The use of a noninvasive hemoglobin monitor for determining fluid distribution and elimination in pediatric patients undergoing minor surgery.

In pediatric fluid therapy it would be preferable to describe distribution and elimination a fluid bolus based on repetitive hemoglobin (Hb) according to kinetic principles. Pulse CO-Oximetry is a recent advancement in patient monitoring that allows for the continuous noninvasive measurement of Hb (SpHb). The aim of this study was to describe the distribution and elimination of hydroxyethylstarch (HES) 130/0.4 in combination with crystalloids using a noninvasive Hb monitor in two cohorts of young children undergoing minor surgeries under general anesthesia. Two cohorts, 16 children aged 1-3 years and 12 aged 4-6 years, were investigated during anesthesia and minor surgical procedures. They were given a maintenance solution of lactated Ringer's and a fluid bolus of HES 130/0.4, 6 mL/kg over a period of 20 min. The whole procedure lasted 120 min, and SpHb values were measured every 10 min. The SpHb values were used to calculate plasma dilution, net volume, and mean residence time (MRT) of the infused fluid. A total of 377 measured SpHbs generated individual dilution plots that showed variability, particularly for the older cohort. Distribution and elimination rates of the infused fluid were calculated. Mean dilution plots were generated. There were no significant differences in dilution, net volume or MRT between groups. A non invasive Hb analyzer could be used to calculate fluid distribution. The variability in the data can probably be explained by reactions to anesthetic drugs, variability in measurement technique, variability in generating the complex capillary signals, and individual variability in baseline fluid status. The latter finding is important because this is a prerequisite for perioperative fluid planning for each individual.

The use of a noninvasive hemoglobin monitor for volume kinetic analysis in an emergency room setting.

BACKGROUND: Distribution and clearance of an infused bolus can be studied by repetitive sampling of invasive total hemoglobin (tHb) using volume kinetic equations. Pulse CO-oximetry, a recent advancement in patient monitoring that allows for the continuous and noninvasive estimation of hemoglobin concentration (SpHb), would greatly facilitate the scientific and clinical use of the volume kinetic parameters. In the present study, we examined whether serial measurements of SpHb in an emergency room setting can be used to calculate distribution volume (V) and clearance (Cl) rate of an infused bolus. METHODS: This was a prospective, observational study of patients in 2 age groups admitted for various reasons to the emergency room of a tertiary care center. IV catheters were placed in both arms of the subjects to induce plasma volume expansion by infusion of a buffered crystalloid glucose solution and for withdrawing venous blood samples for analysis of tHb at 0, 5, 10, 15, 30, 45, 60, 75, and 90 minutes after start of infusion. During these interventions, subjects were simultaneously monitored by pulse CO-oximetry for measurement of SpHb (Masimo Radical-7, Rev E ReSposable Sensor). Bias, precision, and limits of agreement were calculated in Bland-Altman plots to compare the accuracy of SpHb with invasive tHb measurements. Using volume kinetic (pharmacokinetics for fluids) equations, V and Cl were determined. RESULTS: Thirty patients (14 from the young group with a mean age of 30 years, and 16 from the geriatric group with mean age of 84 years) were enrolled in the study. When all data were included, this yielded 242 data pairs with a bias of -0.47 (95% confidence interval, -0.62 to -0.32) between SpHb and tHb. However, 5 patients were omitted because of low quality signals, leaving 193 hemoglobin data pairs for further analysis. Bias was then -0.24 (95% confidence interval, -0.39 to -0.09). The biases show that the device on average slightly underestimates tHb values. The precision of SpHb decreases when the low signal quality indicator is present. For the 27 subjects for whom the V and Cl were calculated, there were no significant differences in the estimation of the distribution volumes using either tHb or SpHb values. Clearance constants were also estimated, but with less accuracy. CONCLUSIONS: Our data show that SpHb by pulse CO-oximetry may be used to calculate volume of distribution in an emergency room setting.

