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.

Short use of muscle relaxants / relaxant following single stage laryngotracheoplasty in children.
Roeleveld PP, Hoeve LJ, Joosten KF, de Hoog M.
Erasmus MC-Sophia Children's Hospital, Department of Pediatric Intensive Care, Dr. Molewaterplein 60, 3015 GJ Rotterdam, Netherlands. pproeleveld@hetnet.nl
OBJECTIVE: The postoperative management of children undergoing single stage laryngotracheoplasty (SSLTP) includes intubation and muscle paralysis to secure the airway and protect the wound. We reduced the period of postoperative muscle paralysis in an attempt to decrease the incidence of pulmonary complications. The objective of this study was to evaluate the influence of the duration of muscle paralysis on pulmonary complications and outcome. METHODS: Medical records of all children admitted, between 1994 and 2002, to the pediatric intensive care unit following SSLTP were analysed. Children were grouped according to the number of days muscle paralysis was used. RESULTS: Thirty-six children (15 male, 21 female, mean age 32 months (9-162 months)) underwent SSLTP for laryngeal stenosis. Prior to surgery 29 needed a tracheotomy (mean duration 11.1 months). Shorter muscle paralysis leads to shorter intubation and mechanical ventilation and therefore PICU and hospital length of stay were 12.4 and 9.9days shorter in the group with short use of muscle paralysis (p<0.001 and p=0.002, respectively). There was no significant difference in postoperative complications, but a trend towards fewer atelectases in children with short muscle paralysis could be recognised. Postoperatively we observed no auto-extubations in either group and success rate of SSLTP was comparable in both groups (94 and 95%). CONCLUSION: Children undergoing SSLTP can safely benefit from a postoperative strategy using a short duration of muscle relaxants. They have fewer days on mechanical ventilation with a concomitant decrease in duration of hospital stay.


Weight and height gain after intrathecal baclofen pump implantation in children with spastic tetraparesis'.

Bertolasi L.

Baclofen toxicity in an 8-year-old with an intrathecal baclofen pump.

Baclofen delivered by intrathecal pumps (ITB) is increasingly being utilized in the pediatric population, however, resources and education to support problems with these devices are limited. Typical management strategies for systemic baclofen overdose include removal of baclofen from the device reservoir or removal of cerebrospinal fluid from the adjacent device catheter. Appropriate care of these patients requires awareness of the clinical patterns of toxicity and mechanics of the ITB pump delivery system. This report describes the clinical presentation, unfamiliar dilemmas, and the management of a pediatric patient with intrathecal baclofen toxicity, noting problems that may arise in the care of these patients.

Pharmacologic management of spasticity following stroke.

Montefiore Medical Center--The Jack D Weiler Hospital of the Albert Einstein College of Medicine, 1825 Eastchester Rd, Bronx, NY 10461, USA.

Effects of ephedrine on intubating conditions following priming with rocuronium.
Leykin Y, Pellis T, Lucca M, Gullo A.
Department of Anaesthesia, Pain, Perioperative Medicine and Intensive Care, Santa Maria degli Angeli Hospital, Pordenone, Italy.
Background: Onset of action of muscle relaxants / relaxant is influenced by cardiac output and muscle blood flow. Ephedrine reduces the onset time of rocuronium. Onset is also shortened by priming. Accordingly, we hypothesized that priming combined with ephedrine is superior to either technique used separately. Methods: Four groups of randomly allocated patients (n = 31), ASA I - II, were induced with propofol 2.5 mg kg(-1). In groups I and II, 0.04 mg kg(-1) of rocuronium was followed by a 3-min priming interval. Induction was followed by an intubation dose of 0.04 mg kg(-1). Then a 30-s intubation was attempted. In groups III and IV the same sequence was repeated except for sham priming and an intubation dose of 0.44 mg kg(-1). In groups I and II, ephedrine (210 microg kg(-1)) was injected before propofol. In groups II and V, an equivalent volume of normal saline was injected. Jaw relaxation, vocal cord position, and diaphragmatic response were used to assess intubating conditions. Results: All patients of group I were intubated 30 s after the intubating dose and within a 20-s interval compared with 74% of patients in groups II and III, and 84% of patients in group IV. Intubating conditions were graded good to excellent in all patients in group I compared with 42% of those in group II, 35% in group III and 52% in group IV (P < 0.01 vs. group I). During the priming interval, no adverse effects were observed or reported. Conclusions: Ephedrine in combination with propofol significantly improved clinical intubating conditions at 30 s following priming with rocuronium compared with priming with ephedrine without priming.


