Opioid Dose Requirements Research Articles

Effect of Neuromuscular Blockade Reversal on Postoperative Gastrointestinal Motility after Laparoscopic Cholecystectomy: Neostigmine / Atropine versus Sugammadex.

To compare sugammadex with neostigmine / atropine combination for reversal of neuromuscular blocker agents in terms of postoperative gastrointestinal motility in patients who underwent laparoscopic cholecystectomy. Experimental study. Place and Duration of the Study: University of Health Sciences, Izmir Bozyaka Training and Research Hospital, Izmir, Turkiye, between December 2020 and June 2021. Seventy-two patients undergoing laparoscopic cholecystectomy were included. At the end of the surgery, patients were antagonised for neuromuscular blockers either by atropine / neostigmine or sugammadex by an anaesthesiologist who was not involved in the study. Total anaesthesia time, pneumoperitoneum time, surgery time, number of postoperative opioid dose requirements and total opioid dose administered, number of medication requirements for postoperative nausea and vomiting, postoperative hospital stay, and first gas and stool output time of all the cases were evaluated by the researcher who was unaware of the medicines used for antagonisation. There were no statistically significant differences between the two groups in terms of their effects on postoperative gastrointestinal motility (first gas and stool output time), duration of anaesthesia, duration of surgery, duration of pneumoperitoneum, the number of postoperative opioid dose requirements, the number of drug requirements for postoperative nausea / vomiting, and the postoperative hospitalisation duration of the cases. Effects of reversal agents on postoperative gastrointestinal motility are still debated. Studies on this subject in the literature are both limited in number and have been conducted with different medicine combinations in a wide variety of patient populations. The authors thought that further prospective randomised studies are needed to interpret this effect more clearly. Sugammadex, Neostigmine / atropine, Gastrointestinal motility, Laparoscopic cholecystectomy.

Postoperative pain management using an intravenous combination of ibuprofen and acetaminophen compared with acetaminophen alone after thyroidectomy: A prospective randomized controlled trial.

Multiple medications are more effective than single agents for postoperative pain management. We investigated the analgesic effects of an intravenous combination of acetaminophen and ibuprofen immediately after thyroidectomy. In this double-blind clinical trial, 62 patients who underwent thyroidectomies were randomized to either the treatment (1000 mg acetaminophen, 300 mg ibuprofen) or control (1000 mg acetaminophen) group. Postoperative pain intensity was assessed using the visual analog scale (VAS) 0, 15, and 30 min after recovery room admission. Opioid rescue consumption was also recorded. The VAS scores were significantly lower in the treatment than in the control group 15 [3 (2-4.3) vs. 5 (3-6); p = 0.015] and 30 [3 (2-4.3) vs. 4 (3-5); p = 0.018] min after recovery room admission, as were the opioid rescue dose requirements (p = 0.033). Combined intravenous acetaminophen and ibuprofen may be better than acetaminophen alone for immediately acute postoperative pain after thyroidectomy.

The effects of OPRM1 118A>G on methadone response in pain management in advanced cancer at end of life

Cancer pain is the most feared symptom at end of life. Methadone has advantages over other opioids but is associated with significant variability in clinical response, making dosing challenging in practice. OPRM1 is the most studied pharmacogene associated with the pharmacodynamics of opioids, however reports on the association of the A118G polymorphism on opioid dose requirements are conflicting, with no reports including methadone as the primary intervention. This association study on OPRM1 A118G and response to methadone for pain management, includes a review of this genetic factor’s role in inter-patient variability. Fifty-four adult patients with advanced cancer were recruited in a prospective, multi-centre, open label dose individualization study. Patient characteristics were not shown to influence methadone response, and no significant associations were observed for methadone dose or pain score. The findings of our review of association studies for OPRM1 A118G in advanced cancer pain demonstrate the importance of taking ancestry into account. While our sample size was small, our results were consistent with European populations, but in contrast to studies in Chinese patients, where carriers of the A118G polymorphism were associated with higher opioid dose requirements. Pharmacogenetic studies in palliative care are challenging, continued contribution will support future genotype-based drug dosing guidelines.

