Nociceptive improvements and kynurenine pathway alterations with diclofenac treatment in a rat model of neuropathic pain created by partial sciatic nerve ligation.

OBJECTIVE: Neuropathic pain is regulated by several metabolites of the kynurenine pathway (KYNA-kynurenic acid, and QA-quinolinic acid). Diclofenac exerts analgesic and anti-hyperalgesic effects and also alters KYNA levels, indicating a potential for therapy. We aimed to assess the nociceptive effects of different doses of diclofenac treatment in a rat model of neuropathic pain and to determine potential relationships with KYNA and QA levels (Graphical Abstract). MATERIALS AND METHODS: Twenty-eight Sprague-Dawley rats were divided into four groups: 40 mg/kg/day diclofenac (high-dose), 20 mg/kg/day diclofenac (normal-dose), non-treatment, and sham. Except for the sham group, the others underwent partial sciatic nerve ligation (left). Baseline (day 0) and post-treatment (day 3) KYNA and QA levels were measured. Allodynia and pain detection were assessed with the von Frey and hot plate tests. RESULTS: Baseline findings were similar in all groups. Compared to baseline, the non-treatment group had significantly worse allodynia on day 3. Baseline and post-treatment von Frey results (left) remained similar in the normal-dose diclofenac group (p=0.336); however, this benefit was not observed in the high-dose group. Relative to baseline, normal-dose diclofenac recipients had significantly higher KYNA concentration (p=0.046) and KYNA-to-QA ratio (p=0.028) on day 3. CONCLUSIONS: Our results show that 3-day therapy with 20 mg/kg/day diclofenac can improve nociceptive findings in neuropathic pain, and that this effect may be associated with increased KYNA or KYNA-to-QA ratio. The lack of dose-dependent effects may be associated with potential adverse influences of exceedingly high diclofenac dosage.

Effect of coenzyme Q10 on organ damage in sepsis.

OBJECTIVE: Investigating the effects of coenzyme Q10 on organ damage and survival on mice in cecal ligation perforation (CLP) model in sepsis. BACKGROUND: Coenzyme Q10 is an antioxidant molecule playing an important role in mitochondria. Mitochondrial dysfunction is an important mechanism in sepsis pathophysiology. METHODS: Nintyfour Swiss Albino male mice were divided into 8 groups. CLP was performed in Group I. Coenzyme Q10, 100 mg/kg subcutaneously, was given 5 hours after CLP to Group II and 20 hours after CLP to Group III. Sham operation was performed in Group IV, 100 mg/kg coenzyme Q10 subcutaneously was given 5 hours after sham operation to Group V and 20 hours after sham operation to Group VI. No operation was performed in Group VII; coenzyme Q10, 100 mg/kg subcutaneously, was given to Group VIII. Antibiotics and fluid replacement were applied for 3 days. The mice still living were sacrificed at 576th hour. The organ damages were scored under light microscopy. RESULTS: The survival of Group I and Group II was lower than that of the control groups, but the survival in the Group III was similar to control groups. It was established that spleen, kidney, heart damage and total organ damage were decreased when compared to CLP group. CONCLUSIONS: Coenzyme Q10 is effective in decreasing histological organ damage in sepsis (Tab. 3. Fig. 1, Ref. 30).

Homocysteine levels and bad obstetric outcome among female operating room personnel occupationally exposed to nitrous oxide.

It is known that nitrous oxide (N2O) inactivates vitamin B12 and causes hyperhomocysteinemia. The personnel working at the operating theatres are repeatedly exposed to N2O in the ambient air. This prompted us to investigate the biochemical indices of vitamin B12 metabolic status among female personnel working under various levels of N2O exposure. In this study, the homocysteine and folic acid levels were assessed and bad obstetric outcome was questioned. Sixty operating theatre female personnel were examined. Vitamin B12 and folic acid, total homocysteine level, anticardiolipin IgM, IgG, antiphospholipid IgM, IgG levels were measured in serum. A questionnaire inquiring about obstetric history was given. The serum concentration of folic acid was 10 ± 3.3 nmol liter-1. The vitamin B12 level was 332 ± 134 pmol liter-1, the serum concentration of homocysteine was 9.1 ± 2.4 nmol liter-1 and all were within normal ranges. There was no difference regarding homocysteine, folic acid, vitamin B12 levels and the obstetric history between the subjects who had abortus history and the subjects who had not abortus history. Exposure to N2O in healthcare workers was not associated with alterations of homocysteine, folic acid status and bad obstetric outcome (Tab. 4, Ref. 18).

