Patterns of potentially inappropriate medication use across three cohorts of older medicaid recipients.
Rigler SK, Jachna CM, Perera S, Shireman TI, Eng ML.
Department of Medicine, Research Faculty, Landon Center on Aging, School of Medicine, University of Kansas, Kansas City, KS.
BACKGROUND: Potentially inappropriate medication use is a serious quality concern, especially when it occurs in more vulnerable older adults or for extended durations. OBJECTIVE: To characterize patterns of inappropriate medication use and duration among 3 cohorts with differing health status. METHODS: We identified unconditionally inappropriate drug use, using Beers 1997 criteria, among 3185 older Kansas Medicaid beneficiaries. Claims from May 2000 to April 2001 provided data for 3 cohorts: nursing facility (NF) residents, recipients of home- and community-based services through the Frail Elderly (FE) program, and persons with neither NF/FE care (Ambulatory). Duration, categorized as short-term (1-9 mo), or chronic (>9-12 mo), was determined for each drug and cohort. Drug-disease associations were explored. RESULTS: Any inappropriate medication use occurred in 21%, 48%, and 38% of Ambulatory, FE, and NF cohorts, respectively. Inappropriate analgesics, antihistamines, antidepressants, muscle relaxants, and oxybutynin were most common, but prevalence and duration varied by cohort. Short-term analgesic and antihistamine use was common. FE cohort members had the highest use rates for all drugs. The NF cohort had less antidepressant and muscle relaxant / relaxants use. Drug-disease associations were noted for amitriptyline use in diabetes mellitus, propoxyphene use in musculoskeletal and upper gastrointestinal conditions, and muscle relaxant / relaxants use in musculoskeletal conditions. CONCLUSIONS: Cross-sectional, one-year prevalence figures are comprised of both short- and long-term use that varies by drug and cohort. NF residence is associated with reduced use of drugs scrutinized during mandated medication review. Relevant diseases are associated with specific inappropriate prescribing. Future efforts should target extended and chronic duration of use and persons at highest risk for adverse effects, including recipients of home- and community-based care.


Intrathecal baclofen withdrawal syndrome caused by low residual volume in the pump reservoir: a report of 2 cases.
Rigoli G, Terrini G, Cordioli Z.
Department of Physical Medicine and Rehabilitation, Unita Gravi Cerebrolesioni, Unita Spinale, Ospedale Sacro Cuore, Negrar, Verona, Italy. gianfranco.rigoli@sacrocuore.it
Intrathecal baclofen (ITB) is an effective treatment for spasticity caused by spinal or cerebral pathologies. Severe withdrawal symptoms can result, however, if ITB is abruptly withdrawn as a result of equipment malfunctions or human error. We describe 2 cases of severe ITB withdrawal syndrome. In the first case, the symptoms appeared 5 months after pump placement, when residual volume was 2.0 mL; in the second case, symptoms appeared 2 months after the replacement of a new pump, when residual volume was 0.9 mL. In both cases, there was no evidence of system malfunction or human error. The syndrome occurred from up to 72 hours before the scheduled refilling procedure, and the residual volume in the Medtronic SynchroMed EL pump reservoir was either at, or significantly lower than, the recommended 2 mL. These cases suggest that the SynchroMed EL pump reservoir should be refilled, to avoid potentially serious consequences, when the residual volume is not lower than 3 mL by programming the alarm to sound at a volume larger than the recommended 2 mL.


Subdural catheter migration may lead to baclofen pump dysfunction.

OBJECTIVES: To report an unusual cause of intrathecal drug delivery failure in baclofen pump device. STUDY DESIGN: A case report of an SCI patient treated with intrathecal baclofen, presenting a drug withdrawal. SETTING: Regional spinal cord injuries centre in Geneva (Switzerland). METHODS: We present a case of a 38-year-old male with complete T9 spastic paraplegia for 15 years, treated with intrathecal baclofen for 11 years. He recently presented to our centre with a spastic hypertonic episode, associated with rhabdomyolysis. RESULTS: Standard investigations were unrevealing. However, a CT scan performed after injecting a radio-opaque solution by the side port of the pump, showed an unexpected catheter migration into the subdural space. Surgical revision reversed withdrawal symptoms. CONCLUSIONS: Subdural catheter migration must be considered in the differential diagnosis of intrathecal drug delivery system failures. We recommend the use of the CT scan after contrast injection, to detect the localization of the distal catheter tip and confirm the normal diffusion into the subarachnoid space.

