Prescription analgesic and antidepressant utilization and cost among elderly Medicaid beneficiaries before and after nursing home admission.

OBJECTIVES: The objectives of this study were to describe changes in prescription analgesic and antidepressant medications and to track the costs associated with these medication changes when elderly Medicaid beneficiaries move from the community to a nursing home setting. DESIGN: Retrospective analysis of Medicaid long-term care and drugs claims data for fiscal year 2000 from three different states. SETTING: Long-term care facilities in three different states. PARTICIPANTS: We studied 1321 elderly Medicaid beneficiaries newly admitted to a nursing home during the study period. MEASUREMENTS: Pain medications were grouped into four different categories and all antidepressants were grouped into one category. For each medication category, we obtained the number of unique patients for whom it was prescribed, the number of days it was prescribed, and the amount paid by Medicaid. We then calculated the percentage of subjects prescribed and the amount paid per day for each medication class before and after nursing home admission. RESULTS: Except for skeletal muscle relaxants, 21% to 39% of beneficiaries already had claims linked to each medication class while still living in the community. After nursing home admission, the percentage of beneficiaries exposed to each medication class increased by 2% to 33%. Cost per day of therapy increased by 10% to 83%. There was significant variation among the states in utilization and cost per day of therapy. CONCLUSIONS: We draw three major conclusions: (1) community-dwelling elderly Medicaid beneficiaries in this study use more prescription analgesics and antidepressants than community-dwelling elders in prior studies; (2) there is a significant increase in medication utilization and cost on nursing home admission; and (3) significant variability in medication use and cost exists among the three states examined. Further investigation to elucidate the reasons for these differences could assist legislators in formulating sound public policy to contain Medicaid expenditures without sacrificing patient care.

Dantrolene--a review of its pharmacology, therapeutic use and new developments.

Human malignant hyperthermia is a life-threatening genetic sensitivity of skeletal muscles to volatile anaesthetics and depolarizing neuromuscular blocking drugs occurring during or after anaesthesia. The skeletal muscle relaxant / relaxants dantrolene is the only currently available drug for specific and effective therapy of this syndrome in man. After its introduction, the mortality of malignant hyperthermia decreased from 80% in the 1960s to < 10% today. It was soon discovered that dantrolene depresses the intrinsic mechanisms of excitation-contraction coupling in skeletal muscle. However, its precise mechanism of action and its molecular targets are still incompletely known. Recent studies have identified the ryanodine receptor as a dantrolene-binding site. A direct or indirect inhibition of the ryanodine receptor, the major calcium release channel of the skeletal muscle sarcoplasmic reticulum, is thought to be fundamental in the molecular action of dantrolene in decreasing intracellular calcium concentration. Dantrolene is not only used for the treatment of malignant hyperthermia, but also in the management of neuroleptic malignant syndrome, spasticity and Ecstasy intoxication. The main disadvantage of dantrolene is its poor water solubility, and hence difficulties are experienced in rapidly preparing intravenous solutions in emergency situations. Due to economic considerations, no other similar drugs have been introduced into routine clinical practice.

Effect of oral administration of dantrolene sodium on serum creatine kinase activity after exercise in horses with recurrent exertional rhabdomyolysis.

OBJECTIVE: To determine the effect of oral administration of dantrolene sodium on serum creatine kinase (CK) activity after exercise in horses with recurrent exertional rhabdomyolysis (RER). ANIMALS: 2 healthy horses and 5 Thoroughbreds with RER. PROCEDURE: 3 horses received 2 doses of dantrolene (4, 6, or 8 mg/kg, p.o., with and without withdrawal of food) 2 days apart; 90 minutes after dosing, plasma dantrolene concentration was measured spectrofluorometrically. On the basis of these results, 5 Thoroughbreds with RER from which food was withheld received dantrolene (4 mg/kg) or an inert treatment (water [20 mL]) orally 90 minutes before treadmill exercise (30 minutes, 5 d/wk) during two 3-week periods. Serum CK activity was determined 4 hours after exercise. Plasma dantrolene concentration was measured before and 90 minutes after dosing on the first and last days of dantrolene treatment and before dosing on the first day of the inert treatment period, RESULTS: 90 minutes after dosing, mean +/- SEM plasma dantrolene concentration was 0.62 +/- 0.13 and 0 microg/mL in the dantrolene and inert treatment groups, respectively. Serum CK activity was lower in dantrolene-treated horses (264 +/- 13 U/L), compared with activity in water-treated horses (1,088 +/- 264 U/L). Two horses displayed marked muscle stiffness on the inert treatment. CONCLUSIONS AND CLINICAL RELEVANCE: In 5 horses with RER from which food had been withheld, 4 mg of dantrolene/kg administered orally provided measurable, though variable, plasma concentrations and significantly decreased serum CK activity after exercise in 4 of those horses.

