Requirements and Application Guide for the Use of Quality Indicators in Medical Care: Results of a Systematic Review.

Background: Quality indicators are employed in the assessment of quality of medical care. Valid measurement and reporting of quality are essential for maintenance and enhancement of high-quality medical care. The aim of this study was to identify the requirements for quality indicators and their successful implementation in routine care. Method: A systematic literature search conducted in Medline using MESH keywords resulted in 573 hits. A complementary hand search additionally identified 153 papers, so that in all 726 abstracts were screened. In conformity with the PRISMA Statement, 83 papers were finally included in this review. Results: Quality criteria are described in 48 publications and requirements for the application of quality indicators in medical care are given in 41 publications. Validity (n=19), feasibility (n=16), reliability (n=15), and interpretability of the quality indicator (n=14) are the most frequently named quality criteria, followed by relevance (n=10), sensitivity (n=8) and risk adjustment (n=6). The most common requirements for the application of quality indicators are integration of quality indicators in the given healthcare setting (n=15) and ability to derive potential improvement (n=11), data validity (n=8), data availability (n=7) as well as acceptance of the measurement in the given setting (n=6). Conclusion: Plausible quality measurements help improve healthcare structures and processes and provide patients and professionals with valid statements on the quality of care. The original articles examined focus primarily on the validity of quality indicators. A consensus on methodological criteria for the development, implementation and application of quality indicators is required. Furthermore, the practical applicability of quality criteria should be tested empirically.

[Does intrathecal clonidine prolong the effect of spinal anesthesia with hyperbaric mepivacaine? A randomized double-blind study]. / Verlängert intrathekal injiziertes Clonidin die Wirkung einer Spinalanästhesie mit hyperbarem Mepivacain? Eine randomisierte Doppelblindstudie.

BACKGROUND: Clonidine, an alpha 2-receptor agonist, has been reported to prolong the blocking actions of local anaesthetics. The aim of this study was to investigate the effects of spinally injected clonidine on the duration of spinal anaesthesia by mepivacaine and on the postoperative demand for analgesics. METHODS: Forty-five patients who had transurethral urological surgery under spinal anaesthesia were randomized to 3 groups (n = 15 each) and studied in a double-blind fashion. Group I received 80 mg mepivacaine 4% only, while in group II mepivacaine was combined with 75 micrograms clonidine intraspinally and in group III with 150 micrograms clonidine. Onset time, spread of anaesthesia, duration of sensory and motor blockade, regression of anaesthesia and postoperative demand for analgesics were recorded. In addition heart rate and mean arterial pressure were measured at regular intervals. RESULTS: Clonidine had no effect on the onset time and spread or intensity of spinal anaesthesia. The higher dose of clonidine significantly prolonged the duration of sensory blockade by 50 min and the duration of motor block by 40 min, while 75 micrograms had no significant effect. Heart rate and mean arterial pressure were significantly reduced in both clonidine groups when compared to plain mepivacaine. There was no significant reduction in postoperative analgesic demand. CONCLUSION: While clonidine prolonged sensory analgesia, there was also an undesirable prolongation of motor block postoperatively. In addition, there was a significant and long lasting reduction in heart rate and mean arterial pressure in both clonidine groups. Unfavourably, postoperative demand of analgesics was not reduced by spinal injection of clonidine. Thus, the routine addition of clonidine for spinal anaesthesia with local anaesthetics is not recommended.

Propofol binding to human blood proteins.

The binding of the intravenous anesthetic propofol (CAS 2078-54-8) to human native plasma, hemoglobin and serum albumin was studied by means of equilibrium dialysis. Propofol binding to plasma over the large concentration range from 0.04 to 150 micrograms/ml was independent on the substrate concentration and amounted 97.4-98.6%. Serum albumin and hemoglobin also showed a marked binding for propofol. A 4% solution of albumin bound 88.7% and hemoglobin 86.2% of the anesthetic. In studies with constant protein concentration and variation of the propofol concentration a decrease of the percentage bound with increasing substrate concentration was seen for hemoglobin, indicating saturable binding sites. The opposite was found for the interaction between propofol and albumin: increase of the binding extent with increasing substrate concentration.

