Anesthesia and analgesia
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Anesthesia and analgesia · Oct 1998
Fundamental properties of local anesthetics: half-maximal blocking concentrations for tonic block of Na+ and K+ channels in peripheral nerve.
Local anesthetics suppress excitability by interfering with ion channel function. Ensheathment of peripheral nerve fibers, however, impedes diffusion of drugs to the ion channels and may influence the evaluation of local anesthetic potencies. Investigating ion channels in excised membrane patches avoids these diffusion barriers. We investigated the effect of local anesthetics with voltage-dependent Na+ and K+ channels in enzymatically dissociated sciatic nerve fibers of Xenopus laevis using the patch clamp method. The outside-out configuration was chosen to apply drugs to the external face of the membrane. Local anesthetics reversibly blocked the transient Na+ inward current, as well as the steady-state K+ outward current. Half-maximal tonic inhibiting concentrations (IC50), as obtained from concentration-effect curves for Na+ current block were: tetracaine 0.7 microM, etidocaine 18 microM, bupivacaine 27 microM, procaine 60 microM, mepivacaine 149 microM, and lidocaine 204 microM. The values for voltage-dependent K+ current block were: bupivacaine 92 microM, etidocaine 176 microM, tetracaine 946 microM, lidocaine 1118 microM, mepivacaine 2305 microM, and procaine 6302 microM. Correlation of potencies with octanol:buffer partition coefficients (logP0) revealed that ester-bound local anesthetics were more potent in blocking Na+ channels than amide drugs. Within these groups, lipophilicity governed local anesthetic potency. We conclude that local anesthetic action on peripheral nerve ion channels is mediated via lipophilic drug-channel interactions. ⋯ Half-maximal blocking concentrations of commonly used local anesthetics for Na+ and K+ channel block were determined on small membrane patches of peripheral nerve fibers. Because drugs can directly diffuse to the ion channel in this model, these data result from direct interactions of the drugs with ion channels.
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Anesthesia and analgesia · Oct 1998
Jet ventilation in upper airway obstruction: description and model lung testing of a new jetting device.
Patients with critical upper airway stenosis require a tracheotomy for corrective surgery. We describe a new transtracheal device that permits safe ventilation of these patients without tracheotomy. It is based on a coaxial bicannular design that allows "push-pull" ventilation by jetting gas through the inner cannula and applying suction through the outer cannula. It further allows monitoring of airway pressure, tidal volume, and end-tidal CO2. The device was placed in the "trachea" of an artificial lung, and the preparation was made airtight by sealing the proximal end of the trachea. Tidal volumes and their associated pressures were measured simultaneously at different parts of the airway at several lung compliances and airway resistance settings while varying the jet and suction pressures. A large range of tidal volumes was achieved at safe airway pressures using clinically relevant airway resistance and lung compliance settings. Airway pressures measured through the device correlated well with pressures measured directly in the airways at the same time. Tidal volumes, measured through a Wright respirometer in the suction line, exceeded actual values at high suction settings and decreased below actual values at low suction settings. This new form of jet ventilation allowed efficient ventilation of the artificial lung with a totally occluded upper airway. ⋯ Tracheotomy is required for surgery to relieve stridor because gas forced into the trachea at high pressures through a percutaneously placed needle (jetting) cannot be exhaled quickly enough for respiration. We describe a device that allows jetting in the stridorous patient by actively assisting expiration, thereby eliminating the tracheotomy requirement.