Effects of repeated doses of paracetamol administration during pregnancy on lung, kidney, and liver tissues of pregnant rats.

OBJECTIVES: Paracetamol is one of the most widely used analgesics and antipyretics in the world. It is the most commonly used analgesic and antipyretic agent in pregnancy. Paracetamol is known to have toxic effects on the liver, lung, and kidney. In this study, we investigated the effects of long-term chronic paracetamol exposure on the lung, liver, and kidney in newborn rats at different trimesters of pregnancy. METHODS: In our study, we formed control (group C), first trimester (group A), and third trimester (group B) groups. Group A had the first seven days of pregnancy and group B had days 15-21. Paracetamol was given orally during the specified periods. On the third postnatal day, pups were euthanized by applying 50 mg/kg ketamine intraperitoneally, and then lung, liver, and kidney tissues were kept under appropriate conditions for examination. A total of 70 pups underwent histopathological examination. RESULTS: The lung revealed congestion (p<0.0001), and erythrocytes (p<0.0001), the liver revealed significant histopathological findings in terms of the presence of inflammation (p<0.0001), vacuolar degeneration (p<0.0001), and sinusoidal dilatation in groups A and B compared to the control group under light microscopy. MDA and free radical metabolism enzyme activities, CAT, GSH, and SOD were evaluated. While there were no significant differences between the groups in lung and kidney tissues, oxidant parameters were significant in liver tissues. CONCLUSION: Our data point out that subacute doses of paracetamol used chronically in different trimesters caused damage to the lung, liver, and kidney tissues of pups.

Greater occipital nerve block in migraine prophylaxis: Narrative review.

OBJECTIVES: The importance and popularity of peripheral nerve block procedures have increased in the treatment of migraine. Greater occipital nerve (GON) block is a commonly used peripheral nerve block method, and there are numerous researches on its use in migraine treatment. MATERIALS AND METHODS: A search of PubMed for English-language randomized controlled trials (RCT) and open studies on greater occipital nerve block between 1995 and 2018 was performed using greater occipital nerve, headache, and migraine as keywords. RESULTS: In total, 242 potentially relevant PubMed studies were found. A sum of 228 of them which were non-English articles and reviews, case reports, letters and meta-analyses were excluded. The remaining articles were reviewed, and 14 clinical trials, seven of which were randomized-controlled on greater occipital nerve block in migraine patients, were identified and reviewed. CONCLUSIONS: Although clinicians commonly use greater occipital nerve block in migraine patients, the procedure has yet to be standardized. The present study reviewed the techniques, drugs and dosages, the frequency of administration, side effects, and efficacy of greater occipital nerve block in migraine patients.

Effectiveness of Greater Occipital Nerve Blocks in Migraine Prophylaxis.

INTRODUCTION: Peripheral nerve blocks have been used in primary headache treatment since a long time. In this study, we aimed to examine the efficiency of greater occipital nerve (GON) block in migraine prophylaxis. METHODS: Data from migraine without aura patients who had GON block were collected and divided into two groups: Group PGON (n=25), which included patients who were under medical prophylaxis and had GON block, and Group GON (n=53), which included patients who had only GON blocks. Migraine was diagnosed using International Headache Society (IHS) classification. Data of 78 patients were analyzed. Headache attack frequency, headache duration, and severity were compared between and within groups in a 3-month follow-up period. RESULTS: The decrease in headache parameters after GON block in both groups was significantly similar. Headache attack frequency decreased from 15.73±7.21 (pretreatment) to 4.52±3.61 (3rd month) in Group GON and from 13.76±8.07 to 3.28±2.15 in Group PGON (p<0.05). Headache duration decreased from 18.51±9.43 to 8.02±5.58 at 3rd month in Group GON and from 15.20±9.16 to 7.20±4.16 in Group PGON (p<0.05). Headache severity decreased from 8.26±1.32 to 5.16±2.64 in Group GON and from 8.08±0.90 to 5.96±1.20 in Group PGON (p<0.05). There was no statistically significant difference between the groups in 3rd month after treatment (p>0.05). CONCLUSION: This study showed significant decreases in headache parameters in both groups. As GON blocks were performed in patients unresponsive to medical prophylaxis, a decrease in the headache parameters in Group PGON similar to that in Group GON can be attributed to GON blocks. Consequently, these results show that repeated GON blocks with local anesthetic can be an effective alternative treatment in migraine patients who are unresponsive to medical prophylaxis or who do not prefer to use medical prophylaxis.

