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Biomedical subjects

B A Boucher

Publications and source records attributed to B A Boucher.

At least 37 records · Page 2Linked to original sources
PubMed1991

The prognostic inflammatory and nutritional index in traumatized patients receiving enteral nutrition support.

The prognostic inflammatory and nutritional index (PINI) is a clinical assessment tool which aggregates serum C-reactive protein (CRP), alpha 1-acid glycoprotein (AAG), prealbumin (PA), and albumin (ALB) concentrations into a single score. This study was conducted to characterize the index and its determinants over time in 15 critically ill trauma patients receiving enteral nutritional support (ENS). Patients received 1.4 g of protein/kg/day and 32 kcal/kg/day for at least 7 days using a nutritionally complete formula supplemented with whey protein. The PINI was calculated at baseline and on days 4, 7, 10, 14, 21, and 28. The PINI decreased significantly from baseline (186 +/- 202) to day 4 (116 +/- 86) and reached a nadir at day 14 (27 +/- 40). Serum CRP concentrations decreased significantly during the study period, while PA and ALB concentrations increased significantly. There was no change in the AAG concentration. Nitrogen balance increased significantly during the study period. The PINI was positively correlated with CRP concentration (r = 0.72, p = 0.0001) and negatively correlated with PA concentration (r = 0.56, p = 0.0004 and nitrogen balance (r = -0.51, p = 0.0018). The PINI decreased significantly during ENS of critically ill trauma patients, influenced primarily by a decrease in CRP concentration. Further studies are needed to characterize the PINI's performance as a prognostic tool.

Adolescent↗
PubMed1990

Negative inotropic effect of intravenous nifedipine in coronary artery disease: relation to plasma levels.

The relative extent of the vasodilator versus direct negative inotropic effects of nifedipine was studied in 15 male patients with documented coronary artery disease and normal left ventricular function. At the time of diagnostic cardiac catheterization, three groups of five patients received dose of 1, 2, and 3 mg intravenous nifedipine at a rate of 0.33 mg/min. Hemodynamic measurements and blood collections were made before, during, and every 5 minutes for 30 minutes after infusion of nifedipine. Heart rate increased and mean arterial pressure decreased significantly after the 2 and 3 mg doses of nifedipine. Systemic vascular resistance was significantly decreased and cardiac index increased after all doses of nifedipine. Maximal left ventricular dp/dt (dp/dtmax) was significantly decreased after the 3 mg infusion. The reduction in dp/dtmax was most consistent with a reduction in left ventricular contractility as opposed to changes in loading conditions. Plasma concentrations of nifedipine were significantly correlated with bidirectional changes in dp/dtmax (r = 0.86). Nifedipine concentrations below 28.2 ng/ml were associated with a rise in dp/dtmax, whereas concentrations above that level were associated with a reduction in dp/dtmax. These data indicate that intravenous nifedipine produces dose- and concentration-dependent depression of myocardial contractility in patients with coronary artery disease. Nifedipine concentrations associated with negative inotropic effects are readily achievable with common oral and sublingual doses.

Adult↗
PubMed1990

Algorithm for assessing renal dysfunction risk in critically ill trauma patients receiving aminoglycosides.

A recent retrospective study proposed that the following screening criteria be used in identifying critically ill trauma patients receiving aminoglycosides who are at significant risk to develop renal dysfunction: (1) post-admission shock, (2) minimum serum concentration more than 2 mg/L, and (3) diagnosis of septicemia. The major purpose of the present study was to validate these criteria and design a corresponding algorithm for clinical use. All patients admitted to a trauma intensive care unit and receiving an aminoglycosides was also studied. All patients studied over a 7-month period. A control group not receiving aminoglycosides was also studied. All patients were evaluated for the presence of renal dysfunction (i.e., serum creatinine increase greater than or equal to 0.5 mg/dL). Univariate and multivariate statistical analyses were used to compare potential associated risk factors. The overall renal dysfunction incidence was 10% in the treatment patients (n = 93) versus 5% in the control patients (n = 199) (p = 0.13). Sensitivity and specificity of the screening criteria were 67% and 92%, respectively. The predictive values of a positive and negative test relative to correctly labeling patients at high risk or low risk to develop renal dysfunction were 46% and 96%, respectively. Major risk factors associated with renal dysfunction in the treatment group were post-admission shock, minimum serum concentration more than 2 mg/L, and liver dysfunction. Use of three major risk factors has excellent predictive value in identifying severely traumatized patients at low risk for developing renal dysfunction while receiving aminoglycosides. The modest predictive value of a positive test results in conservative management of patients by avoidance of aminoglycosides, i.e., use of alternative antimicrobial agents.

