Personalisation and embodiment in e-Learning for health professionals: A randomised controlled trial.

PURPOSE: Mayer's theory of multimedia learning proposes that personalisation and embodiment (P/E) can improve outcomes in e-Learning. The authors hypothesised that an e-Learning module enhanced by P/E principles would lead to higher knowledge, perceived P/E and motivation among health care professionals, compared with an unenhanced module. METHODS: The authors conducted a randomised trial comparing two versions of a 30-minute multimedia e-Learning module addressing the antibiotic management of pneumonia. The unenhanced format used slides with voiceover (human voice but no visible speaker), formal language and no specific P/E strategies. The enhanced format additionally implemented P/E strategies including conversational style, polite language, visible author, social congruence, human-like presence and professional presence by subtly changing the script and substituting several short videos of subject matter experts. Participants included pharmacists, physicians and advanced practice providers from three academic and several community hospitals. Outcomes included knowledge, perceived P/E (assessed by the Congruence Personalisation Questionnaire, CPQ), motivation (assessed via the Instructional Materials Motivation Survey [IMMS] and Motivated Strategies for Learning Questionnaire [MSLQ]) and course satisfaction. RESULTS: There were 406 participants including 225 pharmacists, 109 physicians and 72 advanced practice providers. Post-module knowledge was slightly higher for the enhanced versus the unenhanced format, but the difference did not reach statistical significance (adjusted mean difference, 0.04 of 10 possible, [95% CI -0.26, 0.34], p = 0.78; Cohen d 0.02). Participant perceptions of P/E (measured via CPQ) were significantly greater for the enhanced format (difference 0.46 of 5 possible [0.35, 0.56], p < 0.001; Cohen d 0.85), as were motivational features of the e-Learning course (measured via IMMS) (difference 0.14 of 5 possible [0.02, 0.26], p = 0.02; Cohen d 0.24). Participants' overall motivational orientation (measured via MSLQ) and course satisfaction were not significantly different between the two formats (p > 0.05). CONCLUSION: Application of P/E principles to an e-Learning module led to greater perceived P/E and motivational features but did not influence knowledge.

The Incidence of Torsades de Pointes With Perioperative Triple Antiemetic Administration.

BACKGROUND: The safety of triple antiemetic therapy consisting of ondansetron, haloperidol, and a steroid, to surgical patients is unknown. OBJECTIVE: To determine the incidence of torsade de pointes (TdP) or death following perioperative administration of triple antiemetic therapy. METHODS: A retrospective cohort study identified 19,874 patients who received 22,202 doses of triple antiemetics during the 2.5-year time frame from March 4, 2020 to September 7, 2022 for surgical nausea prophylaxis or treatment of nausea. These patients above were cross-matched with an electrocardiogram and adverse outcome database; this identified 226 patients with documentation of a QTc > 450 ms, all ventricular tachycardias including TdP within 48 hours of receiving triple antiemetic therapy, or death within 7 days of receiving ondansetron. RESULTS: There were 3 patients who had documented VT (n = 3), but there were no documented incidents of TdP (n = 0). There were 9 codes called on patients within 48 hours of medication administration, and none of them were due to ventricular arrythmias (n = 0). A total of 11 patients died within 7 days of triple antiemetic therapy. Ten of the 11 deaths were determined to not be from the triple antiemetic. One patient died at home within 24 hours of the procedure of an unknown cause (n = 1). CONCLUSIONS AND RELEVANCE: No episodes of TdP were identified in patients receiving triple antiemetic therapy perioperatively, though the cause of death in 1 patient could not be determined. This suggest that low-dose triple antiemetic therapy is low risk for the development of TdP.

Nine-gene pharmacogenomics profile service: The Mayo Clinic experience.