Epileptic seizure following IV tramadol in a patient with mental retardation and cerebellar ataxia.

OBJECTIVE: To present a case of an epileptic seizure related to intravenous (IV) tramadol for pain control following a total abdominal hysterectomy operation on a patient with mental retardation and cerebellar ataxia. BACKGROUND: Tramadol is an analgesic with a dual mechanism of action and has several side effects, one of which is epileptic seizure. CASE REPORT: A 42-year-old female with mental retardation and cerebellar ataxia presented with an epileptic seizure after administration of IV tramadol for postoperative pain. Magnetic resonance imaging scans were normal, but laboratory tests showed hypocalcemia. Next, calcium replacement was administered. Postoperative pain treatment with tramadol was discontinued because tramadol was felt to be a possible cause of the seizure observed in this patient. In order to treat the epileptic seizure, IV phenytoin sodium infusion was started. On the second postoperative day, calcium levels were found to be normal, and the IV antiepileptic medication was changed to an oral form. The patient had no subsequent seizures during the clinical follow-up. She was discharged on the fourth postoperative day without any other complications. CONCLUSION: Even in recommended doses, IV tramadol may cause epileptic seizures on predisposed patients.

Postoperative analgesic efficacy of intravenous dexketoprofen in lumbar disc surgery.

BACKGROUND: We investigated the postoperative analgesic efficacy and effect on total tramadol consumption of intravenous dexketoprofen trometamol, a new nonsteroidal anti-inflammatory drug, in patients that had undergone lumbar disc surgery. METHODS: Sixty patients were included in this placebo-controlled, randomized, double-blind study. General anesthesia was applied to both groups. Group D (n=30) received dexketoprofen (50 mg) intravenously 30 minutes before the end of surgery and at the postoperative 12th hour, whereas group C (n=30) received 2 mL of 0.9% NaCL intravenously at the same time points. All patients received a patient controlled analgesia device with a tramadol, 25 mg bolus, 15 minutes lockout protocol, and were followed with visual analog scale, verbal rating scale, modified Aldrete recovery scoring system, and Ramsay sedation scale in the postoperative period. RESULTS: There was no significant difference between the groups for demographic data, duration of surgery, mean arterial pressure, and heart rate. The time to first postoperative analgesic requirement was significantly longer in group D (151.33±81.98 min) than group C (19±5.78 min) (P<0.001). Total tramadol consumption was significantly lower in group D (117.50±48.31 mg) than group C (311.67±59.35 mg) (P<0.05). Visual analog scale and verbal rating scale values in group D were significantly lower than group C at all follow-up periods (P<0.001). There was a significant difference between the groups for the modified Aldrete recovery scoring system (P<0.05) but not for Ramsay sedation scale. The instances of nausea and vomiting among the side effects were significantly lower in group D (P<0.05). CONCLUSION: We found that dexketoprofen was an effective analgesic for postdiscectomy pain when used alone or in addition to opioids. It is easy to administer and decreases tramadol consumption and opioid-related side effects.

[The effects of two different multimodal analgesic regimens in total hip replacement surgery]. / Total kalça protezi operasyonlarinda iki multimodal analjezi yönteminin etkinligi.

