Levels of Albumin and Impact on Loop Diuretic and Albumin Co-administration in Heart Failure.

ABSTRACT: Management of heart failure (HF) requires the use of loop diuretics to relieve congestion and improve symptoms. When loop diuretics alone fail to induce adequate diuresis, albumin has been proposed to enhance loop diuretic delivery and promote redistribution of fluid for excretion by the kidneys. Despite the theoretical benefits of albumin, studies suggesting its benefit in HF are scarce and the co-administration of loop diuretics and albumin remains controversial. This retrospective, observational study evaluated patients with HF 18 years or older who received concomitant intravenous loop diuretic and albumin administration. The primary objective was to evaluate the association of serum albumin level with urine output (UOP) in hospitalized patients with HF who received concomitant albumin and loop diuretic therapy. Secondary endpoints included total weight loss after 72 hours, and ICU and hospital lengths of stay. In total, 276 patients were included for analysis. There was no association between initial serum albumin level and 72-hour UOP (coefficient -623.1, 95% confidence interval -1558.6 to 312.4; P = 0.191) or weight difference at 72 hours (coefficient -1.0, 95% confidence interval -2.4 to 0.3; P = 0.131). Lower albumin levels were associated with longer ICU ( P = 0.034) and hospital ( P = 0.039) lengths of stay. Concomitant thiazide diuretic use and increasing loop diuretic doses were associated with increased 72-hour UOP. The results of our study suggests that providers should avoid using baseline albumin levels as guidance for albumin dosing in HF. Given the lack of comparator groups, larger randomized controlled trials should be done to provide a definitive role for albumin to enhance diuresis in patients with HF on intravenous loop diuretics.

An update on drug-drug interactions for care of the acutely ill in the era of COVID-19.

PURPOSE: To provide key pharmacological concepts underlying drug-drug interactions (DDIs), a decision-making framework, and a list of DDIs that should be considered in the context of contemporary acutely ill patients with COVID-19. SUMMARY: DDIs are frequently encountered in the acutely ill. The implications of DDIs include either increased risk of drug toxicity or decreased effectiveness, which may have severe consequences in the acutely ill due to lower physiological and neurocognitive reserves in these patients. In addition, an array of additional therapies and drug classes have been used for COVID-19 that were not typically used in the acute care setting. In this update on DDIs in the acutely ill, we provide key pharmacological concepts underlying DDIs, including a discussion of the gastric environment, the cytochrome P-450 (CYP) isozyme system, transporters, and pharmacodynamics in relation to DDIs. We also provide a decision-making framework that elucidates the identification of DDIs, risk assessment, selection of alternative therapies, and monitoring. Finally, important DDIs pertaining to contemporary acute care clinical practice related to COVID-19 are discussed. CONCLUSION: Interpreting and managing DDIs should follow a pharmacologically based approach and a systematic decision-making process to optimize patient outcomes.

Comparison of 2 different inhaled epoprostenol dosing strategies for acute respiratory distress syndrome in critically ill adults: Weight-based vs fixed-dose administration.

PURPOSE: Inhaled epoprostenol (iEPO) is a viable, temporizing option for acute respiratory distress syndrome (ARDS), although the optimal iEPO dosing strategy remains inconclusive. The purpose of this study was to evaluate oxygenation and ventilation parameters in a comparison of weight-based and fixed-dose iEPO in adult patients with moderate-to-severe ARDS. METHODS: A retrospective cohort study was conducted at 2 academic medical centers in adult intensive care unit (ICU) patients administered either fixed-dose or weight-based iEPO for moderate-to-severe ARDS. The primary endpoint was the highest recorded change in the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) within 4 hours of baseline. Secondary analyses compared responder rates within 4 hours of initiation, oxygenation and ventilation parameters, in-hospital mortality rates, mechanical ventilation duration, length of stay (ICU and hospital), and tracheostomy rates between the study groups. RESULTS: A total of 294 patients were included, n = 194 with 100 (34.0%) and 194 (66.0%) in the weight-based and fixed-dose iEPO groups, respectively. The mean (SD) change in the highest recorded PaO2/FiO2 value from baseline up to 4 hours after initiation in the fixed-dose and weight-based groups was 81.1 (106.0) and 41.0 (72.5) mm Hg, respectively (P = 0.0015). The responder rate at 4 hours after iEPO initiation was significantly higher in the fixed-dose group (69.9%) than in the weight-based group (30.1%) (P = 0.02). The only predictor of response was fixed-dose administration (odds ratio, 3.28; 95% confidence interval, 1.6-6.7; P = 0.0012). Clinical outcomes were comparable between the groups. CONCLUSION: Fixed-dose iEPO was associated with significantly higher response rates then weight-based iEPO during the first 4 hours of therapy. Fixed-dose iEPO is a more convenient strategy than weight-based approaches.

