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PubMed2004

[Intravenous morphine titration].

OBJECTIVES: To describe principles of intravenous (i.v.) morphine titration. To analyse current knowledge based on the experimental and clinical studies. To describe clinical implications in the operating room, postanaesthesia care unit (PACU), prehospital care, emergency and intensive care units (ICU), and cancerology. To provide recommendations for clinical practice. DATA SOURCES: Search in the Medline database without limitation, using the following keywords: morphine titration. STUDY SELECTION: All types of articles were selected including prospective randomised (or not randomised) studies in adults and children, practice guidelines, reviews, editorials and case reports. DATA SYNTHESIS: Intravenous (i.v.) morphine titration is a pharmacological method which involves morphine boluses administration until pain relief, allowing a limitation in morphine side effects which are mainly dose dependent. I.v. morphine titration is widely used in prehospital care, emergency unit, PACU, ICU, and cancerology, in young and elderly patients. In the PACU, when the VAS (visual analogue scale) increases to more than 30 mm, i.v. morphine titration every five minutes with an unlimited number of 2 or 3 mg boluses provides an efficient analgesic regimen in adults. Titration is performed until pain relief (VAS < or =30), sedation that is the most frequent side effect during i.v. morphine titration (Ramsay score >1), severe side effects (like respiratory depression). CONCLUSION: Because of important pharmacological variability in morphine need, iv morphine titration is a simple method which allows a rapid and efficient pain relief notably in the postoperative care.

Analgesics, Opioid↗
PubMed2005

Role of different nocturnal monitorings in the evaluation of CPAP titration by autoCPAP devices.

The aim of the study was to assess how the analysis of different signals recorded during application of automatic continuous positive airway pressure (autoCPAP) devices improves the evaluation of pressure titration in patients with obstructive sleep apnea syndrome (OSAS) naive to treatment. Seventy-two patients underwent nocturnal polysomnography during autoCPAP (Autoset T, ResMed, Sydney, Australia) application. Progressively more complex combinations of signals were analysed in consecutive steps. According to the analysis of oxyhemoglobin saturation (SaO(2)) alone, a fixed CPAP level suitable for treatment could not be identified in 3 subjects. When analysis of posture was added, titration was considered unsatisfactory in 1 more subject, due to a short time spent supine. Further, addition of flow and respiratory movements led to consider titration unsatisfactory in 1 more subject. Analysis of all polysomnographic signals demonstrated a not fully reliable titration in 9 subjects: 1 with short sleep duration, 2 without REM sleep, 4 with a short sleep time spent supine, and 3 subjects (already identified by SaO(2)) with insufficient correction of respiratory disorders even when a relatively high CPAP was administered. Mask leaks did not hamper titration. CPAP titration by automatic devices alone results in imperfect titration in >10% subjects naive to ventilatory treatment. Only polysomnographic recording ensures titration reliability in all patients. Further research is needed to identify simple and economic methods to reliably start the CPAP treatment.

Continuous Positive Airway Pressure↗
PubMed1999

Oral transmucosal fentanyl citrate (OTFC) for the treatment of breakthrough pain in cancer patients: a controlled dose titration study.

