Influence of Potential Gene Polymorphisms on Propofol Dosage Regimen in Patients Undergoing Abdominal Hysterectomy.

Propofol (2,6-diisopropylphenol) is the most common intravenous anesthetic used in modern medicine. It is postulated that individual differences in genetic factors [polymorphism of single nucleotide polymorphisms (SNPs)] in the genes encoding metabolic enzymes, molecular targets and molecular binding sites of propofol can be responsible for susceptibility to propofol effects. The aim of our study was to investigate the influence of the cytochrome P450 2B6 isozyme CYP2B6 (rs3745274), γ-aminobutyric acid type A (GABAA) receptor α1 subunit GABRA1 (rs2279020) and ATP-binding cassette subfamily B member 1 ABCB1 (rs1045642) gene polymorphisms on propofol therapeutic outcomes in the patients undergoing abdominal hysterectomy. Ninety patients aged 29-74 years, with different ethnicities were included in this study. The presence of polymorphisms was analyzed using TaqMan SNP genotype analysis on Stratagene MxPro 3005P real-time polymerase chain reaction (qPCR). The distribution of all three genetic variants was within the Hardy-Weinberg equilibrium. There was no significant difference (p >0.05) in the allelic frequencies of polymorphic variants and genotype distributions between adult and older patients and between patients of different ethnicities. Our study did not detect a statistically significant influence of the CYP2B6 (c.516G>A), GABRA1 (c.1059+15G>A) and ABCB1 (c.3435T>C) variants on the variability of clinical parameters (doses for induction in anesthesia, additional doses, induction time and wake time after anesthesia and side effects of propofol). However, the observed trend on the possible influence of the CYP2B6 (c.516G>A) and GABRA1 (c.1059+15G>A) variants warrant an extension of these studies on a larger number of patients.

Traumatic axonal injury, a clinical-pathological correlation.

Traumatic axonal injury (TAI) is a distinct clinicopathological entity that can cause serious impairment of the brain function and can sometimes be found as a concrete cause of death. It has been discussed from the perspective of its biomechanical importance, and also from the standpoint of certain criteria for the pathological diagnosis of TAI. However, since the time when DAI (diffuse axonal injury) was initially described, there have been few, if any, discussions about the clinical-pathological correlation in TAI. This paper is an attempt to address this issue. For the purpose of certain pathological diagnoses of TAI, 63 cases with closed head injuries have been subjected to the complete forensic-neuropathological examination, involving immunohistochemistry with antibody against ß-APP. In the diagnosis of TAI strict criteria have been followed. Then, retrograde analysis of the clinical parameters has been performed in order to determine some clinical-pathological correlation. The following two most reliable parameters of the impairment of the brain function have been analyzed: the impairment of the consciousness and the time of survival. Comparing the two groups, the one with TAI and the other without TAI, and using appropriate statistical evaluation, our results show that TAI is not a significant contributing factor to the lethal outcome in the early post injury period (24 h), but it is undoubtedly a contributing factor for the severe impairment of the brain function indicated through the status of the consciousness.

Caesarean section in isobaric spinal anesthesia with and without direct preoperative hydration with crystalloids.

BACKGROUND: Because the direct preoperative hydration with crystalloids (20 ml/kg) does not adequately prevent spinal hypotension during cesarean section, the authors investigated whether a continuous intravenous infusion of ephedrine (50 mg/500 ml of Ringer solution) without preoperative hydration would prevent the spinal hypotension more effectively. METHODS: Forty parturients with ASA status I were randomized either to receive a preoperative hydration with 20 ml/kg of Ringer solution, or to receive continuous ephedrine infusion, simultaneously with spinal anesthesia. The infusion rate was adjusted according to systolic blood pressure. Significant hypotension was defined as a systolic blood pressure below 100 mmHg. Rescue boluses consisted of ephedrine 10 mg in parturients with prehydration and ephedrine 5 mg in parturients with ephedrine infusion. RESULTS: Significant hypotension occurred less frequently in the ephedrine group than in the volume group: 40% versus 60% (p < 0.05). Nausea and vomiting occurred less frequently in the ephedrine group than in the volume group: 40% and 30% versus 60% and 50%, respectively (p < 0.05). The mean quantity of infused Ringer solution was 370 ml +/- 31 in the ephedrine group, i.e. significantly lower than 1,640 ml +/- 192 in the volume group (p < 0.05). The mean quantity of ephedrine given in the ephedrine group was 30 mg +/- 4.1. The mean quantity of ephedrine given in the volume group was 25 mg +/- 2. The difference was not significant. Apgar scores were similarly good in both groups. CONCLUSION: The continuous infusion of ephedrine simultaneously with spinal anesthesia is superior to direct preoperative hydration with crystalloids in preventing the spinal hypotension and its clinical manifestations in parturients delivered with C-section (Tab. 3, Ref. 20).

Spinal anaesthesia for cesarean section with reduced dose of intrathecal bupivacaine plus fentanyl.

BACKGROUND AND OBJECTIVES: The hypotension following spinal anesthesia remains common place in cesarean delivery. The combination of reduced dose of local anesthetics with intrathecal opioids makes it possible to achieve adequate spinal anesthesia with minimum hypotension. We investigate whether this synergistic phenomenon could be used to provide less frequent hypotension while incurring adequate spinal anesthesia for cesarean section. METHODS: Forty women scheduled for cesarean delivery (twenty in each group) were divided into two groups of patients who received a spinal injection of either 13.5 mg of standardized isobaric 0.5% bupivacaine or 9 mg of isobaric bupivacaine with 20 microgr fentanyl added. Each measurement of a systolic blood pressure less than 95 mm Hg or a decrease in systolic pressure of greater than 25% from baseline was considered as hypotension and treated with a bolus of 5 to 10 mg of intravenous ephedrine. The quality of surgical anesthesia was evaluated also. RESULTS: Spinal block provided excellent surgical anesthesia in almost all patients. Peak sensory level was higher (Th 2-3 vs. Th 4-5) and motor block was more intense in the plain bupivacaine group; the patients from standardized bupivacaine group were more likely to require treatment for hypotension (75% vs 15%) and had more persistent hypotension (4.6 vs. 1.0 hypotensive measurements per patient) than patients in the reduced bupivacaine-fentanyl group. Mean ephedrine requirements were 22.0 mg and 3.5 mg, respectively. Patients in the bupivacaine group also complained of emetic effects more frequently than patients in the reduced dose bupivacaine-fentanyl group. CONCLUSIONS: Bupivacaine 9 mg plus fentanyl 20 microgr provided spinal anesthesia for cesarean delivery with less hypotension and vasopressor requirements while ensuring excellent perioperative surgical anesthesia.