Analgesic Dose Research Articles

Development and validation of a mouse model to investigate post surgical pain after laparotomy

BackgroundPostoperative pain following abdominal surgery is a significant obstacle to patient recovery, often necessitating high analgesic doses associated with adverse effects like cognitive impairment and cardiorespiratory depression. Reliable animal models are crucial for understanding the pathophysiology of post surgical pain and developing more effective pain-relieving strategies. MethodsWe developed a mouse model to replicate peritoneal trauma induced by abdominal surgery. 30 C57BL/6 mice underwent laparotomy, with half undergoing standardised peritoneal abrasion and the rest serving as controls. Mouse recovery was assessed using two validated scoring systems of surgical recovery: Post surgery Severity Assessment (PSSA) and Mouse Grimace Score (MGS). Blood samples were taken for cytokine analysis. Adhesions were evaluated on day 6, and peritoneal tissue was examined for healing markers. ResultsAfter laparotomy, all mice exhibited expected pain profiles. Mice with peritoneal abrasion had significantly higher PSSA (7.2 ± 1.2 vs 4.68 ± 0.82, p ≤ 0.001) and MGS scores (3.62 ± 0.74 vs 0.82 ± 0.40, p ≤ 0.05) with slower recovery. Serum inflammatory cytokine levels were significantly elevated in the abraded group, and adhesion formation was higher in this group. Immunohistochemical analysis showed significantly increased expression of α-SMA, CD31, CD68, and F4/80 in peritoneal tissue in the abraded group. DiscussionA mouse model involving laparotomy and standardised peritoneal abrasion replicates the expected pathophysiological changes following abdominal surgery. It will be a useful model for better understanding the mechanisms of post surgical pain and developing improved pain-relief strategies. It also has utility for the study of intra-abdominal adhesion formation. Key messageTo understand the intricate relationship between peritoneal trauma-induced pain, cytokine response, and post-operative adhesion formation in mouse models for advancing therapeutic interventions and enhancing post-operative recovery outcomes.

The effects of smoking on pain scores, vital signs, and analgesic consumption in patients undergoing tympanomastoidectomy surgery.

In this study, we investigate the effects of smoking on pain scores, vital signs, and analgesic consumption in the intraoperative and postoperative period in patients undergoing tympanomastoidectomy surgery. A total of 100 patients with American Society of Anesthesiologists I-II status, aged 18-55 years, and who were planned to undergo tympanomastoidectomy surgery were divided into two groups: smokers (Group 1) and non-smokers (Group 2). The patients were compared for preoperative, intraoperative, and 24-hour postoperative carboxyhemoglobin, blood pressure, oxygen saturation, respiratory rate, heart rate, pain intensity and verbal numerical rating scales, the extent of patient-controlled tramadol dose, nausea, and vomiting. There were 50 individuals in each group. Postoperative analgesic consumption and pain scores were higher in Group 1, and the first postoperative pain was felt earlier. Furthermore, in Group 1, preoperative carboxyhemoglobin levels and postoperative nausea were statistically higher before, after, and at the tenth minute after induction, whereas oxygen saturation was lower. The two groups had no statistical difference regarding intraoperative and postoperative vital signs. Postoperative analgesic consumption was not affected by age or gender. Smoking changes postoperative pain management, especially for this kind of operation, and these patients feel more pain and need more postoperative analgesic doses. Therefore, effective postoperative pain control should take account of smoking behavior, and analgesic doses may need to be adjusted for patients who smoke.

Programmed Intermittent Epidural Bolus Reduces Workloads in Labor Analgesia: A Single Center's Experience.

Background and Objectives: Labor epidural analgesia can be maintained through programmed intermittent epidural bolus (PIEB), continuous epidural infusion (CEI), or patient-controlled epidural analgesia (PCEA). Our department changed from CEI+PCEA to PIEB+PCEA as the maintenance method. The higher hourly dose setting in the current regimen brought to our concern that side effects would increase with proportional staff workloads. This study aimed to investigate the validity of our proposal that PIEB+PCEA may function as a feasible tool in reducing the amount of work in the obstetrics anesthesia units. Materials and methods: This 2-year retrospective review included parturients with vaginal deliveries under epidural analgesia. We compared the staff burden before and after the switch from CEI (6 mL/h, PCEA 6 mL lockout 15 min, group A) to PIEB (8 mL/h, PCEA 8 mL lockout 10 min, group B). The primary outcome was the difference of proportion of parturients requiring unscheduled visits between groups. Side effects and labor and neonatal outcomes were compared. Results: Of the 694 parturients analyzed, the proportion of those requiring unscheduled visits were significantly reduced in group B (20.8% vs. 27.7%, chi-square test, p = 0.033). The multivariate logistic regression showed that PIEB was associated with fewer unscheduled visits than CEI (OR = 0.53, 95% CI [0.36-0.80], p < 0.01). Group B exhibited a significantly lower incidence of asymmetric blockade, as well as motor blockade. In nulliparous subjects, obstetric anal sphincter injury occurred less frequently when PIEB+PCEA was used. Significantly more multiparous women experienced vacuum extraction delivery in group B than in group A, and they had a longer second stage of labor. Conclusions: The PIEB+PCEA protocol in our study reduced workloads in labor epidural analgesia as compared to CEI+PCEA, despite that a higher dose of analgesics was administered. Future studies are warranted to investigate the effect of manipulating the PIEB settings on the labor outcomes.

