Maureen A. Smythe

Patient-controlled analgesia : a review

The patient‐activated analgesic system was introduced in 1968. Early trials, although uncontrolled, supported the safety and efficacy of patient‐controlled analgesia (PCA) in several kinds of pain, such as that relating to surgery, cancer, trauma, and obstetric procedures. In the past decade, prospective, randomized trials have reported several advantages of PCA over conventional analgesia in the early postoperative period. Although not supported by all controlled trials, they include improved pain relief, less sedation, lower level of narcotic consumption, fewer postoperative complications, greater patient satisfaction, and improved pulmonary function. Preliminary results in the management of chronic pain indicate that PCA can lead to significant lifestyle improvements in ambulatory patients with cancer. The most significant, although infrequent, adverse effect is respiratory depression, the majority of cases occurring in patients predisposed secondary to concomitant illness or as a result of human error. The clinical use of PCA will likely see a significant increase among persons with cancer, and an increase in epidural administration. The cost benefit of PCA has yet to be assessed in inpatient and outpatient settings.

Heparin-induced thrombocytopenia : Treatment options and special considerations

Heparin‐induced thrombocytopenia (HIT) is an immune‐mediated adverse effect that typically manifests several days after the start of heparin therapy, although both rapid‐ and delayed‐onset HIT have been described. Its most serious complication is thrombosis. Although not all patients develop thrombosis, it can be life threatening. The risk of developing HIT is related to many factors, including the type of heparin product administered, route of administration, duration of therapy, patient population, and previous exposure to heparin. The diagnosis of HIT is typically based on clinical presentation, exposure to heparin, and presence of thrombocytopenia with or without thrombosis. Antigen and activation laboratory assays are available to support the diagnosis of HIT. However, because of the limited sensitivity and specificity of these assays, bedside probability scales for HIT were developed. When HIT is suspected, prompt cessation of all heparin therapy is necessary, along with initiation of alternative anticoagulant therapy. Two direct thrombin inhibitors—argatroban and lepirudin—are approved for the management of HIT in the United States, and bivalirudin is approved for use in patients with HIT who are undergoing percutaneous coronary intervention. Other agents, although not approved to manage HIT, have also been used; however, their role in therapy requires further evaluation. A comprehensive HIT management strategy involves the evaluation of numerous factors. Many patients, including those undergoing coronary artery bypass surgery, those with acute coronary syndromes, those with hepatic or renal insufficiency, and children, require special attention. Clinicians must become familiar with the available information on this serious adverse effect and its treatment so that optimum patient management strategies may be formulated.

Drug-induced thrombocytopenia in critically ill patients.

Thrombocytopenia occurs in 15% to 58% of intensive care unit patients. The incidence varies based upon patient population, timing and frequency of platelet monitoring, and definition of thrombocytopenia. Up to 25% of acutely ill patients develop drug-induced thrombocytopenia. When drug-induced thrombocytopenia is suspected, nondrug related causes must be evaluated and excluded. Establishing the diagnosis of drug-induced thrombocytopenia is challenging, as hundreds of medications have been implicated. Medications commonly associated with drug-induced thrombocytopenia include glycoprotein IIb/IIIa inhibitors, cinchona alkaloids, antibiotics, anticonvulsants, and heparin. Once the diagnosis is suspected, clinicians should identify the start date of medications to assess the timeline of development. The likelihood of each medication causing thrombocytopenia must be evaluated. The risk vs. benefit of discontinuing the suspected medication and availability of alternative medications must be assessed. The role of corticosteroids, immune globulin, and plasmapheresis is uncertain. Once the offending agent has been discontinued, the overall prognosis is excellent. In the case of suspected or confirmed heparin-induced thrombocytopenia, an alternative anticoagulant should be initiated. Drug-induced thrombocytopenia should be documented in the medical record and reported according to institutional and national standards. This review focuses on immune-mediated drug-induced thrombocytopenia from medications commonly utilized in the critically ill patient.

