Trial protocol for a multicenter randomized controlled trial to assess the efficacy and safety of intravenous ketamine for chronic daily headaches: the "KetHead" trial.

BACKGROUND: Chronic daily headaches (CDH) are common and associated with significant morbidity, poor quality of life, and substantial burden on the healthcare system. CDH tends to be refractory to conventional medical management and/or patients cannot afford expensive treatments. It is stipulated that CDH share a mechanism of central sensitization in the trigeminocervical complex, mediated by activation of the N-methyl-D-aspartate (NMDA) receptors. Ketamine, a non-competitive NMDA antagonist, has been used in the treatment of chronic pain, but its role in CDH has not been completely established. This trial aims to evaluate the effect of high-dose IV ketamine infusions (compared to placebo) on the number of headache days at 28 days post-infusion. METHODS: A multicenter, placebo-controlled, randomized controlled trial will be conducted with two parallel groups and blinding of participants and outcome assessors. The study will include 56 adults with a CDH diagnosis as per ICHD-3 criteria. Participants will be randomized (1:1) to either ketamine (1 mg. kg-1 bolus followed by infusion of 1 mg. kg-1. h-1 for 6 h) or placebo (0.9% saline in the same volume and infusion rate as the trial medication) bolus and infusion for 6 h. The impact on the number of monthly headache days, headache intensity, physical activity, mood, sleep, quality of life, analgesic consumption, and adverse effects will be recorded at baseline, immediately post-infusion, and from 1 to 28 days, 29 to 56 days, and 57 to 84 days after the infusion DISCUSSION: Despite advancements in treatment, many patients continue to suffer from CDH. This trial investigates whether high-dose IV ketamine infusions can effectively and safely improve the CDH burden as compared to a placebo infusion. This treatment could become a safe, affordable, and widely available option for patients living with refractory headache. TRIAL REGISTRATION: ClinicalTrials.gov NCT05306899. Registered on April 1, 2022.

User Engagement and Clinical Impact of the Manage My Pain App in Patients With Chronic Pain: A Real-World, Multi-site Trial.

BACKGROUND: Chronic pain imposes a large burden on individuals and society. A patient-centric digital chronic pain management app called Manage My Pain (MMP) can be used to enhance communication between providers and patients and promote self-management. OBJECTIVE: The purpose of this study was to evaluate the real-world engagement of patients in urban and rural settings in Ontario, Canada with the MMP app alongside their standard of care and assess the impact of its usage on clinical outcomes of pain and related mental health. METHODS: A total of 246 participants with chronic pain at a rural and 2 urban pain clinics were recruited into this prospective, open-label, exploratory study that compared the use of MMP, a digital health app for pain that incorporates validated questionnaires and provides patients with summarized reports of their progress in combination with standard care (app group), against data entered on paper-based questionnaires (nonapp group). Participants completed validated questionnaires on anxiety, depression, pain catastrophizing, satisfaction, and daily opioid consumption up to 4.5 months after the initial visit (short-term follow-up) and between 4.5 and 7 months after the initial visit (long-term follow-up). Engagement and clinical outcomes were compared between participants in the two groups. RESULTS: A total of 73.6% (181/246) of the participants agreed to use the app, with 63.4% (111/175) of them using it for at least one month. Individuals who used the app rated lower anxiety (reduction in Generalized Anxiety Disorder 7-item questionnaire score by 2.10 points, 95% CI -3.96 to -0.24) at short-term follow-up and had a greater reduction in pain catastrophizing (reduction in Pain Catastrophizing Scale score by 5.23 points, 95% CI -9.55 to -0.91) at long-term follow-up relative to patients with pain who did not engage with the MMP app. CONCLUSIONS: The use of MMP by patients with chronic pain is associated with engagement and improvements in self-reported anxiety and pain catastrophizing. Further research is required to understand factors that impact continued engagement and clinical outcomes in patients with chronic pain. TRIAL REGISTRATION: ClinicalTrials.gov NCT04762329; https://clinicaltrials.gov/ct2/show/NCT04762329.

Weeding Out the Problem: The Impact of Preoperative Cannabinoid Use on Pain in the Perioperative Period.

