A Novel Approach to Avoid Baclofen Withdrawal When Faced With Infected Baclofen Pumps.

BACKGROUND: Intrathecal (IT) Baclofen is beneficial for spasticity, but if pumps become infected necessitating removal, baclofen withdrawal is difficult to manage and life-threatening. Furthermore there is no consistency between dosing and severity of withdrawal. Case reports detail full baclofen withdrawal at dosages of 260 µg/day. OBJECTIVE: To demonstrate that in patients on stable IT baclofen for prolonged periods, externalizing a patient's original IT pump is a safe, effective way to wean IT doses. METHODS: Here, we describe a technique of continuing IT baclofen when urgent pump removal is needed. Specifically, we remove the infected pump. Then using a new or existing lumbar drain based on extent of infection, we reconnect the pump after cleaning with betadine and administer therapy externally during IT weaning. RESULTS: Hundred forty seven baclofen pumps were implanted or replaced within four years. Infections occurred in seven patients. We utilized this technique in five of seven patients. Mean IT dose at time of explant was 400.5 ± 285.3 µg/day. We titrated the dose by 20-50% per day based on clinical response over a mean of 6.2 ± 1.3 days. The catheter was removed at bedside once weaning was complete. No patients had any signs of withdrawal, excluding minimal spasticity increases while optimizing oral treatment. CONCLUSION: Here, we show preliminary evidence that an externalized IT pump is an effective means of weaning IT baclofen when infection of the pump occurs. This treatment strategy warrants further investigation, but appears to be a safe and effective. CONFLICT OF INTEREST: Dr. Pilitsis is a consultant for Medtronic, Boston Scientific, Nevro, Jazz Pharmaceuticals, Neurobridge Therapeutics, and Abbott and receives grant support from Medtronic, Boston Scientific, Abbott, Nevro, Jazz Pharmaceuticals, GE Global Research and NIH 1R01CA166379. She is medical advisor for Centauri and Karuna and has stock equity. Dr. Sukul receives consultant fees from Medtronic. Julia Prusik receives grant support from Jazz Pharmaceuticals.

Spontaneous Gingival Bleeding A Surprising and Sinister Etiology: A Case Report.

It is rare for a dentist to be confronted with a situation where the immediate well-being of a patient is dependent upon his or her diagnosis. Spontaneous gingival bleeding, as in this case report, may present such a situation. The patient had no remarkable medical history, was not taking medication and had a recent (two weeks) normal CBC. Only by noticing petechiae on the patient's palate and buccal mucosa was the dentist convinced of an underlying clotting problem. A patient visit to his physician confirmed thrombocytopenia due to quinine in the tonic water he was taking.

Randomized-controlled trial of methocarbamol as a novel treatment for muscle cramps in cirrhotic patients.

BACKGROUND: Muscle cramps occur in 29-88% of patients with liver cirrhosis. They adversely affect quality of life. This study aimed to evaluate the efficacy and safety of methocarbamol as a novel therapy in controlling muscle cramps in cirrhotic patients. PATIENTS AND METHODS: This study was carried on 100 patients with liver cirrhosis in addition to chronic hepatitis C who presented with frequent muscle cramps (≥three cramps per week). Half of these patients received methocarbamol and the other half received placebo. This was done through equal randomization. Questionnaires on muscle cramp were answered. Patients were evaluated before, after 1 month of treatment, and 2 weeks after washout of treatment in terms of severity, duration, and frequency of cramps. Liver, renal functions, and electrolytes were analyzed. Also, any side effect was detected. RESULTS: Patients who were treated with methocarbamol showed a significant decrease in the frequency and duration of cramps. Also, the pain score improved significantly. However, no significant changes were observed in the placebo group. Few side effects of methocarbamol were recorded, including dry mouth and drowsiness. CONCLUSION: Methocarbamol seems to be a promising safe and well-tolerated medication, and plays a role in the treatment of muscle cramps in patients with liver cirrhosis.

Efficacy and safety of combined piroxicam, dexamethasone, orphenadrine, and cyanocobalamin treatment in mandibular molar surgery.

