INTRATHECAL BACLOFEN OVERDOSE - REPORT OF 7 EVENTS IN 5 PATIENTS AND REVIEW OF THE LITERATURE

This study is intended to alert the clinician to the insidious symptoms of baclofen overdose, its prevention and treatment. In a group of 43 patients suffering from previously intractable spasticity and a total treatment time of 2,422 weeks, 7 events of intrathecal baclofen overdose happened in 5 patients. On two occasions, a bolus injection caused an overdose (dose 50 and 280-mu-g). The 5 events during continuous infusion intoxication only happened in high dosed patients. The overdose symptoms occurred in one patient when she was lying in supine position (800-mu-g/24 h), in another patient after repair of CSF leakage by an autologous epidural bloodpatch (1,920-mu-g/24 h) and in tolerant patients, once during maximal dose adjustments (2,400-mu-g/24 h) and twice ca. 6 hours following reinitiation of the intrathecal baclofen infusion after a "drug holiday" treatment (27 and 55-mu-g/h). We could not confirm the reported similarity of baclofen overdose with the anticholinergic syndrome. Especially, the bradycardia and hypotension are more in accord with the reported clinical picture of oral baclofen overdose. In the absence of a pure baclofen antagonist and the varying symptoms of intrathecal baclofen, intoxication make rational treatment difficult. We observed that the advised physostigmine therapy is not always effective and safe. The occasionally doubtful antidotal benefits of physostigmine must be weighed against major side-effects. The classical approach of decreasing the absorption of a drug by lowering baclofen levels in the CSF by lumbar puncture drainage was successful. This approach together with conservative symptomatic treatment in an intensive care environment is probably a better and safer alternative than physostigmine alone as an antidote

Isotopic Scintigraphy in Intrathecal Drug Delivery Failure: A Single-Institution Case Series

Background: The aim of this study was to assess the feasibility and diagnostic accuracy of an optimized 111Indium-diethylenetriamine-penta-acetic-acid single-photon-emission computed tomography (CT) (111In-DTPA SPECT-CT) examination

Creation and application of virtual patient cohorts of heart models

Patient-specific cardiac models are now being used to guide therapies. The increased use of patient-specific cardiac simulations in clinical care will give rise to the development of virtual cohorts of cardiac models. These cohorts will allow cardiac simulations to capture and quantify inter-patient variability. However, the development of virtual cohorts of cardiac models will require the transformation of cardiac modelling from small numbers of bespoke models to robust and rapid workflows that can create large numbers of models. In this review, we describe the state of the art in virtual cohorts of cardiac models, the process of creating virtual cohorts of cardiac models, and how to generate the individual cohort member models, followed by a discussion of the potential and future applications of virtual cohorts of cardiac models. This article is part of the theme issue 'Uncertainty quantification in cardiac and cardiovascular modelling and simulation'

Advanced and controlled drug delivery systems in clinical disease management

Advanced and controlled drug delivery systems are important for clinical disease management. In this review the most important new systems which have reached clinical application are highlighted. Microbiologically controlled drug delivery is important for gastrointestinal diseases like ulcerative colitis and distally controlled release systems have improved patient compliance and decreased side effects. In the treatment of intractable pain the spinal and transdermal route is well documented. In neurology the flattened peak-through levels of antiepileptic drugs and anti Parkinson's drugs represents a more predictable kinetic profile. Tracheal delivery of corticosteroids and sympaticommimetics in asthma and Chronic Obstructive Pulmonary Disease is fully accepted in clinical practice: delivery by this route results in better efficacy and a better safety profile. In gynaecology the delivery of pulsatile hormones (LHRH) is used for pregnancy induction, while transdermal oestrogens are promising in the prevention of osteoporosis. In surgical practice the use of antibiotic impregnated bone cement and antibiotic impregnated biodegradable collagens is well established. To prevent infections intravascular catheters coated with heparin or antibiotics are used. In ophthalmology the Ocusert(R) systems provide a controlled release of different drugs in the eye. Most spectacular is the clinical introduction of the first liposomal drugs: amfotericine B and daunorubicine. Liposomal formulations of these drugs have enhanced activity and decreased toxicity compared to conventional formulations