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Biomedical subjects

D F Driscoll

Publications and source records attributed to D F Driscoll.

At least 19 recordsLinked to original sources
PubMed1992

Tumor and host response to arginine and branched chain amino acid-enriched total parenteral nutrition. A study involving Walker 256 carcinosarcoma-bearing rats.

The metabolic effects of total parenteral nutrition (TPN) solutions containing different profiles of individual amino acids were investigated in the rats bearing Walker 256 carcinosarcoma. The rats were subcutaneously inoculated with 10(7) tumor cells and 6 days later were continuously infused intravenously for 8 days with three different TPN solutions. The experimental and control solutions were composed of high concentrations of branched chain amino acids (BCAA) and arginine (high Arg + BCAA TPN), high concentrations of BCAA (high BCAA TPN) and regular amino acids (regular TPN), respectively, and were isonitrogenous, isocaloric, and isovolemic. Rats receiving subcutaneous injection of saline rather than tumor cells received high Arg + BCAA TPN as pair-fed controls. The flooding dose method of 14C-leucine was used for the analysis of protein synthesis. With the feeding of high Arg + BCAA TPN, the tumor-bearing rats revealed a smaller increase of tumor volume and lower tumor fractional rates of growth (Kg) and synthesis (Ks) as well as protein synthesis (PS), compared with the high BCAA TPN and regular TPN in tumor-bearing rats. There were no significant differences of Ks and PS in liver and muscle between TPN groups, whereas tumor-bearing rats infused with high Arg + BCAA TPN displayed higher levels of whole-body Ks and PS than other TPN groups in tumor-bearing rats and pair-fed nontumorous rats. Except for liver RNA content which showed a lower level in tumor-bearing rats with high Arg + BCAA TPN, no other differences of DNA and RNA contents were found in tumor, liver, and muscle of the different TPN groups. The current results indicate that individual amino acids can influence tumor growth and protein metabolism, and that arginine, in combination with BCAA, may reduce tumor growth through a reduction in protein synthesis.

Amino Acids, Branched-Chain↗
PubMed1991

Parenteral nutrient admixtures as drug vehicles: theory and practice in the critical care setting.

Parenteral nutrient (PN) admixtures are the most complex, extemporaneously compounded formulations routinely prepared for hospitalized and home-based patients. In addition, drugs are added with increasing frequency to PN admixtures, thus presenting even greater physicochemical challenges to this highly complex pharmaceutical product. The continuous infusion of selected drugs may provide pharmacokinetic and therapeutic advantages over conventional, intermittent, bolus methods of administration. Fluid conservation, cost savings, and a possible decrease in the risk of infection through reduced catheter manipulation and simplification of therapy provide additional incentives to consider the use of PN admixtures. The many advantages of PN admixtures make them an attractive approach to cost-effective care, with special clinical benefits achieved in the critical care setting. This article reviews our clinical experience using PN admixtures as drug vehicles for selected drugs and presents some theoretical as well as actual benefits associated with this practice.

Aminophylline↗
PubMed1990

Postoperative fluid overload: not a benign problem.

The incidence and consequences of fluid overload in the surgical ICU (SICU) have not been well defined, but may influence length of stay, days requiring mechanical ventilation, and mortality. Forty-eight consecutive patients admitted to our SICU were prospectively monitored for acute changes in weight and its impact on clinical management and outcome. When defined as a gain greater than 10% from their preoperative or premorbid weight (or an approximately 20% increase in total body water), 40% of patients had fluid overload. Patients were divided into three groups: those who had gained less than or equal to 10%, those with a weight gain between 11% and 20%, and those with greater than 20% increase in weight. Significant differences were found with respect to vasopressor dependence, colloid administration, and mortality. When indexed by initial Acute Physiology and Chronic Health Evaluation (APACHE II) mortality prediction scores, all groups had similar degrees of illness. On average, presumably due to volume limitations, patients were inadequately nourished during 85% of their SICU stay. Our results suggest that the morbidity of fluid overload can be significant, and warrants a fresh look at the methods of intraoperative fluid resuscitation.

Adult↗
PubMed1990

Clinical issues regarding the use of total nutrient admixtures.

The introduction of total nutrient admixtures (TNAs) has offered several clinical advantages. Substituting a portion of the daily dextrose calories with lipids may reduce the incidence of carbohydrate-associated complications (e.g., disturbances in glucose control and immune function). In addition, providing intravenous lipids continuously over 24 hours as a TNA appears to be better utilized by the liver and less likely to interfere with reticuloendothelial system function when compared with conventionally administered, discontinuous lipid infusions. If the peripheral vein is used as a route for parenteral nutrition, the addition of fat to the admixture provides the advantage of enhancing caloric density, while contributing significantly less tonicity than dextrose. Certain pharmaceutical and microbiological issues need to be considered to ensure the intravenous administration of a safe and homogenous dispersion. Attention to established guidelines provided by the lipid manufacturers, as well as careful extrapolation of TNA stability data, will avert the dangers associated with infusion of coalesced lipid particles. This article reviews the evidence supporting the use of lipids as daily caloric sources, with particular emphasis on the role of the total nutrient admixtures as the primary vehicle for administration.

