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

Abbott Labs, Bristol-Myers Squibb, Eli Lilly, and Express Scripts. Dr. George participates in the American Association of Critical Care Nurses (journal article reviews for continuing education); and she disclosed that she had a onetime contract with Medtronic for speaking engagement on capnography, presented at the American Association of Critical Care Nurses National Teaching Institute (May 2016). The remaining authors have disclosed that they do not have any potential conflicts of interest.

Despite regular use of drugs for critically ill patients, overall data are limited regarding the impact of critical illness on pharmacokinetics (PK). Designing safe and effective drug regimens for patients with critical illness requires an understanding of PK. This article reviews general principles of PK, including absorption, distribution, metabolism, and elimination, and how critical illness can influence these parameters. In the area of drug absorption, we discuss the impact of vasopressor use, delayed gastric emptying and feeding tubes, and nutrient interactions. On the topic of drug distribution, we review fluid resuscitation, alterations in plasma protein binding, and tissue perfusion. With drug metabolism, we discuss hepatic enzyme activity, protein binding, and hepatic blood flow. Finally, we review drug elimination in the critically ill patient and discuss the impact of augmented renal clearance and acute kidney injury on drug therapies. In each section, we highlight select literature reviewing the PK impact of these conditions on a drug PK profile and, where appropriate, provide general suggestions for clinicians on how to modify drug regimens to manage PK challenges.

OBJECTIVES:Dose calculations using three variations of patient weight estimates (actual body weight [ABW], ideal body weight [IBW], and the Broselow Pediatric Emergency Tape [BPET, a length-based weight estimation tool]) were compared to administered doses of cardiopulmonary resuscitation medications in overweight and obese children to assess for differences in dose.METHODS:This retrospective cohort analysis included 54 consecutive pediatric patients who underwent emergency resuscitation at UMass Memorial Medical Center between January 2000 and October 2008. Patients were identified using ICD-9 codes related to cardiopulmonary resuscitation. Patients were included if they were overweight or obese, less than 12 years of age, less than 146 centimeters in length, and received emergency resuscitation medication(s). Doses of administered medications were recorded and compared to potential doses calculated based on ABW, IBW and the dose recommended by the BPET. Dose differences greater than 10% were considered clinically significant and dose differences greater than 20% were considered to be potential medication errors.RESULTS:Out of 54 possible patients, four overweight patients were included; none were obese. Ten total medication doses were assessed (minimum two per patient). In all patients, at least one comparator dose varied by greater than 20% from the administered dose. Four out of 10 doses calculated according to ABW, eight out of 10 doses calculated with IBW, and eight out of 10 doses recommended by the BPET all differed by greater than 20% from the administered dose.CONCLUSIONS:Dosing variations were observed when the dose received was compared to dosing using three variants of patient weight estimates. The largest dosing differences were observed upon comparison of the administered dose versus the dose recommended by the BPET.

Hepatic dysfunction in the critically ill patient presents a unique challenge to clinicians when designing pharmacotherapeutic treatment plans. Overall, the literature regarding drug dosing in critically ill patients with hepatic dysfunction is incomplete and current tools available to bedside clinicians have limitations. Despite these challenges, rational drug regimens can be implemented by critical care nurses who consider the potential impact of hepatic dysfunction on drug pharmacokinetics. This information can be applied clinically and careful monitoring plans can be implemented to assess a drug for efficacy and safety. This article reviews the pharmacokinetic changes that can occur in hepatic failure, identifies practical ways to quantify the severity of dysfunction, and discusses general drug dosing strategies in this patient population.

Purpose. The quantity of aluminum in common ingredients used to compound parenteral nutrient (PN) solutions was calculated to quantify the actual aluminum content, and opportunities to modify the aluminum content by changing the manufacturer of the ingredients were explored.Methods. A retrospective evaluation of a random sample of 10 neonatal, 10 pediatric, and 10 adult patients who received PN solutions was performed to quantify the aluminum content in these solutions on the basis of the ingredients used at the authors' institution. A recalculation was performed using the lowest aluminum-containing ingredients to determine the potential for aluminum minimization in each PN solution.Results. Various manufacturers produce each ingredient required to make PN solutions. Significant variation exists among manufacturers, vial size, and concentrations. Statistically significant differences in the mean aluminum content of PN solutions before and after aluminum minimization were found to exist within each sample of patients. Among the neonatal PN solutions, aluminum content was significantly reduced from a mean +/- S.D. of 84.16 +/- 47.61 to 33.6 +/- 16.69 mu g/kg/day. The pediatric PN solutions had a significant decline in aluminum content from a mean S.D. of 16.24 +/- 3.66 to 6.84 +/- 2.66 mu g/kg/day. Aluminum content in the high-risk adult PN solutions significantly decreased from a mean S.D. of 4.58 coproduct 2.06 to 2.31 +/- 0.63 mu g/kg/day.Conclusion. There is wide variability in the aluminum concentration of injectable products used in the compounding of PN solutions. Selecting products with low aluminum concentration may substantially reduce the amount of the element administered to patients.

