Mohamed Sa

Long-term antalgic effects of repetitive transcranial magnetic stimulation of motor cortex and serum beta-endorphin in patients with phantom pain

Abstract Objectives: To assess the long-term analgesic effect of repetitive transcranial stimulation (rTMS) on chronic phantom pain using high frequency stimulation and to measure the serum beta-endorphin level pre- and post-rTMS. Material and methods: The study included 27 patients with unilateral amputation; all patients had chronic phantom pain. The patients were classified into two groups. Seventeen patients received 10 minutes real rTMS over the hand area of motor cortex (20 Hz, 10 second trains, intensity 80% of motor threshold) every day for five consecutive days and 10 patients received sham stimulation. Pain was assessed using a visual analogue scale (VAS) and the Leeds assessment of neuropathic symptoms and signs (LANSS) scale, before and after the first, fifth sessions, one and two months after the last session. Quantitative determination of serum beta-endorphin before and after five sessions was measured. Results: There was no significant difference between true and sham groups in the duration of illness, VAS, LANSS scores and resting motor threshold in upper and lower limb amputation at the base line. VAS and LANS scores of the patients who received real rTMS decreased more over the course of the treatment through the different points of follow-up (after five sessions, one and two months) than those who received sham stimulation. Serum beta-endorphin was increased significantly after real stimulation with no changes in patients received shame. Serum beta-endorphin showed no significant correlation to Hamilton depression, anxiety, VAS and LANS scores in true or sham groups before or after five sessions for rTMS. Conclusion: These results confirm that five daily sessions of rTMS over motor cortex can produce long lasting pain relief in patients with phantom pain and it might be related to an elevation of serum beta-endorphin concentration.

Effect of the addition of clonidine to locally administered bupivacaine on acute and chronic postmastectomy pain.

STUDY OBJECTIVES To investigate the analgesic effect of adding clonidine to topical bupivacaine for acute and chronic postmastectomy pain. DESIGN Randomized, prospective, double-blinded study. SETTING Cancer institute and university hospital. PATIENTS 140 ASA physical status 1 and II women, aged 30 to 50 years, scheduled for modified radical mastectomy with axillary dissection for breast carcinoma. INTERVENTIONS Patients were divided into 4 groups of 35 patients each, to receive either saline 0. 9% (control group), plain bupivacaine 0.5% (Bupivacaine group), plain bupivacaine 0.5% and 150 μg of clonidine (Clonidine150 group), or plain bupivacaine 0.5% and 250 μg of clonidine (Clonidine250 group). Study drugs were irrigated into the surgical field before skin closure. MEASUREMENTS AND MAIN RESULTS Pain severity, time to first request of rescue analgesia, analgesic consumption, hemodynamics, and side effects were recorded in the first 48 hours postoperatively. The frequency of neuropathic pain was assessed using the Douleur Neuropathique 4-question survey (DN4) in the first and second postoperative months. Mean time to first postoperative analgesic request was significantly prolonged in the Bupivacaine (5.76 ± 0.85 hrs), Clonidine150 (11.6 ± 2.38 hrs), and Clonidine250 (17.4 ± 3.27 hrs) groups compared with the control group (1.86 ± 0.65 hrs). Postoperative tramadol consumption and visual analog scores (VAS) were significantly reduced in the Bupivacaine, Clonidine150, and Clonidine250 groups. Clonidine250 group patients had the lowest VAS scores from 2 to 48 hours postoperatively. Lower mean DN4 scores (P = 0.000) and a significantly reduced frequency of neuropathic pain (P < 0.04) were recorded in the Bupivacaine, Clonidine150, and Clonidine250 groups, with a nonsignificant difference noted among the treatment groups. CONCLUSIONS The addition of clonidine to topical bupivacaine accentuated its early postoperative analgesic efficacy.

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.

Comparison Between the Effects of Intravenous Morphine, Tramadol, and Ketorolac on Stress and Immune Responses in Patients Undergoing Modified Radical Mastectomy.

Objectives:Analgesics had been suspected of impairing various immune functions either directly or indirectly. Our primary objective was to compare the effects of intravenous (IV) morphine, tramadol, and ketorolac on stress and immune responses in patients who underwent modified radical mastectomy. Patients:Sixty patients randomly assigned to receive IV morphine 5 mg (group M, n=20), tramadol 100 mg (group T, n=20), or ketorolac 60 mg (group K, n=20) at the end of surgery. Methods:Serum cortisol, prolactin were measured immediately, 40 minutes, and 24 hours postoperatively. Expressions of peripheral T lymphocytes (CD3+, CD3+CD4+, CD3+CD8+) and natural killer cells (CD3+, CD56+) were measured as percentages of total lymphocytes by flow cytometry immediately, 90 minutes, and 24 hours postoperatively. Results:After 40 minutes, cortisol level increased but prolactin decreased significantly (P=0.001), then both decreased after 24 hours (P=0.001) compared with baseline within the 3 groups. CD3, CD4, CD8, and CD56 significantly decreased at 90 minutes and 24 hours (P⩽0.033) compared with baseline in the 3 groups. CD4, CD8, and CD56 significantly decreased in group M, compared with group T and K (P⩽0.016) and CD3, CD8, and CD56 in group T compared with group K at 90 minutes (P⩽0.024) postoperatively. After 24 hours, CD4, and CD8 decreased in group M compared with group T (P⩽0.048) and CD4 and CD56 in groups M and T compared with group K (P⩽0.049). Conclusions:IV morphine, tramadol, and ketorolac suppressed stress and immune responses. Ketorolac was the least immunosuppressive among the 3 drugs.

