Tissue pulsatility imaging of cerebral vasoreactivity during hyperventilation

Tissue pulsatility imaging (TPI) is an ultrasonic technique that is being developed at the University of Washington to measure tissue displacement or strain as a result of blood flow over the cardiac and respiratory cycles. This technique is based in principle on plethysmography, an older nonultrasound technology for measuring expansion of a whole limb or body part due to perfusion. TPI adapts tissue Doppler signal processing methods to measure the "plethysmographic" signal from hundreds or thousands of sample volumes in an ultrasound image plane. This paper presents a feasibility study to determine if TPI can be used to assess cerebral vasoreactivity. Ultrasound data were collected transcranially through the temporal acoustic window from four subjects before, during and after voluntary hyperventilation. In each subject, decreases in tissue pulsatility during hyperventilation were observed that were statistically correlated with the subject's end-tidal CO2 measurements. (     

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.     

Corpus Callosum Morphometrics in Young Children with Autism Spectrum Disorder

This study assessed midsagittal corpus callosum cross sectional areas in 3–4 year olds with autism spectrum disorder (ASD) compared to typically developing (TD) and developmentally delayed (DD) children. Though not different in absolute size compared to TD, ASD callosums were disproportionately small adjusted for increased ASD cerebral volume. ASD clinical subgroup analysis revealed greater proportional callosum reduction in the more severely affected autistic disorder (AD) than in pervasive developmental disorder-not otherwise specified (PDD-NOS) children. DD children had smaller absolute callosums than ASD and TD. Subregion analysis revealed widely distributed callosum differences between ASD and TD children. Results could reflect decreased inter-hemispheric connectivity or cerebral enlargement due to increase in tissues less represented in the corpus callosum in ASD.     

Considerations for drug dosing post coronary artery bypass graft surgery

Acute physiologic changes after bypass graft surgery may temporarily result in reduced drug elimination and dosing requirements for the desired effect. Substantially lower doses for drugs such as the direct thrombin inhibitor argatroban may need to be considered when initiating therapy soon after surgery if the therapeutic window is narrow and impaired liver, kidney, or cardiac function is present. Initial dosing approaches, with follow-up infusion rate adjustments and allowances for the extended time needed to establish and maintain an activated partial thromboplastin time value in the target ratio range, also need to consider the risk of thrombosis or bleeding complications. The duration of reduced dosing may depend on several variables, and, as systems recover, the dosage may need to be adjusted upwards. Retrospective analysis for identifying heparin-induced thrombocytopenia may be difficult in situations where other causes of thrombocytopenia are present, suggesting that posttest scoring methods also be considered to confirm its presence until better, validated methods become available.     

Pharmacotherapy considerations in advanced cardiac life support

Cardiac arrest and sudden cardiac death remain major causes of mortality. Early intervention has been facilitated by emergency medical response systems and the development of training programs in basic life support and advanced cardiac life support (ACLS). Despite the implementation of these programs, the likelihood of a meaningful outcome in many life-threatening situations remains poor. Pharmacotherapy plays a role in the management of patients with cardiac arrest, with new guidelines for ACLS available in 2005 providing recommendations for the role of specific drug therapies. Epinephrine continues as a recommended means to facilitate defibrillation in patients with pulseless ventricular tachycardia or ventricular fibrillation; vasopressin is an alternative. Amiodarone is the primary antiarrhythmic drug that has been shown to be effective for facilitation of defibrillation in patients with pulseless ventricular tachycardia or fibrillation and is also used for the management of atrial fibrillation and hemodynamically stable ventricular tachycardia. Epinephrine and atropine are the primary agents used for the management of asystole and pulseless electrical activity. Treatment of electrolyte abnormalities, severe hypotension, pulmonary embolism, acute ischemic stroke, and toxicologic emergencies are important components of ACLS management. Selection of the appropriate drug, dose, and timing and route of administration are among the many challenges faced in this setting. Pharmacists who are properly educated and trained regarding the use of pharmacotherapy for patients requiring ACLS can help maximize the likelihood of positive patient outcomes.     