Acute Kidney Injury↗
PubMed1990

Imipenem pharmacokinetics in patients with burns.

The pharmacokinetics of imipenem were studied in 11 adult patients with severe burns who were receiving a therapeutic regimen of imipenem-cilastatin 500 mg intravenously every 6 hours. Serial blood samples for measuring imipenem and 24-hour urine collections for creatinine clearance (CrCl) were obtained after the initial dose and after multiple dosing. Plasma was assayed for imipenem by use of HPLC. A two-compartment model provided a superior fit to the data compared with a one-compartment model in 9 of the 11 patients. There was no significant difference in any pharmacokinetic parameter between the initial dose and after multiple dosing (p greater than 0.05). Combined mean (+/- SD) parameter estimates for the two dosing periods were as follows: VC, 0.11 +/- 0.06 L/kg; Vss, 0.22 +/- 0.06 L/kg; CL, 12.5 +/- 3.6 L/hr/1.73 m2; t1/2 alpha, 0.18 +/- 0.13 hr; t1/2 beta, 1.12 +/- 0.44 hr. Mean clearance in two patients with creatinine clearance values greater than 150 ml/min/1.73 m2 was 17.7 L/hr/1.73 m2. Mean clearance in two patients with creatinine clearance values less than 50 ml/min/1.73 m2 was 8.5 L/hr/1.73 m2. No pharmacokinetic parameter was significantly different from previously reported parameters in normal volunteers (p greater than 0.05). Creatinine clearance ranged from 17 to 218 ml/min/1.73 m2. Imipenem clearance was significantly related to creatinine clearance (CL = 63 + 0.059 CLCR; r2 = 0.60, p = 0.001). No significant association was found between total body surface area burns and imipenem clearance (p greater than 0.05). Our data suggest imipenem pharmacokinetics in patients with burns are comparable to those in normal volunteers although substantial intersubject variability exists.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Prophylaxis of posttraumatic seizures.

The issue of routine anticonvulsant prophylaxis for early and late posttraumatic epilepsy (PTE) has received much attention in the medical literature. Such problems as lack of standard definitions for early and late PTE, the retrospective design of most studies, the wide variability of inclusion and exclusion criteria, and the varied duration of follow-up make this body of literature extremely difficult to evaluate. Severe head trauma appears to cause injured neurons to become hyperexcitable; this in turn brings about the formation of an epileptogenic focus during the time between trauma and seizure occurrence. Both military and civilian head injury populations have been used to evaluate the incidence of PTE. Early seizures (i.e., less than 7 days) occur in approximately 3-5 percent of the head injury patients in both the military and civilian groups. Factors increasing this incidence include intracranial hematoma, focal neurologic deficits, posttraumatic amnesia (PTA) lasting greater than 24 hours, depressed skull fracture, and age less than 5 years. The incidence of late seizures is directly related to the extent of brain damage. The military population, composed primarily of cases with penetrating head injury, is associated with a late PTE incidence of approximately 30-50 percent. Closed head injuries in the military population involve a 5-15 percent seizure incidence. Late PTE incidence after head injuries in the civilian population is less than 5 percent. Risk factors associated with late PTE include loss of consciousness or PTA lasting greater than 24 hours, dural lacerations, depressed skull fractures, and various computerized tomography deficits. These factors vary slightly between the military and civilian populations.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1990

Pharmacokinetics and safety of a phenytoin prodrug given i.v. or i.m. in patients.