PURPOSE: The Pharmacogenomics (PGx) Profile Service was a proof-of-concept project to implement PGx in patient care at Mayo Clinic. METHODS: Eighty-two healthy individuals aged 18 and older underwent genotyping of CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, SLCO1B1, HLA-B*58:01, and VKORC1. A PGx pharmacist was involved in ordering, meeting with patients, interpreting, reviewing, and documenting results. RESULTS: Ninety three percent were CYP1A2 rapid metabolizers, 92% CYP3A4 normal metabolizers, and 88% CYP3A5 poor metabolizers; phenotype frequencies for CYP2C19 and CYP2D6 varied. Seventy-three percent had normal functioning SLCO1B1 transporter, 4% carried the HLA-B*58:01 risk variant, and 35% carried VKORC1 and CYP2C9 variants that increased warfarin sensitivity. CONCLUSION: Pre-emptive PGx testing offered medication improvement opportunity in 56% of participants for commonly used medications. A collaborative approach involving a PGx pharmacist integrated within a clinical practice with regards to utility of PGx results allowed for implementation of the PGx Profile Service. KEY POINTS: The Mayo Clinic PGx (PGx) Profile Service was a proof-of-concept project to utilize PGx testing as another clinical tool to enhance medication selection and decrease serious adverse reactions or medication failures. Over one-half of participants in the pilot using the PGx Profile Service were predicted to benefit from pre-emptive PGx testing to guide pharmacotherapy. PGx pharmacists played a crucial role in the PGx Profile Service by educating participants, identifying medication-gene interactions, and providing evidence-based (CPIC and DPWG) PGx recommendations for past, current, and future medication us.

Implementation of preemptive DNA sequence-based pharmacogenomics testing across a large academic medical center: The Mayo-Baylor RIGHT 10K Study.

PURPOSE: The Mayo-Baylor RIGHT 10K Study enabled preemptive, sequence-based pharmacogenomics (PGx)-driven drug prescribing practices in routine clinical care within a large cohort. We also generated the tools and resources necessary for clinical PGx implementation and identified challenges that need to be overcome. Furthermore, we measured the frequency of both common genetic variation for which clinical guidelines already exist and rare variation that could be detected by DNA sequencing, rather than genotyping. METHODS: Targeted oligonucleotide-capture sequencing of 77 pharmacogenes was performed using DNA from 10,077 consented Mayo Clinic Biobank volunteers. The resulting predicted drug response-related phenotypes for 13 genes, including CYP2D6 and HLA, affecting 21 drug-gene pairs, were deposited preemptively in the Mayo electronic health record. RESULTS: For the 13 pharmacogenes of interest, the genomes of 79% of participants carried clinically actionable variants in 3 or more genes, and DNA sequencing identified an average of 3.3 additional conservatively predicted deleterious variants that would not have been evident using genotyping. CONCLUSION: Implementation of preemptive rather than reactive and sequence-based rather than genotype-based PGx prescribing revealed nearly universal patient applicability and required integrated institution-wide resources to fully realize individualized drug therapy and to show more efficient use of health care resources.

Incidence, Course, and Characteristics of Hydralazine-Associated Tachycardia During Phase I Postanesthesia Recovery.

PURPOSE: This study aims to characterize the development of tachycardia after intravenous hydralazine administration during Phase I recovery. DESIGN: Retrospective observational study design. METHODS: The medical records of 745 adult surgical patients who were administered hydralazine during Phase I recovery between January 1, 2010 and December 31, 2014 were electronically reviewed to characterize episodes of tachycardia. FINDINGS: Seventy patients (94.0 cases per 1,000 administrations; 95% confidence interval = 74.0 to 117.2) developed tachycardia with a median increase of 23 beats per minute (bpm; interquartile range [IQR] = 15 to 37), a maximum rate of 106 bpm (IQR = 103 to 111; range = 101 to 131), and duration of 28 minutes (IQR = 5 to 86). The median onset of tachycardia was 43 minutes (IQR = 20 to 93), with 40% occurring after the first hour. Tachycardia was associated with female sex (P < .001), younger age (P < .001), and those with lesser comorbidities (P < .009). CONCLUSIONS: A sizeable proportion of cases of tachycardia associated with hydralazine administration occurred after 1 hour, suggesting that these patients who may not tolerate a faster heart rate warrant longer duration of monitoring.

Rapid-sequence intubation: a review of the process and considerations when choosing medications.