Continuous Erector Spinae Plane Block for Postoperative Analgesia in Elderly Patients After Thoracoscopic Lobectomy

PurposeCompared the effect of ultrasound-guided continuous erector spinae plane block to continuous thoracic paravertebral block on postoperative analgesia in elderly patients underwent thoracoscopic lobectomy. DesignThe patients who underwent non-emergent thoracoscopic lobectomy in thoracic surgery department of our hospital from January 2019 to December 2020 were selected and randomly divided into continuous erector spinae block(ESPB) group and continuous thoracic paravertebral block(TPVB) group. MethodsFifty elderly patients with thoracoscopic lobectomy under general anesthesia from January 2019 to December 2020 were selected and randomly divided into continuous erector spinae block(ESPB) group and continuous thoracic paravertebral block(TPVB) group, with 25 patients in each group. The patients in the two groups were guided by ultrasound with ESPB or TPVB before anesthesia induction. The visual analog scale (VAS) at rest and cough in 2h, 6h, 8h, 12h, 24h, 48h after surgery, the supplementary analgesic dosage of tramadol, time of tube placement, the stay time in post-anesthesia care unit(PACU), the first ambulation time after surgery, the length of postoperative hospital stay and postoperative complications were recorded. FindingsThere were no significant differences between the two groups in VAS score at rest and cough at each time point and supplementary analgesic dosage of tramadol within 48h after surgery (p>0.05). The time of tube placement and the postoperative hospital stay in ESPB group was significantly shorter than that in TPVB group(p<0.05). There were no differences in PACU residence time and first ambulation time between the two groups(p>0.05). There were 4 patients in TPVB group and 2 patients in ESPB group occurred nausea and vomiting(P>0.05), 1 case of pneumothorax and 1 case of fever occurred in TPVB group. There were no incision infection or respiratory depression requiring clinical intervention occurred in both groups. ConclusionsBoth ESPB and TPVB alleviated the patients postoperative pain effectively for elderly patients underwent thoracoscopic lobectomy. Compared with TPVB, ESPB have shorter tube placement time, fewer complications and faster postoperative recovery. Unitsmg/kg, Milligram per kilogram; mL, Millilitres; ml/h, Millilitres per hour; ug/kg, Microgram per kilogram; ml/kg, Millilitres per kilogram; ml/kg/h, Millilitres per kilogram per hour; mg, Milligram. FootnotesNot applicable.

Comparison of Intravenous Paracetamol and Intravenous Ketorolac in Postoperative Pain Control After Hip Surgery

Objective: To compare the analgesic effects of intravenous paracetamol versus ketorolac to control pain after hip surgery. Methodology: This prospective comparative study was conducted at Ali Medical Centre Islamabad from Dec 2022-Dec 2023. One hundred and eighteen (n=118) patients who underwent hip surgeries were included in this study. Patients were equally distributed into two groups. In group A, intravenous Paracetamol was administered for post-surgery analgesia. In group B, intravenous ketorolac was utilized for pain relief. A Visual Analogue Scale (VAS) was used to assess pain in both groups at 2, 6-, 12-, 24-, and 48-hours post-surgery. Collected data was analyzed using the SPSS version 23. Results: One hundred and eighteen (n=118) patients had a mean age of 61.5±0.5 years. 43(36.4%) patients were male and 75(63.6%) patients were female. Significant pain (VAS score &gt;4) in Group A at 2, 6-, 12-, 24-, and 48-hours post-surgery was present in 29(49.1%), 9(15.2%), 9(15.2%), 7(11.8%), and 18(30.5%) patients respectively. In Group B, the significant pain (VAS score &gt;4) was recorded at the same time intervals, in 6(10.1%), 4(6.7%), 2(3.3%), 1(1.6%), and 3(5.0%) patients respectively. The mean doses of rescue analgesia required in Group A was 1.3±0.5 and in Group B, it was 0.3±0.6 (p-value ? 0.001). Conclusion: Intravenous ketorolac provides better analgesia than paracetamol after hip surgery. Moreover, doses of rescue analgesia required with intravenous paracetamol were more as compared to ketorolac.

