Transdermal Fentanyl for Cancer Pain Management in Opioid-Naive Pediatric Cancer Patients.

BACKGROUND: Transdermal therapeutic system fentanyl with a drug release rate of 12 µg/h should be of special value in pediatric cancer pain control. Such a fentanyl formulation allows for a stepwise dose increase, similar to that reported for sustained-release morphine. PATIENTS AND METHODS: Sixty-four male and female pediatric patients with moderate to severe chronic cancer pain, ages ranging 2-14 years, were included. Patients did not receive opioids prior to enrollment. Patients were observed for pain relief using the Visual Analog Scale and the Wong-Baker FACES Pain Rating Scale, play performance score, and for side effects. RESULTS: There was significant improvement of visual analog scale and FACES pain scores from the baseline to the second day of application (P < 0.001). By the 15th day, scores reached 1.18 ± 0.393 and 1.13 ± 0.35, respectively (P < 0.001). Play performance scale improved from the third day of application of the patch when compared with the baseline (P < 0.001), reaching 55.02 ± 8.35 (P < 0.001) at the end of the study. The sedation score increased on the second day to 2 in 10 patients and to 3 in 54 patients. By the seventh day, 56 patients had a sedation score of 1. All patients returned to baseline by the 15th day. Itching was reported in 16 cases, and erythema occurred in 10 cases. No significant side effects were reported. CONCLUSION: Transdermal fentanyl was found to be an effective, safe, and well-tolerated treatment for pediatric cancer-related pain in opioid-naive patients with chronic moderate to severe pain. In this study population, evaluation of vital signs and physical examination did not suggest any safety concerns while using transdermal fentanyl.

Management of hot flushes in breast cancer survivors: comparison between stellate ganglion block and pregabalin.

BACKGROUND: Women who have survived breast cancer have hot flushes that are "significantly more frequent, severe, distressing, and of greater duration" than in other women. We compared the efficacy and safety of stellate ganglion block and pregabalin for the relief of hot flushes in breast cancer survivors. PATIENTS AND METHODS: Forty patients who were breast cancer survivors and were suffering from hot flushes to the degree that they seeked for treatment were included in the study and randomly divided into two groups: group I: (N = 20) stellate ganglion block was done for the patients of this group; and group II: (N = 20) in this group, the patients received 75 mg pregabalin twice daily. In both groups self-completed daily hot flush diaries and monthly symptom questionnaires were obtained at baseline and for the following 3 months. RESULTS: Our results showed that group I (stellate ganglion block) had significant (P < 0.05) decline in the frequency of mild, moderate, very severe, and total hot flushes in comparison with group II (pregabalin 75 mg twice daily) throughout the 3 months of follow up period. CONCLUSION: The stellate ganglion block had superior efficacy in the management of hot flushes in breast cancer survivors.

The role of duloxetine in reducing opioid consumption after thoracotomy: a prospective, randomized, double-blinded, placebo-controlled pilot trial.

BACKGROUND: Exploration of the thoracic cavity through a thoracotomy incision for thoracic malignancies is accompanied by severe, excruciating acute postoperative pain. The objective of this study is to evaluate the efficacy of perioperative duloxetine when given as part of a multimodal analgesia in reducing the dose of opioids needed to treat acute postoperative pain after thoracotomy. METHODS: Sixty patients scheduled for thoracotomy were randomly assigned to one of two treatment groups. The duloxetine group (D) received duloxetine 60 mg orally two hours before the surgical procedure and 24 hours after surgery, and the placebo group (P) received oral equivalent placebo capsules during the same time schedule. The primary outcome was the postoperative consumption of narcotics. Secondary outcome measures were assessment of postoperative pain scores (VAS) during rest, walking and coughing, hemodynamic variables and development of any side effects. RESULTS: Total dose of morphine needed to treat postoperative pain in first 48 hours, intraoperative isoflurane concentrations, intra- and postoperative epidural infusion rates all were significantly lower in group D (P<0.001). Postoperative pain at rest (VAS-R) was significantly less frequent in group D compared to group P at all-time intervals so as during walking (VAS-W) (P<0.001). While during cough (VAS-C), it was comparable at all time point except at 12 hours which was significantly low in group D (P<0.001). The intra-, postoperative mean blood pressure and development of side effects were comparable between the two groups. CONCLUSIONS: Oral duloxetine used perioperatively during thoracic surgery may play an important role as multimodal analgesia for acute postoperative pain without any added side effects.

