Efficacy of perioperative duloxetine as a part of multimodal analgesia in laparoscopic colorectal cancer surgeries.

BACKGROUND: Although laparoscopic surgery provides earlier recovery, less morbidity and hospital stay, however, severe pain is still a problem after it. Duloxetine has been recently used in postoperative pain management. We tested perioperative duloxetine to evaluate its effect on patients undergoing laparoscopic colorectal cancer surgery. METHODS: Sixty patients were enrolled in this study divided into two equal groups; duloxetine group each patient received an oral duloxetine capsule (60 mg) 1st dose at night before surgery, the 2nd dose 1 h preoperative, and the 3rd dose 24 h postoperative. Placebo group received placebo capsules at the same times. The cumulative morphine consumption in 48 h, postoperative VAS score, quality of recovery (QoR-40 score), sedation, and adverse effects were evaluated. RESULTS: Duloxetine group had lower VAS scores compared to placebo group, (3 ± 0.69) VS. (4.17 ± 0.83), (2.5 ± 0.6) VS. (4.3 ± 0.9), (2.2 ± 0.7) VS. (3.9 ± 0.6), (1.6 ± 0.7) VS. (3.6 ± 0.8), (1.1 ± 0.8) VS. (3.7 ± 0.7), (0.7 ± 0.7) VS. (3.5 ± 0.8), (0.6 ± 0.7) VS. (3.5 ± 0.8) respectively, P ˂0.01. The cumulative morphine consumption was significantly reduced in the Duloxetine group compared to the placebo group (4.6 ± 2.9 vs. 11.3 ± 1.7 mg), P < 0.01. The total QoR-40 score for duloxetine group was (180.8 ± 4.5) vs. (156 ± 5.9) in placebo group (P < 0.01). Patients in Duloxetine group were more sedated in all the 48 h postoperatively in comparison to placebo group. CONCLUSIONS: Perioperative duloxetine had reduced postoperative pain, decreased opioid consumption, and improved the quality of recovery in patients undergoing laparoscopic colorectal surgery.

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.

Effect of Transcranial Direct Current Brain Stimulation of the Motor Cortex on Chemotherapy-Induced Nausea and Vomiting in Female Patients with Breast Cancer.

OBJECTIVE: Chemotherapy-induced nausea and vomiting (CINV) is an adverse outcome associated with chemotherapy and is sometimes difficult to manage. This study aimed to examine the impact of a single session of transcranial direct current brain stimulation (tDCS; 2 mA) over the motor cortex for 20 minutes before chemotherapy in patients receiving a highly emetogenic chemotherapy. STUDY DESIGN: Prospective randomized double-blind sham-controlled study. SETTING: Academic medical center. METHOD: Sixty patients with breast cancer who were scheduled for chemotherapy treatment were selected and allocated randomly into two equal groups: a stimulation group and a sham group. tDCS was implemented over the primary motor area (M1) (2 mA) for 20 minutes. Patients' nausea was measured by a cumulative index of nausea, a visual analog scale for nausea (VAS-N), episodes of vomiting, and the Edmonton Symptoms Assessment Scale (ESAS) to assess symptoms like pain, malaise, and sense of well-being. Evaluation was done before stimulation and every 24 hours for 72 hours after the end of infusion of chemotherapy. RESULTS: The tDCS group showed a reduction in the cumulative index of nausea (P < 0.001, F = 50), the VAS-N (P < 0.001, F = 52), the ESAS malaise score (P < 0.001, F = 37.6), and the sense of well-being score (P < 0.001, F = 25) vs the sham group. Six patients (20%) in the tDCS group required rescue antiemtic therapy vs 14 patients (46.7%) in the sham group (P < 0.028). CONCLUSION: A single session of M1 tDCS is suggested as an effective adjuvant therapy to control CINV in female patients suffering from breast cancer and receiving highly emetogenic chemotherapy. Corroboratory studies are needed.

Effect of Transcranial Direct Current Stimulation of the Motor Cortex on Visceral Pain in Patients with Hepatocellular Carcinoma.

Objective: Hepatocellular carcinoma (HCC) is frequently associated with visceral pain. Transcranial direct current stimulation (tDCS) has been proven to reduce chronic pain; however, its effectiveness in malignant visceral pain is unknown. This study aimed to investigate the effects of tDCS in patients with visceral pain due to HCC. Design: This is a randomized, sham-controlled, double-blind, prospective study. Forty patients with visceral pain due to HCC were enrolled and randomly assigned into two groups: a real and a sham group; tDCS was applied over the primary motor area (M1) for 10 consecutive days (2 mA, 30 minutes). Patient's pain was evaluated by visual analog scale (VAS) and verbal descriptor scale (VDS) and for depression by Hamilton rating scale (HAM-D). Evaluation was done at prestimulation, after the first, fifth, and 10th sessions, and one month after the end of stimulation sessions. Results: Real tDCS showed a reduction of VDS (P = 0.001, F = 4.01) and VAS (P = 0.001, F = 6.817) for HAM-D (P = 0.012, F = 5,077); the effect started from the fifth session and continued to one month after stimulation, while in the sham group the effect persisted for five days only. Percentage reduction in all scales in the real group after the 10th session was as follows: VDS P = 0.008, VAS P = 0.001, HAM-D = 0.001; for one month after the end of stimulation, it was as follows: VDS P = 0.001, VAS P = 0.037, HAM-D = 0.002. Conclusions: tDCS proved to be an effective and clinically relevant therapeutic strategy for visceral pain due to HCC.

The effect of morphine added to bupivacaine in ultrasound guided transversus abdominis plane (TAP) block for postoperative analgesia following lower abdominal cancer surgery, a randomized controlled study.

OBJECTIVES: Transversus abdominis plane (TAP) block used for management of surgical abdominal pain by injecting local anesthetics into the plane between the internal oblique and transversus abdominis muscles. We aimed to explore the effect of adding morphine to bupivacaine in ultrasound guided TAP-block in patients undergoing lower abdominal cancer surgery. STUDY DESIGN: Randomized, double-blind, prospective study. Clinical trial identifier: NCT02566096. SETTING: Academic medical center. PATIENTS: Sixty patients were enrolled in this study after ethical committee approval. INTERVENTIONS: Patients divided into 2 groups (30 each): Bupivacaine group (GB): given ultrasound guided TAP-block 20ml 0.5% bupivacaine diluted in 20ml saline; Morphine group (GM): given ultrasound guided TAP-block with 20ml 0.5% bupivacaine+10mg morphine sulphate diluted in 20ml saline. MEASUREMENTS: Patients were observed for total morphine consumption, time for first request of rescue analgesia, sedation scores, hemodynamics and side effects for 24h postoperatively. RESULTS: Morphine added to bupivacaine in TAP block compared to bupivacaine alone reduced total morphine consumption (5.33±1.28mg) (10.70±3.09mg) respectively (p<0.001), prolonged the time to first request of analgesia (10.40±4.96h) (6.97±3.26h) respectively (p<0.008), with a statistically significant decrease in (VAS-M) in GM compared with GB at 12h postoperatively (p<0.002). No significant differences in hemodynamics, respiratory rate, oxygen saturation, sedation score, and side effects except for nausea were observed (p>0.05). CONCLUSION: Addition of morphine to bupivacaine in TAP block is effective method for pain management in patients undergoing major abdominal cancer surgery without serious side effects.

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.