Inguinal hernia repair in day surgery: the role of MAC (Monitored Anesthesia Care) with remifentanil.

BACKGROUND: The extension of indications for procedures in a Day Surgery (DS) setting has led to changes in the anesthetic and surgical treatment of Inguinal Hernias (IH). According to the recommendations of the European Hernia Society, the treatment of IH in DS units should be performed under Monitored Anesthesia Care (MAC). PATIENTS AND METHODS: 960 patients underwent IH repairs over a period of 24 months. The patients were randomly divided into two groups: R (remifentanil) and F (fentanyl); the group F was considered as a control group. The exclusion criteria in both group were: morbid obesity (BMI>40 or BMI>35 in association with high blood pressure or diabetes); coagulopathy; OSAS (obstructive sleep apnea syndrome) with AHI >10; cardiovascular, respiratory, renal, hepatic or metabolic disease; history of substances abuse; GERD-related esophagitis (gastro-esophageal reflux disease); chronic analgesic use; allergy to local anesthetic and ASA>III. Patients reported their level of pain on a verbal numeric scale (VNS), with scores ranging from 0 to 10. For each patient systolic and diastolic blood pressure (SBP and DBP), mean arterial pressure (MAP), heart rate (HR) and peripheral oxygen saturation (SpO2) were recorded. The results are presented as the mean value ± standard deviations; statistical analysis was performed using Student's t-test. RESULTS: Amongst the 960 procedures, complications or side effects related to the anesthetic techniques didn't occur; no procedure-related complications requiring mechanical ventilation support were reported. Our research focused on evaluating remifentanil effectiveness in pain control and its impact on hemodynamic stability and respiratory function. There was a significant difference between the two groups with regard to the VNS. CONCLUSIONS: Remifentanil, is an excellent drug for pain control during intra-operative procedures, that allows an optimal hemodynamic stability for IH repairs in a DS setting, due to its pharmacokinetic and pharmacodynamic properties and few adverse effects.

Measurement of intra-abdominal pressure in large incisional hernia repair to prevent abdominal compartmental syndrome.

INTRODUCTION: The repair of large incisional hernias may occasionally lead to a substantial increase in intra-abdominal pressure (IAP), and rarely to abdominal compartmental syndrome (ACS) with subsequent respiratory, vascular, and visceral complications. Measurement of the IAP has recently become a common practice in monitoring critical patients, even though such measurements were obtained in the early 1900s. PATIENTS AND METHODS: A prospective study involving 54 patients undergoing elective abdominal wall gap repair (mean length, 17.4 cm) with a tension-free technique after incisional hernia was conducted. The purpose of the study was to determine whether or not urinary pressure for indirect IAP measurement is a reliable method for the early identification of patients with a higher risk of developing ACS. IAP measurements were performed using a Foley catheter connected to a HOLTECH® medical manometer. IAP values were determined preoperatively, after anesthetic induction, upon patient awakening, upon patient arrival in the ward after surgery, and 24 h after surgery before removing the catheter. All patients were treated by the same surgical team using a prosthetic composite mesh (PARIETEX®). RESULTS: Incisional hernia repair caused an increase in the mean IAP score of 2.68 mmHg in 47 of 54 patients (87.04%); the IAP was decreased in two patients (3.7%) and remained equal in five patients before and 24 h after surgery (9.26%). FEV-1, measured 24 h after surgery, increased in 50 patients (92.6%), remained stable in two patients (3.7%), and decreased in two patients (3.7%). The mean increase in FEV-1 was 0.0676 L (maximum increase = 0.42 L and minimum increase = 0.01 L) in any patient who developed ACS. CONCLUSIONS: Measurement of urinary bladder pressure has been shown to be easy to perform and free of complications. Measurement of urinary bladder pressure can also be a useful tool to identify patients with a higher risk of developing ACS.

Biological and environmental agents in the preservation of ancient human remains.

In osteological studies, the state of preservation of the material assumes great importance in the case of histopathological, histomorphological and histomorphometric analyses of thin sections. The aims of the present study were to compare osteological samples from graves of different eras and geographical sites in order to identify possible similarities or differences in the quantitative and qualitative action of fungal and bacterial contaminants and to throw light on the importance of the diagenetic processes that the bone undergoes from the moment of its deposition in the ground to its conservation in laboratories and museums. Analysis by polarized light microscopy revealed large qualitative and quantitative differences between the samples and great variability in the modalities of infestation. The present study demonstrates that post-mortem alterations due to the action of biological agents can in some cases invalidate the analysis of osteological samples, by rendering the material unsuitable for observation and diagnosis.

Brief communication: a test and correction of the clavicle method of Stout and Paine for histological age estimation of skeletal remains.

The histological method developed by Stout and Paine ([1992] Aln. J. Phys. Antropol. 87:111-115) for estimating age at death using the clavicle is tested on a known age independent sample from a nineteenth century cemetery near Spitalfriedhof St. Johann in Basel, Switzerland. The mean absolute difference between reported ages and histologically predicted ages is 5.5 years. Mean predicted age for the sample is different from mean reported age. This difference is accounted for by differences in the age distributions between the original autopsy sample used to derive the histological age-predicting formula and the cemetery sample, and an inherent loss of reliability of histological age predictions for the skeletal remains of older individuals. A new formula based upon the combined original autopsy sample of Stout and Paine (1992) and the Swiss cemetery sample is presented. It is recommended that this formula be used when estimating ages for older individuals or archaeological skeletal samples.

