,353). A multivariable regression model was developed on the log of total costs for a unit stay, using severity of illness, unit admitting diagnosis, mortality in the unit, daily unit occupancy (occupying a bed at midnight), and length of mechanical ventilation. This model had an r of 0.67 and a median difference between observed and expected costs of $437. The first few days of care and the first day receiving mechanical ventilation had the largest effect on total costs. Patients dying before unit discharge had 12.4% greater costs than survivors (p < 0.01; 99% CI = 9.3-15.5%) after multivariable adjustment. This effect was most pronounced for patients with an extended ICU stay who were receiving mechanical ventilation. CONCLUSIONS: While the largest drivers of ICU costs at the patient level are day 1 room occupancy and day 1 mechanical ventilation, mortality before unit discharge is associated with substantially higher costs. The increase was most evident for patients with an extended ICU stay who were receiving mechanical ventilation. Studies evaluating costs among ICUs need to take mortality into account.

Clinical Practice Guideline: Safe Medication Use in the ICU.

OBJECTIVE: To provide ICU clinicians with evidence-based guidance on safe medication use practices for the critically ill. DATA SOURCES: PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, CINAHL, Scopus, and ISI Web of Science for relevant material to December 2015. STUDY SELECTION: Based on three key components: 1) environment and patients, 2) the medication use process, and 3) the patient safety surveillance system. The committee collectively developed Population, Intervention, Comparator, Outcome questions and quality of evidence statements pertaining to medication errors and adverse drug events addressing the key components. A total of 34 Population, Intervention, Comparator, Outcome questions, five quality of evidence statements, and one commentary on disclosure was developed. DATA EXTRACTION: Subcommittee members were assigned selected Population, Intervention, Comparator, Outcome questions or quality of evidence statements. Subcommittee members completed their Grading of Recommendations Assessment, Development, and Evaluation of the question with his/her quality of evidence assessment and proposed strength of recommendation, then the draft was reviewed by the relevant subcommittee. The subcommittee collectively reviewed the evidence profiles for each question they developed. After the draft was discussed and approved by the entire committee, then the document was circulated among all members for voting on the quality of evidence and strength of recommendation. DATA SYNTHESIS: The committee followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation system to determine quality of evidence and strength of recommendations. CONCLUSIONS: This guideline evaluates the ICU environment as a risk for medication-related events and the environmental changes that are possible to improve safe medication use. Prevention strategies for medication-related events are reviewed by medication use process node (prescribing, distribution, administration, monitoring). Detailed considerations to an active surveillance system that includes reporting, identification, and evaluation are discussed. Also, highlighted is the need for future research for safe medication practices that is specific to critically ill patients.

Drug Class Combination-Associated Acute Kidney Injury.

OBJECTIVE: To evaluate the quality of available evidence of drug class combinations and their association with the development of acute kidney injury (AKI). DATA SOURCES: A search of MEDLINE and Embase databases was completed using the following terms: "risk factor AND (acute kidney injury or acute kidney failure) AND (drug or medication)." STUDY SELECTION AND DATA EXTRACTION: Inclusion criteria were the following: English language, full-text availability, and at least 1 drug-combination. Each citation was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria. The literature was evaluated using the quality of evidence component of GRADE. No standardized definition of AKI was applied throughout.. DATA SYNTHESIS: Out of 2139 total citations, 151 were assessed for full-text review, with 121 citations (6%) meeting inclusion criteria, producing76 unique drug class combinations. Overall, 56 combinations (73.7%) were considered very low quality; 12 (15.8%) were considered low quality. There were 8 (10.5%) of moderate quality, and no combination was considered high quality. 58 (76%) combinations that had a single citation,with a mean of 1.6 citations per drug class combination. The combination of nonsteroidal anti-inflammatory drugs (NSAIDs) and diuretics was reported in 10 citations, the largest number of citations. CONCLUSIONS: Our study demonstrates a lack of well-designed studies addressing drug class combination-associated AKI. The combination of NSAIDs and diuretics with or without additional renin-angiotensin aldosterone agents had the strongest level of evidence. Despite limitations, the information included in this review may result in additional scrutiny about combining certain individual nephrotoxic drugs.

Current treatment practice and outcomes. Report of the hyponatremia registry.