Third molar extraction is a common procedure frequently accompanied by moderate or severe pain, and involves sufficient numbers of patients to make studies relatively easy to perform. The aim of the present study was to determine the efficacy and safety of the therapeutic combination of 10 mg piroxicam, 1 mg dexamethasone, 35 mg orphenadrine citrate, and 2.5 mg cyanocobalamin (Rheumazin) when compared with 20 mg piroxicam alone (Feldene) in mandibular third molar surgery. Eighty patients scheduled for removal of the third molar were included in this randomized and double-blind study. They received (vo) Rheumazin or Feldene 30 min after tooth extraction and once daily for 4 consecutive days. Pain was determined by a visual analogue scale and by the need for escape analgesia (paracetamol). Facial swelling was evaluated with a measuring tape and adverse effects and patient satisfaction were recorded. There was no statistically significant difference in facial swelling between Rheumazin and Feldene (control group). Both drugs were equally effective in the control of pain, with Rheumazin displaying less adverse effects than Feldene. Therefore, Rheumazin appears to provide a better risk/benefit ratio in the mandibular molar surgery. Since the side effects resulting from nonsteroidal anti-inflammatory drug administration are a severe limitation to the routine use of these drugs in clinical practice, our results suggest that Rheumazin can be a good choice for third molar removal treatment.

Relationship of the antispasticity effect of tizanidine to plasma concentration in patients with multiple sclerosis.

BACKGROUND: Spasticity is a serious problem in multiple sclerosis (MS) and many patients do not achieve a satisfactory response to currently available oral antispasticity drugs. Tizanidine hydrochloride, an alpha 2-noradrenergic agonist, has been shown to have an antispasticity effect in single center trials of patients with MS. OBJECTIVE: To compare plasma concentrations of tizanidine with objective measures of muscle tone in patients with MS with moderate to severe spasticity. SETTING: Ten centers, all tertiary referral centers for the specialized treatment of patients with MS, in the United States and Canada. DESIGN: A randomized, double-blind, placebo-controlled, dose-response study of tizanidine hydrochloride (8 or 16 mg). PATIENTS: One hundred forty-two patients with spastic MS who were not taking any interfering medication, such as an antispasticity drug or other alpha-noradrenergic agonist, entered the trial. RESULTS: Tizanidine treatment reduced muscle tone significantly, as shown by improved Ashworth scores and increased knee swing amplitude recorded by the pendulum test, both of which correlated significantly with plasma concentration. Placebo had no significant effect on muscle tone. Dizziness, drowsiness, dry mouth, and fatigue were reported most often in the group treated with tizanidine at peak plasma concentration. CONCLUSIONS: Tizanidine reduces spasticity in MS, and both therapeutic effects and side effects are related to the plasma drug levels.

Summary of combined clinical analysis of controlled clinical trials with tizanidine.

Data from three placebo-controlled and 11 active-controlled studies of tizanidine were combined to permit analysis of the subsets, which were too small to evaluate within the individual studies. Overall analysis of placebo-controlled data confirms the effectiveness of tizanidine in reducing muscle tone in patients with spasticity of spinal cord origin. Subset analyses suggest that patients with more severe spasticity are more likely to respond, but age, sex, and race were not predictive of response. Comparisons of tizanidine with active controls showed no differences in efficacy compared with baclofen or diazepam. However, when compared with controls, patients treated with tizanidine did not experience increased weakness. Furthermore, patients tolerated tizanidine better than the control medications. More patients experienced adverse events during tizanidine treatment than did patients receiving placebo. The most common adverse events reported were dry mouth, somnolence, asthenia, and dizziness. Mild elevations in liver function tests were noted occasionally, but improved in all patients with dose reduction or withdrawal. Three patients from the double-blind database reported formed visual hallucinations. All three cleared; two continued tizanidine, and one discontinued.

Quinine induced coagulopathy--a near fatal experience.

A 67 year old man presented to his local dentist for restorative treatment. He stated he was fit and well and denied taking any medications. When he was given an inferior alveolar nerve block, excessive bleeding was noted at the injection site and the dentist advised the patient see an oral and maxillofacial surgeon. An appointment was made for the patient but he did not attend. Three days later, he presented with evidence of massive deep haemorrhage to the point of airway compromise. He underwent hospital admission, early intubation, intensive care for nine days and hospitalization for six weeks. The cause of his bleeding was a severe thrombocytopoaenia, induced by chronic ingestion of quinine. He was self-medicating with this to relieve muscular cramps. Despite this experience, the patient continued to deny that quinine was the cause of his problem and that he had failed in his obligations to advise the dentist of his drug history. Dentists need to be alert to the risk that patients may not reveal their true medical history. There are, however, obligations on the dentist to ensure the accuracy of information the patient gives and to ensure that patients whom they believe are at risk follow their advice. Teamwork and skillful airway management prevented this patient's demise.

