Aminoglycoside Pharmacokinetics in Critically Ill Patients Undergoing Continuous Renal Replacement Therapy.

BACKGROUND: There are few studies describing aminoglycoside pharmacokinetics during continuous renal replacement therapy (CRRT). OBJECTIVE: To characterize the effect of CRRT on aminoglycoside clearance and volume of distribution (Vd). METHODS: Retrospective observational pharmacokinetic study of adult critically ill oncologic patients who received a first dose of amikacin or tobramycin during CRRT between February 2012 and May 2017. Study outcomes included aminoglycoside clearance, Vd, and attainment of the target peak: MIC (minimum inhibitory concentration) ratio as a surrogate for dosing appropriateness. RESULTS: In total, 80 patients were included, sustained low-efficiency dialysis (SLED), n = 49; continuous venovenous hemodialysis (CVVHD), n = 19; continuous venovenous hemofiltration (CVVH), n = 12. Fifty-one patients received amikacin at a median dose of 14.5 mg/kg per actual body weight and achieved a median peak level of 26.7 mg/L. Twenty-nine patients received tobramycin at a median dose of 6.5 mg/kg actual body weight and achieved a median peak level of 10.3 mg/L. The median aminoglycoside clearance was 63.1 mL/min and was similar between CRRT modality groups (P = 0.97). The median Vd was 0.47 L/kg and was different between the SLED and CVVH groups (P = 0.007). Attainment of target peak: MIC occurred in 29% in the total study population and 44% in the subgroup of 23 patients with isolates tested for aminoglycoside susceptibility. CONCLUSION AND RELEVANCE: Critically ill oncology patients undergoing CRRT exhibited reduced clearance and expanded Vd that was not significantly different between CRRT modalities. Current dosing regimens led to low peak concentrations and poor attainment of pharmacokinetic targets.

Program development of a preceptor bootcamp for operational pharmacy preceptors.

PURPOSE: To describe the development, design, and implementation of a pilot preceptor development bootcamp and feedback related to its feasibility and impact on operational pharmacy preceptors. SUMMARY: The University of Texas MD Anderson Cancer Center designed and implemented a pilot preceptor development bootcamp for operational staff pharmacists serving as residency preceptors for longitudinal weekend staffing experiences. A systematic, multipronged approach was taken to identify preceptor development gaps and design a full-day bootcamp curriculum. The resultant curriculum was comprised of content in major functional areas including using the 4 preceptor roles, documenting performance, giving and receiving feedback, and dealing with difficult situations or learners. The impact of the pilot preceptor development bootcamp was assessed using survey methodology and qualitative feedback from debrief discussions. CONCLUSION: Implementation of a pilot preceptor bootcamp program addressing major areas of precepting skill was well received, resulted in positive feedback from operational pharmacy preceptors, and was feasible to implement at a large academic medical center.

Stress Ulcer Prophylaxis.

OBJECTIVES: Stress ulcer prophylaxis is commonly administered to critically ill patients for the prevention of clinically important stress-related mucosal bleeding from the upper gastrointestinal tract. Despite widespread incorporation of stress ulcer prophylaxis into practice around the world, questions are emerging about its indications and impact. This clinically focused article will review current controversies related to stress ulcer prophylaxis for critically ill adult patients, including bleeding frequency, risk factors, comparative efficacy, adverse effect profile, and overall cost-effectiveness of the available stress ulcer prophylaxis regimens. DATA SOURCES: A MEDLINE search was conducted from inception through August 2015. STUDY SELECTION: Selected publications describing stress ulcer prophylaxis in adult patients were retrieved (original research, systematic reviews, and practice guidelines); their bibliographies were also reviewed to identify additional pertinent publications. DATA EXTRACTION: Data from relevant publications were abstracted and summarized. DATA SYNTHESIS: The existing evidence is organized to describe the patients most likely to benefit from stress ulcer prophylaxis, review the comparative efficacy of proton pump inhibitors and histamine 2 receptor antagonists, the adverse effects of stress ulcer prophylaxis, and overall cost-effectiveness. CONCLUSIONS: Many stress ulcer prophylaxis recommendations are based on older studies at risk of bias, which may not be applicable to modern practice. Stress ulcer prophylaxis should be limited to patients considered to be at high risk for clinically important bleeding. When evaluating only the trials at low risk for bias, the evidence does not clearly support lower bleeding rates with proton pump inhibitors over histamine 2 receptor antagonists; however, proton pump inhibitors appear to be the dominant drug class used worldwide today. The current rate of upper gastrointestinal bleeding and the relative adverse effects of acid suppression on infectious risk may drive not only the effectiveness, but also the cost-effectiveness of stress ulcer prophylaxis today. Research is currently underway to better address these issues.

