Impact of different intraoperative CO2 pressure levels (8 and 15 mmHg) during laparoscopic hysterectomy performed due to benign uterine pathologies on postoperative pain and arterial pCO2 : a prospective randomised controlled clinical trial.

OBJECTIVE: To compare the effects of two different intraoperative CO2 pressures (8 and 15 mmHg) during laparoscopic hysterectomy for benign uterine pathologies in terms of postoperative abdominal and shoulder pain, laparoscopy-mediated vegetative alterations, pain medication requirement, arterial CO2 pressure (pCO2 ), surgical parameters, and safety. DESIGN: Prospective randomised controlled study. SETTING: German university hospital. POPULATION: Female patients undergoing laparoscopic hysterectomy for benign uterine pathologies. METHODS: Patients were randomised to a standard pressure (SP; 15 mmHg, control) or low-pressure (LP; 8 mmHg, experimental) group. MAIN OUTCOME MEASURES: Primary outcomes were postoperative abdominal and shoulder pain intensities, measured via numeric rating scale (NRS) and vegetative parameters (fatigue, nausea, vomiting, bloating) at 3, 24, and 48 hours postoperatively. Secondary outcomes were pain medication requirement (mg) and arterial pCO2 (mmHg). Surgical parameters and intra- and postoperative complications were also recorded. RESULTS: In total, 178 patients were included. Patients in the LP group (n = 91) showed significantly lower postoperative abdominal and shoulder pain scores, fewer vegetative alterations, lower pain medication requirements, a shorter postoperative hospitalization, and lower intra- and postoperative arterial pCO2 values compared with the SP group (n = 87; P ≤ 0.01). No differences in intra- and postoperative complications were observed between groups. CONCLUSIONS: Low-pressure laparoscopy seems to be an effective and safe technique for the reduction of postoperative pain and laparoscopy-induced metabolic and vegetative alterations following laparoscopic hysterectomy for benign indications. TWEETABLE ABSTRACT: Low-pressure laparoscopy seems to be an effective and safe technique for reduction of pain following laparoscopic hysterectomy.

[PONV after strabismus surgery : Risk adapted prophylaxis?]. / PONV nach Strabismus-OP : Risikoadaptierte Prophylaxe?

BACKGROUND: Following strabismus surgery, patients frequently develop variable degrees of postoperative nausea and vomiting (PONV). These symptoms cause discomfort and result in serious complications such as intramuscular bleeding and subconjunctival hemorrhage. In children long lasting PONV can lead to and electrolyte imbalance and dehydration. A prolonged course of recovery is the consequence. For the hospital, PONV can also involve negative economic impacts because of a damaged public reputation of the institution. There is still an ongoing debate on wether prophylaxis of PONV is necessary and how the prophylaxis of PONV should be performed. On one hand, there are proponents of a liberal prophylaxis. These intend to treat almost all patients regardless of their individual risk for PONV. On the other hand, opponents point out that every medication has to be indicated individually. In their view, risk scores should be the base of a risk-adapted approach. OBJECTIVES: The aim of the study was to reduce the frequency of PONV by using an anesthetic technique adapted to the individual risk for PONV. Until now, all trials studying the efficiency of a score-based antiemetic prophylaxis were performed on adult patients. In this study, a risk-adapted approach was evaluated on children for the first time. PATIENTS AND METHODS: In 92 patients, the incidence of PONV was analyzed after strabismus surgery. Before surgery we evaluated the risk factors for PONV according to the POVOC score in children (n = 45, 49 %) and the Apfel's score in adults (n = 47, 51 %). Patients with 0-2 risk factors received a balanced anesthesia (n = 47, 51 %). Those with 3-4 risk factors were operated in total IV anesthesia (TIVA) with propofol (n = 45, 49 %). In addition, as an antiemetic prophylaxis, 0.15 mg/kg dexamethason and 0.1 mg/kg ondansetron were applied in the latter patients. we documented the symptoms and severity of PONV 2, 6 and 24 h after surgery by means of a standardized questionnaire for PONV (Wengritzky-Score). RESULTS: The incidence of PONV was 17 % (n = 16) in all of the patients. The incidence in low-risk patients receiving a BA without prophylaxis were 21 % in adults and 38 % in children. Of the patients at high risk for PONV receiving the multimodal antiemetic approach 8 % (adults) and 9 % (children) suffered from PONV. The combination of TIVA and antiemetics could reduce the incidence of PONV compared to the predicted values in a clinically relevant manner (OR = 0.26, KI: 0.76-0.87). CONCLUSION: The overall incidence could be reduced to a level below 20 %. Particularly in patients with a high risk of PONV, TIVA could clearly reduce the incidence. However, the incidence in patients with 2 risk factors is still high (30-39 %). Therefore, it is important to reconsider the effort involved with risk screening and individually adapting anesthesia. Risk stratification means a pre- and perioperative effort. Therefore, we advocate a more liberal approach for PONV prophylaxis.