Arterial oxygen saturation in infants at risk of sudden death: influence of sleeping position.

To study the possible influence of sleeping position on arterial oxygen saturation, measured by pulse oximetry (SpO2), 7-h overnight recordings of breathing movements and ECG were performed in 43 infants (median age 2.4 months, range 0.2-11 months) at increased risk of sudden infant death syndrome (SIDS). Infants were randomly allocated to start sleeping either in their usual sleeping position or in the opposite position. After 3.5 h, all infants were gently turned over. Thus, each infant served as their own control. Recordings were analysed for sleep time, baseline SpO2 (only during regular breathing), and the number and duration of desaturations (a decrease in SpO2 to < or = 80%). In the prone position, a significantly higher proportion of time was spent asleep (median 79% versus 70%; p < 0.05). Median baseline SpO2 was 98.8% (91.7-100%) in the prone and 99.0% (92.0-100%) in the supine position (ns). A total of 191 desaturations were found in 29 recordings; 96 in the prone and 95 in the supine position (ns). One infant subsequently died of SIDS while sleeping in the prone position. He had a relatively high number of desaturations (n = 12) which all occurred in the prone position. These results confirm earlier studies which could not find a significant influence of sleeping position on baseline oxygenation. The occurrence of desaturations in the prone position only in the infant who subsequently died requires further investigation.

[Effects of propofol and fentanyl on the baroreceptor reflex in geriatric patients]. / Wirkungen von Propofol und Fentanyl auf die Baroreflexaktivität geriatrischer Patienten.

OBJECTIVE: Increasing age and anaesthetics diminish the baroreflex response to acute changes in blood pressure. This study was designed to investigate the effects of propofol and the combination of propofol with fentanyl on the baroreflex activity in geriatric patients. METHODS: Baroreflex sensitivity was studied by the method of Smyth et al. in 10 elderly (72 +/- 6 yrs) and in 10 younger (48 +/- 6 yrs) patients. Nitroprusside (depressor test) and phenylephrine (pressor test) were used to induce changes in blood pressure of 20 mmHg each to alter the stimulation of the baroreceptor sites. Anaesthesia was induced with propofol, 2 mg x kg-1 b.w.m, and maintained by a continuous infusion of 12 mg x kg-1 x h-1 for 10 min and thereafter with 6 mg x kg-1 x h-1. Then a bolus of fentanyl, 7 micrograms x kg-1 b.w. was injected. Haemodynamic parameters and baroreflex activity were measured in the awake state, 10 min after induction of anaesthesia and 10 min after the administration of fentanyl. Plasma propofol concentrations were determined by HPLC 10 min after induction of anaesthesia with propofol and 10 min after injection of fentanyl. The slope of the linear regression changes in RR-interval [ms] per changes in systolic pressure [mmHg] was used as an index of the baroreflex sensitivity. RESULTS: In the awake state the depressor slopes were significantly reduced by 60% in the elderly patients when compared to the younger patients. In both groups propofol decreased reflex sensitivity by 38% and 41% respectively; this effect was enhanced by the addition of fentanyl in the younger patients, while there was no further effect in the elderly. The pressor slopes did not change significantly in both groups neither with propofol nor with the combination of fentanyl, but again reflex response was significantly less in the elderly patients. CONCLUSION: Our data demonstrate that in geriatric patients the baroreflex control of heart rate already is attenuated in the awake state. Propofol produces a further reduction in reflex sensitivity to an acute decrease in blood pressure; this effect is more pronounced in elderly patients as compared to younger individuals. Acute changes in posture or circulating blood volume during propofol anaesthesia may result in greater cardiovascular instability in older patients due to the greater impairment of circulatory control mechanisms.

HPLC assay for atropine in serum and protein solutions after in vitro addition of the tropane alkaloid.

