Pharmacokinetics and Pharmacodynamics of Dexmedetomidine Administered as an Adjunct to Bupivacaine for Transversus Abdominis Plane Block in Patients Undergoing Lower Abdominal Cancer Surgery.

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).

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.

Effect of Dexmedetomidine Added to Modified Pectoral Block on Postoperative Pain and Stress Response in Patient Undergoing Modified Radical Mastectomy.

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.

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.