Magnesium Sulfate in Pediatric Abdominal Cancer Surgery: Safety and Efficacy in Ultrasound-Guided Transversus Abdominis Plane (US-TAP) Block in Conjugation with Levobupivacaine.

Purpose: Magnesium sulfate (MgSO4) may enhance the effects of local anesthetics when used as an adjuvant in peripheral nerve blocks. Our objective was to evaluate efficiency and safety of utilizing MgSO4 alongside levobupivacaine in bilateral ultrasound-guided transversus abdominis plane (US-TAP) block for postoperative pain in pediatric cancer patients who underwent abdominal surgery. Methodology: A randomized double-blinded controlled trial at South Egypt Cancer Institute, Assiut University, Assiut, Egypt, included that 40 pediatric patients with Wilms' tumor or neuroblastoma were randomly allocated to get bilateral (US-TAP) block and divided into two groups; M group: received US-TAP with 0.6 mL/kg levobupivacaine 0.25% + 2 mg/kg MgSO4 and C group: received with 0.6 mL/kg levobupivacaine 0.25% only. FLACC scores (Face, Leg, Activity, Cry, Consolability) were used to evaluate post-operative pain, first analgesic request, total analgesic consumption, adverse effects, as well as hemodynamics were monitored for 24 h and recorded at time points (2, 4, 6, 8, 12, 18, and 24h). Parent's satisfaction at discharge, also, was evaluated. Results: FLACC score in M group was significantly lower than in C group from 4 h to 24 h with the first analgesic request being longer (15.95 ± 1.99 vs 7.70 ± 0.80 (h); p < 0.001) and lower total analgesic consumption (231.75 ± 36.57 vs 576.00 ± 170.71 (mg); p < 0.001) when comparing M group to C group, respectively. Both groups had insignificant differences regarding hemodynamics, parent satisfaction, postoperative agitation, and side effects except vomiting occurred in two patients in the C group and one patient in the M group. Conclusion: We conclude that adding magnesium sulphate as an adjuvant to local anaesthetic in US-TAP block for pain management in pediatric abdominal cancer surgeries resulted in better and longer analgesia, with less consumption of rescue analgesics with no serious side effects.

Immunosuppressive Effect of Intrathecal Morphine, Dexmedetomidine, or Both in Combination with Bupivacaine on Patients Undergoing Major Abdominal Cancer Surgery.

BACKGROUND: An impaired immune system in the perioperative period has important clinical implications in patients with cancer. Despite the immunosuppressive properties of opioid therapy, it is still commonly utilized in the intrathecal or epidural space for the treatment of postoperative pain. Also, intrathecal dexmedetomidine has extended analgesic efficacy in postoperative pain; it can significantly affect immune function in perioperative patients. OBJECTIVE: To investigate the effect of intrathecal morphine, dexmedetomidine, or both in combination with bupivacaine on cellular immunity and cytokine production in cancer surgical patients. STUDY DESIGN: A prospective randomized clinical study. SETTING: South Egypt Cancer Institute, Assiut University. METHODS: Ninety patients were randomly assigned to receive intrathecal morphine 0.5 mg (Group M, n = 30), dexmedetomidine 0.5 µg/kg (Group D, n = 30) or morphine 0.5 mg with dexmedetomidine 0.5 µg/kg (Group MD n = 30); 2 mL bupivacaine 0.5% was added to injected drugs in all groups.  Blood samples were collected preoperative (T0), immediate postoperative (T1), 4 hours postoperative (T2), and 24 hours postoperative (T3) for measurement of CD3, CD4, CD4/CD8 and CD16+56(NK), interleukin(IL)-1beta (IL-1beta), IL-6, IL-10 and tumor necrosis factor alpha (TNF-alpha). RESULTS: A significant reduction in cellular immunity (CD3, CD4, CD8, CD4/CD8, CD 16+56) was noticed in the 24-hour postoperative period in all 3 studied groups, with a marked reduction in Group M in comparison to Group MD and Group D. Regarding inflammatory mediators, IL-10 and IL-1beta  showed significant reduction in Group M in the first 24-hour postoperative period in comparison to Group MD and Group D, while IL-6 was significantly reduced in Group MD and Group D in comparison to Group M in the same period. TNF-alpha was significantly increased postoperative at T1 and T2 in the 3 studied groups, then at T3 it decreased without a statistically significant difference with the preoperative level. LIMITATIONS: Our study has some limitations, such as the short period of follow-up and lack of postoperative clinical follow-up of patients to discover the association between immunity and patient outcomes. CONCLUSION: Intrathecal dexmedetomidine has the least immunosuppressive effect than morphine and morphine-dexmedetomidine, in combination with bupivacaine.