ACC-9653, a prodrug of phenytoin synthesized to be water soluble, is converted to phenytoin by phosphatases. In this study, 43 patients received ACC-9653 IV or IM. Side effects were transient and minor. The conversion half-lives of ACC-9653 after intravenous and intramuscular administration averaged 8.4 and 32.7 minutes, respectively. Peak phenytoin concentrations occurred 42 minutes after IV and 151 minutes after IM administration.

Adult↗
PubMed1990

Use of selected visceral protein measurements in the comparison of branched-chain amino acids with standard amino acids in parenteral nutrition support of injured patients.

Twenty injured patients in the intensive care unit were randomized to receive parenteral nutrition with either 21% (STD) or 46% (HBC) branched-chain amino acids to compare the response of nitrogen balance (NB), somatomedin-C/insulin-like growth factor I (SMC), circulating fibronectin (FBN), and prealbumin (PA). NB was measured and serum collected for SMC, FBN, and PA on days 1, 4, 7, 14, and 21 of nutritional intervention. The treatment groups did not differ significantly for age, weight, injury severity score, trauma score, Apache II score, acute-phase protein concentrations, or type of injury. Comparison of baseline measurements revealed no significant differences in SMC, FBN, or PA. Both groups received similar doses of nonprotein energy and nitrogen. Baseline urea nitrogen excretion was slightly higher in the STD group (216 +/- 55 vs 268 +/- 54 mg/kg/day p = 0.049). Although NB was significantly improved over baseline during subsequent study days, there were no differences between groups after the day-1 measurement. SMC increased significantly from baseline on day 4 in the STD group, on day 7 in the HBC group, and on days 14 and 21 in both groups. There was no significant difference in SMC concentrations between groups on any day. Each group demonstrated a significant increase in PA from baseline on days 7, 14, and 21; however, no difference was seen when groups were compared. FBN increased significantly from baseline on day 14 in the HBC group and on days 7 and 14 in the STD group. FBN measurements were significantly different between groups on day 14 (STD, 179 +/- 71 vs HBC, 229 +/- 59 micrograms/ml; p less than 0.05). NB, PA, SMC, and FBN improve significantly during parenteral nutrition of traumatized patients. With the measured variables, there appears to be no significant difference between STD or HBC amino acids when used as part of parenteral nutrition in injured patients.

Amino Acids↗
PubMed1990

Drug use in a trauma intensive-care unit.

Medication prescribing patterns and costs of specific drug therapies in a trauma intensive-care unit (TICU) were studied. Demographic data and total drug use (scheduled, p.r.n., and single-dose medications) were recorded for all patients admitted to a TICU whose length of stay exceeded 24 hours. Scheduled and p.r.n. medications were categorized into major drug classes for purposes of analysis. Cost estimates were calculated for all scheduled medications. Correlations were made between demographic variables, injury severity indices, drug use, and length of stay by using simple linear regression. A one-way ANOVA was used to compare drug use between the trauma types. For the 278 patients who met the inclusion criteria, the mean +/- S.D. number of drugs prescribed was 9.1 +/- 6.5. Scheduled medications accounted for 58% of total drug use. Mean +/- S.D. duration of scheduled drug therapy was 5.0 +/- 4.8 days. Age (by decade), injury severity score, trauma score, and length of stay correlated with total and scheduled drug use per patient. Drug use (total, scheduled, and p.r.n.) did not differ significantly by trauma type. Antimicrobial therapy, stress ulcer prophylaxis, and bronchodilator therapy accounted for more than 66% of all scheduled drugs used; total cost estimates for these three drug categories exceeded $47,000 over the six-month study period. Analgesics, antipyretics, sedatives, and muscle relaxants constituted nearly 75% of all p.r.n. drug orders. Drug use in the TICU was extensive. The drug categories identified in this study may be useful in future cost containment efforts and initiation of drug use evaluations.

