Managing dental pain in medically compromised patients poses clinical challenges due to altered drug metabolism, systemic contraindications, and increased risk of adverse effects. Existing guidelines often lack specificity for this group, highlighting the need for a tailored approach to analgesic prescribing. This review aimed to survey the literature and propose an evidence-informed analgesic ladder for dental care in medically vulnerable patients. A comprehensive review was conducted using structured searches of PubMed, Scopus, Web of Science, and the Cochrane Library for studies published from January 2000 to May 2025. Eligible studies included randomized controlled trials (RCTs), systematic and narrative reviews, and clinical guidelines addressing dental analgesia in patients with conditions such as cardiovascular disease, renal or hepatic impairment, asthma, diabetes, and cancer. Forty-nine studies met the inclusion criteria. Findings were thematically analyzed by pain severity and patient-specific risk factors, forming the basis of a five-step analgesic ladder. The proposed ladder offers a structured framework to guide dental clinicians in selecting analgesics based on pain intensity and patient medical conditions. It incorporates stepwise recommendations accounting for common comorbidities and contraindications, with emphasis on dose adjustment, combination therapy, and selective use of adjunctive analgesics. This review presents a practical, patient-centered analgesic ladder to support safer dental pain management in medically compromised individuals. Despite the limited availability of RCTs, this framework offers an evidence-informed tool for personalized dental pain care. Further research is needed to validate the model and explore the role of adjunctive analgesia.

Stakeholder perspectives on the reduction of opioid exposure in ICU: A modified Delphi survey.

Headache management after acute brain injury (ABI) is challenging. Although opioids are commonly used, selective cyclooxygenase 2 inhibitors (COXIBs) may be promising alternatives. However, concerns about cardiovascular effects and bleeding risk have limited their use. We aimed at summarizing available data on efficacy of COXIBs for headache management following ABI. A systematic review was conducted through MEDLINE and Embase for articles published through September 2023 (PROSPERO identifier: CRD42022320453). No language filters were applied to the initial searches. Interventional or observational studies and systematic reviews assessing efficacy of COXIBs for headache in adults with ABI were eligible. Article selection was performed by two independent reviewers using DistillerSR. Descriptive statistics were used for data analysis, and meta-analysis was unfeasible because of study heterogeneity. Of 3190 articles identified, 6 studies met inclusion criteria: 4 randomized controlled trials and 2 retrospective cohort studies, all conducted in elective cranial neurosurgical patients (total N = 738) between 2006 and 2022. Five studies used COXIBs in the intervention group only. Of the six studies, four found a reduction in overall pain scores in the intervention group, whereas one showed improvement only at 6h postoperatively, and one did not find significant differences. Pain scores decreased between 4 and 15%, the largest shift being from moderate to mild severity. Three studies found an overall opioid use reduction throughout hospitalization in the intervention group, whereas one reported a reduction at 12h postoperatively only. Opioid consumption decreased between 9 and 90%. Two studies found a decrease in hospital length of stay by ~ 1day in the intervention group. The one study reporting postoperative hemorrhage found a statistically nonsignificant 3% reduction in the intervention group. COXIBs may serve as opioid-sparing adjunctive analgesics for headache control after elective cranial surgery. Limited or no literature exists for other forms of ABI, and additional safety data remain to be elucidated.