Efficacy of Ketamine versus Magnesium Sulphate as Adjuvants to Levobupivacaine in Ultrasound Bilevel Erector Spinae Block in Breast Cancer Surgery (a Double-Blinded Randomized Controlled Study).

Purpose: Breast surgeons seek simple, safe, effective, and novel regional anesthesia techniques for postoperative analgesia. Erector spinae plane (ESP) block is a new ultrasound-guided technique. We aimed to explore the analgesic effect of adding ketamine and magnesium sulfate as adjuvants to levobupivacaine in ESP. Patients and Methods: Sixty female patients (aged 18-60 years) with breast cancer, weighing 50-90 kg who were scheduled for modified radical mastectomy (MRM) were randomly allocated into three groups (20 patients each) to receive an ESP block with 20 mL 0.25% levobupivacaine with adjuvants according to the following groups: group C: levobupivacaine; group K: levobupivacaine + 2 mg/kg ketamine; and group M: levobupivacaine + 2 mg/kg magnesium sulfate. The block was administered preoperatively before anesthesia induction. Postoperatively, hemodynamics, visual analog scale scores, the first request for analgesia, total analgesic consumption, and side effects were observed for 48 hours. Results: The total amount of Morphine rescue analgesia was significantly lower in groups M (7.00 ± 0.61 mg) and K (7.50 ± 0.58 mg) than in group C (14.40 ± 3.47 mg) during the first 48 h postoperatively. Nine (45%) patients in group M and 13 (65%) patients in K, compared with 20 (100%) patients in group C, requested analgesia. The time to first request of analgesia was significantly longer in groups M (30 h) and K (24 h) than in group C (7 h). No hemodynamic changes or serious side effects were observed. Conclusion: Magnesium sulphate and ketamine seem to be both effective adjuvants to levobupivacaine in ESP blocks for postoperative analgesia in patients undergoing MRM, with slightly better analgesia provided by magnesium sulphate.

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.

Analgesic Effect of Intrathecal Fentanyl vs Dexmedetomidine as Adjuvants to Bupivacaine Following Abdominal Surgery for Cancer in Children, a Randomized Trial.

BACKGROUND: Intrathecal fentanyl in spinal anesthesia improves intra- and postoperative analgesia. Dexmedetomidine is a fascinating adjuvant with regards to neuraxial anesthesia in children experiencing surgery for abdominal malignancy. PATIENTS AND METHODS: After endorsement by the institutional reviewing board (IRB) and guardians' written informed consent, this research was carried out on 60 pediatric malignancy patients scheduled for major abdominal surgery. Children were randomly distributed into three groups (20 patients each): Group C: given 2 mL of bupivacaine 0.5% (0.4 mg/kg) intrathecally, injected gradually over 20 seconds. Group F: the same as group C, plus fentanyl 0.2 µg/kg. Group D: the same as group C, plus dexmedetomidine 0.2 µg/kg. Pain at zero, two, four, six, 12, 18, and 24 hours postoperatively was evaluated by Face, Legs, Activity, Crying, and Consolability (FLACC) score. First analgesic request and postoperative unfavorable effects were recorded for 24 hours postoperatively. RESULTS: A significant decrease was recognized in the mean FLACC score in groups D and F at six, eight, and 12 hours postoperatively, in contrast to group C (P ≤ 0.05). First analgesic request was significantly prolonged in group D (7.67 ± 0.57 hours), in contrast to groups F and C (5.40 ± 1.09 hours and 4.23 ± 3.27 hours, respectively, P < 0.04). Paracetamol utilization was significantly decreased in group D (316.67 ± 28.86 mg), in contrast to group C (391.00 ± 52.00 mg, P < 0.03), without a significant difference between group F (354.44 ± 46.67 mg) and groups D and C (P > 0.05). CONCLUSIONS: Adding dexmedetomidine and fentanyl to intrathecal bupivacaine improved postoperative analgesia following abdominal surgery for cancer in children, with better overall analgesia of dexmedetomidine compared with fentanyl.