Oral transmucosal fentanyl citrate (OTFC) is a novel opioid formulation in which the potent synthetic mu-agonist fentanyl is embedded in a sweetened matrix that is dissolved in the mouth. It is undergoing investigation as a treatment for cancer-related breakthrough pain, a prevalent phenomenon defined as a transitory flare of moderate to severe pain that interrupts otherwise controlled persistent pain. There have been no controlled trials of other treatments for this condition. To evaluate the safety and efficacy of ascending doses of OTFC, a novel controlled dose titration methodology was developed that applied blinding and randomization procedures to the evaluation of recurrent pains in the home environment. The study was a multicenter, randomized, double-blind dose titration study in ambulatory cancer patients. The sample comprised adult patients receiving a scheduled oral opioid regimen equivalent to 60-1000 mg oral morphine per day, who were experiencing at least one episode per day of breakthrough pain and had achieved at least partial relief of this pain by use of an oral opioid rescue dose. After collection of 2 days of baseline data concerning the efficacy of the usual rescue drug, patients were randomly treated with either 200 or 400 microg OTFC unit doses in double-blind fashion. Up to two breakthrough pains each day could be treated with up to four OTFC unit doses per pain. OTFC in unit doses containing 200, 400, 600, 800, 1200 or 1600 microg of fentanyl citrate were available for the study. The unit dose was titrated upward in steps until the patient had 2 consecutive days on which breakthrough pain could be treated with the single unit dose, titration was ineffective at a 1600 microg unit dose, or 20 days elapsed. To maintain the double-blind, orders to titrate up were ignored one-third of the time according to a pre-defined randomization schedule accessible only to an unblinded study pharmacist. Main outcome measures included, numeric or categorical measures of pain intensity, pain relief, and global assessment of drug performance. Dose response relationships were found suggesting that the methodology was sensitive to opioid effects. Seventy-four percent of patients were successfully titrated. There was no relationship between the total daily dose of the fixed schedule opioid regimen and the dose of OTFC required to manage the breakthrough pain. Although the study was not designed to provide a definitive comparison between OTFC and the usual rescue drug, exploratory analyses found that OTFC provided significantly greater analgesic effect at 15, 30 and 60 min, and a more rapid onset of effect, than the usual rescue drug. Adverse effects of the OTFC were typically opioid-related, specifically somnolence, nausea and dizziness. Very few adverse events were severe or serious. This study demonstrated the feasibility of controlled trial methodology in studies of breakthrough pain. OTFC appears to be a safe and effective therapy for breakthrough pain, and dose titration can usually identify a unit dose capable of providing adequate analgesia. If the lack of a relationship between the effective OTFC dose and fixed schedule opioid regimen is confirmed, dose titration may be needed in the clinical use of this formulation. Further investigation of OTFC as a specific treatment for breakthrough pain is warranted.

Administration, Oral↗
PubMed2003

Specialist nurse supervised in-hospital titration to target dose ACE inhibitor--is it safe and feasible in a community heart failure population?

BACKGROUND: Recently published guidelines from the ESC and practical recommendations from an international group of experts support the up-titration of ACE inhibitors at 1- to 2-week intervals. Observance of these guidelines could contribute to the under-dosing of ACE inhibitors at discharge in patients admitted with heart failure. Specialist heart failure nurse supervision of ACE inhibitor titration during the in-hospital stay could be a safe and effective means of avoiding this problem. OBJECTIVE: This observational study examines the feasibility of specialist heart failure nurse supervised rapid titration of ACE inhibition to at least target dose in sequential, class IV heart failure patients admitted to the cardiology service with left ventricular failure and not previously treated with an ACE inhibitor. METHODS: Fifty-two patients (mean age 71.9+/-11.6 years) were initiated on perindopril and titrated to maximally tolerated dose during the in-hospital phase. Indices of renal function (creatinine, urea, potassium) and systolic blood pressure were observed at baseline and at discharge from hospital and at 3 months. Lengths of stay and titration intervals were recorded. RESULTS: The mean length of stay was 10.3+/-7.7 days and 98% of patients achieved at least target dose of perindopril before discharge. The average time to titration to final dose was 5.5+/-4.2 days. Systolic blood pressure decreased significantly from 132+/-28 mmHg on admission to 117+/-18 mmHg on discharge. Mean baseline urea, creatinine and potassium did not change from admission to discharge (urea 8.4+/-2.5 to 9.2+/-3.9 mmol/l, P=0.15; creatinine 122.7+/-30.3 to 122.4+/-35.4 micromol/l, P=0.93; potassium 4.0+/-0.5 to 4.0+/-0.3 mEq/l, P=0.86). No significant changes were observed in these parameters at 12 weeks. There were no recorded incidences of symptomatic hypotension or progressive renal dysfunction even in patients (n=25) with evidence of chronic renal impairment (creatinine >120 micromol/l). CONCLUSIONS: Specialist heart failure nurse supervised initiation and rapid in-hospital titration of ACE inhibitor to at least target dose is feasible and safe in a severe heart failure population admitted with class IV heart failure. Routine application of this approach may help avoid under-dosing of ACE inhibitors without increasing length of hospital stay, and may reduce outpatient visits to heart failure clinics for titration.

Aged↗
PubMed2001

A novel view of pH titration in biomolecules.