Differential Regulation of CD45 Expression on Granulocytes, Lymphocytes, and Monocytes in COVID-19.

CD45 is a transmembrane glycoprotein and protein tyrosine phosphatase expressed on the surface of all nucleated hematopoietic cells. While there is increasing evidence demonstrating the involvement of CD45 in immune system regulation, no information on CD45 expression in inflammation and sepsis is currently available. Therefore, we determined the CD45 surface expression on granulocytes, lymphocytes, and monocytes in patients with COVID-19 and healthy volunteers in both absence and presence of lipopolysaccharide (LPS). Following approval by the local ethics committee, whole blood samples were obtained from patients with COVID-19 infection on day 1 of hospital admission and healthy volunteers. Samples were incubated in absence and presence of LPS and CD45 was measured in granulocytes, lymphocytes, and monocytes using flow cytometry. In comparison with healthy individuals, COVID-19 patients showed an increased CD45 expression on the surface of granulocytes (+35%, p < 0.02) and lymphocytes (+39%, p < 0.0001), but a reduced CD45 expression on monocytes (−35%, p < 0.0001). LPS incubation of whole blood from healthy individuals increased the CD45 expression on granulocytes (+430%, p < 0.0001), lymphocytes (+32%, p = 0.0012), and monocytes (+36%, p = 0.0005), respectively. LPS incubation of whole blood samples from COVID-19 patients increased the CD45 expression on granulocytes and monocytes, and decreased the CD45 expression on lymphocytes. In conclusion, CD45 expression on leucocytes is altered: (1) in COVID-19 patients, and (2) in in vitro endotoxemia in a complex cell-specific way, thus representing a new immunoregulatory mechanism.

The Role of Double Modality Ultrasonographic and Fluoroscopic Guided Superior Hypogastric Plexus Neurolysis in Treating Intractable Pelvic Cancer Pain: A Comparative Study.

BACKGROUND: Superior hypogastric neurolytic block is performed to block visceral pelvic pain. This could be performed through the anterior approach guided by CT or ultrasound and through a posterior approach, guided by fluoroscopy or CT. METHODS: Sixty adult patients with severe visceral pelvic pain (VAS>70 mm) were randomly divided into two groups. Group S: SHP block was done ultrasound guided using the anterior approach and confirmed by fluoroscopy. Group F: SHP block was done fluoroscopic guided using the posterior oblique approach. The VAS (visual analog scale), duration of the technique, time of X-ray exposure, patient satisfaction score, patient global impression of change (PGIC), quality of life score, and daily morphine consumption (mg/day) were measured pre-procedure and at the 1st, 4th, 8th, and 12th week after the procedure. In addition, any side effects of the procedure were recorded. RESULTS: There was a significant difference in VAS between the two groups (P<0.01) (better in group S). The quality of life score was improved from the pre-procedure in both groups (P<0.05), and morphine consumption was significantly lower in group S than in group F (P<0.05) at the 1st, 4th, and 8th week and not significant at the 12th week. The two groups show a statistically significant difference as regards the duration of the procedure and X-ray exposure (P<0.01). There was a statistically significant difference in the satisfactory score between the two groups at the 1st, 4th, 8th, and 12th week (P<0.01). As regards the PGIC score, there was no statistically significant difference between the two groups (P>0.05). In group S, no back pain was reported, while 11 patients of group F complained from post-procedure back pain (P<0.001). CONCLUSION: The anterior ultrasound guided SHPB aided by fluoroscopy is suggested to be more superior to the standard fluoroscopic guided technique in relieving pelvic cancer pain and decreasing morphine consumption.