MP-13, a novel chimeric peptide of morphiceptin and pepcan-9, produces potent antinociception with limited side effects

Pharmacological investigations have substantiated the potential of bifunctional opioid/cannabinoid agonists in delivering potent analgesia while minimizing adverse reactions. Peptide modulators of cannabinoid receptors, known as pepcans, have been investigated before. In this study, we designed a series of chimeric peptides based on pepcans and morphiceptin (YPFP-NH2). Here, we combined injections of pepcans and morphiceptin to investigate the combination treatment of opioids and cannabis and compared the analgesic effect with chimeric compounds. Subsequently, we employed computational docking to screen the compounds against opioid and cannabinoid receptors, along with an acute pain model, to identify the most promising peptide. Among these peptides, MP-13, a morphiceptin and pepcan-9 (PVNFKLLSH) construct, exhibited superior supraspinal analgesic efficacy in the tail-flick test, with an ED50 value at 1.43 nmol/mouse, outperforming its parent peptides and other chimeric analogs. Additionally, MP-13 displayed potent analgesic activity mediated by mu-opioid receptor (MOR), delta-opioid receptor (DOR), and cannabinoid type 1 (CB1) receptor pathways. Furthermore, MP-13 did not induce psychological dependence and gastrointestinal motility inhibition at the effective analgesic doses, and it maintained non-tolerance-forming antinociception throughout a 7-day treatment regimen, with an unaltered count of microglial cells in the periaqueductal gray region, supporting this observation. Moreover, intracerebroventricular administration of MP-13 demonstrated dose-dependent antinociception in murine models of neuropathic, inflammatory, and visceral pain. Our findings provide promising insights for the development of opioid/cannabinoid peptide agonists, addressing a crucial gap in the field and holding significant potential for future research and development. PerspectiveThis article offers insights into the combination treatment of pepcans with morphiceptin. Among the chimeric peptides, MP-13 exhibited potent analgesic effects in a series of preclinical pain models with a favorable side-effect profile.

Exploring the rationale of performing vaginal hysterectomy under local anaesthesia: A single-centre experience

IntroductionVaginal hysterectomy (VH) is usually performed under general (GA) or regional anaesthesia. In recent years, the possibility of performing vaginal hysterectomy under local anaesthesia (LA) has also been explored. Our aim was to compare intraoperative and early postoperative outcomes in women who underwent VH under LA with intravenous sedation or GA. MethodsIn this retrospective study, we collected data of patients who underwent VH at our department from June 2021 to December 2022. For every patient, the following data was obtained: hospitalisation duration, type of anaesthesia (LA or GA), accompanying procedures, the dosage of used local anaesthetic in the LA group, maximal pain score for each day of hospitalisation after the procedure, procedure duration, intraoperative blood loss, and postoperative complication rate. Data was analysed using the SPSS Statistics programme. Statistical significance was set at p < 0.05. ResultsSeventy patients were included in the study. The mean age was significantly higher in the LA group compared to GA group (73.8 ± 8.0 years vs. 67.1 ± 9.3 respectively, p-value = 0.003). LA was associated with statistically lower pain scores in the first two days after the procedure (p = 0.003), and shorter procedure duration (p-value <0.001) as well as hospitalisation duration (p < 0.001). Furthermore, the cumulative dosage of different analgesics used during hospitalisation was higher in the GA group. ConclusionsOur results show that LA is a feasible option for patients undergoing VH. Vaginal surgical procedures under LA could be especially beneficial for older patients with medical comorbidities in whom GA would be particularly hazardous.

A randomized trial of topical cannabis balms for the treatment of aromatase inhibitor–associated musculoskeletal syndrome (AIMSS).