[The Effect of Non-Depolarising Muscle Relaxants on Ocular Pulse Amplitude and Intraocular Pressure]. / Beeinflussung der okulären Pulsamplitude und des Intraokulardrucks durch nicht depolarisierende Muskelrelaxanzien.

AIM: In general anaesthesia (GA) for ocular surgery the chosen non-depolarising muscle relaxant has a high influence on the fluctuations of intraocular pressure (IOP) and ocular pulse amplitude (OPA). PATIENTS AND METHODS: In 229 patients, who needed GA for their ophthalmic surgery, OPA and IOP were measured with the dynamic contour tonometer (DCT) before and 5 minutes after intubation. For GA, three groups of non-depolarising muscle relaxants, namely, mivacurium (n = 71), atracurium (n = 91) and rocuronium (n = 67) were used. RESULTS: The IOP decreased by about 4.0 ± 2.3 mmHg using mivacurium in GA, by about 6.1 ± 2.2 mmHg using atracurium and by about 7.4 ± 1.7 mmHg using rocuronium (p < 0.001). The relative decrease of the IOP was 20% for mivacurium, 31% for atracurium and 37% for rocuronium. For mivacurium the OPA decreased from 3.4 ± 1.5 mmHg to 2.2 ± 1.1 mmHg (p < 0.001) in contrast to atracurium (decrease from 3.6 ± 1.5 mmHg to 1.8 ± 0.8 mmHg; p < 0.001) and rocuronium (decrease from 3.1 ± 1.6 mmHg to 1.7 ± 0.9 mmHg; p < 0.001). Mean OPA reduction was lowest with mivacurium (1.3 mmHg) and the highest with atracurium (1.7 mmHg). The mean relative decrease of the OPA was 34% with mivacurium, 46% with atracurium and 43% with rocuronium (p < 0.001). There was no linear correlation between the relative OPA decrease and the relative IOP decrease. CONCLUSION: Risks for ophthalmic surgery may be minimised by avoiding mivacurium in general anaesthesia. Due to its negative effects on IOP and OPA mivacurium does not seem to be suitable for operations with a large opening in the eye such as penetrating keratoplasty and block excision. Rocuronium can be used because it induces a favourised intraoperative decrease of the IOP.

Absence of toxic effects in F344/N rats and B6C3F1 mice following subchronic administration of chromium picolinate monohydrate.

Chromium picolinate monohydrate (CPM) is a synthetic compound heavily marketed to consumers in the United States for use as a dietary supplement for muscle building and weight loss. The National Toxicology Program (NTP) tested the toxicity of this compound based on the potential for widespread consumer exposure and lack of information about its toxicity. Groups of 10 male and 10 female F344/N rats and B6C3F(1) mice were exposed to 0, 80, 240, 2000, 10,000, or 50,000 ppm CPM in feed for 13 weeks. CPM administration produced no effect on body weight gain or survival of rats or mice. Organ weights and organ/body weight ratios in exposed animals were generally unaffected by CPM. No compound-related changes in hematology and clinical chemistry parameters were observed. There were no histopathological lesions attributed to CPM in rats or mice.