Hypoproteinemia does not alter plasma volume expansion in response to a 0.9% saline bolus in awake sheep.

OBJECTIVE: To test the hypothesis that hypoproteinemia reduces plasma volume expansion produced by a bolus of crystalloid solution given to awake sheep. DESIGN: Prospective and observational. SETTING: Laboratory. SUBJECTS: Five female merino sheep (n = 5) weighing 37 ± 3 kg were anesthetized. INTERVENTIONS: Each animal was subjected to a 5-day test period: day 1: 50 mL/min 0.9% saline infusion over 20 mins. Days 2-4: daily plasmapheresis and replacement of the shed plasma with 6 L of 0.9% saline were performed in increments. MEASUREMENTS AND MAIN RESULTS: Fractional plasma volume expansion after rapid infusion of saline on days 1 and 5 was calculated from changes in hemoglobin concentration. There was a significant reduction in total plasma protein concentration after plasmapheresis (p < .05). Colloid osmotic pressures were also significantly lowered (p < .05). A crystalloid infusion of 0.9% saline did not alter any of these values compared with baseline. The hemodynamic measurements did not show significant differences between the experiments. The plasma volume expansion reached approximately 20% at the end of infusion and stayed at 10-15% during the experiments. No difference was found in plasma volume expansion produced by a bolus of 50 mL/min of 0.9% in the hypoproteinemic state when compared with the euproteinemic state (p = .61). No difference in cumulative urinary output was found between the two states. CONCLUSIONS: In contrast to our hypothesis, severe acute hypoproteinemia does not reduce plasma volume expansion in response to 50 mL/min 0.9% saline infusion in nonspleenectomized sheep when compared with the resultant plasma volume expansion after a 50 mL/min of 0.9% infusion in the euproteinemic state.

Arteriovenous differences in plasma dilution and the distribution kinetics of lactated ringer's solution.

BACKGROUND: Conventional concept suggests that infused crystalloid fluid is first distributed in the plasma volume and then, since the capillary permeability for fluid is very high, almost instantly equilibrates with the extracellular fluid space. We challenge whether this view is consistent with findings based on volume kinetic analysis. METHODS: Fifteen volunteers received an IV infusion of 15 mL/kg of lactated Ringer's solution during 10 min. Simultaneous arterial and venous blood hemoglobin (Hgb) samples were obtained and Hgb concentrations measured. The arteriovenous (AV) difference in Hgb dilution in the forearm was determined and a volume kinetic model was fitted to the series of Hgb concentrations in arterial and venous blood. RESULTS: The AV difference in plasma dilution was only positive during the infusion and for 2.5 min thereafter, which represents the period of net flow of fluid from plasma to tissue. Kinetic analysis showed that volume expansion of the peripheral fluid space began to decrease 14 min (arterial blood) and 20 min (venous blood) after the infusion ended. Distribution of lactated Ringer's solution apparently occurs much faster in the forearm than in the body as a whole. Therefore, the AV difference in the arm does not accurately reflect the distribution of Ringer's solutions or whole-body changes in plasma volume. CONCLUSIONS: The relatively slow whole-body distribution of lactated Ringer's solution, which boosts the plasma volume expansion during and for up to 30 min after an infusion, is probably governed by a joint effect of capillary permeability and differences in tissue perfusion between body regions.

Isoflurane inhibits compensatory intravascular volume expansion after hemorrhage in sheep.

