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PubMed2005

Bispectral index as a guide for titration of propofol during procedural sedation among children.

OBJECTIVE: To determine whether the bispectral index (BIS) monitor could be used to guide physicians in titrating propofol to an effective safe level of deep sedation for children undergoing painful medical procedures. DESIGN: Multiphase clinical trial. SETTING: Outpatient treatment center of a university children's hospital. PATIENTS: Pediatric outpatients undergoing painful medical procedures. INTERVENTIONS: Patients were sedated with propofol for the procedures. Patients were monitored with a BIS monitor, and the BIS score was correlated with the patient's clinical level of sedation. The BIS score was then used as a guide to titrate propofol in the last phase of the study. MEASUREMENTS AND MAIN RESULTS: The study consisted of 3 phases. In a chart review of data for 154 children who underwent 212 procedures, propofol was found to be safe and effective, with consistent dosing among the intensivists administering the medication. The children received a mean bolus dose of propofol of 1.56 mg/kg, with a mean total dose of propofol of 0.33 mg/kg per minute for the duration of the procedure. In the second phase, 21 patients ranging in age from 27 weeks to 18 years, with normal neurologic function, were sedated with propofol. An observer who was blinded to the BIS scores recorded clinical levels of sedation and reactivity (with a modified Ramsay scale and reactivity score) every 1 to 3 minutes. Another observer recorded the BIS scores at the same times. A total of 275 data points were collected and evaluated. All data points from the times at which patients were considered to be sedated adequately were used to construct a normal distribution of BIS scores. The mean BIS score was 62. This distribution was used to predict that a maximal BIS score of 47 was needed to ensure adequate sedation for 90% of the population. In the third phase of the study, an algorithm was devised to determine the target BIS score necessary for adequate sedation of 95% of the patients. We chose an initial BIS score of 50 (at which 85% of the patients in phase 2 were sedated) because of the possibility of data from phase 2 being skewed toward oversedation. Propofol was administered by an intensivist in an attempt to maintain the target BIS score. A blinded observer noted the patient's clinical level of sedation. In this group, there were 2 failures, ie, patients were clinically uncomfortable despite a BIS score of < or =50, representing only 90% success. Therefore, with the algorithm, propofol was titrated to sedate the next patients to a BIS score of 45. These patients required a mean bolus dose of 1.47 mg/kg and a mean total dose of 0.51 mg/kg per minute to maintain a BIS score of 45. They awakened in 12.75 minutes. All patients were sedated adequately, all procedures were successful, and no patients experienced complications from the sedation. To eliminate variability in the way propofol was dosed, the next 10 patients were given propofol according to a standardized protocol. These 10 children received an initial bolus of 1 mg/kg, with incremental bolus doses of 0.5 mg/kg per dose (maximum: 20 mg) to achieve and to maintain a BIS score of 45. With this protocol, all patients were sedated adequately and none experienced complications from the sedation. The patients required a mean bolus dose of 2.23 mg/kg and a mean dose of 0.52 mg/kg per minute to maintain a BIS score of 45. The mean time until awakening was 14.9 minutes. Regarding the total dose over time and the time until awakening, there was no statistical significance between this group and the group sedated to a BIS score of 45 without the dosing protocol. CONCLUSION: The BIS monitor can be a useful monitoring guide for the titration of propofol by physicians who are competent in airway and hemodynamic management, to achieve deep sedation for children undergoing painful procedures.

Adolescent↗
PubMed1995

A colorimetric LDH assay for the titration of infectivity and the evaluation of anti-viral activity against ortho- and paramyxoviruses.

