Richard D. Leff

Influence of infusion pump operation and flow rate on hemodynamic stability during epinephrine infusion

ObjectiveTo determine whether variations in the flow rate of epinephrine solutions administered via commonly available infusion pumps lead to significant variations in blood pressure (BP) in vivo. DesignProspective, randomized, crossover study with factorial design, using infusion pumps with four different operating mechanisms (pulsatile diaphragm, linear piston/syringe, cyclic piston-valve, and linear peristaltic) and three drug delivery rates (1, 5, and 10 mL/hr). SubjectsTwo healthy, mixed-breed dogs (12 to 16 kg). InterventionsDogs were made hypotensive with methohexital bolus and continuous infusion. BP was restored to normal with constantdose epinephrine infusion via two pumps at each rate. MeasurementsFemoral mean arterial pressure (MAP) was recorded every 10 secs. Pumpflow continuity was quantitated in vitro using a digital gravimetric technique. Variations in MAP and flow continuity were expressed by the coefficient of variation; analysis of variance was used for comparisons. ResultsThe mean coefficients of variations for MAP varied from 3.8 ± 3.1% (linear piston/syringe) to 6.1 ± 6.6% (linear peristaltic), and from 3.4 ± 2.2% (10 mL/hr) to 7.9 ± 6.6% (1 mL/hr). The coefficients of variation for in vitro flow continuity ranged from 9 ± 8% (linear pistonsyringe) to 250 ± 162% (pulsatile diaphragm), and from 35 ± 44% (10 mL/hr) to 138 ± 196% (1 mL/hr). Both the type of pump and infusion rate significantly (p < .001) influenced variation in drug delivery rate. The 1 mL/hr infusion rate significantly (p < .01) influenced MAP variation. Cyclic fluctuations in MAP of ≤30 mm Hg were observed using the pulsatile diaphragm pump at 1 mL/hr. ConclusionFactors inherent in the operating mechanisms of infusion pumps may result in clinically important hemodynamic fluctuations when administering a concentrated short-acting vasoactive medication at slow infusion rates. (Crit Care Med 1993; 21:1213–1217)

Methods for intravenous drug administration in the pediatric patient

Variation in the rate of iv drug delivery to the patient occurs secondary to influences of the site selected for injection of the drug into the iv system, the rate of flow of the iv solution, and the drug dosage volume. The involvement of each of these factors in producing varying rates of iv drug infusion is virtually assured by the wide range of drug dosage volumes and iv fluid rates required within the pediatric population. Because of the importance of delivering medications at a known rate, a uniform protocol for iv drug therapy was developed for pediatric patients and implemented at the university of Iowa Hospitals and Clinics. The protocol, which utilizes either a syringe infusion pump or manual retrograde injection technique, has been shown to be a practical, safe, dependable, and effective means to deliver both iv fluids and medications at a desired or known rate.

Influence of infusion pumps on the pharmacologic response to nitroprusside.

ObjectiveTo compare the relationship between variability in nitroprusside delivery from five infusion pumps and the resulting variability in mean arterial pressure (MAP). DesignRandomized, crossover study design. SettingA pediatric ICU in a university hospital. PatientsInformed parental consent was obtained for six patients who were hemodynamically stable and receiving a continuous nitroprusside infusion for a clinical application. Subjects ranged in age from 11 months to 9 yr. InterventionsAll of the subjects were administered nitroprusside using selected infusion pumps, which included Abbott (Micro), 3M/AVI (210), IMED (965), IVAC (565), and Kendall McGraw (MicroRate). Measurements and Main ResultsAfter an initial equilibration interval for each device, MAP was measured and recorded at 10-sec intervals for ≥90-min intervals using a computerized data collection technique. Variation in nitroprusside administration (flow continuity) for each infusion pump was determined in vitro using a computerized gravimetric technique. Variation in both MAP and flow continuity was mathematically expressed as the coefficient of variance (CV) of the measured values for each of the respective infusion pumps. For the Abbott, IMED, 3M/AVI, IVAC, and Kendall McGaw infusion pumps, mean ± SD continuity CV values were 85 ± 31%, 39 ± 26%, 19 ± 8%, 17 ± 3%, and 12 ± 3%, respectively, and MAP CV values were 18 ± 21%, 15 ± 11%, 8 ± 2%, and 16 ± 10%, respectively. ConclusionAn apparent direct relationship between MAP variability and flow continuity was observed. We speculate that variation in effect of potent short-acting drugs may, in part, be due to infusion pump operation. (Crit Care Med 1991; 19:98)