Anticoagulation Monitoring Part 2: Unfractionated Heparin and Low-Molecular-Weight Heparin

OBJECTIVE To review the availability, mechanisms, limitations, and clinical application of point-of-care (POC) devices used in monitoring anticoagulation with unfractionated heparin (UFH) and low-molecular-weight heparins (LMWHs). DATA SOURCES Articles were identified through a MEDLINE search (1966–August 2004), device manufacturer Web sites, additional references listed in articles and Web sites, and abstracts from scientific meetings. STUDY SELECTION AND DATA EXTRACTION English-language literature from clinical trials was reviewed to evaluate the accuracy, reliability, and clinical application of POC monitoring devices. DATA SYNTHESIS The activated partial thromboplastin time (aPTT) and activated clotting time (ACT) are common tests for monitoring anticoagulation with UFH. Multiple devices are available for POC aPTT, ACT, and heparin concentration testing. The aPTT therapeutic range for UFH will vary depending upon the reagent and instrument employed. Although recommended by the American College of Chest Physicians Seventh Conference on Antithrombotic and Thrombolytic Therapy, establishing a heparin concentration–derived therapeutic range for UFH is rarely performed. Additional research evaluating anti-factor Xa monitoring of LMWHs using POC testing is necessary. CONCLUSIONS Multiple POC devices are available to monitor anticoagulation with UFH. For each test, there is some variability in results between devices and between reagents used in the same device. Despite these limitations, POC anticoagulation monitoring of UFH using aPTT and, more often, ACT is common in clinical practice, particularly when evaluating anticoagulation associated with interventional cardiology procedures and cardiopulmonary bypass surgery.

Changing Perspectives of Stress Gastritis Prophylaxis

OBJECTIVE: To present recent advances in stress gastritis prophylaxis in the critically ill and review considerations in selection of a prophylactic agent. DATA SOURCES: Information was obtained from MEDLINE search, reference lists from articles identified in search, and from review articles. STUDY SELECTION: Emphasis was placed on controlled trials conducted within the last 5 years. DATA EXTRACTION: All literature was assessed for methodology, results, and conclusions. Results of prospective, randomized trials, and meta-analyses are summarized. DATA SYNTHESIS: Histamine2-receptor antagonists, antacids, and sucralfate appear equally effective in preventing stress gastritis in the critically ill. A definitive cause–effect relationship between histamine2-receptor antagonists and increased incidence of nosocomial pneumonia has not yet been established. The indications for using a prophylactic agent and consideration in selecting an agent should include an evaluation of the following: Risk factors for gastritis including the type of intensive care patient, comparative efficacy, adverse effects, drug interactions, cost, and ease of administration. The least expensive, safest agent requiring minimal monitoring is sucralfate. Prevention of stress gastritis has never been shown to reduce morbidity or mortality significantly. CONCLUSIONS: Controversies still exist regarding the need to provide prophylaxis, the choice of an agent, and the relative importance of previously identified risk factors. Further well-designed studies are needed before consensus can be reached.

Correlation of activated clotting time and activated partial thromboplastin time to plasma heparin concentration.

Study Objective. To determine the correlation between activated clotting time (ACT) or activated partial thromboplastin time (aPTT) and plasma heparin concentration.

An exploratory analysis of medication utilization in a medical intensive care unit

ObjectivesTo evaluate patterns of medication use in a medical intensive care unit (ICU) and to explore relationships between drug use, patient age, admitting diagnosis, Acute Physiology and Chronic Health Evaluation (APACHE II) scores, length of stay, and survival. DesignCombination prospective and retrospective study. SettingMedical ICU in a large teaching institution. PatientsPatient admissions (n = 191) to a medical ICU during a 4-month study period. InterventionsThe following data were collected: age, length of stay, diagnosis, physiologic variables necessary for APACHE II scores, medications administered, and survival. Measurements and Main ResultsThe mean length of stay of the study patients was 5.2 ± 9.8 days. Overall mortality rate was 33%. The mean age of survivors, 62.7 yrs, was significantly (p<.05) lower than that value for nonsurvivors (68.6 yrs). Postcardiopulmonary resuscitation (CPR) or-stroke patients had a mortality rate that was higher than the overall mortality rate (p<.05), APACHE II scores of >19 were associated with a reduced survival rate when compared with the overall mortality rate. The mean daily and mean total number of medications administered per patient were 7.5 ± 3.4 and 12.1 RpM 7.6, respectively. Antihypertensives/vasodilators and gastrointestinal prophylaxis medications were administered most commonly in 69% and 65% of patients, respectively. The median total drug use per patient was significantly greater in nonsurvivors vs. survivors (13 and 10, respectively, p<.02). There was a positive linear relationship between total medication use and log length of stay (r2 = .62). Patients admitted post-CPR or with seizures received the highest number of medications (p<.05). ConclusionsPatients admitted to the medical ICU receive multiple medications from a variety of pharmacologic classes. Prolonged length of stay, certain admitting diagnoses, and death are associated with increased medication administration. Age, certain admitting diagnoses, and APACHE II scores are significantly related to survival. (Crit Care Med 1993; 21:1319–1323)