When individual titratable sites in a molecule interact with each other, their pH titration can be considerably more complex than that of an independent site described by the classical Henderson-Hasselbalch equation. We propose a novel framework that decomposes any complex titration behavior into simple standard components. The approach maps the set of N interacting sites in the molecule onto a set of N independent, noninteracting quasi-sites, each characterized by a pK'(a) value. The titration curve of an individual site in the molecule is a weighted sum of Henderson-Hasselbalch curves corresponding to the quasi-sites. The total protonation curve is the unweighted sum of these Henderson-Hasselbalch curves. We show that pK'(a) values correspond to deprotonation constants available from methods that can be used to assess total proton uptake or release, and establish their connection to protonation curves of individual residues obtained by NMR or infrared spectroscopy. The new framework is tested on a small molecule diethylenetriaminepentaacetate (DTPA) exhibiting nonmonotonic titration curves, where it gives an excellent fit to experimental data. We demonstrate that the titration curve of a site in a group of interacting sites can be accurately reconstructed, if titration curves of the other sites are known. The application of the new framework to the protein rubredoxin demonstrates its usefulness in calculating and interpreting complicated titration curves.

Binding Sites↗
PubMed2006

Potentiometric titration of metal ions in ethanol.

The potentiometric titrations of Zn2+, Cu2+ and 12 Ln3+ metal ions were obtained in ethanol to determine the titration constants (defined as the at which the [-OEt]/[Mx+]t ratios are 0.5, 1.5, and 2.5) and in two cases (La3+ and Zn2+) a complete speciation diagram. Several simple monobasic acids and aminium ions were also titrated to test the validity of experimental titration measurements and to establish new constants in this medium that will be useful for the preparation of buffers and standard solutions. The dependence of the titration constants on the concentration and type of metal ion and specific counterion effects is discussed. In selected cases, the titration profiles were analyzed using a commercially available fitting program to obtain information about the species present in solution, including La3+ for which a dimer model is proposed. The fitting provides the microscopic values for deprotonation of one to four metal-bound ethanol molecules. Kinetics for the La3+-catalyzed ethanolysis of paraoxon as a function of are presented and analyzed in terms of La3+ speciation as determined by the analysis of potentiometric titration curves. The stability constants for the formation of Zn2+ and Cu2+ complexes with 1,5,9-triazacyclododecane as determined by potentiometric titration are presented.

Journal Article↗
PubMed1991

The origin of multiply sigmoid curves of pH-dependence. The partitioning of groups among titration pK values.

An acid, HnA, with n ionizing groups is known to have the same titration curve as an equimolar mixture of n hypothetical monobasic acids, whose dissociation constants are known as the 'titration constants' of the real acid. We show that the pH-dependence of any property of HnA is also represented by the sum of one-site titration curves, characterized by these same titration constants. Since one such property is the degree of dissociation of one of the dissociating groups, a fraction of each group shows each of the various titration pK values, so that the group partitions among them. The n groups therefore share the same n titration pK values but differ in the fractions belonging to each. The one H+ ion per molecule that titrates with each pK is thus made up of the fractions, one from each group, that share this pK value. A group may possess a single pK value, in that it contributes virtually all of this pK and almost nothing to the others, only if either (1) in titrates in a different pH range from the other groups or (2) its affinity for H+ is unaffected by their ionization state.

Acids↗
PubMed2003

Sleep during titration predicts continuous positive airway pressure compliance.

STUDY OBJECTIVES: Poor compliance with continuous positive airway pressure (CPAP) has been identified as a significant obstacle in the treatment of obstructive sleep apnea. While previous studies have focused on diagnostic screening variables, side effects, health beliefs, and measures of disease severity, investigators have generally ignored sleep parameters assessed during CPAP titration as predictors of compliance. As the titration night represents patients' initial exposure to nocturnal CPAP treatment, we hypothesized that nocturnal polysomnographic (PSG) variables, representing improved sleep at this time, would predict higher subsequent compliance. DESIGN: Prospective analyses of a sequential case series were undertaken using nocturnal PSG variables during titration as early predictors of CPAP compliance. SETTING: Accredited sleep center. PATIENTS: Seventy-one patients with sleep apnea, aged 31-78 years, with a mean respiratory disturbance index of 62.0 +/- 32.2. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Compliance was calculated as mean hours per night of CPAP use over the initial follow-up period (mean 46.9 days). Standard PSG variables and subjective reports of sleep were used as predictive variables in multivariate analyses. Mean objective compliance was 5.04 hours per night +/- 2.59. Consistent with our hypothesis, the best predictor of compliance was change in sleep efficiency (SE) from diagnostic to titration night [F (1,66) = 17.31, p < .000 (r = .48)], indicating that patients whose sleep improved most on the titration night had the highest levels of compliance. This relationship was also significant after controlling for measures of disease severity obtained during the diagnostic testing night. Importantly, individuals whose sleep improved on the CPAP titration night had nightly compliance rates of approximately 2 hours greater than patients whose sleep did not improve during titration. CONCLUSIONS: The findings suggest that patients' initial experience with CPAP treatment and, in particular, the degree of improvement in sleep during CPAP titration may be crucial factors in determining their subsequent use of this treatment modality.