[Reduction of intraocular pressure and ocular pulse amplitude during general anesthesia]. / Sinken des Augeninnendrucks und der okularen Pulsamplitude während der Intubationsnarkose.

AIM: Measurement of the intraocular pressure (IOP) is an important tool for glaucoma diagnostics in children or patients with impaired cooperation. General anesthesia (GA) may significantly influence the IOP. This study aimed to evaluate the reduction of IOP during GA. PATIENTS AND METHODS: The IOP was measured in 229 patients in a recumbent position in the non-operated eye prior to and 5 min after the beginning of GA with a dynamic contour tonometer (DCT). RESULTS: The average IOP decreased from 19.9 ± 3.7 mmHg prior to GA to 14.1 ± 3.5 mmHg 5 min after beginning GA (p < 0.0001, IOP decrease 30 %). The GA caused a decrease of up to 2 mmHg in 6.1 %, 2-4 mmHg in 18.8 %, 4-6 mmHg in 21.0 %, 6-8 mmHg in 36.6 %, 8-10 mmHg in 13.6 %, 10-12 mmHg in 2.2 % and more than 12 mmHg in 1.7 % of the eyes. The ocular pulse amplitude (OPA) decreased from a mean of 3.4 ± 1.5 mmHg to 1.9 ± 1.0 mmHg (p < 0.0001, OPA decrease 41 %) under GA. CONCLUSION: A significant decrease of IOP (mean 6 mmHg) occurs during GA and under extreme conditions up to 13.8 mmHg. A decrease of OPA of 1.5 mmHg should be taken into consideration for patients under general anesthesia and under extreme conditions up to 7 mmHg.

DNA adducts: effects of low exposure to ethylene oxide, vinyl chloride and butadiene.

Dose-response relationships of genotoxic agents differ greatly depending on the agent and the endpoint being evaluated. Simple conclusions that genotoxic effects are linear cannot be applied universally. The shape of the molecular dose of DNA adducts varies from linear, to supralinear, to sublinear depending on metabolic activation and detoxication, and repair of individual types of DNA adducts. For mutagenesis and other genotoxicity endpoints, the dose-response reflects the molecular dose of each type of DNA adduct, cell proliferation, as well as endogenous factors that lead to mutagenesis such as the formation and repair of endogenous DNA adducts. These same factors are important when interpreting the shape of dose-response data for carcinogenesis of genotoxic agents, however, tumor background variability adds additional complexity. Endogenously formed DNA adducts may be identical to those formed by chemicals, as in the case of vinyl chloride and ethylene oxide, or they may be those associated with oxidative stress. Data presented in this paper demonstrate that the exogenous number of adducts induced by 5 days of exposure to 10 ppm vinyl chloride is only 2. 2-fold greater than that present as a steady-state amount in unexposed control rats. Similar data are shown for ethylene oxide. Extremely sensitive methods have been developed for measuring the molecular dose of genotoxins. These methods can detect DNA adducts as low as 1 per 10(9) to 10(10). However, in view of the high number of endogenous DNA adducts that are present in all cells, it is unlikely that causal relationships can be attributed to very low numbers of such DNA adducts. Effects of both exogenous and endogenous DNA adducts need to be factored into the interpretation of chemical exposures.

[One stop surgery in pediatric surgery. Preliminary report]. / One-Stop Surgery in chirurgia pediatrica. Esperienza preliminare.

The One-Stop Surgery (OSS) is a new method of Day Surgery, which combines preoperative evaluation and subsequent operation into one visit. This report describes the initial experience of the authors. Referring physicians were informed by fax about method and selected surgical procedures. Included form helped them to gain anamnestic data and to inform parents about preoperative fast. Form was then sent back by fax to the pediatric surgeon and anesthesiologist who determined the patient suitability and scheduled the day of the surgery. At hospital admission, if the diagnosis was confirmed and no anesthesiologic contraindications were discovered, the patient underwent the prescheduled surgical procedure and was discharged as a day case. Another form containing informations about home postoperative care and telephone numbers for emergency call was gave to the parents. From November 2000 through February 2001 43 patients, aged from 2 to 7 years, underwent one-stop surgical procedure: central venous catheter removal (n = 16), umbilical (n = 2) and inguinal (n = 10) hernia repair, prepuce dorsal slit (n = 15). Recovery of all patient was uneventful. None of them called during the period considered necessary for postoperative follow-up. Decreased costs and increased satisfaction of the patients and parents are the most important advantages of the OSS. Potential disadvantages are a not appropriate indication for the planned procedure and/or an anesthesiologic contraindication at hospital admission. It could involve a waste of human and financial resources and an useless psychologic stress for the family. Authors conclude it is not advisable the OSS use on a large scale without a sound experience in pediatric Day Surgery.