Impact of Pharmacists to Improve Patient Care in the Critically Ill: A Large Multicenter Analysis Using Meaningful Metrics With the Medication Regimen Complexity-ICU (MRC-ICU) Score.

OBJECTIVES: Despite the established role of the critical care pharmacist on the ICU multiprofessional team, critical care pharmacist workloads are likely not optimized in the ICU. Medication regimen complexity (as measured by the Medication Regimen Complexity-ICU [MRC-ICU] scoring tool) has been proposed as a potential metric to optimize critical care pharmacist workload but has lacked robust external validation. The purpose of this study was to test the hypothesis that MRC-ICU is related to both patient outcomes and pharmacist interventions in a diverse ICU population. DESIGN: This was a multicenter, observational cohort study. SETTING: Twenty-eight ICUs in the United States. PATIENTS: Adult ICU patients. INTERVENTIONS: Critical care pharmacist interventions (quantity and type) on the medication regimens of critically ill patients over a 4-week period were prospectively captured. MRC-ICU and patient outcomes (i.e., mortality and length of stay [LOS]) were recorded retrospectively. MEASUREMENTS AND MAIN RESULTS: A total of 3,908 patients at 28 centers were included. Following analysis of variance, MRC-ICU was significantly associated with mortality (odds ratio, 1.09; 95% CI, 1.08-1.11; p < 0.01), ICU LOS (ß coefficient, 0.41; 95% CI, 00.37-0.45; p < 0.01), total pharmacist interventions (ß coefficient, 0.07; 95% CI, 0.04-0.09; p < 0.01), and a composite intensity score of pharmacist interventions (ß coefficient, 0.19; 95% CI, 0.11-0.28; p < 0.01). In multivariable regression analysis, increased patient: pharmacist ratio (indicating more patients per clinician) was significantly associated with increased ICU LOS (ß coefficient, 0.02; 0.00-0.04; p = 0.02) and reduced quantity (ß coefficient, -0.03; 95% CI, -0.04 to -0.02; p < 0.01) and intensity of interventions (ß coefficient, -0.05; 95% CI, -0.09 to -0.01). CONCLUSIONS: Increased medication regimen complexity, defined by the MRC-ICU, is associated with increased mortality, LOS, intervention quantity, and intervention intensity. Further, these results suggest that increased pharmacist workload is associated with decreased care provided and worsened patient outcomes, which warrants further exploration into staffing models and patient outcomes.

Intravenous to Oral Transition of Amiodarone (IOTA): Effect of Various Durations of Overlap on Atrial Fibrillation Recurrence After Cardiothoracic Surgery.

ABSTRACT: The use of amiodarone for postoperative atrial fibrillation (AF) is widespread; however, there is a paucity of data on the optimal duration of overlap when transitioning from intravenous (IV) to oral amiodarone. The objective of this study was to evaluate the safety and efficacy of varying durations of overlap when amiodarone IV infusion is transitioned to oral administration in cardiothoracic surgery patients. This retrospective, observational, single-center study included cardiothoracic surgery patients who were initiated on IV amiodarone for supraventricular arrhythmia and subsequently transitioned to oral amiodarone. The primary outcome was AF recurrence within 24 hours after IV amiodarone discontinuation. Safety outcomes include occurrence of bradycardia or hypotension while on amiodarone. A total of 184 patients were included for analysis. AF recurrence occurred in 24.5% of patients (n = 45). No significant association was found between various overlap durations and AF recurrence (odds ratio (OR) 1.00, 95% CI 1.00-1.01, P = 0.9). In addition, no significant association was found between duration of overlap and rates of bradycardia (OR 1.00, 95% confidence interval (CI) 0.99-1.00, P = 0.08) or hypotension (OR 1.00, 95% CI 0.99-1.00, P = 0.21), which occurred in 35.9% and 47.3% of patients, respectively. Our study suggests following conversion to normal sinus rhythm; cardiothoracic surgery patients can effectively and safely be transitioned from IV to oral amiodarone without the need for specific overlap duration or transition strategy.