Adult↗
PubMed2004

One-year follow-up of patients with acromegaly treated with fixed or titrated doses of lanreotide Autogel.

OBJECTIVE: Somatostatin analogue treatment is first-line medical therapy for acromegaly. This study compared the efficacy and tolerability of titrated doses of the long-acting somatostatin analogue preparation lanreotide Autogel with fixed doses and with lanreotide prolonged release (PR) 30 mg microparticles. PATIENTS: Patients entering the initial study had received a diagnosis of active acromegaly within the previous 5 years. DESIGN: This open, comparative, multicentre study was a 1-year extension of a previous trial during which patients with acromegaly had switched from lanreotide PR 30 mg microparticles injected intramuscularly every 7, 10 or 14 days, for at least 3 months, to one of three fixed doses of lanreotide Autogel (120, 90, or 60 mg every 28 days, respectively). In this extension study, patients continued to receive 60, 90, or 120 mg of lanreotide Autogel by deep subcutaneous injection every 28 days for 1 year. Doses could be titrated at entry or after four or eight injections, according to the GH/IGF-I response (dose increased if GH > 2.5 micro g/l, or decreased if GH < 1 micro g/l with normal IGF-I). MEASUREMENTS: Mean +/- SEM GH and IGF-I concentrations were analysed and gallbladder echography performed at weeks 0, 16, 32, and 48. Acromegaly symptoms were recorded monthly and tolerance and side-effects were monitored throughout the study. RESULTS: In total, 130 patients entered this extension phase. After 1 year of treatment with titrated doses of lanreotide Autogel, mean GH (2.4 +/- 0.2 micro g/l) and IGF-I (287 +/- 12 micro g/l) concentrations were significantly lower than with lanreotide microparticles (GH, 2.8 +/- 0.2 micro g/l, P < 0.001; IGF-I, 332 +/- 15 micro g/l, P < 0.01) or with fixed-dose lanreotide Autogel (GH, 3.0 +/- 0.2 micro g/l, P < 0.001; IGF-I, 310 +/- 14 micro g/l, P = 0.02). GH hypersecretion was reduced to </= 2.5 micro g/l in 68% of patients with titrated-dose lanreotide Autogel compared with 49% with microparticles (P < 0.001) and 56% with fixed-dose lanreotide Autogel (P </= 0.005). In the 65 patients who did not require any dose titration, there was no substantial change in serum lanreotide concentration, GH or IGF-I levels over the 12-month study duration. Acromegaly was effectively controlled (GH </= 2.5 micro g/l and normalized IGF-I) in significantly more patients (43%) compared with microparticles (32%; P < 0.05). There was a trend for improved control of acromegalic symptoms with dose titration, whereas the incidence of gastrointestinal symptoms and local tolerance was similar with lanreotide Autogel and lanreotide microparticles. Gallbladder echographies showed new lithiasis in 8% of lanreotide Autogel patients. CONCLUSION: Dose titration of lanreotide Autogel improved GH and IGF-I control in patients with acromegaly beyond that achieved using fixed doses of lanreotide Autogel or lanreotide microparticles. Titrated long-term lanreotide Autogel treatment is well tolerated.

Acromegaly↗
PubMed2006

Reduction in anaesthetic drug consumption is correlated with mean titrated intra-operative Bispectral Index values.