Adolescent↗
PubMed1989

Phenytoin prodrug 3-phosphoryloxymethyl phenytoin (ACC-9653): pharmacokinetics in patients following intravenous and intramuscular administration.

A phenytoin prodrug, 3-phosphoryloxymethyl phenytoin (ACC-9653; 1), has been developed with more favorable physicochemical properties than phenytoin for parenteral administration. The purpose of this study was to evaluate the pharmacokinetic profile of 1 following iv and im administration in adult patients receiving chronic oral phenytoin monotherapy. Each patient (9 males, 1 female) received a single iv dose of undiluted 1 equivalent to their twice daily phenytoin dose (100-200 mg). An equivalent dose of im 1 was administered in the gluteus maximus muscle one week later. Serial blood samples were obtained after each dose. Phenytoin and 1 concentrations were measured using HPLC. Compartmental analysis using weighted nonlinear least squares, and noncompartmental pharmacokinetic analysis were performed on each patient's concentration-time data. Data following iv 1 in eight of ten patients were best described using a two-compartment model. Mean pharmacokinetic parameter estimates for iv 1 in these patients were central volume of distribution (Vdc) of 0.040 +/- 0.0084 L/kg and plasma disappearance half-life (t1/2 alpha) of 8.0 +/- 2.9 min ("conversion" t1/2). Overall mean clearance (CL) was 0.24 +/- 0.080 L/kg/h in the 10 patients. Mean pharmacokinetic parameter estimates for im 1 were a rate constant (ka) of 2.47 +/- 1.41 h-1 and an absolute bioavailability (F) of 100.5 +/- 20.3%. Mean observed tmax values for phenytoin were 0.57 +/- 0.26 and 1.46 +/- 0.76 h following iv and im 1, respectively. Model-independent estimates of clearance agreed well with the compartmental analyses. Steady-state predose phenytoin concentrations did not significantly vary from the comparable concentrations following iv 1 administration (p = 0.22).(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, High Pressure Liquid↗
PubMed1989

Use of fibronectin and somatomedin-C as nutritional markers in the enteral nutrition support of traumatized patients.

Enteral nutrition support was provided to 12 critically ill, traumatized patients by continuous NG infusion with a nutritionally complete formula for at least 7 consecutive days. Serum for fibronectin (Fn) and somatomedin-C (Sm-C) was collected and nitrogen balance (NB) was measured on days 1, 4, 7, 14, 21, and 28 of the study period. Estimated energy and protein requirements were based, respectively, on the patient's calculated basal energy expenditure multiplied by a stress factor and urea nitrogen excretion (plus 4) during 24-h urine collections. Enteral feedings were started 5.3 +/- 3.8 days after injury; patients received an average of 33.2 +/- 3.9 kcal/kg.day and 1.5 +/- 0.4 g protein/kg.day. Fn concentrations increased significantly (p less than .05) from baseline on study days 7, 14, 21, and 28, whereas NB increased significantly (p less than .05) on study days 4, 7, 14, 21, and 28. Significant correlations were found between Fn and NB (r = .52, p less than .005), Fn and cumulative caloric intake (r = .54, p less than .005), and Fn and cumulative nitrogen intake (r = .62, p less than .005). There were no significant changes observed with Sm-C concentrations during the study period. Measurement of Fn concentrations appears to have potential as a nutrition support marker in traumatized patients, particularly in monitoring short courses of nutrition support. The role of Sm-C as a nutrition marker requires further investigation.

Adolescent↗
PubMed1988

Phenytoin pharmacokinetics in critically ill trauma patients.