Analgesic Effect of Morphine Added to Bupivacaine in Serratus Anterior Plane Block Following Modified Radical Mastectomy. Only a Local Effect? Randomized Clinical Trial.

BACKGROUND: Serratus anterior plane (SAP) block, a novel regional anesthetic procedure, involves the anterolateral chest wall. Opioid receptors have been found on peripheral nerve terminals, so morphine may have a local action. OBJECTIVE: This work aimed at exploring the analgesic efficacy of morphine added to bupivacaine in SAPB in patients for whom modified radical mastectomy was conducted and whether it is a mere local effect. METHODS: Forty female patients were planned to have modified radical mastectomy participated in the study. Patients were randomly divided into two groups; Control group (C): received ultrasound-guided serratus anterior plane block with 20 mL of bupivacaine hydrochloride 0.25%; Morphine group (M): received the same in addition to 10 mg morphine sulfate. Intra- and post-operative blood samples were taken for the assessment of morphine serum levels. All patients were assessed for VAS scores during rest and movement (VAS-R and VAS-M). Time to the first request and the total amount of the rescue analgesia were recorded. RESULTS: In group M, Morphine was not detected in the plasma of all patients. Both VAS-R and VAS-M were significantly higher in group C than in group M (P<0.001) and (P≤0.003), respectively. Time to the first request of rescue analgesia was 8.5 h in group C compared to 20 h in group M (P=0.005) with a median dose of acetaminophen consumption of 2 g in group C compared to 1 g in group M (P=0.006). CONCLUSION: Ten mg of morphine, when added to bupivacaine in SAPB, improved postoperative analgesia in patients to whom modified radical mastectomy was conducted. This effect seems to be attributed merely to local mechanisms. REGISTRATION: The registration number of this study is NCT02962024 at www.clinicaltrial.gov.

Effect of Preperitoneal Versus Epidural Analgesia on Postoperative Inflammatory Response and Pain Following Radical Cystectomy: A Prospective, Randomized Trial.

OBJECTIVES: Continuous wound infiltration of local anesthetics has been proposed as an alternative to epidural analgesia during abdominal surgery. Cytokines have a major role in inflammatory changes caused by surgery. This study aimed to compare the effects of continuous preperitoneal versus epidural analgesia on inflammatory cytokines postoperatively. MATERIALS AND METHODS: Forty patients scheduled for radical cystectomy were included in this observer-blinded, randomized trial; patients were randomly assigned into 2 groups to receive; continuous preperitoneal wound infiltration (PPB) or epidural analgesia (EDB). Serum levels of interleukins (IL1ß, IL6, IL10, and tumor necrosis factor α) were measured at baseline (before induction of anesthesia), preinfusion (before the start of local anesthetic infusion), 6 and 24 hours postoperatively. Visual Analog Scale at rest/movement (VAS-R/M), time to the first request of analgesia, total morphine consumption, sedation score, hemodynamics, and side effects were observed 24 hours postoperatively. RESULTS: There was a significant reduction in IL6, IL1ß and increase in IL10 in PPB compared with EDB at 6 and 24 hours postoperatively and compared with preinfusion levels (P≤0.001). In EDB, a significant increase in IL1ß, IL10, and tumor necrosis factor α at 6 hours compared with preinfusion levels (P≤0.002). VAS-R/M was significantly decreased at 2, 4, 6, 8, and 12 hours in EDB compared with PPB (P≤0.014), with no significant difference in the mean time to the first request of analgesia and total morphine consumption between the 2 groups. CONCLUSION: Continuous preperitoneal analgesia better attenuated postoperative inflammatory response and provided a comparable overall analgesia to that with continuous epidural analgesia following radical cystectomy.

Antimicrobial and Cytotoxicity Effects of Synthesized Silver Nanoparticles from Punica granatum Peel Extract.

