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.

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.

Efficacy of Postoperative Analgesia of Local Ketamine Wound Instillation Following Total Thyroidectomy: A Randomized, Double-blind, Controlled Clinical Trial.

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.

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.

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, 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.

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.