Flow rate variability from electronic infusion devices

During continuous drug administration to pediatric patients, unfavorable pharmacologic effects have occurred. These effects were attributed to variations in flow from electronic infusion devices (EIDs). The intent of this investigation was to evaluate the influence of microrate (0.1 to 99.9 ml/h) EID on the accuracy, continuity, and pattern of flow of continuously effused fluid. Using a factorial study design, iv fluid was effused through iv delivery systems using combinations of five microrate EIDs, three iv flow rates, and three sample-collection intervals. Serial weights were measured at the appropriate sample-collection time using a computerized gravimetric technique to determine accuracy, continuity, and pattern of flow. All the EIDs produced accurate flow within 5% of the desired rate of 5 and 10 ml/h. At 1 ml/h, the actual iv flow rate ranged from 65.1% to 91% of the desired rate. Each of the respective EIDs produced various levels of flow continuity; each flow pattern characterized the mechanism of pump operation for each device. Thus, alteration in response (e.g., increased toxicity or decreased efficacy) to a continuous drug infusion must not be attributed exclusively to the drug or clinical condition of the patient. Serious consideration should also be given to the method of drug delivery and, in particular, the continuity of flow that results from a particular EID.

Phenytoin metabolism in infants following intravenous and oral administration

The disposition of phenytoin was examined in 7 infants with a mean age of 22 days and a mean weight of 3,756 g. Multiple doses of phenytoin were administered intravenously and/or orally as a part of required medical care. Gas chromatography/mass spectrometry was employed for analyses of phenytoin and three metabolites - 5-(4-hydroxyphenyl)-5-phenylhydantoin, methylated 3,4-catechol, and 3,4-dihydrodiol - in blood, urine, and feces. Data from identical studies previously conducted in adults were utilized for comparison with the infants. The mean phenytoin dose (+/- SD) in infants was 8.1 +/- 4.4 mg/kg/day, and the mean serum concentration (+/- SD) was 4.8 +/- 4.6 micrograms/ml. In adults, the mean dose was 5.3 +/- 0.6 mg/kg/day, and the mean serum concentration was 12.0 +/- 1.9 micrograms/ml. No significant differences were found between infants and adults in the pattern of urinary metabolites or in the total recovery of phenytoin and metabolites in 24-hour urine samples. These results indicate that pathways for phenytoin metabolism are the same in infants and adults. Absorption of an oral dose of phenytoin in infants appeared to be completely based on recoveries of drug and metabolites in urine and on the fact that less than 3% of an oral dose could be found in stools. The results of these studies indicate that the low blood concentrations of phenytoin resulting from the relatively high daily dosage of phenytoin in infants, when compared to adults, cannot be explained on the basis of poor oral absorption of phenytoin. These age-related differences must be due to a relatively high metabolic clearance of the drug in infants.

Decreased flow accuracy from volumetric infusion pumps.