Association Between Postoperative Methocarbamol and Postoperative Pain Opioid Dose Requirements: A Retrospective Cohort Study.

We tested the hypothesis that patients who received methocarbamol postoperatively experience less severe pain and require smaller doses of opioids than those who did not receive methocarbamol. This is a retrospective cohort study of patients undergoing surgery involving the musculoskeletal system. Of 9089 patients, 704 received methocarbamol during 48 hours postoperatively, while 8385 did not receive methocarbamol. The patients who received methocarbamol postoperatively and the patients who did not receive methocarbamol were compared on the time-weighted average (TWA) pain score and opioid dose requirements in morphine milligram equivalents (MME) during the first 48 hours postoperatively, using propensity score-weighted regression models to adjusting for preoperative and intraoperative covariates. Postoperative 48-hour TWA pain scores were 5.5±1.7 (mean±SD), and 4.3±2.1 for methocarbamol and non-methocarbamol patients. Postoperative 48-hour opioid dose requirements in MME were 276 [170-347] (median [interquartile range (IQR)]) mg, and 190 [60-248] mg for methocarbamol and non-methocarbamol patients. In propensity score-weighted regression models, receiving methocarbamol postoperatively was associated with 0.97-point higher postoperative TWA pain score (95% CI, 0.83-1.11; P <0.001), and 93.6-MME higher postoperative opioid dose requirements (95% CI, 79.9 to 107.4; P <0.001), compared with not receiving methocarbamol postoperatively. Postoperative methocarbamol was associated with significantly higher acute postoperative pain burden and opioid dose requirements. Although the results of the study are influenced by residual confounding, they suggest a limited-if any-benefit of methocarbamol as an adjunct of postoperative pain management.

Sex Differences in Opioid Response Linked to OPRM1 and COMT genes DNA Methylation/Genotypes Changes in Patients with Chronic Pain.

Analgesic-response variability in chronic noncancer pain (CNCP) has been reported due to several biological and environmental factors. This study was undertaken to explore sex differences linked to OPRM1 and COMT DNA methylation changes and genetic variants in analgesic response. A retrospective study with 250 real-world CNCP outpatients was performed in which data from demographic, clinical, and pharmacological variables were collected. DNA methylation levels (CpG island) were evaluated by pyrosequencing, and their interaction with the OPRM1 (A118G) and COMT (G472A) gene polymorphisms was studied. A priori-planned statistical analyses were conducted to compare responses between females and males. Sex-differential OPRM1 DNA methylation was observed to be linked to lower opioid use disorder (OUD) cases for females (p = 0.006). Patients with lower OPRM1 DNA methylation and the presence of the mutant G-allele reduced opioid dose requirements (p = 0.001), equal for both sexes. Moreover, COMT DNA methylation levels were negatively related to pain relief (p = 0.020), quality of life (p = 0.046), and some adverse events (probability > 90%) such as constipation, insomnia, or nervousness. Females were, significantly, 5 years older with high anxiety levels and a different side-effects distribution than males. The analyses demonstrated significant differences between females and males related to OPRM1 signalling efficiency and OUD, with a genetic-epigenetic interaction in opioid requirements. These findings support the importance of sex as a biological variable to be factored into chronic pain-management studies.

Genetic Polymorphisms of ENPP2 Are Possibly Associated with Pain Severity and Opioid Dose Requirements in Patients with Inflammatory Pain Conditions: Clinical Observation Study.

