Acute fluid shifts influence the assessment of serum vitamin D status in critically ill patients

Introduction Recent reports have highlighted the prevalence of vitamin D deficiency and suggested an association with excess mortality in critically ill patients. Serum vitamin D concentrations in these studies were measured following resuscitation. It is unclear whether aggressive fluid resuscitation independently influences serum vitamin D. Methods Nineteen patients undergoing cardiopulmonary bypass were studied. Serum 25(OH)D3, 1α,25(OH)2D3, parathyroid hormone, C-reactive protein (CRP), and ionised calcium were measured at five defined timepoints: T1 - baseline, T2 - 5 minutes after onset of cardiopulmonary bypass (CPB) (time of maximal fluid effect), T3 - on return to the intensive care unit, T4 - 24 hrs after surgery and T5 - 5 days after surgery. Linear mixed models were used to compare measures at T2-T5 with baseline measures. Results Acute fluid loading resulted in a 35% reduction in 25(OH)D3 (59 ± 16 to 38 ± 14 nmol/L, P < 0.0001) and a 45% reduction in 1α,25(OH)2D3 (99 ± 40 to 54 ± 22 pmol/L P < 0.0001) and i(Ca) (P < 0.01), with elevation in parathyroid hormone (P < 0.0001). Serum 25(OH)D3 returned to baseline only at T5 while 1α,25(OH)2D3 demonstrated an overshoot above baseline at T5 (P < 0.0001). There was a delayed rise in CRP at T4 and T5; this was not associated with a reduction in vitamin D levels at these time points. Conclusions Hemodilution significantly lowers serum 25(OH)D3 and 1α,25(OH)2D3, which may take up to 24 hours to resolve. Moreover, delayed overshoot of 1α,25(OH)2D3 needs consideration. We urge caution in interpreting serum vitamin D in critically ill patients in the context of major resuscitation, and would advocate repeating the measurement once the effects of the resuscitation have abated.

Fluid shifts have no influence on ciprofloxacin pharmacokinetics in intensive care patients with intra-abdominal sepsis

This study aimed to investigate whether fluid shifts alter ciprofloxacin pharmacokinetics in critically ill patients over time. Patients >= 18 years, with normal renal function, requiring intensive care treatment and parenteral antibiotics were enrolled. Group A (22 patients) included patients with documented intra-abdominal infections. Group B (18 patients) included patients with severe sepsis from other causes. All patients received intravenous ciprofloxacin 400 mg every 8 h infused over 60 min. Eight timed blood specimens were taken on days 0, 2 and 7. Ciprofloxacin plasma concentrations were determined using high performance liquid chromatography. There were no significant differences between the pharmacokinetics of the two groups or over time. Ciprofloxacin pharmacokinetics in critically ill patients do not change over time, and intra-abdominal sepsis does not alter ciprofloxacin pharmacokinetic parameters to a greater degree than sepsis from other causes in critically ill patients. (c) 2005 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Obstructive Sleep Apnea Severity and Overnight Body Fluid Shift before and after Hemodialysis.

BACKGROUND AND OBJECTIVES: Obstructive sleep apnea is associated with significantly increased cardiovascular morbidity and mortality. Fluid overload may promote obstructive sleep apnea in patients with ESRD through an overnight fluid shift from the legs to the neck soft tissues. Body fluid shift and severity of obstructive sleep apnea before and after hemodialysis were compared in patients with ESRD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Seventeen patients with hemodialysis and moderate to severe obstructive sleep apnea were included. Polysomnographies were performed the night before and after hemodialysis to assess obstructive sleep apnea, and bioimpedance was used to measure fluid overload and leg fluid volume. RESULTS: The mean overnight rostral fluid shift was 1.27±0.41 L prehemodialysis; it correlated positively with fluid overload volume (r=0.39; P=0.02) and was significantly lower posthemodialysis (0.78±0.38 L; P<0.001). There was no significant difference in the mean obstructive apnea-hypopnea index before and after hemodialysis (46.8±22.0 versus 42.1±18.6 per hour; P=0.21), but obstructive apnea-hypopnea index was significantly lower posthemodialysis (-10.1±10.8 per hour) in the group of 12 patients, with a concomitant reduction of fluid overload compared with participants without change in fluid overload (obstructive apnea-hypopnea index +8.2±16.1 per hour; P<0.01). A lower fluid overload after hemodialysis was significantly correlated (r=0.49; P=0.04) with a lower obstructive apnea-hypopnea index. Fluid overload-assessed by bioimpedance-was the best predictor of the change in obstructive apnea-hypopnea index observed after hemodialysis (standardized r=-0.68; P=0.01) in multivariate regression analysis. CONCLUSIONS: Fluid overload influences overnight rostral fluid shift and obstructive sleep apnea severity in patients with ESRD undergoing intermittent hemodialysis. Although no benefit of hemodialysis on obstructive sleep apnea severity was observed in the whole group, the change in obstructive apnea-hypopnea index was significantly correlated with the change in fluid overload after hemodialysis. Moreover, the subgroup with lower fluid overload posthemodialysis showed a significantly lower obstructive sleep apnea severity, which provides a strong incentive to further study whether optimizing fluid status in patients with obstructive sleep apnea and ESRD will improve the obstructive apnea-hypopnea index.