Accurate flow from infusion pumps should be maintained when exposed to a variety of clinical conditions. The intent of this study was to evaluate in vitro flow rate accuracy of three infusion pumps subjected to the influences of variable back-pressure, solution viscosity, and infusion rates. A factorial study design was selected to determine the influence of three flow rates (5, 10, and 20 ml/h), three back-pressures (100, 200, and 300 mm Hg), and two solution viscosities (5%, 25% dextrose in water) on flow rate accuracy from three infusion pumps (Abbott 4P, IVAC 560, and Travenol 6200) using a standard gravimetric technique. Mean +/- SD accuracy values were -9.4 +/- 6.4% (range -29.1 to -0.7), 0.5 +/- 2.2% (range -4.2 to 6.3), and -0.5 +/- 4.7% (range -8.5 to 9.9) of the desired rate for the Abbott, IVAC, and Travenol devices, respectively. Back-pressure was the only factor to influence significantly flow accuracy for the Abbott device (r = .81). All factors significantly influenced accuracy for the Travenol device (r = .55). No factor influenced accuracy for the IVAC infusion pump. Both the IVAC 560 and Travenol 6200 have acceptable flow accuracy values within the range of study factors examined. The Abbott 4P had significant decreases in flow accuracy in response to increasing back-pressure.

Influence of physical characteristics of intravenous systems on drug delivery

The influence of multiple intravenous system factors on the time required to deliver a drug dose was evaluated in vitro using a factorial study design. The study factors included (1) 5 intraluminal tubing diameters, (2) 2 intravenous tubing positions, (3) 2 intravenous infusion rates, and (4) 2 intravenous tubing lengths. For each intravenous system that represented the respective combination of study factors, a 1-ml dose of 14C-labeled potassium penicillin G was administered and the effusate was collected over time. A liquid scintillation technique was used to quantitate the amount of drug delivered. In-line pressures that resulted from the experimental conditions were measured in order to examine for correlations between in-line pressure and alterations in drug delivery time. Analysis of variance and stepwise procedures were used to determine significance of these factors on drug delivery time. It was determined that complex fluid dynamics resulting from the combined influences of tubing diameter, tubing length and infusion rate appears to have a significant influence on drug delivery time. It is important to use efficient intravenous systems for intravenous therapy in order to predict and control intravenous drug delivery.

Flow rate variability from selected syringe and mobile infusion pumps

Alterations in response to pharmacological agents have been attributed to flow rate variation produced by intravenous infusion devices during drug delivery. A wide range of variation has been shown to occur with large-volume infusion devices. The intent of this investigation was to examine flow variation resulting from the use of selected small-volume syringe and mobile infusion devices and determine whether these devices have greater flow continuity than large-volume infusion pumps. Each syringe and mobile infusion device delivered iv fluid at three flow rates (1, 5, and 10 ml/h). The effusate was collected in a tared beaker and serial weights were measured every ten seconds using a computerized, gravimetric technique. Accuracy, continuity, and pattern of flow were determined for each of the syringe and mobile infusion devices. All of the devices produced accurate flow, within ± 10 percent of the desired 5 and 10 ml/h rates. However, the actual iv flow rate ranged from 53 to 93 percent for the 1 ml/h rate. Continuity and pattern of flow resulting from each device were diverse. When compared with large-volume, microrate infusion devices, no significant differences could be observed. Therefore, no clear advantage to delivering drug solutions on a continuous basis can be expected from the use of small-volume devices. Specific infusion devices may be preferable for certain clinical applications; flow continuity data may be valuable when selecting an infusion device.

Results of the First Double Blind Placebo (Pl) Controlled Study of Caffeine Citrate (Cc) for the Treatment of Apnea of Prematurity (Aop) † 1001

Results of the First Double Blind Placebo (Pl) Controlled Study of Caffeine Citrate (Cc) for the Treatment of Apnea of Prematurity (Aop) † 1001

Simplified gentamicin dosing in neonates: a time-and cost-efficient approach

A nomogram-based method for monitoring gentamicin therapy in neonates was developed and evaluated prospectively. Gentamicin dosage adjustment, based on analysis of a single blood sample collected between 8 and 12 hours after dose administration, resulted in satisfactory serum levels in 79% of the neonates. When compared to dosage adjustment methods requiring multiple blood samples, the nomogram method is a cost-effective and time-efficient technique for screening the appropriateness of gentamicin dosages in neonates.