Narrowing antibiotic spectrum of activity for trauma-associated pneumonia through the use of a disease-specific antibiogram.

BACKGROUND: Organism susceptibilities for trauma-associated pneumonia (TAP) differ from those in other patient populations, including the critically ill. The purpose of this study was to identify common organisms and their susceptibilities in the respiratory isolates of trauma patients diagnosed with pneumonia within the first 7 days of hospital admission, and to create a TAP-specific disease-state antibiogram to guide empiric antibiotic therapy in this patient population. METHODS: This study was a retrospective review of adult trauma patients with pneumonia admitted between September 1, 2015 and August 31, 2018. Patients included were diagnosed with and treated for pneumonia, with respiratory cultures drawn within the first 7 hospital-days; both culture-positive and culture-negative patients were included. Subgroup antibiograms were made for diagnosis made on days 1-3, 4-5, and 6-7. RESULTS: There were 131 patients included with a median age of 45; 85% were male, and 31% were illicit drug users. Most patients (63%) had ventilator-associated pneumonia, and most respiratory samples (77%) were obtained via bronchoalveolar lavage. Cultures were positive in 109 patients and negative in 22. There were 144 total isolates; 54% were Gram-negative bacteria. The most common Gram-negative pathogens were Haemophilus influenzae (16%) and Klebsiella pneumoniae (15%). The most common Gram-positive pathogen was Staphylococcus aureus; methicillin-resistant S. aureus (MRSA) constituted 8% of all isolates. With culture-negative patients counted as susceptible, ceftriaxone monotherapy and ceftriaxone+vancomycin susceptibilities were 85% and 94%, respectively. Susceptibilities to cefazolin, ampicillin/sulbactam, cefepime, piperacillin/tazobactam, and levofloxacin were 49%, 69%, 91%, 90%, and 92%, respectively. Illicit drug use and day of pneumonia diagnosis did not appreciably affect antibiotic susceptibilities. CONCLUSIONS: For TAP diagnosed within the first 7 days of hospital admission, ceftriaxone monotherapy is adequate as empiric therapy, including in ventilated patients. The addition of vancomycin can be considered in patients with MRSA risk factors or who are critically ill. LEVEL OF EVIDENCE: Level III, prognostic and epidemiological.

Mean arterial pressure maintenance following spinal cord injury: Does meeting the target matter?

INTRODUCTION: Neurosurgical guidelines recommend maintaining mean arterial pressure (MAP) between 85 and 90 mm Hg following acute spinal cord injury (SCI). In our hospital, SCI patients receive orders for MAP targeting for 72 hours following admission, but it is unclear how often the patient's MAP meets the target and whether or not this affects outcome. We hypothesized that the proportion of MAP measurements ≥85 mm Hg would be associated with neurologic recovery. METHODS: Spinal cord injury patients with blunt mechanism of injury admitted between 2014 and 2019 were identified from the registry of a level 1 trauma center. Proportion of MAP values ≥85 mm Hg was calculated for each patient. Neurologic improvement, as measured by positive change in American Spinal Injury Association (ASIA) impairment scale by ≥1 level from admission to discharge was evaluated with respect to proportion of elevated MAP values. RESULTS: A total of 136 SCI patients were evaluated. Average proportion of elevated MAP values was 75%. Admission ASIA grades were as follows: A, 30 (22.1%); B, 20 (14.7%); C, 28 (20.6%); and D, 58 (42.6%). One hundred six patients (77.9%) required vasopressors to elevate MAP (ASIA A, 86.7%; B, 95.0%; C, 92.9%; D, 60.3%). Forty patients (29.4%) were observed to have improvement in ASIA grade by discharge (admission ASIA A, 15%; B, 33%; C, 40%; D, 13%). The proportion of elevated MAP values was higher for patients with neurologic improvement (0.81 ± 0.15 vs. 0.72 ± 0.25, p = 0.014). Multivariate modeling demonstrated a significant association between proportion of elevated MAP values and neurologic improvement (p = 0.028). An interaction revealed this association to be moderated by vasopressor dose (p = 0.032). CONCLUSION: The proportion of MAP measurements ≥85 mm Hg was determined to be an independent predictor of neurologic improvement. Increased vigilance regarding MAP maintenance above 85 mm Hg is warranted to optimize neurologic recovery following SCI. LEVEL OF EVIDENCE: Therapeutic/care management, level IV.