BACKGROUND: Several studies have shown a reduction in anaesthetic drug consumption with Bispectral Index (BIS) titration compared with standard clinical practice. However, the amount of reduction varied widely between 1% and 40%. We investigated the correlation between reduction in anaesthetic drug consumption and mean titrated BIS values. METHODS: An analysis upon randomized controlled trials cited until January 2006 in MEDLINE and other databases investigating the potential reduction in anaesthetic (hypnotic) drug consumption with BIS titration was performed. Investigations with a marked difference (> 15%) in opioid drug consumption between the BIS group and the standard practice group were excluded. Correlations between amount of reduction in hypnotic drug use and the mean titrated BIS value were analysed with linear regression. RESULTS: Fourteen manuscripts covering 2582 patients were included into the analysis. The mean BIS value in the standard clinical practice group averaged over all studies was 43.6 +/- 3.2 and the mean BIS value in the BIS-titrated group was 49.9 +/- 5.4. The amount of reduction in hypnotic drug use correlated significantly with the mean BIS values in the BIS-titrated groups (r =0.68) and with the differences between the mean BIS value in the BIS-titrated group and the mean BIS value in the standard clinical practice group (r = 0.70). Every point of BIS difference between the two groups resulted in a reduced hypnotic drug use of approximately 2%. CONCLUSION: Despite differences in the study designs and in the drugs used, a linear correlation between the mean titrated BIS value and the hypnotic drug saving potential was found.

Anesthetics↗
PubMed1996

Unattended continuous positive airway pressure titration. Clinical relevance and cardiorespiratory hazards of the method.

The high cost of in-laboratory sleep studies and the insufficiency of available nights in most sleep laboratories has prompted clinical trials in an attempt to find an effective and safe method for continuous positive airway pressure (CPAP) titration in the unsupervised home environment. Earlier publications focused on the effectiveness of this new method but did not indicate the potential hazard and the selection criteria of patients. We accomplished a prospective study to evaluate a machine-controlled CPAP titration method in an unselected group of 21 patients with obstructive sleep apnea (OSA) requiring CPAP therapy. Unattended CPAP titrations were completed in the sleep laboratory, followed by conventional CPAP titration night. The CPAP levels assessed through automatic titrations showed strong agreement with those from the control nights. Fifteen patients had no pathologic cardiorespiratory events during machine-controlled titration. Undesirable cardiorespiratory complications developed in six patients with underlying cardiorespiratory disorder. Two patients had to stop the procedure. Two patients needed a reset of the actual pressure to baseline because of central apneas and one patient because of high-grade arrhythmia. The machine-controlled CPAP titration enabled reliable assessment of an effective pressure and appeared to be safe in selected patients with OSA. However, because the method caused significant adverse effects in some patients, we recommend that unattended CPAP titration not be attempted in patients with underlying cardiorespiratory disease.

Arrhythmias, Cardiac↗
PubMed2004

Alternative methods of titrating continuous positive airway pressure: a large multicenter study.

Standard practice for continuous positive airway pressure (CPAP) treatment in sleep apnea and hypopnea syndrome (SAHS) requires pressure titration during attended laboratory polysomnography. However, polysomnographic titration is expensive and time-consuming. The aim of this study was to ascertain, in a large sample of CPAP-naive patients, whether CPAP titration performed by an unattended domiciliary autoadjusted CPAP device or with a predicted formula was as effective as CPAP titration performed by full polysomnography. The main outcomes were the apnea-hypopnea index and the subjective daytime sleepiness. We included 360 patients with SAHS requiring CPAP treatment. Patients were randomly allocated into three groups: standard, autoadjusted, and predicted formula titration with domiciliary adjustment. The follow-up period was 12 weeks. With CPAP treatment, the improvement in subjective sleepiness and apnea-hypopnea index was very similar in the three groups. There were no differences in the objective compliance of CPAP treatment and in the dropout rate of the three groups at the end of the follow-up. Autoadjusted titration at home and predicted formula titration with domiciliary adjustment can replace standard titration. These procedures could lead to considerable savings in cost and to significant reductions in the waiting list.

Adult↗
PubMedDate not supplied

Effects of dose titration on tolerability and efficacy of interferon beta-1b in people with multiple sclerosis.