Abstract Background: Pediatric patients require pharmacological management of pain and agitation associated with mechanical ventilation. Pain and agitation may be refractory to opioids and alpha-2 agonists, prompting the use of adjunctive analgesics and sedatives with alternative mechanisms. The purpose of this study was to describe the use of phenobarbital as an adjunctive agent for refractory agitation in critically ill, mechanically ventilated pediatric patients. Subjects and Methods: This was a single-center, retrospective chart review at a pediatric intensive care unit (PICU) at a pediatric academic medical center in America between 2016 and 2021. Children aged 2 months to 18 years old were admitted to the PICU were mechanically ventilated and received phenobarbital for adjunct sedation. Sixty-three patients had phenobarbital dosing data evaluated, and the 38 patients who were not receiving continuous neuromuscular blockade were included in the primary and secondary outcome analysis of time within the goal sedation score. Descriptive statistics was used to assess baseline characteristics and the primary outcome. Wilcoxon signed-rank tests were used to evaluate secondary outcomes. Results: Patients spent significantly more time within the goal sedation score range after phenobarbital compared to before phenobarbital. The median number of rescue sedative boluses, morphine equivalents (MEs), and benzodiazepine equivalents (BZDE) significantly decreased 2 days after the first phenobarbital dose compared to the 2 days before the first phenobarbital dose. Conclusions: The use of phenobarbital as an adjunct sedative was associated with a statistically significant increase in time spent in the goal sedation score range and decrease in ME, BZDE, and concomitant sedative boluses.

Cervical spine surgery may be needed in those with refractory pain or neurologic deficits to improve outcomes in patients with cervical spine disease. However, consensus varies in the literature on the effect of surgery on opioid use. The objectives of this study were to analyze prescription rates of multiple controlled substances before and after cervical spine surgery and distinguish factors that may have contributed to opioid use after surgery. This is a retrospective cohort study analyzing prescription trends of various controlled substances in 632 patients who underwent cervical spine surgery from 2019 to 2021. Opioids have the largest rise in prescriptions at 3- and 6-mo time points after cervical spine surgery. A significant association ( P < 0.001) was found between opioid use 1 yr before and 1 yr after cervical spine surgery. Exposure to opioids before surgery (odds ratio = 2.77, 95% confidence interval = 1.43-5.51, P = 0.003) and higher morphine milligram equivalent dose (odds ratio = 1.02, 95% confidence interval =1.01-1.04, P = 0.012) were found to be associated with opioid use after surgery. Significantly more females were prescribed controlled substances ( P = 0002). Higher morphine milligram equivalent dose and opioid exposure before surgery are important factors in predicting postsurgical opioid use.

Osteoarthritis is a common condition in dogs, particularly affecting elderly individuals, and the chronic pain it causes significantly impacts the quality of life of affected dogs. First, we will focus on the joint, the physiopathology of osteoarthritis, and the mechanisms of arthritic pain production, and then discuss the existing treatments. There are numerous treatments available for managing this complex osteoarticular condition, but unconventional therapies are increasingly of interest to owners of canine species. Phytotherapy harnesses the healing properties of plants for treatment in a less toxic, more natural, and more cost-effective manner, offering a wide range of therapeutic options for animals. The objective of this review is to evaluate the present evidence backing treatments for canine osteoarthritis. This includes non-steroidal anti-inflammatory drugs, piprants, monoclonal antibodies, adjunctive analgesics, structuremodifying osteoarthritis drugs, phytotherapy, and regenerative therapies.

This prospective, randomized, double-blinded, active controlled trial assessed whether a single preoperative administration of 40 mg of duloxetine could decrease postoperative pain and numbness after posterior lumbar interbody fusion surgery (PLIF). Patients with an American Society of Anesthesiologists physical status I or II undergoing PLIF were included. At 2 hours before inducing anesthesia, patients were administered 40 mg duloxetine or 4 mg diazepam (control drug). Postoperative pain and other symptoms were evaluated on the basis of a visual analog scale, amount of fentanyl used, fentanyl dose request times, rate of use of adjunctive analgesics (diclofenac sodium or pentazocine), and lower limb numbness score (0-3) during the first 2 postoperative days. Forty-six patients were randomly assigned to the duloxetine and diazepam groups (n = 23 each); 6 were lost to follow-up, and analysis was performed on data from 22 patients in the duloxetine group and 18 in the diazepam group. No significant differences were detected in the patient background, postoperative visual analog scale score at rest in the lumbar region and lower limbs, fentanyl use, rate of analgesic adjuvant use, or incidence of side effects. The numbness score in the lower limbs, however, was significantly lower in the duloxetine group. A single preoperative 40-mg dose of duloxetine did not improve postoperative pain after PLIF, but did improve lower limb numbness. Duloxetine may suppress neuropathic pain-like symptoms after PLIF surgery.