OBJECTIVE: To summarize published data regarding the steps of rapid-sequence intubation (RSI); review premedications, induction agents, neuromuscular blockers (NMB), and studies supporting use or avoidance; and discuss the benefits and deficits of combinations of induction agents and NMBs used when drug shortages occur. DATA SOURCE: A search of Medline databases (1966-October 2013) was conducted. STUDY SELECTION AND DATA EXTRACTION: Databases were searched using the terms rapid-sequence intubation, fentanyl, midazolam, atropine, lidocaine, phenylephrine, ketamine, propofol, etomidate thiopental, succinylcholine, vecuronium, atracurium, and rocuronium. Citations from publications were reviewed for additional references. DATA SYNTHESIS: Data were reviewed to support the use or avoidance of premedications, induction agents, and paralytics and combinations to consider when drug shortages occur. CONCLUSIONS: RSI is used to secure a definitive airway in often uncooperative, nonfasted, unstable, and/or critically ill patients. Choosing the appropriate premedication, induction drug, and paralytic will maximize the success of tracheal intubation and minimize complications.

Intravenous metoprolol versus diltiazem for rate control in noncardiac, nonthoracic postoperative atrial fibrillation.

BACKGROUND: Little guidance exists on effective management of postoperative atrial fibrillation (POAF) following noncardiac, nonthoracic (NCNT) surgery. OBJECTIVES: The purpose of this study was to identify whether a difference exists between intravenous (IV) metoprolol and diltiazem when used to achieve hemodynamically stable rate control in POAF following NCNT surgery. METHODS: This retrospective cohort study examined critically ill adult surgical patients experiencing POAF with rapid ventricular response. Inclusion in the metoprolol or diltiazem treatment group was determined by the initial rate control agent chosen by the prescriber. The primary end point was hemodynamically stable rate control, defined by heart rate (HR) <110 beats/min and blood pressure >90 mm Hg, maintained for 6 hours. MAIN RESULTS: Patients on metoprolol (n = 66) and diltiazem (n = 55) were similar in age, comorbidities, surgical procedure distribution, acuity of illness, and home rate and rhythm control medications continued during hospitalization; 76% of diltiazem-treated patients achieved hemodynamically stable rate control, compared with only 53% of those receiving metoprolol (P = .005). Safety end points were similar between groups, including the portion requiring a new vasopressor or fluid bolus for hemodynamic support. CONCLUSIONS: In NCNT surgery, patients with POAF, IV diltiazem more effectively controlled HR and hemodynamics compared with metoprolol. Results warrant further research into optimal medical management of POAF in this population using these 2 agents.

The incidence of torsades de pointes with peri-operative low-dose ondansetron administration.

STUDY OBJECTIVE: The primary objective of this retrospective safety study was to determine the incidence of torsades de pointes (TdP) or death following perioperative administration of low-dose, 4 mg, ondansetron for postoperative nausea and vomiting. DESIGN AND SETTING: This is a single-center retrospective clinical trial. PATIENTS: The authors identified 32,737 patients who received 37,589 doses of ondansetron during a 2-year time frame between March 2009 and February 2011 for surgical nausea prophylaxis or treatment of nausea. MEASUREMENTS AND MAIN RESULTS: Patients were cross-matched with an electrocardiogram and adverse outcome database; this identified 4759 patients with documentation of a QTc >450 milliseconds (ms), all ventricular tachycardias including TdP within 48 hours of receiving ondansetron, or death within 7 days of receiving ondansetron. No patients developed TdP or died as a direct result of ondansetron administration (n = 0; event rate = 0.0 per 10,000, 95% CI 0.0 to 1.1 per 10,000). Forty-six of 32,737 surgical patients had documented monomorphic ventricular tachycardia (VT) (n = 14; event rate = 4.3 per 10,000, 95% CI 2.3 to 7.2 per 10,000) or died (n = 32; event rate = 9.8 per 10,000, 95% CI 6.7 to 13.8 per 10,000) within 48 h of ondansetron administration. All monomorphic VT episodes were precipitated by existing cardiovascular disease; and 7 of 14 patients had documented monomorphic VT prior to receiving ondansetron. Of the 32 surgical patients who died, all deaths were precipitated by pre-existing disease. CONCLUSION: No episodes of TdP were identified in patients receiving ondansetron perioperatively. This suggests that low-dose ondansetron does not contribute to the development of TdP.