Should people with nocturnal leg cramps drink tonic water and bitter lemon?

A literature search from 1993 to 1997 using MEDLINE and key-words beverages, muscle cramp, and quinine was performed. Three beverages containing quinine were examined in grocery stores. Analysis indicate that leg cramps are a common phenomenon associated with many comorbid disorders especially peripheral vascular and neurologic disorders. Thus, evaluation of a patient's complaining of leg cramps appropriately includes vascular, neurologic, and musculoskeletal examinations. Laboratory investigation of the symptom of leg cramps warrants as a minimum, assessment of thyroid function and determination of platelet counts and serum levels of electrolytes, calcium, and magnesium. A few small studies suggest that quinine is effective in decreasing the frequency of nocturnal leg cramps but not their severity or duration. Quinine consumed in commercial beverages has been reported to cause potentially fatal immunologically mediated hypersensitivity reactions. The concentration of quinine in commercial beverages varies greatly. Although commercial beverages containing quinine generally are labeled "Contains quinine," they typically lack both nutritional information about the amount of quinine and warnings of the health risks. It appears that 325 milligrams of quinine taken by mouth at bedtime typically relieves nocturnal leg cramps, but lower starting doses are appropriate for senior citizens and individuals with impaired renal function. In general, quinine in any form should be avoided by pregnant women and people with hepatic failure. Quinine consumed for the treatment of leg cramps should be prescribed and monitored by physicians, and people who consume quinine in commercial beverages must be warned of the health risks.

Time to recovery in patients with acute painful musculoskeletal conditions treated with extended-release or immediate-release cyclobenzaprine.

INTRODUCTION: This post-hoc analysis examined time to recovery in patients with acute, painful musculoskeletal conditions following cyclobenzaprine extended release (CER; AMRIX(®), Cephalon, Inc., Frazer, PA, USA), cyclobenzaprine immediate release (CIR; Flexeril(®), Pliva, Pomona, NY, USA), or placebo administration. METHODS: Data were pooled from two identically designed, double-blind, placebo-controlled, parallel-group studies. Adults with acute, painful local muscle spasm were randomized to once-daily CER 15 mg, once-daily CER 30 mg, three-times-daily CIR 10 mg, or placebo for 14 days. Efficacy assessments were time to first rating of "a lot" or "complete" relief from local pain or restriction of movement and patient-rated medication helpfulness. RESULTS: A total of 504 patients were randomized, and 330 (65.5%) completed the studies. Median times to "a lot" or "complete" relief from local pain were faster with CER 15 mg (6 days, P=0.016), CER 30 mg (5 days, P=0.002), and CIR (5 days, P=0.002) versus placebo (8 days). Time to "a lot" or "complete" relief from restriction of movement was faster with CER 30 mg (5 days, P=0.004) and CIR (5 days, P=0.009) versus placebo (7 days). Median times to "very good" or "excellent" medication helpfulness were 10 days (CER 15 mg, P=0.020), 8 days (CER 30 mg, P=0.004), and 7 days (CIR, P<0.001) versus >14 days (placebo). Dry mouth, constipation, dizziness, headache, and somnolence were the most commonly reported adverse events. Somnolence rates were lower with CER 15 mg (0.8%, P=0.008) and CER 30 mg (1.6%, P=0.028) versus CIR (7.3%). CONCLUSION: Relief from local pain and restriction of movement occurred sooner with CER and CIR than placebo. CER was associated with less somnolence than CIR.

Efficacy and tolerability of cyclobenzaprine extended release for acute muscle spasm: a pooled analysis.