A simple and sensitive method for the determination of atropine in serum and protein solutions is presented. Atropine and procaine (internal standard) were extracted with diethylether from protein containing solutions after alkalinization. The residue of the evaporized ether phase, redissolved in diluted sulfuric acid, was injected directly onto a LiChrosorbR column. Atropine, procaine and serum constituents were separated by HPLC using an ion-pair containing mobile phase. The limit for the detection of atropine was 200 ng/ml. The method was used for the determination of atropine in a binding study. Percent binding values to human serum, human serum albumin and human alpha 1-acid glycoprotein were evaluated by equilibrium dialysis.

Rapid and sensitive pre-column extraction high-performance liquid chromatographic assay for propofol in biological fluids.

A completely automated high-performance liquid chromatographic system is described for the determination of the phenolic anaesthetic propofol. The method is based on pre-column extraction in a closed system allowing direct injection of biological samples without any sample pretreatment. The assay is sensitive (limit of quantification is 5 ng/ml serum), reliable (the variability within a series is 2%) and rapid (results are available after 6 min).

Uptake and effects of thiopental in isolated heart preparations of the rat in the presence of halothane.

The uptake of thiopental (CAS 76-75-5) (0.13-0.27 mmol.l-1) into tissue of rat hearts (Langendorff's preparation) was studied in the presence of halothane (CAS 151-67-7). Up to a thiopental concentration of 0.19 mmol.l-1 in the perfusion medium its concentration in heart tissue was significantly increased vs. control when halothane (0.8 vol%) simultaneously was present; using 0.13 mmol.l-1 thiopental and 0.8, 1.5 or 2.0 vol% halothane this increase amounted +12%, +29% and +43%, respectively. Frequency of spontaneously beating rat hearts decreased in the presence of increasing thiopental concentrations. 0.8 vol% halothane (without thiopental) did not influence heart rate; in the presence of thiopental it attenuated heart rate reduction. This attenuation was absent in hearts of rats pretreated with reserpine. 1.5 vol% halothane (itself also without influence on heart rate) increased the negative chronotropic action of thiopental. In isolated right and left atria of rat hearts frequency and contractility decreased concentration-dependently in the presence of thiopental; simultaneously present halothane additionally increased this negative chronotropic and negative inotropic effect of thiopental.

Interactions between thiopental and volatile anesthetics (halothane and isoflurane) in isolated heart preparations of the rat.

Thiopental uptake into heart muscle tissue was studied in spontaneously beating rat hearts (Langendorff preparation, 0.13-0.27 mmol/l thiopental in the perfusion fluid). Up to 0.19 mmol/l the concentration of thiopental in heart muscle tissue was increased vs. control when halothane (0.8 vol%) was present. Using a constant thiopental concentration (0.13 mmol/l) and 0.8, 1.5 or 2.0 vol% halothane +12%, +29% or +43% more thiopental was taken up into heart muscle tissue compared to the control. This increased uptake was not seen in the presence of 1.2 and 2.0 vol% isoflurane. Frequency of right rat atria was decreased by increasing thiopental concentrations (0.02-0.23 mmol/l in the incubation medium). Halothane (0.8 and 1.5 vol%) and isoflurane (1.0 and 2.0 vol%) alone had no influence on frequency of right atria. Both volatile anesthetics additionally increased the negative chronotropic action of thiopental when the corresponding higher concentration was applied. Contractile force of left rat atria was decreased concentration-dependently by thiopental (0.02-0.23 mmol/l). Halothane and isoflurane alone decreased contractility. Dependent on the concentration used, both volatile anesthetics further increased the negative inotropic action of thiopental, yet preferentially at higher barbiturate concentrations.

Increase of thiopental concentration in rat tissues due to anesthesia with isoflurane.

Thiopental distribution was studied in rats (30 mg/kg i.v.) anesthetized simultaneously with 1.25 "rat"-MAC isoflurane. The thiopental concentration in serum and several tissues was determined UV-photometrically at 305 nm after extraction and TLC. In the serum of rats anesthetized with isoflurane the thiopental concentration was significantly increased to +39----+74% in comparison to controls during 30 min following the barbiturate injection. Also in liver, brain, heart, kidney, lung and spleen of rats anesthetized with isoflurane the thiopental concentration was significantly increased at 3 and 10 min; at 30 min the difference vs. control had vanished in brain, heart, lung and spleen. Obviously, thiopental was transiently "trapped" during the early distribution phase to a considerable amount in these vessel-rich tissues when anesthesia with isoflurane was simultaneously performed; this pharmacokinetic interaction might be explained at least to some extent hemodynamically; in many tissues regional blood flow is reduced during anesthesia with isoflurane; thereby the "washout" of thiopental from the tissues and the redistribution are delayed.