Influence of posture and frequency modes in total body water estimation using bioelectrical impedance spectroscopy in boys and adult males

The aim of the study was to examine differences in total body water (TBW) measured using single-frequency (SF) and multi-frequency (MF) modes of bioelectrical impedance spectroscopy (BIS) in children and adults measured in different postures using the deuterium (2H) dilution technique as the reference. Twenty-three boys and 26 adult males underwent assessment of TBW using the dilution technique and BIS measured in supine and standing positions using two frequencies of the SF mode (50 kHz and 100 kHz) and the MF mode. While TBW estimated from the MF mode was comparable, extra-cellular fluid (ECF) and intra-cellular fluid (ICF) values differed significantly (p < 0.01) between the different postures in both groups. In addition, while estimated TBW in adult males using the MF mode was significantly (p < 0.01) greater than the result from the dilution technique, TBW estimated using the SF mode and prediction equation was significantly (p < 0.01) lower in boys. Measurement posture may not affect estimation of TBW in boys and adult males, however, body fluid shifts may still occur. In addition, technical factors, including selection of prediction equation, may be important when TBW is estimated from measured impedance.

Alkalosis increases muscle K+ release, but lowers plasma [K+] and delays fatigue during dynamic forearm exercise

Alkalosis enhances human exercise performance, and reduces K⁺ loss in contracting rat muscle. We investigated alkalosis effects on K⁺ regulation, ionic regulation and fatigue during intense exercise in nine untrained volunteers. Concentric finger flexions were conducted at 75% peak work rate (-3 W) until fatigue, under alkalosis (Alk, NaHCO₃, 0.3 g kg⁻¹) and control (Con, CaCO₃) conditions, 1 month apart in a randomised, double-blind, crossover design. Deep antecubital venous (v) and radial arterial (a) blood was drawn at rest, during exercise and recovery, to determine arterio-venous differences for electrolytes, fluid shifts, acid–base and gas exchange. Finger flexion exercise barely perturbed arterial plasma ions and acid–base status, but induced marked arterio-venous changes. Alk elevated [HCO₃⁻] and P^CO2, and lowered [H+] (P < 0.05). Time to fatigue increased substantially during Alk (25 ± 8%, P < 0.05), whilst both [K⁺]_a and [K⁺]_v were reduced (P < 0.01) and [K⁺]_a-v during exercise tended to be greater (P= 0.056, n= 8). Muscle K⁺ efflux at fatigue was greater in Alk (21.2 ± 7.6 µmol min⁻¹, 32 ± 7%, P < 0.05, n= 6), but peak K⁺ uptake rate was elevated during recovery (15 ± 7%, P < 0.05) suggesting increased muscle Na⁺,K^+-ATPase activity. Alk induced greater [Na⁺]_a, [Cl⁻]_v, muscle Cl⁻ influx and muscle lactate concentration ([Lac⁻]) efflux during exercise and recovery (P < 0.05). The lower circulating [K⁺] and greater muscle K⁺ uptake, Na⁺ delivery and Cl⁻ uptake with Alk, are all consistent with preservation of membrane excitability during exercise. This suggests that lesser exercise-induced membrane depolarization may be an important mechanism underlying enhanced exercise performance with Alk. Thus Alk was associated with improved regulation of K⁺, Na⁺, Cl⁻ and Lac⁻.

Spontaneous peristaltic airway contractions propel lung liquid through the bronchial tree of intact and fetal lung explants