OBJECTIVE: To assess the efficacy and tolerability of once-daily cyclobenzaprine extended release (CER) 15 and 30 mg in relieving acute muscle spasm. METHODS: This is a pooled analysis of 2 randomized, double-blind, placebo-controlled, parallel-group studies of identical design. Adults with local muscle spasm associated with neck/low back pain were randomized to treatment with once-daily CER 15 (n = 127) or 30 mg (n = 126), cyclobenzaprine immediate release (CIR) 10 mg 3 times daily (n = 123), or placebo (n = 128) for 14 days. Primary outcome measures were the patient's rating of medication helpfulness and physician's clinical global assessment of response to therapy at day 4. RESULTS: Of 504 patients, 330 (65.5%) completed the studies. Significantly greater improvements in patient's rating of medication helpfulness were reported with CER 15 and 30 mg versus placebo at day 4 (P < 0.025). No differences were reported between groups in physician's clinical global assessment. Significantly greater improvements (P < 0.025) were noted in patient-rated secondary measures versus placebo: relief from local pain at days 4 (CER 30 mg) and 8 (CER 15 and 30 mg), global impression of change at days 4 and 8 (CER 30 mg), and restriction of movement at day 4 (CER 30 mg). Improvements with CER 15 and 30 mg on most efficacy measures were similar to CIR. There was less reported daytime drowsiness with CER 15 and 30 mg than with CIR (P < 0.05). Most adverse events (AEs) were mild in intensity. The most common AEs for all groups were dry mouth, constipation, dizziness, headache, and somnolence. The rate of somnolence reported as an AE was lower (P < 0.05) with CER 15 (0.8%) and 30 mg (1.6%) than with CIR (7.3%). CONCLUSION: Once-daily CER was effective in relieving acute muscle spasm based on patient's rating of medication helpfulness at day 4 and was generally well tolerated with a low rate of reported somnolence.

An indication for spontaneous respiration.

A case is reported of a patient with a facial defect and fixation of the jaw which caused ventilation and intubation problems.

Is systematic preoperative screening for muscle relaxant and latex allergy advisable?

We investigated a female population prior to general anaesthesia, using skin prick tests with latex and muscle relaxants to appraise the validity and feasibility of a systematic preoperative screening for these substances. Anaesthetists performed skin tests, and positive and doubtful tests were checked in our allergy department. Of 114 patients, 42 had uninterpretable tests because of dermographism (28 patients) or suppression of skin reactivity (14 patients). Among the other 72, nine had a positive or doubtful test to latex, and seven a positive or doubtful test to one or more muscle relaxants. After checking, only four sensitizations to latex and one to muscle relaxant were confirmed. In conclusion, a systematic screening for latex and muscle relaxant allergy is not advisable. In contrast, screening for latex allergy in selected high-risk groups (spina bifida, health-care workers) is necessary.

[Diagnosis and treatment of the patient with trigeminal neuralgia]. / Diagnóstico y tratamiento del paciente con neuralgia del trigémino.

Neuralgia of the trigeminus (NT) is the most common of cranial nerve neuralgias. Its diagnosis is entirely clinical and its most common form of presentation is well understood. Questions of differential diagnosis can emerge with certain entities such as atypical trigeminal neuralgia, short-duration unilateral neuralgiform cephalea of the trigeminus (SUNCT) arising from injection to the conjunctival, lacrimal or other glands, cluster headache, chronic paroxymal hemicrania, pain arising in the teeth and myofacial pain syndrome. The three main causative factors of NT are compression of the nerve root by an artery in the prepontine space, thereby creating an area of demyelinization, compression of the nerve by a tumor, and multiple sclerosis. The first is the most common of the three. NT can be classified as essential in 10 to 30% of patients. Recent advances in magnetic resonance (MR), and its advantages over other imaging systems, have made MR the diagnostic method of choice. The first treatment is medical and the basic drugs involved can be considered classic. Other therapies have been suggested in recent years, however, and should probably be studied further. Two substances stand out among those proposed: tocainide, an antiarrhythmic drug, and pimozide, an antipsychotic. Surgical treatment of NT can address either the cause (tumor or vascular compression) or symptoms, the latter being indicated when medical treatment fails. Surgery can be performed on peripheral nerves, on the gasserian ganglion and on the posterior fossa. The indications, outcomes and possible complications are quite different for each approach, making choice controversial.

[Diclofenac/orphenadrine infusion therapy in patients with active arthrosis]. / Diclofenac/Orphenadrin-Infusionstherapie bei Patienten mit aktivierten Arthrosen.