Current management practices for hyponatremia (HN) are incompletely understood. The HN Registry has recorded diagnostic measures, utilization, efficacy, and outcomes of therapy for eu- or hypervolemic HN. To better understand current practices, we analyzed data from 3087 adjudicated adult patients in the registry with serum sodium concentration of 130 mEq/l or less from 225 sites in the United States and European Union. Common initial monotherapy treatments were fluid restriction (35%), administration of isotonic (15%) or hypertonic saline (2%), and tolvaptan (5%); 17% received no active agent. Median (interquartile range) mEq/l serum sodium increases during the first day were as follows: no treatment, 1.0 (0.0-4.0); fluid restriction, 2.0 (0.0-4.0); isotonic saline, 3.0 (0.0-5.0); hypertonic saline, 5.0 (1.0-9.0); and tolvaptan, 4.0 (2.0-9.0). Adjusting for initial serum sodium concentration with logistic regression, the relative likelihoods for correction by 5 mEq/l or more (referent, fluid restriction) were 1.60 for hypertonic saline and 2.55 for tolvaptan. At discharge, serum sodium concentration was under 135 mEq/l in 78% of patients and 130 mEq/l or less in 49%. Overly rapid correction occurred in 7.9%. Thus, initial HN treatment often uses maneuvers of limited efficacy. Despite an association with poor outcomes and availability of effective therapy, most patients with HN are discharged from hospital still hyponatremic. Studies to assess short- and long-term benefits of correction of HN with effective therapies are needed.

A multicenter study of the point prevalence of drug-induced hypotension in the ICU.

OBJECTIVE: To determine the point prevalence of drug-induced hypotension episodes in critically ill patients, to assess the episodes resulting from error, and to describe how episodes are treated. DESIGN: Multicenter observational, 24-hour snapshot study. SETTING: Forty-seven ICUs in 27 institutions located in the United States, Canada, and Singapore. PATIENTS: A total of 688 ICU patients were evaluated. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were included in the study if they had an episode of hypotension in the 24 hours prior to the clinical pharmacists' evaluation. The definition for a hypotensive episode is either a systolic blood pressure less than 90 mm Hg or a decrease in systolic blood pressure of 30 mm Hg over a 2-hour period. Each episode of unintentional hypotension was assessed for suspected drug-related causes. When a drug-related cause was suspected, an objective assessment tool, the modified Kramer, was used to determine causality. A score of at least "possible" was considered drug induced, referred to as a "drug-related hazardous condition." A drug-related hazardous condition is the temporal gap (intermediate stage) between the identification of an adverse drug reaction and the subsequent onset of drug-induced injury, known as an "adverse drug event." Drug-induced episodes were evaluated for medication errors and treatment. One hundred fifty-eight patients experienced 204 hypotensive episodes that were considered unintentional and drug related. Common drugs implicated included propofol, fentanyl, metoprolol, lorazepam, hydralazine, and furosemide. A total of 54 episodes (26.5%) resulted from medication errors. Common error types were improper dose/quantity (46%) and prescribing (25%). A total of 56.9% episodes were treated. CONCLUSIONS: Many hypotensive episodes in the ICU are drug related and require treatment. A substantial portion of these episodes result from errors and are therefore preventable. This presents opportunities to improve prescribing including optimizing drug dosing to avoid possible patient harm from drug-induced hypotension.

Benzodiazepine versus nonbenzodiazepine-based sedation for mechanically ventilated, critically ill adults: a systematic review and meta-analysis of randomized trials.