e24129 Background: Aromatase inhibitors (AIs) are commonly used for postmenopausal women with hormone receptor positive breast cancer. Nearly 2 of 3 women on AIs complain of AIMSS leading to poor adherence. Preclinical and clinical pilot data suggest topical cannabinoids can reduce inflammation in arthritis. Methods: We conducted a randomized controlled trial assessing the feasibility and acceptability of two different topical medical cannabis balms for AIMSS. Women with stage 1-3 breast cancer with AIMSS [scoring 4 or higher on at least one of the four screening Modified Score for the Assessment and Quantification of Chronic Rheumatoid Affectations of the Hands (M-SACRAH) questions] were eligible. Patients with skin lesions, use of any cannabis in prior 4 weeks, acupuncture, or plans to increase doses of other analgesics were excluded. Women were randomized 1:1 to cannabidiol (CBD) (2210mg CBD/ &lt; 0.3% THC) vs delta-9-tetrahydrocannabinol (THC) (375mg THC/ &lt; 20mg CBD) predominant balm. Participants enrolled in the Minnesota Medical Cannabis Program and were dispensed balms at state-registered dispensaries. 125cc of balm was applied 3 times daily to hands for 2 weeks. M-SACRAH, brief pain inventory (BPI), and NCI Patient Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE) measures were captured weekly. Results: 20 women were enrolled from one academic and one community oncology practice in Minnesota over a 10-month period. Reasons patients with AIMSS did not enroll included patient/clinician not interested, AIMSS not meeting M-SACRAH severity, and patient already using cannabis. Adherence to study protocol through week 2 was 85%. Mean age was 54 years, 85% White/15% Asian, 45% received adjuvant chemotherapy, and 50% reported no lifetime cannabis use. Participants reported improvement in M-SACRAH, BPI, and PRO-CTCAE pain scores from baseline to week 2 (Table 1). No skin toxicity was reported by patients. One patient discontinued balm due to greasy texture. Conclusions: Conducting a randomized trial of topical cannabis using state approved dispensaries is feasible. Both THC and CBD predominant topical balms are well tolerated and appear to reduce AIMSS severity in this pilot study of breast cancer survivors. Further confirmatory studies are warranted. Clinical trial information: NCT05935891 . [Table: see text]

Intravenous ketorolac versus intravenous dexmedetomidine for postoperative analgesia after hypospadias repair

ABSTRACT Hypospadias repair surgery, though necessary, can be painful after the procedure, especially for children. Effective pain management is essential in all surgeries, but particularly in pediatric procedures. The current study was conducted to evaluate the analgesic efficacy of intravenous ketorolac versus dexmedetomidine after hypospadias repair surgery. Patients and methods A total of 60 children aged between 2 and 7 years old undergoing hypospadias repair under general anesthesia enrolled in the study. Those children were randomly divided into either group Ketorolac (group A) or Dexmedetomidine group (group B). Group (A) included 30 patients who received IV ketorolac in a dose 0.9 mg/kg after intubation for general anesthesia while group (B) included 30 patients who received IV dexmedetomidine in a dose 1 μg/kg after intubation. Pain scores (FLACC), sedation and emergence agitation (EA) scores, 1st analgesic dose, hemodynamics, and any side events were recorded. Results The main finding in this study was that group (B) had significantly lower FLACC at different postoperative times compared to group n(A)with p < 0.05; with exception at 4th and 12th hours. It was found that FLACC was zero in group (B) till the 6th hour postoperatively. All patients in the studied groups had sedation scale was 3 starting from the 4th postoperative hour. Immediate and 2-hour postoperatively, the score was significantly higher among the dexmedetomidine group.Two patients developed EA in group A but non in group B. Conclusion Adjuvant intravenous dexmedetomidine is more effective than intravenous ketorolac in postoperative analgesia children after hypospadias repair surgery under general anaesthesia.

Comparison of Different Ketofol Procedural Sedation and Analgesic Doses during Orthopedic Procedures in Patients Referred to the Emergency Department: A Double-Blind Randomized Clinical Trial

Background: Orthopedic procedures are one of the most common medical procedures in the emergency department (ED) and are also among the most painful procedures performed on the conscious patient. This study aimed to compare different doses of ketofol in procedural sedation and analgesia (PSA) in patients referred to the EDs. Methods: In this double-blinded clinical trial, 296 patients aged 18 years or over who presented with the need for orthopedic procedures in the three academic EDs in 2020 were studied. After completing the written consent, the patients were randomly assigned to four treatment groups. Demographic information, underlying diseases, patients' physical condition, type of orthopedic injuries requiring intervention, and patients' vital signs were recorded in a checklist for each patient. Results: In this study, the mean age, gender, level of education, addiction, patients' physical condition, type of procedures performed, apnea, hypoventilation, bradycardia, hypotension, and agitation in all four treatment groups were not statistically different, but hallucination and hypoxia in group C (propofol 1 mg/kg plus ketamine 0.33 mg/kg) were much less than other groups; thus, oxygen administration was more common in other groups. Conclusion: By testing different doses of ketamine, we concluded that doses of 1 mg and 0.5 mg were associated with more side effects. A dose of 0.33 mg of ketamine has fewer side effects while causing analgesia and sedation as in the above doses. A dose of 0.25 mg of ketamine increases the likelihood of requiring subsequent doses. Therefore, it seems that 0.33 mg of ketamine is the best dose of choice.