A rapid and precise screening assay was developed for in vitro evaluation of anti-orthomyxo- and anti-paramyxovirus agents. The procedure is spectrophotometrical assessment for viability of cells via extracellular leakage of lactic dehydrogenase (LDH). HMV-II cells, a human melanoma cell line was found to be suitable for the titration of virus infectivity and screening of anti-viral agents for orthomyxo- and paramyxoviruses. Comparative titration of infectivity of stock viruses by the LDH and the MTT in site reduction of 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) methods with HMV-II cells as well as plaque titration with MDCK, Vero and HeLa cells was carried out. The LDH method was comparable or more sensitive for influenza viruses (FLUV)-A, B, C, parainfluenza viruses (PFLUV)-1, 2 and less sensitive for PFLUV-3, mumps virus (MPSV), measles viruses (MLSV) and respiratory syncytial virus (RSV) than the plaque titration. The 50% effective concentration (EC50) of 1-beta-D-ribofuranosyl-1, 2, 4-triazol-3-carboxamide (ribavirin) and 5-ethynyl-1-beta-D-ribofuranosyl-imidazole-4-carboxamide (EICAR) against orthomyxo- and paramyxoviruses were examined comparatively by the LDH, MTT and plaque reduction (PR) methods. The EC50 values of FLUV-C and PFLUV-1 were able to be evaluated only by the LDH but not by the MTT and PR methods. The LDH method with HMV-II cells simplifies the assay procedure and permits the evaluation of a large number of compounds for anti-orthomyxo- and anti-paramyxoviruses activity in vitro.

Antiviral Agents↗
PubMed1975

Effect of an increase in cardiac output on the in vivo C02 titration curve of mixed venous blood.

The slope of the in vivo CO2 titration curve of blood (pH-[HCO3-]p relationship, in vivo slope, unit: slyke) expresses the buffering capacity of blood for CO2 in vivo or the buffering capacity of extracellular fluid for CO2. It depends on the extent of contributions by chemical and physiological buffering processes for CO2 occurring during CO2 titration. Theoretically, the in vivo slope obtained for mixed venous blood is independent of cardiac output during CO2 titration. The present study was attempted to confirm this theoretical concept experimentally. Anesthetized dogs were allowed to breathe air and then 10% CO2-25% 02 in N2 for 60 min for the titration in vivo. During the CO2 breathing period the legs were exercised through direct electrical stimulation of the muscles; this also induced an increase in cardiac output 130% above the air breathing period. The in vivo slope (delta[HCO3-]p/delta/pH-]p/"pH) of the mixed venous blood at an apparent steady state in the CO2 breathing period was 16 slyke, which was 5 slyke higher than in other dogs breathing CO2 at rest with a 60% increase in cardiac output observed in our previous study. This finding was discussed in relation to a greater contribution of tissue fluid for buffering of CO2. The present study suggests that cardiac output is a significant determinant of the buffering capacity of extracellular fluid.

Acid-Base Equilibrium↗
PubMed2005

Dermatology precautions and slower titration yield low incidence of lamotrigine treatment-emergent rash.

OBJECTIVE: To assess treatment-emergent rash incidence when using dermatology precautions (limited antigen exposure) and slower titration during lamotrigine initiation. METHOD: We assessed rash incidence in 100 patients with DSM-IV bipolar disorder instructed, for their first 3 months taking lamotrigine, to avoid other new medicines and new foods, cosmetics, conditioners, deodorants, detergents, and fabric softeners, as well as sunburn and exposure to poison ivy/oak. Lamotrigine was not started within 2 weeks of a rash, viral syndrome, or vaccination. In addition, lamotrigine was titrated more slowly than in the prescribing information. Patients were monitored for rash and clinical phenomena using the Systematic Treatment Enhancement Program for Bipolar Disorder Clinical Monitoring Form. Descriptive statistics were compiled. RESULTS: No patient had serious rash. Benign rash occurred in 5 patients (5%) and resolved uneventfully in 3 patients discontinuing and 2 patients continuing lamotrigine. Two patients with rash were found to be not adherent to dermatology precautions. Therefore, among the remaining patients, only 3/98 (3.1%) had benign rashes. CONCLUSION: The observed rate of benign rash was lower than the 10% incidence in other clinical studies. The design of this study confounds efforts to determine the relative contributions of slower titration versus dermatology precautions to the low rate of rash. Systematic studies are needed to confirm these preliminary findings, which suggest that adhering to dermatology precautions with slower titration may yield a low incidence of rash with lamotrigine.

Adult↗
PubMed2006

Microbiological profiles, pH, and titratable acidity of chorizo and salchichón (two Spanish dry fermented sausages) manufactured with ostrich, deer, or pork meat.