BACKGROUND: Use of dexmedetomidine or propofol rather than a benzodiazepine sedation strategy may improve ICU outcomes. We reviewed randomized trials comparing a benzodiazepine and nonbenzodiazepine regimen in mechanically ventilated adult ICU patients to determine if differences exist between these sedation strategies with respect to ICU length of stay, time on the ventilator, delirium prevalence, and short-term mortality. METHODS: We searched CINAHL, MEDLINE, the Cochrane databases, and the American College of Critical Care Medicine's Pain, Agitation, Delirium Management Guidelines' literature database from 1996 to 2013. Citations were screened for randomized trials that enrolled critically ill, mechanically ventilated adults comparing an IV benzodiazepine-based to a nonbenzodiazepine-based sedative regimen and reported duration of ICU length of stay, duration of mechanical ventilation, delirium prevalence, and/or short-term mortality. Trial characteristics and results were abstracted in duplicate and independently, and the Cochrane risk of bias tool was used for quality assessment. We performed random effects model meta-analyses where possible. RESULTS: We included six trials enrolling 1,235 patients: midazolam versus dexmedetomidine (n = 3), lorazepam versus dexmedetomidine (n = 1), midazolam versus propofol (n = 1), and lorazepam versus propofol (n = 1). Compared to a benzodiazepine sedative strategy, a nonbenzodiazepine sedative strategy was associated with a shorter ICU length of stay (n = 6 studies; difference = 1.62 d; 95% CI, 0.68-2.55; I = 0%; p = 0.0007) and duration of mechanical ventilation (n = 4 studies; difference = 1.9 d; 95% CI, 1.70-2.09; I2 = 0%; p < 0.00001) but a similar prevalence of delirium (n = 2; risk ratio = 0.83; 95% CI, 0.61-1.11; I2 = 84%; p = 0.19) and short-term mortality rate (n = 4; risk ratio = 0.98; 95% CI, 0.76-1.27; I2 = 30%; p = 0.88). CONCLUSIONS: Current controlled data suggest that use of a dexmedetomidine- or propofol-based sedation regimen rather than a benzodiazepine-based sedation regimen in critically ill adults may reduce ICU length of stay and duration of mechanical ventilation. Larger controlled studies are needed to further define the impact of nonbenzodiazepine sedative regimens on delirium and short-term mortality.

Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit.

OBJECTIVE: To revise the "Clinical Practice Guidelines for the Sustained Use of Sedatives and Analgesics in the Critically Ill Adult" published in Critical Care Medicine in 2002. METHODS: The American College of Critical Care Medicine assembled a 20-person, multidisciplinary, multi-institutional task force with expertise in guideline development, pain, agitation and sedation, delirium management, and associated outcomes in adult critically ill patients. The task force, divided into four subcommittees, collaborated over 6 yr in person, via teleconferences, and via electronic communication. Subcommittees were responsible for developing relevant clinical questions, using the Grading of Recommendations Assessment, Development and Evaluation method (http://www.gradeworkinggroup.org) to review, evaluate, and summarize the literature, and to develop clinical statements (descriptive) and recommendations (actionable). With the help of a professional librarian and Refworks database software, they developed a Web-based electronic database of over 19,000 references extracted from eight clinical search engines, related to pain and analgesia, agitation and sedation, delirium, and related clinical outcomes in adult ICU patients. The group also used psychometric analyses to evaluate and compare pain, agitation/sedation, and delirium assessment tools. All task force members were allowed to review the literature supporting each statement and recommendation and provided feedback to the subcommittees. Group consensus was achieved for all statements and recommendations using the nominal group technique and the modified Delphi method, with anonymous voting by all task force members using E-Survey (http://www.esurvey.com). All voting was completed in December 2010. Relevant studies published after this date and prior to publication of these guidelines were referenced in the text. The quality of evidence for each statement and recommendation was ranked as high (A), moderate (B), or low/very low (C). The strength of recommendations was ranked as strong (1) or weak (2), and either in favor of (+) or against (-) an intervention. A strong recommendation (either for or against) indicated that the intervention's desirable effects either clearly outweighed its undesirable effects (risks, burdens, and costs) or it did not. For all strong recommendations, the phrase "We recommend …" is used throughout. A weak recommendation, either for or against an intervention, indicated that the trade-off between desirable and undesirable effects was less clear. For all weak recommendations, the phrase "We suggest …" is used throughout. In the absence of sufficient evidence, or when group consensus could not be achieved, no recommendation (0) was made. Consensus based on expert opinion was not used as a substitute for a lack of evidence. A consistent method for addressing potential conflict of interest was followed if task force members were coauthors of related research. The development of this guideline was independent of any industry funding. CONCLUSION: These guidelines provide a roadmap for developing integrated, evidence-based, and patient-centered protocols for preventing and treating pain, agitation, and delirium in critically ill patients.