The influence of patient sex on paramedic administration of analgesia for acute abdominal pain in an Australian ambulance service

Objective: Pain is a subjective experience that encapsulates a physical, emotional, and mental response. An individual's sex is a factor that may influence how pain is experienced. It can be assumed that if females and males present with pain differently, then pain management may also differ. This research aimed to determine the influence of patients’ sex on paramedic administration of analgesia in cases of acute abdominal pain. Methods: A retrospective analytical cohort study included patients between the ages of 16 and 65 with a complaint of abdominal pain who were seen by paramedics employed by a jurisdictional ambulance service between July 2019 and June 2020. The data extracted included sex, age, pain score, type of analgesia administered, and analgesia dosage. The data were analysed using descriptive statistics, chi-square tests, and univariate and multivariate logistic regression. Results: The study sample comprised of 26,417 patients with 61.6% (n = 16,271) females. Analgesia was administered to 65.9% (n = 17,404) of patients, of whom 38.5% (n = 10,177) received an opioid, with the most administered analgesia being morphine (n = 8456; 32%). Chi-square testing identified significant associations between sex and analgesic administration (χ2(1, n = 26,417) = 7.32, p = .01, Φ = −0.02) and opioid administration (χ2(1, n = 26,417) = 25.51, p &lt; .001, Φ = 0.03). Multivariate regression identified that sex had no influence on analgesic administration in general, however found that male sex was a statistically significant predictor of opioid administration. Adjusted for age and pain severity, females were at lower odds of opioid administration than males (adjusted odds ratio 0.86; 95% confidence interval 0.80–0.91; p &lt; .001). Conclusions: Equity in pain management was demonstrated in relation to overall analgesic administration between the sexes. However, this research suggests that while females presented more commonly with abdominal pain, females had lower odds of being administered an opioid than their male counterparts. Further research is required on gender bias in relation to abdominal pain management practices by paramedics, to promote equitable access to analgesia.

Exploring Differences in Intraoperative Medication Use Between African American and Non-Hispanic White Patients During General Anesthesia: Retrospective Observational Cohort Study.

This study aimed to explore whether differences exist in anesthesia care providers' use of intraoperative medication between African American and non-Hispanic White patients in adult surgical patients who underwent noncardiothoracic nonobstetric surgeries with general anesthesia. A retrospective observational cohort study used electronic health records between January 1, 2018 and August 31, 2019 at a large academic health system in the southeastern United States. To evaluate the isolated impact of race on intraoperative medication use, inverse probability of treatment weighting using the propensity scores was used to balance the covariates between African American and non-Hispanic White patients. Regression analyses were then performed to evaluate the impact of race on the total dose of opioid analgesia administered, and the use of midazolam, sugammadex, antihypotensive drugs, and antihypertensive drugs. Of the 31,790 patients included in the sample, 58.9% were non-Hispanic Whites and 13.6% were African American patients. After adjusting for significant covariates, African American patients were more likely to receive midazolam premedication (p < .0001; adjusted odds ratio [aOR] = 1.17, 99.9% CI [1.06, 1.30]), and antihypertensive drugs (p = .0002; aOR = 1.15, 99.9% CI [1.02, 1.30]), and less likely to receive antihypotensive drugs (p < .0001; aOR = 0.85, 99.9% CI [0.76, 0.95]) than non-Hispanic White patients. However, we did not find significant differences in the total dose of opioid analgesia administered, or sugammadex. This study identified differences in intraoperative anesthesia care delivery between African American and non-Hispanic White patients; however, future research is needed to understand mechanisms that contribute to these differences and whether these differences are associated with patient outcomes.

Biasing Gβγ Downstream Signaling with Gallein Inhibits Development of Morphine Tolerance and Potentiates Morphine-Induced Nociception in a Tolerant State.