Increased binding of thiopental in tissue homogenates of the rat in the presence of a volatile anesthetic.

Thiopental (CAS 76-75-5) binding (0.4 mmol.l-1) in tissue homogenate of rats (liver, brain, heart, kidney, lung, spleen and skeletal muscle) was studied by equilibrium dialysis. Percentage of thiopental bound was relatively low in homogenate of brain, lung, spleen and skeletal muscle (14-19%); it was much higher in that of liver, heart and kidney (24-27%). Simultaneously present halothane (11.8 mmol.l-1) increased the percentage of thiopental bound in the homogenate of all tissues investigated at least to a factor of 1.4 (spleen) and maximally of 2.4 (brain). The same phenomenon of an increased thiopental binding in tissue homogenate was found in the presence of 10.3 mmol.l-1 enflurane (except skeletal muscle) and 10.2 mmol.l-1 isoflurane (except kidney, spleen and skeletal muscle), yet to a significantly lower extent in the presence of these halogenated ethers as compared with halothane.

Increase of thiopental concentration in tissues of the rat due to an anesthesia with halothane.

In rats anesthetized with halothane (CAS 151-67-7) (1.5 vol%) and rats without any further treatment (control) the early distribution phase of thiopental (CAS 76-75-5) (i.v. 30 mg/kg) was studied. In serum and 8 tissues thiopental concentration (T) was determined using ultraviolet detection at 305 nm after extraction and TLC. In rats anesthetized with halothane, T in serum was significantly higher during the 30 min following the thiopental injection (at least +27% and maximally +51%) as compared to the control (same dose), and several pharmacokinetic parameters (e.g. central volume of distribution) were found to be changed thereby; furthermore, at 3, 10 and 30 min T was significantly increased in liver, brain, heart, lung and spleen; in kidney and skeletal muscle a rise of T was also seen, however, it occurred later (after 10 and 30 min). T in fat tissue increased time-dependently; a T-difference in adipose tissue between both groups was not observed. Thiopental was "trapped" during the early distribution phase to a considerable extent in the vessel-rich tissues of rats simultaneously anesthetized with halothane; this pharmacokinetic interaction might be explained hemodynamically: in many tissues regional blood flow is reduced by halothane; thereby a delayed "washout" of thiopental from the vessel-rich tissues could take place and redistribution would be delayed; additional factors as e.g. an increased binding of thiopental at tissue proteins could also play a role. An unusually high T was found at least temporarily in myocardial tissue due to this interaction between the two anesthetics.

[Oral premedication with midazolam in children]. / Die orale Prämedikation mit Midazolam bei Kindern.

One hundred children aged between 6 months and 10 years undergoing elective urological surgery, received 0.4 mg/kg midazolam orally about 20 minutes prior to the arrival in the operation theatre. The physiological state of the children was estimated and recorded pre- and postoperatively at defined, comparable and representative circumstances by a specially developed design. In the preoperative period orally administered midazolam had only a mild or non sedative effect in 76-84% of the children, 67-88% of the small patients behaved cooperatively or passively and 70-84% showed an indifferent or euphoric state of mind. Postoperatively 57-89% of the children were markedly sedated; therefore, the estimation of behaviour and state of mind was of minor significance. The circulatory parameters were altered only minimally. Systolic blood pressure and heart rate changed slightly but significantly compared to the preoperative values the day before surgery: a preoperative increase to a maximum immediately after the insertion of the venous cannula and a postoperative maximum after recovery. Side effects were rare (hiccough 5%, vomitus 4%, laryngospasm 1%, stridor 1%). Our results suggest that oral premedication with midazolam in children can be recommended to avoid traumatic or unpleasant alterations resulting from intramuscular injections or rectal applications. Therefore, we prefer this kind of premedication in paediatric patients.

pH-dependent interaction of halothane upon thiopental binding to human serum albumin.