Pharmacological management of sedation and delirium in mechanically ventilated ICU patients: remaining evidence gaps and controversies.

Although pharmacotherapy remains the mainstay for the prevention and treatment of pain, anxiety, and delirium (PAD) in the intensive care unit (ICU), many of the PAD-related medications currently used may lead to unintended consequences, particularly when these agents are administered at excessive doses for prolonged periods. The method by which these medications are administered and titrated is increasingly being recognized as potentially affecting patient outcomes as much as the drug itself. Drugs once thought to have a pharmacologically desirable profile in reducing PAD have been shown to have either little benefit, the potential for significant risk associated with any benefit, or in some cases, the potential to worsen patient outcome. The recently published American College of Critical Care Medicine (ACCM) Pain, Agitation, and Delirium Clinical Practice Guidelines provide 12 medication-related recommendations surrounding the prevention and treatment of PAD. This paper (1) provides the ICU bedside clinician with more background on the most important, and in some cases most contentious and challenging areas, of sedation and delirium pharmacotherapy in the critical care setting; (2) provides an update on the most recent evidence surrounding the prevention and treatment of agitation and delirium in ICU; and (3) highlights areas that require further investigation and provide practical strategies by which to apply current evidence in this area to daily ICU practice.

Analgosedation: a paradigm shift in intensive care unit sedation practice.

OBJECTIVE: To critically evaluate the use of analgosedation in the management of agitation in critically ill mechanically ventilated patients. DATA SOURCES: Literature was accessed through MEDLINE (1948-November 2011) and Cochrane Library (2011, issue 1) using the terms analgosedation, analgosedation, or analgesia-based sedation alone or in combination with intensive care unit or critically ill. Reference lists of related publications were also reviewed. STUDY SELECTION AND DATA EXTRACTION: All articles published in English were evaluated. Randomized controlled trials examining critically ill mechanically ventilated patients older than 18 years were included. DATA SYNTHESIS: Limitations of current sedation practices include serious adverse drug events, prolonged mechanical ventilation time, and intensive care unit (ICU) length of stay. Studies have demonstrated that analgosedation, a strategy that manages patient pain and discomfort first, before providing sedative therapy, results in improved patient outcomes compared to standard sedative-hypnotic regimens. Nine randomized controlled trials comparing remifentanil-based analgosedation to other commonly used agents (fentanyl, midazolam, morphine, and propofol) for ICU sedation and 1 trial comparing morphine to daily sedation interruption with propofol or midazolam were reviewed. Remifentanil is an ideal agent for analgosedation due to its easy titratability and organ-independent metabolism. When compared to sedative-hypnotic regimens, remifentanil-based regimens were associated with shorter duration of mechanical ventilation, more rapid weaning from the ventilator, and shorter ICU length of stay. Compared to fentanyl-based regimens, remifentanil had similar efficacy with the exception of increased pain requirements upon remifentanil discontinuation. Analgosedation was well tolerated, with no significant differences in hemodynamic stability compared to sedative-hypnotic regimens. CONCLUSIONS: Analgosedation is an efficacious and well-tolerated approach to management of ICU sedation with improved patient outcomes compared to sedative-hypnotic approaches. Additional well-designed trials are warranted to clarify the role of analgosedation in the management of ICU sedation, including trials with nonopioid analgesics.

Acute kidney injury and cardiovascular outcomes in acute severe hypertension.