Simultaneous quantitation of N(2),3-ethenoguanine and 1,N(2)-ethenoguanine with an immunoaffinity/gas chromatography/high-resolution mass spectrometry assay.

We have previously described an immunoaffinity/gas chromatography/electron capture negative chemical ionization high-resolution mass spectrometry (IA/GC/ECNCI-HRMS) assay for quantitation of the promutagenic DNA adduct N(2),3-ethenoguanine (N(2),3-epsilonGua) in vivo. Here we present an expanded assay that allows simultaneous quantitation of its structural isomer, 1,N(2)-ethenoguanine (1,N(2)-epsilonGua), in the same DNA sample. 1,N(2)-epsilonGua and N(2),3-epsilonGua were purified together from hydrolyzed DNA using two immobilized polyclonal antibodies. GC/ECNCI-HRMS was used to quantitate the 3,5-bis(pentafluorobenzyl) (PFB) derivative of each adduct against an isotopically labeled analogue. Selected ion monitoring was used to detect the [M - 181](-) fragments of 3,5-(PFB)(2)-N(2),3-epsilonGua and 3,5-(PFB)(2)-[(13)C(4),(15)N(2)]-N(2),3-epsilonGua and the [M - 201](-) fragments of 3,5-(PFB)(2)-1,N(2)-epsilonGua and 3,5-(PFB)(2)-[(13)C(3)]-1,N(2)-epsilonGua. The demonstrated limits of quantitation in hydrolyzed DNA were 7.6 fmol of N(2),3-epsilonGua and 15 fmol of 1,N(2)-epsilonGua in approximately 250 microg of DNA, which corresponded to 5.0 N(2),3-epsilonGua and 8.7 1,N(2)-epsilonGua adducts/10(8) unmodified Gua bases, respectively. 1,N(2)-epsilonGua was found to be the predominant ethenoguanine adduct formed in reactions of lipid peroxidation products with DNA. The respective ratios of 1,N(2)-epsilonGua to N(2),3-epsilonGua were 5:1 and 38:1 when calf thymus DNA was treated with ethyl linoleate or 4-hydroxynonenal, respectively, under peroxidizing conditions. Only N(2),3-epsilonGua was detected in DNA treated with the vinyl chloride (VC) metabolite 2-chloroethylene oxide and in hepatocyte DNA from rats exposed to 1100 ppm VC for 4 weeks (6 h/day for 5 days/week). These data suggest that 1,N(2)-epsilonGua plays a minor role relative to N(2),3-epsilonGua in VC-induced carcinogenesis, but that 1,N(2)-epsilonGua may be formed to a larger extent from endogenous oxidative processes.

Immunoaffinity/gas chromatography/high-resolution mass spectrometry method for the detection of N(2),3-ethenoguanine.