At pH 7.4 the binding of thiopental to human serum albumin (HSA) was increased in the presence of halothane. In order to obtain information about the mechanism of this interaction, in vitro binding experiments by means of equilibrium dialysis were carried out at different pH values. At pH 4.97 the binding of thiopental to HSA 1% was low (23% bound) and not influenced by halothane. An increase of thiopental binding caused by halothane could be seen at pH 7.4 (55% bound vs. 41% in the control = without halothane) and at pH 8.23 (62% vs. 54%). At pH 10.15 an opposite interaction was found: in the presence of halothane thiopental binding was considerably decreased (36.2% vs. 47.0% in the control). Evaluation of the binding parameters of experiments using increasing substrate concentrations (Scatchard plot) revealed quite different changes of the two classes of binding sites of HSA for thiopental. It is assumed that halothane causes reversible conformational changes of the albumin molecule resulting in altered binding characteristics for thiopental.

[Psychosomatic, sedative and hemodynamic reactions following preoperative administration of midazolam in children]. / Psychosomatische, sedative und hämodynamische Reaktionen nach präoperativer oraler Gabe von Midazolam bei Kindern.

Since children's intellectual perception is limited, the preoperative visit by an anesthesiologist alone can rarely help to free the small patients from fear and restlessness prior to elective surgery. In order to relieve anxiety which should be the primary goal of premedication in any patient - children need anxiolytic premedication agents. Drugs for premedication administered by intramuscular or rectal route in children often cause pain, fear and discomfort. The present study was performed in order to investigate oral given midazolam in the premedication of children with special regard to the practical suitability of this method. 100 children, 0.5 to 10 years of age (group A: 0.5-4 years, group B: 5-10 years) undergoing elective urological surgery received 0.4 mg/kg midazolam orally about 20 minutes prior to the arrival in the operation unit. After insertion of a venous cannula into a forearm vein anesthesia was induced with thiopental and maintained by inhalation with Isoflurane, nitrous oxide and oxygen (fi O2:0.3). Degree of sedation, state of mind and behaviour (for 100 children) as well as blood pressure and heart rate (separately for group A and B) were registered preoperatively at defined, comparable and representative circumstances. Side effects prior and during induction phase of anesthesia were documented. The personal data are representative for a normal population of children with typical urological diseases. Oral administered midazolam had only a mild or non sedative effect in 76-84% of the children 70-84% of the small patients showed an indifferent or euphoric state of mind and 67-88% behaved cooperatively or passively.(ABSTRACT TRUNCATED AT 250 WORDS)

Thiopental binding to human serum albumin in the presence of halothane.

In vitro thiopental binding (substrate concentration 0.04.10(-3) M = 10 micrograms/ml) to 1% human serum albumin (HSA) increased significantly from 40.2% (= control) to 47.3% in the presence of 1.18.10(-3) M = 2.84 vol% halothane. A 4-fold higher halothane concentration (4.71.10(-3) M) had an even greater effect with an increase in the thiopental fraction bound to 55.5%. With a constant HSA concentration (1% or 5%) and thiopental concentrations in the range 0.01-1.5.10(-3) M or 0.01-0.38.10(-3) M, respectively, the halothane effect (increase in thiopental binding) was always evident, as well as in other experiments with constant thiopental concentration (0.04.10(-3) M) and variation in the HSA concentration (0.5-10%). Two classes of binding sites for thiopental were apparent at the HSA molecule. In the control experiments the following binding parameters were found: n1 = 0.01, k1 = 181.10(3) M-1; n2 = 45.73, k2 = 0.08.10(3) M-1, K = 5.47.10(3) M-1. In the presence of halothane the binding parameters changed as follows: n1 = 0.14, k1 = 29.4.10(3) M-1; n2 = 11.68, k2 = 0.42.10(3) M-1, K = 9.02.10(3) M-1.