Abstract Calcium channel blockers have been postulated as opioid adjuncts, due to their complementary mechanism of action, which may reduce pain signal transduction. The purpose of this study was to conduct a literature review regarding the safety and efficacy of calcium channel blockers alongside opioids in pain management. From August 2020 to January 2021, PubMed, Scopus, and ProQuest were searched using the following terminology: calcium channel blocker OR verapamil OR diltiazem OR amlodipine OR nicardipine OR nimodipine OR nifedipine AND analgesia. Studies included were those with adult human subjects that had reported efficacy and safety outcomes for calcium channel blocker use as opioid adjuncts. Exclusion criteria for the analysis were articles including pregnant patients, those not readily translatable to English and those detailing the use of calcium channel blockers for an alternative diagnosis or indication. Ten studies were included in this review. Five were randomised controlled trials, one involving verapamil, one addressing diltiazem, one including nifedipine and three examining nimodipine. A sixth clinical trial involving verapamil, diltiazem and nimodipine was reviewed. The seventh and final clinical trial included nimodipine or nifedipine use during aorto‐coronary bypass surgery. One conclusive study addressed nimodipine’s use in cancer patients treated with morphine and the other nifedipine’s morphine adjunct potential postoperatively. Currently, there is insufficient data to support the use of calcium channel blockers as adjuncts to opioid therapy in pain management. When compared, the studies came to varying conclusions and demonstrated conflicting data indicating the need for more research regarding this topic.

Patients undergoing surgical procedures are one of the few populations that still require substantial doses of opioid medications to provide analgesia, despite the best efforts of clinicians to integrate non-opioid adjunctive analgesics into practice. While many options exist with varying degrees of evidence, one drug class that deserves renewed consideration are muscle relaxants. Although these medications have differing mechanisms of action and require a more thorough evaluation of patient parameters prior to administration as opposed to other adjunctive analgesics, it is readily apparent by the results of this review that these agents may be able to mitigate pain and limit opioid usage. The objective of this review was to determine the efficacy and safety of adjunctive muscle relaxers for the purposes of analgesia in the perioperative setting.

Objective: To determine the efficacy and safety of second-generation antipsychotics (SGAs) as adjunctive analgesics. Data Sources: A comprehensive literature review was conducted between August 2020 and January 2021 on PubMed, Scopus, and ProQuest Central. Study Selection and Data Extraction: Keyword and Boolean phrase searches using the following terminology were conducted: "Quetiapine" OR "Risperidone" OR "Olanzapine" OR "Ziprasidone" AND "Analgesia" NOT "Psychosis" NOT "Psych." Articles that involved human adult patients who received any of the SGAs mentioned in the searching filter with an opioid were included. Articles that described pediatrics, pregnant women, patients who received any of these agents for treatment of psychosis and articles that were not in English, or readily translatable to English, were excluded. Data Synthesis: Three articles were selected for inclusion in this review, with 2 articles detailing reports with olanzapine and 1 article describing a randomized, controlled trial with extended-release quetiapine. Both olanzapine and quetiapine were able to decrease pain scores on the numeric rating scale, indicating a reduction pain experienced, and additionally reduced opioid craving behavior in patients. Depression scores and quality-of-life indicators improved with quetiapine, though those metrics were not studied with olanzapine. Conclusions: Select SGAs, specifically extended-release quetiapine and olanzapine, may serve as an appropriate adjunctive analgesic choice in select patients. Further research is required in a clinical setting to determine the exact role of this drug class in pain management.