Epidural dexmedetomidine infusion for perioperative analgesia in patients undergoing abdominal cancer surgery: randomized trial.

OBJECTIVE: To assess the postoperative analgesic efficacy of epidural dexmedetomidine added to bupivacaine infusion for patients undergoing major abdominal cancer surgery. METHODS: Patients scheduled for major upper abdominal cancer surgery were allocated to group bupivacaine (n =32), in which patients received epidural bupivacaine infusion (6 mL/h bupivacaine 0.1%) for 48 hours postoperatively, or group bupivacaine + dexmedetomidine (n=32), in which patients received epidural dexmedetomidine added to bupivacaine infusion (6 mL/h of bupivacaine 0.1% + dexmedetomidine, 0.5 µg/mL) for 48 hours postoperatively. The cumulative morphine consumption, the time to first analgesic request, and the VAS pain score were evaluated. RESULTS: The cumulative morphine consumption was significantly reduced in group bupivacaine + dexmedetomidine compared with group bupivacaine: mean ± SD of 10.40±5.16 mg vs 23.23±8.37 mg with an estimated difference (95% CI) of -12.83 (-16.43, -9.24), (P<0.001). The time to the first analgesic demand was significantly delayed in group bupivacaine + dexmedetomidine compared with group bupivacaine: median (IQR) of 6 (1.75, 8.25) h vs 1 (0, 4)h, (P<0.001). The mean collapsed over time of overall VAS pain scores at rest and movement was significantly reduced in group bupivacaine + dexmedetomidine compared with group bupivacaine : mean ± SE of 1.6±0.08 vs 2.38±0.08 with an estimated difference (95% CI) of -0.8 (-1, -0.86), (P<0.001), and mean ± SE of 2.17±0.07 vs 3.25±0.07 with an estimated difference (95% CI) of -1.1 (-1.27, - 0.89), (P<0.001), respectively. CONCLUSION: Epidural infusion of dexmedetomidine added to bupivacaine for patients undergoing major abdominal cancer surgery significantly reduced morphine consumption, delayed time to first analgesic supplementation, and decreased pain intensity during the first 48 hours postoperatively without harmful derangement on hemodynamics.

Effect of Topical Morphine on Acute and Chronic Postmastectomy Pain: What Is the Optimum Dose?

