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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.

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Purpose: A subcostal flank incision is required for open radical nephrectomy, which is a surgical procedure used to remove tumors of the kidney that are malignant. The erector spinae plane block (ESPB) and continuous catheter use in children are receiving more and more support by paediatric regional anaesthesiologists. Our objective was to compare systemic analgesic to continuous ESPB for pain relief in paediatric patients undergoing open radical nephrectomy. Methods: Sixty children with cancer ASA I or II and undergoing open radical nephrectomy between the ages of two and seven participated in this prospective, randomized, controlled, and open label study. The cases were divided into two equal groups (E and T groups); Group E received ipsilateral continuous ultrasound-guided ESPB at T9 (thoracic vertebrae), with a bolus of 0.4 mL/kg bupivacaine 0.25%. Immediately postoperatively, Group E (ESPB group) received continuous ESPB with a PCA (patient controlled analgesia) pump at a rate of 0.2 mL/kg/hour bupivacaine 0.125%. Group T (Tramadol group), Tramadol hydrochloride was administered intravenously at a dose of 2 mg/kg/8hour, which could be increased to 2 mg/kg/6hours. Then, we followed up on patients' total analgesic consumption for 48 hours following surgery, as well as the time it took for them to request rescue analgesic, their FLACC and sedation scores, and their hemodynamics and side effects immediately following surgery as well as at 2, 4, 6, 8, 12, 18, 24, 36, and 48 hours. Results: A highly significant difference in total tramadol consumed in group T 11.97 ± 1.13 mg/kg while group E was 2.07± 1.54 mg/kg (p < 0.001). 100% patients in group T requested analgesia compared to 46.7% patients in group E (p < 0.001). From 2 to 48 hour, FLACC significantly decreased in E compared to T group (p≤ 0.006) at all-time points. Conclusion: Ultrasound-guided continuous ESPB significantly provided better postoperative pain relief, reduced postoperative tramadol consumption and reduced pain scores compared with the use of tramadol alone, in paediatric cancer patients undergoing nephrectomy.

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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.

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BACKGROUND: Despite the growing interest in dexmedetomidine as an adjunct to truncal blocks, little is known about the systemic absorption of dexmedetomidine after these blocks and its role in analgesia and in hemodynamics. OBJECTIVE: We investigated the pharmacokinetics and pharmacodynamics of dexmedetomidine as an adjunct to transversus abdominis plane (TAP) block in patients undergoing lower abdominal cancer surgery. METHODS: Twenty-four adult patients were randomized to receive a bilateral single-injection TAP block before surgery with 20 mL of bupivacaine 0.5% (TAP group, n = 12) or combined with 1 µg/kg dexmedetomidine (TAP-DEX group, n = 12) and diluted with saline to a volume of 40 mL (20 mL on each side). Plasma concentrations of dexmedetomidine and its pharmacokinetics were investigated using non-compartmental methods, postoperative analgesia, hemodynamics, and adverse events (nausea, vomiting, itching, hypotension, bradycardia, and respiratory depression). RESULTS: Dexmedetomidine was detected in the plasma of 11 patients in the TAP-DEX group. The mean dexmedetomidine peak plasma concentration (Cmax) was 0.158 ± 0.085 (range, 0.045-0.31) ng/mL. The median time to reach peak plasma concentration of dexmedetomidine (Tmax) was 15 (15-45) min. From 2 to 8 h postoperatively, visual analog pain scale (VAS) scores at rest and during movement were significantly lower in the TAP-DEX group. Analgesia time was (11.3 ± 3.12 vs 9.0 ± 4.69 h; P = 0.213) and postoperative morphine consumption was (7.4 ± 3.24 vs 11.5 ± 4.46 mg; P = 0.033) in TAP-DEX and TAP groups, respectively. Lower mean heart rate and mean blood pressure were recorded in the TAP-DEX group intraoperatively and 2 h postoperatively (P < 0.05). Except for mild nausea and vomiting, no adverse events were recorded in either group. CONCLUSION: Systemic absorption of dexmedetomidine administered in a TAP block is common. Direct central effects on the locus coeruleus caused by this systemic absorption may play a role in the analgesia and hemodynamic effects produced by TAP-dexmedetomidine in addition to local mechanisms. TRIAL REGISTRATION: ClinicalTrial.gov (identifier: NCT03328299).

