IV Ibuprofen for Post-Electroconvulsive Therapy Myalgia
IV Ibuprofen for Post-Electroconvulsive Therapy Myalgia
Post-procedure myalgia (muscle ache) is a well-known and common complication of
 Electro-convulsive Treatment (ECT). Myalgias are a serious concern of patients and occur in
 approximately 50% of these cases. The pain is usually described as muscle soreness, similar
 to that resulting from strenuous exercise. The myalgias typically begin shortly after the
 procedure, lasting approximately 2-7 days in total. A recent study reported that 89% of
 patients considered prevention significant and would be willing to pay a median of $33 out of
 pocket to avoid this side effect. In addition to patient discomfort, myalgias can have a
 further financial burden if these patients are unable to return to work or resume previous
 daily activities in the days following the procedure. An agent that could treat and possibly
 even prevent these myalgias has the potential to be very beneficial to these patients. IV
 ibuprofen (trade name Caldolor) is a novel therapeutic modality approved by the US Food and
 Drug Administration (FDA) in June 2009 for the treatment of mild to moderate pain, as an
 adjunct to opioid analgesics, and for the reduction of fever.
IV ibuprofen (trade name Caldolor) is a novel therapeutic modality approved by the US Food
 and Drug Administration (FDA) in June 2009 for the treatment of mild to moderate pain, as an
 adjunct to opioid analgesics, and for the reduction of fever. Ibuprofen is a non-steroidal
 anti-inflammatory drug (NSAID), which produces its effect through inhibition of the enzyme
 cyclooxygenase (COX). There are at least 2 variations of cyclooxygenase (COX-1 and COX-2) and
 ibuprofen non-selectively inhibits both, thus decreasing prostaglandin synthesis. This action
 gives ibuprofen its analgesic, anti-pyretic, and anti-inflammatory properties. NSAIDs have an
 established history of efficacy in the treatment of both acute and chronic somatic pain.
 Caldolor, being an intravenous formulation, offers a distinct advantage in patients who
 either are unable to take medications orally or are fasting preoperatively.

 Post-procedure myalgia is a well-known and common complication of ECT. Although the exact
 etiology is unknown, the myalgias are believed to result from a combination of
 succinylcholine administration and the seizure activity induced by the ECT procedure itself.
 Succinylcholine-induced postoperative myalgias are a well-known phenomenon, initially
 described in the early 1950's. The exact pathogenesis is unknown, with muscle damage from
 succinylcholine-induced fasciculations or calcium-mediated phospholipase A2 activation and
 prostaglandin production being proposed as possible etiologies. The latter mechanism provides
 the rationale for using NSAID therapy. However, succinylcholine is unlikely to be the only
 factor involved in the development of myalgias following ECT, as a recent study showed that
 dose adjustments to succinylcholine did not affect rates of myalgia in these patients.
 Furthermore, seizures can also cause direct muscle injury and there have been reports of
 muscle pain after ECT both with and without succinylcholine.

 A thorough literature search using Medline, Ovid, and scholar.google failed to find any
 research articles evaluating pretreatment therapy for myalgias in post-ECT patients. The
 current practice for the treatment of myalgias following ECT has been extrapolated from
 research on succinylcholine-induced myalgia in post-surgical patients. Previous studies have
 shown at least partial efficacy with pretreatment of nondepolarizing neuromuscular blocking
 agents, benzodiazepines, sodium channel blockers (predominantly lidocaine), and nonsteroidal
 anti-inflammatory drugs. The nature of the ECT procedure itself makes several of these
 modalities undesirable. Both Lidocaine and benzodiazepines can alter the seizure threshold
 and the short duration of the procedure possibly increases the risks associated with longer
 acting nondepolarizing muscle relaxants (ie. blurred vision, diplopia, difficulty breathing
 and swallowing). Therefore, the options for pretreatment are limited. In addition, a recent
 meta-analysis of randomized trials determined NSAIDs to cumulatively have the best efficacy
 of any pretreatment therapy in the prevention of post-procedural myalgias. Due to its
 intravenous formulation, some practitioners have administered ketorolac to ECT patients
 before the procedure. However, despite a proven efficacy in myalgia prevention shown by
 NSAIDs as a class, a study specifically examining the use of ketorolac in this regard failed
 to show any benefit. The use of Ibuprofen has yet to be examined.

 Myalgias are a serious concern of patients and occur in approximately 50% of these cases. The
 pain is usually described as muscle soreness, similar to that resulting from strenuous
 exercise. The myalgias typically begin shortly after the procedure, lasting approximately 2-7
 days in total. A recent study reported that 89% of patients considered prevention significant
 and would be willing to pay a median of $33 out of pocket to avoid this side effect. In
 addition to patient discomfort, myalgias can have a further financial burden if these
 patients are unable to return to work or resume previous daily activities in the days
 following the procedure. An agent that could treat and possibly even prevent these myalgias
 has the potential to be very beneficial to these patients.