To address the growing challenges from drug-resistant microbes and tumor incidence, approaches are being undertaken to phytosynthesize metal nanoparticles, particularly silver nanoparticles, to get remedial measure. In this study, an attempt has been made to utilize a major biowaste product, pomegranate fruit peel (Punica granatum), to synthesize silver nanoparticles. The silver nanoparticles (AgNPs) were synthesized using the aqueous extract of pomegranate peel. The formation of synthesized AgNPs was confirmed through UV-Vis spectroscopy, X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDX) as well as through the change of the colorless aqueous solution to a dark brown solution. Using UV-Vis spectroscopy, the dark brown solution showed a Plasmon resonance band peak at 378 nm in UV-Vis spectroscopy after reacting for 24, 48, and 72 h. The XRD report revealed that the AgNPs had a cubic structure. The TEM and SEM report showed the nanoparticles were equally distributed in the solution, with a spherical shape and size ranging from 20 to 40 nm and with an average particle size of 26.95 nm. EDX imaging also confirmed the presence of AgNPs. The synthesized AgNPs were found to exhibit good antimicrobial effects on Gram-negative and Gram-positive bacteria, particularly the pathogens Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27584), Proteus vulgaris (ATCC 8427), Salmonella typhi (ATCC 14028), Staphylococcus aureus (ATCC 29213), Staphylococcus epidermidis (MTCC 3615), and Klebsiella pneumonia. The cytotoxic effects of AgNPs were also tested against a colon cancer cell line (RKO: ATCC® CRL-2577™), and it was observed that the viabilities were 56% and 61% on days 3 and 5, respectively, with exposure to 12.5 µg of AgNPs. This simple, economic, and eco-friendly method suggests that the AgNPs biosynthesized using pomegranate peel extract may be a novel, potent solution for the development of a drug for colon cancer that also has antibacterial activity.

Comparison of three different doses sugammadex based on ideal body weight for reversal of moderate rocuronium-induced neuromuscular blockade in laparoscopic bariatric surgery.

BACKGROUND: The majority of authors and the literature recommend sugammadex dose to be calculated according to RBW without taking fat content into consideration. Our aim was to compare the efficacy and safety of sugammadex at doses of 1.5, 2, and 4 mg/kg, calculated according to ideal body weight basis, for the reversal of moderate rocuronium-induced neuromuscular blockade in laparoscopic bariatric surgery. METHODS: One-hundred and eighty morbidly obese patients were randomly assigned into three groups according to sugammadex dose administrated (based on IBW after reaching T2 of TOF): Group I: patients were given 1.5 mg/kg. Group II: patients were given 2 mg/kg. Group III: patients were given 4 mg/kg. Both sugammadex and extubation times were recorded. RESULTS: Sugammadex time was significantly longer in groups I and II versus III (P=0.000, 0.005 respectively). Difference between groups I and II was insignificant. The extubation time was insignificantly different in the three groups (P>0.05). CONCLUSIONS: A dose of sugammadex of 1.5 mg/kg calculated according to IBW successfully reversed moderate rocuronium-induced NMB in laparoscopic bariatric surgeries.

Efficacy and Safety of Ketamine Added to Local Anesthetic in Modified Pectoral Block for Management of Postoperative Pain in Patients Undergoing Modified Radical Mastectomy.