Purpose. The effect of pharmacist-conducted medication reconciliation on compliance with a hospital's medication reconciliation policy was studied.Methods. In this eight-week pilot study, one pharmacist worked in the emergency department (ED) to facilitate the safe and accurate transfer of medication histories for admitted patients. During the first four weeks, retrospective chart review was performed for 100 patients in March 2006 to determine the compliance rate to the hospital's medication reconciliation policy (medication reconciliation completed for every patient using the hospital-approved form). Over the next four weeks, the same pharmacist prospectively obtained medication histories from consecutive patients in April 2006; these patients comprised the study group. The pharmacist completed the medication reconciliation form and identified and corrected all discrepancies. Unpaired t tests and Fisher's exact test were used to determine significant differences between groups.Results. The hospital-approved medication form was used for 78% of patients in the control group (78 of 100) and 100% of patients in the study group (60 of 60). The mean +/- S.D. number of errors per form was significantly higher in the control group than in the study group, and the percentage of forms containing at least one error was significantly higher in the control group (p = 0.001 for both comparisons). Allergy documentation was recorded for 62 patients in the study group versus all 60 in the study group (p = 0.001).Conclusion. Pharmacist-conducted medication reconciliation in the ED increased compliance to the institution's medication reconciliation policy for admitted patients. Pharmacist-acquired medication histories had significantly fewer errors in documentation and had more documentation of patient allergies.

The use of sedative and analgesic drug therapy is often necessary for the care of critically ill patients. Renal and hepatic dysfunction, which occurs frequently in this patient population, can significantly alter drugs' pharmacokinetic and pharmacodynamics properties. By anticipating how these medications may be affected by liver or kidney dysfunction, health care practitioners may be able to provide tailored dosing regimens that ensure optimal comfort while minimizing the risk of adverse events.

Purpose Patients with severe sepsis are critically ill and use a high level of health care resources. The high resource utilization and lack of a specific diagnosis related group may lead to a significant loss in revenue for health care organizations secondary to inadequate reimbursement. The primary objective of this study is to quantify the difference in total cost and reimbursement in patients with severe sepsis treated with drotrecogin alfa (activated) (DAA) at our institution. Methods All patients between December 2001 and December 2003 diagnosed with severe sepsis and treated with DAA were evaluated. Demographic data, primary payer, diagnosis related group, hospital length of stay, length of medical/surgical stay, length of Intensive Care Unit stay, days on mechanical ventilation, total costs, and total reimbursement were determined by chart review and our institution's information systems. Results Data from a total of 71 patients were included. The total treatment cost was $6,294,590, and the total reimbursement received was $4,295,950. This represents a loss of $1,998,640 or $28,150 per patient. The primary factor contributing to this loss was Intensive Care Unit length of stay (P = 0.011). Conclusion Management of patients with severe sepsis is costly and strains hospital resources. The current reimbursement system does not allow for appropriate compensation. Therefore, in addition to efforts directed toward improved treatment strategies for severe sepsis, health care practitioners must target interventions to reduce hospital length of stay and maximize reimbursement.

Four patients with severe burn injuries received enoxaparin 40 mg twice/day subcutaneously for the prophylaxis of venous thromboembolism (VTE). Peak antifactor Xa levels were measured 4 hours after administration of a dose, and trough antifactor Xa levels were measured 30 minutes before the next scheduled dose. Ultrasonography was performed once/week to assess the presence of VTE. Any occurrence of major bleeding was documented in the patients' charts. All patients had trough antifactor Xa levels below 0.1 U/ml. Enoxaparin dosages were subsequently adjusted to achieve trough antifactor Xa levels of 0.1–0.2 U/ml. This required dosages higher than those typically recommended for VTE prophylaxis (40 mg every 24 hrs or 30 mg every 12 hrs). One patient needed more than 60 mg every 12 hours. No patient had a venous thromboembolic event or major bleeding. The low antifactor Xa levels that were observed suggest that a reduced dose‐response relationship may exist between subcutaneously administered enoxaparin and antifactor Xa activity in patients with severe burn injuries. Prospective studies should be performed to further investigate this relationship.