Opioid analgesics are widely used as a treatment option for pain management and relief. However, the misuse of opioid analgesics has contributed to the current opioid epidemic in the United States. Prescribed opioids such as morphine, codeine, oxycodone, and fentanyl are mu-opioid receptor (MOR) agonists primarily used in the clinic to treat pain or during medical procedures, but development of tolerance limits their utility for treatment of chronic pain. Here we explored the effects of biasing Gβγ signaling on tolerance development after chronic morphine treatment in vivo. We hypothesized that biasing Gβγ signaling with gallein could prevent activation of regulatory signaling pathways that result in tolerance to antinociceptive effects of MOR agonists. Gallein has been shown to bind to Gβγ and inhibit interactions of Gβγ with phospholipase-Cβ3 (PLCβ3) or G-protein-coupled receptor kinase 2 (GRK2) but not G-protein inwardly rectifying potassium (GIRK) channels. In mice, morphine-induced antinociception was evaluated in the 55°C warm water tail withdrawal assay. We used two paradigms for gallein treatment: administration during and after three times-daily morphine administration. Our results show that gallein cotreatment during repeated administration of morphine decreased opioid tolerance development and that gallein treatment in an opioid-tolerant state enhanced the potency of morphine. Mechanistically, our data suggest that PLCβ3 is necessary for potentiating effects of gallein in an opioid-tolerant state but not in preventing the development of tolerance. These studies demonstrate that small molecules that target Gβγ signaling could reduce the need for large doses of opioid analgesics to treat pain by producing an opioid-sparing effect. SIGNIFICANCE STATEMENT: Biasing Gβγ signaling prevents tolerance to repeated morphine administration in vivo and potentiates the antinociceptive effects of morphine in an opioid-tolerant state. Mechanistically, phospholipase-Cβ is necessary for potentiating effects of gallein in an opioid-tolerant state but not in preventing the development of tolerance. This study identifies a novel treatment strategy to decrease the development of tolerance to the analgesic effects of mu-opioid receptor agonists, which are necessary to improve pain treatment and decrease the incidence of opioid use disorder.

An observational study of gastric contents in pediatric patients with long bone fracture using gastric ultrasound.

The retention of gastric contents at surgery presentation is a risk factor for perioperative aspiration. A preoperative fasting (nil per os; NPO) interval is widely used to reduce this risk, but this approach is based on assumptions about the prevalence of typical gastric emptying rates. We assessed NPO guidelines' reliability with ultrasound (US) imaging and suction in pediatric patients presenting for single long-bone fracture repair after appropriate NPO intervals, when nearly all should have had empty stomachs. This prospective cross-sectional observational study comprised 200 pediatric surgical patients. As their NPO times varied by food/drink type, we defined "weighted NPO units" as the lowest multiple of elapsed recommended NPO times between consumption and surgery for each type of food or drink. We used US to image the stomach and its contents before anesthesia induction, followed by gastric suction. We evaluated the relationships between weighted NPO units, US gastric contents grade, opioid analgesic dosage and timing, and suctioned volume. Despite meeting typical NPO standards (median 14 h fasting), many patients retained nontrivial quantities of gastric contents at surgery. Weighted NPO units did not exhibit statistically-significant relationships with either suctioned volume or US grade. However, suctioned volume did correspond well to US grade. NPO status may be a less reliable predictor of gastric contents at anesthesia induction in this patient population than has been assumed. Bedside US screening appears to provide more useful information for the planning of airway management.

Effects of a Modified Long-Acting Cocktail on Analgesia and Enhanced Recovery After Total Hip Arthroplasty: A Double-Blinded Randomized Clinical Trial

BackgroundWe compared the efficacy and safety of a modified cocktail for postoperative analgesia and early functional rehabilitation in patients undergoing total hip arthroplasty (THA). MethodsMagnesium sulfate and sodium bicarbonate were added to a cocktail of ropivacaine, epinephrine, and dexamethasone. Primary outcome measures were visual analog scale (VAS) pain scores at various intervals after surgery, morphine consumption for rescue analgesia after surgery, and time to first rescue analgesia. Secondary outcomes were hip function after surgery, daily walking distance, quadriceps muscle strength, and the incidence of postoperative adverse reactions. ResultsMorphine consumption was significantly lower in the modified cocktail group than in the control group in the first 24 hours after surgery (6.2 ± 6.0 versus 14.2 ± 6.4 mg, P < .001), as was total morphine consumption (10.0 ± 8.6 versus 19.2 ± 10.1 mg, P < .001). The duration of the first rescue analgesia was significantly prolonged (23.7 ± 10.3 versus 11.9 ± 5.8 mg, P < .001). Morphine consumption was also reduced in the magnesium sulfate and sodium bicarbonate groups over a 24-hour period compared to the control group (P < .001). The modified cocktail group had significantly lower resting VAS pain scores than the control group within 24 hours after surgery (P < .050). The VAS pain scores during movement within 12 hours after surgery were also lower (P < .050). The experimental groups showed better hip range of motion (P < .050) and longer walking distance (P < .050) on the first postoperative day, and levels of inflammatory markers were significantly reduced. The incidence of postoperative adverse reactions was similar among the 4 groups. ConclusionsThe modified cocktail with a new adjuvant can prolong the duration of postoperative analgesia, reduce the dosage of rescue analgesics, and accelerate early postoperative functional recovery in patients undergoing THA.

Comparative Study of Levobupivacaine Versus Levobupivacaine With Dexmedetomidine as an Adjuvant in Transversus Abdominis Block for Postoperative Pain Relief in Abdominal Hysterectomy Patients: A Randomized, Double-Blind Study.

