Çetin Kaymak

Treatment of Post‐Dural Puncture Headache With Bilateral Greater Occipital Nerve Block

(Headache 2010;50:869‐881)

Genoprotective role of vitamin E and selenium in rabbits anaesthetized with sevoflurane

In this study, genotoxic effects of repeated sevoflurane anaesthesia were investigated in rabbits with or without antioxidant supplementation. Twenty-one New Zealand male rabbits were included in the study and randomized into three groups as: placebo treated (Group I), vitamin E supplemented (Group II) and selenium supplemented (Group III). Vitamin E and selenium were given intraperitoneally for 15 days before anaesthesia treatment. Anaesthesia was administered using 3% sevoflurane in 4 L/min oxygen for a 3-hour period and continued for 3 days. Blood samples were collected before anaesthesia (Sample 1), after the first, second and third days of sevoflurane administration (Sample 2, Sample 3 and Sample 4 respectively) and the last samples were taken 5 days after the last sevoflurane administration (Sample 5). Genotoxic damage was examined using the comet assay. The degree of damage is assessed by grading the cells into three categories of no migration (NM), low migration (LM) and high migration (HM) depending on the fraction of DNA pulled out into the tail under the influence of the electric field. The number of comets in each sample was calculated (1 × number of comets in category NM + 2 × number of comets in category LM + 3 ×number of comets in category HM) and expressed as the total comet score (TCS), which summarizes the damage frequencies. In Group I, a significant increase in the mean TCSs was observed for Samples 3 and 4 as compared with Sample 1. However, there were no significant differences between Samples 1, 2 and 5. The mean TCS of Sample 4 was significantly higher than Sample 1, 2 and 3 in Group II. Group III demonstrated no significant mean TCSs for any experimental conditions. Statistical differences were also observed between the groups with significant P values. This experimental study points out the presence of DNA damage with repeated sevoflurane anaesthesia and the genoprotective role of antioxidant supplementation on DNA damage in mononuclear leukocytes of rabbits by highly sensitive comet assay.

Assessment of genotoxic damage in nurses occupationally exposed to anaesthetic gases or antineoplastic drugs by the comet assay.

The potential mutagenic/carcinogenic action of waste anaesthetic gases and antineoplastic drugs in occupationally exposed human populations has been previously reported in several studies. Antineoplastic agents discovered in the first two decades of cancer therapy (1950 to 1970) largely interact with DNA or precursors, inhibiting the synthesis of DNA or causing irreparable damage to DNA itself. Considering the mechanisms of the antineoplastic drugs that are used, it is not surprising that many persons involved in health care, especially nurses, are worried about the health effects of these drugs. Experimental and epidemiological studies suggest that genotoxic effects can arise from inhalation anaesthetics. Due to their widespread use in operating rooms, there is a great concern that operating room personnel as well as patients might be at health risk from anaesthetics. The aim of the present study was to assess the possible genotoxic risk, by the alkaline comet assay, in the peripheral blood lymphocytes of nurses who are handling antineoplastic drugs or are exposed to waste anaesthetic gases.

Oxidative DNA damage and total antioxidant status in rats during experimental gram-negative sepsis

Sepsis and septic shock remains as leading cause of death in adult intensive care units. It is widely accepted that gram-negative bacteria and their endotoxins cause sepsis and septic shock, predominantly. Enhanced generation of reactive oxygen species may be responsible for tissue injury in septic shock and endotoxemia. The aim of this study was to assess oxidative DNA damage and the total antioxidant status (TAS) in peripheral lymphocytes of rats during different intraperitoneal gram-negative sepsis stages. Adult male Sprague-Dawley rats were divided randomly into four groups. Control group was intraperitoneally inoculated with 2 mL of pyrogene-free saline (Group I, n = 6), and the other rats received an intraperitoneal inoculum with 2 mL of saline containing 2 × 108 CFU of Escherichia coli. The animals were killed at time zero (Group I, n = 6), at 6th (Group II, n = 7), 12th (Group III, n = 7), and 24th (Group IV, n = 7) hour after the E. coli inoculation. Oxidative DNA damage in peripheral lymphocytes of rats was evaluated by modified comet assay (single-cell gel electrophoresis). Formamidopyrimidine DNA glycosylase (Fpg) and Endonuclease III (Endo III) were used to detect oxidized purines and pyrimidines, respectively. Total antioxidant quantification was carried out using ABTS+ (2,2′-Azino-di-[3 ethylbenzthiazoline sulphonate]) radical formation kinetics (Randox kit) in serum samples. Significant elevations of basal levels of strand breaks (SB) in Group IV were observed as compared with Group I, II, and III. There was a significant increase in Fpg sites in Group III as compared with Group I and II. However, there was no significant difference in terms of Endo III sites in any of the groups. Although the TAS was decreased with the stages of sepsis, this moderate decrease was significant in only Group IV as compared with Group I. There was no statistically significant correlation between DNA damage and TAS for any of the groups.