Comparison of shock reversal with high or low dose hydrocortisone in intensive care unit patients with septic shock: A retrospective cohort study.

PURPOSE: This study aims to describe differences in shock reversal between hydrocortisone 200 mg and 300 mg per day dosing regimens in patients with septic shock. METHODS: This is a multi-center retrospective study including patients admitted to intensive care units with septic shock receiving vasopressors and hydrocortisone between 2013 and 2018. We compared patients who received low dose hydrocortisone (50 mg every 6 h) versus high dose hydrocortisone (100 mg every 8 h) on the primary outcome of shock reversal. RESULTS: 319 patients (low dose group, n = 134 and high dose group, n = 185) were included. In the multivariate regression model, high-dose steroids were associated with shock reversal [OR (95% CI) = 2.278 (1.063-4.880), p = 0.034]. This was not confirmed in the propensity score matched analysis [OR (95% CI) =2.202 (0.892-5.437), p = 0.087]. High dose steroids were associated with a lower need for additional vasopressor therapy (22% vs. 34%, p = 0.012) and lower shock recurrence (6.7% vs. 16%, p = 0.013), which was confirmed with propensity score matching. CONCLUSIONS: Low and high dose hydrocortisone have similar rates of shock reversal in septic shock patients. Hydrocortisone 100 mg every 8 h may reduce rates of recurrence of shock and reduce the need for additional vasopressors.

Transitioning From Intravenous to Subcutaneous Prostacyclin Therapy in Neonates With Severe Pulmonary Hypertension.

This article aims to present our neonatal intensive care unit experience transitioning from intravenous epoprostenol to IV and subcutaneous treprostinil in patients with persistent pulmonary hypertension of the neonate. This was a retrospective chart review at an academic teaching hospital. Neonates with a diagnosis of persistent pulmonary hypertension of the neonate (PPHN) who were started on IV prostacyclin therapy while admitted to the NICU between August 2017 and October 2019 were included. Of the 5 patients included, gestational ages ranged from 24 to 38 weeks. All patients were treated with inhaled nitric oxide and sildenafil before being initiated on IV or SQ prostacyclin therapy. Intravenous epoprostenol dosing was initiated at 1 ng/kg/min and was increased by 1 ng/kg/min every 12 hours until the provider was satisfied with the clinical response. Once the dose was stable for a few days epoprostenol was transitioned to IV treprostinil using double the last epoprostenol dose. A few days later infants were switched to SQ treprostinil using the same dose by stopping the IV infusion and starting the SQ infusion. All patients survived to hospital discharge and were sent home on SQ treprostinil. Minimal adverse effects were seen; patients experienced some slight hypotension, tachycardia, and diarrhea. Severe pulmonary hypertension is a common occurrence and a significant cause of mortality in the NICU. Our patients demonstrate that IV and SQ prostacyclin therapy is a therapeutic option for PPHN. Additionally, rapid high-dose transition from IV epoprostenol to IV treprostinil and then to SQ treprostinil is well tolerated in neonates, with minimal adverse effects.

Rapid transition from oral selexipag to parenteral treprostinil in a patient with mixed-etiology pulmonary hypertension.