BACKGROUND: Little is known about the association of kidney dysfunction and outcome in acute severe hypertension. This study aimed to measure the association between baseline chronic kidney disease (estimated glomerular filtration rate), acute kidney injury (AKI, decrease in estimated glomerular filtration rate > or =25% from baseline) and outcome in patients hospitalized with acute severe hypertension. METHODS AND RESULTS: The Studying the Treatment of Acute Hypertension (STAT) registry enrolled patients with acute severe hypertension, defined as > or =1 blood pressure measurement >180 mm Hg systolic and/or >110 mm Hg diastolic and treated with intravenous antihypertensive therapy. Data were compared across groups categorized by admission estimated glomerular filtration rate and AKI during admission. On admission, 79% of the cohort (n=1566) had at least mild chronic kidney disease (estimated glomerular filtration rate <60 mL/min in 46%, <30 mL/min in 22%). Chronic kidney disease patients were more likely to develop heart failure (P<0.0001), non-ST-elevation myocardial infarction (P=0.003), and AKI (P<0.007). AKI patients were at greater risk of heart failure and cardiac arrest (P< or =0.0001 for both). Subjects with AKI experienced higher mortality at 90 days (P=0.003). Any acute loss of estimated glomerular filtration rate during hospitalization was independently associated with an increased risk of death (odds ratio, 1.05; P=0.03 per 10-mL/min decline). Other independent predictors of mortality included increasing age (P<0.0001), male gender (P=0.016), white versus black race (P=0.003), and worse baseline kidney function (P=0.003). CONCLUSIONS: Chronic kidney disease is a common comorbidity among patients admitted with acute severe hypertension, and AKI is a frequent form of acute target organ dysfunction, particularly in those with baseline chronic kidney disease. Any degree of AKI is associated with a greater risk of morbidity and mortality.

Terlipressin in hepatorenal syndrome.

OBJECTIVE: To compare the pharmacology, dosing, and adverse reactions of vasopressin and terlipressin for the treatment of hepatorenal syndrome (HRS) and assess the efficacy of the investigational drug terlipressin for HRS. DATA SOURCES: Articles evaluating prospective studies for vasopressin and terlipressin were discussed after being identified through PubMed (1966-November 2010), International Pharmaceutical Abstracts (1970-November 2010), and EMBASE (1985-November 2010) with combinations of the following terms: vasopressin, terlipressin, and hepatorenal syndrome. In addition, reference citations from publications identified were reviewed. Thirteen studies were identified for terlipressin, along with 4 meta-analyses and 1 case report. For vasopressin, 2 studies were identified. STUDY SELECTION AND DATA EXTRACTION: Prospective clinical studies directly comparing terlipressin and vasopressin were evaluated, as well as prospective clinical studies and meta-analyses for terlipressin in HRS. DATA SYNTHESIS: No randomized, placebo-controlled trials using vasopressin for the treatment of type I HRS have been published, and 4 randomized studies involving 197 patients provide the most current outcome data for use of terlipressin in HRS. Terlipressin differs significantly from vasopressin with regard to its pharmacology, dosing, and adverse drug reaction profile. There is a paucity of data on vasopressin for HRS. CONCLUSIONS: No definitive recommendations can be made for the use of terlipressin for this indication until further, well-conducted studies are performed.

Predictors of 90-day readmission among patients with acute severe hypertension. The cross-sectional observational Studying the Treatment of Acute hyperTension (STAT) study.

BACKGROUND: Acute severe hypertension can be a life-threatening emergency. The objective of this study was to describe the frequency of rehospitalization for patients with acute severe hypertension and to identify clinical predictors of 90-day rehospitalization. METHODS: In this observational cross-sectional study, consecutive patients were identified retrospectively (January 2007 to April 2008) through uniform data query of hospital pharmacy databases in 25 hospitals in the United States. Eligible patients were > or =18 years old, had systolic blood pressure >180 mm Hg and/or diastolic blood pressure >110 mm Hg, and had received intravenous antihypertensive therapy within 24 hours of presentation. Data were collected on patient demographics, medical history, laboratory findings, antihypertensive therapies, resource utilization, hospital-associated events, readmission within 90 days of hospital discharge, and death up to 6 months following the index hospitalization. RESULTS: The 90-day readmission rate was 35% (354/1,009) of patients discharged home alive and with known readmission status; 41% (144/354) were readmitted more than once. Of these 354 patients, readmission was for acute severe hypertension in 29% (n = 101). Eighteen (1.9%) patients died between hospital discharge and 90 days. Factors associated with readmission for hypertension included previous hospitalization for acute severe hypertension, history of drug abuse, and presenting with seizures or shortness of breath. Patients with an admitting diagnosis of hypertension were 94% more likely to be readmitted. CONCLUSIONS: More than one third of patients discharged home after hospitalization for severe hypertension were rehospitalized at least once within 90 days, more than one quarter for acute severe hypertension. Further studies are warranted to determine the impact of other variables on readmission rates and clinical outcomes in this population.

A cost-minimization analysis of dexmedetomidine compared with midazolam for long-term sedation in the intensive care unit.