OBJECTIVES: This study evaluated the effectiveness of two different multimodal analgesia protocols in terms of postoperative pain relief, tramadol consumption during patient-controlled analgesia (PCA) and side effects after total hip replacement surgery. METHODS: Group F (n=18) received general anesthesia after a 3-in-1 femoral nerve block (FNB) was applied using 40 ml of bupivacaine 0.25%. Group FD (n=18) received general anesthesia after the same block and dexketoprofen p.o. was given. All patients received intravenous tramadol at the end of surgery via a PCA device. Group FD was given dexketoprofen 75 mg/day for 48 hours postoperatively. Pain scores were evaluated at 0, 1/2, 1, 4, 8, 12, 24 and 48h at rest and on movement of the hip. Side effects and global satisfaction scores in both groups were also evaluated in this setting. RESULTS: Total tramadol consumption was lower in Group FD (377.7+/-137.4) than in Group F (593.9+/-132.3) (p<0.05). Visual analogue scale (VAS) scores were

Effect of hydroxyethyl starch 130/0.4 on ischaemia/reperfusion in rabbit skeletal muscle.

BACKGROUND AND OBJECTIVE: Tourniquet use is a common tool in surgical procedures of the limbs. Hydroxyethyl starch (HES) 130/0.4 not only has a role in replacement of the liquid deficits due to trauma, bleeding or shock, but it is also effective in enhancing tissue oxygen tension and regulation of microcirculation. The aim of this study was to investigate how 6% HES 130/0.4 affects ischaemia and reperfusion in skeletal muscle. METHODS: An ischaemia/reperfusion model (3 and 2 h, respectively) was applied in 14 rabbits. Group S (n = 7) was infused with 0.9% NaCl (0.2 ml kg(-1) min(-1)) and group HES was infused with 6% HES 130/0.4 (0.2 ml kg(-1) min(-1)). The total liquid was divided into equal one-thirds and given in the preischaemia, ischaemia and reperfusion phases. Ketamine HCl (30 mg kg(-1)) was used for anaesthesia, and blood pressure, pulse and blood gases were monitored. Muscle biopsies were taken in the preischaemic (A), ischaemic (B) and reperfusion (C) phases. In these samples, nitrite, nitrate, reduced glutathione (GSH) and myeloperoxidase (MPO) were measured to assess oxidative stress elements, and malondialdehyde (MDA) was measured to assess lipid peroxidation. Repeated variance analysis, Mann-Whitney U test and Student's t test were used for statistical analysis of these parameters. RESULTS: In group S, the MPO levels were significantly increased in the reperfusion phase compared with baseline, whereas there was a decrease in MPO levels in the reperfusion period in the HES group. This difference between groups was statistically significant (P = 0.011). CONCLUSION: The results of this study showed that 6% HES 130/0.4 solution is more effective in the prevention of ischaemia/reperfusion injury than saline when given in the same volume.

Intravenous paracetamol improves the quality of postoperative analgesia but does not decrease narcotic requirements.

Paracetamol, a centrally acting inhibitor of cyclooxygenase, has less gastrointestinal and platelet-inhibiting side effects and is clinically better tolerated than nonsteroidal anti-inflammatory drugs. Therefore, it will be ideally suited for postoperative pain relief. In this prospective, double-blind, randomized, placebo-controlled study, we evaluated the analgesic efficacy, opioid-sparing effect and effects on opioid-related adverse effects of intravenous (IV) paracetamol in combination with IV morphine after lumbar laminectomy and discectomy. Forty patients were divided into 2 groups (n=20 each) to receive either paracetamol 1 g (group 1) or 0.9% NaCl 100 ml (group 2) at the end of the operation and at 6-hour intervals over 24 hours. IV patient-controlled analgesia with morphine was used as a rescue analgesic in both groups. Pain was evaluated at rest and on movement at the 1st, 2nd, 4th, 6th, 12th, 18th, and 24th hours using a visual analog scale. Hemodynamic parameters, morphine usage, patient satisfaction, and probable side effects were also evaluated. Pain scores at rest and on movement at the 12th, 18th, and 24th hours were significantly lower in group 1 (P<0.001). Morphine consumption was not statistically significantly different between the groups (P>0.05). Vomiting in group 2 was significantly higher (P=0.027). Significantly more patients in the paracetamol group rated their pain management as excellent (45% vs. 5%). Although repeated IV paracetamol usage after lumbar laminectomy and discectomy did not demonstrate a significant opioid-sparing effect, it did decrease visual analog scale scores at certain evaluation times and incidence of vomiting and increase patient satisfaction.