Anticoagulation in COVID-19: A Systematic Review, Meta-analysis, and Rapid Guidance From Mayo Clinic.

A higher risk of thrombosis has been described as a prominent feature of coronavirus disease 2019 (COVID-19). This systematic review synthesizes current data on thrombosis risk, prognostic implications, and anticoagulation effects in COVID-19. We included 37 studies from 4070 unique citations. Meta-analysis was performed when feasible. Coagulopathy and thrombotic events were frequent among patients with COVID-19 and further increased in those with more severe forms of the disease. We also present guidance on the prevention and management of thrombosis from a multidisciplinary panel of specialists from Mayo Clinic. The current certainty of evidence is generally very low and continues to evolve.

Lack of an effect of body mass on the hemodynamic response to arginine vasopressin during septic shock.

STUDY OBJECTIVE: To determine whether body mass alters the effectiveness of a fixed-dose infusion of arginine vasopressin. DESIGN: Retrospective medical record review. SETTING: All intensive care units of a tertiary medical center. PATIENTS: Sixty-six mechanically ventilated patients who received a fixed-dose intravenous infusion of arginine vasopressin at 0.04 U/minute as the sole agent for hemodynamic support during septic shock. MEASUREMENTS AND MAIN RESULTS: Patients were divided into four groups on the basis of body mass index. Effectiveness was measured as hemodynamic stability, which was defined as the proportion of patients achieving a mean arterial pressure (MAP) of 65 mm Hg or higher, the magnitude of the change in MAP at 1 hour, and the need for additional rescue vasopressors. Secondary outcomes included mortality and length of stay. Baseline characteristics of all four groups were comparable for age, sex, and severity of illness determined by using Acute Physiology and Chronic Health Evaluation II (APACHE II), Simplified Acute Physiology II (SAPS II), and Sequential Organ Failure Assessment (SOFA) scores. The only significant differences in baseline characteristics among the groups were in their central venous pressures. The four groups similarly achieved hemodynamic stability at 1 hour after the administration of arginine vasopressin (p=0.41). We observed no significant differences among groups in the magnitude of MAP change (p=0.62), need for rescue catecholamine vasopressors (p=0.17), 28-day mortality rates (p=0.31), or length of stay in the intensive care unit (p=0.43). CONCLUSION: Body mass index did not alter the effects of arginine vasopressin on hemodynamic stability or changes in MAP when the drug was administered as a fixed-dose infusion of 0.04 U/minute. Our results do not support weight-based dosing of vasopressin, unlike the dosing for catecholamine vasopressors.

A preliminary study of a new tranexamic acid dosing schedule for cardiac surgery.

OBJECTIVE(S): The authors have developed an alternative dosing schedule for tranexamic acid that incorporates the effects of renal function on tranexamic acid concentrations. The objectives of this study were to determine if this new dosing schedule can achieve the desired plasma concentration of tranexamic acid and reduce intra- and interpatient variability in tranexamic acid plasma concentrations relative to the current dosing schedule. DESIGN: A prospective randomized trial. SETTING: A tertiary referral medical center hospital. PARTICIPANTS: Cardiac surgery patients. INTERVENTIONS: Cardiac surgery patients were randomly assigned to receive the authors' standard tranexamic acid loading dosage of 10 mg/kg given over 20 minutes, followed by an infusion of 1 mg/kg/h (9 patients), or the new drug dosage schedule described later (11 patients). MEASUREMENTS AND MAIN RESULTS: Perioperative plasma tranexamic acid concentrations were measured using high-performance liquid chromatography. From repeated-measures analysis of variance, a significant (p < 0.001) time-by-treatment interaction effect was detected indicating that differences in mean tranexamic acid concentration between treatment groups were dependent on time period. Among patients receiving the standard dosing regimen, those with renal insufficiency had lower tranexamic acid concentration at 5 minutes on cardiopulmonary bypass (p = 0.003). For patients receiving the experimental regimen, the mean tranexamic acid concentration did not differ significantly at any time point between patients with and without renal insufficiency (p > 0.20 at all time points). CONCLUSIONS: The new dosing protocol for tranexamic acid resulted in more consistent blood concentrations of tranexamic acid, but not stable tranexamic acid levels >20 microg/mL on cardiopulmonary bypass.

