Intravenous Ketamine for Cancer Pain: A Single-Center Retrospective Analysis Comparing Fixed-Rate Versus Weight-Based Dosing.

Although weak evidence exists to support subanesthetic ketamine for cancer pain treatment, successful use may be hindered in the absence of standardized dosing guidance. We aimed to compare the success rates of intravenous ketamine fixed-rate versus weight-based dosing strategies for cancer pain treatment, and to assess patient characteristics that correlate with treatment success. We conducted a single-center retrospective review including non-critically ill adults with cancer pain who received subanesthetic ketamine for at least 24-h. All patients received fixed-rate ketamine; weight-based doses were retrospectively determined using total body weight. Treatment was considered successful if after reaching the maximum prescribed ketamine dose the patient had a 30% reduction in: baseline pain score, as-needed opioid use, or total morphine equivalent daily dose over a standardized 24-h. Of 105 included patients, 51 (48.6%) successfully responded to ketamine. Responders had lower fixed-rate ketamine doses compared to non-responders (median[IQR] 15 mg/hr[10-15] vs. 15 mg/hr[15-20], p = 0.043), but no difference in retrospectively calculated weight-based doses (0.201 ± 0.09 mg/kg/hr vs. 0.209 ± 0.08 mg/kg/hr, p = 0.59). Responders had higher daily opioid requirements at baseline compared to non-responders (p = 0.04). Though underpowered, our findings suggest that weight-based ketamine dosing may not convey additional benefit over fixed-rate dosing.

Risk Factors for the Development of Neuropsychiatric Adverse Effects in Ketamine-Treated Pain.

Ketamine use has increased recently for the management of acute and chronic pain. Ketamine can cause a variety of neuropsychiatric adverse effects, such as hallucinations, dysphoria, and nightmares. The objective of this study was to explore risk factors for the development of neuropsychiatric adverse effects in ketamine-treated pain. This was a retrospective, single-center cohort study of hospitalized patients who received low dose intravenous (IV) ketamine or oral ketamine for pain. Patients who had a neuropsychiatric adverse effect were compared to those who did not. One hundred and seventy-one patients were included, with 155 receiving IV ketamine and 16 receiving oral ketamine. Overall, 50 (29.2%) had a neuropsychiatric adverse effect and 26 (15.2%) required treatment discontinuation. No significant differences were found between patients who tolerated ketamine and those who did not. Patients who had an adverse effect were numerically less likely to receive benzodiazepines (28% vs 39.7%, p = 0.153), as were patients who required discontinuation of ketamine (23.1% vs. 41.4%, p = 0.08). In patients receiving ketamine for pain, predicting who may be more likely to experience neuropsychiatric adverse effects remains difficult. Further research is warranted to determine whether benzodiazepines are safe and effective for mitigating these adverse effects in this setting.

Buprenorphine initiation strategies for opioid use disorder and pain management: A systematic review.

Buprenorphine possesses many unique attributes that make it a practical agent for adults and adolescents with opioid use disorder (OUD) and/or acute or chronic pain. Sublingual buprenorphine has been the standard of care for treating OUD, but its use in pain management is not as clearly defined. Current practice guidelines recommend a period of mild-to-moderate withdrawal from opioids before transitioning to buprenorphine due to its ability to displace full agonists from the µ-opioid receptor. However, this strategy can lead to negative physical and psychological outcomes for patients. Novel initiation strategies suggest that concomitant administration of small doses of buprenorphine with opioids can avoid the unwanted withdrawal associated with buprenorphine initiation. We aim to systematically review the buprenorphine initiation strategies that have emerged in the last decade. Embase, PubMed, and Cochrane Databases were searched for relevant literature. Studies were included if they were published in the English language and described the transition to buprenorphine from opioids. Data were collected from each study and synthesized using descriptive statistics. This review included 7 observational studies, 1 feasibility study, and 39 case reports/series which included 924 patients. The strategies utilized between the literature included traditional initiation (47.9%), microdosing with various buprenorphine formulations (16%), and miscellaneous methods (36.1%). Traditional initiation and microdosing initiation were compared in the data synthesis and analysis; miscellaneous methods were omitted given the high variability between methods. Overall, 95.6% of patients in the traditional initiation group and 96% of patients in the microdosing group successfully rotated to sublingual buprenorphine. Initiation regimens can vary widely depending on patient-specific factors and buprenorphine formulation. A variety of buprenorphine transition strategies are published in the literature, many of which were effective for patients with OUD, pain, or both.

Buprenorphine Microdosing for the Pain and Palliative Care Clinician.

