Arthroscopic irrigation solution and method for peripheral vasoconstriction and inhibition of pain and inflammation

Abstract

A method and solution for perioperatively inhibiting a variety of pain and inflammation processes during arthroscopic procedures. The solution preferably includes a vasoconstrictor that demonstrates substantial agonist activity at alpha adrenergic receptors and that is selected for peripheral (local) vasoconstriction and one or more additional pain and inflammation inhibitory agents at dilute concentration in a physiologic carrier, such as saline or lactated Ringer's solution. The solution is applied by continuous irrigation of a wound during a surgical procedure for peripheral vasoconstriction and inhibition of pain and/or inflammation while avoiding undesirable side effects associated with systemic application of larger doses of the agents.

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows: 
     
         1 . A method of inhibiting pain and inflammation at a joint during an arthroscopic surgical procedure, comprising delivering to a joint during an arthroscopic procedure a solution comprising:
 oxymetazoline,   a non-selective cyclooxygenase inhibitor; and   a liquid carrier, wherein the solution is applied locally and perioperatively to the joint.   
     
     
         2 . The method of  claim 1 , wherein the non-selective cyclooxygenase inhibitor is selected from the group consisting of diclofenac, naproxen, indomethacin, ibuprofen, ketorolac and ketoprofen. 
     
     
         3 . The method of  claim 1 , wherein the solution further comprises amitriptyline. 
     
     
         4 . The method of  claim 1 , comprising continuously applying the solution to the joint. 
     
     
         5 . The method of  claim 4 , comprising continuously irrigating the joint with the solution. 
     
     
         6 . The method of  claim 1 , wherein the solution is applied by irrigation of the joint. 
     
     
         7 . The method of  claim 1 , wherein the solution is locally applied to the joint in the absence of metabolic transformation. 
     
     
         8 . The method of  claim 1 , wherein the perioperative application of the solution comprises intraprocedural application together with preprocedural or postprocedural application of the solution. 
     
     
         9 . The method of  claim 8 , wherein the perioperative application of the solution comprises preprocedural, intraprocedural and postprocedural application of the solution. 
     
     
         10 . The method of  claim 1 , wherein the oxymetazoline in the solution is delivered locally at a concentration of no greater than 300,000 nanomolar. 
     
     
         11 . The method of  claim 10 , wherein the oxymetazoline in the solution is delivered locally at a concentration of no greater than 75,000 nanomolar. 
     
     
         12 . The method of  claim 11 , wherein the non-selective cyclooxygenase inhibitor in the solution is delivered locally at a concentration of no greater than 500,000 nanomolar. 
     
     
         13 . The method of  claim 12 , wherein the non-selective cyclooxygenase inhibitor in the solution is delivered locally at a concentration of no greater than 100,000 nanomolar. 
     
     
         14 . The method of  claim 1 , wherein each of the agents in the solution is included at a concentration or dosage that is sufficient to provide a level of pain/inflammation inhibitory or vasoconstrictive effect at the joint when delivered locally to the joint and that results in a plasma concentration that is less than a plasma concentration that would be required to achieve the same level of inhibitory or therapeutic effect at the joint when delivered systemically. 
     
     
         15 . The method of  claim 1 , comprising intermittently applying the solution to the joint. 
     
     
         16 . A method of inhibiting pain and inflammation at a joint of an extremity during an arthroscopic or open surgical procedure or other extremity procedure, comprising delivering to the surgical site during the procedure a solution comprising:
 oxymetazoline,   a non-selective cyclooxygenase inhibitor; and   a liquid carrier, wherein the solution is applied locally and perioperatively to the surgical site.   
     
     
         17 . The method of  claim 16 , wherein the non-selective cyclooxygenase inhibitor is selected from the group consisting of diclofenac, naproxen, indomethacin, ibuprofen, ketorolac and ketoprofen. 
     
     
         18 . The method of  claim 16 , wherein the solution further comprises amitriptyline. 
     
     
         19 . The method of  claim 16 , comprising continuously applying the solution to the surgical site. 
     
     
         20 . The method of  claim 16 , wherein the solution is applied by irrigation of the surgical site. 
     
     
         21 . The method of  claim 16 , wherein the perioperative application of the solution comprises intraprocedural application together with preprocedural or postprocedural application of the solution. 
     
     
         22 . The method of  claim 21 , wherein the perioperative application of the solution comprises preprocedural, intraprocedural and postprocedural application of the solution. 
     
     
         23 . The method of  claim 16 , wherein each of the agents in the solution is included at a concentration or dosage that is sufficient to provide a level of pain/inflammation inhibitory or vasoconstrictive effect at the surgical site when delivered locally to the surgical site and that results in a plasma concentration that is less than a plasma concentration that would be required to achieve the same level of inhibitory or therapeutic effect at the surgical site when delivered systemically. 
     
     
         24 . The method of  claim 16 , wherein the procedure during which the solution is delivered comprises an open joint procedure. 
     
     
         25 . The method of  claim 24 , wherein the procedure during which the solution is delivered comprises a total joint replacement. 
     
     
         26 . The method of  claim 25 , wherein the solution is applied by intermittent irrigation during the procedure. 
     
     
         27 . The method of  claim 16 , comprising intermittently applying the solution to the joint. 
     
     
         28 . A method of inhibiting pain and inflammation at a surgical or operative/procedural sites during an oral/dental surgery, ocular surgery or burn treatment procedures, comprising delivering to a site during an oral/dental surgery, ocular surgery or burn treatment procedure a solution comprising:
 oxymetazoline,   a non-selective cyclooxygenase inhibitor, and   a liquid carrier, wherein the solution is applied locally and perioperatively to the site.   
     
     
         29 . The method of  claim 28 , wherein the non-selective cyclooxygenase inhibitor is selected from the group consisting of diclofenac, naproxen, indomethacin, ibuprofen, ketorolac and ketoprofen. 
     
     
         30 . The method of  claim 28 , wherein the solution further comprises amitriptyline. 
     
     
         31 . The method of  claim 28 , comprising continuously applying the solution to the surgical site. 
     
     
         32 . The method of  claim 28 , wherein the solution is applied by irrigation of the surgical site. 
     
     
         33 . The method of  claim 28 , wherein each of the agents in the solution is included at a concentration or dosage that is sufficient to provide a level of pain/inflammation inhibitory or vasoconstrictive effect at the surgical site when delivered locally to the surgical site and that results in a plasma concentration that is less than a plasma concentration that would be required to achieve the same level of inhibitory or therapeutic effect at the surgical site when delivered systemically.