Binding of thiopental to human serum albumin in the presence of halogenated hydrocarbons and ethers.

Thiopental binding (substrate concentration 0.04.10(-3) M = 10 micrograms/ml) to 1% human serum albumin (HSA) studied by equilibrium dialysis in 1/15 M phosphate buffer solution (pH 7.4) was increased significantly from 40.2% (= control) to 55% in the presence of 4.71.10(-3) M halothane (= 11.36 vol%); 1.18.10(-3) M = 2.84 vol% halothane caused a lesser but still significant increase (vs. control) of thiopental binding. This halothane effect on the binding of thiopental to HSA was studied under several experimental conditions (variation of thiopental concentration, HSA concentration, pH of the buffer solution, temperature). Other halogenated hydrocarbons such as chloroform (6.2.10(-3) M) and carbon tetrachloride (5.2.10(-3) M) also markedly increased the binding of thiopental to HSA as compared to the control (percentage of fraction bound, 53 and 61%, respectively); the same effect, but to a lesser extent, was obtained under the influence of three halogenated ethers, i.e., enflurane (4.1.10(-3) M--greater than 45% thiopental bound), isoflurane (4.1.10(-3) M--greater than 50% bound) and methoxyflurane (4.3.10(-3) M--greater than 47% bound). Under the same experimental conditions, ethanol (up to 8.9.10(-2) M) and diethylether (up to 4.9.10(-2) M) did not increase the percentage of thiopental bound to HSA.

[Anesthesia during extracorporeal shock wave lithotripsy]. / Die Anästhesie bei extrakorporaler Stosswellenlithotripsie (ESWL).

Three important anaesthesiological methods are considered to be appropriate in anaesthetizing patients undergoing extracorporal shock wave lithotripsy: general anaesthesia, epidural anaesthesia and recently opioid analgesia. In 161 patients who underwent ESWL in epidural anaesthesia, the dosage of the local anaesthetic (bupivacaine 0.5% without adrenaline) was dependent on the level of insertion of the Tuohy-needle and on the age of the patients. Under a sufficient therapy with crystalloids and colloids, cardiovascular parameters such as blood pressure and heart rate remained remarkably stable. In 10 patients the influence of epidural anaesthesia during ESWL on the glomerular filtration rate (GFR) was investigated. After the injection of radio-labelled 51-Cr-EDTA the GFR was significantly reduced by the epidural block. Under the influence of extracorporal shock waves the GFR increased significantly and in some cases exceeded the original value. Opioid analgesia with alfentanil in awake, spontaneously breathing patients is well accepted by patients with kidney stone disease who have to undergo ESWL. The analgesia is achieved by administering an initial bolus injection (30 micrograms/kg) of alfentanil and applying additional injections--each 15 micrograms/kg--on demand. A study with 360 patients was performed in order to investigate the suitability of opioid analgesia during ESWL with special regard to cardiovascular and respiratory depression and other side-effects. Mean systolic and diastolic blood pressure and heart rate were almost not affected. Under insufflation of oxygen by a nasal tube, the mean PaCO2 always showed normal values. Mean PaCO2 increased to 50 mm Hg. A mild drowsiness could be observed in all patients. Two of them developed a complete respiratory arrest accompanied by a muscular rigidity of the chest wall so that respiratory support by mask ventilation became necessary. The "extracorporal piezoelectric lithotripsy" (EPL) is a new method of non-invasive disintegration of kidney stones and can be performed in the non-anaesthetized patient. The efficacy of this much more profitable procedure is equivalent to the ESWL, so that the EPL seems to have a great future.

Sensitive HPLC assay for thiopental in human serum after simple preparation of the samples. Its application for clinical research.

A simple, precise and sensitive micro method for the determination of thiopental in human serum is presented. After deproteinization with acetonitrile the supernatant was directly injected into a reversed phase HPLC system with UV photometrical detection at 280 nm. The limit for the detection of thiopental was less than 0.1 microgram/ml serum. Time consuming extraction of the serum sample was not necessary. The method can be recommended for clinical routine analysis; its suitability has been demonstrated in several studies.