GHB-C rats: the control line of GHB-sensitive (GHB-S) and GHB-resistant (GHB-R) rats.
Lobina C, Colombo G, Orru A, Maccioni P, Gessa GL, Carai MA.
Brodie Department of Neuroscience, University of Cagliari, Viale Diaz 182, I-09126 Cagliari, Italy.
Gamma-hydroxybutyric acid (GHB)-sensitive (GHB-S) and GHB-resistant (GHB-R) rats have been selectively bred for their opposite sensitivity to the sedative/hypnotic effect of GHB. This opposite sensitivity has been found to generalize to the GABA(B) receptor agonist, baclofen. A control line [named GHB-control (GHB-C)] has been derived from the foundation stock of GHB-S and GHB-R rats. GHB-C rats have been bred without any evaluation of their sensitivity to GHB. The experiments described here were designed to evaluate the sensitivity of GHB-C rats, from the 13th generation, to the sedative/hypnotic effect of GHB (1 g/kg, i.p.) and baclofen (20 mg/kg, i.p.). All measures (onset, sleep time and r = sleep time/onset) of sensitivity to GHB- and baclofen-induced sedation/hypnosis in GHB-C rats were significantly different from and intermediate to those recorded in GHB-S and GHB-R rats. Furthermore, these values were similar to those recorded in the foundation stock. These results suggest that GHB-C rats may constitute a valid control line for GHB-S and GHB-R rats, representing the "general population" from which GHB-S and GHB-R rats were derived. Furthermore, the relative equidistance of sensitivity to GHB- and baclofen-induced sedation/hypnosis of GHB-C rats from those of GHB-S and GHB-R rats suggests that genetic factors contributes to the development of both sensitivity in GHB-S rats and resistance in GHB-R rats.

Dantrolene stabilizes domain interactions within the ryanodine receptor.
Kobayashi S, Bannister ML, Gangopadhyay JP, Hamada T, Parness J, Ikemoto N.
Boston Biomedical Research Institute, Watertown, Massachusetts 02472, USA.
Interdomain interactions between N-terminal and central domains serving as a "domain switch" are believed to be essential to the functional regulation of the skeletal muscle ryanodine receptor-1 Ca(2+) channel. Mutational destabilization of the domain switch in malignant hyperthermia (MH), a genetic sensitivity to volatile anesthetics, causes functional instability of the channel. Dantrolene, a drug used to treat MH, binds to a region within this proposed domain switch. To explore its mechanism of action, the effect of dantrolene on MH-like channel activation by the synthetic domain peptide DP4 or anti-DP4 antibody was examined. A fluorescence probe, methylcoumarin acetate, was covalently attached to the domain switch using DP4 as a delivery vehicle. The magnitude of domain unzipping was determined from the accessibility of methylcoumarin acetate to a macromolecular fluorescence quencher. The Stern-Volmer quenching constant (K(Q)) increased with the addition of DP4 or anti-DP4 antibody. This increase was reversed by dantrolene at both 37 and 22 degrees C and was unaffected by calmodulin. [(3)H]Ryanodine binding to the sarcoplasmic reticulum and activation of sarcoplasmic reticulum Ca(2+) release, both measures of channel activation, were enhanced by DP4. These activities were inhibited by dantrolene at 37 degrees C, yet required the presence of calmodulin at 22 degrees C. These results suggest that the mechanism of action of dantrolene involves stabilization of domain-domain interactions within the domain switch, preventing domain unzipping-induced channel dysfunction. We suggest that temperature and calmodulin primarily affect the coupling between the domain switch and the downstream mechanism of regulation of Ca(2+) channel opening rather than the domain switch itself.

Prescription of nonsteroidal anti-inflammatory drugs and muscle relaxants / relaxant for back pain in the United States.
Luo X, Pietrobon R, Curtis LH, Hey LA.
Center for Clinical Effectiveness, Duke Clinical Research Institute, Duke University Medical Center, Durham, NC 27710, USA. luo00003@mc.duke.edu
STUDY DESIGN: Secondary analysis of the 2000 Medical Expenditure Panel Survey (MEPS). OBJECTIVE.: To examine national prescription patterns of nonsteroidal anti-inflammatory drugs (NSAIDs) and muscle relaxants / relaxant among individuals with back pain in the United States. SUMMARY OF BACKGROUND DATA: There is a lack of information on national prescription patterns of NSAIDs and muscle relaxants / relaxant among individuals with back pain in the United States. METHODS: Traditional NSAIDs, cyclooxygenase-2-specific (COX-2) inhibitors, and muscle relaxants / relaxant were investigated. Individuals with back pain were stratified by socio-demographic characteristics and geographic regions. For each medication category, overall prescribing frequency was compared across different strata and individual drug prescription was analyzed. RESULTS: Traditional NSAIDs, COX-2 inhibitors, and muscle relaxants, respectively, accounted for 16.3%, 10%, and 18.5% of total prescriptions for back pain in 2000. Among individual drugs, ibuprofen and naproxen accounted for most of the prescriptions for traditional NSAIDs (60%), whereas two thirds of the prescriptions for muscle relaxants / relaxant were attributable to Cyclobenzaprine, Flexeril, Carisoprodol ( Soma ), and methocarbamol. Prescription of COX-2 inhibitors or muscle relaxants / relaxant demonstrated wide variations across different regions. Several individual characteristics including age, race, and educational level were associated with the prescription of some of the medications. CONCLUSIONS: Neither traditional NSAIDs, nor COX-2 inhibitors, nor muscle relaxants / relaxant dominated prescriptions for back pain. However, a small number of individual drugs were attributable to most of the prescriptions for traditional NSAIDs or muscle relaxants. The prescription of some of the medications demonstrated wide variations across different regions or different racial and educational groups. More studies are needed to understand the source of the variations and what constitutes optimal prescribing.


