Methods for Delivering Volatile Anesthetics for Regional Anesthesia and/or Pain Relief

Abstract

The present invention provides methods for reducing pain in a subject in need of such pain reduction by delivering, e.g., intrathecally or epidurally, a volatile anesthetic such as a halogenated ether compound in an amount effective to reduce pain. Chronic or acute pain may be treated, or the anesthetic may be delivered to the subject to anesthetize the subject prior to a surgery. In certain embodiments, isoflurane, halothane, enflurane, sevoflurane, desflurane, methoxyflurane, xenon, and mixtures thereof may be used. Dosing regimens including a one-time administration, continuous and/or periodic administration are contemplated.

1 . A method for reducing pain in a subject in need of such pain reduction comprising parenterally delivering to the subject by a route other than intravenously a volatile anesthetic dissolved in a solution in an amount effective to reduce pain. 
   
   
       2 . The method of  claim 1 , wherein the anesthetic is delivered locally or regionally. 
   
   
       3 . The method of  claim 1 , wherein the volatile anesthetic is a halogenated ether anesthetic. 
   
   
       4 . The method of  claim 1 , wherein the anesthetic is delivered intrathecally, epidurally, or in a nerve block procedure. 
   
   
       5 . The method of  claim 1 , wherein the pain is chronic pain. 
   
   
       6 . The method of  claim 1 , wherein the pain is acute pain. 
   
   
       7 . The method of  claim 1 , wherein the anesthetic is delivered to anesthetize a portion of the subject prior to a surgery. 
   
   
       8 . The method of  claim 1 , wherein the volatile anesthetic is selected from the group consisting of isoflurane, halothane, enflurane, sevoflurane, desflurane, methoxyflurane, and mixtures thereof. 
   
   
       9 . The method of  claim 8 , wherein the volatile anesthetic is isoflurane. 
   
   
       10 . The method of  claim 1 , wherein the solution comprises the anesthetic in an amount ranging from about 5 ng/ml to about 100 ng/ml. 
   
   
       11 . The method of  claim 1 , wherein the solution comprises from about 5% to about 75% v/v anesthetic in solution. 
   
   
       12 . The method of  claim 11 , wherein the solution comprises from about 10% to about 50% v/v anesthetic in solution. 
   
   
       13 . The method of  claim 12 , wherein the anesthetic is isoflurane. 
   
   
       14 . The method of  claim 12 , wherein the solution is artificial cerebrospinal fluid. 
   
   
       15 . The method of  claim 12 , wherein the solution comprises about 10% v/v anesthetic in solution. 
   
   
       16 . The method of  claim 15 , wherein the anesthetic is isoflurane and the solution is artificial cerebrospinal fluid. 
   
   
       17 . The method of  claim 1 , wherein the solution is delivered epidurally or intrathecally to achieve a dose range of 250 ng/ml to 50,000 ng/ml active agent in the spinal fluid. 
   
   
       18 . The method of  claim 8 , wherein the halogenated compound is sevoflurane. 
   
   
       19 . The method of  claim 1 , wherein the delivery of the active agent is continuous. 
   
   
       20 . The method of  claim 1 , wherein the delivery of the active agent is periodic. 
   
   
       21 . The method of  claim 1 , wherein the delivery of the active agent is a one-time event. 
   
   
       22 . The method of  claim 1 , wherein the delivery of the active agent is both periodically administered and continuously administered to the subject on separate occasions. 
   
   
       23 . The method of  claim 1 , wherein the reduction comprises elimination of pain perception of a portion of the body of the subject. 
   
   
       24 . The method of  claim 1 , wherein the solution comprising the volatile anesthetic is sterile. 
   
   
       25 . The method of  claim 1 , wherein the subject is a human. 
   
   
       26 . The method of  claim 1 , wherein the subject is a mouse or a rat. 
   
   
       27 . The method of  claim 1 , wherein the solution is essentially free of an oil-in-water lipid emulsion. 
   
   
       28 . The method of  claim 1 , wherein the solution is saline or artificial cerebrospinal fluid. 
   
   
       29 . The method of  claim 28 , wherein the saline is normal saline. 
   
   
       30 . A pharmaceutically acceptable composition comprising a metered amount of a volatile anesthetic dissolved in an aqueous solution; wherein the composition is comprised in a pharmaceutically acceptable excipient; and wherein the composition is essentially free of a lipid emulsion. 
   
   
       31 . The composition of  claim 30 , wherein the composition is sterile. 
   
   
       32 . The composition of  claim 30 , wherein the composition is formulated for intrathecal administration, epidural administration, or administration via a nerve block. 
   
   
       33 . The composition of  claim 30 , wherein the solution comprises a saline solution or artificial cerebrospinal fluid. 
   
   
       34 . The composition of  claim 33 , wherein the saline solution is normal saline solution. 
   
   
       35 . The composition of  claim 30 , wherein the volatile anesthetic is selected from the group consisting of isoflurane, halothane, enflurane, sevoflurane, desflurane, methoxyflurane, and mixtures thereof. 
   
   
       36 . The composition of  claim 35 , wherein the volatile anesthetic is isoflurane. 
   
   
       37 . The composition of  claim 35 , wherein the volatile anesthetic is dissolved in the aqueous solution at a concentration of from about 10% to about 50% v/v. 
   
   
       38 . The composition of  claim 37 , wherein the volatile anesthetic is dissolved in the aqueous solution at a concentration of about 10% v/v. 
   
   
       39 . The composition of  claim 37 , wherein the volatile anesthetic is isoflurane and the aqueous solution is artificial cerebrospinal fluid. 
   
   
       40 . A sealed container comprising the anesthetic solution of any one of  claim 30 . 
   
   
       41 . The sealed container of  claim 40 , wherein the interior of the container is sterile. 
   
   
       42 . The sealed container of  claim 41 , wherein the container comprises a rubber stopper which may be easily pierced by an injection needle. 
   
   
       43 . The sealed container of  claim 41 , wherein the container comprises the chamber portion of a syringe. 
   
   
       44 . The container of  claim 41 , wherein the container comprises a drip chamber. 
   
   
       45 . The container of  claim 44 , wherein the drip chamber is coupled to a catheter. 
   
   
       46 . The container of  claim 45 , wherein the catheter is an epidural catheter or an intrathecal catheter. 
   
   
       47 . The container of  claim 41 , wherein the container is a plastic bag, a glass bottle, or a plastic bottle. 
   
   
       48 . The container of  claim 41 , wherein the container is coupled to an infusion pump. 
   
   
       49 . The container of  claim 48 , wherein the infusion pump is an intrathecal pump, an epidural delivery infusion pump, or a patient control analgesia (PCA) pump. 
   
   
       50 . The container of  claim 48 , wherein the infusion pump is programmable.