[Evidence-based medicine in surgical practice - locating clinical studies and systematic reviews by searching the Medline database]. / Evidenzbasierte Medizin in der chirurgischen Praxis - Die Literatursuche nach klinischen Studien und systematischen Übersichtsarbeiten in der Datenbank Medline.

BACKGROUND: Every day approximately 75 clinical trials and 11 systematic reviews are published in the health-care intervention and medical field. Due to this growing number of publications it is a challenge for every practicing clinician to keep track with the latest research. The implementation of new and effective diagnostic and therapeutic interventions into daily clinical routine may thus be delayed. Conversely, ineffective or even harmful interventions might still be in use. Decision-making in evidence-based medicine (EBM) requires consideration of the most recent high quality evidence. Randomised controlled trials (RCTs) are regarded as the "gold standard" to prove the efficacy of surgical interventions in patient-oriented research. Systematic reviews combine results from RCTs by summarising single RCTs which answer a particular clinical question. Some basic knowledge in systematic literature searching is required and helpful for detecting relevant publications. MATERIAL AND METHODS: This article shows various possibilities for locating clinical studies and systematic reviews in the database Medline on the basis of illustrative step-by-step instructions. RESULTS AND CONCLUSION. Depending on the aim and topic of the literature search, the time required for the task may vary. In routine practice, a systematic literature search is unrealistic in most cases. Clinicians in need of a quick update of current evidence on a certain clinical topic may make use of up-to-date systematic reviews. During a systematic literature search, different approaches and strategies might be necessary.

Stability of methadone hydrochloride in 0.9% sodium chloride injection in single-dose plastic containers.

The stability of methadone hydrochloride in 0.9% sodium chloride injection in flexible polyvinyl chloride containers was studied. Commercially available methadone hydrochloride 20 mg/mL and 25-mL single-dose bags of 0.9% sodium chloride injection were used. Six samples each were prepared at methadone hydrochloride concentrations of 1, 2, and 5 mg/mL. The solutions were stored at room temperature and were not protected from light. Immediately after preparation and after two, three, and four weeks of storage, each of the 18 samples was divided into three aliquots, each of which was analyzed in duplicate for methadone hydrochloride concentration by gas chromatography. There was less than 10% change in methadone hydrochloride concentration in any sample throughout the four-week study period. Methadone hydrochloride at concentrations of 1, 2, and 5 mg/mL prepared in commercially available flexible polyvinyl chloride containers of 0.9% sodium chloride injection and stored at room temperature without deliberate protection from light is stable for at least four weeks.

Pharmacokinetics of coumarin and 7-hydroxycoumarin in the rhesus monkey after intravenous and peroral administration.

Coumarin (C, Venalot) and 7-hydroxycoumarin (7-OHC) were administered in a dose of 1 mg/kg to rhesus monkeys intravenously and perorally. The concentrations of C, 7-OHC and their metabolite, 7-hydroxycoumarin glucuronide (7-OHCG) were measured in whole blood. The terminal half-life, t1/2, the apparent distribution volume, Vd, and the total clearance, CL, of C and 7-OHC after i.v. administration are 1.64 +/- 0.41 h and 0.8 +/- 0.29 h, 2.55 +/- 0.95 l/kg and 6.96 +/- 3.44 l/kg, and 19.05 +/- 5.41 ml/min/kg and 103.7 +/- 34.4 ml/min/kg (mean +/- SEM), respectively. The rates of absorption of C and 7-OHC are 12.8 +/- 2.38 and 4.62 +/- 1.08 h-1, respectively. The rate of metabolism of C via 7-OHC to 7-OHCG is 7.96 +/- 2.16 h-1 and that of 7-OHC to 7-OHCG is 27.99 +/- 11.73. The p.o. absolute bioavailability is 45 +/- 14% for C and 17.0 +/- 5% for 7-OHC. The pharmacokinetics of C in the rhesus monkey are similar to that in the dog. In man the p.o. absolute bioavailability is only 3.4%.

Rapid estimation of unbound lidocaine clearance in cardiac patients: implications for reducing toxicity.