Abstract Introduction Large quantities of analgesics are prescribed to control pain among patients with burn injuries and may lead to chronic use and dependency. This study aimed to determine whether patients are overprescribed analgesics at discharge and to identify factors that influence prescribing patterns. Methods A retrospective review of patient charts (n = 199) between July 1, 2015 - 2018 were reviewed from a registry at a single burn center. Opioid, neuropathic pain agent (NPAs), acetaminophen, and ibuprofen quantities given before and at discharge were compared. Linear mixed regression models were used to identify factors that increased the amount of analgesics prescribed among burn care providers. Results On average, patients were prescribed significantly more analgesics at discharge compared to what was consumed pre-discharge (p &amp;lt; 0.0001). Specifically, on average, providers did not overprescribe the daily dose of analgesics, but overprescribed the duration of pain medications required. For every increase in percent TBSA, 14 MEQ more opioids, 203 mg more NPAs, 843 mg more acetaminophen, and 126 mg more ibuprofen were prescribed (p &amp;lt; 0.05). Surgery was a predictor for higher opioid and NPA prescriptions (p = 0.03), while length of stay was associated with fewer NPAs prescribed (p = 0.04). Fewer ibuprofen were given to patients with a history of substance misuse (p = 0.01). Conclusions The quantity of analgesics prescribed at discharge varied widely and often prescribed for long durations of time. Standardized prescribing guidelines should be developed to optimize how analgesics are prescribed at discharge.

Abstract The pursuit of ideal multi‐modal analgesic strategies remains ongoing, though the use of select antiepileptic drugs as adjunctive analgesics to opioids has been previously studied and postulated to have varying degrees of success. The objective of this review was to determine the efficacy and safety of select antiepileptic drugs as adjunctive analgesics in an update to a previously published Cochrane review on the subject in 2013. A comprehensive literature review was conducted using PubMed, MEDLINE, Scopus, and Web of Science between January 2013–August 2020 using: “carbamazepine” OR “oxcarbazepine” OR “lacosamide” AND “analgesia”. The use of one of the study drugs as an adjunctive analgesic to opioids was included. Thirty‐five articles were identified through database inquiries, though only two reports met inclusion criteria, with one focusing on carbamazepine and one focusing on oxcarbazepine. No articles detailing lacosamide in accordance with the scope of this review were identified. Both carbamazepine and oxcarbazepine demonstrated safety and efficacy as adjunctive analgesics across numerous indications, including postoperative neuropathies and neuropathies associated with spinal cord injuries. While the search for a universal or definitive multi‐modal pain management regimen remains elusive, carbamazepine and oxcarbazepine have demonstrated clinical utility in pain syndromes beyond their historic relegation to trigeminal neuralgia. Limited evaluation and data has been derived regarding the use of carbamazepine, oxcarbazepine, and lacosamide since the previous Cochrane review in 2013. The results of this review solidify the need for continued future investigation. Additional data is necessary to define the role of lacosamide for this indication.

Prescribing patterns of opioids and adjunctive analgesics for patients with burn injuries

Background: Health care providers routinely rely on tertiary drug information resources to affirm knowledge or proactively verify the safety and efficacy of medications. Though all patient care areas are affected, the reliability of these resources is perhaps nowhere as poignant as it is in high-acuity settings, including the emergency department and the intensive care unit. As providers seek to identify adjunctive analgesics for acute pain in these areas, they must be able to rely on the integrity to whichever resource their institution has granted access. Objective: To determine the congruency of drug-drug interaction information found on 3 tertiary drug resources. Methods: A drug-drug interaction analysis was conducted on Micromedex, Lexicomp, and Medscape. Adjunctive analgesics included dexmedetomidine and ketamine, which were compared with the intravenous opioid products morphine, fentanyl, and hydromorphone. Results: Significant discrepancies were appreciated with regard to the severity of drug-drug interactions. In addition, the heterogeneity in which reaction severity and likelihood are described by each respective resource makes direct comparisons difficult. Interaction warnings for dexmedetomidine and fentanyl included a "major interaction" from Micromedex, whereas Lexicomp did not identify a risk and Medscape only recommended increased monitoring on the grounds of respiratory and central nervous system depression. Conclusions: Health care providers must remain vigilant when reviewing tertiary drug information resources. Pharmacists possess the training and skills necessary to assist interdisciplinary medical teams in providing optimal patient care through evaluating and applying the information gleaned from these resources.