Effect of intra-articular injection of levobupivacaine on articular cartilage and synovium in rats.

OBJECTIVE: Intra-articular local anesthetics are often used for prevention of pain after arthroscopic knee surgery. However, the effect of local anesthetics other than bupivacaine on articular cartilage and synovium has not been studied. Also, complications associated with the injection of intra-articular bupivacaine have appeared in the literature. The aim of this study was to evaluate the effects of levobupivacaine on the articular cartilage and the synovium in rats. METHODS: Under aseptic conditions 0.25 ml (5 mg/ml) of levobupivacaine was injected into the right knee joint while 0.25 ml of saline was simultaneously injected into the left knee joint of 20 adult Sprague-Dawley rats. The purpose of saline injections was to serve as a control group. Groups of five rats were killed on days 1, 7, 14 and 21 after administration of injections. The knee joint samples were evaluated for the presence of inflammation in the articular and periarticular tissues and the synovium. RESULTS: There were no significant differences between the levobupivacaine and control groups with respect to inflammation in the articular and periarticular tissues and the synovium. CONCLUSIONS: Although more studies are needed before final recommendations can be made, by evaluating the results obtained from this study, the clinical use of intra-articular levobupivacaine can be recommended for arthroscopic knee surgery.

WITHDRAWN The analgesic effect of paracetamol when added to lidocaine for intravenous regional anesthesia.

Ahead of Print article withdrawn by publisher AIM: Intravenous regional anesthesia (IVRA) is frequently used in patients who will undergo upper extremity surgical operations for its ease of use, rapid effectiveness and short hospitalization period. Different drug combinations have been used to overcome some systemic adverse effects and to increase the postoperative analgesic effectiveness. In our study, we evaluated the effects of paracetamol (Perfalgan) when added to lidocaine for IVRA, looking specifically at tourniquet pain and postoperative pain. METHODS: Ninety patients undergoing elective hand surgery with IVRA were randomly assigned to three groups to receive either IV saline and C-IVRA with 0.5% lidocaine 3 mg/kg (control group, N=30), IV saline and IVRA with 0.5% lidocaine and 20 mL paracetamol (10 mg/cc) (P-IVRA group, N=30) or IV paracetamol and IVRA with 0.5% lidocaine (L-IV group, N=30). The following were measured: 1) sensory and motor block onset and recovery time, 2) tourniquet pain after tourniquet application and at 10, 20 and 30 min after tourniquet deflation, 3) the visual analog scale (VAS) scores of tourniquet pain at 30 min and 1, 2, 4, 6 and 24 h postoperatively, 4) the time to first analgesic requirement, 5) total analgesic consumption in 24 h and 6) side effects. RESULTS: Sensory and motor block onset and recovery times were similar in both groups. VAS scores of tourniquet pain were lower in group P-IRVA at 1, 2, 4, 6, and 24 h, postoperatively (P<0.01). Anesthesia quality, as determined by the anesthesiologist and surgeon, was similar in both groups. The time to the first postoperative analgesic request was 67.83±57.48 min in group C-IRVA and 93±80.79 min in group P-IRVA (P<0.05). Paracetamol consumption was significantly less in group P-IRVA (1.60± 1 [tablets]) when compared with group C-IRVA (2.45±0.9; P<0.05). CONCLUSIONS: Perfalgan as an adjunct to lidocaine improves postoperative analgesia in IVRA without adverse effects.

Efficacy of intravenous acetaminophen and lidocaine on propofol injection pain.

BACKGROUND: Different methods and propofol formulations have been used to decrease propofol injection pain, but it remains an unresolved problem. We aimed to investigate the effect of i.v. acetaminophen pretreatment on the propofol injection pain. METHODS: One hundred and fifty ASA I-II patients undergoing general anaesthesia were randomly allocated into three groups. A 20-gauge catheter was inserted into a superficial radial vein of the left hand, and after the occlusion of venous drainage, Groups I, II, and III were pretreated with 40 mg of lidocaine in saline, 50 mg of i.v. acetaminophen, and 5 ml of saline, respectively. The occlusion was released after 2 min and one-fourth of the total propofol dose was injected into the vein over a period of 5 s. During the injection of both pretreatment solution and propofol, patients' pain was assessed and recorded as 0-3, corresponding to no, mild, moderate or severe pain, respectively. Chi2 and Kruskal-Wallis tests were used for the statistical analysis. For all analyses, differences were considered to be significant at P<0.05. RESULTS: Patient characteristics were similar among the groups. Incidence of pain on injection of propofol in control, i.v. acetaminophen, and lidocaine groups was 64%, 22% and 8%, respectively (P<0.05). CONCLUSIONS: Pretreatment with i.v. acetaminophen seems to be effective in attenuating pain during i.v. injection of propofol.