 Experimental Plan:

 The study will be a prospective, randomized, double-blinded placebo-controlled clinical
 trial. The subject population will consist of patients undergoing first time
 electroconvulsive therapy, ranging in age from 18 to 80 years. Subjects will be given a
 Mini-Mental State Examination at the time of their presentation for ECT to assess their
 cognitive ability. If the patient consents and fits the inclusion criteria, patients will be
 randomized to one treatment modality, which they will receive for the first three treatment
 sessions. The subject and the person collecting the data will both be blinded as to what
 treatment modality the subject belongs to. The patients will be divided into two groups,
 Group 1 and Group 2. Group 1 will be treated with IV ibuprofen 800mg/8ml given over 30
 minutes, prior to induction for ECT; while Group 2 will receive an identically appearing
 placebo dose, also administered IV, over that same time period. Both groups will receive a
 standardized anesthetic consisting of methohexital at 1 mg/kg IV for induction and
 succinylcholine 1 mg/kg IV for muscle paralysis. Other medications (eg. anticholinergic or
 antihypertensive drugs) will be administered at the discretion of the anesthesiologist. ECT
 will be administered by the psychiatrist in order to achieve a seizure with a motor component
 of > 15 second duration. Patients will be transported to the recovery room for
 post-anesthesia care. Rescue analgesics (Tylenol 500mg PO, Tylenol with codeine 300/30mg PO,
 Fentanyl 25 mcg IV) will be available to any patient with complaints of myalgia or headache
 pain of VAS >4.

 Measurement Tools:

 Severity of myalgias will be assessed based on a self-reported assessment utilizing a
 numerical rating scale (NRS). The scale will be rated as 0 meaning no pain at all and 10
 meaning that pain is so severe as to interfere with daily activities.

 Questionnaire:

 Do you have any muscle aches or pain right now? If yes, how would you rate that muscle
 ache/pain on a scale of 0 to 10, with 0 being no pain and 10 being pain that is the worst
 imaginable?

 Example:

 0 = No pain 1-3 = Mild Pain (nagging, annoying, little interference with everyday activities)
 4-6 = Moderate Pain (interferes significantly with everyday activities) 7-10 = Severe Pain
 (unable to perform everyday activities) Have you had to take any medications to treat your
 muscle aches? If yes, what medication did you take? How many pills? What was the strength of
 the medication? Do you have a headache right now? If yes, how would you rate that headache on
 a scale of 0 to 10, with 0 being no pain and 10 being pain that is the worst imaginable?

 Measurements:

 Each patient will have a self-reported numerical pain score assessed at baseline before
 therapy, 1 hour post-ECT, 6 hours post-ECT, 24 hours post-ECT, and finally at 48 hours
 post-ECT. The 6, 24 and 48 hour post-ECT assessments will be conducted via a telephone
 conversation. The use of rescue analgesics during recovery will also be documented as well as
 time from the end of procedure to discharge. The presence of headache will also be documented
 in each patient.
Inclusion Criteria:

 -  Capable of providing informed consent

 -  American Society Anesthesiologists (ASA) rating I-III

 -  Subjects age 18-80 capable of providing consent.

 -  Subjects undergoing electroconvulsive therapy using succinylcholine as the sole
 neuromuscular blocking agent.

 -  Subjects who have scored ≥23 on the Mini-Mental State Examination.

 Exclusion Criteria:

 -  Subjects who have had a recent thrombotic event, myocardial infarction or stroke or
 episode of Congestive Heart Failure (CHF) within less than 3 months.

 -  Subjects who have had a recent cardiovascular surgery within the last 3 months.

 -  Subjects with active Gastrointestinal bleeding

 -  Subjects who have asthma, itching or allergic type reaction following aspirin or other
 NSAID administration

 -  Subjects with a known hypersensitivity to ibuprofen

 -  Subjects with heart failure, bleeding disorders or kidney failure

 -  Subjects taking aspirin, Angiotensin converting enzyme (ACE) inhibitors, or
 anticoagulants within one month.

 -  Subjects with any devices used to treat pain (intrathecal pumps, spinal cord
 stimulators etc)

 -  Subjects with a history of fibromyalgia or chronic myositis

 -  Subjects who are pregnant

 -  Subjects who do not have a phone

 -  Subjects who have had previous ECT

 -  Subjects receiving toradol (Ketorolac)

 -  Subjects with reported renal disease within less than 3 months.

 -  Subjects who have had previous electroconvulsive therapy within the last 3 months