Fentanyl HCl iontophoretic transdermal system versus morphine IV-PCA for postoperative pain management: survey of healthcare provider opinion.

OBJECTIVE: This survey estimated differences in staff time requirements between fentanyl HCl iontophoretic transdermal system (fentanyl ITS) and intravenous patient-controlled analgesia (IV-PCA) in post-operative pain management. RESEARCH DESIGN AND METHODS: European Delphi panels of nurses and anaesthesiologists, who had practical experience with both fentanyl ITS and IV-PCA, were provided a task list, developed from a previous clinical trial, associated with each modality. The panellists were asked to estimate time spent on each task. Estimates were calculated by multiplying the estimated patient proportion for whom the task was performed by the expected frequency of task performance, by the estimated task time. RESULTS: Data is presented as mean minutes (standard deviation). Fentanyl ITS use was estimated to save an average of 68.7 min total staff time per patient per treatment period compared to IV-PCA (86.5 (20.3)) vs. 156.4 (55.2); respectively; p < 0.001), the largest amount of savings being in the 'Setup' category (19.4 (6.7) vs. 47.8 (17.5), respectively; p < 0.001), and mostly due to IV-PCA task elimination. Significant time savings were estimated using fentanyl ITS over IV-PCA in the 'Discontinuation' category (4.8 (2.4) vs. 20.6 (3.3), respectively; p < 0.001). Panellists agreed that fentanyl ITS use would decrease staff assistance time required for helping patients during self-care routines and it may also decrease the patient's time to ambulation. Survey limitations included: possible recall bias due to the observational nature of the data; task list descriptions resulting in possible double-counting of data; no sensitivity analyses; and the declarative nature of the responses possibly leading to a dilution of survey findings. CONCLUSIONS: Fentanyl ITS use was estimated, by expert opinion, to require 44% less staff time than IV-PCA use.

Determination of nutritional requirements in rats: variation with time of weight gain responses to indispensable amino acids.

The Saturation Kinetics Model (SKM) can be used to describe physiological responses as functions of a limiting dietary nutrient. Physiological responses also vary with time, and, by graphing each parameter of the SKM as a function of time, the model equation can be used to produce a three-dimensional response surface, allowing the investigator to predict requirement as a function of both dietary nutrient concentration and time. To test this hypothesis, rats were fed diets containing graded levels of indispensable amino acids (0-10 g/100 g). The inhibition form of the SKM was able to predict the complete response range of weight gain, food intake, weight-specific weight gain and weight-specific food intake for each amino acid on a day-by-day basis. With a complete response range established, nutrient requirements (defined as maximum responses) could be determined explicitly by the equation: Requirement = (K0.5.KS)0.5, where K0.5 and KS are parameters of the SKM. No arbitrary decisions (such as break points, slopes, percentages of maximum, etc.) were necessary to accomplish this. This approach allows one to set nutritional requirements and optimize responses in a dynamic system without causing inhibiting and/or toxic responses. In each case (valine, methionine, threonine and histidine), the dietary amino acid concentration required for maximal weight gain exceeded current NRC recommendations, which may be low because they fall in the more time-dependent portion of the response curve whereas maximum responses do not.

Histidine, histamine, and the neuroregulation of food intake: a review and hypothesis.

Feeding, a behavior regulated by the central nervous system (CNS), includes the acquisition of specific essential nutrients and the maintenance of energy balance. Modulation of feeding behavior is a normal part of survival, but certain pathological conditions interrupt or modify regulatory aspects of feeding, thereby leading to inappropriate intake. This review examines aspects of metabolism associated with the anorexia seen in animals suffering from protein-energy malnutrition (PEM). The main focus is the indispensable amino acid histidine (His), the biosynthetic precursor of the neurotransmitter histamine (HA). In kwashiorkor-like PEM, His is elevated in plasma and brain, whereas all other indispensable amino acids are decreased. The elevation of His in the brain is to concentrations five times normal. Because the rate of HA synthesis in the brain is a function of the His concentration, His elevation raises the possibility of a profound direct effect of CNS function. In children, PEM consistently produces the symptoms of depressed food intake, edema, growth failure, and psychomotor changes. One known central effect of HA is the stimulation of ACTH and corticosteroid release. Based on these observations, the hypothesis being examined is as follows: one component of the pathophysiological neuroregulation of food intake involved the His-induced variation of HA concentration in the hypothalamus and the subsequently altered neurochemical activity at the corticotropin-releasing factor (CRF) neurons o the paraventricular nucleus (PVN).