The analgesic effect of 8 and 16 mg lornoxicam administered before shock wave lithotripsy: a randomized, double-blind, controlled study.

OBJECTIVES: To evaluate the efficacy of 2 different doses of intravenous lornoxicam for pain relief during shock wave lithotripsy (SWL). METHODS: In this randomized, controlled, double-blind study, 60 ASA I-II patients undergoing SWL were randomly divided into 3 groups. Fifteen minutes before SWL, 4 mL of saline solution was given to the patients in group I, 8 mg lornoxicam in group II, and 16 mg lornoxicam in group III. All groups received 1 mcg/kg fentanyl intravenously 3 minutes before SWL. Pain scores, blood pressure, heart rate, respiratory rate, and oxygen saturation were noted before SWL, at 1 minute and every 5 minutes during the procedure. Also, additional fentanyl consumption, oxygen support requirements, time for recovery room discharge, adverse effects, and patient satisfaction were recorded. RESULTS: The mean blood pressure, heart rate, and SpO(2) values were significantly lower in group I at 5 and 10 minutes (P < .01). The mean visual analogue scale scores and fentanyl consumption were higher in group I (P < .001). The additional meperidine requirement was higher in group I (P = .014). In group I, oxygen requirement was higher and recovery room period was longer than in the other 2 groups (P < .001), and 2 patients from group I had respiratory depression develop. The incidence of nausea and vomiting was higher in group I (P < .05). The patients' satisfaction scores were higher in groups II and III than in group I (P = .001). CONCLUSIONS: Eight milligrams of intravenously administered lornoxicam 15 minutes before SWL provides pain relief and patient satisfaction during the procedure, reducing opioid requirements as well as decreasing the incidence of side effects.

Parapharyngeal tumor mimicking cervicogenic headache.

Nasopharyngeal cancer can occur in any age group and is often misdiagnosed. Cervicogenic headache (CEH) is a clinical condition, putatively originating from nociceptive structures in the neck. A patient with CEH-like symptoms occurring as a result of nasopharyngeal cancer invasion is reported. A 77-year-old man was admitted to the anesthesiology department (pain unit) with a 3-month history of severe unilateral headache. The headache began in the right part of the neck and spread to the right frontoorbital region and was always unilateral. There was no history of neck trauma, and the headache did not increase with neck movement. Analgesics were ineffective. The visual analog scale score for pain was 6. Neurological examination demonstrated tenderness over the right greater occipital nerve and reduced range of motion in the cervical spine. Cervical computerized tomography revealed a solid tumor in the right parapharyngeal region, adjacent to the C2-C3 vertebrae. To the authors' knowledge, this is the first case in the literature of tumoral invasion of nasopharyngeal cancer presenting as CEH. Cervical neuroimaging is obligatory in patients with late-onset, severe CEH.

Greater occipital nevre block in migraine headache: preliminary results of 10 patients.