Abstract Background: Dinutuximab is a chimeric anti-GD-2 (disialoganglioside) antibody approved for use in post-consolidation care of patients with high-risk neuroblastoma. GD-2 receptors are also expressed in cerebellar neurons, melanocytes, and peripheral sensory nerve fibers in normal human tissue. Given this pattern of expression, pain is a common and often infusion rate-limiting adverse effect, with greater than 50% of patients experiencing severe (Grade 3 or above) pain. Standard pain management for dinutuximab infusions at our center includes initiation of continuous infusion of opioid patient-controlled analgesia along with demand, loading, and boluses doses. Little to no data exist in the literature to describe opioid use in pediatric patients with acute, episodic pain. Therefore, this study aims to characterize opioid use in this setting. Methods: Data were collected retrospectively from the electronic medical record under a study protocol approved by the Institutional Review Board at the University of Michigan, C.S. Mott Children's Hospital. Patients were included in the study if they had a clinical diagnosis of metastatic or relapsed high-risk neuroblastoma, received at least one dinutuximab cycle, and were aged 2-14 at the time of admission. Daily amount of opioids, calculated as the oral morphine equivalent daily dose (MEDD), acetaminophen, and gabapentin administered were calculated. Repeated measures ANOVA was used to evaluate within-subjects changes. Results: The average age of patients was 5.7 years [range 2-14 years]. Four of eleven (36.4%) were female and 7/11 (63.6%) were male. All patients received four days of dinutuximab infusions for an average length of 11.8 hours (SD=2.0) per day. All patients received gabapentin prophylactic treatment and an average of 3387 mg (SD=1275.5). Average total MEDD across all patients was 184.7 mg (SD=137.6) during the inpatient hospitalization. Females (p=0.003) and older patients (p=0.04) had significantly increased daily MEDD as compared to their day 1 intake. All patients experienced a fever spike and received acetaminophen (2915 mg, SD=1737.8) Older patients received higher doses of acetaminophen (p=0.007) Only 1 patient met definition of a chronic opioid user and was discharged with an outpatient opioid prescription. The remaining opioid-naïve patients were discontinued on opioid treatment at the time of discharge. Conclusions: Pediatric patients on dinutuximab therapy received a high MEDD parenteral opioids dose alongside adjunctive analgesics. Future studies are needed to determine opioid requirement trends across gender, age, and cycles in a larger cohort of patients, as well as to determine the risk of chronic opioid use in this patient population. Citation Format: Jola Mehmeti, Jae Eun Choi, Ian Wolfe, Juan Cata, Rajen Mody. Characterization of inpatient opioid use among pediatric neuroblastoma patients during dinutuximab therapy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2045.