BACKGROUND AND OBJECTIVES: Poorly controlled postoperative pain is strongly associated with the development of chronic pain. We aimed to investigate the effect of topical morphine (in 1 of 3 doses: 5, 10, or 15 mg) on acute and chronic neuropathic pain after modified radical mastectomy for cancer breast. METHODS: In this registered clinical trial (ClinicalTrials.gov identifier: NCT02462577), 90 patients were allocated to receive 10 mL plain bupivacaine 0.5% plus either 5, 10, or 15 mg morphine (designated by the group names Morphine5, Morphine10, and Morphine15, respectively). The combination was diluted by saline 0.9% to 20 mL and irrigated in the wound before skin closure. Groups were compared for the following: time to first postoperative analgesia; intravenous patient-controlled analgesia (PCA) morphine consumption; pain scores; hemodynamics; sedation; adverse events in first postoperative 48 hours; and Leeds Assessment of Neuropathic Symptoms and Signs scores in first and third postoperative months. RESULTS: No patient in the Morphine15 group requested postoperative PCA morphine versus 19 and 8 in the Morphine5 and Morphine10 groups, respectively (P < 0.002). Time to first analgesic request and total consumption of PCA morphine analgesia were 7.31 ± 3.12 hours versus 14.00 ± 3.54 hours (P < 0.000) and 1.42 ± 0.50 mg versus 1.00 ± 0.00 mg (P = 0.371) in the Morphine5 and Morphine10 groups, respectively. Lowest scores on visual analog pain scale at rest (P < 0.001) and visual analog pain scale during movement (P < 0.01) were recorded in the Morphine15 group, followed by Morphine10 then Morphine5 group. Lowest Leeds Assessment of Neuropathic Symptoms and Signs scores were recorded in the Morphine15 group in the first month (1.10 ± 0.37 vs 5.76 ± 3.26 and 4.73 ± 2.87, P < 0.0001) and third postoperative month (4.40 ± 1.77 vs 6.33 ± 3.21 and 5.43 ± 2.67, P < 0.006) compared with Morphine5 and Morphine10 groups, respectively. No patient in the Morphine15 group developed chronic pain versus 4 and 2 in Morphine5 and Morphine10 groups, respectively. CONCLUSIONS: Topical morphine controlled acute postmastectomy pain in a dose-dependent manner and reduced the incidence and severity of chronic postmastectomy pain syndrome.

Combined Intrathecal Morphine and Dexmedetomidine for Postoperative Analgesia in Patients Undergoing Major Abdominal Cancer Surgery.

OBJECTIVE: To compare the analgesic effect of combined intrathecal morphine and dexmedetomidine with either drug alone for postoperative analgesia in patients undergoing major abdominal cancer surgery. METHODS: Ninety patients were allocated to receive intrathecal 10 mg bupivacaine 0.5% (bupivacaine group, n = 30), 10 mg bupivacaine 0.5% and 0.5 mg morphine (Morphine Group, n = 30), or 10 mg bupivacaine 0.5%, 0.5 mg morphine and 5 µg dexmedetomidine (morphine-Dex group, n = 30). The groups were compared with time to first postoperative analgesia, iv patient-controlled analgesia (PCA) morphine consumption, pain scores, hemodynamics, sedation, and adverse events in the first 48h postoperative. RESULTS: The time to first use of morphine PCA was longer in morphine (22.13 ± 5.21h, P = 0.000) and morphine-Dex (23.46 ± 4.69h, P = 0.000) groups compared with bupivacaine group (0.50 ± 0.09h). Dexmedetomidine addition increased the duration of intrathecal morphine (ITM) analgesia by 1.33 h (P = 0.485). Morphine consumption was less in morphine (10.83 ± 2.96 mg, P = 0.000) and morphine-Dex (11.00 ± 3.32 mg, P = 0.000) groups than in bupivacaine group (27.5 ± 4.30 mg), with a nonsignificant difference between morphine and morphine-Dex groups (P = 0.375). Morphine and morphine-Dex groups showed lower pain scores (P < 0.001). Intraoperative blood pressure and heart rate were lower in morphine and morphine-Dex groups (P < 0.05) with no significant difference between groups in postoperative hemodynamics. Patients in bupivacaine group showed a higher incidence of postoperative nausea (P < 0.03) and vomiting (P < 0.01), while patients in morphine and morphine-Dex groups had a higher incidence of pruritus (P < 0.02). CONCLUSIONS: Our results do not support improved analgesia with the combination of intrathecal morphine and dexmedetomidine, despite the absence of significant adverse effects.

Efficacy and safety of intraperitoneal dexmedetomidine with bupivacaine in laparoscopic colorectal cancer surgery, a randomized trial.

