Drug management of low back pain.
Matsudaira K, Kawaguchi H.
Department of Orthopedic Surgery, Faculty of Medicine, The University of Tokyo.
NSAIDs and muscle relaxants / relaxant effectively reduce acute nonspecific low back pain (LBP), different types of both drugs being equally effective. In general, there is no strong evidence for the effectiveness of medication for chronic nonspecific LBP. However, there is a possibility that administration of antidepressants is an intervention worthy of consideration in cases of LBP with no identifiable organic cause and resistant to other treatments.


Implementation of RCGP guidelines for acute low back pain: a cluster randomised controlled trial.

BACKGROUND: The Royal College of General Practitioners (RCGP) has produced guidelines for the management of acute low back pain in primary care. AIM: To investigate the impact on patient management of an educational strategy to promote these guidelines among general practitioners (GPs). DESIGN OF STUDY: Group randomised controlled trial, using the health centre as the unit of randomisation. SETTING: Primary care teams in north-west England. METHOD: Twenty-four health centres were randomly allocated to an intervention or control arm. Practices in the intervention arm were offered outreach visits to promote national guidelines on acute low back pain, as well as access to fast-track physiotherapy and to a triage service for patients with persistent symptoms. RESULTS: Twenty-four centres were randomised. Two thousand, one hundred and eighty-seven eligible patients presented with acute low back pain during the study period: 1049 in the intervention group and 1138 in the control group. There were no significant differences between study groups in the proportion of patients who were referred for X-ray, issued with a sickness certificate, prescribed opioids or muscle relaxants, or who were referred to secondary care, but significantly more patients in the intervention group were referred to physiotherapy or the back pain unit (difference in proportion = 12.2%, 95% confidence interval [CI] = 2.8% to 21.6%). CONCLUSION: The management of patients presenting with low back pain to primary care was mostly unchanged by an outreach educational strategy to promote greater adherence to RCGP guidelines among GPs. An increase in referral to physiotherapy or educational programmes followed the provision of a triage service.

Anesthesia in the breast feeding period. Excretion of anesthetic agents and adjuvants into breast milk and potential pharmacological side-effects on the suckling infant

Whenever an anesthetic is needed during the breast feeding period, potential pharmacological side-effects imposed on the infant by any kind of anesthetic agent used during both general and regional anesthesia are in contrast to the potential beneficial effects of breast feeding for the infant and the mother. Despite an increasing knowledge and understanding of the mechanisms of excretion of drugs and their metabolites through breast milk, information about most anesthetic drugs are still either inconclusive or contradictory. Often it is impossible to decide whether a certain substance that is potentially excreted through breast milk might be harmless or harmful for the breast-fed infant. In addition to that only few anesthetic agents and drugs used in conjunction with an anesthetic are officially approved for use during pregnancy and the period of breast feeding and for medico-legal reasons pharmaceutical companies generally advise against the use of any of those drugs during this period. However, based on the knowledge of pharmacological properties of commonly used anesthetic agents it is reasonable to assume that continuing breast feeding in the immediate postoperative period after a single anesthetic can be considered safe for the infant since no adverse effects caused by or secondary to the single use of those drugs can be expected. Provided there is a careful choice of anesthetic drugs, there is no need to consider that a single general or regional anesthetic is an indication to stop breast feeding. Even planned elective surgical procedures do not need to be postponed. No scientifically based interval between surgery under general or regional anesthesia and resumption of breast feeding can be recommended. Instead current opinion is that breast feeding can be resumed as soon as the mother feels physically and mentally capable to do so.

Intrathecal baclofen in severe spasticity due to multiple sclerosis

Intrathecal administration of baclofen via programmable pump is a highly effective treatment method in severe spasticity resistant to oral medications. The authors describe a case of severe spasticity with tetraplegia and painful (> 10 a day) muscle spasms in the upper and lower limbs and paraspinal muscles, in a patient with clinically definite diagnosis of multiple sclerosis (MS). The 34-year-old female patient with a 15-year history of MS, suffering from lower limb spasticity with pes equinovarus since 1995, was treated with very good results with botulinum toxin injections of calf muscles (14 sessions of Dysport 1500iu till 2002). In the early 2002 she developed tetraplegia with severe, generalized and intractable spasticity. After 4 months of ineffective polytherapy (with high doses of oral baclofen, Tizanidine ( Zanaflex ), gabapentine, clonidine, diazepam) and the patient's enormous sufferings (she could neither sit up nor voluntarily change her position in bed), a programmable baclofen pump (Medtronic) was implanted. As soon as a few days after the surgery she could stand, sit and move voluntarily, her painful spasms disappeared, and her bladder catheter was removed. At a 6-month follow-up the effect was stable--she was able to walk a long distance outdoors with the aid of a crutch. The daily dose of the drug is 500 micrograms. No side effects of complications were noted.