Predictors of outcome in prolonged posttraumatic disorders of consciousness and assessment of medication effects: A multicenter study.
Whyte J, Katz D, Long D, DiPasquale MC, Polansky M, Kalmar K, Giacino J, Childs N, Mercer W, Novak P, Maurer P, Eifert B.
Moss Rehabilitation Research Institute/Albert Einstein Healthcare Network, Philadelphia, PA, USA. jwhyte@einstein.edu
OBJECTIVES: To develop predictive models of recovery from the vegetative state (VS) and minimally conscious state (MCS) after traumatic brain injury (TBI) and to gather preliminary evidence on the impact of various psychotropic medications on the recovery process to support future randomized controlled trials. Design Longitudinal observational cohort design, in which demographic information, injury and acute care history, neuroimaging data, and an initial Disability Rating Scale (DRS) score were collected at the time of study enrollment. Weekly follow-up data, consisting of DRS score, current psychoactive medications, and medical complications, were gathered until discharge from inpatient rehabilitation. SETTING: Seven acute inpatient rehabilitation facilities in the United States and Europe with specialized programs for treating patients in the VS and MCS. PARTICIPANTS: People with TBI (N=124) who were in the VS or MCS 4 to 16 weeks after injury. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: DRS score at 16 weeks after injury and time until commands were first followed (among those participants demonstrating no command following at study enrollment). Results DRS score at enrollment, time between injury and enrollment, and rate of DRS change during the first 2 weeks of poststudy observation were all highly predictive of both outcomes. No variables related to injury characteristics or lesions on neuroimaging were significant predictors. Of the psychoactive medications, amantadine hydrochloride was associated with greater recovery and dantrolene sodium was associated with less recovery, in terms of the DRS score at 16 weeks but not the time until commands were followed. More detailed analysis of the timing of functional improvement, with respect to the initiation of amantadine provided suggestive, but not definitive, evidence of the drug's causal role. CONCLUSIONS: These findings show the feasibility of improving outcome prediction from the VS and MCS using readily available clinical variables and provide suggestive evidence for the effects of amantadine and dantrolene, but these results require confirmation through randomized controlled trials.


Serotonin syndrome and the anaesthetist.
Jones D, Story DA.
Department of Anaesthesia, Austin Hospital, Heidelberg, Victoria.
Serotonin syndrome results from excessive activation of serotonin (5-hydroxytryptamine; 5-HT) receptors in the nervous system, on the surface of platelets, and on the vascular endothelium. The clinical manifestations are a triad of altered conscious state, autonomic dysfunction, and neuromuscular excitability. Clinical diagnostic criteria remain poorly defined and unvalidated, and there are no available investigations to confirm the diagnosis. The syndrome is caused by the administration of one or more drugs possessing serotonergic activity. Severe forms of the syndrome usually result from overdose, but can be induced by monotherapy. The exact incidence of serotonin syndrome remains unknown, but is likely to be increasing due to increased prescription of selective serotonin reuptake inhibitor antidepressants and tramadol, as well as recreational use of amphetamine-like substances. Serotonin syndrome may complicate the administration of drugs frequently used in anaesthetic practice, including pethidine and tramadol. Although the majority of cases improve with symptomatic and supportive care, severe cases need intensive care and frequently require mechanical ventilation. Neuromuscular excitability is likely to be the cause of rhabdomyolysis seen in severe cases and should be treated with benzodiazepines and muscle relaxants. Supportive therapies are required to treat hyperthermia and autonomic dysfunction. Cyproheptadine is the most commonly administered serotonergic antagonist, but is unavailable in parenteral form.


Quinine associated blindness.

BACKGROUND: Quinine is commonly prescribed to the elderly for the treatment of benign nocturnal cramps, yet its use is not without complications. OBJECTIVE: This article presents a case of quinine toxicity producing bilateral blindness, followed by a review of the adverse reactions associated with quinine use and its efficacy in treating benign nocturnal muscular cramps. DISCUSSION: Visual loss has been associated with quinine serum concentrations above 10 microg/mL (therapeutic range 2-5 microg/mL). Other adverse reactions include neurological symptoms, haemolysis, acute renal failure and arrhythmia. There is conflicting evidence for the efficacy of quinine for leg cramps in randomised controlled studies, however, meta-analysis of these studies suggests some benefit. Although severe side effects are rare at therapeutic doses, the possibility of overdose needs to be considered when prescribing and an individual risk benefit analysis needs to be made. Benefits and adverse reactions should be closely monitored and medication ceased if appropriate.