Determination of DNA damage after exposure to inhalation anesthetics in human peripheral lymphocytes and sperm cells in vitro by comet assay

In this study, genotoxic activities of four halogenated anesthetics (halothane, isoflurane, sevoflurane and desflurane) were investigated in human peripheral blood lymphocytes (PBLs) and sperm cells in vitro by alkaline comet assay. For this purpose, sperm or lymphocyte suspension was exposed to different concentrations (0.1 mM, 1 mM, 10 mM and 100 mM) of anesthetic agents and 1% dimethyl sulfoxide (DMSO) or phosphate-buffered saline (PBS) as controls. The DNA strand breaks as well as alkali-labile sites were measured as percentage tail intensity with comet assay. The results of this study demonstrate that all analyzed drugs were capable of inducing DNA damage on PBLs in a dose-dependent manner in vitro. However, the results in sperm cells were slightly different since we did not observe any genotoxic effect for desflurane in any of the exposure doses, and the genotoxic effect of halothane was not dose dependent. This experimental study points out to the presence of DNA damage after exposure to halogenated anesthetics in both PBLs and sperm cells, although this effect seems to be higher in PBLs.

β2 Adrenoceptor (ADRB2) Pharmacogenetics and Cardiovascular Phenotypes during Laryngoscopy and Tracheal Intubation

Pharmacogenetics is the study of genetic variations that cause a variable drug response characterized by alteration in drug metabolism or in pharmacodynamics. The polymorphisms in genes encoding receptors relevant to treatment cause variation in sensitivity to many drugs. β2 Adrenoceptor genetic variation contributes to regulation of blood pressure and hemodynamic changes by mediating peripheral vasodilatation. Laryngoscopy and tracheal intubation associated with hemodynamic changes. Although there are four nonsynomic single-nucleotide polymorphisms (SNPs) of β2 adrenoceptor gene, codon 16 (Arg16Gly) and codon 27 (Gln27Glu) SNPs are both common and functionally important. In this paper, the authors investigated the β2 adrenoceptor Gly16 and Glu27 SNPs in response to drugs relevant to anesthesia and how these SNPs impacted upon the cardiovascular phenotypes. The authors measured arterial systolic and diastolic blood pressure, heart rate, and rate-pressure product before induction of anesthesia and 1 min following laryngoscopy and tracheal intubation. Genomic DNA was amplified and genotyped using allele-specific polymerase chain reaction (ASPCR) and restriction fragment length polymorphism (RFLP) assays, respectively. When the authors compared hemodynamic results according to genotypes, the patients with Gln homozygote allele at codon 27 exhibited significant increase of heart rate than patients with Glu allele after laryngoscope and tracheal intubation.

Association between GSTP1 gene polymorphism and serum α-GST concentrations undergoing sevoflurane anaesthesia

Background and objectives: The measurement of &agr;‐glutathione‐S‐transferase enzyme is one of the most sensitive indicators of hepatocellular function. Variation in the glutathione‐S‐transferase P1 gene clusters has been intensively investigated and polymorphism has been described. The aim of the study was to assess whether an association exists between glutathione‐S‐transferase P1 gene polymorphism and serum &agr;‐glutathione‐S‐transferase concentrations for the first postoperative day in patients who underwent anaesthesia with sevoflurane. Methods: In all, 54 unrelated patients were enrolled in this study. Anaesthesia was induced with thiopental and fentanyl. Vecuronium was used for neuromuscular relaxation before endotracheal intubation. Anaesthesia was maintained with sevoflurane in a gas mixture containing 50% nitrous oxide in oxygen. Peripheral venous blood samples to determine serum &agr;‐glutathione‐S‐transferase concentrations were collected before induction (T1), at the end of anaesthesia (T2) and at 24‐h postoperatively (T3). Enzyme‐linked immunosorbent assay (ELISA) immunoassay was used to measure &agr;‐glutathione‐S‐transferase levels. Genomic DNA was isolated from serum samples using a genomic DNA purification kit. In order to detect the variants of glutathione‐S‐transferase P1, polymerase chain reaction ‐ restriction fragment length polymorphism analysis was employed. Results: Early postoperative serum &agr;‐glutathione‐S‐transferase levels for all patients were significantly increased when compared with preanaesthetic and 24‐h postoperatively (P < 0.05). Serum &agr;‐glutathione‐S‐transferase concentrations, in individuals with glutathione‐S‐transferase P1 Ile105Val genotypes (heterozygote gene), remained elevated at 24 h (P < 0.05), whereas levels in individuals with glutathione‐S‐transferase P1 Ile105Ile (wild gene) decreased (P > 0.05). Conclusions: Although &agr;‐glutathione‐S‐transferase levels were elevated in all patients after sevoflurane anaesthesia, levels remained high at 24 h in patients with glutathione‐S‐transferase P1 Ile105Val genotypes compared to controls.

