Patricia Curiale led an active life until an auto accident in 1998 triggered CRPS. After five years of living with pain that she rates "50 on a scale of 10," she was enrolled in our outpatient program that uses ketamine to treat CRPS when other conventional treatments fail. Ketamine is an anesthetic typically used in the operating room and for victims with unknown medical history (eg, traffic accidents). Ms. Curiale frankly credits the ketamine with saving her life. "I can understand putting a gun to your head to stop the pain," she says. Although she currently rates her pain at "about a 5," she can live with that. Plus, she has been able to get out of her wheelchair and walk, something a previous physician swore would never happen. She is one of many people who have CRPS and who have taken part in a program that I run with Robert J. Schwartzman, MD, Drexel University College of Medicine in Philadelphia. Currently we are collecting data on an outpatient "awake" ketamine protocol for patients who have tried more conventional therapies without long-term benefit. Elena King-Stoltz, who has full-body CRPS, had tried Bier blocks, spinal blocks, an intrathecal pump and other treatments since being diagnosed in 1992, but still experienced high levels of pain. She has been on the ketamine program for almost a year now. "I mowed my lawn for the first time in 10 years," she says.
The program can be done on both an inpatient and outpatient basis. Before beginning either therapy, we do laboratory and cardiac evaluations. While we have had No significant adverse events, we have been extremely cautious in screening patients with concurrent medical problems. The two most common reasons a patient would be eliminated are a psychiatric history of note (apart from the depression due to chronic pain) and cardiopulmonary disease. Hospital-based infusions The hospital-based infusions require a five-day in-patient stay. An intravenous (IV) line is inserted and the patient is started on a dose of 20mg of ketamine per hour, which is increased by 5- increments to a maximum of 40mg per hour. As an adjunct, we are using clonidine, 0.1mg (per FDA). We use small doses of lorazepam (Ativan®), 1 to 2 mg, for any dysphoria or hallucinations. The most common adverse event is fatigue. There have been some instances of short-term hallucinations related to dosage, but these have disappeared within an hour of lowering the dosage. Pat found the ketamine treatment very draining and the drug left her feeling "loopy," but she saw results from the beginning. She stopped the treatment in the fall of 2005 at her request. In addition, she had been taking oral ketamine but stopped a couple of months ago because she felt it was affecting her ability to concentrate. The accumulated data over two years denotes no significant lasting adverse events. Dr. Schwartzman and I have treated more than 100 patients. We had one patient with bradycardia in which the 5-day infusion was terminated.
Following discharge from the hospital, patients enroll in an outpatient infusion program of varying degrees and lengths. Initially, they go to the hospital's outpatient department 1-to-2 times a week for a 4-hour IV infusion of 70mg-to-100 mg of ketamine. At the beginning of the infusion, the patient is given 2mg of midazolam. Most patients sleep through the procedure. The frequency of outpatient treatments is weaned over time.
Currently, we are using a protocol that consists of two outpatient treatments a week every other week for one month, then one treatment every other week for a month, then monthly for three months,then every three months. This protocol is merely a general guideline however and varies at times. Then one outpatient treatment the following month, after which we reassess the patient. Outpatient visits are then monthly, or at 3-month intervals, depending on the patient.
Alternatively, the patients are given therapy only on an outpatient basis. They are given 10 daily treatments initially in two consecutive weeks in an outpatient infusion suite. They are administered from 70mg-to-100mg of ketamine per day in titrating doses over the 10-day timeframe and then they are placed in the outpatient program as described above. Again, there have been few adverse events and most of them have been dosage-related. As before, the most common is fatigue on the day of the infusion. There have been NO long term side effects. Most patients are given 2mg of midazolam and sleep through the procedure. Ms. King-Stoltz, an exception to the aforementioned protocol does the outpatient protocol once or twice a week. She spends 4 hours in the hospital and says she has no serious side effects. She is a little tired afterwards, but it goes away quickly.
The results obtained so far have been promising. We measure outcomes using pain scales, physical exams, psychologic profiles, and activity increase.
Rough estimates shows approximately 85% of those undergoing the hospital-stay protocol have shown improvement measured by increased activity, reduction of medication, and improved lifestyles. For example, some have discarded wheelchairs, walkers, and canes, and others have increased activities or have returned to work. Those beginning with outpatient therapy have similarly improved, but to a lesser degree (approximately 60% to 70%). All patients receive the follow-up outpatient boosters. Ms. King-Stoltz says that although she still has pain, it is manageable and she is doing things she hadn't done for years, such as walking and doing chores around the house. The ketamine treatment has given her back some degree of independence. The one major problem with ketamine infusion therapy is the inability to "hold" the improvement achieved by the five-day inpatient or 10-day outpatient regimen. Without the infusion boosters, the patients almost universally return to their pre-treatment state. It is therefore necessary to combine the initial start-up therapy on an inpatient or outpatient basis with follow-up boosters in order to maintain the level of pain relief. Virtually all participants in the program have continued the out-patient ketamine infusions. None of the patients treated by Dr. Schwartzman and myself have discontinued treating due to side effects. More study will be necessary to determine such factors as dosages and long-term time frame to be treated. Studies are currently ongoing to combine other drugs on an outpatient basis with ketamine to try and "hold" the improvement for a longer duration. Most patients get sustained relief for 4 to 6 months. Some have been fortunate enough to get a longer term benefit. I believe that ketamine provides the best chance of improvement from a therapeutic modality today. While it involves the use of medications besides ketamine, the use of IV drug therapy, a great deal of time and effort on the part of the patients and their families, it has certainly shown great promise in patients who do not find relief from other treatment. Certainly the drug is not for everyone-approximately 20% of people show little to no improvement. However, some have benefited dramatically. We continue the treatment program in the hope that more patient evaluations and the use on concurrent medication can affect a more long-lasting improvement in individuals with multi-limb or multi-system disease.
For now, however, we at least appear to be heading in a positive direction, helping many individuals who, up to this point in time, have received no or little benefit from the more "conventional" treatment modalities.
Philip Getson, DO, is a Board Certified Family Practitioner and an Associate Professor OF Neurology at the Drexel University college of Medicine in Philadelphia.Sphere: Related Content