Etheno adducts are formed after exposure to a number of carcinogens, including vinyl chloride, as well as endogenously as a result of lipid peroxidation. A sensitive and selective assay for N(2), 3-ethenoguanine (epsilonGua) was developed using immunoaffinity (IA) columns made with polyclonal antibodies to epsilonGua followed by gas chromatography/electron capture negative chemical ionization/high-resolution mass spectrometry (GC/ECNCI/HRMS) analysis of its pentafluorobenzyl derivative. These IA columns were specific for epsilonGua and did not bind guanine, deoxyguanosine, 1, N(6)-ethenoadenine, or 1,N(2)-ethenoguanine. The level of recovery of standards from the IA columns was 107 +/- 7% and throughout the entire method (using nucleoside enzymatic digestion) with or without DNA was 72 +/- 6%. Four different hydrolysis/digestion procedures were compared, nucleoside enzymatic (EZ), neutral thermal hydrolysis (NT), formic acid hydrolysis (FA), and HCl hydrolysis. All hydrolysis methods with subsequent IA chromatography produced linear standard curves with r(2) values of 0.999 or better. The level of epsilonGua in chloroethylene oxide-treated calf thymus DNA (CEO-ctDNA) was 38 +/- 2, 42 +/- 3, and 49 +/- 2 fmol of epsilonGua/microg of DNA using EZ, NT, and FA, respectively. These numbers remained consistent when the amount of DNA processed was doubled or tripled. These numbers were comparable to the previously published value of 55 +/- 8 fmol of epsilonGua/micrograms of DNA for the same DNA using HCl hydrolysis, cation exchange cleanup, and LC/MS analysis [Yen, T. Y., et al. (1996) J. Mass Spectrom. 31, 1271-1276]. Additionally, HCl hydrolysis of rat liver DNA from control and vinyl fluoride-exposed rats gave similar epsilonGua results when compared to those from enzymatic digestion using this method. This method gave a detection limit of 5 epsilonGua adducts/10(8) normal dGuo nucleosides in 150 micrograms of DNA using EZ and somewhat lower detection limits using NT and HCl hydrolysis. The method is more sensitive and selective than previously used methods for the quantitation of this adduct.

Formation and repair of DNA adducts in vinyl chloride- and vinyl fluoride-induced carcinogenesis.

Vinyl chloride is a known human and animal carcinogen that induces angiosarcomas of the liver. We review here studies on the formation and repair of DNA adducts associated with vinyl chloride and vinyl fluoride in exposed and control rodents and unexposed humans. These vinyl halides induce etheno (epsilon) adducts that are identical to those formed after lipid peroxidation. Of these adducts, N2,3-ethenoguanine (epsilon G) is present in greatest amounts in tissues of exposed animals. After exposure to vinyl chloride for four weeks, epsilon G levels attain steady-state concentrations, such that the amount of newly formed adducts equals the number of adducts that are lost each day. We report the first dosimetry of epsilon G in rats exposed to 0, 10, 100 or 1100 ppm vinyl chloride for five days or four weeks. The number of adducts increased in a supralinear manner. Exposure to 10 ppm vinyl chloride for five days caused a two- to threefold increase in epsilon G over that of the controls, while four weeks' exposure resulted in a fivefold increase. This was confirmed with [13C2]vinyl chloride and by measuring exogenous and endogenous adducts in the same animals. Exposure to 100 ppm vinyl chloride for four weeks caused a 25-fold increase in epsilon G levels over that found in control rats, while exposure to 1100 ppm resulted in a 42-fold increase. The amount of endogenous epsilon G was similar in liver DNA from rats and humans. A comparable response to exposure was seen in rats and mice exposed to 0, 25, 250 or 2500 ppm vinyl fluoride for 12 months. There was a very high correlation between epsilon G levels in rat and mouse liver at 12 months and the incidence of haemangiosarcoma at two years. We were able to demonstrate that the target cell population for angiosarcoma, the nonparenchymal cells, contained more epsilon G than hepatocytes, even though nonparenchymal cells are exposed by diffusion of vinyl halide metabolites formed in hepatocytes. The expression of N-methylpurine-DNA glycosylase mRNA was induced in rat liver after exposure to either 25 or 2500 ppm vinyl fluoride. When this induction was investigated in hepatocytes and nonparenchymal cells, it was found that the latter had only 20% of the N-methylpurine-DNA glycosylase mRNA of hepatocytes, and that only the hepatocytes had induction of this expression after exposure to vinyl fluoride. Thus, the target cells for vinyl halide carcinogenesis have much lower expression of this DNA repair enzyme, which has been associated with etheno adduct repair.