After hemorrhage, blood volume is partially restored by transcapillary refill, a process of spontaneous compensatory intravascular volume expansion that we hypothesized would be inhibited by anesthesia. Six chronically instrumented sheep were subjected to four randomly ordered experiments while conscious or during anesthesia with isoflurane. After plasma volume measurement (indocyanine green), 15% or 45% of the blood volume was withdrawn. To quantify transcapillary refill, mass balance and kinetic calculations utilized repeated measurements of hemoglobin concentration, assuming that transcapillary refill would dilute hemoglobin concentration. After 15% hemorrhage, mean arterial blood pressure remained stable in both conscious and isoflurane-anesthetized sheep (normotensive hemorrhage) but decreased after 45% hemorrhage (hypotensive hemorrhage). After either normotensive or hypotensive hemorrhage, transcapillary refill occurred more rapidly during the first 40 min than during the next 140 min (P < 0.001). In conscious sheep, at 180 min, 57% and 42% of the bled volume had been restored after normotensive and hypotensive hemorrhage, respectively, in contrast to only 13% and 27% (P < 0.001) in isoflurane-anesthetized sheep. A novel kinetic model implicated hemodynamic factors in rapid, early transcapillary refill and decreased plasma oncotic pressure in subsequent slower filling. We conclude that isoflurane inhibits transcapillary refill after both normotensive and hypotensive hemorrhage in sheep.

The maintenance and monitoring of perioperative blood volume.

The assessment and maintenance of perioperative blood volume is important because fluid therapy is a routine part of intraoperative care. In the past, patients undergoing major surgery were given large amounts of fluids because health-care providers were concerned about preoperative dehydration and intraoperative losses to a third space. In the last decade it has become clear that fluid therapy has to be more individualized. Because the exact determination of blood volume is not clinically possible at every timepoint, there have been different approaches to assess fluid requirements, such as goal-directed protocols guided by invasive and less invasive devices.This article focuses on laboratory volume determination, capillary dynamics, aspects of different fluids and how to clinically assess and monitor perioperative blood volume.

Modelling of peripheral fluid accumulation after a crystalloid bolus in female volunteers - a mathematical study.

OBJECTIVE: To simultaneously model plasma dilution and urinary output in female volunteers. METHODS: Ten healthy female non-pregnant volunteers, aged 21-39 years (mean 29), with a bodyweight of 58-67 kg (mean 62.5 kg) participated. No oral fluid or food was allowed between midnight and completion of the experiment. The protocol included an infusion of acetated Ringer's solution, 25 ml/kg over 30 min. Blood samples (4 ml) were taken every 5 min during the first 120 min, and thereafter the sampling rate was every 10 min until the end of the experiment at 240 min. A standard bladder catheter connected to a drip counter to monitor urine excretion continuously was used. The data were analysed by empirical calculations as well as by a mathematical model. RESULTS: Maximum urinary output rate was found to be 19 (13-31) ml/min. The subjects were likely to accumulate three times as much of the infused fluid peripherally as centrally; 1/µ = 2.7 (2.0-5.7). Elimination efficacy, E(eff), was 24 (5-35), and the basal elimination k(b) was 1.11 (0.28-2.90). The total time delay T(tot) of urinary output was estimated as 17 (11-31) min. CONCLUSION: The experimental results showed a large variability in spite of a homogenous volunteer group. It was possible to compute the infusion amount, plasma dilution and simultaneous urinary output for each consecutive time point and thereby the empirical peripheral fluid accumulation. The variability between individuals may be explained by differences in tissue and hormonal responses to fluid boluses, which needs to be further explored.

Pharmacokinetic aspects of fluid therapy.

Peri-operative fluid therapy continues to be an exercise in empiricism, with nagging questions about efficacy and complications. Pharmacokinetics is used for studying the time dependency of administered drugs. Volume kinetics is a pharmacokinetic approach describing the peak effects and clearance of intravenously infused fluids. It clarifies the absorption, distribution, metabolism and excretion of an intravenous fluid bolus. This could possibly allow for more rational design of intravenous fluid paradigms to improve clinical fluid therapy. This chapter briefly summarizes currently accepted principles of fluid therapy, discusses the general approach to kinetic analysis of fluid therapy, reviews currently available data defining kinetic responses to fluid therapy, and speculates about future applications of this approach.