This study investigated the efficacy and safety of a diclofenac/orphenadrin infusion in 21 female and 1 male patients with clinically and radiologically diagnosed inflammatory osteoarthritis of the big joints, especially the knee and hip joints. The patients received 1 infusion per day over 2 h for 10 days. Efficacy and safety were assessed by measuring the subjective pain intensity at rest and during exercise on a visual analogue scale and on an ordinal rating scale before and after every infusion. The patients were interviewed daily for possible side effects. After the 10-days treatment course a 5% reduction of pain at rest and a 37.5% reduction of pain during exercise was observed. Subjective pain intensity was reduced by an average of 32.5%. In most cases relief was noticeable after the 4th infusion. 9 patients rated the medication safety as "very good", 11 patients as "good". A total of 12 patients reported mainly mild side effects such as vertigo, dry mouth, and temporarily reduced visual acuity. Based on its rapid onset of action and its efficacy, it can be stated that the investigated diclofenac/orphenadrin infusion is a valuable extension of the therapeutic methods in patients with inflammatory osteoarthritis.

Cyproheptadine for intrathecal baclofen withdrawal.

OBJECTIVE: To evaluate the efficacy of cyproheptadine in the management of acute intrathecal baclofen (ITB) withdrawal. DESIGN: Descriptive case series. SETTING: University hospital with a comprehensive in- and outpatient rehabilitation center. PARTICIPANTS: Four patients (3 with spinal cord injury, 1 with cerebral palsy) with implanted ITB infusion pumps for treatment of severe spasticity, who had ITB withdrawal syndrome because of interruption of ITB infusion. INTERVENTIONS: Patients were treated with 4 to 8mg of cyproheptadine by mouth every 6 to 8 hours, 5 to 10mg of diazepam by mouth every 6 to 12 hours, 10 to 20mg of baclofen by mouth every 6 hours, and ITB boluses in some cases. MAIN OUTCOME MEASURES: Clinical signs and symptoms of ITB withdrawal of varying severity were assessed by vital signs (temperature, heart rate), physical examination (reflexes, tone, clonus), and patient report of symptoms (itching, nausea, headache, malaise). RESULTS: The patients in our series improved significantly when the serotonin antagonist cyproheptadine was added to their regimens. Fever dropped at least 1.5 degrees C, and heart rate dropped from rates of 120 to 140 to less than 100bpm. Reflexes, tone, and myoclonus also decreased. Patients reported dramatic reduction in itching after cyproheptadine. These changes were associated temporally with cyproheptadine dosing. DISCUSSION: Acute ITB withdrawal syndrome occurs frequently in cases of malfunctioning intrathecal infusion pumps or catheters. The syndrome commonly presents with pruritus and increased muscle tone. It can progress rapidly to high fever, altered mental status, seizures, profound muscle rigidity, rhabdomyolysis, brain injury, and death. Current therapy with oral baclofen and benzodiazepines is useful but has variable success, particularly in severe cases. We note that ITB withdrawal is similar to serotonergic syndromes, such as in overdoses of selective serotonin reuptake inhibitors or the popular drug of abuse 3,4-methylenedioxymethamphetamine (Ecstasy). We postulate that ITB withdrawal may be a form of serotonergic syndrome that occurs from loss of gamma-aminobutyric acid B receptor-mediated presynaptic inhibition of serotonin. CONCLUSION: Cyproheptadine may be a useful adjunct to baclofen and benzodiazepines in the management of acute ITB withdrawal syndrome.

Efficacy and safety of combined piroxicam, dexamethasone, orphenadrine, and cyanocobalamin treatment in mandibular molar surgery

Third molar extraction is a common procedure frequently accompanied by moderate or severe pain, and involves sufficient numbers of patients to make studies relatively easy to perform. The aim of the present study was to determine the efficacy and safety of the therapeutic combination of 10 mg piroxicam, 1 mg dexamethasone, 35 mg orphenadrine citrate, and 2.5 mg cyanocobalamin (Rheumazin®) when compared with 20 mg piroxicam alone (Feldene®) in mandibular third molar surgery. Eighty patients scheduled for removal of the third molar were included in this randomized and double-blind study. They received (vo) Rheumazin or Feldene 30 min after tooth extraction and once daily for 4 consecutive days. Pain was determined by a visual analogue scale and by the need for escape analgesia (paracetamol). Facial swelling was evaluated with a measuring tape and adverse effects and patient satisfaction were recorded. There was no statistically significant difference in facial swelling between Rheumazin and Feldene (control group). Both drugs were equally effective in the control of pain, with Rheumazin displaying less adverse effects than Feldene. Therefore, Rheumazin appears to provide a better risk/benefit ratio in the mandibular molar surgery. Since the side effects resulting from nonsteroidal anti-inflammatory drug administration are a severe limitation to the routine use of these drugs in clinical practice, our results suggest that Rheumazin can be a good choice for third molar removal treatment.