Association Between Cannabis Use and Opioid Consumption, Pain, and Respiratory Complications After Surgery: A Retrospective Cohort Analysis.

BACKGROUND: Cannabis is a widely used illicit drug with effects on different pain pathways. However, interactions between cannabis and postoperative pain are unclear. Cannabis smoking also affects the lungs, but the impact of cannabis use on postoperative pulmonary complications is unknown. We hypothesized that preoperative cannabis use in adults having elective surgery is associated with higher postoperative opioid consumption. Secondarily, we tested the hypothesis that cannabis use is associated with higher pain scores, hypoxemia (oxygen saturation [Spo2]/fraction of inspired oxygen [Fio2] ratio), and higher postoperative pulmonary complications compared to nonuse of cannabis. METHODS: In this retrospective study, we included adult patients who had elective surgeries at Cleveland Clinic Main Campus between January 2010 and December 2020. The exposure was use of cannabis within 30 days before surgery, and the control group never used cannabis. Patients who had regional anesthesia or chronic pain diagnosis were excluded. The primary outcome was postoperative opioid consumption; 3 secondary outcomes were time-weighted average (TWA) postoperative pain score, TWA Spo2/Fio2 ratio, and composite of pulmonary complications after surgery. We assessed the association between cannabis use and opioid consumption during the first 24 postoperative hours using linear regression on log-transformed opioid consumption with a propensity score-based method (inverse probability of treatment weighting [IPTW]) adjusting for confounders. We further adjusted for imbalanced confounding variables after IPTW was applied. RESULTS: In total, 1683 of 34,521 patients were identified as cannabis users. Cannabis use was associated with increased opioid consumption, with an adjusted ratio of geometric means (95% confidence interval [CI]) of 1.30 (1.22-1.38; P < .0001) for cannabis users versus nonusers. Secondarily, (1) cannabis use was associated with increased TWA pain score, with a difference in means of 0.57 (95% CI, 0.46-0.67; P < .0001); (2) cannabis use was not associated with TWA Spo2/Fio2, with an adjusted difference in means of 0.5 (95% CI, -3.1 to 4.2; P = .76); and (3) cannabis use was not associated with a collapsed composite of pulmonary complications, with estimated odds ratio of 0.90 (95% CI, 0.71-1.13; P = .34). CONCLUSIONS: Adult cannabis users undergoing surgeries were found to have significantly higher postoperative opioid consumption and pain scores than nonusers. Cannabis use did not have a clinically meaningful association with hypoxia or composite pulmonary complications.

Nanoanesthesia: a novel, intravenous approach to ankle block in the rat by magnet-directed concentration of ropivacaine-associated nanoparticles.

BACKGROUND: As an alternative to current methods of local nerve block, we studied the feasibility of producing ankle block in the rat with IV injection of magnetic nanoparticles (MNPs) associated with ropivacaine and application of a magnet at the ankle. METHODS: The anesthetic effect of magnet-directed ropivacaine-associated MNPs (MNP/Ropiv) was tested in the rat using paw withdrawal latencies from thermal stimuli applied to the hindpaw. The MNP/Ropiv complexes consisted of 0.7% w/v ropivacaine and 0.8% w/v MNPs containing 12% w/w magnetite (F3O4). The effect of IV injection of MNP/Ropiv with 15, 30, and 60-minute magnet application to the right ankle was compared with the effect without magnet application on the left hindpaw, to conventional ankle block with 0.1% or 0.2% ropivacaine, and to IV injection of MNPs alone with 30-minute magnet application to the right ankle. In addition, the pharmacokinetics of the MNP/Ropiv complexes were determined. RESULTS: IV injection of MNP/Ropiv with magnet application at the ankle significantly increased paw withdrawal latencies from thermal stimuli compared with pretreatment baselines in the same paw (P < 0.0001) and compared with the contralateral paw without magnet application (P < 0.0001). IV injection of MNPs alone had no significant effect on paw withdrawal latency. Absolute ropivacaine concentrations in ankle tissue, and ankle tissue-to-plasma concentration ratios were higher in the MNP/Ropiv group with 30-minute magnet application compared with MNP/Ropiv group without magnet application (mean ± SEM, 150 ± 10 ng/g vs 105 ± 15 ng/g, respectively, and 6.1 ± 0.8 vs 4.2 ± 0.7, respectively). CONCLUSIONS: The current study establishes proof of principle that it is possible to produce ankle block in the rat by IV injection of MNP/Ropiv complexes and magnet application at the ankle. The results indicate that further study of this approach is warranted.

Pantoprazole associated dyspepsia hypocalcemia and hyponatremia: A disproportionality analysis in FDA adverse event reporting system (FAERS) database.