Despite a favorable clinical experience, there are little evidence existing about the effects of greater occipital nerve (GON) block in migraine treatment. In an open, preliminary trial we evaluated the use of GON block with 0,5 % bupivacaine, in prevention of migraine attacks. Ten women suffering from migraine diagnosed according to International Headache Society criteria were evaluated in a six-month study period. During the treatment and entire follow-up period, the patients avoided prophylactic therapy. Patients were given 3 times GON blocks with 0.5 % bupivacaine one week intervally. Afterwards blocks were repeated for a maximum 5 sessions depending on the clinical response. Clinical evaluation was assessed using a monthly Total Pain Index (TPI), and recording of the number of migraine attacks and analgesic consumption per month. At the end of the first month, TPI reduced from 308.3+/-55.2 to 114,1+/-4.7 (p=0,005). When compared to the values before treatment, it was seen that during the first month mean number of migraine attacks reduced from 12.6+/-4.8 to 4.9+/-1.8, mean analgesic consumption reduced from 11.0+/-3.4 to 4.9+/-1.1, and these reductions lasted up to six months. During the treatment no severe advers effect was seen in all cases. Although preliminary and obtained on a limited number of patients, our results show that the GON block with 1.5 ml of 0.5% bupivacaine does not have any severe advers effect and is effective in the prevention of migraine attacks.

The effect of opioid administration by different routes on the psychological functions of elderly patients.

Psychological status of patients during epidural and intravenous (i.v.) morphine administration are not known enough. It's known that after administration of morphine epidurally and intravenously plasma concentrations are similar but the concentrations in cerebrospinal fluide are different. The effects of two postoperative analgesia treatment regimens on the psychological and mental functions of the elderly after major orthopedic surgery were investigated in this randomized, blinded study. Morphine was used epidurally in Group E and intravenously in Group IV with patient controlled analgesia method for postoperative analgesia treatment. All patients were assessed for psychological status the day before surgery and 2 days after surgery using the Brief Symptom Inventory (BSI). The results of the BSI were assessed with the Global Severity Index (GSI). Nine subscales were also derived: depression, somatization, obsessive-compulsive, anxiety, interpersonal sensitivity, hostility, phobic anxiety, paranoid ideation, and psychoticism. There was not significant difference between the groups for preoperative and postoperative GSI results (p>0.05). Only interpersonal sensitivity subscale results in Group i.v. were decreased compared to the baseline (p<0.001). Preoperative BSI and submeasurement test scores revealed no correlation with total morphine consumption in both groups (p>0.05). Mental changes like agitation, time and place disorientation were seen equally in both groups. This study showed that after epidural and intravenouse morphine administration, no psychologycal changes were observed in the postoperative period compared with baseline. Patients who received morphine intravenously were showed less interpersonal sensitivity in the postoperative period.

Is there a role for nitric oxide activity in cervicogenic headache?

Cervicogenic headache (CEH) is a unilateral headache that can be provoked by neck movement, awkward head positions or pressure on tender points in the neck. The mechanisms underlying the stimulation of pain in CEH are not clearly known. In this study, we measured serum nitrate and nitrite levels as an index of nitric oxide (NO) activity in 15 patients with CEH during headache and headache-free periods and in 15 healthy controls. Total nitrate+nitrite levels were found to be higher in CEH patients during headache periods than in healthy controls (20.7+/-3.8 micromol/l vs 14.4+/-3.6 micromol/l, p<0.001), but not in CEH patients during headache-free periods (16.1+/-2.2 micromol/l) compared with the controls (p>0.05). In the patients with CEH, serum total nitrate+nitrite levels were found to be higher during headache periods than during headache-free periods (p=0.001). It can thus be hypothesized that the changes observed are a cause of the attack rather than a consequence of the disease process.

Efficacy of lornoxicam in postoperative analgesia after total knee replacement surgery.

