Curtis E. Haas

Recommendations for end-of-life care in the intensive care unit: A consensus statement by the American College of Critical Care Medicine

Background:These recommendations have been developed to improve the care of intensive care unit (ICU) patients during the dying process. The recommendations build on those published in 2003 and highlight recent developments in the field from a U.S. perspective. They do not use an evidence grading system because most of the recommendations are based on ethical and legal principles that are not derived from empirically based evidence. Principal Findings:Family-centered care, which emphasizes the importance of the social structure within which patients are embedded, has emerged as a comprehensive ideal for managing end-of-life care in the ICU. ICU clinicians should be competent in all aspects of this care, including the practical and ethical aspects of withdrawing different modalities of life-sustaining treatment and the use of sedatives, analgesics, and nonpharmacologic approaches to easing the suffering of the dying process. Several key ethical concepts play a foundational role in guiding end-of-life care, including the distinctions between withholding and withdrawing treatments, between actions of killing and allowing to die, and between consequences that are intended vs. those that are merely foreseen (the doctrine of double effect). Improved communication with the family has been shown to improve patient care and family outcomes. Other knowledge unique to end-of-life care includes principles for notifying families of a patient’s death and compassionate approaches to discussing options for organ donation. End-of-life care continues even after the death of the patient, and ICUs should consider developing comprehensive bereavement programs to support both families and the needs of the clinical staff. Finally, a comprehensive agenda for improving end-of-life care in the ICU has been developed to guide research, quality improvement efforts, and educational curricula. Conclusions:End-of-life care is emerging as a comprehensive area of expertise in the ICU and demands the same high level of knowledge and competence as all other areas of ICU practice.

In vitro selection of resistant Helicobacter pylori.

Four strains of Helicobacter pylori were subjected to an in vitro serial passage technique to compare the propensity of the organisms to develop resistance to seven classes of antibacterial agents. The passages were made on serially doubling concentrations of antibacterial agents incorporated into agar starting at one-half the base-line MIC. The frequency of spontaneous resistance was also determined for each strain at four and eight times the MIC of each antibacterial agent. Strains resistant to ciprofloxacin, metronidazole, erythromycin, and tobramycin were isolated. The experiments failed to select organisms resistant to bismuth subsalicylate, furazolidone, or amoxicillin, although the MIC of amoxicillin was increased 4- to 16-fold. With the exception of erythromycin, organisms with the selected resistance were stable after at least three passages on antibacterial agent-free medium. Spontaneous resistance rates were generally of a low magnitude and were not predictive of the serial passage results.

The Influence of St. John's Wort on the Pharmacokinetics and Protein Binding of Imatinib Mesylate

Study Objective. To determine the effect of St. Johns wort on the pharmacokinetics of imatinib mesylate.

Cytochrome P450 3A4 activity after surgical stress

ObjectiveTo evaluate the relationship between the acute inflammatory response after surgical trauma and changes in hepatic cytochrome P450 3A4 activity, compare changes in cytochrome P450 3A4 activity after procedures with varying degrees of surgical stress, and to explore the time course of any potential drug-cytokine interaction after surgery. DesignProspective, open-label study with each patient serving as his or her own control. SettingUniversity-affiliated, acute care, general hospital. PatientsA total of 16 patients scheduled for elective repair of an abdominal aortic aneurysm (n = 5), complete or partial colectomy (n = 6), or peripheral vascular surgery with graft (n = 5). InterventionsCytochrome P450 3A4 activity was estimated using the carbon-14 [14C]erythromycin breath test (ERMBT) before surgery and 24, 48, and 72 hrs after surgery. Abdominal aortic aneurysm and colectomy patients also had an ERMBT performed at discharge. Blood samples were obtained before surgery, immediately after surgery, and 6, 24, 32, 48, and 72 hrs after surgery for determination of plasma concentrations of interleukin-6, interleukin-1&bgr;, and tumor necrosis factor-&agr;. Clinical markers of surgical stress that were collected included duration of surgery, estimated blood loss, and volume of fluids administered in the operating room. Measurements and Main ResultsERMBT results significantly declined in all three surgical groups, with the lowest value at the time of the 72-hr study in all three groups. There was a trend toward differences in ERMBT results among groups that did not reach statistical significance (p = .06). The nadir ERMBT result was significantly and negatively correlated with both peak interleukin-6 concentration (rs = −.541, p = .03) and log interleukin-6 area under the curve from 0 to 72 hrs (rs = −.597, p = .014). Subjects with a peak interleukin-6 of >100 pg/mL had a significantly lower nadir ERMBT compared with subjects with a peak interleukin-6 of <100 pg/mL (35.5% ± 5.2% vs. 74.7% ± 5.1%, p < .001). ConclusionsAcute inflammation after elective surgery was associated with a significant decline in cytochrome P450 3A4 activity, which is predictive of clinically important changes in the metabolism of commonly used drugs that are substrates for this enzyme.

Lithium pharmacokinetics in the obese

The purpose of this study was to investigate the disposition of lithium in obese subjects compared with the disposition in normal weight volunteers.