Comparison of a nurse initiated insulin infusion protocol for intensive insulin therapy between adult surgical trauma, medical and coronary care intensive care patients.

BACKGROUND: Sustained hyperglycemia is a known risk factor for adverse outcomes in critically ill patients. The specific aim was to determine if a nurse initiated insulin infusion protocol (IIP) was effective in maintaining blood glucose values (BG) within a target goal of 100-150 mg/dL across different intensive care units (ICUs) and to describe glycemic control during the 48 hours after protocol discontinuation. METHODS: A descriptive, retrospective review of 366 patients having 28,192 blood glucose values in three intensive care units, Surgical Trauma Intensive Care Unit (STICU), Medical (MICU) and Coronary Care Unit (CCU) in a quaternary care hospital was conducted. Patients were > 15 years of age, admitted to STICU (n = 162), MICU (n = 110) or CCU (n = 94) over 8 months; October 2003-June 2004 and who had an initial blood glucose level > 150 mg/dL. We summarized the effectiveness and safety of a nurse initiated IIP, and compared these endpoints among STICU, MICU and CCU patients. RESULTS: The median blood glucose values (mg/dL) at initiation of insulin infusion protocol were lower in STICU (188; IQR, 162-217) than in MICU, (201; IQR, 170-268) and CCU (227; IQR, 178-313); p < 0.0001. Mean time to achieving a target glucose level (100-150 mg/dL) was similar between the three units: 4.6 hours in STICU, 4.7 hours in MICU and 4.9 hours in CCU (p = 0.27). Hypoglycemia (BG < 60 mg/dL) occurred in 7% of STICU, 5% of MICU, and 5% of CCU patients (p = 0.85). Protocol violations were uncommon in all three ICUs. Mean blood glucose 48 hours following IIP discontinuation was significantly different for each population: 142 mg/dL in STICU, 167 mg/dL in MICU, and 160 mg/dL in CCU (p < 0.0001). CONCLUSION: The safety and effectiveness of nurse initiated IIP was similar across different ICUs in our hospital. Marked variability in glucose control after the protocol discontinuation suggests the need for further research regarding glucose control in patients transitioning out of the ICU.

Oxygen therapeutics: oxygen delivery without blood.

Nearly 14 million units of packed red blood cells are transfused in the United States each year. According to the U.S. Department of Health and Human Services, in 1999, 6% of hospitals reported a shortage of blood, resulting in the cancellation or postponement of surgical procedures. The many limitations and risks of transfusions of packed red blood cells in critically ill patients have facilitated interest in developing alternative agents for oxygen delivery. Over the past few decades, safe and effective substitutes have been in development. However, no currently approved agent provides both oxygen transport and volume in place of packed red blood cells. Oxygen therapeutic products have several advantages compared with packed red blood cells, including a prolonged shelf-life, lack of a cross-matching requirement, and minimal infectious risks or concerns about immunogenicity. Hemoglobin-based oxygen carriers and perfluorocarbons are being developed. Two products are undergoing clinical trials. Polyheme is undergoing a phase III study in trauma patients, and Hemopure is being evaluated in a phase II study in patients undergoing cardiopulmonary bypass surgery. A third product (Hemolink) was being evaluated in a phase III study in patients undergoing coronary artery bypass grafting surgery; however, the trial was suspended. In addition, several other hemoglobin-based oxygen carriers are in the preclinical stages. Oxygen therapeutics have several potential clinical applications in the management of perioperative blood loss, trauma, acute normovolemic hemodilution, traumatic brain injury, and blood requirements in patients who refuse or have contraindications to transfusions of red blood cells.

Agreement between bedside blood and plasma glucose measurement in the ICU setting.