Multiple sclerosis (MS) treatment with interferon beta is associated with well-known, easily managed adverse events, including influenza-like symptoms and injection-site reactions that decline over time. Initial dose titration has been shown to be one way of limiting these adverse events. Hence, a placebo-controlled, multicentre study of 98 patients was set up to explore whether a slower, four-stage, 4-week titration to a final dose of 250 microg subcutaneous interferon beta-1b might improve tolerability over a more rapid two-stage, 2-week titration in patients with relapsing-remitting MS. Frequency of adverse events was found to be similar between the two regimens: notably, no difference in the incidence of injection-site reactions, with a trend towards fewer influenza-like symptoms in the slow-titration group. Relative to placebo, significantly fewer patients receiving interferon beta-1b relapsed. This was more pronounced in the rapid-titration group than in the slow-titration group, showing that rapid and significant improvements in relapse rates were achieved within 90 days of starting interferon beta-1b. Although a rapid-titration regimen results in a quicker onset of clinical benefit, slow titration showed a non-significant trend towards reduced influenza-like symptoms.

Adjuvants, Immunologic↗
PubMed2001

Efficacy of daytime continuous positive airway pressure titration in severe obstructive sleep apnoea.

The aim of this study was to evaluate manual nasal continuous positive airway pressure (nCPAP) titration during daytime polysomnography compared with conventional overnight titration for patients with severe obstructive sleep apnoea. Thirty-two patients who underwent daytime titration were retrospectively matched (for age, sex, body mass index and apnoea/hypopnoea index (AHI)) to a group titrated overnight during the same period. Successful titration was defined as the identification of the nCPAP level (effective nCPAP (Peff)) required to eliminate respiratory events during all sleep stages. After 3 months of therapy on nCPAP at Peff, nCPAP utilization history was obtained and a group of patients underwent a repeat polysomnogram (PSG) and completed a follow-up Epworth Sleepiness Scale (ESS) score. Initial titration was successful in 91% of daytime patients and 91% of overnight patients. The success of daytime titration was not related to diagnostic AHI or ESS score. Subjective nCPAP utilization was statistically similar in both groups. On the follow-up PSG, there were no significant differences between daytime (n=11) and overnight (n=11) patients in measures of sleep quality or respiratory disturbance. Both groups demonstrated similar and significant improvements in ESS score. These findings suggest that the effective nasal continuous positive airway pressure can be accurately established during daytime titration in a substantial proportion of severe, symptomatic obstructive sleep apnoea patients.

Female↗
PubMed1997

AutoSet nasal CPAP titration: constancy of pressure, compliance and effectiveness at 8 month follow-up.

We have previously shown that AutoSet satisfactorily improves sleep-disordered breathing and sleep architecture in subjects with obstructive sleep apnoea (OSA) syndrome. The aim of this study was to determine, in subjects treated with long-term conventional fixed pressure continuous positive airway pressure (CPAP) at the AutoSet recommended pressure, whether: the long-term compliance is satisfactory; the improvement persists once initial rebound is over; the titration pressure is stable with time; and the titration pressure is comparable with manual titration pressure using a similar end-point. Twenty males with OSA, previously studied with full polysomnography on their diagnostic night, at manual and AutoSet titration, and at the AutoSet recommended fixed pressure, were re-studied after a mean of 3 and 8 months of treatment at the recommended fixed pressure. Re-study included home respiratory monitoring (Nellcor EdenTrace), and repeated manual and AutoSet titration with polysomnography. Compliance was assessed with hour-meter readings. Mean (+/-SEM) usage was 5.7 +/- 0.1 h.night-1 at 3 and 8 months. The arousal index remained normalized. Diagnostic respiratory disturbance index (RDI) was 60.3 +/- 5.7 events.h-1. On AutoSet at fixed CPAP, RDI was initially 2.6 +/- 0.7 events.h-1, then rose slightly (p < 0.001) to 4.3 +/- 0.6 events.h-1 at 3 months, and was 3.6 +/- 0.5 events.h-1 at 8 months. AutoSet titration pressure was: 9.9 +/- 0.4 cmH2O initially, 10.6 +/- 0.4 cmH2O at 3 months, and 9.7 +/- 0.5 cmH2O at 8 months (NS). Manual titration pressure at 8 months was 10.4 +/- 0.4 cmH2O. The standard deviation of the discrepancy with AutoSet was 0.84 cmH2O. In conclusion, the AutoSet recommended pressure varies little with time, and closely predicts the final manual titration pressure; the improvement in respiratory disturbance index was largely maintained, and compliance was good, although probably enhanced by close supervision.