OBJECTIVE: Our objective is to investigate the efficacy and safety of intraperitoneal dexmedetomidine (Dex) combined with bupivacaine in patients undergoing laparoscopic colorectal cancer surgery. DESIGN: Randomized double-blind study. SETTING: Academic medical center. PATIENTS AND METHODS: Forty-five patients scheduled for laparoscopic colorectal cancer surgery were randomly assigned for intraperitoneal administration of 50 mL saline (control group; GI, n = 15), 50 mL bupivacaine 0.25% (125 mg; GII, n = 15), or 50 mL bupivacaine 0.25% (125 mg) +1 µg/kg Dex (GIII, n = 15). Patients were assessed during the first 24 hours postoperatively for hemodynamics, visual analogue scale (VAS), time to first request of analgesia, total analgesic consumption, shoulder pain, and side effects. RESULTS: A significant reduction was observed in VAS in GIII at base line, 2, 4, and 24 hours postoperatively in comparison to GI and GII (P < 0.05). The time to first analgesic requirement was significantly prolonged in GIII (P < 0.05). The mean total consumption of rescue analgesia was significantly reduced in GIII. CONCLUSION: We conclude that intraperitoneal administration of Dex 1 µg/kg combined with bupivacaine improves the quality and the duration of postoperative analgesia and provides an analgesic sparing effect compared to bupivacaine alone without significant adverse effects in patients undergoing laparoscopic colorectal cancer surgery.

High dose intrathecal morphine for major abdominal cancer surgery: a prospective double-blind, dose-finding clinical study.

BACKGROUND: Despite 30 years of clinical research, we still do not know the optimal dose of intrathecal morphine (ITM) when used alone. OBJECTIVES: A safety investigation and comparison of the analgesic efficacy of ITM 0.2 mg, 0.5 mg, and 1 mg in patients undergoing major abdominal cancer surgery. STUDY DESIGN: A randomized, double-blind trial. SETTING: Academic medical center. METHODS: Ninety patients were randomly assigned to receive morphine intrathecally either 0.2 mg (Group I, ITM 0.2 mg, n = 30), 0.5 mg (Group II, ITM 0.5 mg, n = 30), or 1 mg (Group III, ITM 1 mg, n = 30) dissolved in 5 mL physiological saline before general anesthesia. Assessment parameters included hemodynamics, respiratory rate, peripheral arterial oxygenation, sedation score, pain severity, time of first analgesic request, total analgesic consumption, and side effects in the first 72 hours. RESULTS: The mean time to first request for rescue analgesia was significantly prolonged in Group II (22.13 ± 5.21 hours, P < 0.001) and Group III (30.83 ± 4.89 h, P < 0.001), compared with Group I (0.50 ± 0.66 hours). The mean tramadol consumption dose was significantly reduced in Group II (383.33 ± 91.28 mg, P < 0.001) and Group III (300 ± 69.48 mg, P < 0.001) compared with Group I (770 ± 114.92 mg). Patients received 1 mg ITM showed lower VAS scores in the first 48 h postoperative (P < 0.04) compared with Group I and Group II. No significant differences were observed in the mean systolic and diastolic blood pressure values, respiratory rate, and peripheral arterial oxygen saturation between groups. Lower mean heart rate values were observed in Group III patients at 6 hours (P < 0.01) and 12 hours (P < 0.03) postoperative compared with Group I and Group II patients. Six patients (20%) in Group II and 8 (26.7%) in Group III exhibited pruritus compared with 2 patients (6.66%) in Group I (P < 0.01). No intergroup statistical differences were observed for other studied side effects. LIMITATIONS: This study is limited by its small sample size. CONCLUSION: One mg ITM provided superior analgesia for 48 hours postoperative compared with 0.2 mg and 0.5 mg ITM with a nonsignificant difference in the incidence of side effects. Further studies of larger sample size are recommended to confirm these findings.

Efficacy of intrathecally administered dexmedetomidine versus dexmedetomidine with fentanyl in patients undergoing major abdominal cancer surgery.