Dosage of intrathecal baclofen maintenance therapy in the spastic syndromes.
Fares Y, Khazim RM, del Barrio ER, Burzaco JA.
Neurosurgical Service, Ntra Sra Clinic of the Conception (Jimenez Diaz Foundation), Madrid, Spain. Faresdr@hotmail.com
Twenty-three patients affected with severe spasticity as a result of several clinical pathologies were treated with intrathecal Baclofen and administered at a lumbar level by means of an implantable infusion system. The system allows programming of any drug dosage in a continuous infusion fashion in the subarachnoid space. The appropriate patients were selected using specific criteria and the patients were regularly reviewed regarding the level of the spasticity and functional capacity. The required daily doses were determined using a specific detailed system. The doses needed varied according to the pathologic or clinical diagnosis. The doses administered by the global method at the beginning of the treatment were 91.96 microg/day and 137.81 microg/day in the final phase. These doses were higher in patients with medullary traumatic lesion, diffuse cerebral lesion and spastic idiopathic paraparesis. Relatively mild side effects were produced by the therapeutic doses used.

Recent advances in neuromuscular blocking agents.
Zlotos DP.
Pharmaceutical Institute, University of Wurzburg, Am Hubland, 97074 Wurzburg, Germany. zlotos@pzlc.uni-wuerzburg.de
Since the introduction of (+)-tubocurarine into anaesthetic and surgical practice (1942), a number of non-depolarizing neuromuscular blocking agents (NMBs) with improved pharmacological properties have been developed during the last sixty years. However, after withdrawal of rapacuronium from clinical use, there is still a need for an ultra-short acting non-depolarizing muscle relaxant / relaxants with rapid onset as substitution for the polarizing suxamethonium, which has several undesirable side-effects. In this paper, structure-activity relationships within four different series of NMBs (tetrahydroisoquinolinium, bistropinyl diester, aminosteroid, and amino peptide analogues) published in this millennium have been reviewed. The NMB properties of the most promising drug candidates from each series were discussed and compared to those of the already existing muscle relaxants.


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.

Spasticity in adults living in a developmental center.

OBJECTIVES: To ascertain the prevalence of spasticity among adults living in a developmental center and to document the development of spasticity treatment plans for this population. DESIGN: Descriptions of the clinical features of medical disorders and a prevalence survey. SETTING: Residential developmental center. PARTICIPANTS: One hundred three adults. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Characteristics described included the prevalence of spasticity in this population, the specific spasticity diagnosis, functional goals for spasticity treatment identified by the participants' multidisciplinary teams, and the specific treatment indicated by the neurologist. RESULTS: Of the 103 people diagnosed by the neurologist, 24 had diplegic spasticity, 4 had hemiplegic spasticity, 44 had quadriplegic spasticity, and 31 had no spasticity. Functional goals identified by multidisciplinary teams were undergarment change (46.3% of the persons for whom goals were identified), splinting hands (11%), dressing (57.4%), hygiene (20.4%), wheelchair positioning (25.9%), ambulation improvement (14.8%), and transfers (9.3%). After physical and occupational therapy, the first invasive treatments indicated for people with spasticity included botulinum toxin injections (60%), intrathecal baclofen (26.4%), orthopedic surgery (5.6%), and medication (1.4%). No treatment was recommended for 25% of the spasticity patients. CONCLUSIONS: The prevalence of spasticity was 35% in this developmental center population of 205 individuals. A multidisciplinary team approach to the evaluation of adults with spasticity who live in a developmental center makes it possible to identify functional goals that are amenable to spasticity treatment and minimizes treatment that does not target specific functional goals.