Buprenorphine (BUP) can be a safe and effective alternative to traditional opioids for many patients with chronic pain. For patients on higher doses of opioids, rotation to BUP is complicated by the requirement of an opioid-free interval or withdrawal during the transition. Microdosing inductions, in which BUP is gradually titrated, while full agonist opioids are continued, are a viable alternative to traditional inductions. The objective of this article is to review the current literature on BUP microdosing induction, with a focus on patients using opioids for pain. A literature review of the PubMed database was performed in the United States on articles published from inception to May 2021. A total of 34 publications were included. The most commonly utilized microdosing strategy involved administering divided doses of sublingual (SL) products marketed for opioid use disorder treatment, with 25 (73.5%) articles reporting use of partial SL tablets or films (ranging from 1/8 to 1/2 of a 2 mg product) at some point during the induction. Transdermal patches, low-dose SL BUP available in Europe, intravenous BUP, and buccal BUP have also been used. Beyond the products used, the speed of the microinduction, setting, final BUP dosing, and management of concomitant full agonists vary widely in the literature. Microdosing regimens should be individualized based on local guidelines and patient-specific factors. Further studies comparing the safety and efficacy of different protocols are warranted.

Strategies for Rotation between Gabapentinoids in the Inpatient Setting.

Guidance and evidence to support best practices in rotating between gabapentinoids is lacking. This retrospective cohort study was performed to describe and evaluate strategies for rotation. Patients rotated while admitted from June 1st, 2014 to April 25th, 2020 at a large, academic medical center were included. The primary outcome was the proportion of rotations using a direct switch strategy compared to a cross-taper strategy. Secondary outcomes were successful rotation, defined as stable or improved pain scores pre- to post-rotation, dose ratios, and adverse effects. A total of 67 patients were included. Median age was 50 years (35 - 59) and 58% (38) were male. The majority used a direct switch strategy (87%). Ninety-five percent of patients using the direct switch strategy and 78% of patients using the cross-taper strategy were successful. There was no difference in strategies between those who were successful and those who were not. Post hoc analysis of patients with normal renal function (eGFR ≥ 50 mL/min/1.73 m2) found that those who were successful were more likely to have used a direct switch strategy (p = 0.048). There were no differences in adverse effects. These findings suggest that either strategy is reasonable for gabapentinoid rotation in the inpatient setting.

Acetaminophen in Patients Receiving Strong Opioids for Cancer Pain.

The mainstay of treatment in advanced cancer pain is opioids; however, non-opioid medications such as acetaminophen continue to be included in guidelines despite a lack of clear, convincing evidence for their use. The aim of our study was to determine if acetaminophen improves pain control or reduces opioid utilization in hospitalized patients receiving strong opioids for cancer pain managed by the palliative care consult service (PCCS). We carried out at single-center retrospective cohort study of 194 adult cancer patients seen by the PCCS and who received strong opioids. Patients who received acetaminophen during their admission were compared to those who did not. The primary outcome was a 30% reduction in average daily pain score from admission to discharge using a numeric rating scale. There was no difference between groups in achieving a 30% reduction in pain (35.8% vs. 35.4%, adjusted odds ratio 0.87, 95% confidence interval [CI] 0.46 to 1.63). Acetaminophen was associated with a longer LOS (8 days vs. 6 days, adjusted relative risk 1.67, 95% CI 1.30 to 2.15). In this study of cancer patients receiving strong opioids, acetaminophen use was not associated with improved pain control or reduced opioid utilization, but was associated with a greater LOS.

Sublingual Buprenorphine for Pediatric Cancer Pain: A Case Report and Review of the Literature.

Pain is a common symptom in pediatric patients with cancer, and most patients in palliative care will receive opioids. Traditional opioids have several drawbacks, including their adverse effects, inconsistent or diminishing efficacy, and limited available routes of administration. Buprenorphine is an attractive option for pain management because of its safety profile, unique pharmacology, and availability in transdermal, buccal, parenteral, and sublingual (SL) dosage forms. Unfortunately, data supporting the use of buprenorphine in pediatric pain patients, particularly SL buprenorphine, are lacking. This case report describes the feasibility of SL buprenorphine use in pediatric patients with complex cancer-related pain.

Comparing Methadone Rotation to Consensus Opinion.

CONTEXT: Methadone is a complex but useful medication for pain management in palliative care. Recent expert opinions have been published on the safe and effective use of methadone. OBJECTIVES: To determine the success of methadone rotations and evaluate concordance with consensus recommendations by a palliative care consult service. METHODS: A retrospective study of methadone rotation practice by a palliative care consult service and outcomes for patients hospitalized between January 1, 2012 and December 31, 2018 at a single academic medical center. A successful rotation was defined as a 30% reduction in pain or as-needed medication use sustained for at least three consecutive days. Patient outcomes were compared with expert consensus recommendations. RESULTS: About 59 patients met the inclusion criteria. The study population was mostly Caucasian men and women of equal proportions who were started on methadone for inadequate pain control. Sixty-eight percent of patients were successfully rotated. Subjects who were rotated using a standardized protocol were six times more likely to have a successful rotation (odds ratio 6.28 [1.25-30.92]; P = 0.0238). CONCLUSION: The utilization of a standardized protocol was associated with better patient outcomes.