Quality of life of patients with telemetric pumps for intrathecal baclofen infusion: data and limitations of assessment scales.
Bramanti P, D'Aleo G, Rifici C, Alagna A, Cannata A, Sessa E, Di Bella P, Marra G.
Centro Studi Neurolesi, University of Messina, Italy.
Over the past three decades, telemetric pumps have been used for the infusion of intrathecal baclofen in patients with severe spasticity, but the correlation between pump implantation and quality of life (QoL) has rarely been studied. The aim of this study was therefore to quantify QoL in these patients. We assessed 15 candidates for intrathecal baclofen infusion pump implantation using three scales: Self-Evaluation of Life Function, Quality of Life Index, and Quality of Well-Being Scale. These scales were administered a week before pump implantation and 12 months after reaching the optimal dosage. The first scale revealed a significant increase in QoL, whereas on the other two the increase was not significant. These results encourage us to continue this study in a larger patient sample, considering different types of pathology and presence/absence of caregivers.

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.


Postoperative hyperthermia of unknown origin treated with dantrolene sodium.
Inada H, Jinno S, Kohase H, Fukayama H, Umino M.
Section of Anesthesiology and Clinical Physiology, Department of Oral Restitution, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan. inada.anph@tmd.ac.jp
An 11-year-old girl was scheduled for alveolar cleft bone grafting with an iliac bone under general anesthesia. Anesthesia was performed with 70% nitrous oxide, 30% oxygen, and propofol. On the first and second postoperative day, persistent hyperthermia was observed. Because the administration of diclofenac sodium had not been effective for the hyperthermia, dantrolene sodium was given. Her body temperature gradually dropped and returned to normal level on the fifth postoperative day. The hyperthermia in the present case might have been caused by a rapidly elevated muscle metabolism in response to pain and stress after the propofol anesthesia. The oral administration of dantrolene sodium successfully lowered the patient's high body temperature.


Analysis of the pharmacodynamic parameters in a model for neuromuscular block.
Nigrovic V, Anton A, Bengez R.
Department of Anesthesiology, Medical College of Ohio, Toledo, OH 43614-2598, USA. vnigrovic@mco.edu
BACKGROUND: The study examines the roles of the pharmacodynamic parameters and of the assumptions underlying the pharmacokinetic-pharmacodynamic model proposed by Sheiner and coworkers to interpret the time course of neuromuscular block (NMB) produced by nondepolarizing muscle relaxants. MATERIAL/METHODS: The model of Sheiner et al. was modified by considering (a) a multiexponential equation for the time course of the relaxant's concentrations in plasma, (b) the transport of a hypothetical muscle relaxant / relaxants from plasma to the site of action via diffusion, and (c) NMB as a function of the relaxant's concentration at the site of action, of gamma and IC50. The feasibility of obtaining reliable estimates of the PD parameters was evaluated for either a complete or an incomplete NMB. RESULTS: The results confirmed that reliable estimates of the PD parameters, i.e., of the transport rate constant, gamma, and IC50, may be obtained simultaneously if NMB is incomplete. Estimates of the same parameters obtained from a complete NMB are interdependent and, hence, unreliable. The assumptions in the original model of (i) a negligibly small amount of the relaxant in the effect compartment, (ii) steady state plasma concentration at half-maximal NMB, Cp(ss)(50), and (iii) transport of the muscle relaxant / relaxants from the effect compartment to "Outside", are neither needed nor are justified. CONCLUSIONS: The model proposed by Sheiner et al. interprets well the time course of an incomplete NMB even without the three assumptions. The simulations suggest methods to verify independently the estimates for the transport rate constant and gamma.

Benzodiazepines affect channel opening of GABA A receptors induced by either agonist binding site.
Baur R, Sigel E.
Department of Pharmacology, Friedbuehlstrasse 49, CH-3010 Bern, Switzerland.
Benzodiazepines are widely used as anxiolytics, sedatives, muscle relaxants, and anticonvulsants. They allosterically modulate GABA type A (GABA(A)) receptors by increasing the apparent affinity of the agonist GABA to elicit chloride currents. Such an increase in apparent affinity of channel gating could either be caused by an increase in affinity for GABA or by a facilitation of channel opening. In the first case, conformation of the affected sites would have to be altered. In the second case, the affected sites are not necessarily altered, because diazepam could facilitate conformational changes leading to the open channel. It is controversial as to whether benzodiazepines affect only channel opening induced by the occupation of one of the two agonist binding sites or by both. We used receptors formed by concatenated subunits to selectively destroy one of the two agonist sites by point mutation. Both of the receptors harboring only one active agonist site could be stimulated by diazepam. We therefore present evidence that binding of diazepam can affect channel opening induced by either agonist binding site.

Twenty years of pharmacology.
Glenn MB, Wroblewski B.
Outpatient and Community Brain Injury Rehabilitation Programs, Harvard Medical School, Boston, MA 02114, USA. mglenn@partners.com
During the past 20 years in pharmacology, a number of innovations have appeared that have resulted in significant changes in the drugs available for people with traumatic brain injury. Among the anticonvulsants, antidepressants, and antipsychotics, new drugs have appeared with fewer cognitive side effects. In these classes of drugs, as well as among central nervous system stimulants, once-daily or other sustained-release preparations have been introduced that make it considerably more likely that the patient will take his or her medication, with smaller fluctuations in drug levels as well. New drugs have also resulted in a greater number of medications for the clinician to choose from. The overall effect has been a dramatic change in pharmacology that has benefited people with traumatic brain injury.