PURPOSE: Selexipag is an oral nonprostanoid IP prostacyclin receptor agonist that is indicated for treatment of pulmonary arterial hypertension (PAH). In patients with continued symptoms of PAH despite maximized oral therapy with selexipag and other oral therapies, a transition to parenteral prostacyclin may be warranted. There is a paucity of data regarding how to safely transition from oral selexipag to parenteral treprostinil. We describe rapid transition from oral selexipag to parenteral treprostinil in this case report. SUMMARY: A 65-year-old female with mixed-etiology PAH as result of pulmonary fibrosis related to polymyositis was admitted to the intensive care unit to be transitioned from selexipag to treprostinil due to dyspnea at rest despite therapy with selexipag 1,600 mg twice daily and macitentan 10 mg daily for 3 years. At baseline the patient required oxygen support (4 L/min) at rest to maintain oxygen saturation at or above 90%. Right heart catheterization performed 8 weeks prior to admission revealed severe PAH, with a pulmonary arterial pressure of 73/27 mm Hg and pulmonary vascular resistance of 10 Wood units. On the day of admission the patient was given selexipag 800 µg at 9 am and simultaneously started on intravenous (i.v.) treprostinil at a dose of 2 ng/kg/min. The treprostinil dose was increased by 2 ng/kg/min every 3 hours until a target dose of 22 ng/kg/min was achieved, at which point the patient had experienced dyspnea improvement. She experienced a mild headache and flushing during rapid treprostinil dose escalation. After 30 hours of i.v. treprostinil infusion, the patient was transitioned to subcutaneous treprostinil therapy and discharged. CONCLUSION: In this case the patient was rapidly transitioned from oral selexipag to i.v. and then subcutaneous treprostinil therapy over a 30-hour period, with minimal adverse effects.

Treprostinil in the treatment of pulmonary arterial hypertension.

Despite progress over the past 30 years, pulmonary arterial hypertension remains a condition with high morbidity and mortality. Pharmacological and technological advances have shifted the approach to treating pulmonary arterial hypertension. Recent developments revolve heavily around novel routes of drug administration and delivery. In 2009, inhaled treprostinil was approved followed by oral treprostinil in 2013 providing patients with more convenient routes of administration compared with the parenteral alternatives. We are on the cusp of having the first fully implantable infusion pump for continuous intravenous treprostinil delivery. In 2019, generic treprostinil was approved, making the medication much more affordable for patients. In this review, we discuss in detail the recent developments surrounding both traditional and novel treprostinil products.

Patient-Controlled Analgesia Following Lumbar Spinal Fusion Surgery Is Associated With Increased Opioid Consumption and Opioid-Related Adverse Events.

BACKGROUND: Optimal postoperative pain control is critical after spinal fusion surgery. There remains significant variability in the use of postoperative intravenous opioid patient-controlled analgesia (PCA) and few data evaluating its utility compared with nurse-controlled analgesia (NCA) among patients with lumbar fusion. OBJECTIVE: To investigate the efficacy of postoperative PCA compared with NCA to improve opiate prescription practices. METHODS: A retrospective review from a single institution was conducted in consecutive patients treated with posterior lumbar spinal fusion for degenerative pathology. Patients were divided into cohorts on the basis of postoperative treatment with PCA or NCA. Postoperative pain scores, length of stay, and total opioid consumption data were collected. Patients were stratified according to preoperative opioid consumption as opioid naive (0 morphine milligram equivalents [MME] daily), low consumption (1-60 MME), high consumption (61-90 MME), or very high consumption (>90 MME). RESULTS: A total of 240 patients were identified, including 62 in the PCA group and 178 in the NCA group. PCA patients had higher mean preoperative opioid consumption than NCA patients (49.2 vs 24.3 MME, P = .009). PCA patients had higher mean opioid consumption in the first 72 h in all 4 of the preoperative opioid consumption subcategories. Pain control and adverse event rates were similar between PCA and NCA in the low to high preoperative opioid consumption groups. CONCLUSION: Postoperative PCA is associated with significantly more opioid consumption in the first 72 h after surgery and equal or worse postoperative pain scores compared with NCA after lumbar spinal fusion surgery.

Opioid exposure after injury in United States trauma centers: A prospective, multicenter observational study.