Probable Nonconvulsive Status Epilepticus With the Use of High-Dose Continuous Infusion Ceftazidime.

Multidrug resistant (MDR) bacterial infections are a major concern of health care providers due to their increasing incidence and associated mortality. In some cases, few or no antibiotics have preserved activity. Beta-lactam administration via continuous infusion can optimize time over minimum inhibitory concentration (MIC). In some cases, use of high-dose continuous infusion (HDCI) may be necessary to achieve serum levels in excess of nonsusceptible MIC values. The use of HDCI beta-lactams is not without risk, specifically neurotoxic adverse effects, which appear dose related. We describe a 64-year-old male who experienced myoclonus and nonconvulsive status epilepticus while receiving HDCI ceftazidime for treatment of multidrug resistant Pseudomonas aeruginosa bacteremia. This report serves as a cautionary example of the potential toxicities associated with HDCI beta-lactams and supports the importance of risk-benefit analysis prior to and during treatment. Additionally, the use of serum drug level monitoring may be necessary to better prevent or predict toxicity.

Development of a combination antibiogram for Pseudomonas aeruginosa bacteremia in an oncology population.

PURPOSE: Development of a combination antibiogram to identify combinations of antibiotics that have the highest likelihood of attaining one active agent in the empiric management of presumed Pseudomonas aeruginosa bacteremia. METHODS: Patients with cancer and P. aeruginosa bacteremia from January 1 to December 31, 2012 were included in this analysis. The primary outcome was identification of effective combinations of beta-lactam and non-betalactam agents. An effective combination was defined as one which achieved in-vitro activity to greater than or equal to 85% of isolates collected. Furthermore, the addition of the non-beta-lactam agent was required to increase the in-vitro activity by at least 5% over beta-lactam monotherapy. Multiple secondary outcomes were evaluated. RESULTS: One hundred and twenty-three P. aeruginosa isolates were included from 99 patients. Single agent beta-lactam sensitivities ranged from 72.4 to 79.7%. Combination regimen sensitivities ranged from 73.5 to 96.7%. All combination regimens that included a beta-lactam plus an aminoglycoside were found to be effective per the study definition. Independent risk factors for MDR P. aeruginosa were receipt of intravenous (IV) antibiotics within 90 days and hospital length of stay (LOS) greater than or equal to five days. Increasing the number of antibiotics received was associated with a decrease in survival to hospital discharge. CONCLUSIONS: Effective combination regimens included all beta-lactam aminoglycoside regimens. Receipt of IV antibiotics within 90 days and hospital LOS greater than or equal to five days were independent risk factors for MDR isolates.

First-dose pharmacokinetics of aminoglycosides in critically ill haematological malignancy patients.