Autotaxin, encoded by the ENPP2 gene, is a known key element of neuropathic pain; however, its involvement in nociceptive pain processing remains unclear. We explored the associations between postoperative pain intensity, 24-h postoperative opioid dose requirements, and 93 ENNP2-gene single-nucleotide polymorphisms (SNPs) in 362 healthy patients who underwent cosmetic surgery using the dominant, recessive, and genotypic models. Next, we validated the associations between relevant SNPs on the one hand and pain intensity and daily opioid dosages on the other in 89 patients with cancer-related pain. In this validation study, a Bonferroni correction for multiplicity was applied on all relevant SNPs of the ENPP2 gene and their respective models. In the exploratory study, three models of two SNPs (rs7832704 and rs2249015) were significantly associated with postoperative opioid doses, although the postoperative pain intensity was comparable. In the validation study, the three models of the two SNPs were also significantly associated with cancer pain intensity (p < 0.017). Patients with a minor allele homozygosity complained of more severe pain compared with patients with other genotypes when using comparable daily opioid doses. Our findings might suggest that autotaxin is associated with nociceptive pain processing and the regulation of opioid requirements.

Evidence Regarding Pharmacogenetics in Pain Management and Cancer.

Patients experience interindividual variation in response to analgesics, which may be partially explained by genetics. This commentary discusses a recently published trial on COMT genotype and opioid dose requirements and describes the potential role for COMT and other genes (eg, CYP2D6) on opioid therapy and the current evidence for germline pharmacogenetics and resources for opioid pharmacogenetics.

Pharmacogenomics of Cancer Pain Treatment Outcomes in Asian Populations: A Review

In advanced cancer, pain is a poor prognostic factor, significantly impacting patients' quality of life. It has been shown that up to 30% of cancer patients in Southeast Asian countries may receive inadequate analgesia from opioid therapy. This significant under-management of cancer pain is largely due to the inter-individual variability in opioid dosage and relative efficacy of available opioids, leading to unpredictable clinical responses to opioid treatment. Single nucleotide polymorphisms (SNPs) cause the variability in opioid treatment outcomes, yet their association in Asian populations remains unclear. Therefore, this review aimed to evaluate the association of SNPs with variability in opioid treatment responses in Asian populations. A literature search was conducted in Medline and Embase databases and included primary studies investigating the association of SNPs in opioid treatment outcomes, namely pharmacokinetics, opioid dose requirements, and pain control among Asian cancer patients. The results show that CYP2D6*10 has the most clinical relevance in tramadol treatment. Other SNPs such as rs7439366 (UGT2B7), rs1641025 (ABAT) and rs1718125 (P2RX7) though significant have limited pharmacogenetic implications due to insufficient evidence. OPRM1 rs1799971, COMT rs4680 and ABCB1 (rs1045642, rs1128503, and rs2032582) need to be further explored in future for relevance in Asian populations.

Opioid-sparing effect of cannabinoids for analgesia: an updated systematic review and meta-analysis of preclinical and clinical studies

Cannabinoid co-administration may enable reduced opioid doses for analgesia. This updated systematic review on the opioid-sparing effects of cannabinoids considered preclinical and clinical studies where the outcome was analgesia or opioid dose requirements. We searched Scopus, Cochrane Central Registry of Controlled Trials, Medline, and Embase (2016 onwards). Ninety-two studies met the search criteria including 15 ongoing trials. Meta-analysis of seven preclinical studies found the median effective dose (ED50) of morphine administered with delta-9-tetrahydrocannabinol was 3.5 times lower (95% CI 2.04, 6.03) than the ED50 of morphine alone. Six preclinical studies found no evidence of increased opioid abuse liability with cannabinoid administration. Of five healthy-volunteer experimental pain studies, two found increased pain, two found decreased pain and one found reduced pain bothersomeness with cannabinoid administration; three demonstrated that cannabinoid co-administration may increase opioid abuse liability. Three randomized controlled trials (RCTs) found no evidence of opioid-sparing effects of cannabinoids in acute pain. Meta-analysis of four RCTs in patients with cancer pain found no effect of cannabinoid administration on opioid dose (mean difference −3.8 mg, 95% CI −10.97, 3.37) or percentage change in pain scores (mean difference 1.84, 95% CI −2.05, 5.72); five studies found more adverse events with cannabinoids compared with placebo (risk ratio 1.13, 95% CI 1.03, 1.24). Of five controlled chronic non-cancer pain trials; one low-quality study with no control arm, and one single-dose study reported reduced pain scores with cannabinoids. Three RCTs found no treatment effect of dronabinol. Meta-analyses of observational studies found 39% reported opioid cessation (95% CI 0.15, 0.64, I2 95.5%, eight studies), and 85% reported reduction (95% CI 0.64, 0.99, I2 92.8%, seven studies). In summary, preclinical and observational studies demonstrate the potential opioid-sparing effects of cannabinoids in the context of analgesia, in contrast to higher-quality RCTs that did not provide evidence of opioid-sparing effects.