The clearance (CL), volume of distribution (Vd) and elimination half-life (t1/2), based on unbound and total concentration-time data, were estimated using two serum lidocaine concentrations drawn approximately 6 and 12 hours after the initiation of continuous intravenous lidocaine therapy in nine patients with myocardial infarction (MI) (in the immediate postinfarct period) and in 12 patients with ventricular arrhythmias. No significant intergroup differences were found for any of the parameters based on unbound or total lidocaine concentration-time data. A significant (P less than .01) correlation was found between measured unbound lidocaine and unbound lidocaine concentrations predicted using alpha-1-acid glycoprotein (AAGP) and total serum lidocaine concentrations. However, the predicted values were significantly lower than the measured values for both groups (P less than .001). Significant correlations were found between total and unbound volumes of distribution and between total and unbound clearances. Coefficients of determination (r2) for these correlations were 0.6906 and 0.9178 respectively. The relationship between total and unbound clearance allows rapid estimation of unbound clearance from two total serum lidocaine concentrations. Unbound clearance can then be used to determine patient-specific maximum infusion rates and reduce the risk of central nervous system toxicity from lidocaine.

Rectal bioavailability of lidocaine in the dog: evaluation of first-pass elimination.

The disposition of lidocaine was studied in beagle dogs after I.V., P.O. and rectal administration. Lidocaine HCl solution was used for the I.V. and P.O. studies. For rectal administration 3 gels were prepared: 1) lidocaine base in a hydrophilic vehicle, 2) lidocaine HCl in a hydrophilic vehicle, and 3) lidocaine base in a lipophilic vehicle. The gels were administered 3 cm deep in the rectum. Additionally, the gel of lidocaine HCl in a hydrophilic vehicle was also administered 10 cm deep in the rectum. No significant differences between I.V. and all extravascular administrations were observed for terminal half-life, total clearance and apparent volume of distribution. The systemic bioavailability after P.O. was 31%, and between 32% and 53% for the rectal dosage forms. The lidocaine base in lipophilic vehicle had the lowest systemic availability, the lowest peak concentration and the longest time to peak, whereas the lidocaine HCl in a hydrophilic vehicle, inserted 10 cm deep into the rectum, had the highest systemic bioavailability, highest peak concentration and shortest time to peak. The dog seems to be an excellent model for evaluation of peroral and rectal first-pass elimination.

Experimental cerebral infarction in Mongolian gerbils: effects of vincamine on lesion size, survival and behavior.

Vincamine was administered to gerbils at doses of 0, 1, 2, 10 and 40 mg/kg/d to study its effect on survival, extent of ischemic brain lesion, locomotor activity, neurologic signs, stool production, and food and water intake after unilateral carotid occlusion. Drug and placebo were delivered by implantation of osmotic minipumps. The three most important criteria, increase in survival, reduction in cerebral lesion in survivors, and functional recovery of locomotor activity were all significantly improved by vincamine treatment at all doses. Since the lowest dose produced as much improvement as the higher doses it was concluded that increasing dose beyond 1 mg/kg/d was not beneficial using the measures reported here.

Pharmacokinetics of PFA (trisodium phosphonoformate) after i.v. and p.o. administration to beagle dogs and rabbits.

The antiviral substance PFA (trisodium phosphonoformate) was administered I.V. and P.O. to six young female Beagle dogs, and to white New Zealand rabbits using a randomized crossover design. The pharmacokinetics of PFA was determined from the I.V. concentration-time data by polyexponential curve fitting and by a compartment model independent analysis. In dogs the I.V. data were best fit to three exponential terms. The terminal half-life ranged from 2.6 to 7.9 hours (mean 4.03 h +/- 2.04 S.D.). The mean volumes of distribution for the central compartment, Vc, at steady state, Vss and during the terminal phase, Vz, were 0.15, 0.65 and 1.32 L/kg, respectively. The two methods for generation of pharmacokinetic parameters resulted in practically identical values. After extravascular administration, the concentration-time data were subjected to compartment model independent analysis. The mean absolute bioavailability was 10% after P.O. administration. In rabbits, 11 out of 12 I.V. data sets were best fit to two exponential terms; one set was best fit to 3 exponential terms. The terminal half-life ranged from 1.47 to 4.15 hours (mean 2.18 h +/- 0.87 S.D.). The mean volumes of distribution for Vc, Vss and Vz were 0.32, 0.45 and 0.96 L/kg, respectively. After P.O. dosing the t 1/2 was about 4.4 h and the apparent volume of distribution about 1.2 L/kg. The mean absolute bioavailability after P.O. administration was 95%. The difference in P.O. bioavailability between dog and rabbit may be due to intragastric pH differences between the two species.

