Development and Prospective Federal State-Wide Evaluation of a Device for Height-Based Dose Recommendations in Prehospital Pediatric Emergencies: A Simple Tool to Prevent Most Severe Drug Errors.

OBJECTIVE: Drug dosing errors pose a particular threat to children in prehospital emergency care. With the Pediatric emergency ruler (PaedER), we developed a simple height-based dose recommendation system and evaluated its effectiveness in a pre-post interventional trial as the Ethics Committee disapproved randomization due to the expected positive effect of the PaedER on outcome. METHODS: Pre-interventional data were retrospectively retrieved from the electronic records and medical protocols of the Cologne Emergency Medical Service over a two-year period prior to the introduction of the PaedER. Post-interventional data were collected prospectively over a six-year period in a federal state-wide open trial. The administered doses of either intravenous or intraosseous fentanyl, midazolam, ketamine or epinephrine were recorded. Primary outcome measure was the number and severity of drug dose deviation from recommended dose (DRD) based on the patient's weight. RESULTS: Fifty-nine pre-interventional and 91 post-interventional prehospital drug administrations in children were analyzed. The rate of DRD > 300% overall medications were 22.0% in the pre- and 2.2% in the post-interventional group (p < 0.001). All administrations of epinephrine occurred excessive (DRD > 300%) in pre-interventional and none in post-interventional patients (p < 0.001). CONCLUSIONS: The use of the PaedER resulted in a 90% reduction of medication errors (95% CI: 57% to 98%; p < 0.001) and prevented all potentially life-threatening errors associated with epinephrine administration. There is an urgent need to increase the safety of emergency drug dosing in children during emergencies. A simple height-based system can support health care providers and helps to avoid life-threatening medication errors.

Quaternary Lidocaine Derivative QX-314 Activates and Permeates Human TRPV1 and TRPA1 to Produce Inhibition of Sodium Channels and Cytotoxicity.

BACKGROUND: The relatively membrane-impermeable lidocaine derivative QX-314 has been reported to permeate the ion channels transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential cation channel, subfamily A, member 1 (TRPA1) to induce a selective inhibition of sensory neurons. This approach is effective in rodents, but it also seems to be associated with neurotoxicity. The authors examined whether the human isoforms of TRPV1 and TRPA1 allow intracellular entry of QX-314 to mediate sodium channel inhibition and cytotoxicity. METHODS: Human embryonic kidney 293 (HEK-293) cells expressing wild-type or mutant human (h) TRPV1 or TRPA1 constructs as well as the sodium channel Nav1.7 were investigated by means of patch clamp and ratiometric calcium imaging. Cytotoxicity was examined by flow cytometry. RESULTS: Activation of hTRPA1 by carvacrol and hTRPV1 by capsaicin produced a QX-314-independent reduction of sodium current amplitudes. However, permeation of QX-314 through hTRPV1 or hTRPA1 was evident by a concentration-dependent, use-dependent inhibition of Nav1.7 activated at 10 Hz. Five and 30 mM QX-314 activated hTRPV1 via mechanisms involving the intracellular vanilloid-binding domain and hTRPA1 via unknown mechanisms independent of intracellular cysteins. Expression of hTRPV1, but not hTRPA1, was associated with a QX-314-induced cytotoxicity (viable cells 48 ± 5% after 30 mM QX-314) that was ameliorated by the TRPV1 antagonist 4-(3-chloro-2-pyridinyl)-N-[4-(1,1-dimethylethyl)phenyl]-1-piperazinecarboxamide (viable cells 81 ± 5%). CONCLUSIONS: The study data demonstrate that QX-314 directly activates and permeates the human isoforms of TRPV1 and TRPA1 to induce inhibition of sodium channels, but also a TRPV1-dependent cytotoxicity. These results warrant further validation of this approach in more intact preparations and may be valuable for the development of this concept into clinical practice.