STUDY OBJECTIVE: To assess the agreement between bedside glucose (bGlu) measurements and laboratory plasma glucose (pGlu) measurements in the ICU setting. DESIGN: Retrospective study. SETTING: ICU of a tertiary academic medical center. PATIENTS: One hundred ninety-seven patients admitted to the ICU from January through December 2002 who underwent 816 simultaneous bGlu and pGlu measurements. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: To calculate the agreement between the two methods of glucose measurement, the mean difference was obtained, and the limits of the agreement were calculated as the mean difference +/- 2 SDs. On 767 occasions, the mean bGlu was 159 mg/dL and the mean pGlu was 151 mg/dL (p < 0.001). The mean difference between the two techniques was 7.9 mg/dL (SD, 17.6 mg/dL), and the limits of agreement were + 43.1 and -27.2. On 31 occasions, the bGlu was reported as > 400 mg/dL, and in these cases the mean pGlu was 423 mg/dL (range, 300 to 900 mg/dL). On 18 occasions, the bGlu was reported as < 50 mg/dL, and in these cases the mean pGlu was 66.9 mg/dL (range, 13 to 198 mg/dL). CONCLUSIONS: On average, bGlu provides a reasonable estimate for pGlu. However, for the individual patient, bGlu gives an unreliable estimate for pGlu. All of those taking care of critically ill patients should be aware of the limitations of bedside glucometry.

Hospital rules-based system: the next generation of medical informatics for patient safety.

PURPOSE: The hospital rules-based system (HRBS) and its subsystems at a major medical center are described. SUMMARY: The HRBS was implemented at the Mayo Clinic to rapidly identify and communicate crucial information to the clinician in order to optimize patient care. The system also enhances workload efficiency and improves documentation and communication. The system is used by the infectious-diseases division, pharmacy services, nutritional support services, infection control, and the nursing department. The six HRBS subsystems are Web-based programs that share a common structural design and integrate computerized information from multiple institutional databases. The integrated data are presented in a user-friendly format that improves the efficiency of data retrieval. Information, such as monitoring notes and intervention information, can be entered for specific patients. The subsystems use rules designed to detect suboptimal therapy or monitoring and identify opportunities for cost savings in a timely manner. CONCLUSION: The HRBS enhances the identification of drug-related problems while optimizing patient care and improving communication and efficiency at a major medical center.

Dosing of unfractionated heparin in acute coronary syndromes.

Although the use of low-molecular-weight heparins for treatment of acute coronary syndromes (ACS) has increased in recent years, unfractionated heparin (UFH) remains the drug of choice for many patients and institutions. One reason is that this agent is safe for patients with renal dysfunction as well as those who undergo percutaneous coronary intervention or coronary artery bypass graft. The use of UFH is complicated by the increased risk of bleeding due to concurrent administration of numerous antiplatelet drugs in most patients with ACS, the limited data regarding ideal therapeutic range, and the wide variability of patient response. Knowledge regarding the optimal therapeutic range and how to achieve it efficiently may enable clinicians to improve clinical outcomes in patients with ACS. We reviewed and analyzed the available evidence to clarify how to best manage UFH therapy in patients with ACS. Current data support the use of a lower and narrower therapeutic range for patients with ACS than the range that is used for venous thromboembolism. Many factors in addition to weight affect patient response to UFH, including age, sex, diabetes mellitus, smoking status, and obesity.

Fixed-dose vasopressin compared with titrated dopamine and norepinephrine as initial vasopressor therapy for septic shock.

STUDY OBJECTIVE: To investigate the early blood pressure effects of vasopressin compared with titrated catecholamines as initial drug therapy in patients with septic shock. DESIGN: Retrospective cohort, single-center study. SETTING: Intensive care units at the Mayo Clinic, Rochester, Minnesota. PATIENTS: Fifty, 49, and 51 intensive care patients treated initially with vasopressin, norepinephrine, and dopamine, respectively. INTERVENTION: Patients received either intravenous infusion of fixed-dose vasopressin 0.04 U/minute or titrated infusions of norepinephrine or dopamine for low systemic arterial pressures. MEASUREMENTS AND MAIN RESULTS: Patients treated with vasopressin, norepinephrine, and dopamine were similar in all measured characteristics except for their score on the Acute Physiology and Chronic Health Evaluation (APACHE) III (dopamine > vasopressin, p=0.049), renal comorbidities (dopamine > vasopressin, p=0.03) and baseline mean arterial pressure (MAP) (norepinephrine < vasopressin, p=0.005 or dopamine < vasopressin, p=0.05). In all patients, MAP 1 hour before and 1 hour afte intervention, heart rate, and systolic blood pressure were obtained. No treatment differences were identified in achieving postvasopressin MAP after adjusting for APACHE III score, renal dysfunction, and baseline MAP. In patients receiving vasopressin, 28-day mortality was 52%, similar to those receiving norepinephrine (65%, p=0.28) and dopamine (60%, p=0.53). CONCLUSION: Initial, fixed-dose vasopressin infusions increased MAP to 70 mm Hg or greater at 1 hour in intensive care patients with septic shock, similar to titrated norepinephrine or dopamine. Fixed-dose vasopressin appears appropriate as an alternative agent for hemodynamic support in patients with septic shock.