STOP Pain Project-Opioid Response in Pediatric Cancer Patients and Gene Polymorphisms of Cytokine Pathways.

Moderate to severe cancer pain treatment in children is based on the use of weak and strong opioids. Pharmacogenetics play a central role in developing personalized pain therapies, as well as avoiding treatment failure and/or intolerable adverse drug reactions. This observational study aimed to investigate the association between IL-6, IL-8, and TNFα genetic single nucleotide polymorphisms (SNPs) and response to opioid therapy in a cohort of pediatric cancer patients. Pain intensity before treatment (PIt0) significantly differed according to IL-6 rs1800797 SNP, with a higher PI for A/G and G/G individuals (p = 0.017), who required a higher dose of opioids (p = 0.047). Moreover, compared to G/G subjects, heterozygous or homozygous individuals for the A allele of IL-6 rs1800797 SNP had a lower risk of having a PIt0 > 4. Dose24h and Dosetot were both higher in G/G individuals for TNFα rs1800629 (p = 0.010 and p = 0.031, respectively), while risk of having a PIt0 > 4 and a ∆VAS > 2 was higher for G/G subjects for IL-6 rs1800795 SNP compared to carriers of the C allele. No statistically significant association between genotypes and safety outcomes was found. Thus, IL-6 and TNFα SNPs could be potential markers of baseline pain intensity and opioid dose requirements in pediatric cancer patients.

Comparison Between Preoperative Methadone and Buprenorphine Use on Postoperative Opioid Requirement: A Retrospective Cohort Study.

Buprenorphine is a partial agonist at mu-opioid receptors and competes for these receptors with other opioids in vitro. Whether patients on buprenorphine maintenance require high doses of opioid analgesics to attain adequate postoperative pain control has not been determined. We evaluated differences in acute postoperative opioid consumption and pain burden between patients taking buprenorphine and those taking methadone preoperatively. A retrospective review of medical records of 928 patients, of whom 195 were on buprenorphine and 733 were on methadone preoperatively, was performed. Among methadone and buprenorphine patients, 615 and 89, respectively, continued to receive the medications postoperatively. Buprenorphine patients were compared with methadone patients for the first 48 hours postoperatively with regard to acute opioid dose requirements (morphine milligram equivalents [MME] above their baseline buprenorphine and methadone doses) and time-weighted average (TWA) pain scores (using targeted maximum likelihood estimation). Opioid dose requirements for 48 hours postoperatively were 150 (22 to 297) (median [interquartile range]) and 220 [90 to 360] MME for buprenorphine and methadone patients, respectively. Preoperative buprenorphine was associated with a 59.9% lower postoperative MME (95% confidence interval: 46.6%-69.8%, P<0.0001) compared with methadone. Postoperative TWA pain scores for the first 48 hours were 5.0±2.7 (mean±SD), and 5.4±2.3 for buprenorphine and methadone patients, respectively. Preoperative buprenorphine was associated with a 0.37-point lower TWA pain score (95% confidence interval: 0.14-0.61, P=0.002) compared with methadone. Preoperative buprenorphine use was associated with >50% reduction in postoperative opioid dose requirement and a statistically significant, though clinically unimportant, reduction in acute pain burden in comparison to methadone. The study is limited by several important factors such as the exclusion of patients requiring intravenous patient-controlled analgesia, small number of patients were on higher dose of buprenorphine, and a large percentage of methadone patients were not on a stable dose of methadone yet.