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.

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.

Effect of Intrathecally Administered Ketamine, Morphine, and Their Combination Added to Bupivacaine in Patients Undergoing Major Abdominal Cancer Surgery a Randomized, Double-Blind Study

Objective Effective postoperative pain control reduces postoperative morbidity. In this study, we investigated the effects of intrathecal morphine, ketamine, and their combination with bupivacaine for postoperative analgesia in major abdominal cancer surgery. Study Design Prospective, randomized, double-blind. Setting Academic medical center. Patients and Methods Ninety ASA I-III patients age 30 to 50 years were divided randomly into three groups: the morphine group (group M) received 10 mg of hyperbaric bupivacaine 0.5% in 2 mL volume and 0.3 mg morphine in 1 mL volume intrathecally. The ketamine group (group K) received 0.1 mg/kg ketamine in 1 mL volume instead of morphine. The morphine + ketamine group (group K + M) received both 0.3 mg morphine and 0.1 mg/kg ketamine in 1 mL volume intrathecally. Postoperative total morphine consumption, first request of analgesia, visual analog score (VAS), and side effects were recorded. Results Total PCA morphine was significantly decreased in group M + K compared with groups M and K. Time to first request of analgesia was prolonged in groups M and M + K compared with group K (P < 0.001). VAS in group M + K was reduced from two to 24 hours, and in group M from 12 and 18 hours postoperation compared with group K, with an overall good analgesia in the three groups. Sedation was significantly higher in group M + K compared with group M until six hours postoperation. No other side effects were observed. Conclusions Adding intrathecal ketamine 0.1 mg/kg to morphine 0.3 mg in patients who underwent major abdominal cancer surgery reduced the total postoperative morphine consumption in comparison with either drug alone, with an overall good postoperative analgesia in all groups, with no side effects apart from sedation.

Effect of local wound infiltration with ketamine versus dexmedetomidine on postoperative pain and stress after abdominal hysterectomy, a randomized trial

Postoperative pain and stress elicit hormonal changes. We aimed at comparing the effects of wound infiltration with ketamine versus dexmedetomidine on postoperative pain and stress response.

Comparison of nebulised dexmedetomidine, ketamine, or midazolam for premedication in preschool children undergoing bone marrow biopsy

Background The aim of our study was to compare the efficacy of dexmedetomidine, ketamine, and midazolam for sedative premedication administered by nebuliser 30 min before general anaesthesia in preschool children undergoing bone marrow biopsy and aspiration. Methods Ninety children aged 3–7 yr were randomly allocated into three equal groups to be premedicated with either nebulised ketamine 2 mg kg−1 (Group K), dexmedetomidine 2 &mgr;g kg−1 (Group D), or midazolam 0.2 mg kg−1 (Group M). The primary endpoint was a five‐point sedation score on arrival in the operating room 30 min after end of study drug administration. Secondary outcomes included: parental separation anxiety scale; medication and mask acceptance scales; haemodynamic variables; recovery time; postoperative face, legs, activity, cry, and consolability scale; emergence agitation scale; and adverse effects. Results The median (range) sedation score on arrival in the operating room was 3.5 (1–4), 2.0 (2–3) and 2.0 (1–3) in Groups M, D, and K, respectively (P=0.000). Subjects in Group D showed higher medication (P<0.03) and mask acceptance scores (P<0.015) and more satisfactory parental separation anxiety scale (P<0.044). The median (range) recovery time was significantly shorter in Group D [5.5 (4–8) min] compared with Group K [10.0 (5–15) min, P=0.000] and M [8.0 (6–15) min, P=0.000]. The incidence of emergence agitation was lower in Group D (P<0.008). Conclusions Preschool children premedicated with nebulised dexmedetomidine had more satisfactory sedation, shorter recovery time, and less postoperative agitation than those who received nebulised ketamine or midazolam. Clinical trial registration NCT02935959.

The Effect of Anesthetic Technique on Cardiac Troponin-T and Systemic Inflammatory Response after Major Abdominal Cancer Surgery

Objectives: this study aims at assessment of acute inflammatory response; measured by high sensitivity C-reactive protein (hs-CRP), and myocardial injury; measured by serum cardiac troponin-T (Tn-T) in patients undergoing elective major abdominal cancer surgery with general anaesthesia or combined general and lumbar epidural anesthesia. Methods: The study included 60 ischemic patients undergoing elective major abdominal cancer surgery with risk factor(s) like(history of myocardial infraction, diabetes, hypertension, obesity or heavy smoking)randomly assigned into 2 groups; 30 patients each to receive general anesthesia (G1) or combined general and epidural anesthesia (G2). Pain severity, time to first request of rescue analgesic, analgesic consumption, hemodynamics and side effects were recorded in first 72 hrs postoperative. Serum Tn-T and hs-CRP, ECG were assessed peroperatively and 1,2,3 days postoperativly also 12-lead ECGs were recorded before and 1,2,3 days after surgery. Results: The mean VAS scores were significantly reduced in G2 allover time in comparison to G1 (p 0.03ng/ml. Regarding ECGs changes there were 2 patients (6.6%) in G1 and one patient (3.3%) in G2 showed new ischemic changes postoperatively in the form of depressed ST segment >1mm. Conclusion: The use of LEA with general anesthesia in high risk patients with ischemic heart disease undergoing major non-cardiac surgery is associated with less perioperative acute inflammatory response, less post-operative pain and can reduce the perioperative myocardial damage.