Update on the management of neuromuscular block: focus on sugammadex

Steroidal neuromuscular blocking agents (NMBAs), such as rocuronium, are widely used in clinical anesthesia and emergency medicine to facilitate endotracheal intubation and artificial ventilation and to allow surgical access to body cavities. Reversal of neuromuscular blockade is important for the acceleration of patient recovery and prevention of postoperative residual neuromuscular blockade and reduces the incidence of severe morbidity and mortality associated with anesthesia management. Sugammadex is the first selective relaxant binding agent (SRBA) and has been designed to reverse the steroidal neuromuscular blocking drug rocuronium. Encapsulation of the rocuronium molecule by sugammadex results in a rapid decrease in free rocuronium in the plasma and subsequently at the nicotinic receptor at the motor endplate. After encapsulation, rocuronium is not available to bind to the nicotinic receptor in the neuromuscular junction. This promotes the liberation of acetylcholine receptors, and muscle activity reappears. This new concept of reversal of neuromuscular block induced by rocuronium (or vecuronium) led to impressive results in animal and phase 1 and 2 studies. Sugammadex is currently in phase 3 clinical studies and may be commercially available by 2008.     

Colchicine-induced lesion of rat hippocampal granular cells prevents conditioned active avoidance with perforant path stimulation as conditioned stimulus, but not conditioned emotion

Successful acquisition of active avoidance by rats with low frequency (15 cps) stimulation of the perforant path as a conditioning stimulus is correlated with a slowly developing long-term enhancement of perforant path-granular cell synapses. After selective destruction of granular cells of the stimulated side by unilateral microinjection of 1.6 micrograms/0.2 microliter colchicine into the dentate area, field potentials could no longer be evoked by test stimuli and animals subsequently failed to acquire the conditioned active avoidance with perforant path stimulation as a CS. However, colchicine-treated animals showed the same development of conditioned emotional responses as saline controls and they could also successfully be conditioned with light and tone as the CS. These results suggest that the granular cells are necessarily involved in the conditioning pathway for the active avoidance with perforant path stimulation as the CS. Other targets of the perforant path, e.g., ipsi- and contralateral CA1 pyramidal cells and contralateral granular cells, or antidromic activation of the entorhinal cortex seem an insufficient substitute for granular cells in the pathway for this conditioned active avoidance, but would probably participate in the conditioned emotional responses. The results additionally support our hypothesis, that post-conditioning LTP in granular cell synapses contribute to the acquisition and/or the storage of a memory trace.     

Incompatibility of contrast agents with intravascular medications. Work in progress

In vitro and in vivo precipitation of iodinated contrast agents when ioxaglate and papaverine are given together has been reported. To verify these reports and to investigate other medications not previously tested, the authors analyzed mixtures of contrast agents and medications in vitro with a light spectrophotometer and observed them for visible precipitates for up to 120 minutes. Previously reported incompatibilities between ionic or low-osmolality contrast media and medications were verified, and several new incompatibilities were discovered. No incompatibilities were found when the drugs tested were mixed with the new nonionic contrast media.     

Long-term benefit to pallidal deep brain stimulation in a case of dystonia secondary to pantothenate kinase-associated neurodegeneration.

Pantothenate kinase-associated neurodegeneration (PKAN) is a rare autosomal recessive disorder with onset in childhood and rapid progression. There is no causative and insufficient symptomatic drug therapy. Deep brain stimulation (DBS) of the internal pallidum (GPi) has been reported to improve motor function. Most case reports, however, are limited to short observational periods. The impact of DBS on the progression and life expectancy in PKAN is unknown. We present a 5-year outcome and video documentation of bilateral GPi-DBS of an adolescent patient suffering from genetically defined PKAN.     

Evaluation and audit in a paediatric disability service

Parental and professional responses to questionnaires evaluating a paediatric disability service are reported and the viability of auditing structural, process, and outcome aspects of clinical practice are discussed. Expectations of waiting time to first appointment (met for only 52% of consumers) illustrate structural issues. Process issues are reflected in consumer reactions to outreach work (for example, 94% of parents and 84% of professionals found this supportive). Outcome measures such as consumer satisfaction with the service (76% of consumers reported being 'very satisfied' and 20% 'fairly satisfied') suggest that service aims are being met. Good concurrence of service aims with consumer needs is indicated by parental reasons for referral (for example, 75% for diagnostic help, 73% for a better understanding of the disorder, 88% for practical help), referrers' reasons (for example, 55% for a second diagnostic opinion, 45% due to lack of local expertise), and reports from most other professionals involved with the case that a similar service was not provided locally.     

Efficacy of pyrimethamine/sulfadoxine in the prevention of toxoplasmic encephalitis relapses andPneumocystis carinii pneumonia in HIV-infected patients

The efficacy and safety of 25 mg pyrimethamine plus 500 mg sulfadoxine given twice a week in preventing relapses of AIDS-related toxoplasmic encephalitis was evaluated in an open study. The 56 HIV-infected patients evaluated had responded to intensive treatment with pyrimethamine/clindamycin prior to starting the present prophylactic regimen. Four patients (7 %) experienced relapse while on pyrimethamine/sulfadoxine. The probability of freedom from relapse was >90 % for 12 months and >80 % for 24 months. Side effects comprised mild or moderate allergic reactions which occurred in 23 patients (41 %), leading to discontinuation in four patients (7%). Forty-nine of the 56 patients did not have a history ofPneumocystis carinii pneumonia and did not receive antiparasitic prophylaxis other than pyrimethamine/sulfadoxine; two of them (4 %) developed pneumocystosis. The probability of freedom from pneumocystosis was about 90 % for 24 months. Pyrimethamine/sulfadoxine twice a week appears to be a promising regimen for prevention of toxoplasmic encephalitis, and also appears to provide protection againstPneumocystis carinii pneumonia. Although allergic reactions are usually mild and disappear on continuation, they may limit the value of this regimen.     

Bilateral simultaneous tubal sextuplets: pregnancy after in-vitro fertilization--embryo transfer following salpingectomy

The presence of a damaged tube has been suggested in recent studies to have a negative effect on in-vitro fertilization (IVF) outcome. Performing bilateral salpingectomy prior to IVF to maximize pregnancy rates may also result in unnecessary surgery. This case is also an example of the occurrence of interstitial pregnancy after salpingectomy. This unusual type of ectopic pregnancy must be kept in mind when evaluating a patient suspected of a possible early abnormal gestation after assisted reproductive technolologies.