Cardiomyopathy developed in the postoperative period in a patient with amyotrophic lateral sclerosis

Department of Intensive and Critical Care Medicine, Dokkyo University School of Medicine, Tochigi 321-0207. A 75-year-old woman with amyotrophic lateral sclerosis (ALS) underwent surgical gastrostomy and repair of incisional hernia. Anesthesia was induced with propofol and high concentrations of sevoflurane. Tracheal intubation was performed without muscle relaxants. Anesthesia was maintained with sevoflurane and thoracic epidural anesthesia (bupivacaine and fentanyl). Surgery, emergence and extubation were completed uneventfully. She was transferred to ICU for postoperative observation. On the 2 nd POD, however, she was re-intubated due to sudden dyspnea and desaturation caused by failed sputum exhaustion. Simultaneously, her ECG showed ischemic change in leads I, III, aVF, and V3-6. Left ventriculogram showed an "Ampulla" or so called "Takotsubo" shape with intact coronary angiogram. After medication with nitroglycerin and diltiazem, her ECG returned to normal. She showed no deterioration of neurological symptoms. No respiratory and cardiac events were reported until her discharge from hospital. We conclude that an extreme care is required in patient with ALS to avoid perioperative complications.

Subthalamic deep brain stimulation masking possible malignant syndrome in Parkinson disease.

Centro de Neurologia y Neurocirugia funcional, Clinica Quiron, San Sebastian, Spain.

Cross-reactivity among drugs: clinical problems.
Romano A, Gueant-Rodriguez RM, Viola M, Gaeta F, Caruso C, Gueant JL.
Department of Internal Medicine and Geriatrics, UCSC-Allergy Unit, Unita di Allergologia, Complesso Integrato Columbus, Via G. Moscati 31, 00168 Rome, Italy. columbus.romano@linet.it
Cross-reactivity among drugs is either mediated by immunologic mechanisms or not. The former kind is usually explained by the presence of common antigenic determinants in the cross-reacting drugs. In the case of compounds provoking non-allergic hypersensitivity reactions, cross-reactivity is explained by a common pharmacological characteristic, such as the inhibitory effect of non-steroidal anti-inflammatory drugs on cyclooxygenase-1 and the capability of muscle relaxants / relaxant or contrast media to release histamine through a non-immunologic mechanism. The main clinical problem deriving from cross-reactivity among drugs is the compelling need to choose a potentially cross-reactive compound and, therefore, to assess cross-reactivity by diagnostic tests. In choosing alternative compounds, skin testing has been used in evaluating IgE-mediated cross-reactivity between penicillins and cephalosporins, as well as among muscle relaxants. In assessing T cell-mediated cross-reactivity among contrast media, corticosteroids, anticonvulsants and heparins, delayed-reading intradermal tests and patch tests, together with lymphocyte transformation tests, can be performed. Because of the limited sensitivity of in vivo and in vitro testing, the most prudent way of establishing the tolerability of a compound of the same group in patients who especially require one is a graded challenge when other allergologic tests are negative.


Can first responders achieve and maintain normocapnia when sequentially ventilating with a bag-valve device and two oxygen-driven resuscitators? A controlled clinical trial in 104 patients.

BACKGROUND AND OBJECTIVE: To evaluate the capability of first responders to achieve and maintain normal ventilation of the lungs of victims employing a bag-valve device and two oxygen-driven resuscitators. METHODS: Prospective, controlled, blinded, single-centre clinical trial using a bag-valve device and one of two FR-300 devices, with 20 cmH2O working pressure, and flows of either 24 or 30 L min(-1). One hundred and four patients were analysed. Induction of anaesthesia followed by ventilation of the lungs with a bag-valve device and an Oxylator in manual and automatic modes performed by a fireman first responder. Each series was repeated for three conditions (anaesthesia; anaesthesia plus muscle relaxation, both with facemask; anaesthesia plus relaxation using an endotracheal tube). RESULTS: Patients age 49 +/- 17 yr; 47% males, 48-132 kg. Normocapnia was achieved and maintained in 66% (bag-valve device), 82% (Oxylator). CONCLUSIONS: The use of an oxygen-driven device improves the ability of first responders to achieve and maintain normocapnia even when distracted. Use of the Oxylators improves performance (P < 0.001) vs. the bag-valve device significantly.