Predictors of prolonged vasopressin infusion for the treatment of septic shock.

PURPOSE: Prolonged catecholamine use has been linked with poor clinical outcomes, including higher mortality. The objective was to identify characteristics that may be predictive of prolonged arginine vasopressin (AVP) use for 7 days or more in patients with septic shock. MATERIALS AND METHODS: This was a retrospective nested cohort analysis of adult patients receiving AVP as initial hemodynamic support for septic shock, either alone or in combination with norepinephrine, between 2008 and 2010. RESULTS: Univariate factors predictive of patients requiring extended AVP support were peripheral vascular disease (PVD) (48% vs 18%, P = .001), congestive heart failure (30% vs 12%, P = .024), and acute kidney injury (AKI) (83% vs 49%, P = .003). Patients requiring extended AVP support more frequently experienced a new intensive care unit (ICU) arrhythmia, typically atrial fibrillation (39% vs 7%, P < .001), and had higher 28-day mortality (74% vs 20%, P < .001). Multivariate analysis revealed that the strongest independent predictors of prolonged AVP dependence were new ICU arrhythmia (odds ratio [OR], 5.3; 95% confidence interval [CI], 1.6-17.8), PVD (OR, 4.3; 95% CI, 1.4-13.1), and AKI (OR, 3.9; 95% CI, 1.1-14.5). CONCLUSIONS: Patients with preexisting PVD and AKI and those experiencing a new ICU arrhythmia on AVP may be more likely to remain on AVP for 7 or more days.

Effect of body mass index on bleeding frequency and activated partial thromboplastin time in weight-based dosing of unfractionated heparin: a retrospective cohort study.

OBJECTIVE: To assess bleeding and activated partial thromboplastin time (APTT) in relation to body mass index (BMI) in patients prescribed weight-based dosing of intravenous unfractionated heparin (UFH) for cardiac indications without a maximum (dose-capped) initial bolus or capped initial infusion rate. PATIENTS AND METHODS: Consecutive patients admitted to an academic medical center from February 1, 2002, through November 31, 2003, who were treated with a UFH nomogram consisting of a 60-U/kg intravenous bolus plus an initial continuous intravenous infusion of 12 U/kg hourly and titrated to a goal APTT range corresponding to thromboplastin-adjusted target heparin levels of 0.3 to 0.7 U/mL by anti-Xa assay were evaluated for this retrospective cohort study. Patients were excluded if they concomitantly received a fibrinolytic, glycoprotein IIb/IIIa inhibitor, or any other antithrombotic agent (except warfarin). Study patients were divided into quartiles by BMI. RESULTS: Of the 1054 patients included in the study, 807 (76.6%) had an initial bolus dose higher than 4000 U, and 477 (45.3%) had an initial infusion rate higher than 1000 U/h. Despite a significant difference among BMI quartiles in proportion of supratherapeutic first APTT values (P<.001), no statistically significant difference was found in bleeding frequency (P=.26) or frequency of first APTT within the goal range (P=.27). Logistic regression analyses revealed that BMI was not a significant predictor of bleeding or first APTT within the goal range. CONCLUSION: We did not find any difference in the proportion of first APTT values in the goal range or an increased risk of bleeding in obese patients treated with UFH without a capped initial dose. Our data demonstrate the safe use of weight-based UFH without a capped initial bolus dose or capped initial infusion rate in patients with medical cardiac conditions.