Journal Article Recommended and actual lepirudin doses in patients with renal insufficiency Get access Sarah B. Saxer, Pharm.D., Sarah B. Saxer, Pharm.D. Clinical Pharmacy Specialist, Solid Organ Transplantation Department of Pharmacy, UMass Memorial Medical Center, Worcester Address correspondence to Dr. Saxer at the Department of Pharmacy, UMass Memorial Medical Center, 55 Lake Avenue North, Worcester, MA 01655 saxers@ummhc.org. Search for other works by this author on: Oxford Academic Google Scholar Brian S. Smith, Pharm.D., Brian S. Smith, Pharm.D. Clinical Pharmacy Specialist, Surgical Intensive Care Department of Pharmacy, UMass Memorial Medical Center, Worcester Search for other works by this author on: Oxford Academic Google Scholar Pritesh J. Gandhi, Pharm.D., BCPS, Pritesh J. Gandhi, Pharm.D., BCPS Assistant Professor of Clinical Pharmacy Massachusetts College of Pharmacy and Health Sciences, Worcester Search for other works by this author on: Oxford Academic Google Scholar Gary R. Tataronis, M.S., Gary R. Tataronis, M.S. Associate Professor of Mathematics/ Statistics Massachusetts College of Pharmacy and Health Sciences, Worcester Search for other works by this author on: Oxford Academic Google Scholar Susan A. Krikorian, M.S. Susan A. Krikorian, M.S. Associate Professor of Pharmacy Practice Massachusetts College of Pharmacy and Health Sciences, Worcester Search for other works by this author on: Oxford Academic Google Scholar American Journal of Health-System Pharmacy, Volume 60, Issue 24, 15 December 2003, Pages 2588–2593, https://doi.org/10.1093/ajhp/60.24.2588 Published: 15 December 2003

Data regarding the use of low-molecular-weight heparins (LMWHs) and glycoprotein (GP) IIb/IIIa receptor antagonists in patients with renal failure are limited. Renal failure has the potential to increase the risk of adverse drug events associated with LMWHs and GP IIb/IIIa receptor antagonists. This is due to changes in the pharmacokinetic and pharmacodynamic profiles of these agents in patients with renal failure. Until more data are available, clinicians should consider alternative therapies in this patient population.

Abstract Gastric acid and peristaltic movements are two major mechanisms in preventing bacterial overgrowth of the upper gastrointestinal tract. Reduced acid secretions and/or altered peristalsis can disrupt normal flora and may result in bacterial overgrowth. Bacterial overgrowth can lead to malabsorption of fats and other nutrients. Fat malabsorption is thought to occur due to overgrowth of bile deconjugating anaerobic organisms. Bile acids are necessary for proper fat absorption; when organisms deconjugate bile acids, fat malabsorption may occur. Acid‐reducing drugs such as omeprazole have been implicated in causing bacterial overgrowth of the upper gastrointestinal tract. Most studies indicate that omeprazole treatment causes an overgrowth primarily of normal swallowed flora that are not capable of deconjugating bile acids, though a few studies do suggest that overgrowth of anaerobes and bile acid deconjugation does occur. At this time, the role of omeprazole as a cause of fat malabsorption is not clear. More studies are needed to determine the extent and clinical significance of omeprazole‐induced fat malabsorption.

We have observed marked depletion of epidermal dendritic cells, defined by monoclonal antibodies directed against HLA-DR (Ia-like) and T6 antigens, after allogeneic bone marrow transplantation. To more precisely characterize this observation, we examined a total of 39 sequential biopsies from 15 patients both before and after allogeneic bone marrow transplantation. Profound depletion of HLA-DR and T6-positive epidermal dendritic cells was observed early after transplantation (1-4 weeks), followed by gradual and variable repopulation. Transmission electron microscopy confirmed absence of dendritic cells in selected biopsies. Depletion of dendritic cells did not appear to be related to development of clinical or histologic evidence of graft-versus-host disease, suggesting that depletion may relate to pretransplant conditioning regimens. The rate of return of these cells, however, may be influenced by the presence or persistence of clinical disease. Repopulation of epidermal dendritic cells after initial depletion in bone marrow transplantation represents a human model relevant to studies concerned with the origin and kinetics of Langerhans cells.