Pharmacokinetics and molecular detoxication.

This paper presents a comprehensive overview of the pharmacokinetic parameters used from in vivo and in vitro studies that are important in order to understand the major conceptual approaches of toxicokinetics and the disposition of environmental chemicals. In vitro biochemical information concerning the detoxication of environmental chemicals is also presented. The discussion leads to a more complete appreciation for the use of in vitro measurements for in vivo correlations. The concept of interspecies scaling in the interpolation and extrapolation of fundamental biochemical metabolic processes is illustrated with a number of examples. Additional examples of in vitro-in vivo correlations are presented in the evaluation of the impact of chemical exposure to humans. Finally, several important metabolic detoxication enzymes are presented, including the mammalian microsomal cytochrome P450 and flavin-containing monooxygenases as well as carboxylesterases and glucuronosyltransferases, to provide insight into the processes of chemical detoxication in mammalian tissue and blood. Because interspecies scaling and the pharmacokinetics of chemical disposition have already shown their usefulness in understanding some examples of chemical disposition, our summary focuses on showing the usefulness of the pharmacokinetic equations and providing confidence in using the approach for in vitro-in vivo correlations. Ultimately, the presentation may provide the reader with a conceptual framework for future evaluation of the human health risks associated with environmental toxicants.

Effect of cannabidiol pretreatment on the kinetics of tetrahydrocannabinol metabolites in mouse brain.

Tetrahydrocannabinol (THC), a major constituent of marijuana, and several of its metabolites are psychoactive in humans. Cannabidiol (CBD), a nonpsychoactive cannabinoid, inhibits hepatic microsomal THC metabolism and also modulates subjective psychological responses to THC in humans. Treatment of mice with CBD markedly decreased the hepatic microsomal in vitro formation of the major THC metabolites, 6 alpha-OH-THC and 7-OH-THC and increased formation of the minor metabolite 6 beta-OH-THC. THC blood levels were modestly elevated after CBD pretreatment and THC administration, compared with untreated controls, and area under the curve (AUC) of THC increased 50% as a function of decreased clearance. CBD pretreatment modestly increased the Cmax, AUC, or t1/2 of the major THC metabolites in the blood, whereas those kinetic parameters for 6 beta-OH-THC were dramatically increased. Changes in brain concentrations and kinetic parameters of the major THC metabolites did not reflect the relatively modest changes found in blood levels after CBD pretreatment, but exhibited large increases in AUC (7- to 15-fold) and t1/2 (2- to 4-fold), as well as in tmax. Changes in brain concentrations and kinetic parameters for 6 beta-OH-THC reflected the marked changes observed in blood levels after CBD pretreatment. Thus, CBD pretreatment resulted in large increases in AUC and t1/2 of all THC metabolites in brain, with a modest increase in AUC of THC. These changes in THC metabolite brain pharmacokinetics may contribute to the modulation of psychological responses to THC observed after CBD treatment.

HPLC assay for FK 506 and two metabolites in isolated rat hepatocytes and rat liver microsomes.

Despite the current use of a standard two-step enzyme immunoassay in the clinical monitoring of the immunosuppressant FK 506, the lack of specificity for the parent drug in this assay renders it unsuitable for drug metabolism studies. An HPLC assay has been developed for studying the metabolism of FK 506 in isolated hepatocytes and microsomal mixtures. This assay allows simultaneous measurement of the parent drug and two of its time dependent metabolites. Metabolism of this drug was studied in intact rat liver cells and rat liver microsomes. We have shown that the metabolites observed are products of phase 1 oxidation reactions. Correlation of the 6 beta-testosterone hydroxylase activity with the FK 506 metabolite (M1) initial formation rate is consistent with the belief that CYP 3A isozymes are involved in FK 506 metabolism in male rats.

FK 506 metabolism in male and female rat liver microsomes.

The main metabolite of the immunosuppressant FK 506 in hepatic microsomes from male and female Sprague-Dawley rats was identified by mass spectrometry as an O-desmethyl derivative. The rate of formation of the metabolite exhibited saturation kinetics in the range of 0.6-40 microM with Vmax and KM equal to 0.66 +/- 0.47 nmol/min/mg protein and 24 +/- 18 microM, respectively, for microsomes from male rats, and 0.28 +/- 0.15 nmol/min/mg protein and 24 +/- 16 microM, respectively, for microsomes from female rats. CYP3A enzymes are thought to be responsible for metabolizing FK 506 in male rats. Because untreated female rats show no classical CYP3A activity, our work suggests that other CYP enzymes metabolize FK 506 in untreated female rats. O-Desmethyl FK 506 did not cross-react in the standard clinical ELISA assay for FK 506. This suggests that demethylation had occurred at the C13-methoxy group.