BACKGROUND: Efforts to reduce opioid use in trauma patients are currently hampered by an incomplete understanding of the baseline opioid exposure and variation in United States. The purpose of this project was to obtain a global estimate of opioid exposure following injury and to quantify the variability of opioid exposure between and within United States trauma centers. STUDY DESIGN: Prospective observational study was performed to calculate opioid exposure by converting all sources of opioids to oral morphine milligram equivalents (MMEs). To estimate variation, an intraclass correlation was calculated from a multilevel generalized linear model adjusting for the a priori selected variables Injury Severity Score and prior opioid use. RESULTS: The centers enrolled 1,731 patients. The median opioid exposure among all sites was 45 MMEs per day, equivalent to 30 mg of oxycodone or 45 mg of hydrocodone per day. Variation in opioid exposure was identified both between and within trauma centers with the vast majority of variation (93%) occurring within trauma centers. Opioid exposure increased with injury severity, in male patients, and patients suffering penetrating trauma. CONCLUSION: The overall median opioid exposure was 45 MMEs per day. Despite significant differences in opioid exposure between trauma centers, the majority of variation was actually within centers. This suggests that efforts to minimize opioid exposure after injury should focus within trauma centers and not on high-level efforts to affect all trauma centers. LEVEL OF EVIDENCE: Epidemiological, level III.

Comparison of Ketamine- Versus Nonketamine-Based Sedation on Delirium and Coma in the Intensive Care Unit.

BACKGROUND: At this time, there are no studies evaluating the risk of delirium or coma with the use of ketamine in mechanically ventilated adult patients, compared to conventional therapies such as propofol or dexmedetomidine. OBJECTIVE: The objective of this study was to evaluate the number of days alive without delirium or coma in mechanically ventilated patients in the intensive care unit receiving analgosedation infusions with ketamine versus without ketamine. METHODS: This was a retrospective cohort study conducted at an academic medical center in the United States. Consecutive mechanically ventilated adult patients between November 2015 and April 2017 were evaluated. Patients were divided into 2 groups based on the sedative regimen used: ketamine based or nonketamine based. The primary outcome was the number of days alive without delirium or coma. The secondary outcomes were incidence of delirium, incidence of coma, and ventilator-free days at day 28. RESULTS: The study cohort consisted of 79 patients, of which 39 received ketamine- and 40 received nonketamine-based sedation. The number of days alive without delirium or coma was 6 days (interquartile range [IQR]: 2-9 days) with ketamine and 4 days (IQR: 3-7 days) with nonketamine (P = .351). Delirium occurred in 29 (74%) of 39 patients with ketamine and 34 (85%) of 40 patients with nonketamine (P = .274). Coma occurred in 16 (41%) of 39 patients with ketamine and 6 (15%) of 40 patients with nonketamine (P = .013). The median ventilator-free days were 13 days (IQR: 0-23 days) with ketamine and 21 days (0-25 days) with nonketamine (P = .229). CONCLUSIONS: Sustained ketamine-based sedation in mechanically ventilated patients may be associated with a higher rate of observed coma but similar delirium- and coma-free days compared nonketamine-based regimens.

Cefazolin Monotherapy Versus Cefazolin Plus Aminoglycosides for Antimicrobial Prophylaxis of Type III Open Fractures.

BACKGROUND: There are conflicting recommendations between organizations regarding aminoglycoside use for the prophylaxis of type III open fractures. STUDY QUESTION: To compare cefazolin monotherapy versus cefazolin plus aminoglycoside therapy for prophylaxis of type III open fractures in trauma patients. STUDY DESIGN: This was a multicenter, retrospective, cohort study conducted in 3 academic medical centers in the United States. Consecutive adult trauma patients with type III open fractures between January 2014 and September 2016 were included. Patients were divided into 2 groups: (1) cefazolin monotherapy versus (2) cefazolin plus aminoglycoside. MEASURES AND OUTCOMES: The primary outcome measure was the occurrence of infection at the open fracture site. The secondary outcome measure was the occurrence of acute kidney injury. RESULTS: There were 134 patients included in the study cohort. Of these, 39 received cefazolin monotherapy and 95 received cefazolin plus aminoglycoside. Overall, the mean age was 39 ± 15 years, 105 (78%) were male, and the most common fracture location was tibia/fibula (n = 74, 56%). Infection at the open fracture site occurred in 6 of 39 patients (15%) in the cefazolin monotherapy group and 15 of 95 patients (16%) in the cefazolin plus aminoglycoside group (P = 1.000). Acute kidney injury occurred in 0 of 39 (0%) in the cefazolin monotherapy group and 1 of 95 (1%) in the cefazolin plus aminoglycoside group (P = 1.000). CONCLUSIONS: Cefazolin monotherapy may be appropriate for antimicrobial prophylaxis of type III open fractures in trauma patients.