Intravenous opioids for chemotherapy-induced severe mucositis pain in children: Systematic review and single-center case series of management with patient- or nurse-controlled analgesia (PCA/NCA).

Chemotherapy-induced oral mucositis can result in severe pain. Intravenous (IV) opioids are recommended, but management protocols vary. We systematically reviewed studies reporting IV opioid use for pain related to chemotherapy-induced severe oral mucositis in children and conducted a large single-center case series. Ovid MEDLINE, PubMed, and Cochrane databases were searched for studies reporting IV opioid duration and/or dose requirements for severe mucositis. Secondly, our pain service database was interrogated to describe episodes of opioid administration by patient- or nurse-controlled analgesia (PCA/NCA) for children with mucositis and cancer treatment-related pain. Seventeen studies (six randomized trials, two prospective observational, three retrospective cohort, six retrospective case series) included IV opioid in 618 patients (age 0.3-22.3years), but reported parameters varied. Mucositis severity and chemotherapy indication influenced IV opioid requirements, with duration ranging from 3 to 68days and variable dose trajectories (hourly morphine or equivalent 0-97mcg/kg/h). Our 7-year series included PCA/NCA for 364 episodes of severe mucositis (302 patients; age 0.12-17.2years). Duration ranged from 1 to 107days and dose requirements in the first 3days from 1 to 110mcg/kg/h morphine. Longer PCA/NCA duration was associated with: higher initial morphine requirements (ρ=0.46 [95% CI 0.35, 0.57]); subsequent increased pain and need for ketamine co-analgesia (118/364 episodes with opioid/ketamine 13.9 [9.8-22.2] days vs opioid alone 6.0 [3.9-10.8] days; median [IQR]); but not with age or sex. Management of severe mucositis pain can require prolonged IV opioid therapy. Individual and treatment-related variability in analgesic requirements highlight the need for regular review, titration, and management by specialist services.

Postoperative Pain and Opioid Dose Requirements in Patients on Sublingual Buprenorphine: A Retrospective Cohort Study for Comparison Between Postoperative Continuation and Discontinuation of Buprenorphine.

To test the hypothesis that patients who continued buprenorphine postoperatively experience less severe pain and require a smaller dose of opioids than those who discontinued buprenorphine. This is a retrospective cohort study of surgical patients who were on buprenorphine preoperatively. Using our previous study's data as pilot data, we selected the covariates to be included in 2 regression models with postoperative time-weighted average pain score and opioid dose requirements in morphine milligram equivalents during 48 hours after surgery as the outcomes. Both contained preoperative daily buprenorphine dose, whether buprenorphine was continued postoperatively, and the preoperative daily dose-by-postoperative continuation interaction as predictors. Precision variables were identified by exhaustive search of perioperative parameters with the exposure variables (preoperative daily dose, postoperative continuation, and their interaction) included in the regression model. The model selected by using the pilot data was estimated again using the new data extracted for this study to make inference about the effect of the 2 exposures (postoperative buprenorphine continuation and preoperative daily buprenorphine dose) and their interaction on the outcomes. Continuing buprenorphine was associated with a 1.3-point lower time-weighted average pain score than discontinuing (95% confidence interval, 0.39-2.21; P=0.005) but was not associated with a difference in opioid dose requirements (P=0.48). Continuing buprenorphine was associated with lower postoperative pain levels than discontinuing. Our results were primarily driven by patients on lower buprenorphine dose as only 22% of patients were on daily doses of 24 mg or above.

Acute Pain Burden and Opioid Dose Requirements after Cesarean Delivery in Parturients with Preexisting Chronic Back Pain and Migraine.