BACKGROUND: Breast surgery is an exceedingly common procedure with an increased incidence of acute and chronic pain. Pectoral nerve block is a novel peripheral nerve block alternative to neuro-axial and paravertebral blocks for ambulatory breast surgeries. OBJECTIVES: This study aims to compare the analgesic efficacy and safety of modified Pecs block with ketamine plus bupivacaine versus bupivacaine in patients undergoing breast cancer surgery. STUDY DESIGN: A randomized, double-blind, prospective study. SETTING: Academic medical center. METHODS: This study is registered at www.clinicaltrials.gov under number: (NCT02620371) after approval by the ethics committee of South Egypt Cancer Institute, Assuit University, Assuit, Egypt. Sixty patients aged 18 - 60 years scheduled for modified radical mastectomy were enrolled and randomly assigned into 2 groups (30 patients each): Control group patients were given ultrasound-guided, Pecs block with 30 mL of 0.25% bupivacaine only. Ketamine group patients were given ultrasound-guided, Pecs block with 30 mL of 0.25% bupivacaine plus ketamine hydrochloride (1 mg/kg). Patients were followed up for 48 hours postoperatively for vital signs, VAS score, first request of rescue analgesia and total morphine consumption, sedation score, and side effects. RESULTS: Ketamine plus bupivacaine in Pecs block compared to bupivacaine alone prolonged the mean time of first request of analgesia (18.25 ± 1.98), (12.56 ± 2.64), respectively (P < 0.001), reduced total morphine consumption (12.50 ± 4.63), (18.86 ± 6.28), respectively (P = 0.016). With no significant difference in hemodynamics, respiratory rate, oxygen saturation, VAS and sedation scores, and side effects observed between the 2 groups (P > 0.05). LIMITATIONS: This study is limited by its sample size. CONCLUSION: The addition of ketamine to modified Pecs block prolonged the time to first request of analgesia and reduced total opioid consumption without serious side effects in patients who underwent a modified radical mastectomy. KEY WORDS: Ketamine, bupivacaine, pecs block, postoperative, pain, breast cancer.

Efficacy and safety of dexmedetomidine added to caudal bupivacaine in pediatric major abdominal cancer surgery.

BACKGROUND: Caudal analgesia has been prolonged by the addition of various adjuvants. Dexmedetomidine is a highly selective alpha-2 agonist with sedative and analgesic properties. OBJECTIVE: To investigate the effect of addition of dexmedetomidine to 0.25% bupivacaine for caudal analgesia in children undergoing major abdominal cancer surgery. STUDY DESIGN: A randomized double-blind trial. SETTING: Academic medical center. METHODS: Forty pediatric patients, aged 3 - 12 years, weighting 10 - 40 kg, and of American Society of Anesthesiologists (ASA) physical status I and II scheduled for major abdominal cancer surgeries under general anesthesia combined with caudal analgesia were enrolled. They were randomly allocated into 2 groups: Group I (BD): (n = 20) received 1 mL/kg bupivacaine 0.25% with dexmedetomidine 1 µg/kg and group II (B): (n = 20) received 1 mL/kg bupivacaine 0.25%. Heart rate (HR), mean arterial pressure (MAP), and oxygen saturation (SPO2) were recorded for 120 minutes. Pain was assessed immediately postoperative and at hours 2, 4, 6, 12, 18, and 24 of postoperative period by Face, Legs, Activity, Cry and Consolability (FLACC) score. Time to first request for analgesia and total analgesic consumption in the first 24 hours were recorded. The level of sedation was recorded using Ramsay's sedation scale [Intravenous acetaminophen 15mg/kg (perfalgan, Squibb)]. Adverse effects were recorded and treated. RESULTS: There was significant reduction in FLACC score in group BD at 2, 4, 6, and 12 hours postoperatively compared to group B. At the eighteenth and twenty-fourth hour there was no significant difference. Time of the first rescue analgesic requirement was significantly prolonged in group BD compared to group B. The mean total consumption of rescue analgesia in the 24 hours of the postoperative period was significantly decreased in group BD (405.00 ± 215.03) mg when compared with group B (810.35 ± 200.93) mg. LIMITATIONS: This study is limited by its small sample size. CONCLUSION: Addition of dexmedetomidine (1 µg/kg) to caudal bupivacaine 0.25% (1 mL/kg) in pediatric major abdominal cancer surgeries achieved significant postoperative pain relief for up to 19 hours, with less use of postoperative analgesics, and prolonged duration of arousable sedation. Hemodynamic changes were statistically significant, yet of no clinical significance.