We searched PubMed, Embase, the Cochrane Library, CINAHL Plus, and Web of Science. Two independent reviewers screened citations. Eligible studies included randomized controlled trials comparing efficacy and safety of an adjuvant-plus-opioid regimen to opioids alone in adult ICU patients. We conducted duplicate screening of citations and data abstraction. Of 10,949 initial citations, we identified 34 eligible trials. These trials examined acetaminophen, carbamazepine, clonidine, dexmedetomidine, gabapentin, ketamine, magnesium sulfate, nefopam, nonsteroidal anti-inflammatory drugs (including diclofenac, indomethacin, and ketoprofen), pregabalin, and tramadol as adjunctive analgesics. Use of any adjuvant in addition to an opioid as compared to an opioid alone led to reductions in patient-reported pain scores at 24 hours (standard mean difference, -0.88; 95% CI, -1.29 to -0.47; low certainty) and decreased opioid consumption (in oral morphine equivalents over 24 hr; mean difference, 25.89 mg less; 95% CI, 19.97-31.81 mg less; low certainty). In terms of individual medications, reductions in opioid use were demonstrated with acetaminophen (mean difference, 36.17 mg less; 95% CI, 7.86-64.47 mg less; low certainty), carbamazepine (mean difference, 54.69 mg less; 95% CI, 40.39-to 68.99 mg less; moderate certainty), dexmedetomidine (mean difference, 10.21 mg less; 95% CI, 1.06-19.37 mg less; low certainty), ketamine (mean difference, 36.81 mg less; 95% CI, 27.32-46.30 mg less; low certainty), nefopam (mean difference, 70.89 mg less; 95% CI, 64.46-77.32 mg less; low certainty), nonsteroidal anti-inflammatory drugs (mean difference, 11.07 mg less; 95% CI, 2.7-19.44 mg less; low certainty), and tramadol (mean difference, 22.14 mg less; 95% CI, 6.67-37.61 mg less; moderate certainty). Clinicians should consider using adjunct agents to limit opioid exposure and improve pain scores in critically ill patients.

Our aim was to give an overview of the effectiveness of adjunctive analgesics in head and neck cancer (HNC) patients receiving (chemo-) radiotherapy. Systematic review. This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Embase, Web of Science, the Cochrane Library, and ClinicalTrials.gov were searched for studies concerning "head neck cancer," "adjunctive analgesics," "pain," and "radiotherapy." Pain outcome, adverse events, and toxicity and other reported outcomes, for example, mucositis, quality of life, depression, etc. Nine studies were included in our synthesis. Most studies were of low quality and had a high risk of bias on several domains of the Cochrane Collaboration tool. Only two studies comprised high-quality randomized controlled trials in which pregabalin and a doxepin rinse showed their effectiveness for the treatment of neuropathic pain and pain from oral mucositis, respectively, in HNC patients receiving (chemo-) radiotherapy. More high-quality trials are necessary to provide clear evidence on the effectiveness of adjunctive analgesics in the treatment of HNC (chemo-) radiation-induced pain.

Benefit of subcutaneous patient controlled analgesia after total knee arthroplasty

Perioperative implications of common and newer psychotropic medications used in clinical practice.

Results of an interprofessional formulary initiative to decrease postoperative prescribing of i.v. acetaminophen are reported. After a medical center added i.v. acetaminophen to its formulary, increased prescribing of the i.v. formulation and a 3-fold price increase resulted in monthly spending of more than $40,000, prompting an organizationwide effort to curtail that cost while maintaining effective pain management. The surgery, anesthesia, and pharmacy departments applied the Institute for Healthcare Improvement's Model for Improvement to implement (1) pharmacist-led enforcement of prescribing restrictions, (2) retrospective evaluation of i.v. acetaminophen's impact on rates of opioid-related adverse effects, (3) restriction of prescribing of the drug to 1 postoperative dose on select patient care services, and (4) guideline-driven pain management according to an enhanced recovery after surgery (ERAS) protocol. Monitored metrics included the monthly i.v. acetaminophen prescribing rate, the proportion of i.v. acetaminophen orders requiring pharmacist intervention to enforce prescribing restrictions, and prescribing rates for select adjunctive analgesics. Within a year of project implementation, the mean monthly i.v. acetaminophen prescribing rate decreased by 83% from baseline to about 6 doses per 100 patient-days, with a decline in the monthly drug cost to about $4,000. Documented pharmacist interventions increased 2.7-fold, and use of oral acetaminophen, ketorolac, and gabapentin in ERAS areas increased by 18% overall. An interprofessional initiative at a large medical center reduced postoperative use of i.v. acetaminophen by more than 80% and yielded over $400,000 in annual cost savings.