Preliminary data have suggested that phenytoin systemic clearance may increase during initial therapy in critically ill patients. The objectives for this study were to model the time-variant phenytoin clearance and evaluate concomitant changes in protein binding and urinary metabolite elimination. Phenytoin was given as an intravenous loading dose of 15 mg/kg followed by an initial maintenance dose of 6 mg/kg/day in 10 adult critically ill trauma patients. Phenytoin bound and unbound plasma concentrations were determined in 10 patients and urinary excretion of the metabolite p-hydroxyphenyl phenylhydantoin (p-HPPH) was measured in seven patients for 7 to 14 days. A Michaelis-Menten one-compartment model incorporating a time-variant maximal velocity (Vmax) was sufficient to describe the data and superior to a conventional time-invariant Michaelis-Menten model. Vmax for the time-variant model was defined as V'max + Vmax delta (1 - e(-kindt)). Vmax infinity is the value for Vmax when t is large. The median values (ranges) for the parameters were Km = 4.8 (2.6 to 20) mg/L, Vmax infinity = 1348 (372 to 4741) mg/day, and kind = 0.0115 (0.0045 to 0.132) hr-1. Phenytoin free fraction increased in a majority of patients during the study period, with a binding ratio inversely related to albumin. Measured urinary p-HPPH data were consistent with the proposed model. A loading and constant maintenance dose of phenytoin frequently yielded a substantial, clinically significant fall in plasma concentrations with a pattern of apparently increasing clearance that may be a consequence of changes in protein binding, induction of metabolism, or the influence of stress on hepatic metabolic capacity.

Adult↗
PubMed1987

The acute effects of the enkephalin analogue BW 942C in humans.

BW 942C hydrochloride is an enkephalin analogue that has exhibited a wide separation between antidiarrheal dosages and dosages inducing adverse effects in animals. This has likewise been the case in humans when administered orally. In this study, the safety and tolerance of single 0.5-mg doses of intravenous BW 942C compared with placebo were assessed in humans. Four healthy male volunteers received BW 942C, and two received placebo. The effects of BW 942C on serum growth hormone (GH), luteinizing hormone (LH), prolactin (PR), and follicle-stimulating hormone (FSH) were assessed in three of these volunteers. No significant changes were apparent in vital signs, in clinical chemistry, hematologic and urine studies following BW 942C administration. BW 942C did not appear to alter mood as assessed by two psychologic mood scales. Prolactin levels tended to increase in volunteers receiving BW 942C two hours postinfusion. Luteinizing hormone concentrations decreased slightly at two and six hours. No trends in FSH or GH could be identified. Pulmonary function testing did not reveal any significant changes in oximetry, spirometry, or plethysmography in any of the subjects. A marked decrease in CO2 responsiveness in two subjects may indicate that BW 942C has mild ventilatory depressant effects. Untoward effects experienced in volunteers receiving BW 942C included heaviness in the limbs, nasal stuffiness, mouth dryness, facial flushing, skin rash, and prickling sensations. These effects bear a striking similarity to those experienced after parenteral administration of other enkephalin analogues. Intravenous administration of BW 942C up to 0.5 mg appears safe from a laboratory, physiologic, and clinical perspective with unusual untoward effects that may preclude rational use of the drug by the parenteral route.

Adult↗
PubMed1987

Lidocaine protein binding in preeclampsia.

The effect of preeclampsia on the binding of lidocaine to serum proteins was studied in 25 term parturients with severe preeclampsia and in 21 normal parturients serving as controls. There were no statistically significant differences in mean lidocaine free fraction, binding ratio, or serum AAG levels in the control vs preeclamptic patients, respectively. Binding ratio was strongly correlated with AAG concentration for the control (r = 0.91) and preeclamptic (r = 0.85) patients. A statistically significant difference was observed in the slopes of the lines relating binding ratio to AAG. Preeclampsia had little affect on serum AAG concentrations and lidocaine binding ratio. Preeclampsia may alter the interaction of lidocaine with binding sites on AAG without a significant change in lidocaine free fraction.

Blood Proteins↗
PubMed1987

Disposition of phenytoin in critically ill trauma patients.