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BACKGROUND: Buccal dexmedetomidine (DEX) produces adequate preoperative sedation and anxiolysis when used as a premedication. Formulating the drug as a gel decreases oral losses and improves the absorption of buccal DEX. We compared pharmacokinetic and pharmacodynamic properties of 3 doses of buccal DEX gel formulated in our pharmaceutical laboratory for sedative premedication in women undergoing modified radical mastectomy for breast cancer. METHODS: Thirty-six patients enrolled in 3 groups (n = 12) to receive buccal DEX gel 30 minutes before surgery at 0.5 µg/kg (DEX 0.5 group), 0.75 µg/kg (DEX 0.75 group), or 1 µg/kg (DEX 1 group). Assessments included plasma concentrations of DEX, and pharmacokinetic variables calculated with noncompartmental methods, sedative, hemodynamic and analgesic effects, and adverse effects. RESULTS: The median time to reach peak serum concentration of DEX (Tmax) was significantly shorter in patients who received 1 µg/kg (60 minutes) compared with those who received 0.5 µg/kg (120 minutes; P = .003) and 0.75 µg/kg (120 minutes; P = .004). The median (first quartile-third quartile) peak concentration of DEX (maximum plasma concentration [Cmax]) in plasma was 0.35 ng/mL (0.31-0.49), 0.37 ng/mL (0.34-0.40), and 0.54 ng/mL (0.45-0.61) in DEX 0.5, DEX 0.75, and DEX 1 groups (P = .082). The 3 doses did not produce preoperative sedation. The 1 µg/kg buccal DEX gel produced early postoperative sedation and lower intraoperative and postoperative heart rate values. Postoperative analgesia was evident in the 3 doses in a dose-dependent manner with no adverse effects. CONCLUSIONS: Provided that it is administered 60-120 minutes before surgery, sublingual administration of DEX formulated as an oral-mucosal gel may provide a safe and practical means of sedative premedication in adults.

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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.

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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.

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BACKGROUND: The most common surgical procedure for breast cancer is the modified radical mastectomy (MRM), but it is associated with significant postoperative pain. Regional anesthesia can reduce the stress response associated with surgical trauma. OBJECTIVES: Our aim is to explore the efficacy of 1 µg/kg dexmedetomedine added to an ultrasound (US)-modified pectoral (Pecs) block on postoperative pain and stress response in patients undergoing MRM. STUDY DESIGN: A randomized, double-blind, prospective study. SETTING: An academic medical center. METHODS: Sixty patients with American Society of Anesthesiologists (ASA) physical status I-II (18-60 years old and weighing 50-90 kg) scheduled for MRM were enrolled and randomly assigned into 2 groups (30 in each) to receive a preoperative US Pecs block with 30 mL of 0.25% bupivacaine only (group 1, bupivacaine group [GB]) or 30 mL of 0.25% bupivacaine plus 1 µg/kg dexmedetomidine (group II, dexmedetomidine group [GD]). The patients were followed-up 48 hours postoperatively for vital signs (heart rate [HR], noninvasive blood pressure [NIBP], respiratory rate [RR], and oxygen saturation [Sao2]), visual analog scale (VAS) scores, time to first request of rescue analgesia, total morphine consumption, and side effects. Serum levels of cortisol and prolactin were assessed at baseline and at 1 and 24 hours postoperatively. RESULTS: A significant reduction in the intraoperative HR, systolic blood pressure (SBP), and diastolic blood pressure (DBP) starting at 30 minutes until 120 minutes in the GD group compared to the GB group (P < 0.05) was observed. The VAS scores showed a statistically significant reduction in the GD group compared to the GB group, which started immediately up until 12 hours postoperatively (P < 0.05). There was a delayed time to first request of analgesia in the GD group (25.4 ± 16.4 hrs) compared to the GB group (17 ± 12 hrs) (P = 0.029), and there was a significant decrease of the total amount of morphine consumption in the GD group (9 + 3.6 mg) compared to the GB group (12 + 3.6 mg) (P = 0.001). There was a significant reduction in the mean serum cortisol and prolactin levels at 1 and 24 hours postoperative in the GD patients compared to the GB patients (P < 0.05). LIMITATIONS: This study was limited by its sample size. CONCLUSION: The addition of 1 µg/kg dexmedetomidine to an US-modified Pecs block has superior analgesia and more attenuation to stress hormone levels without serious side effects, compared to a regular Pecs block in patients who underwent MRM. KEY WORDS: Postoperative pain, dexmedetomidine, Pecs block, stress response, breast surgery.