Chemistry, Pharmaceutical↗
PubMed1990

Total parenteral nutrition 1990. A review of its current status in hospitalised patients, and the need for patient-specific feeding.

The decision to initiate total parenteral nutrition (TPN) in hospitalised patients should be based on the presence of clinically significant starvation and dysfunction of the gastrointestinal tract. It must also take into account the clinical status of the patient, considering major treatment strategies and the need for prolonged hospitalisation, the benefits of feeding and the attendant risks of central venous alimentation. Recent evidence in surgical patients in intensive care provides the impetus for early parenteral feeding; withholding TPN and inducing a cumulative caloric deficit of greater than or equal to 10,000 calories has been associated with a survival disadvantage compared to those patients with a positive caloric balance. Moreover, the incidence of serious organ failure was consistently higher in the group with cumulative caloric deficits. Additional evidence favouring the provision of TPN exists, but the axiom 'if the gut works, use it' still prevails. Exceptions to this precept do exist, however, particularly in critically ill patients. The metabolic derangements encountered in these patients could be so severe that it may be impossible to correct the electrolyte and acid-base abnormalities via the enteral route. For example, such patients may have large potassium requirements and/or severe alkalaemia necessitating systemic acidification with hydrochloric acid, precluding enteral delivery due to gastrointestinal intolerance. In this setting, combined enteral feeding with 10 to 20 ml/h to maintain gut integrity (via a post-pyloric feeding tube) and TPN during the acute phases of illness is an exciting possibility. Once the decision to feed is made, the amount of nutrition prescribed may assume equal importance with respect to patient outcome. The frequent use of the Harris-Benedict equation, plus a multiplying factor for stress, may overestimate caloric requirements; this is particularly true during critical illness. The dangers of overfeeding may be just as harmful as not feeding at all. The use of indirect calorimetry provides the most accurate measurement of resting energy expenditure. However, in the absence of indirect calorimetry, modified equations to estimate caloric needs are available. Caution must be observed as caloric intakes exceeding the range of 25 to 35 kcal/kg may be dangerous, particularly in the severely ill patient with preexisting organ failure. The amount of protein and the 'calorie-mix' necessary for optimal nutritional support is open to debate. Recent evidence has demonstrated no additional benefit to nitrogen balance in severely septic patients when protein was given at a level exceeding 1.5 g/kg/day.(ABSTRACT TRUNCATED AT 400 WORDS)

Critical Care↗
PubMed1989

Drug-induced metabolic disorders and parenteral nutrition in the intensive care unit: a pharmaceutical and metabolic perspective.

Since its inception, the field of parenteral nutrition has continued to evolve requiring the expertise of several health care disciplines. This feature has made nutrition support unique among clinical subspecialties. As a member of this team, the pharmacist plays a critical role in the provision of sterile admixtures, compatible nutritional formulations, and cost-effective, therapeutically equivalent strategies. The pharmacist has become more involved in the clinical care of the patient, with particular emphasis on the development of drug-induced metabolic disorders. The multitude of drugs prescribed to hospitalized patients increases the potential for serious metabolic disturbances. This is especially true in the critical care setting where sudden changes in metabolism (e.g., acid-base homeostasis, fluid and electrolyte balance) may result in profoundly negative effects. The critical care setting also represents the most sensitive period of hospitalization where even subtle changes in metabolic homeostasis may assume major clinical significance. Early recognition of offending agents and the institution of appropriate intervention may avert serious iatrogenic diseases. The nutrition support team is in a unique position to address many such disorders through selective manipulation of the various components in the parenteral nutrient admixture. The ability of the pharmacist to recognize the development of drug-induced metabolic disorders lends further support for clinical pharmacy in nutrition support services.

Enteral Nutrition↗
PubMed1987

Development of metabolic alkalosis after massive transfusion during orthotopic liver transplantation.

Five patients undergoing orthotopic liver transplantation were investigated for changes in acid-base homeostasis secondary to large volume transfusions. All patients developed a transient acidemia during the operative period, followed by alkalemia which persisted into the early postoperative period. The patients received an estimated mean of 750 mEq of citrate, which appeared to cause metabolic alkalosis. The biochemical basis underlying the regulation of citrate metabolism that may have led to the timing, extent, and duration of the subsequent metabolic alkalosis is presented. Finally, the time course for the development of metabolic alkalosis may be a potentially sensitive indicator of early allograft function.

Acid-Base Imbalance↗
PubMed1987

Clinical issues in the therapeutic monitoring of total parenteral nutrition.

The provision of total parenteral nutrition involves the participation of several health profession disciplines. Each specialty makes significant contributions toward the safe and efficacious delivery of this complex therapy. Recognition of the need for a multidisciplinary approach assists in the successful management of the hospitalized patient requiring total parenteral nutrition.

