In vivo effects of different anesthetic agents on apoptosis / 대한마취과학회지

BACKGROUND: This study was designed to measure in vivo effects of propofol, isoflurane and sevoflurane on apoptosis by measuring caspase-3 and tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) blood level as apoptotic markers. METHODS: After obtaining ethical committee approval and informed written consents, sixty adult patients ASA I scheduled for open cholecystectomy participated in this study. They were randomally allocated into one of three equal groups to receive propofol infusion, low-flow isoflurane or sevoflurane for maintenance of anesthesia. Venous blood samples were collected preoperatively, immediately postoperative and after 24 hours to measure hemoglobin, hematocrit, creatinine, liver enzymes, serum TRAIL and caspase-3 levels. RESULTS: There was no significant difference in hematological markers and serum creatinine. Liver enzymes showed significant postoperative rise (P < 0.05). In Propofol group, TRAIL and caspase-3 levels were significantly elevated immediately postoperative then decreased significantly after 24-hours (P < 0.05). In Isoflurane group, immediate postoperative level of TRAIL was significantly higher than 24 hours reading and significantly lower than its level in Propofol group at the same timing meanwhile caspase-3 levels were comparable at different timings. In Sevoflurane group, TRAIL and caspase-3 levels increased significantly in both postoperative samples than preoperative level and than those of Isoflurane and Propofol groups after 24 hours concerning TRAIL (P & 0.05). CONCLUSIONS: This study concluded that isoflurane is superior and sevoflurane is the least effective among the three anesthetics in protection against apoptosis. This study neither proved nor excluded propofol-induced apoptosis. Further studies are required during lengthy procedure and in compromised patients.

Perioperative effects of various anesthetic adjuvants with TIVA guided by bispectral index / 대한마취과학회지

BACKGROUND: This prospective, randomized, double blinded, controlled study was designed to compare effects of intravenous co-administration of clonidine, magnesium, or ketamine on anesthetic consumption, intraoperative hemodynamics, postoperative analgesia and recovery indices during Bispectral Index (BIS) guided total intravenous anesthesia (TIVA). METHODS: After ethical committee approval and written informed consent, 120 adult patients ASA I and II scheduled for open cholecystectomy were randomly assigned to one of 4 equal groups. Group CL received clonidine 3 microg/kg and maintained by 2 microg/kg/h. Group MG received magnesium sulphate 50 mg/kg and maintained by 8 mg/kg/h. Group KET received racemic ketamine 0.4 mg/kg and maintained by 0.2 mg/kg/h. Control group (CT) received the same volume of isotonic saline. Anesthesia was induced and maintained by fentanyl, propofol and rocuronium. Propofol infusion was adjusted to keep the BIS value between 45-55. Intraoperative hemodynamics, induction time, anesthetic consumption, recovery indices, and PACU discharge were recorded. RESULTS: Induction time, propofol requirements for induction and maintenance of anesthesia, intraoperative fentanyl and hemodynamic values were significantly lower with Groups CL and MG compared to Groups KET and CT (P < 0.05). Patients in Group MG showed significantly lower muscle relaxant consumption, delayed recovery and PACU discharge than other groups (P < 0.05). First, analgesic requirement was significantly longer and total postoperative analgesic consumption was significantly lower in the adjuvant groups versus Group CT (P < 0.05). CONCLUSIONS: Clonidine, magnesium, and ketamine can be useful adjuvant agents to BIS-guided TIVA. Pharmacokinetic studies of such drug combinations were recommended to investigate their interaction.

Sub-antibiotic doses of erythromycin as a prokinetic in abdominal surgeries: reviving the old

All patients undergoing major abdominal procedures have some degree of gastric atony in the immediate postoperative period, presenting mainly with vomiting. Many prokinetic agents have been used in the past, but none is a universal remedy. Studies showed that subantibiotic doses of erythromycin, a macrolide. antibiotic and motilin agonist, accelerates gastric emptying. This study investigated whether preoperative subantibiotic dose oral erythromycin [250 mg], altered residual gastric volume and postoperative adverse effects in patients scheduled for abdominal surgeries. Erythromycin was compared with the commonly used prokinetic metoclopramide and antiemetic ondansetron, in terms of prokinetic efficacy, cost and adverse effects. In a double-blind study, eighty patients [20 each] were allocated randomly to receive orally, either erythromycin 250 mg [E250] or erythromycin 500 mg [E500], or 10 mg metoclopramide [M], or 4mg ondansetron [Z], an hour pre-induction of anesthesia. Preoperative oral erythromycin in subantibiotic dose 250mg elicited a significantly lower residual gastric volume [P<0.001] and a lower VAS for vomiting, compared with ondansetron. As for metoclopramide and erythromycin 500, residual gastric volume was comparable, but E 250 had a lower VAS for vomiting than both groups. Rescue remedy for vomiting was required for groups E500, M and Z [100, 10 and 10 %] compared to 0% in group E250. Ultimately, subantibiotic oral dose of erythromycin [250 mg], given1 hr preoperatively, is an inexpensive prokinetic alternative with a promising post-operative profile which may be superior to the inexpensive prokinetic metoclopramide with known adverse effects, and the expensive antiemetic ondansetron