The primary objective of this study was to determine the volume of distribution (Vd) (L/kg) of intravenous aminoglycosides (AGs) in critically ill haematological malignancy patients. Secondary objectives were to determine the body weight (actual, ideal, adjusted or lean) that yields the most precise estimate of Vd when normalised in L/kg as well as the frequency that current first-dose strategies result in post-distributional peak concentrations (C(peak)) within the target range (tobramycin 16-24 mg/L; amikacin 32-48 mg/L). In total, 58 AG doses were included (tobramycin, n = 34; amikacin, n = 24). Median Vd was 0.38 L/kg normalised per the most precise dose weight, which was actual body weight (ABW). The median dose was 445 mg (5.8 mg/kg ABW) for tobramycin and 1200 mg (13.8 mg/kg ABW) for amikacin. Target C(peak) (tobramycin 20mg/L; amikacin 40 mg/L) was achieved in only 25% of all AG episodes, with 4% exceeding the target and 71% falling below the target. Twenty-four organisms were isolated in the study sample; target C(peak) achievement (tobramycin 20 mg/L; amikacin 40 mg/L) would yield a peak:minimum inhibitory concentration of 10 in 75% and 52% of organisms, respectively. In conclusion, an increased Vd of AGs was identified in this critically ill haematological malignancy patient sample, and current dosing yielded a suboptimal C(peak) in the majority of patients.

US practitioner opinions and prescribing practices regarding corticosteroid therapy for severe sepsis and septic shock.

PURPOSE: The aim of this study was to examine opinions and practices of US critical care practitioners (USCCPs) toward corticosteroid therapy in adult patients with severe sepsis or septic shock. MATERIALS AND METHODS: A multicenter, electronic survey of USCCP members of the Society of Critical Care Medicine was conducted between March 18 and July 31, 2009. RESULTS: A total of 542 USCCPs responded to the survey. The majority (83%) do not commonly use corticosteroids in adult patients with severe sepsis; however, up to 81% report use of corticosteroids for septic shock. Twenty-eight percent believe that corticosteroids reduce mortality in septic shock, whereas 27% do not and 45% are unsure. The decision to initiate therapy is based, more often, on a patient's clinical status (65%) vs serum cortisol analysis (35%). Hydrocortisone is the most common corticosteroid prescribed (93%), with a median dosage of 200 mg/d and administration via intermittent intravenous injection. The Corticosteroid Therapy of Septic Shock trial had a large impact on survey respondents, with 62% reporting a practice change. Among the 19% of practitioners who do not prescribe corticosteroids, the most common reason was lack of proven survival benefit. CONCLUSIONS: Corticosteroids are commonly used by USCCPs in adult patients with septic shock; however, criteria used to initiate therapy and opinions regarding their impact vary.

Prolonged propofol use in a critically ill pregnant patient.

OBJECTIVE: To describe the prolonged use of propofol for sedation of a critically ill pregnant patient in her second trimester. CASE SUMMARY: A 20-year-old pregnant woman at 14 weeks' gestation with non-Hodgkin's lymphoma required intubation and mechanical ventilation secondary to tumor-related airway obstruction. Immediately after intubation, propofol was initiated for sedation and maintained for 51 days with only one 5-day interruption in therapy. Over the course of the patient's stay in the intensive care unit, systemic chemotherapy was administered, resulting in a reduction in tumor burden and allowing for successful extubation. Ultimately, the fetus was deemed nonviable and the pregnancy was terminated. DISCUSSION: Propofol is an intravenous anesthetic agent commonly used for the sedation of mechanically ventilated patients and is the only sedative agent that carries a pregnancy category B rating. Fetal outcomes following long-term use of propofol during the first trimester have not been formally evaluated and few reports of propofol use outside of early pregnancy termination, outpatient procedures, or parturition exist in the medical literature. Our patient required early termination of pregnancy; however, we were unable to determine whether fetal loss was a result of propofol use, chemotherapy administration, the use of other pharmacologic agents, or perhaps a combined effect. CONCLUSIONS: Despite propofol's pregnancy category B rating, data are lacking in humans regarding its safe use during pregnancy and long-term developmental outcomes in children after exposure to propofol in utero. The safety of propofol as a sedative agent for critically ill pregnant patients remains unknown.

Intensive care unit delirium.