BACKGROUND AND STUDY AIM: The study was designed to detect novel Adverse Events (AEs) of pantoprazole by disproportionality analysis in the FDA (Food and Drug Administration) database of Adverse Event Reporting System (FAERS) using Data Mining Algorithms (DMAs). Pantoprazole, the most commonly over-utilized Over The Counter (OTC) medication, was selected to assess any short-term or long-term AEs. The study aimed to analyze the novel adverse events of pantoprazole using the FAERS database. MATERIALS AND METHODS: A retrospective case/non-case disproportionality analysis was performed in the FAERS database. This study was based on AEs reported to FAERS from 2006Q1-2021Q3. Openvigil 2.1 was used for data extraction. Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), and Information Component (IC) were applied to measure the disproportionality in reporting. A value of ROR-1.96SE > 1, PRR ≥ 2, and IC-2SD > 0 were considered as the threshold for a positive signal. RESULTS: A total of 1050 reports of dyspepsia, 7248 reports of hypocalcemia and 995 reports of hyponatremia were identified. A potential positive signal for dyspepsia (ROR-1.96SE = 2.231, PRR = 2.359, IC-2SD = 1.13), hypocalcemia (4.961, 5.45, 2.23) and hyponatremia (3.948, 4.179, 1.92) were identified for pantoprazole. CONCLUSION: Data mining in the FAERS database produced three potential signals associated with pantoprazole. As a result, further clinical surveillance is needed to quantify and validate potential hazards associated with pantoprazole-related adverse events.

Regional anesthesia for thoracic surgery: a narrative review of indications and clinical considerations.

Background and Objective: Surgical procedures involving incisions of the chest wall regularly pose challenges for intra- and postoperative analgesia. For many decades, opioids have been widely administered to target both, acute and subsequent chronic incisional pain. Opioids are potent and highly addictive drugs that can provide sufficient pain relief, but simultaneously cause unwanted effects ranging from nausea, vomiting and constipation to respiratory depression, sedation and even death. Multimodal analgesia consists of the administration of two or more medications or analgesia techniques that act by different mechanisms for providing analgesia. Thus, multimodal analgesia aims to improve pain relief while reducing opioid requirements and opioid-related side effects. Regional anesthesia techniques are an important component of this approach. Methods: For this narrative review, authors summarized currently used regional anesthesia techniques and performed an extensive literature search to summarize specific current evidence. For this, related articles from January 1985 to March 2022 were taken from PubMed, Web of Science, Embase and Cochrane Library databases. Terms such as "pectoral nerve blocks", "serratus plane block", "erector spinae plane block" belonging to blocks used in thoracic surgery were searched in different combinations. Key Content and Findings: Potential advantages of regional anesthesia as part of multimodal analgesia regiments are reduced surgical stress response, improved analgesia, reduced opioid consumption, reduced risk of postoperative nausea and vomiting, and early mobilization. Potential disadvantages include the possibility of bleeding related to regional anesthesia procedure (particularly epidural hematoma), dural puncture with subsequent dural headache, systemic hypotension, urine retention, allergic reactions, local anesthetic toxicity, injuries to organs including pneumothorax, and a relatively high failure especially with continuous techniques. Conclusions: This narrative review summarizes regional anesthetic techniques, specific indications, and clinical considerations for patients undergoing thoracic surgery, with evidence from studies performed. However, there is a need for more studies comparing new block methods with standard methods so that clinical applications can increase patient satisfaction.

Genomic loci and candidate genes underlying inflammatory nociception.

Heritable genetic factors contribute significantly to inflammatory nociception. To determine candidate genes underlying inflammatory nociception, the current study used a mouse model of abdominal inflammatory pain. BXD recombinant inbred (RI) mouse strains were administered the intraperitoneal acetic acid test, and genome-wide quantitative trait locus (QTL) mapping was performed on the mean number of abdominal contraction and extension movements in 3 distinct groups of BXD RI mouse strains in 2 separate experiments. Combined mapping results detected 2 QTLs on chromosomes (Chr) 3 and 10 across experiments and groups of mice; an additional sex-specific QTL was detected on Chr 16. The results replicate previous findings of a significant QTL, Nociq2, on distal Chr 10 for formalin-induced inflammatory nociception and will aid in identification of the underlying candidate genes. Comparisons of sensitivity to intraperitoneal acetic acid in BXD RI mouse strains with microarray mRNA transcript expression profiles in specific brain areas detected covarying expression of candidate genes that are also found in the detected QTL confidence intervals. The results indicate that common and distinct genetic mechanisms underlie heritable sensitivity to diverse inflammatory insults, and provide a discrete set of high-priority candidate genes to investigate further in rodents and human association studies. Novel genomic regions linked to inflammatory nociception were detected, a previously reported locus was confirmed, and high-priority candidate genes for inflammatory nociception and pain were identified.