OBJECTIVE: To compare the intensive care unit costs and determine factors influencing these costs in mechanically ventilated patients randomized to dexmedetomidine or midazolam by continuous infusion. DESIGN: Cost minimization analysis of a double-blind, multicenter clinical trial randomizing patients 2:1 to receive dexmedetomidine or midazolam from the institutional perspective. SETTING: Sixty-eight intensive care units in the United States, Australia, New Zealand, Brazil, and Argentina. PATIENTS: A total of 366 intubated intensive care unit patients anticipated to require sedation for >24 hrs. MEASUREMENTS AND MAIN RESULTS: Intensive care unit resource use was compared within the two treatment arms, using the U.S. representative costs for these resources. The analyses characterized patient costs from start of study drug until intensive care unit discharge including costs associated with the intensive care unit stay, costs during mechanical ventilation, study drug acquisition cost, and costs of treating adverse drug reactions probably or possibly related to study drugs. Blinded to treatment group, costs were calculated using Medicare reimbursement schedules, average IMS drug costs, expert opinion, and peer-reviewed literature. Censored lengths of intensive care unit stay and mechanical ventilation were imputed, using a nonparametric adjustment algorithm. Crude and multivariate median regressions were performed to relate intensive care unit cost and treatment. Including drug acquisition cost, sedation with dexmedetomidine was associated with a median total intensive care unit cost savings of $9679 (confidence interval, $2314-$17,045) compared with midazolam. The primary cost drivers were reduced costs of intensive care unit stay (median savings, $6584, 95% confidence interval, $727-$12,440) and reduced costs of mechanical ventilation (median savings, $2958, 95% confidence interval, $698-$5219). CONCLUSIONS: Continuous sedation with dexmedetomidine results in significantly lower total intensive care unit costs compared with midazolam infusion for intensive care unit sedation, primarily due to decreased intensive care unit stay costs and reduced mechanical ventilation costs.

State of the art review: Intravenous fat emulsions: Current applications, safety profile, and clinical implications.

OBJECTIVE: To review the current state of the science regarding intravenous fat emulsions (IVFEs), with an emphasis on their safety profile. DATA SOURCES: Articles were identified via a search of the MEDLINE database, including publications from 1979 to December 2009, using a search string that included the terms parenteral nutrition, lipid emulsion, fat emulsion, IVFE, safety, adverse effect, neonate intralipid, and terms describing a range of specific adverse events (AEs) such as pancreatitis. STUDY SELECTION AND DATA EXTRACTION: We selected articles that allowed us to compare the results of clinical trials involving delivery of medications via IVFEs with the historical use and effects of IVFEs in parenteral nutrition, with an emphasis on AEs. We focused on 2 drugs in current use that are administered intravenously in lipid emulsions: propofol and clevidipine. DATA SYNTHESIS: Clearance of the fat particles in IVFEs is mediated by the enzyme lipoprotein lipase. AEs are more likely if the rate or duration of IVFE administration exceeds the enzyme's clearance capacity. AEs are also more likely after administration of a 10% IVFE formulation than a 20% formulation, because the higher concentration of free phospholipid in the 10% formulation interferes with lipoprotein lipase activity. AEs can be reduced by administering IVFEs at a dosage < or = 2.5 g/kg/day and at a rate < or = 0.11 g/kg/h. The anesthetic agent propofol, which is formulated in a 10% IVFE, has been used clinically for 25 years. Typical AEs associated with propofol use include infection, high plasma triglyceride concentrations, and pancreatitis. Recent clinical trials involving clevidipine, which is formulated in a 20% IVFE, have demonstrated a low rate of lipid-related AEs. CONCLUSIONS: The results of this review demonstrate that IVFEs are well tolerated when administered in accordance with guideline recommendations.

Intravenous to oral conversion of antihypertensives: a toolkit for guideline development.