Renal safety and extrahepatic defluorination of sevoflurane in hepatic transplantations.

BACKGROUND: The main metabolic pathway for defluorination of sevoflurane in the liver produces inorganic fluoride (Fl). The metabolism and effect of sevoflurane on the kidney is not clear during anhepatic phase in liver transplantation. The goal of the present study was to investigate the metabolism and renal effect of sevoflurane by measuring plasma and urine inorganic fluoride, urinary N-acetyl-glucosaminidase (NAG), and plasma creatinine levels in patients undergoing liver transplantations. METHODS: After institutional approval and informed consent, we studied nine cases of orthotopic liver transplantation after anesthesia was induced with 5 mg . kg(-1) thiopental, 1 mug . kg(-1) fentanyl intravenously, the trachea was intubated after vecuronium bromide 0.1 mg . kg(-1). Anesthesia was maintained with sevoflurane (2%), O(2), and N(2)O at a total gas flow of 6 L . min(-1) using a semiclosed circle system with a sodalime canister. Blood and urine samples were obtained to measure plasma and urine fluoride concentrations and urinary NAG excretions before induction (P0), hourly during resection (P1, P2, P3), every 15 minutes during anhepatic phase (A1, A2, A3), hourly after reperfusion (neohepatic phase) (N1, N2, N3), and postoperative first hour (Po1). Preoperative (T0) and postoperative day 1 (T1), 3 (T3), 7 (T7) plasma blood urea nitrogen (BUN) and creatinine (Cr) levels were also recorded. RESULTS: Mean duration of surgery was 9:06 +/- 0:09 hours. Mean inorganic fluoride concentrations in plasma were in the range of 0.71 +/- 0.30 to 28.73 +/- 3.31 mumole . L(-1). In P3, N1, N2, N3, increases in plasma inorganic fluoride concentrations were significant (P < .05) and reached a peak value at Po1. The mean urine inorganic fluoride concentrations were 12.49 +/- 2.04 to 256.7 +/- 49.62 mumole . L(-1). In A2, A3, N1, N2, and N3, mean urine inorganic fluoride concentrations were significantly increased (P < .05) and the peak value was observed at Po1. Mean NAG concentrations in urine varied (5.6 +/- 1.6 IU . L(-1) to 12.5 +/- 1.14 IU . L(-1)) and peak level was observed at 30 minutes of the anhepatic phase (A2), which did not exceed the normal values for urine NAG levels (1.5 to 6.1 U . L(-1)). No impairment was observed in serum BUN and creatinine levels at any time. While there was only a slight increase in NAG during anhepatic phase, there was no change in plasma F1. CONCLUSIONS: Sevoflurane seemed to have minimal effect on kidney functions of BUN and Cr levels during liver transplantation. Although urine F1 and NAG levels increased during the anhepatic phase plasma F1, BUN, and Cr levels did not, suggesting that renal F1 production may occur in the absence of hepatic function. The renal effect of sevoflurane in chronic liver disease is controversial and must be investigated in further studies.

Extrahepatic metabolism and renal effects of sevoflurane in a case of liver transplantation.

In a case of liver transplantation, sevoflurane metabolism was studied to investigate if sevoflurane has an extrahepatic metabolism or possible nephrotoxicity in the presence of chronic liver disease. Plasma blood urea nitrogen (BUN) and creatinine and urine levels of N-acetyl glycosaminidase (NAG) and beta2 microglobulin were assessed intraoperatively and for 11 days postoperatively. We observed a close relation between urine NAG excretion and urine inorganic fluoride levels in the intraoperative period and early postoperative days. The NAG levels were greater than normal despite the peak serum inorganic fluoride concentration of 18.94 micromol/L. No impairment was observed in serum BUN or creatinine levels in these periods.

Perioperative anxiety and postoperative behavioural disturbances in children: comparison between induction techniques.