Microbial counts, pH, and titratable acidity were determined in 102 Spanish dry fermented sausages (chorizo and salchichón) made with ostrich, deer, or pork meat. Average microbial counts (log CFU per gram) varied from 5.46 +/- 0.24 to 8.25 +/- 0.80 (total viable counts), from 4.79 +/- 0.36 to 7.99 +/- 0.20 (psychrotrophs), from 0.00 +/- 0.00 to 0.99 +/- 1.10 (undetectable values were assumed to be zero) (Enterobacteriaceae), from 0.00 +/- 0.00 to 4.27 +/- 1.47 (enterococci), from 5.15 +/- 1.15 to 8.46 +/- 0.49 (lactic acid bacteria), from 3.08 +/- 0.44 to 6.59 +/- 1.76 (Micrococcaceae), from 2.27 +/- 1.53 to 5.11 +/- 1.81 (molds and yeasts), from 0.00 +/- 0.00 to 2.25 +/- 0.81 (pseudomonads), and from 0.00 +/- 0.00 to 2.78 +/- 0.46 (Brochothrix thermosphacta). Average pH and titratable acidity varied from 5.07 +/- 0.25 to 5.63 +/- 0.51 (pH units) and from 0.30 +/- 0.01 to 0.86 +/- 0.19 (% lactic acid). Both type of sausage (P < 0.05) and species of meat (P < 0.001) influenced microbial counts. Salchich6n samples showed lower average values than chorizo samples for most microbial groups (significant for Enterobacteriaceae, lactic acid bacteria, and B. thermosphacta) and titratable acidity. Sausages made from pork showed the highest microbial loads for total viable counts, psychrotrophs, Enterobacteriaceae, enterococci, lactic acid bacteria, and yeasts and molds. Higher counts were observed only for pseudomonads in ostrich sausages. B. thermosphacta levels were similar for all species of meat. The highest average pH value was observed in sausages made from ostrich meat, and the lowest titratable acidity level was found in pork sausages.

Animals↗
PubMed2000

Monitoring unfractionated heparin therapy: relationship between eight anti-Xa assays and a protamine titration assay.

Several studies have demonstrated that heparin assays, such as anti-activated factor X (anti-Xa) assays, can be successfully substituted for activated partial thromboplastin time for heparin dosage monitoring. A number of different assays are available and the relationship between results with different techniques is largely unknown. The aim of the present study was to assess the relationship between heparin assays by protamine titration and anti-Xa assays. Samples were collected from 43 patients receiving unfractionated heparin (UFH). In each sample, the heparin level was determined using a protamine titration assay and eight commercially available anti-Xa assays. The mean heparin level by protamine titration was 0.31 U/ml. Mean anti-Xa activity results ranged from 0.40 to 0.42 IU/ml for the three clotting-based assays, and from 0.32 to 0.40 IU/ml for five chromogenic assays. Thus mean results of different anti-Xa assays varied by up to 30%. The range of anti-Xa activity equivalent, on average, to 0.2-0.4 U/ml by protamine titration, considered to be the therapeutic range, was approximately 0.25-0.5 IU/ml, depending on the assay. The relationship between results of clotting and chromogenic methods was similar irrespective of whether or not warfarin-induced prolongation of international normalized ratios was present.

Antibodies↗
PubMed2000

[Titration of an effective positive pressure level in the treatment of obstructive sleep apnea syndromes using continuous positive pressure ventilation].

The efficacy of continuous airway positive pressure ventilation with a nasal mask mainly depends on the appropriateness of the effective positive pressure level. Conventionally, this level is determined from polysomnographic recordings using progressively increasing pressure levels to determine the point where episodes of apnea, hypopnea and snoring regress in all sleep phases and in all body positions. Since the first description of this method, many other titration methods have been proposed. Some use sophisticated signals such as the analysis of respiratory exertion level or limitation of inspiratory flow to provide a more precise titration which is particularly useful in cases where the classical titration method is insufficiently effective. Inversely, simplified methods have been examined from an economic point of view. These methods do not require the presence of a technician in a specialized laboratory where the waiting list for diagnostic tests is often long. Recordings during naps or short nights have been proposed for the more severe cases. Likewise titrations during simple polygraphy recordings or with an autoCPAP device have been shown to be effective in one-night laboratory recordings. Much work remains to be done to determine the effectiveness of these methods when used in the patient's home as well the long-term effects.