Introduction Preexisting chronic pain has been reported to be a consistent risk factor for severe acute postoperative pain. However, each specific chronic pain condition has unique pathophysiology, and it is possible that the effect of each condition on postoperative pain is different. Methods This is a retrospective cohort study of pregnant women with preexisting chronic pain conditions (i.e., migraine, chronic back pain, and the combination of migraine + chronic back pain), who underwent cesarean delivery. The effects of the three chronic pain conditions on time-weighted average (TWA) pain score (primary outcome) and opioid dose requirements in morphine milligram equivalents (MME) during postoperative 48 hours were compared. Results The TWA pain score was similar in preexisting migraine and chronic back pain. Chronic back pain was associated with significantly greater opioid dose requirements than migraine (12.92 MME, 95% CI: 0.41 to 25.43, P=0.041). Preoperative opioid use (P < 0.001) was associated with a greater TWA pain score. Preoperative opioid use (P < 0.001), smoking (P=0.004), and lower postoperative ibuprofen dose (P=0.002) were associated with greater opioid dose requirements. Conclusions Findings suggest women with chronic back pain and migraine do not report different postpartum pain intensities; however, women with preexisting chronic back pain required 13 MME greater opioid dose than those with migraine during 48 hours after cesarean delivery.

Opioids and Chronic Pain: An Analytic Review of the Clinical Evidence.

We conducted an analytic review of the clinical scientific literature bearing on the use of opioids for treatment of chronic non-cancer pain in the United States. There is substantial, albeit not definitive, scientific evidence of the effectiveness of opioids in treating pain and of high variability in opioid dose requirements and side effects. The estimated risk of death from opioid treatment involving doses above 100 MMED is ~0.25%/year. Multiple large studies refute the concept that short-term use of opioids to treat acute pain predisposes to development of opioid use disorder. The prevalence of opioid use disorder associated with prescription opioids is likely <3%. Morbidity, mortality, and financial costs of inadequate treatment of the 18 million Americans with moderate to severe chronic pain are high. Because of the absence of comparative effectiveness studies, there are no scientific grounds for considering alternative non-pharmacologic treatments as an adequate substitute for opioid therapy but these treatments might serve to augment opioid therapy, thereby reducing dosage. There are reasons to question the ostensible risks of co-prescription of opioids and benzodiazepines. As the causes of the opioid crisis have come into focus, it has become clear that the crisis resides predominantly in the streets and that efforts to curtail it by constraining opioid treatment in the clinic are unlikely to succeed.

P67. Does a high postoperative opioid dose predict chronic use after ACDF?

<h3>BACKGROUND CONTEXT</h3> Currently there is an incomplete understanding of the patient level risk factors for chronic opioid use after anterior cervical discectomy and fusion (ACDF). Postoperative opioid prescriptions in spine surgery have been found to commonly exceed the dose necessary for return to function and pain relief, however the direct relationship between postsurgical opioid dose and chronic opioid abuse has yet to be explored. <h3>PURPOSE</h3> To determine if increased postoperative prescription opioid dosing is an isolated predictor of chronic opioid use after ACDF. <h3>STUDY DESIGN/SETTING</h3> Retrospective Cohort Analysis. <h3>PATIENT SAMPLE</h3> All patients over age 18 who underwent one- to four-level primary or revision ACDF for cervical spondylosis associated with radiculopathy and/or myelopathy at an academic center between 2016- 2019 were retrospectively identified. Patients lacking descriptive data or opioid utilization records or who had surgery performed for trauma, infection, or malignancy were excluded. <h3>OUTCOME MEASURES</h3> Postoperative opioid use prescription metrics: mean morphine equivalent (MME) opioid dose, duration of usage, and the number of prescriptions and pharmacies utilized. Preoperative opioid and benzodiazepine tolerance. Chronicity of postoperative opioid use. <h3>METHODS</h3> Pre- and postsurgical opioid and benzodiazepine prescriptions, including the postoperative peak MME and duration of use, were obtained from the Pennsylvania Prescription Drug Monitoring Program (PDMP). Univariate analysis compared patient demographics and surgical factors across two binary groups of high vs low postoperative opioid dose (high: MME≥ 90, low: MME< 90) and chronic vs short-term opioid use (chronic: ≥120 days or >10 prescriptions). The relationship between chronic opioid use and patterns of immediate postoperative opioid use was evaluated. Binary logistic regressions were created to identify patient specific predictors of high opioid dose and chronic use. <h3>RESULTS</h3> A total of 385 patients met the inclusion criteria. Preoperative opioid tolerance and history of tobacco use were found to be associated with both high postoperative opioid dose and chronic postoperative usage. In addition, younger age correlated with receiving high dose prescriptions and obesity and preoperative benzodiazepine use were associated with chronic opioid use patterns. Chronicity of postoperative opioid use correlated meaningfully with immediate postoperative opioid use metrics including high single prescription dose, change in opioid prescribed, private pay scripatients, and greater than one prescriber and pharmacy. High postoperative opioid dose and preoperative opioid tolerance were identified as isolated predictors of chronic postsurgical opioid use on logistic regression. Regression also determined younger age, increased medical comorbidities, and opioid tolerance were significant predictors for high MME prescriptions. <h3>CONCLUSIONS</h3> High postoperative opioid dose was found to be a significant predictor of chronic opioid use after ACDF regardless of preoperative opioid tolerance. Because a multitude of factors increase patient opioid dose requirements after surgery, further research is required to determine if there exists a causal relationship between high postoperative opioid dosing and chronicity of use. <h3>FDA DEVICE/DRUG STATUS</h3> This abstract does not discuss or include any applicable devices or drugs.