Catecholamine Vasopressor Support Sparing Strategies in Vasodilatory Shock.

Shock syndromes are associated with unacceptably high rates of mortality in critically ill patients despite advances in therapeutic options. Vasodilatory shock is the most common type encountered in the intensive care unit. It is manifested by cardiovascular failure, peripheral vasodilatation, and arterial hypotension leading to tissue hypoperfusion and organ failure. Hemodynamic support is typically initiated with fluid resuscitation strategies and administration of adrenergic vasopressor agents in nonresponsive patients to restore arterial pressure with subsequent adequate organ reperfusion. Unfortunately, high catecholamine dosing requirements may be necessary to achieve targeted hemodynamic goals that may increase the risk of vasopressor-induced adverse events. The purpose of this article is to review the clinical efficacy and safety data and potential role in therapy for catecholamine-sparing agents in vasodilatory shock. Adjunctive therapeutic options to reduce vasoactive support requirements without compromising arterial pressure include arginine vasopressin and analogs, corticosteroids, midodrine, methylene blue, and angiotensin II. Although concomitant vasopressin and corticosteroids have a more defined role in evidence-based guidelines for managing shock, clinicians may consider other potential catecholamine-sparing agents.

Catastrophic circulatory collapse after inadvertent subcutaneous injection of treprostinil.

PURPOSE: A case of life-threatening cardiovascular collapse after inadvertent subcutaneous injection of undiluted treprostinil is reported. SUMMARY: A 29-year-old, 76-kg woman with group 1 pulmonary arterial hypertension managed with subcutaneous treprostinil infusion arrived at the emergency department (ED) with headache, nausea, vomiting, and a syncopal episode. Her vital signs were stable on presentation. Admission orders were placed, and the appropriate 3-mL syringe containing 7.5 mg of treprostinil intended for use with the patient's home microinfusion pump was sent from inpatient pharmacy to the ED. The order in the electronic medical record stated to administer treprostinil as a subcutaneous injection rather than an infusion. The patient's nurse transferred the 7.5 mg (3 mL) of undiluted treprostinil to a standard syringe and administered it as a single subcutaneous injection. Within minutes the patient experienced cardiovascular collapse, with a blood pressure nadir of 50/20 mm Hg. Aggressive resuscitation measures were immediately implemented. Initial management included fluids, bolus-dose vasopressors, multiple high-dose vasopressor infusions, ondansetron, acetaminophen, and loperamide. Hemodynamic stability was achieved, and vasopressors were discontinued 16 hours after the overdose event. Subcutaneous treprostinil was restarted at a reduced dose 12 hours after the overdose event and was adjusted to the patient's home dose 24 hours after the initial event. She was discharged in stable condition 30 hours after the overdose event. CONCLUSION: A patient who received an inadvertent overdose of subcutaneous treprostinil experienced cardiovascular collapse requiring aggressive resuscitation measures. Successful management of the patient was largely supportive, including fluids, bolus-dose vasopressors, multiple high-dose vasopressor infusions, ondansetron, acetaminophen, and loperamide.

Evaluation of the Treatment of Candiduria at an Academic Medical Center.

To evaluate the epidemiology, management, and outcomes associated with candiduria in intensive care unit (ICU) and medical ward (MW) patients. This was a retrospective cohort study conducted in a tertiary care academic medical center. Adult patients aged between 18 and 75 years who were admitted for at least 5 days with a urinary culture that grew a Candida species between July 2010 and June 2011 were included. Medical records were retrospectively reviewed. Laboratory data, urinary symptoms, risk factors for urinary and invasive candidiasis, treatment, and patient outcomes were collected and evaluated. Sixty-seven ICU and 65 MW patients met the inclusion criteria. ICU patients were more likely to have risk factors for invasive candidiasis and candiduria. Candida albicans and Candida glabrata were the most frequently identified urinary isolates. Antifungal therapy was commonly initiated despite rapid replacement or removal of urinary drainage devices and a lack of patient reported symptoms. Fluconazole was the most commonly used antifungal agent, followed by micafungin. Hospital length of stay did not vary significantly between the ICU and MW groups (P = 0.0628). All-cause mortality was higher in the ICU patients compared with that of the MW patients (22.4% vs. 3.1%, P = 0.0012). Differences exist between ICU and MW patients that develop candiduria with respect to risk factors, and outcomes. Antifungals, including fluconazole and micafungin, were often used inappropriately (ie, asymptomatic patients) in this patient cohort. Efforts to improve healthcare provider awareness of the contemporary recommendations to manage candiduria are necessary to improve patient care and antifungal use.