Humans↗
PubMed2000

[Titration of the level of effective positive pressure in the treatment of obstructive sleep apnea syndromes with continuous positive pressure].

The efficacy of continuous airway positive pressure ventilation with a nasal mask mainly depends on the appropriateness of the effective positive pressure level. Conventionally, this level is determined from polysomnographic recordings using progressively increasing pressure levels to determine, the point where episodes of apnea, hypopnea and snoring regress in all sleep phases and in all body positions. Since the first description of this method, many other titration methods have been proposed. Some use sophisticated signals such as the analysis of respiratory exertion level or limitation of inspiratory flow to provide a more precise titration which is particularly useful in cases where the classical titration method is insufficiently effective. Inversely, simplified methods have been examined from an economic point of view. These methods do not require the presence of a technician in a specialized laboratory where the waiting list for diagnostic tests is often long. Recordings during naps or short nights have been proposed for the more severe cases. Likewise titrations during simple polygraphy recordings or with an autoCPAP device have been shown to be effective in one-night laboratory recordings. Much work remains to be done to determine the effectiveness of these methods when used in the patient's home as well the long-term effects.

Home Care Services↗
PubMed2001

Cadmium binding to a histidine-rich glycoprotein from marine mussel blood plasma: potentiometric titration and equilibrium speciation modeling.

Cadmium-binding parameters (conditional stability constants and carrying capacities) of Mytilus edulis blood plasma histidine-rich glycoprotein (HRG) were investigated by potentiometric titrations using a Cd ion-specific electrode. Titration data were applied to a single-component complexation model and expressed as Scatchard plots that were analyzed using the graphical curve peeling method and the algebraic statistical mechanical method. These sets of binding parameters, derived for the purified HRG, were subsequently entered into the geochemical speciation model MINTEQA2 and then used to simulate the experimental titration, thereby determining which set of log K and CL values best represented the titration data. The Cd binding to HRG was best described by a two-class model with log K values of 7.65 +/- 0.10 and 5.41 +/- 0.06 M-1 and carrying capacities of 6.0 +/- 1.2 and 9.5 +/- 0.4 sites/molecule, respectively. At concentration of total Cd measured in the blood plasma of field-collected mussels (< or = 2 x 10(-7) M), plasma Cd speciation would be dominated by the strong affinity sites of HRG (> 93.5% of total Cd binds to HRG), whereas HRG itself would only be 0.05% saturated with Cd, indicating a high-capacity, apparently nonsaturable Cd transport system.

Animals↗
PubMed2001

Titration in the treatment of the more troubled patient.

This article defines and discusses a modification of technique recommended by the authors in the psychoanalytic treatment of more troubled patients--a modification they call titration. Titration is defined as a conscious decision by the analyst to increase or decrease assistance (or gratification) gradually, in order to facilitate the analytic process. The authors emphasize the complexity of decisions in treatment by focusing on the decision-making processes that titration requires. Guidelines and a case vignette are presented. The authors conclude by considering some of the politics involved in the introduction of technique modifications, the salience of the titration concept, and directions for further exploration.

Decision Making↗
PubMed2002

A chromogenic substrate method for detecting and titrating anti-factor VIII antibodies in the presence of lupus anticoagulant.