The effects of vincamine on experimental cerebral infarction in Mongolian gerbils: a pilot study.

Unilateral ligation of the common carotid artery was performed in 134 gerbils. Study I was comprised of 60 controls and 60 animals receiving I.P. vincamine 1 mg/kg q4h. In a small second study 14 animals received vincamine I.P. 40 mg/kg q12h. In all groups ligation of the carotid artery was performed 6 days after starting dosing. The animals were observed for a further 6 days after carotid artery ligation. Whereas vincamine had no effect on the percent of animals in each group dying after carotid ligation, the extent of stroke lesion, measured histometrically, was significantly reduced (P less than 0.05) in the vincamine treated animals.

Pharmacokinetics of coumarin and 7-hydroxycoumarin upon i.v. and p.o. administration in the euthyroid and hypothyroid beagle dog.

The pharmacokinetics of coumarin (C) and 7-hydroxycoumarin (7HC) ahs been studied after i.v. and p.o. administration in beagle dogs. C was given i.v. in doses of 0.25 and 0.5 mg/kg, respectively, and p.o. 1 mg/kg; 7HC was given i.v.in a dose size of 0.5 mg/kg and p.o. 1 mg/kg to euthyroid dogs. Upon administration of C the drug concentration-time profiles were determined for unchanged C and for 7HC after hydrolysis of the glucuronide. Upon administration of 7HC the concentration -time profiles were determined for unchanged 7HC and 7HC after hydrolysis of the glucuronide after i.v. dosing, and of 7HC after deglucuronidation after p.o. dosing. Additionally, the disposition of C upon i.v. administration was studied in hypothyroid beagles. Statistical analysis was performed on the data for the slow disposition rate constant, biological half-life, volume of distribution, total clearance, fraction of drug metabolized and rate of metabolism. Significant differences were found between euthyroid and hypothyroid dogs for both C and 7HC. The pharmacokinetics of C and 7HC in the dog is much different from that in man.

Evaluation of nitroglycerin ointments in the rabbit.

The rate of percutaneous absorption of nitroglycerin from different ointment preparations was studied in the rabbit using an indirect method which suffices bioavailability requirements. Ointment bases of different lipophilic character were compared with a commercially available preparation. Rate of absorption was fastest from the least lipophilic base. A hypothesis is presented regarding the clinical observation that topical use of nitroglycerin may not show enzyme induction as was found in peroral use. According to this hypothesis while achieving therapeutically effective levels the rate of percutaneous absorption should be slow enough not to result in a systemic drug concentration critical to enzyme induction. One experimental preparation (A) resulted in practically identical rate of absorption as obtained with the standard preparation.

Pharmacokinetics of coumarin and its 7-hydroxy-metabolites upon intravenous and peroral administration of coumarin in man.

The pharmacokinetics of coumarin (C) upon i.v. and p.o. administration and its metabolites 7-hydroxy-coumarin (7-HC) and 7-hydroxy-coumarin glucuronide (7-HCG) have been studied. Six healthy volunteers were involved in this investigation. Four of the volunteers participated in a crossover study. Coumarin was administered i.v. and p.o. in dose sizes of 0.25 mg/kg and 0.857 mg/kg, respectively. Coumarin is rapidly absorbed p.o., however the availability to systemic circulation is less than 4%. The rest of the dose appears quantitatively as 7-HC and 7-HCG in systemic circulation suggesting an extensive firstpass effect. Coumarin and 7-HCG are best fitted to an open two-compartment model, whereas 7-HC is best fitted to an open one-compartment model. The biological half-life of both C (0.80 vs. 1.02 h) and 7-HCG (1.47 vs. 1.15 h) was not significantly different for the two routes of administration. The large total clearance of C again suggests a first-pass effect; while that of 7-HCG, which is nearly exclusively eliminated into urine, indicates active tubular secretion of the glucuronide.