A Novel Research Method for Determining Sedative Exposure in Critically Ill Patients.

BACKGROUND: Although potent sedative and opioid drugs are some of the most commonly used medications to manage pain, anxiety, and discomfort in critically ill patients, conducting clinical trials where sedative and opioid medications are outcome variables within a longitudinal research design can be a methodological challenge. OBJECTIVES: The purpose of this article is to provide in detail a conceptual discussion of the concept and analysis of sedative exposure: A novel research analysis method for aggregating sedative and opioid medication doses from disparate drug classes commonly administered to critically ill patients and used by our team in several clinical research studies. METHODS: Comparing the dose of each sedative and opioid administered to an individual patient (within a defined time interval) to all other patients in a research study receiving the same medications allows for ranking of dosages for each medication by quartiles. Rank values for all sedatives and opioids received can be summed to a single value resulting in a Sedation Intensity Score. In addition, a simple count of how many hours at least one dose of a sedative or opioid medication has been administered can determine sedation frequency. RESULTS: This method can allow for comparison of sedative exposure with medications from disparate drug classes and for analysis of estimates of change in medication use over time. DISCUSSION: This novel research analysis method can overcome the challenges and limitations of determining changes in sedative and opioid medication regimens in cohort and clinical trial study designs.

Assessment of Opioid Prescribing Practices Before and After Implementation of a Health System Intervention to Reduce Opioid Overprescribing.

Importance: Overprescribing of opioids has generated and sustains the opioid overdose epidemic. Health systems have a responsibility to lead the effort to reduce overprescribing. Objective: To measure the effects of multilevel interventions on opioid prescribing within a health system. Design, Setting, and Participants: Quality improvement study comparing a 6-month preintervention baseline with a 16-month postintervention period ending in April 2018. Inpatient and outpatient clinical activity within a regional health system including an acute care hospital, same-day surgery, and outpatient clinics. Opioid prescribing activity by hundreds of clinicians involving over a million clinical encounters was measured using a health system's electronic medical record. Interventions: Multiple parallel interventions in different domains, including prescriber education and accountability, enhanced oversight via measurement of individual prescribers, tools to right-size postoperative discharge prescriptions, reduction of default amounts on standard opioid prescription orders, and professionally written patient and public education about opioid risks and alternatives. Main Outcomes and Measures: Morphine milligram equivalents (MME) per encounter per month, MME per opioid prescription, and rate of opioid prescriptions (opioid prescriptions per encounter per month). Results: More than 44 000 clinical encounters per month were recorded. All baseline trends were not significantly different from 0. Total health system MME per encounter decreased 1.0 MME per encounter per month. At the end of the postintervention observation period, the monthly MME per encounter was 58% lower than the average of the 6-month baseline, the MME per opioid prescription per month was 34% less than the average of the baseline, and the opioid prescription rate was 38% lower than the average of the baseline. Conclusions and Relevance: Opioid overprescribing was reduced with multifocal interventions targeting patient and public demand, creating prescriber awareness and accountability, and creating tools for clinical leadership accountability. The interventions described are adoptable by most organized health systems. Reducing total opioid supply within communities should be given high priority by those with a mission to protect and improve public health.

Intrathecal administration of Infumorph® vs compounded morphine for treatment of intractable pain using the Prometra® programmable pump.

OBJECTIVES: The intrathecal administration of morphine sulfate has become an established alternative to oral opiate therapy for the treatment of chronic pain. Currently, Infumorph(®) is the only morphine sulfate approved by the US Food and Drug Administration for continuous intraspinal administration with an infusion pump. However, in order to achieve and maintain adequate pain relief, patients may require concentrations outside of those commercially available products resulting in the use of compounded morphine. METHODS: Accuracy, safety, and efficacy data related to Infumorph and compounded morphine use were collected during clinical trials of a new implantable pump. This report compares those results in a total of 154 subjects implanted with the Prometra programmable pump. RESULTS: The mean drug delivery accuracy using only Infumorph in 31 subjects was 100.1% and was comparable with the accuracy reported for the 71 subjects who received only compounded morphine sulfate (97.4%). The percentage of subjects free from device-related serious adverse events (DRSAEs) was similar in both groups. Compounded morphine showed statistically significant improvements in pain and disability, where Infumorph only showed a statistical improvement in pain. Dosing was higher in the compounded group. Results are also presented for a crossover group that received both types of morphine. CONCLUSIONS: ThePrometra system accurately delivers both Infumorph and compounded morphine with no significant differences in DRSAE rates. These results indicate that compounded morphine delivery effectively treats the chronic pain patient population. Higher doses appear to provide better pain relief; however, optimal pain relief will need to be balanced against the risk of granuloma formation.

[Efficacy comparison between morphine sulfate controlled-released tablet and morphine hydrochloride sustained-released tablet in treating cancer pain].

BACKGROUND & OBJECTIVE: Morphine sulfate controlled-released tablet and morphine hydrochloride sustained-released tablet are preferred medicines for treating moderate-severe cancer pain. There are some differences between the two medicines in their efficacy, metabolism and adverse events. This study was to compare the efficacy and toxicities between morphine sulfate controlled-released tablet and morphine hydrochloride sustained-released tablet in treating moderate-severe cancer pain. METHODS: A total of 121 patients with moderate-severe cancer pain were randomized into two groups: 61 were treated with morphine sulfate controlled-released tablet and 60 were treated with morphine hydrochloride sustained-released tablet. Analgesic efficacy and toxicities of the two medicines were observed. RESULTS: Of the 61 patients treated with morphine sulfate controlled-released tablet, 12 had moderate pain, 49 had severe pain; the total response rate was 91.80%. Of the 60 patients treated with morphine hydrochloride sustained-released tablet, 13 had moderate pain, 47 had severe pain; the total response rate was 91.67%. There was no significant difference in the efficacy between the two medicines. Digestive system adverse events, including nausea, vomiting and constipation, were more common in morphine hydrochloride sustained-released tablet group than in morphine sulfate controlled-released tablet group (66.66% vs. 34.43%, P<0.05). CONCLUSIONS: Both morphine sulfate controlled-released tablet and morphine hydrochloride sustained-released tablet are safety in treating moderate-severe cancer pain and the toxicities are tolerable. We recommend to take morphine sulfate controlled-released tablet for older patients and the patients with digestive disorders.