Background Adjuvants have been discovered to prolong the analgesic impact of local anesthetics (LA), while the transversus abdominis plane (TAP) block offers sufficient postoperative pain relief after various abdominal procedures. Nevertheless, the impact of the given LA will determine the duration of the TAP block. Thus, in this investigation, we aimed to estimate the analgesic impact of combining dexmedetomidine (DEX) with levobupivacaine in the TAP block for patients having an infraumbilical incision for an abdominal hysterectomy while under spinal anesthetic. Aim This study aimed to determine the analgesic effect of DEX (0.5 mcg/kg) to 20 ml of 0.25% levobupivacaine on each side in the TAPblock in patients undergoing total abdominal hysterectomy (TAH). Materials and methods Two groups of 30 patients each, with ASA grades 1 and 2, were randomly selected from patients. Group N, comprising 30 patients, had a bilateral TAP block using 2 mL of normal saline and 20 mL of 0.25% levobupivacaine. Group D (n = 30 patients) was given DEX at a dose of 0.5 mcg/kg (2 mL) in addition to 20 mL of 0.25% levobupivacaine given bilaterally. The TAP block was administered just after skin closure. Time of the initial analgesic dose administration; total fentanyl doses utilized as rescue analgesia; pain scores (numerical rating scale (NRS)) at 2, 4, 6, 8, 12, and 24 hours; and pre- and postoperative cortisol levels were also noted. For each group, 1 gram IV paracetamol was administered every eight hours. Drugs used for rescue analgesia (RA) were diclofenac 75 mg IV stat and fentanyl 1 mcg/kg. Results and discussion In addition to Group N having lower NRS scores at rest, Group D had a considerably longer time for initial rescue analgesia than Group N. There was also a significant decrease in the total fentanyl consumption and postoperative serum cortisol levels in Group D in contrast to Group N. Conclusion Potential adjuvant DEX prolongs postoperative analgesia in patients experiencing abdominal hysterectomy when used alongside LA in TAP.

A Randomized Controlled Study of Epidural Morphine Sulfate-soaked Gelfoam and Morphine Sulfate Instillation in the Management of Postoperative Pain following Lumbar Spinal Fixation Surgery

Abstract Background: Lumbar spinal fixation surgeries play a pivotal role in addressing pain which can be nociceptive, neuropathic, mixed, and nociplastic; however, these surgeries can also cause significant postoperative pain and discomfort, leading to prolonged hospital stays and delayed return to normal activity. Aims and Objectives: The aim of the study was to provide effective postoperative analgesia and to compare the analgesic efficacy by application of Gelfoam-soaked morphine sulfate placed in the epidural space and direct instillation of morphine sulfate in the epidural space in patients undergoing lumbar spinal fixation surgery under general anesthesia. Materials and Methods: A total of 60 patients planned for Lumbar spinal fixation surgeries were selected and sorted into two groups of 30 each after a computer-based randomization. In Group G, a 5 cm × 1 cm piece of absorbable gelatin sponge soaked in 5 mg of morphine sulfate diluted in 0.9% normal saline up to 5 mL was placed in the epidural space. In Group I, 5 mg of morphine sulfate diluted in 0.9% normal saline 5 mL was instilled over the intact epidural space. Pulse rate, mean arterial pressure (MAP), respiratory rate (RR), and peripheral oxygen saturation (SpO2) were observed hourly for the first 6 h, then at 2 hourly intervals till 12 h, and at 4 hourly intervals till 48 h. Postoperatively, pain intensity is assessed by the Visual Analog Scale (VAS) for 24 h, and the time of the first analgesic dose is noted. VAS ranges from 0 (no pain) to 10 (severe pain). Preoperative instructions were given to the patients about the use of VAS. Results: In this study, Group G demonstrated lower postoperative VAS scores and delayed need for rescue analgesia compared to Group I (P &lt; 0.05, P &lt; 0.0001, respectively). Group I had a higher total analgesic requirement (P &lt; 0.0001) and consistently higher heart rates (P &lt; 0.0001) compared to Group G. MAPs were lower in Group G compared to Group I (P &lt; 0.0001). RRs, SpO2, sedation scores, and incidence of nausea and pruritus were similar between the two groups (P &gt; 0.05). Conclusion: Epidural administration of morphine using Gelfoam as a vehicle for sustained release of morphine is a safe and effective method of postoperative analgesia in lumbar spinal fixation surgeries and results in better hemodynamics, prolonged duration of analgesia, and reduced requirement of rescue analgesics, compared to epidural instillation of morphine.