Once considered a benign iatrogenic consequence of intensive care unit (ICU) admission, ICU delirium is now recognized as a prominent disorder that negatively affects patient morbidity and mortality. The primary goal in the detection and treatment of ICU delirium is to ensure the safety of the patient and caregiver(s). Most critically ill patients possess 1 or more risk factors for the development of delirium; therefore, interventions that target delirium assessment and prevention are essential. This article highlights some of the recent data that have emerged regarding ICU delirium, including its definition, incidence, risk factors, diagnostic tools, and treatment.

Stress-related mucosal bleeding in critically ill oncology patients.

OBJECTIVE: To determine the incidence of stress-related mucosal bleeding (SRMB) in a critically ill oncology population receiving stress ulcer prophylaxis (SUP) with either a histamine-2 receptor antagonist (H2RA) or proton pump inhibitor (PPI). DESIGN: Single-center, prospective, observational study. SETTING: Fifty-two bed medical-surgical intensive care unit of an academic oncology institution. PATIENTS: A convenience sample of 100 medical and surgical critically ill oncology patients who received intensive care for more than 24 hours and at least one dose of a H2RA or PPI for prevention of SRMB. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were followed throughout their intensive care unit stay for the development of an overt and/or clinically significant gastrointestinal (GI) bleed. More patients received a PPI (n=81) in contrast to a H2RA (n=19) for SUP. Overall, 94 patients (94%) had at least one risk factor for a SRMB with four patients (4%) experiencing an event (overt bleed, n=3; clinically significant bleed, n=1). All cases of GI bleeding occurred in patients receiving a PPI. No ICU deaths were considered directly related to a GI bleed. CONCLUSIONS: The incidence of SRMB among high-risk critically ill oncology patients receiving SUP appears low; further, large-scale trials are needed to confirm this finding.

Possible pentostatin-induced symptomatic hyponatremia.

Pentostatin is an adenosine deaminase inhibitor used in the treatment of hairy cell leukemia and T-cell lymphomas. A 27-year-old man with refractory cutaneous T-cell lymphoma developed severe hyponatremia 3 days after completing his first cycle of pentostatin therapy. Shortly after hospital admission, he became disoriented and was admitted to the medical intensive care unit and treated with a combination of hypertonic saline, intravenous diuretics, and fluid restriction to reestablish normal sodium homeostasis. The mechanism by which pentostatin may have induced hyponatremia in this patient is unknown; clinical and laboratory findings represented both extrarenal sodium loss and syndrome of inappropriate antidiuretic hormone. Clinicians should be aware of the possible development of life-threatening symptomatic hyponatremia in patients receiving pentostatin.

Herbal use among US elderly: 2002 National Health Interview Survey.

BACKGROUND: Use of herbal products among the elderly is an important concern for healthcare professionals. The presence of polypharmacy and multiple comorbidities places the elderly at high risk for herb-drug and herb-disease interactions. Limited data exist regarding herbal use among the US elderly population. OBJECTIVE: To evaluate the incidence of and attitudes toward herbal use in a nationally representative sample of US elderly patients >/=65 years of age. METHODS: We performed a descriptive analysis of public domain data collected in the 2002 National Health Interview Survey. Statistical analyses were conducted through use of SUDAAN software with Taylor series linearization for variance estimation. RESULTS: Analysis of weighted data revealed that 12.9% +/- 0.5% (mean +/- SE) of US elderly people had used an herbal supplement within the past 12 months. Use was greatest among individuals 65-69 years of age, females, Hispanic and non-Hispanic ethnic minorities, and respondents with a greater income, higher education level, or more positive self-reported health status. Among elderly people purchasing over-the-counter and prescription drugs, herbal use was 13.9% +/- 0.6% and 12.8% +/- 0.6%, respectively. Glucosamine, echinacea, and garlic supplements represented the most common herbals used. Benefit from combined herbal and conventional therapy was the most common reason cited for use; however, 50.9% +/- 2.2% of users did not discuss herbal therapy with a medical professional. Several theoretical herb-disease interactions were identified. CONCLUSIONS: The use of herbal products among the US elderly has risen over the past 5 years, whereas discussion of such use with medical professionals remains suboptimal.