Drug-Induced Alterations in Serum Creatinine Concentrations

OBJECTIVE: To provide a comprehensive review of drug-induced alterations in serum creatinine concentrations (SCrs). DATA SOURCES: Information was obtained from a MEDLINE search, reference lists from articles identified in the search, review articles, and abstracts. STUDY SELECTION: Emphasis was placed on clinical studies of direct relevance to clinical practitioners. DATA EXTRACTION: Literature was assessed for its methodology, results, discussion, and conclusion. DATA SYNTHESIS: Two analytical systems to assay SCr are commonly employed in clinical practice—the Jaffé-based and enzymatic methods. Several drugs have been reported to interfere with SCr results obtained with both analytical systems by producing assay interference. In addition, trimethoprim, cimetidine, and salicylates produce elevations in the SCr by altering the normal elimination pathways of creatinine. Phenacemide has been reported to increase creatinine elimination, but the mechanism of this effect is unknown. CONCLUSIONS: Pharmacists should recognize the clinical significance of drug-induced interference with SCr and propose alternative methods of determining concentrations in selected patients.

Phenytoin hepatotoxicity: a review of the literature

Phenytoin hepatotoxicity is a serious idiosyncratic reaction that occurs in less than one percent of patients. The onset of symptoms occurs early in therapy, usually within the first six weeks. Presenting symptoms often include fever, rash, lymphadenopathy, hepatomegaly, anorexia, and myalgias or arthralgias. Other significant findings that may develop throughout hospitalization are jaundice, periorbital or facial edema, and splenomegaly. The following alterations in liver function tests are associated with phenytoin hepatotoxicity: elevations in serum aminotransferases, lactic dehydrogenase, alkaline phosphatase, bilirubin, and prothrombin time. Rechallenges, lymphocyte stimulation test, and liver biopsy have been used to aid in the diagnosis. Rechallenge is the most definitive diagnostic approach; however, its use is limited by the potential of a fatal reaction. Although the exact mechanism of phenytoin hepatotoxicity is unknown, the majority of literature supports a hypersensitivity mechanism. The severity of this adverse effect ranges from self-limiting to fatal. Since 1965 six fatal cases have been reported. To date, sufficient evidence is not available to establish treatment guidelines. Discontinuation of phenytoin therapy is warranted.

Guidance for the practical management of the heparin anticoagulants in the treatment of venous thromboembolism.

Venous thromboembolism (VTE) is a serious and often fatal medical condition with an increasing incidence. Despite the changing landscape of VTE treatment with the introduction of the new direct oral anticoagulants many uncertainties remain regarding the optimal use of traditional parenteral agents. This manuscript, initiated by the Anticoagulation Forum, provides clinical guidance based on existing guidelines and consensus expert opinion where guidelines are lacking. This specific chapter addresses the practical management of heparins including low molecular weight heparins and fondaparinux. For each anticoagulant a list of the most common practice related questions were created. Each question was addressed using a brief focused literature review followed by a multidisciplinary consensus guidance recommendation. Issues addressed included initial anticoagulant dosing recommendations, recommended baseline laboratory monitoring, managing dose adjustments, evidence to support a relationship between laboratory tests and meaningful clinical outcomes, special patient populations including extremes of weight and renal impairment, duration of necessary parenteral therapy during the transition to oral therapy, candidates for outpatient treatment where appropriate and management of over-anticoagulation and adverse effects including bleeding and heparin induced thrombocytopenia. This article concludes with a concise table of clinical management questions and guidance recommendations to provide a quick reference for the practical management of heparin, low molecular weight heparin and fondaparinux.