Estimates of phenytoin pharmacokinetic variables and protein binding were determined in 10 adult critically ill trauma patients. Each study subject received phenytoin sodium as an intravenous loading dose of 15 mg/kg, followed by an initial intravenous maintenance dose of 6 mg/kg/day. Serial blood samples were obtained throughout the seven-day study period and analyzed for total and unbound serum phenytoin concentrations. The concentration data for each patients were fitted to a one-compartment model with elimination defined by the Michaelis-Menten constant Km and the maximum rate of metabolism (Vmax) and to a one-compartment model with first-order elimination. The Michaelis-Menten model used Bayesian parameter estimation while the linear model used weighted non-linear least-squares regression analysis. Unbound phenytoin fraction ranged from 0.073 to 0.25. Free fraction increased 7% to 108% in 9 of 10 patients (median increase 29%) from day 1 to day 7 of therapy. Variable estimates using the Michaelis-Menten model were as follows: volume of distribution, 0.76 +/- 0.15 L/kg (0.58-1.01 L/kg); Vmax, 568 +/- 197 mg/day (350-937 mg/day); and Km, 4.5 +/- 1.8 mg/L (1.8-6.2 mg/L). These estimates fell within the wide range of values obtained in studies using stable patients or healthy volunteers. The Michaelis-Menten model was significantly less biased and more precise than the linear model. Three of four patients who continued to receive their study maintenance dose had substantially lower measured total serum concentrations of phenytoin than predicted using the study variable estimates.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

The postoperative adverse effects of inhalational anesthetics.

Inhalational general anesthetics can contribute to postoperative morbidity (Table II). Postoperative effects of inhalational anesthetics on the central nervous system are speculative. The "toxic" effects of these agents during the postoperative period are most often an extension of their pharmacologic and physiochemical properties. Inhalational anesthetics may produce a number of varied changes in mental status after surgery such as headache, emergence excitement, and delirium. It is very important for health professionals to be aware of the risk of perioperative myocardial infarction in patients with preexisting heart disease if early detection and treatment are to occur. Relative to the common postoperative problems of atelectasis, pneumonia, and aspiration, inhalational agents may have a contributory role especially in patients with preexisting pulmonary disease. Postoperative nausea and vomiting are other common problems in which inhalational agents may have a role in their development. Although extensively investigated, suspected halothane hepatoxicity is a very rare complication if it exists at all. The renal effects of inhalational anesthetics are usually mild and transitory, although the use of methoxyflurane can produce direct nephrotoxicity. The evidence to support a clinically significant direct immunosuppressant effect of inhalational anesthetics after surgery is inconclusive. A concensus exists that any minor, short-lived effects are in all probability overshadowed by the nonspecific stress of surgery itself. By reducing this stress, anesthetics undoubtedly have a protective effect. There are probably no major mutagenic or carcinogenic effects of inhalational anesthetics under normal conditions. Inhalational anesthetics should be avoided during pregnancy because of their teratogenic potential and their effects on the uterus.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Inhalation↗
PubMed1984

The adult respiratory distress syndrome.

The adult respiratory distress syndrome (ARDS) is a common form of acute respiratory failure that has been increasingly reported as associated with a wide variety of medical conditions. Unlike other identifiable pathological events causing severe lung injury, it is now recognized that ARDS is not a single disease, but a complex interaction of pathophysiological events that result in diffuse injury to lung parenchyma. Only through a thorough understanding of ARDS pathophysiology, pathogenesis, and clinical course can medical intervention be instituted in a judicious and timely manner. This review article is intended to provide an overview of the suspected precipitating causes, discrete pathophysiologic changes, and monitorable clinical events associated with ARDS. With mortality from ARDS high, significant attention is being given to improving therapeutic intervention with such conventional measures as mechanical ventilation, positive end-expiratory pressure, and fluid management, along with corticosteroids and several new experimental pharmacologic approaches.

Adult↗