BACKGROUND AND OBJECTIVES: The development of neutralizing anti-factor VIII antibodies (a-fVIII) is a major clinical complication. Lupus anticoagulant (LA) might affect detection of a-fVIII, since both inhibitors may act on the same coagulation pathway. Our aim was to accomplish unequivocal detection and titration of a-fVIII even in the presence of LA. DESIGN AND METHODS: We evaluated a-fVIII activity by a chromogenic substrate (CS) method in samples with a-fVIII (n=6), LA (n=12) and presumably both LA+a-fVIII (n=5). The inhibition index before (Ii) and after incubation at 37 C (Ii(37)) was estimated. We also performed factor VIII assays (one-stage and CS) and titration methods (Bethesda and CS) in parallel. RESULTS: Inhibition in the a-fVIII group (Ii=5-3200) was potentiated by incubation (Ii(37)=27-5200) as it was in LA+a-fVIII (Ii=9-21; Ii(37)=50-903). LA samples showed no or meaningless inhibitory effect (Ii=0-7; Ii(37)=0-4) or a-fVIII activity (0.00-0.06 CSU/ml) by the CS method; on the contrary, very low to moderate (0.52-7.00 BU/ml) a-fVIII activity was recorded by the Bethesda method. The two titration methods did not correlate (p>0.100) in the presence of LA, or LA+a-fVIII. Differences between factor VIII:C and factor VIIIcs were significant only in LA samples (p=0.005); however, patients with residual factor VIII activity from the LA+a-fVIII group also showed higher factor VIIIcs values than factor VIII:C ones. INTERPRETATION AND CONCLUSIONS: Results indicate the possibility of detecting and titrating a-fVIII without interference of LA by the CS method. This marks a difference with respect to the Bethesda method, in which a measurable effect can be expected in the presence of a strong LA.

Autoantibodies↗
PubMed1975

Nuclear magnetic resonance titration curves of histidine ring protons. Conformational transition affecting three of the histidine residues of ribonuclease.

NMR titration curves are reported for the 4 histidine residues of ribonuclease A in sodium acetate and for ribonuclease S in sodium acetate, phosphate, and sulfate solutions. Evidence is presented that the imidazole side chain of histidine residue 48 undergoes a conformational change, probably also involving the carboxyl side chain of aspartic acid residue 14. This group is considered to be responsible for the low pH inflection with pKa 4.2 present in the NMR titration curve of the C-2 proton resonance of histidine 48. The NMR titration curves of the active site histidine residues 12 and 119 also exhibit inflections at low pH values, although there is no carboxyl group within 9 A of the imidazole side chain of histidine residue 12 in the structure of ribonuclease S determined by x-ray crystallography (Wyckoff, H. W., Tsernoglou, D., Hanson, A. W. Knox, J. R., Lee, B., and Richards, F. M. (1970) J. Biol. Chem. 245, 305-328). Curve fitting was carried out on 11 sets of NMR titration data using a model in which the 3 histidine residues 12, 119, and 48 are assumed to be affected by a common carboxyl group. The results obtained indicate that such a model with fewer parameters gives as good a representation of the data as the model in which each histidine residue is assumed to interact separately with a different carboxyl group. Therefore, it is concluded that the ionization of aspartic acid residue 14 is indirectly experienced by the active site histidine residues through the conformational change at histidine 48. A model assuming mutual interaction of the active site histidine residues does not account for the low pH inflections in these curves.

Acetates↗
PubMedDate not supplied

[Venlafaxine titration dosage in depressive in-patients. A series of cases].

This series of patients was gathered to assess the use of last and slow titration dosage of venlafaxine in in-patients with major depression and to evaluate the action onset. An observational open study was performed in 3 centers in 18 in-patients. Nine patients were included in fast titration dosage group (FT) and 9 in slow titration dosage group (ST). As results, it was found that the FT group showed faster improvement than the ST group in HAM-D score. This improvement was sustained to the final visit, with a lower score in the FT group (6.75) than the ST group (10.67). MADRS scores up to the 15th visit were similar; however, the score was lower in the ST group on the 20th visit. Improvement was sustained to the final visit, the FT group score being lower (6.50) than the ST group score (14). CGI - i mprovement and CGI-seve rity scores we re similar to the above mentioned results. The most common events in both groups were considered mild. The data of these patients show faster response to antidepressant therapy with faster titration dosage, with maintenance of the molecule's tolerability profile.

Adolescent↗
PubMed1977

[Intragastric titration with extragastric pH-metry--a clinically applicable and reliable technique of quantitative analysis of gastric secretion (author's transl)].