In total knee replacement operation, patients have a severe pain in the postoperative period. Because of side effects of opioids, multiple postoperative pain treatment regimens are more suitable in these elderly patients. In this double-blind, randomized, placebo controlled study, the effect of lornoxicam administration (32 mg/48 hour) on morphine consumption and drug-related side effects were investigated in elderly patients undergoing total knee replacement. Group M (n=23) and Group L (n=23) received morphine with patient controlled analgesia (PCA) device postoperatively. Additionally Group L received lornoxicam 16 mg intravenously 15 minutes before surgery and 8 mg at postoperative 12th and 24th hours. Morphine consumption in Group L were significantly lower than in Group M at 2, 3, 6, 8, 24, 36 and 48th postoperative hours (p<0.05). At the end of 48th hour mean total morphine consumptions (mean+/-SD) for Group M and Group L were 63.70+/-15.70 mg and 34.60+/-16.32 mg, respectively. AUC (area under the curve) Morphine 0-48h in Group M was 59+/-13 and in Group L it was 30+/-13 (p<0.001). Incidence of side effects in Group M were 60% and 25% in Group L (p<0.05). In Group M, 8 patients (40%) experienced nausea and 3 (15%) patients experienced itching where as in Group L, 3 patients (15%) experienced nausea, 1 patient (5%) itching, 1 patient (5%) dry mouth. Lornoxicam administration in total knee replacement is associated with decreased morphine consumption for postoperative analgesia and fewer side effects.

The effect of 3-in-1 femoral nerve block with ropivacaine 0.375% on postoperative morphine consumption in elderly patients after total knee replacement surgery.

Total knee replacement (TKR) is one of the most painful orthopedic surgical procedures. This study was aimed to investigate the effect of a single-shot preoperative 3-in-1 femoral nerve block on postoperative pain by using 0.375% ropivacaine, and on the consumption of morphine by using PCA following the TKR surgery. Side effects were also evaluated in this setting. 34 patients were included in this study. Group R (n=17) received a 3-in-1 femoral nerve block (FNB) with 40 mll of ropivacaine 0.375%. Group S (n=17) received only a 2 mg loading dose of morphine 30 minutes before the end of surgery, and no block was performed. Both groups received general anesthesia and postoperatively had a PCA pump programmed to deliver morphine. VAS scores at rest, morphine consumption and adverse effects were recorded. Two patients were excluded from each group. Pain scores at 0, 1, 2, 3, 4, 6, 8 postoperative hours were significantly lower in group R in resting position (p<0.05). Group R experienced no pain at the recovery room and this state lasted 8 hours after the surgery while group S reached the acceptable score (VAS ? 3) one hour after leaving the recovery room. The morphine requirement was significantly lower in Group R at 12, 18, 24, 48 hr after TKR (p<0.001). Side effects were also lower in this group. Preoperative single-shot 3-in-1 FNB with 40 cc of ropivacaine 0.375% provides better VAS scores, less morphine consumption and fewer side effects in elderly patients when compared to the group with no block.

Ketamine combined with morphine for the management of cancer pain in a patient with meperidine tolerance and addiction.

Pain treatment of patients with opioid addiction and tolerance may be challenging due to their unexpectedly higher pain sensitivities and opioid requirements. It has been reported that the N-methyl-D-aspartate receptor is involved in mechanisms of tolerance to opioid analgesics. Recently enhancement of morphine induced analgesia by low dose ketamine addition to the treatment regimen has been reported. We report a cancer patient with meperidine tolerance and psychological dependency to the agent who was afterwards successfully treated with morphine-ketamine combination.

Cervicogenic headache: pathophysiology, diagnostic criteria and treatment.

Cervicogenic headache is a relatively common and still controversial form of headache arising from structures in the neck. Cervicogenic headache is a unilateral fixed headache characterised by pain that starts in the neck and spreads to the ipsilateral oculo-fronto-temporal area. The pathophysiology of cervicogenic headache probably depends on the effects of various local pain-producing or eliciting factors, such as intervertebral dysfunction, cytokines and nitric oxide. A reliable diagnosis of cervicogenic headache can be made based on the criteria established in 1998 by the Cervicogenic Headache International Study Group or the International Headache Society's most recent International Classification of Headache Disorders (2004). Various therapies have been used in the management of cervicogenic headache. These range from lowly invasive, drug-based therapies to highly invasive, surgical-based therapies. Unfortunately, the paucity of experimental models for cervicogenic headache and the relative lack of biomolecular markers for the condition mean much is still unclear about cervicogenic headache and the disorder remains inadequately treated.