BACKGROUND: Most of the clinical experience gained in the use of intrathecal alpha-2- adrenoceptor agonists has been described with clonidine. Human studies using a combination of intrathecal dexmedetomidine and local anesthetics are lacking. OBJECTIVES: A safety investigation and comparison of the analgesic efficacy of intrathecally administered dexmedetomidine or dexmedetomidine combined with fentanyl in patients undergoing major abdominal cancer surgery. STUDY DESIGN: A randomized, double-blind trial. SETTING: Academic medical center. METHODS: Ninety patients were randomly assigned to receive intrathecally either 10 mg bupivacaine 0.5% (control group, n = 30), or 10 mg bupivacaine 0.5% plus 5 µg dexmedetomidine (dexmedetomidine group, n = 30), or 10 mg bupivacaine 0.5% plus 5 µg dexmedetomidine and 25 µg fentanyl (dexmedetomidine= group, n = 30). Assessment parameters included hemodynamics, sedation score, pain severity, time of first analgesics request, total analgesic consumption, and side effects in the first 24 hours. RESULTS: The mean intraoperative heart rate was significantly reduced in the dexmedetomidine group (P < 0.05) and the dexmedetomidine= group (P < 0.05) compared with the control group. Also, there was a significant reduction in mean intraoperative systolic and diastolic blood pressure in the dexmedetomidine group (P < 0.05) and the dexmedetomidine= group (P < 0.05) compared with the control group, with no significant differences in postoperative hemodynamics or sedation scores among all the study groups. The mean visual analog scale scores showed a significant reduction immediately and at 12 hours postoperatively in both the dexmedetomidine and dexmedetomidine= groups compared to the control group. The mean time of the first analgesic request was significantly prolonged in the dexmedetomidine group (3.30 ± 0.87 hours, P < 0.01) and the dexmedetomidine= group (5.41 ± 1.23 hours, P < 0.01) compared with the control group (0.23 ± 0.11 hours). Moreover, postoperative tramadol consumption was significantly reduced in the dexmedetomidine (142.85 ± 13.04 mg, P < 0.01) and the dexmedetomidine= (131.25 ± 11.96 mg, P < 0.01) groups, compared with the control group (310.0 ± 12.08 mg). No significant serious adverse effects were recorded during the study. LIMITATIONS: This study is limited by its sample size. CONCLUSION: Dexmedetomidine 5 µg given intrathecally improves the quality and the duration of postoperative analgesia and also provides an analgesic sparing effect in patients undergoing major abdominal cancer surgery. Furthermore, the addition of intrathecal fentanyl 25 µg has no valuable clinical effect.

Pharmacokinetics of oral tramadol in patients with liver cancer.

BACKGROUND: There are no studies reported on pharmacokinetics of opioids in patients with hepatocellular carcinoma, the fifth most common cancer in the world. METHODS: The authors have studied the pharmacokinetic profile of oral tramadol (50 mg) capsule in 20 patients with liver carcinoma (10 with primary carcinoma on top of chronic hepatitis C and 10 with secondary metastatic liver malignancy as a result of other primary) compared with 10 healthy controls. Plasma tramadol concentrations were measured in venous samples at intervals up to 12 hours by high-pressure liquid chromatography. Allpharmacokinetic variables were evaluated using one-compartment model. RESULTS: Tramadol bioavailability showed a substantial increase in patients with primary liver cancer and secondary metastatic than that of control (98 percent, 75 percent, and 68 percent, respectively). The area under the serum concentration-time curve increased significantly in patients with primary and metastatic cancer of liver than in control [1,933 microg/h/L (SD = 41), 1,327 microg/h/L (SD = 51), 1,138.5 microg/h/L (SD = 31), respectively]. Also, a significant difference in Cmax and Tmax was found between patients with malignant liver and control. Reduced clearance and impaired elimination was significantly observed in patients with liver carcinoma than control. Clearance was reduced to 50 percent of control, and elimination halflife increased up to three folds in patients with primary liver carcinoma than that of control. Satisfactory pain relief with minimal side effects was observed all over study period. CONCLUSION: It is recommended to lengthen the dose interval of oral tramadol, if it is to be used in patients with liver cancer for analgesic purposes, to 50 mg every 12 hours as it is proved to be effective and safe.