Morphologic Severity of Acute Pancreatitis on Imaging Is Independently Associated with Opioid Dose Requirements in Hospitalized Patients.

Prior studies have evaluated clinical characteristics associated with opioid dose requirements in hospitalized patients with acute pancreatitis (AP) but did not incorporate morphologic findings on CT imaging. We sought to determine whether morphologic severity on imaging is independently associated with opioid dose requirements in AP. Adult inpatients with a diagnosis of AP from 2006 to 2017 were reviewed. The highest modified CT severity index (MCTSI) score and the daily oral morphine equivalent (OME) for each patient over the first 7days of hospitalization were used to grade the morphologic severity of AP and calculate mean OME per day(s) of treatment (MOME), respectively. Multiple regression analysis was used to evaluate the association of MOME with MCSTI. There were 249 patients with AP, of whom 196 underwent contrast-enhanced CT. The mean age was 46 ± 13.6years, 57.9% were male, and 60% were black. The mean MOME for the patient cohort was 60 ± 52.8mg/day. MCTSI (β = 3.5 [95% CI 0.3, 6.7], p = 0.03), early hemoconcentration (β = 21[95% CI 4.6, 39], p = 0.01) and first episode ofAP (β = - 17 [95% CI - 32, - 2.7], p = 0.027) were independently associated with MOME. Amongthe 19 patients undergoing ≥ 2 CT scans, no significant differences in MOME were seen between those whose MCTSI score increased (n = 12) versus decreased/remained the same (n = 7). The morphologic severity of AP positively correlated with opioid dose requirements. No difference in opioid dose requirements were seen between those who did versus those who did not experience changes in their morphologic severity.

Opioid Prescribing Patterns After Head and Neck Surgery

Postoperative prescription narcotics increase access to opioids and associated abuse among patients, family, and acquaintances. Judicious opioid stewardship is required. Best practice questions remain for larger head and neck surgeries. We aim to review opioid utilization patterns in an urban patient population to identify patients at risk for poor postoperative pain control. Case series with planned chart review for patients undergoing head and neck surgery (2015-2018). Single urban hospital. Outcome measures included postoperative phone calls and emergency room visits as markers for inadequate pain control. Age, sex, race, body mass index (BMI), smoking status, comorbidities, prior narcotic filling behavior, surgery type, and duration were evaluated as potential risk factors for pain control. Chi-square and Wilcoxon tests were used for group comparisons. In total, 215 patients met inclusion criteria: male (22%), white/Hispanic (47%), and African American (44%). Median BMI was 31.6 kg/m2; median age was 52 years. Surgeries included total thyroidectomy (41%), hemithyroidectomy (27%), and parathyroidectomy (15%). The 23-hour observation patients (n = 175, 81%) had a median of 20 morphine milligram equivalents (MMEs). Sixteen patients experienced inadequate pain control. Female sex (P = .03), younger age (P = .02), current smoker (P = .03), and higher inpatient MME (P = .006) were associated with inadequate pain control. Female sex, younger age, smokers, and high inpatient opioid dose requirements are associated with inadequately controlled pain. These patients may benefit from additional education, earlier postoperative visits, and a more comprehensive nonopioid regimen.