OBJECTIVE: To provide a toolkit of information for hospitals to use in developing intravenous to oral conversion protocols for antihypertensives. DATA SOURCES: Articles describing intravenous to oral conversion protocols for any therapeutic category were identified in an English-language MEDLINE search (1990-April 2010) using a wide variety of MeSH terms. References from selected articles were reviewed for additional material. STUDY SELECTION AND DATA EXTRACTION: Experimental and observational English-language studies and review articles that focused on oral transition of intravenous drugs were selected. DATA SYNTHESIS: Most of the literature on conversion from intravenous to oral formulations involves antimicrobials. There is considerable evidence documenting reduced costs and improved patient flow through the health-care system following implementing these protocols with drugs like antimicrobials, histamine-2 receptor antagonists, and proton pump inhibitors. Although antihypertensives have not been studied, principles and implementation strategies used for other drug classes can be applied to antihypertensives. Guidance is provided on framing the problem, issues surrounding oral absorption principles, information pertaining to oral conversion in specific disease states, and implementation and documentation strategies. Detailed tables of oral and intravenous antihypertensives are provided. CONCLUSIONS: We recommend that hospitals consider developing protocols on conversion of intravenous to oral antihypertensives in an attempt to reduce unnecessarily prolonged intravenous therapy. Information contained in this article can be used as a toolkit to select information specific to the characteristics of individual health-care systems.

Adherence to heart failure management medications following cardiac resynchronization therapy.

Objective: The purpose of this study is to assess the real-world impact of cardiac resynchronization therapy (CRT) on adherence to heart failure (HF) medications.Methods: MarketScan administrative health care claims data from 2008 to 2014 among patients with HF were used. The date of first CRT implantation served as the index date. Adherence to guideline-directed medical therapy (GDMT) classes were compared during pre- and post-index periods using proportion of days covered (PDC). Comparisons between the two periods were made using the Wilcoxon sign-rank test for continuous PDC and McNemar's test for dichotomized PDC.Results: Increases in medication adherence were observed for major classes of HF GDMT medications. Specifically, adherence to angiotensin-converting enzyme inhibitors (ACE-I), angiotensin receptor blockers (ARB), beta blockers (BB), and furosemide increased by 22, 24, 32, and 28% (all p < .001), respectively, in the 12 months pre to 12 months post-CRT. Large increases between the pre- and post-CRT period were also observed when considering adherence as dichotomized PDC ≥0.80 in the 12 months pre- versus post-CRT.Conclusion: Adherence to HF medications significantly improved among HF patients post-CRT implantation. Further research is needed to better understand the underlying determinants of this effect, including whether the effect is attributable to factors such as enhanced patient monitoring and improved access to high-quality specialized HF care among patients receiving CRT.

Practice patterns, outcomes, and end-organ dysfunction for patients with acute severe hypertension: the Studying the Treatment of Acute hyperTension (STAT) registry.

BACKGROUND: Limited data are available on the care of patients with acute severe hypertension requiring hospitalization. We characterized contemporary practice patterns and outcomes for this population. METHODS: STAT is a 25-institution, US registry of consecutive patients with acute severe hypertension (>180 mm Hg systolic and/or >110 mm Hg diastolic; >140 and/or >90 for subarachnoid hemorrhage) treated with intravenous therapy in a critical care setting. RESULTS: One thousand five hundred eighty-eight patients were enrolled (January 2007 to April 2008). Median age was 58 years (interquartile range 49-70 years), 779 (49%) were women, and 892 (56%) were African American; 27% (n = 425) had a prior admission for acute hypertension and 486 (31%) had chronic kidney disease. Median qualifying blood pressure (BP) was 200 (186, 220) systolic and 110 (93, 123) mm Hg diastolic. Initial intravenous antihypertensive therapies used to control BP varied, with 1,009 (64%) patients requiring multiple drugs. Median time to achieve a systolic BP <160 mm Hg (<140 mm Hg for subarachnoid hemorrhage) was 4.0 (0.8, 12) hours; 893 (60%) had reelevation to >180 (>140 for subarachnoid hemorrhage) after initial control; and 63 (4.0%) developed iatrogenic hypotension. Hospital mortality was 6.9% (n = 109) with an aggregate 90-day mortality rate of 11% (174/1,588); 59% (n = 943) had acute/worsening end-organ dysfunction during hospitalization. The 90-day readmission rate was 37% (523/1,415), of which one quarter (132/523) was due to recurrent acute severe hypertension. CONCLUSION: This study highlights heterogeneity in care, BP control, and outcomes of patients hospitalized with acute severe hypertension.