A technique is described by which the secretory capacity of the stomach can be determined. It appears to be superior both to intragastric titration along with intragastric pH-metry and to common analysis of gastric juice obtained by aspiration. There is no essential difference when comparing results obtained intraindividually by intragastric titration with the pH being measured either inside or outside the stomach. When titrating intragastricly with the pH being measured extragastricly, a tube is used which can be check more easily, remains usable much longer, and - as a result of its smaller diameter - is tolerated much better by the patient. In contrast to common analysis of gastric juice obtained by aspiration, by intragastric titration with the pH being measured extragastricly gastric acid can be determined at its site of production (less volume loss and rediffusion of H+ -ions into tissue), the results obtained representing more accurately the true secretory capacity of the stomach. As can be seen from its results, the technique presented here is apt particularly to both testing antacids and the substances interfering with gastric secretion; it also appears to be superior to common analysis of gastric juice obtained by aspiration.

Antacids↗
PubMedDate not supplied

[Analysis of dose-dependent antibody titration curves].

Several types of dose-response titration curves were considered. It was demonstrated that the use of the so-called coordinates of dilution suggested earlier by us allows one to analyze the titration curves, obtained either by ELISA, or by agglutination. Theoretical curves, obtained by the developed theory are very similar to those obtained in experiments. It was shown, that the analysis of the titration curves could give important information concerning antibody-blocking factors in titration sera or other samples of studied antibodies.

Animals↗
PubMedDate not supplied

Analysis of the purity of cetrimide by titrations.

The purity of cetrimide, trimethyl tetradecyl ammonium bromide (TTAB), which is an important preservative of many cosmetic and pharmaceutical products, was determined by three independent methods of titration. Traditionally, cetrimide was analysed by an assay method of the European Pharmacopoeia, which showed consistently a low purity of cetrimide with associated large standard deviations, however. A systematic 3% bias of the European Pharmacopoeia assay method was identified by comparing the result with results of two alternative methods of titration that exhibited high precision and high accuracy. Titration by perchloric acid showed a 99.69% +/- 0.05% purity of cetrimide, and titration by silver nitrate showed a 99.85% +/- 0.05% purity, while the traditional assay method predicted a purity of only 97.1% +/- 0.4%. It was found that the discrepancy could be identified as differences in selectivity during the extraction step of the European Pharmacopoeia assay method. The distribution coefficients between chloroform and water of cetrimide and the corresponding iodide species (TTAI) were thus determined as 2150 +/- 50 M(-1) and 68000 +/- 4000 M(-1), respectively.

Cetrimonium↗
PubMed1979

Microcomputer controlled titration for determination of protein nitrogen in feeds and wheat.

The determination of protein nitrogen in feeds and wheat by microcomputer controlled titration is described. The method involves direct titration of ammonia with standard hypochlorite titrant in the presence of bromide. The titrant is delivered by an automatic buret, and the microcomputer controlled, automatically computed potentiometric end points are precise to 0.1% over a 5-fold concentration range of nitrogen. Digestions performed with both mercury and copper catalysts show comparable results. Samples are weighed before digestion by an electronic balance interfaced to the computer which records sample number and weight. An automatic pipet aliquots, dilutes, and buffers samples directly from the digestion tubes; the samples can be immediately titrated with the automatic titrator. The results for protein in NBS standards and check feed samples from an offical testing program compare closely with average values reported for these standards. Results show that feed and wheat samples contained 10-100% protein. Precision for successive aliquots of the same digests is 0.1-0.4%relative standard deviation; precision for multiple digestions of the same sample is 0.1-0.8%.

Animal Feed↗
PubMed1979

Reversible and irreversible changes in hydrogen ion titration curves of melanins.

Hydrogen ion titration curves obtained on melanins prepared and modified differently show recognizable differences. Melanin prepared with NaOH exhibits irreversible loss of functional groups in the base range once titrated acidic. Melanin prepared with NH4OH shows two main branches selected by incubation at an extreme pH for 24 h. Longer exposure reveals other curves but they disappear once a 24-h schedule of titration is resumed. The existence of two major pH branches appears consistent with the oxidation-reduction properties of melanins. These results demonstrate the ability to obtain a reproducible feature in the hydrogen ion titration curves. Thus it is finally possible to quantitate CO2 adsorbed to melanin in solution at basic pH.

Ammonia↗