Steroid-induced myopathy in patients intubated due to exacerbation of chronic obstructive pulmonary disease.
Amaya-Villar R, Garnacho-Montero J, Garcia-Garmendia JL, Madrazo-Osuna J, Garnacho-Montero MC, Luque R, Ortiz-Leyba C.
Intensive Care Unit, University Hospital Virgen del Rocio, Avenida Manuel Siurot s/n, 41013 Seville, Spain. ramaya@supercable.es
OBJECTIVE: To determine incidence, risk factors and impact on various outcome parameters of the development of acute quadriplegic myopathy in a selected population of critically ill patients. SETTING: A prospective cohort study carried out in the intensive care unit of a tertiary-level university hospital. PATIENTS: All patients admitted due to acute exacerbation of chronic obstructive pulmonary disease who required intubation and mechanical ventilation, and received high doses of intravenous corticosteroids. INTERVENTIONS: A neurophysiological study was performed in all cases at the onset of weaning. Muscular biopsy was taken when the neurophysiological study revealed a myopathic pattern. MEASUREMENTS AND RESULTS: Twenty-six patients were enrolled in the study. Nine patients (34.6%) developed myopathy. Only seven patients were treated with muscle relaxants. Histology confirmed the diagnosis in the three patients who underwent muscle biopsy. APACHE II score at admission, the rate of sepsis and the total doses of corticosteroids were significantly higher in patients with myopathy compared with those patients that did not develop it. Myopathy is associated with an increase in the duration of mechanical ventilation [15.4 (9.2) versus 5.7 (3.9) days; p<0.006], the length of ICU stay [23.6 (10.7) versus 11.4 (7.05) days; p<0.003] and hospital stay [33.3 (19.2) versus 21.2 (16.1) days; p<0.034)]. Myopathy was not associated with increased mortality. CONCLUSIONS: In the population under study, severity of illness at admission, the development of sepsis and the total dose of corticosteroids are factors associated with the occurrence of myopathy after the administration of corticosteroids. Myopathy was associated with prolonged mechanical ventilation and in-hospital stay.

Thoracic epidural catheter insertion using the caudal approach assisted with an electrical nerve stimulator in young children.

OBJECTIVES: We evaluated whether thoracic epidural catheter placement using the caudal approach and assisted with an electrical stimulator could be performed in young children. METHODS: Ten young children (1-4 years) who underwent abdominal surgeries were studied. Under general anesthesia without muscle relaxants, caudal catheter placement was performed using an 18-gauge Crawford-type needle and a 20-gauge radiopaque epidural catheter with a stainless-steel stylet. A metal adapter and a 3-way stopcock were attached to the catheter to connect to an electrical stimulator and to inject physiological saline. Electrical stimulation was performed intermittently while advancing the catheter until it reached the target length. The catheter position was confirmed on postoperative roentgenogram. RESULTS: The mean age of the subjects was 32.2 +/- 10.1 months (13-48 months), and the height was 85.3 +/- 6.1 cm (72-93 cm). In 9 of 10 patients, an epidural catheter could be placed at the first insertion. In 1 patient, the catheter could be placed successfully at the second insertion. The electrical current required for muscle contraction at the target length was 5.8 +/- 1.5 mA. CONCLUSION: Electrical stimulation reliably indicated the location of the catheter tip. This technique for thoracic epidural catheter insertion was easy to perform and could be used in young children.

Adjuvant analgesics in cancer pain management.

Adjuvant analgesics are defined as drugs with a primary indication other than pain that have analgesic properties in some painful conditions. The group includes numerous drugs in diverse classes. Although the widespread use of these drugs as first-line agents in chronic nonmalignant pain syndromes suggests that the term "adjuvant" is a misnomer, they usually are combined with a less-than-satisfactory opioid regimen when administered for cancer pain. Some adjuvant analgesics are useful in several painful conditions and are described as multipurpose adjuvant analgesics (antidepressants, corticosteroids, alpha(2)-adrenergic agonists, neuroleptics), whereas others are specific for neuropathic pain (anticonvulsants, local anesthetics, N-methyl-D-aspartate receptor antagonists), bone pain (calcitonin, bisphosphonates, radiopharmaceuticals), musculoskeletal pain (muscle relaxants), or pain from bowel obstruction (octreotide, anticholinergics). This article reviews the evidence supporting the use of each class of adjuvant analgesic for the treatment of pain in cancer patients and provides a comprehensive outline of dosing recommendations, side effects, and drug interactions.

Is there a link between malignant hyperthermia and exertional heat illness?.
Muldoon S, Deuster P, Brandom B, Bunger R.
Department of Anesthesiology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. smuldoon@usuhs.mil
Exertional heat illness (EHI) and malignant hyperthermia (MH) are two potentially lethal conditions. It has been suggested that a subset of MH susceptible persons may be predisposed to EHI. We examine the current understanding of these disorders and explore evidence of a relationship. Screening for the muscle type I ryanodine receptor gene should help clarify the relationship between MH and EHI.