BACKGROUND: The recreational and medical use of cannabinoids has been increasing. While most studies and reviews have focused on the role of cannabinoids in the management of acute pain, no study has examined the postoperative outcomes of surgical candidates who are on cannabinoids preoperatively. This retrospective cohort study examined the impact of preoperative cannabinoid use on postoperative pain scores and pain-related outcomes in patients undergoing major orthopedic surgery. METHODS: Outcomes of patients who had major orthopedic surgery at our hospital between April 1, 2015 and June 30, 2017 were reviewed. Data were obtained from Networked Online Processing of Acute Pain Information, a locally developed database for our Acute Pain Service. Propensity score matching was used to balance baselines variables including age, sex, type of surgery, history of depression or anxiety, and perioperative use of regional anesthesia between patients who reported use of cannabinoids and those not on this substance. Intensity of pain with movement in the early postoperative period (defined as up to 36 hours after surgery) was the primary outcome of this study. The secondary outcomes (all in early postoperative period) were pain at rest, opioid consumption, incidence of pruritus, nausea and vomiting, sedation, delirium, constipation, impairment of sleep and physical activity, patient satisfaction with analgesia, and the length of Acute Pain Service follow-up. RESULTS: A total of 3793 patients were included in the study. Of these, 155 patients were identified as being on cannabinoids for recreational or medical indications in the preoperative period. After propensity score matching, we compared data from 155 patients who were on cannabinoids and 155 patients who were not on cannabinoids. Patients who were on preoperative cannabinoids had higher pain numerical rating score (median [25th, 75th percentiles]) at rest (5.0 [3.0, 6.1] vs 3.0 [2.0, 5.5], P = .010) and with movement (8.0 [6.0, 9.0] vs 7.0 [3.5, 8.5], P = .003), and a higher incidence of moderate-to-severe pain at rest (62.3% vs 45.5%, respectively, P = .004; odds ratio, 1.98; 95% CI, 1.25-3.14) and with movement (85.7% vs 75.2% respectively, P = .021; odds ratio, 1.98; 95% CI, 1.10-3.57) in the early postoperative period compared to patients who were not on cannabinoids. There was also a higher incidence of sleep interruption in the early postoperative period for patients who used cannabinoids. CONCLUSIONS: This retrospective study with propensity-matched cohorts showed that cannabinoid use was associated with higher pain scores and a poorer quality of sleep in the early postoperative period in patients undergoing major orthopedic surgery.

Comparison of two ultrasound-guided techniques for greater occipital nerve injections in chronic migraine: a double-blind, randomized, controlled trial.

BACKGROUND AND OBJECTIVES: Two ultrasound (US)-guided techniques for greater occipital nerve (GON) block have been described for the management of headache disorders: a "proximal or central" technique targeting the GON at the level of the second cervical vertebra and a "distal or peripheral" technique targeting the GON at the level of the superior nuchal line. In this multicenter, prospective, randomized control trial, we compared accuracy, effectiveness, and safety of these two techniques in patients with chronic migraines (CMs). METHODS: Forty patients with refractory CMs were randomized to receive either a proximal or distal US-guided GON block with bupivacaine and methylprednisolone acetate. The primary outcome was the difference in Numerical Rating Score (NRS) for headache intensity at 1 month. Secondary outcomes were effectiveness, performance, and safety-related. Effectiveness-related outcomes included NRS for headache intensity, number of headache days per week, patient satisfaction, quality of life, assessment of sleep quality, and sleep interruption. Performance-related outcomes included procedure time, accuracy of block, and patient discomfort. Safety-related outcomes included an assessment for adverse effects. RESULTS: NRS pain scores were significantly reduced at 24 hours and at 1 week postprocedure in both cohorts and at 1 and 3 months in the proximal group as compared with the baseline. There was no significant difference in NRS pain scores between the two cohorts at any of the follow-up time points. There was a significant reduction in number of headache days per week at 1 month in both groups, and a significant improvement in sleep interruption at 1 week in both groups. There were no significant adverse effects. CONCLUSIONS: This study was designed to compare two different US-guided approaches for blocking the GON. Our results demonstrate that both distal and proximal techniques can provide a short-term improvement in headache intensity, reduction in number of headache days per week, and an improvement in sleep interruption. The proximal GON technique may confer more sustained analgesic benefit compared with the distal approach in patients with CM headaches. TRIAL REGISTRATION NUMBER: NCT02031822.