Follow-Up Studies↗
PubMed1980

Titratable acidities of crystalline amino acid admixtures.

Titration curves for total parenteral nutrient (TPN) products were developed and used to determine the amount of alkali needed to make various pH changes. Equations and graphs for determining the titratable acidities of TPN solutions are presented. Samples of five crystalline amino acid products and of 1:1 mixtures of the products with 50% dextrose solutions were titrated to pH 7.4 (with a standard sodium bicarbonate solution) or 8.0 (with a standard sodium hydroxide solution). The samples titrated with sodium hydroxide were first adjusted to pH 5.0 with hydrochloric acid. The pH of the sample was measured after each 0.1-ml addition of hydroxide or bicarbonate to develop a titration curve. Titratable acidities for the five crystalline amino acid products varied widely, ranging from 13.4--45.2 meq of hydroxide/liter and from 135--420 meq of bicarbonate/liter. The amino acid/dextrose mixtures had titratable acidities ranging from 7.8--24.8 meq of hydroxide/liter and from 87--226 meq of bicarbonate/liter. The pH titration data can be used as a guide for determining the amount of base to add to TPN solutions to obtain the desired pH.

Amino Acids↗
PubMed1982

On the Hill plot of NMR data for titration of proteins residues.

The Hill plots of NMR titration data for protein residues disclose more clearly than the usual titration curves the presence of multiple weak perturbations originating from other titratable groups, and should be used whenever the conventional curve fitting is poor. For a quantitative interpretation, we derive here expressions for the Hill equation and the Hill coefficient when the titration of the observed group is perturbed by more than one titratable group. When the generalized Hill equation is fitted to the data, values of the interaction parameters between the observed group and the others are extracted provided that there are no mutual interactions between the latter groups. The method is applied to the titration data of two histidyl residues of L-arginine phosphotransferase (E.C. 2.7.3.3.) in the transition state analogue complex (enzyme-Mg2+-ADP-NO3(-)-L-Arg). From the Hill plots, interactions with three titratable groups are disclosed for both residues, and the fitting with the Hill equation reveals that they experience perturbations from the same three groups. Microscopic pK values are obtained for all the involved groups, indicating large changes (up to 3 pH units) upon protonation of the interacting groups. As compared to the conventional fitting procedure, the use and fitting of Hill plots yields from NMR data more information on the neighbourhood of enzyme residues and on the changes intervening therein through the steps involved in the catalysis.

Arginine Kinase↗
PubMed2004

A high initial VAS score and sedation after iv morphine titration are associated with the need for rescue analgesia.

PURPOSE: Administration of sc morphine has been recommended two hours after the end of iv morphine titration in the postanesthesia care unit (PACU), but in some cases patients complain of pain earlier than this. We assessed pain after the end of iv morphine titration and studied the characteristics of patients who needed rescue sc morphine. METHODS: Postoperative pain was assessed using the visual analogue scale (VAS; 0 to 100) and the threshold required to administer morphine in the PACU was a score of 30. VAS was measured every 15 min up to two hours after the end of iv morphine titration. Patients were divided into two groups, those who required sc morphine before two hours and those who did not. Data are expressed as mean +/- SD or odds ratio (OR; 95% confidence interval). RESULTS: Four hundred and two patients were analyzed. Mean age was 51 +/- 19 yr, initial VAS 69 +/- 19, and the dose of iv morphine 11.7 +/- 6.6 mg. The number of patients requiring sc morphine within two hours was 84 (21%). These patients had more severe initial postoperative pain (73 +/- 20 vs 68 +/- 19, P < 0.05), and experienced sedation more frequently during morphine titration (45 vs 25%, P < 0.001). Using a multivariate analysis, occurrence of sedation during titration [OR 2.3 (1.4-3.8), P < 0.001] and an initial pain score > or = 60 [OR 1.9 (1.0-3.4), P < 0.05] were significantly associated with the need for rescue sc morphine. CONCLUSION: Sedation during titration and an initial VAS > or = 60 are characteristics of the patients who require rescue (less than two hours) sc morphine after iv morphine titration.

Aged↗