Effect of cholinergic crisis on the potency of different emergency anaesthesia protocols in soman-poisoned rats

Background: In a military or terrorist scenario, combination of organophosphorus compounds (OP) poisoning with physical trauma requiring surgical treatment and thus general anaesthesia are possible. Previous in vitro studies showed an altered potency of relevant anaesthetics during cholinergic crisis. Hence, it is not clear, which anaesthetics are suitable to achieve the necessary stage of surgical anaesthesia in OP poisoning.

Methods: In the present study, different anaesthetic regimens (ketamine-midazolam, propofol-fentanyl, thiopental-fentanyl), relevant in military emergency medicine, were examined in soman-poisoned rats. Clinical signs and cardiovascular variables were recorded continuously. Blood samples for acetylcholinesterase (AChE) activity were drawn. After euthanasia or death of the animals, brain and diaphragm were collected for cholinesterase assays.

Results: Propofol-fentanyl and thiopental-fentanyl resulted in surgical anaesthesia throughout the experiments. With ketamine-midazolam, surgical anaesthesia without respiratory impairment could not be achieved in pilot experiments (no soman challenge) and was therefore not included in the study. Soman-poisoned and control animals required a comparable amount of propofol-fentanyl or thiopental-fentanyl. In combination with atropine, significantly less propofol was needed. Survival rate was higher with thiopental compared to propofol. Atropine improved survival in both groups. Blood and tissue AChE activities were strongly inhibited after soman administration with and without atropine treatment.

Discussion: The current in vivo study did not confirm concerns of altered potency of existing anaesthetic protocols for the application of propofol or thiopental with fentanyl due to soman poisoning. Despite severe cholinergic crisis, sufficient anaesthetic depth could be achieved in all animals.

Conclusion: Further experiments in in vivo models closer to human pharmaco- and toxicokinetics (e.g., swine) are required for confirmation of the initial findings and for improving extrapolation to humans.     

Sham-Controlled Randomized Trials of Catheter-Based Renal Denervation in Patients With Hypertension

Background

There are conflicting data regarding the relative effectiveness of renal sympathetic denervation (RSD) in patients with hypertension.

Editor's Choice: Medication-indication knowledge bases: a systematic review and critical appraisal

Objective Medication-indication information is a key part of the information needed for providing decision support for and promoting appropriate use of medications. However, this information is not readily available to end users, and a lot of the resources only contain this information in unstructured form (free text). A number of public knowledge bases (KBs) containing structured medication-indication information have been developed over the years, but a direct comparison of these resources has not yet been conducted.Material and Methods We conducted a systematic review of the literature to identify all medication-indication KBs and critically appraised these resources in terms of their scope as well as their support for complex indication information.Results We identified 7 KBs containing medication-indication data. They notably differed from each other in terms of their scope, coverage for on- or off-label indications, source of information, and choice of terminologies for representing the knowledge. The majority of KBs had issues with granularity of the indications as well as with representing duration of therapy, primary choice of treatment, and comedications or comorbidities.Discussion and Conclusion This is the first study directly comparing public KBs of medication indications. We identified several gaps in the existing resources, which can motivate future research.     

Rhabdomyomatous mesenchymal hamartoma presenting as a sacral skin tag in two neonates with spinal dysraphism

Rhabdomyomatous mesenchymal hamartoma (RMH) is a rare congenital malformation involving the dermis and subcutaneous tissue, of which there were 62 reported cases through 2014. We report RMH in two neonates presenting as a sacral skin tag. In both cases, magnetic resonance imaging (MRI) of the spine showed evidence of spinal dysraphism, including a lipomyelomeningocele and a tethered cord. Surgical repair of the defects was performed. Histopathologic examination of the skin tags showed a haphazard arrangement of mature skeletal muscle fibers and adnexal elements, consistent with RMH. The second patient also had a hemangioma on the sacrum and was diagnosed with LUMBAR (lower body hemangioma and other cutaneous defects, urogenital anomalies/ulceration, myelopathy, bony deformities, anorectal/arterial anomalies, and renal anomalies) syndrome, an association between cutaneous infantile hemangiomas of the lower body and regional congenital anomalies. The apparent association of paraspinal RMH with spinal dysraphism suggests that aberrant migration of mesodermally derived tissues (including skeletal muscle fibers) during neural tube development may be responsible for the pathologic findings in the skin. Additional study of patients with spinal dysraphism and congenital cutaneous lesions may further support this hypothesis.