Norepinephrine Dosing in Obese and Nonobese Patients With Septic Shock.

BACKGROUND: Whether or not norepinephrine infusions for support of hemodynamic status in patients with septic shock should be weight based is unknown. This situation is particularly pertinent in patients who are extremely overweight or obese. OBJECTIVE: To compare dosing requirements and effect of norepinephrine on blood pressure in obese and nonobese patients with septic shock. METHODS: In a retrospective cohort study, data on adult patients with septic shock who received norepinephrine infusion for support of hemodynamic status in a tertiary care, academic medical center were analyzed. Patients were categorized as obese (body mass index ≥ 30) or nonobese (body mass index < 30). The primary outcome was dosing requirements of norepinephrine at 60 minutes after the start of the infusion. The secondary outcome was the log-transformed ratio of mean arterial pressure to norepinephrine. RESULTS: The final cohort consisted of 100 obese and 100 nonobese patients. Mean norepinephrine infusion rate at 60 minutes was 0.09 (SD, 0.08) µg/kg per minute in the obese group and 0.13 (SD, 0.14) µg/kg per minute in the nonobese group (P = .006). The non-weight-based dose at 60 minutes was 9 µg/min in obese patients and 8 µg/min in nonobese patients (P = .72). The log transformed mean arterial pressure to norepinephrine ratio at 60 minutes was 2.5 (SD, 0.9) in obese patients and 2.5 (SD, 0.8) in nonobese patients (P = .54) CONCLUSIONS: Compared with nonobese patients, obese patients with septic shock require lower weight-based doses of norepinephrine and similar total norepinephrine doses.

Hepatotoxicity in Obese Versus Nonobese Patients With Acetaminophen Poisoning Who Are Treated With Intravenous N-Acetylcysteine.

There is limited information regarding the outcomes associated with acetaminophen (APAP) poisoning in obese individuals. It is possible that patients who are obese are more susceptible to APAP-induced liver injury, thereby diminishing the efficacy of antidotes such as N-acetylcysteine (NAC). We evaluated the outcomes associated with APAP poisoning in obese versus nonobese adults who are treated with intravenous (IV) NAC. This was a retrospective cohort study conducted in a tertiary care, academic medical center. Adult patients with APAP toxicity, who were treated with IV NAC between June 2005 and August 2012, were included. The patients were categorized into 2 groups based on their body mass index (BMI): (1) obese (BMI ≥ 30.0 kg/m) versus (2) nonobese (BMI 18.5-24.9 kg/m). The primary outcome measure was the proportion of patients who developed hepatotoxicity (aspartate aminotransferase or alanine aminotransferase >1000 IU/L). A total of 80 patients were included in the final cohort (40 in each group). The median BMI for the obese and nonobese groups was 34.5 kg/m [interquartile range (IQR) 31.4-40.2] and 22.4 kg/m (IQR 21.2-23.9), respectively (P < 0.001). Other than more white patients being present in the nonobese group, there were no other baseline differences between groups with regard to demographics, liver function tests, or coagulation studies. Obese patients received a median IV NAC dose of 291.5 mg/kg (IQR 270.8-300.7) compared with 300 mg/kg (IQR 287.8-301.9) in the nonobese group (P = 0.07). Hepatotoxicity occurred in 27.5% of the obese patients and 37.5% of the nonobese patients (P = 0.34). No adverse drug effects were noted in either group. Obese and nonobese patients being treated with IV NAC for APAP toxicity experienced similar rates of hepatotoxicity.