Reversal of elevated international normalized ratios and bleeding with low-dose recombinant activated factor VII in patients receiving warfarin

STUDY OBJECTIVE: To assess the effectiveness of using low-dose recombinant activated factor VII (rFVIIa) to reverse the effects of warfarin in critically ill patients with major bleeding events. DESIGN: Prospective observational study. SETTING: Intensive care unit of a 500-bed university-affiliated hospital. PATIENTS: Sixteen nonhemophiliac patients who had been receiving warfarin and had an acute major bleeding event. INTERVENTION: Patients received rFVIIa 1.2 mg for reversal of anticoagulation. MEASUREMENTS AND MAIN RESULTS: Patients were identified from clinical pharmacology consult service electronic tracking records, and their data were cross-checked with the pharmacy information system. Information collected for each patient included extent of bleeding and magnitude of elevation in international normalized ratio (INR). A mean +/- SD dose of rFVIIa 16.3 +/- 4.1 microg/kg (range 11-25 microg/kg) reduced the mean INR from 2.8 +/- 1.6 (range 1.44-6.34) to 1.07 +/- 0.27 (range 0.86-1.92, p<0.001). A rapid onset of response for achieving a desirable hemostatic effect was observed in 14 of the 16 patients. CONCLUSION: Low-dose rFVIIa appears to be an effective, rapid reversal modality for major bleeding events in the presence of warfarin and an elevated INR. The agent's response is quicker than that expected with fresh frozen plasma combined with vitamin K. In emergency situations, rFVIIa 1.2 mg can be used to reverse the anticoagulant effect of warfarin and other vitamin K antagonists without inducing a hypercoagulable state; the product, however, is expensive.     

Treatment of heparin-induced thrombocytopenia

OBJECTIVE: To describe heparin-induced thrombocytopenia (HIT or HIT-2), an immune-mediated adverse reaction to heparin or low-molecular-weight heparin. Available treatment options and considerations in developing a therapy approach are discussed. DATA SOURCES: A search of the National Library of Medicine (1992-June 2001) was done to identify pertinent literature. Additional references were reviewed from selected articles. STUDY SELECTION: Articles related to laboratory recognition and treatment options of HIT, including the use of agents in selected clinical conditions, were reviewed and included. CONCLUSIONS: HIT is a rare but potentially severe adverse reaction to heparin that was, until recently, poorly understood and had limited treatment options. Recent advances describing the recognition and clinical manifestations of immune-mediated HIT, including recently available antithrombotic treatment options, have dramatically changed outcomes for patients having this syndrome.     

Neuropsychological function in retired workers with previous long-term occupational exposure to solvents

OBJECTIVES: It is plausible that neurodegenerative processes of aging might have a contributing role in the development of chronic effects of exposure to organic solvents. This study evaluated the risk for neuropsychological deficits among retired workers, relative to their histories of exposure to occupational solvents. METHODS: This cross sectional study evaluated retired male workers, 62-74 years of age, including 89 people with previous long-term occupational exposure to solvents (67 retired painters and 22 retired aerospace manufacturing workers), and 126 retired carpenters with relatively minimal previous exposure to solvents. Subjects completed a standardised neuropsychological evaluation and psychiatric interview, structured interviews for histories of occupational exposure and alcohol consumption, and questionnaires assessing neurological and depressive symptoms. RESULTS: By comparison with the carpenters, the painters on average reported greater cumulative alcohol consumption and had lower scores on the WAIS-R vocabulary subtest, usually presumed to reflect premorbid intellectual functioning. These findings, however, were not sufficient to account for the other study findings. Controlling for age, education, vocabulary score, and alcohol use, the painters had lower mean scores on test measures of motor, memory, and reasoning ability; and a subgroup of aerospace workers with moderate to high cumulative exposure to solvents (n = 8) had lower mean scores on measures of visuomotor speed, and motor, attention, memory, and reasoning ability. Subjects were more likely to have an increased number of relatively abnormal test scores (three or more outlier scores on 17 test measures) among both the painter group (odds ratio (OR), 3.1; 95% confidence interval (95% CI) 1.5 to 6.2) and the subgroup of aerospace workers with higher cumulative exposure (OR 5.6; 95% CI 1.0 to 38). The painters, but not the aerospace workers, reported significantly more neurological and depressive symptoms. CONCLUSIONS: The findings are consistent with residual central nervous system dysfunction from long-term exposure to organic solvents, persisting years after the end of exposure.