The determination of nutritional requirements in rats: mathematical modeling of sigmoidal, inhibited nutrient-response curves.

The Saturation Kinetics Model (SKM) is useful in describing many physiological responses as functions of a limiting dietary nutrient. However, as nutrients are fed at higher dietary concentrations, responses become inhibited and diminish from their usual plateaus. By adding an inhibition constant (Ks) to the SKM in a manner consistent with substrate inhibition (based on enzyme kinetics), it becomes possible to predict the inhibited portions of the nutrient-response curve. To test this, rats were fed diets of graded levels of casein (0-75%) or lysine (0-6.2%), and weight gains and food intakes were measured daily for up to 2 wk. The inhibition form of the SKM was able to predict the complete response range of each experiment, producing a Ks (weight gain) at a dietary level of 50.60% for casein and 7.56% for lysine. It was also possible to set up an upper and lower dietary nutrient concentration that encompassed the 100% response range for each response, thereby giving an inhibition or toxicity index of 2.02 for casein and 4.98 for lysine. This index allows one to set nutritional requirement levels precisely, optimizing responses without moving into inhibiting or toxic ranges of nutrients. Based on growth response curves, requirements were 25.61% for casein and 1.97% for lysine.

Brain histidine and food intake in rats fed diets deficient in single amino acids.

Histidine (His) is elevated in plasma and brain during protein deficiency as well as in several pathological conditions, leading to the possibility of a direct effect on central nervous system (CNS) function. In this study, groups of weanling rats were fed diets containing graded levels of casein or a single indispensable amino acid (IAA: Leu, Val, Ile, Phe, Trp, Thr, Met or Lys) in order to produce nutritionally-deficient states. Body weight gains and food intakes were recorded daily for 2 wk. Whole brain and serum samples were obtained and analyzed for amino acid (AA) content. All weight gain and food intake responses could be predicted by the Saturation Kinetics Model. The only consistent pattern observed in AA profiles which could be correlated with food intake was an increase in brain His concentrations. Limiting dietary casein or IAA elevated brain His above controls 2.5- and 1.5-fold, respectively. Food intake was generally depressed by 50% at brain His concentrations above 105 nmol/g. Since His is the precursor of the depressant neurotransmitter histamine (HA), systemic increases may be significant in that HA could be a possible cause of the anorexia observed in protein and IAA deficiency.

New method for formulation of amino acid concentrations and ratios in diets of rats.

Parameters derived from the application of the saturation kinetics model (SKM) to rat growth experiments were used to formulate a complete dietary amino acid mix for weanling rats. Dietary ratios and concentrations for indispensable amino acids (IAA) and arginine were calculated using the parameter K0.5. A curve shift technique was used to determine dietary concentrations for conditionally indispensable amino acids (CAA) and dispensable amino acids (DAA). The model was also used to determine a dietary ratio of (IAA + Arg)/(CAA + DAA). Using the dietary amino acid concentrations suggested by the model and an (IAA + Arg)/(CAA + DAA) ratio of 1, a growth response curve was constructed and compared to a similar curve using the amino acid mix of Rogers and Harper. The modeling approach produced a 10-15% improvement in growth over the Rogers and Harper mix. The SKM is discussed in terms of calculating an ideal nutrient ratio and choosing a desired response level. It is demonstrated that the model can rapidly produce accurate estimates for dietary amino acid levels, while minimizing required numbers of laboratory animals.

Prediction of brain and serum free amino acid profiles in rats fed graded levels of protein.

Daily weight gains and food intakes were measured in male, 120-g rats fed graded levels of dietary casein. After 14 d, serum and brain amino acid concentrations were measured. All physiological responses were tested for a functional relationship to dietary casein concentration. Food intake, weight gain and many serum amino acid profiles were shown to be saturable functions of percent casein in the diet. In general, essential amino acids increased in serum with increasing dietary casein concentration while nonessential amino acids decreased with increasing dietary casein concentration. Brain amino acid concentrations were shown to be linear functions of serum levels with the exceptions of phenylalanine and the acidic amino acids. Most amino acids showed a smaller range of values in brain than in serum. The exceptions were the levels of threonine, glutamine, serine and histidine, which were three times greater in brain than in serum. Brain levels of the neutral amino acids tryptophan and tyrosine were highly correlated with the amino acid/neutral amino acid ratios in serum, whereas leucine was negatively correlated. Brain histidine, which was inversely correlated with dietary casein, was found to correlate with specific food intake patterns. The four-parameter mathematical model for physiological responses was able to predict all the observed saturation type responses in the experiment.