BACKGROUND AND OBJECTIVE: This study was designed to determine if subhypnotic propofol reduces postoperative behavioural disturbances in children undergoing sevoflurane induction compared with intravenous propofol induction for elective adenoidectomy and tonsillectomy. METHODS: Following Ethics Committee approval and parental informed consent, ASA I-II, 120 children (2-10 yr) were recruited. Parents were not allowed to accompany their child. Unpremedicated children were randomly allocated to groups receiving inhalation induction with sevoflurane, 2-2.5 mg kg-1 intravenous propofol induction or inhalation induction with sevoflurane followed by subhypnotic dose of propofol (1 mg kg-1). Anaesthesia was maintained with 2-4% sevoflurane, O2 and N2O. Anxiety on arrival to operating theatre, at anaesthesia induction and 30 min after emergence was assessed. Parents completed a state-trait anxiety inventory test preoperatively and a post hospitalization behaviour questionnaire a week later to assess children's postoperative behavioural disturbances. Kruskal-Wallis test, Wilcoxon signed rank sum test, Bonferroni's test, Paired t-test, t-test, Pearson and Spearman's rank correlation test, chi2-test were used for statistical analysis. RESULTS: The anxiety level at induction was high in all groups (P < 0.05). There was no difference between groups in respect to anxiety at other measurement times. A relation between preoperative anxiety level and postoperative behavioural disturbances was determined (P < 0.05). Some behavioural disturbances as nightmare/night fear and desire of sleeping with parents were rarely seen in intravenous propofol induction group (P < 0.05). CONCLUSION: Addition of subhypnotic dose of propofol to sevoflurane induction did not reduce the incidence of postoperative behavioural disturbances.

The evaluation of propofol dosage for anesthesia induction in children with cerebral palsy with bispectral index (BIS) monitoring.

BACKGROUND: We designed a randomized prospective study to investigate whether developmentally delayed children with cerebral palsy (CP) need a lower dosage of propofol for induction than normal children using bispectral index (BIS) monitoring criteria. METHODS: After approval by the University Ethical Committee and written informed consent obtained from parents, 20 children with noncommunicative/nonverbal CP and 20 normal children requiring general anesthesia for elective orthopedic surgery were enrolled in the study. The patients were not premedicated. BIS leads were placed before the induction of anesthesia. Propofol was administered at a rate of 20 mg.30 s(-1) (i.e. 40 mg.min(-1)). When BIS value had reached a steady number of 35-45, infusion was stopped. RESULTS: There was no significant difference between Group N and Group CP in age and sex distribution (P > 0.05), however children in Group CP weighed less than Group N (P = 0.05). The propofol dosage for induction was significantly lower in Group CP than Group N (P = 0.03). There were no differences in propofol doses administered to children using anticonvulsants and those not on anticonvulsants in Group CP. BIS values were comparable between the two groups (i.e. Group N and Group CP) at baseline and after propofol administration. CONCLUSIONS: Our data suggest that noncommunicative/nonverbal children with CP require less propofol to obtain the same BIS values (i.e. 35-45) than do otherwise healthy children.

Effect of low-dose N-acetyl-cysteine infusion on tourniquet-induced ischaemia-reperfusion injury in arthroscopic knee surgery.

BACKGROUND: Temporary occlusion of blood flow is used during arthroscopic knee surgery in order to provide a bloodless surgical field. The resulting ischaemia-reperfusion causes lipid peroxidation, which contributes to tissue injury. The aim of the study was to investigate the effect of low-dose n-acetyl cysteine (NAC) infusion on oxidative stress by determining malondialdehyde (MDA) levels during arthroscopic knee surgery. METHODS: Thirty patients, ASA I - II, undergoing arthroscopic knee debridement under a tourniquet were divided into NAC and control groups. Anaesthesia was induced with propofol, fentanyl and vecuronium bromide and maintained with desflurane in an equal parts O(2)-N(2)O mixture. In the NAC group, an infusion of NAC, 5 mg kg(-1).h(-1), was started after intubation, and continued until extubation. An equal volume of saline was infused to the control group. Duration of ischaemia, anaesthesia time, total dose of NAC infused were also recorded. Venous blood and synovial membrane tissue samples were obtained 10 min after the onset of NAC infusion but before tourniquet inflation (t1), after 30 min of ischaemia (t2), and after 5 min of reperfusion following tourniquet release (t3). RESULTS: Plasma MDA levels were significantly lower in the NAC group on reperfusion. There were no differences between the groups in tissue MDA levels at ischaemia and reperfusion times. CONCLUSION: Low-dose n-acetyl cysteine infusion attenuates lipid peroxidation and ischaemia-reperfusion injury in arthroscopic knee surgery requiring tourniquet application.