Effects of different dose regimens of magnesium on pharmacodynamics and anesthetic requirements of balanced general anesthesia

The present double- blind, randomized, placebo- controlled study was designed to assess the effect of two different dose regimens of magnesium sulphate [MgSO[4] administration on intraoperative propofol and vecuronium requirements and postoperative fentanyl consumption in patients undergoing hernioraphy. Sixty patients were allocated to three equal groups; two magnesium groups and control group. Magnesium groups received 50 mg kg[-1] of magnesium preoperatively followed by intravenous infusion of magnesium 8 mg kg[-1] h[-1] [Mgl G] or 16 mg kg[-1]h[-1] [Mg2 G]. Patients in control group received the same volume of isotonic solution. Anesthesia was induced and maintained with propofol, fentanyl, and vecuronium. Magnesium Gs required significantly lower propofol [121.0 +/- 4.5, 117.4 +/- 6.3 micro g kg[-1] min.[-1] in Mgl and Mg2 Gs respectively vs. 153.8 +/- 8.4 micro g kg[-1] min.[-1] in control G], and vecuronium requirements [0.097 +/- 0.008, 0.092 +/- 0.006 mg kg[-1] h[-1] in Mgl and Mg2 Gs respectively vs. 0.124 +/- 0.01 mg kg[-1] h in control G]. Magnesium significantly shortened the onset time of vecuronium [154.0 +/- 25.9, 162.0 +/- 22.4 sec. in Mgl and Mg2 Gs respectively vs. 227.4 +/- 10.9 sec. in control], prolonged its clinical duration [44.7 +/- 3.2, 46.4 +/- 5.1 min. in Mgl and Mg2 Gs respectively vs. 26.0 +/- 3.9 min. in control] and prolonged its recovery index which was significantly longest in Mg2 G [25.4 +/- 1.9 min.] compared to Mgl G [20.1 +/- 2.1 min.] and control [15.3 +/- 1.4 min.] Fentanyl consumption on the first postoperative day was significantly higher in control [1.52 +/- 0.08 micro g kg[-1] than in magnesium Gs [0.96 +/- 0.07, 0.91 +/- 0.08 micro g kg[-1] in Mgl and Mg2 Gs respectively]. Postoperative sedation score showed significantly the highest value in Mg2 G compared to Mgl and control Gs. Mean arterial blood pressure and heart rate were lower in magnesium groups with lowest value in Mg2 G. It is concluded that magnesium 50 mg kg[-1] bolus followed by 8 mg kg[-1] h[-1] leads to significant reductions in intraoperative propofol and vecuronium and postoperative fentanyl consumption. Doubling magnesium infusion rate added minimal benefits on the expense of haemodynamic consequences and delayed recovery

Role of cholinesterase activity on pharmacodynamics of mivacurium preceded by pancuronium in elderly and young adults

Mivacurium- pancuronium combination proved to be more potent than either drug given alone. The goal of this study was to evaluate the safety and efficacy of this combination in elderly group and its correlation to plasma butyryl cholinesterase [Bche] activity. Forty patients, ASA I or II scheduled for elective open cholecystectomy were allocated into two groups of twenty patients each: young group [18- 55 years] and elderly group [60-75 years]. Anesthesia was induced with midazolam, fentanyl, and propofol then maintained with isoflurane and opioid supplementation. Neuromuscular blockade [NMB] was monitored by train-of-four [TOF] stimulation of the ulnar nerve. After calibration, NMB was achieved by 16 micro g kg[-1] pancuronium followed by 32 micro g kg[-1] mivacurium. The following parameters were recorded: The onset time, clinical duration, recovery index and the total dose of mivacurium and pancuronium together with hemodynamic data. Three blood samples for Bche activity were collected: before pancuronium injection, 3 min. and 30 min. afterwards in both groups. The onset time and the recovery index of NMB were comparable in both groups. The duration of action was significantly prolonged in elderly group [49.8 +/- 10.48 min.] compared to young one [37.13 +/- 7.81 min.]. The total dose of mivacurium was significantly less in the elderly group [22.56 +/- 2.39 micro g kg[-1] hr[-1]] when compared to the young group [25.78 +/- 3.05 micro g kg[-1] hr[-1]]. For all patients, the preoperative Bche activity was within the normal range. After pancuronium injection, it showed a significant reduction in both groups at three and thirty minutes except a non significant value in young at thirty minutes. This reduction showed a significantly higher percent change in the elderly group [30.37 +/- 22.01] than the young group [8.60 +/- 19.19] at thirty minutes. There were significant intra operative variations in the percent changes of hemodynamic data compared to the preoperative values, yet, still within the clinically acceptable range. So, the use of a small dose of pancuronium followed by a small dose of mivacurium with a ratio of 1:2 can produce synergism without affecting either the recovery profile of mivacurium or the clinical hemodynamic stability even in the elderly group