Sedation Requirements in Patients on Venovenous or Venoarterial Extracorporeal Membrane Oxygenation.

Background:There is a paucity of data evaluating optimal dosing strategies of commonly utilized opioids and sedatives for patients on extracorporeal membrane oxygenation (ECMO) support where pharmacokinetic and pharmacodynamic variables of these administered agents are altered. Objective: To assess the daily dosing requirement of sedatives and analgesics for patients on venovenous (VV) and venoarterial (VA) ECMO after the initial ECMO cannulation period. Methods: We performed a retrospective, observational study of adult patients receiving sedation and analgesia while receiving ECMO support for at least 24 hours. Patients cannulated at an outside hospital more than 24 hours before transfer, those with a history of intravenous drug use or acute alcohol withdrawal, or those who died within 48 hours of ECMO initiation were excluded. Results: We evaluated 26 patients on ECMO, including 13 on VV and 13 on VA ECMO. The median dose of fentanyl was 140 µg/h, with the VV group requiring a higher dose compared with the VA group (167 vs 106 µg/h, P < 0.001). The median doses of dexmedetomidine and propofol were 0.7 µg/kg/h and 26 µg/kg/min, respectively, with no significant differences between groups (P = 0.38 and P = 0.24, respectively). The median daily doses of fentanyl, dexmedetomidine, and propofol did not significantly increase throughout the time on ECMO support. Conclusions and Relevance: We found that the overall opioid daily dosing requirements were lower than previously reported in the literature. Additionally, light sedation strategies with a target RASS of -1 to 0 are feasible in this patient population.

Cannabinoid modulation of opioid analgesia and subjective drug effects in healthy humans.

Dozens of preclinical studies have reported cannabinoid agonist potentiation of the analgesic effects of μ-opioid agonists. The aim of this study was to determine if a cannabinoid agonist could potentiate opioid analgesia in humans using several laboratory pain models. Healthy participants (n = 10) with/out current drug use/pain conditions completed this within-subject, double-blind, placebo-controlled, randomized outpatient study. Nine 8-h sessions were completed during which dronabinol (0, 2.5, 5mg, p.o.) was administered 1h before oxycodone (0, 5, 10mg, p.o.) for a total of 9 test conditions. Outcomes included sensory threshold and tolerance from four experimental pain models (cold pressor, pressure algometer, hot thermode, cold hyperalgesia), along with participant- and observer-rated, performance and physiological effects. Oxycodone produced miosis (p < 0.05) and analgesic responses (e.g., pressure algometer [p < 0.05]), while dronabinol did not (p > 0.05). Depending on the dose combination, dronabinol attenuated or did not alter oxycodone analgesia; for example, dronabinol (2.5mg) decreased the analgesic effects of oxycodone (10mg) on pressure tolerance. Conversely, dronabinol increased oxycodone subjective effects (e.g., drug liking) (p < 0.05); oxycodone (5mg) ratings of "high" were potentiated by 5mg dronabinol (p < 0.05; placebo = 1.1 [± 0.7]; 5mg oxycodone = 4.7 [± 2.2]; 5mg dronabinol = 9.9 [± 8.4]; 5mg oxycodone + 5mg dronabinol = 37.4 [± 11.3]). This study indicates that dronabinol did not enhance the analgesic effects of oxycodone and increased abuse- and impairment-related subjective effects. These data suggest that dronabinol may not be an effective or appropriate opioid adjuvant; it could potentially increase opioid dose requirements, while increasing psychoactive opioid effects.