6287202 Variable dosing of remifentanil analgesia during labour

6287202 Variable dosing of remifentanil analgesia during labour

Lateness of Acetaminophen and Non-steroidal Anti-inflammatory Drug Administrations in a Retrospective Cohort of Medication Administration Records Among Patients After Cesarean Delivery.

In an earlier study of patients after cesarean delivery, the concurrent versus alternating administration of acetaminophen and non-steroidal anti-inflammatory drugs was associated with a substantial reduction in total postoperative opioid use. This likely pharmacodynamic effect may differ if the times when nurses administer acetaminophen and non-steroidal anti-inflammatory drugs often differ substantively from when they are due. Weexamined the "lateness" of analgesic dose administration times, the positive difference ifadministered late, and the negative value ifearly. The retrospective cohort study used all 67,900 medication administration records for scheduled (i.e., not "as needed") acetaminophen, ibuprofen, and ketorolac among all 3,163 cesarean delivery cases at the University of Iowa between January 2021 and December 2023. Barcode scanning at the patient's bedside was used right before each medication administration. There were 95% of doses administered over a 4.8-hour window, from 108 minutes early (97.5% one-sided upper confidence limit 105 minutes early) to 181 minutes late (97.5% one-sided lower limit 179 minutes late). Fewer than half of doses (46%, P <0.0001) were administered ±30minutes of the due time. The intraclass correlation coefficient was approximately 0.11, showing that there were small systematic differences among patients. There likewise were small to no systematic differences in lateness based on concurrent administrations ofacetaminophen and ibuprofen or ketorolac, time of the day that medications were due, weekday, year, or number of medications to be administered among all such patients within 15 minutes. Other hospitals should check the lateness of medication administration when that would change their ability to perform or apply the results of analgesic clinical trials (e.g., simultaneous versus alternating administration).

Ketamine Sedation Decreases Survival after Extremity Trauma and Moderate Hemorrhage in Rats

Objective: Traumatic hemorrhage (HEM) is often associated with pain. The use of ketamine (KET) has increased both on the battlefield and in civilian emergency care for analgesia and sedation. We have reported that an analgesic dose of KET does not impact cardiorespiratory responses or survival after HEM (JAP 130: 1583-1593, 2021). In this study, we measured the effects of a larger, sedative, dose of KET on cardiovascular responses and survival to moderate (37% blood volume) HEM combined with extremity trauma (ET), and whether midazolam (MDZ), a drug often given in combination with KET alters these responses. Hypothesis: We hypothesized that either KET (50 mg/kg) or KET+MDZ (5 mg/kg) would compromise cardiovascular responses to HEM and thereby decrease survival. Methods: Male rats were implanted with a telemetry transmitter to measure mean arterial pressure (MAP) and heart rate (HR); buprenorphine SR was used to relieve pain associated with surgical procedures. Following 2 weeks recovery, rats were anesthetized using isoflurane, and a carotid catheter was implanted. The next day, rats were briefly anesthetized using isoflurane to perform ET (fibular fracture + hindlimb soft tissue crush injury) and were allowed to recover 90 min before starting conscious HEM (time = 0-25 min). Rats received either 1) saline vehicle (VEH, n=8); 2) KET (n=8); or 3) KET followed by MDZ (KET+MDZ; n=9) during a 15 min infusion (t = 25-40 min). The study continued for 200 minutes (time = 40-240 min). Data are mean ± SD. Results: There were no differences between groups in MAP or HR at either baseline (t = 0 min) or at end of HEM (t = 25 min). However, during the 20 min after treatment (t = 40-60 min), MAP and HR were significantly lower (P≤0.05) in KET (46 ± 3 mmHg; 220 ± 11 bpm) and KET+MDZ (45 ± 10 mmHg; 212 ± 24 bpm) compared to VEH (68 ± 20 mmHg; 297 ± 37 bpm). During this time, only 3 of 8 rats in the KET group survived HEM, while all rats survived in VEH and KET+MDZ groups. At the end of the study (t = 240 min), survival rate was significantly lower (P=0.003) in KET (37.5%) compared to VEH (87.5%) or KET+MDZ (100%). Similarly, survival time was significantly lower (P=0.004) in KET (115 ± 103 min) compared to VEH (227 ± 37 min) or KET+MDZ (240 ± 0 min). Summary of Results: A sedative dose of KET decreased survival following HEM, but the same dose of KET followed by MDZ was protective. The MDZ effect was not due to improvements in cardiovascular responses to the HEM. Conclusion: Sedation with ketamine alone after trauma and moderate HEM decreased survival. Further studies of the effects of sedation with KET alone or KET+MDZ on respiration and metabolic responses to HEM may provide insight on the overall effect on survival. Congressionally Directed Medical Research Program (CDMRP). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.