Pharmacist-managed antimicrobial stewardship program for patients discharged from the emergency department

Positive outcomes of antimicrobial stewardship programs in the inpatient setting are well documented, but the benefits for patients not admitted to the hospital remain less clear. This report describes a retrospective case–control study of patients discharged from the emergency department (ED) with subsequent positive cultures conducted to determine whether integrating antimicrobial stewardship responsibilities into practice of the emergency medicine clinical pharmacist (EPh) decreased times to positive culture follow-up, patient or primary care provider (PCP) notification, and appropriateness of antimicrobial therapy. Pre- and post-implementation groups of an EPh-managed antimicrobial stewardship program were compared. Positive cultures were identified in 177 patients, 104 and 73 in pre- and post-implementation groups, respectively. Median time to culture review in the pre-implementation group was 3 days (range 1-15) and 2 days (range 0-4) in the post-implementation group (P = .0001). There were 74 (71.2%) and 36 (49.3%) positive cultures that required notification in the pre- and post-implementation groups, respectively, and the median time to patient or PCP notification was 3 days (range 1-9) and 2 days (range 0-4) in the 2 groups (P = .01). No difference was seen in the appropriateness of therapy. In conclusion, EPh involvement reduced time to positive culture review and time to patient or PCP notification when indicated.

Off-label medication use in adult critical care patients ☆

PURPOSE This study evaluated the use of off-label medications in the intensive care unit (ICU) setting and their varying levels of evidence. MATERIALS AND METHODS Thirty-seven ICUs from 24 US sites participated in this prospective, multicenter, observational study during a single 24-hour period. All medication orders were evaluated for Food and Drug Administration-labeled indications, strength of evidence, and strength of recommendation. Off-label medication orders were evaluated for indication, dose, route of administration, duration of therapy, and whether they were supported by institutional guidelines. RESULTS A total of 414 patients were enrolled, yielding 5237 medication orders for analysis. Of these, 1897 orders (36.2%) were off-label. The 3 drug classes that accounted for the most off-label orders were bronchorespiratory, gastrointestinal, and immunology. The majority of off-label medication orders (89.1%) were initiated after patient admission to the ICU. Nine hundred twenty-eight (48.3%) of the off-label medication orders had grade C or no evidence. CONCLUSIONS The use of off-label medication therapies in the US adult critical care units is common, a majority of which are initiated after admission to the ICU and a significant portion of which are supported with inferior levels of evidence.

A Prospective Evaluation of Propylene Glycol Clearance and Accumulation During Continuous-Infusion Lorazepam in Critically Ill Patients

Propylene glycol is a commonly used diluent in several pharmaceutical preparations, including the sedative lorazepam. Fifty critically ill patients receiving continuous-infusion lorazepam for a minimum of 36 hours were prospectively evaluated to determine the extent of propylene glycol accumulation over time, characterize propylene glycol clearance in the presence of critical illness, and develop a pharmacokinetic model that would predict clearance based on patient-specific clinical, laboratory, and demographic factors. In this cohort, the median lorazepam infusion rate was 2.1 mg/h (0.5-18). Propylene glycol concentration correlated poorly with osmolality, osmol gap, and lactate. In all, 8 patients (16%) had significant propylene glycol accumulation (>25mg/dL). When propylene glycol concentrations were >25 mg/dL, the median lorazepam infusion rate before sample collection was higher, 6.4 (1.9-11.3) versus 2.0 (0.5-7.4) mg/h (P =.0003). A linear first-order model with interoccasion variability on clearance adjusted for total body weight and Acute Physiology and Chronic Health Evaluation II score predicted propylene glycol concentration.

Rhabdomyolysis and Acute Renal Failure following an Ethanol and Diphenhydramine Overdose

OBJECTIVE: To report a case of nontraumatic rhabdomyolysis complicated by oliguric, acute renal failure following an intentional overdose of ethanol and diphenhydramine. CASE SUMMARY: A 21-year-old white man was admitted through the emergency department following an intentional overdose of ethanol and diphenhydramine. The patient subsequently developed acute renal failure, and a diagnosis of nontraumatic rhabdomyolysis was made. With the absence of other common causes in this case, the rhabdomyolysis was believed to be due to the combined ethanol and diphenhydramine overdose. DISCUSSION: Rhabdomyolysis is a severe and life-threatening syndrome caused by various insults to skeletal muscle, including drug-induced injury. Early detection and institution of effective treatments are essential to minimizing the complications of this syndrome. A delay in establishing the diagnosis in this case likely contributed to the severity of the renal failure. CONCLUSIONS: Nontraumatic rhabdomyolysis is an uncommon adverse outcome of drug and toxin ingestion. Due to the potential severity of the complications of this syndrome and the importance of early recognition and treatment to prevent renal failure, clinicians should have a high index of suspicion for rhabdomyolysis following overdoses that involve alcohol or antihistamines.

Interdisciplinary patient care in the intensive care unit: focus on the pharmacist.

The field of critical care medicine began to flourish only within the last 40 years, yet it provides some of the best examples of collaborative pharmacy practice models and evidence for the value of pharmacist involvement in interdisciplinary practice. This collaborative approach is fostered by critical care organizations that have elected pharmacists into leadership positions and recognized pharmacists through various honors. There is substantial literature to support the value of the critical care pharmacist as a member of an interdisciplinary intensive care unit (ICU) team, particularly in terms of patient safety. Furthermore, a number of economic investigations have demonstrated cost savings or cost avoidance with pharmacist involvement. As the published evidence supporting pharmacist involvement in patient care activities in the ICU setting has increased, surveys have demonstrated an increase in the percentage of pharmacists performing clinical activities. In addition, substantial support of pharmacists has been provided by other clinicians, safety officers, and administrative personnel who have been involved with the initiation and expansion of critical care pharmacy services in their own institutions. Although there is still room for improvement in the range of pharmacist involvement, particularly with respect to interdisciplinary activities related to education and scholarship, pharmacists have become essential members of interdisciplinary care teams in ICU settings.