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BACKGROUND: Total thyroidectomy is recommended as a line of management of thyroid cancer in many cases. Our aim was to compare postoperative analgesic effect of local ketamine 1 mg/kg instilled in the wound to that of intramuscular (IM) ketamine and placebo after total thyroidectomy. METHODS: A total of 90 patients aged 18 to 60 years, American Society of Anesthesiologists (ASA) class I to II, with a body weight of 50 to 90 kg, scheduled for total thyroidectomy were enrolled after ethics committee approval in this prospective, randomized, double-blind, controlled study and divided randomly into 3 groups to receive treatment after hemostasis. Group (I) received 1 mg/kg ketamine in a total volume of 10 mL normal saline instilled in the wound. Group (II) received 1 mg/kg of IM ketamine. Group (III) received 10 mL of normal saline instilled in the wound. Total amount of morphine consumption, first request of analgesia, and side effects were recorded. Visual analog scale at rest and movement and hemodynamics were assessed immediately, 1, 2, 4, 6, 12, and 24 hours postoperatively. RESULTS: Total morphine consumption was reduced and first request of analgesia was delayed in group I compared with that in groups II and III, and in group II compared with that in group III (P=0.000). Visual analog scale at rest and movement were decreased immediately postoperatively in groups I and II in comparison with their values in group III; group II had higher sedation scores. CONCLUSIONS: Local wound ketamine instillation provided superior postoperative analgesia with lower incidence of side effects in comparison with IM ketamine and placebo following total thyroidectomy.

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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.

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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.

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BACKGROUND: Pain control after bariatric surgery is a major challenge. Our objective was to study the efficacy and safety of intrathecal (IT) morphine 0.3 mg added to bupivacaine 0.5% for postoperative pain after laparoscopic bariatric surgery. METHODS: After local ethics committee approval, 100 morbidly obese patients scheduled for laparoscopic bariatric surgery were enrolled in this study. Patients were randomly assigned into two groups: Group I received IT 0.3 mg morphine (0.3 mL) added to 1.2 mL of bupivacaine 0.5%; Group II received IT 0.3 mL saline added to 1.2 mL of bupivacaine 0.5%, immediately before induction of general anaesthesia. For both groups, 60 mg ketorolac and 1000 mg paracetamol were infused 30 minutes before the end of surgery. After wound closure, 20 mL bupivacaine 0.25% was infiltrated at wound edges. RESULTS: Visual Analogue Scale (VAS) score was significantly lower in group I immediately, 30 minutes and 1 hour postoperatively. Time to first ambulation, return of intestinal sounds and hospital stay were shorter in group I than group II (p < 0.05); total morphine consumption was significantly lower in group I than group II (p < 0.05). Sedation score was significantly higher in group I immediately postoperatively, while at 30 minutes, 1, 2 and 6 hours postoperatively sedation scores were significantly higher in group II. Itching was significantly higher in group I. CONCLUSION: The addition of IT morphine to a multimodal analgesic regimen after laparoscopic bariatric surgery was an effective and safe method that markedly reduced postoperative pain, systemic opioid consumption and length of hospital stay.

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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.

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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, CD3CD4, CD3CD8) 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.

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