Comparison of prognostic value of N-terminal pro-brain natriuretic peptide in septic and non-septic intensive care patients

Introduction The aim of this study is to compare the prognostic value of N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in septic and non-septic intensive care patients. Material and methods Fifty consecutive patients admitted to the intensive care unit (ICU) were enrolled in either the septic or non-septic group according to the criteria in the International Sepsis Definitions Conference in 2001. Demographic and clinical data, procalcitonin and lactate levels at admission, and death within 28 days were registered. Five blood samples were collected from all patients for NT-proBNP measurements. Results Septic patients had higher APACHE II (19 (16.00–24.25) vs. 16 (13.00–18.25)), and SOFA (8 (5–10) vs. 6 (4–7)) scores (p <0.05). Procalcitonin levels were also higher in septic patients (3.33 (1.06–10.96) vs. 0.46 (0.26–1.01) ng/ml) and more patients required vasopressors in this group (9 (36%) vs. 2 (8%)) (p < 0.05). In the septic group, the correlation between mortality and the level of NT-proBNP was significant for each measurement, starting from the admission. In the non-septic group the correlation between mortality and the level of NT-proBNP was significant only at the 120th h. Conclusions We concluded that the level of NT-proBNP at admission is well correlated with 28-day mortality in septic ICU patients. However, single measurement of NT-proBNP levels in non-septic patients does not correlate with the 28-day mortality. Repeated measurements and an increasing trend of the NT-proBNP levels may show a correlation with mortality in non-septic intensive care patients.

Correlation of computed tomography, magnetic resonance imaging and clinical outcome in acute carbon monoxide poisoning

BACKGROUND AND OBJECTIVES Carbon monoxide is a toxic gas for humans and is still a silent killer in both developed and developing countries. The aim of this case series was to evaluate early radiological images as a predictor of subsequent neuropsychological sequelae, following carbon monoxide poisoning. CASE 1 After carbon monoxide exposure, early computed tomography scans and magnetic resonance imaging findings of a 52-year-old woman showed bilateral lesions in the globus pallidus. This patient was discharged and followed for 90 days. The patient recovered without any neurological sequela. CASE 2 In a 58-year-old woman exposed to carbon monoxide, computed tomography showed lesions in bilateral globus pallidus and periventricular white matter. Early magnetic resonance imaging revealed changes similar to that like in early tomography images. The patient recovered and was discharged from hospital. On the 27th day of exposure, the patient developed disorientation and memory impairment. Late magnetic resonance imaging showed diffuse hyperintensity in the cerebral white matter. CONCLUSION White matter lesions which progress to demyelination and end up in neuropsychological sequelae cannot always be diagnosed by early computed tomography and magnetic resonance imaging in carbon monoxide poisoning.

Mortality of adult intensive care units in Turkey using the APACHE II and SOFA systems (outcome assessment in Turkish intensive care units)

Introduction The aim of this study was to evaluate intensive care unit (ICU) performance using risk-adjusted ICU mortality rates nationally, assessing patients who died or had been discharged from the ICU. For this purpose, this study analyzed the Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) databases, containing detailed clinical and physiological information and mortality of mixed critically ill patients in a medical ICU at secondary and tertiary referral ICUs in Turkey. Material and methods A total of 690 adult intensive care units in Turkey were included in the study. Among 690 ICUs evaluated, 39.7% were secondary and 60.3% were tertiary ICUs. A total of 4188 patients were enrolled in this study. Intensive care units of ministry, university, and private hospitals were evaluated all over Turkey. During the study period, clinical data that were collected concurrently for each patient contained demographic details and the diagnostic category leading to ICU admission. APACHE II and SOFA scores following ICU admission were calculated and recorded. Patients were followed up for outcome data until death or ICU discharge. Results The mean age of patients was 68.8 ±19 and 54% of them were male. The mean APACHE II score was 20 ±8.7. The ICUs’ mortality rate was 46.3%, and mean predicted mortality was 37.2% for APACHE II. The standardized mortality ratio was 1.28 (95% confidence interval: 1.21–1.31). Conclusions There was a wide difference in outcome for patients admitted to different ICUs and severity of illness using risk adjustment methods. The high mortality rate in patients could be related to comorbid diseases, high mechanical ventilation rates and older ages.