Carbohydrates↗
PubMed1987

Infusion phlebitis associated with a programmable syringe-pump system versus gravity-feed minibottles.

The occurrence of infusion phlebitis in patients receiving intravenous antibiotics via a gravity-feed minibottle system versus a new syringe-pump system was compared. Patients at least 18 years old who had indwelling intermittent injection sites inserted for medication administration were randomized to either the minibottle system or the syringe-pump system. Antibiotics in minibottles were diluted in 50-100 mL of 5% dextrose injection; in the syringe-pump group, aminoglycoside antibiotics were diluted in 0.9% sodium chloride injection and all other antibiotics were diluted in sterile water for injection. Antibiotics were not piggybacked into running primary infusions in any of the study patients, and no other medications except for 0.9% sodium chloride flushes were administered through the catheters. All catheters were inserted in peripheral veins and evaluated for phlebitis by i.v. nurse specialists using standardized criteria. Catheters were changed upon the occurrence of grade 1 phlebitis or after a period of three days without the development of phlebitis. Over an 18-week period, 85 catheter sites (53 syringe-pump group versus 32 minibottle group) were evaluated in 30 patients (14 syringe-pump group versus 16 minibottle group). The mean +/- S.D. catheter life in both groups was 50.6 +/- 20 hours. Phlebitis occurred in 62% of syringe-group sites versus 66% of minibottle-group sites; the incidence and severity of phlebitis were not significantly different between groups. The majority of catheter sites were infused with cefazolin sodium. The potential for phlebitis using the syringe-pump system in this study appears to be similar to that of the gravity-feed minibottle system when appropriate diluents, diluent volumes, and infusion rates are used.

Adult↗
PubMed1986

Practical considerations regarding the use of total nutrient admixtures.

The biological concerns, proper storage and administration, and advantages of using total nutrient admixtures (TNAs) for nutritional support are reviewed. In 1983, FDA approved lipid emulsions for administration with dextrose and selected crystalline amino acid preparations (known as three-in-one or total nutrient admixtures). The stability of TNAs is affected by pH, order of mixing, and temperature. Conflicting results have been reported on the issue of microbial growth potential in TNAs. At room temperature, the delivery of the TNA infusate should not exceed 24 hours. Plastic containers that do not contain diethylhexyl phthalate, in sizes up to 3 L, are practical and safe for administration of TNAs. The efficiency of an institution's volumetric pumps should be evaluated before converting to a TNA system because the low final concentrations of lipid emulsion present in the admixtures may render certain pumps inoperable. The practical, nutritional, and potential economic benefits of a TNA delivery system support its use. Further research is needed to determine microbial growth potential, electrolyte and drug compatibilities, and stability under prolonged storage of these admixtures.

Drug Compounding↗
PubMedDate not supplied

Parenteral nutrition in patients with diabetes mellitus: theoretical and practical considerations.

It is estimated that there are 11 million diabetics in the United States. Increasing recognition of the importance of nutrition in clinical medicine coupled with the frequent hospitalizations of the diabetic patient has heightened interest in their nutritional therapy. Patients with diabetes mellitus exhibit many abnormalities in the regulation of carbohydrate metabolism which may be accentuated during illness as part of the metabolic response to injury. An understanding of the effect of injury/illness, parenteral nutrition, and diabetes mellitus on carbohydrate metabolism is essential for the development of a rational approach to the initiation and maintenance of nutritional support in the diabetic patient.

Carbohydrate Metabolism↗
PubMedDate not supplied

Special considerations required for the formulation and administration of total parenteral nutrition therapy in the elderly patient.

Providing total parenteral nutrition (TPN) to hospitalised patients is not a benign procedure and can be associated with appreciable risks including the development of septic, mechanical and/or metabolic complications. In the older patient, the risks are heightened due to the effects of aging on vital organ function, as well as on the body's ability to respond to injury and infection. In addition, the existence of co-morbid disease will increase the rate of complications. The design of nutritional regimens must account for the changes in body composition and function with age in order to reduce the risks of nutrition-related complications. As a consequence of the reduction in lean body mass and organ function, coupled with the need to mobilise endogenous protein during acute metabolic stress, it is prudent to provide protein intakes of 1.5 g/kg/day, similar to amounts given to younger adult populations. In contrast, the caloric intake should be reduced by as much as 30% from amounts given younger adults of equivalent height and weight in order to avoid the dangers of overfeeding. Single-fuel systems may be better choices in those with acute cardiovascular disease, as glucose is a preferred fuel in this setting, whereas a mixed-fuel system will generally allow improved glucose homeostasis in the diabetic patient. Once TPN is instituted, metabolic management may be as important as nutritional support. Critical illness is associated with a variety of electrolyte disorders which are often accentuated by concurrent drug therapy and pre-existing co-morbid disease. The older patient is often less able to withstand abrupt changes in metabolic homeostasis. These points underscore the importance of the careful application of TPN therapy in the older patient.

Aged↗