Spontaneous contractions of the fetal airways are a well recognized but poorly characterized phenomenon. In the present study spontaneous narrowing of the airways was analyzed in freshly isolated lungs from early to late gestation in fetal pigs and rabbits and in cultured fetal mouse lungs. Propagating waves of contraction traveling proximal to distal were observed in fresh lungs throughout gestation which displaced the lung liquid along the lumen. In the pseudoglandular and canalicular stages (fetal pigs) the frequency ranged from 2.3 to 3.3 contractions/min with a 39 to 46% maximum reduction of lumen diameter. In the saccular stage (rabbit) the frequency was 10 to 12/min with a narrowing of approximately 30%. In the organ cultures the waves of narrowing started at the trachea in whole lungs, or at the main bronchus in lobes (5.2 +/- 1.5 contractions/min, 22 +/- 8% reduction of lumen diameter), and as they proceeded distally along the epithelial tubes the luminal liquid was shifted toward the terminal tubules, which expanded the endbuds. As the tubules relaxed the flow of liquid was reversed. Thus the behavior of airway smooth muscle in the fetal lung is phasic in type (like gastrointestinal muscle) in contrast to that in postnatal lung, where it is tonic. An intraluminal positive pressure of 2.33 +/- 0.77 cm H(2)O was recorded in rabbit fetal trachea. It is proposed that the active tone of the smooth muscle maintains the positive intraluminal pressure and acts as a stimulus to lung growth via the force exerted across the airway wall and adjacent parenchyma. The expansion of the compliant endbuds by the fluid shifts at the airway tip may promote their growth into the surrounding mesenchyme.

Antibacterial dosing in intensive care: Pharmacokinetics, degree of disease and pharmacodynamics of sepsis

Treatment of sepsis remains a significant challenge with persisting high mortality and morbidity. Early and appropriate antibacterial therapy remains an important intervention for such patients. To optimise antibacterial therapy, the clinician must possess knowledge of the pharmacokinetic and pharmacodynamic properties of commonly used antibacterials and how these parameters may be affected by the constellation of pathophysiological changes occurring during sepsis. Sepsis, and the treatment thereof, increases renal preload and, via capillary permeability, leads to 'third-spacing', both resulting in higher antibacterial clearances. Alternatively, sepsis can induce multiple organ dysfunction, including renal and/or hepatic dysfunction, causing a decrease in antibacterial clearance. Aminoglycosides are concentration-dependent antibacterials and they display an increased volume of distribution (V-d) in sepsis, resulting in decreased peak serum concentrations. Reduced clearance from renal dysfunction would increase the likelihood of toxicity. Individualised dosing using extended interval dosing, which maximises the peak serum drug concentration (C-max)/minimum inhibitory concentration ratio is recommended. beta-Lactams and carbapenems are time-dependent antibacterials. An increase in Vd and renal clearance will require increased dosing or administration by continuous infusion. If renal impairment occurs a corresponding dose reduction may be required. Vancomycin displays predominantly time-dependent pharmacodynamic properties and probably requires higher than conventionally recommended doses because of an increased V-d and clearance during sepsis without organ dysfunction. However, optimal dosing regimens remain unresolved. The poor penetration of vancomycin into solid organs may require alternative therapies when sepsis involves solid organs (e.g. lung). Ciprofloxacin displays largely concentration-dependent kill characteristics, but also exerts some time-dependent effects. The V-d of ciprofloxacin is not altered with fluid shifts or over time, and thus no alterations of standard doses are required unless renal dysfunction occurs. In order to optimise antibacterial regimens in patients with sepsis, the pathophysiological effects of systemic inflammatory response syndrome need consideration, in conjunction with knowledge of the different kill characteristics of the various antibacterial classes. In conclusion, certain antibacterials can have a very high V-d, therefore leading to a low C-max and if a high peak is needed, then this would lead to underdosing. The Vd of certain antibacterials, namely aminoglycosides and vancomycin, changes over time, which means dosing may need to be altered over time. Some patients with serum creatinine values within the normal range can have very high drug clearances, thereby producing low serum drug levels and again leading to underdosing. Copyright © 2010 Elsevier Inc. All rights reserved.

Turbomachinery computational fluid dynamics: asymptotes and paradigm shifts.

This paper reviews the development of computational fluid dynamics (CFD) specifically for turbomachinery simulations and with a particular focus on application to problems with complex geometry. The review is structured by considering this development as a series of paradigm shifts, followed by asymptotes. The original S1-S2 blade-blade-throughflow model is briefly described, followed by the development of two-dimensional then three-dimensional blade-blade analysis. This in turn evolved from inviscid to viscous analysis and then from steady to unsteady flow simulations. This development trajectory led over a surprisingly small number of years to an accepted approach-a 'CFD orthodoxy'. A very important current area of intense interest and activity in turbomachinery simulation is in accounting for real geometry effects, not just in the secondary air and turbine cooling systems but also associated with the primary path. The requirements here are threefold: capturing and representing these geometries in a computer model; making rapid design changes to these complex geometries; and managing the very large associated computational models on PC clusters. Accordingly, the challenges in the application of the current CFD orthodoxy to complex geometries are described in some detail. The main aim of this paper is to argue that the current CFD orthodoxy is on a new asymptote and is not in fact suited for application to complex geometries and that a paradigm shift must be sought. In particular, the new paradigm must be geometry centric and inherently parallel without serial bottlenecks. The main contribution of this paper is to describe such a potential paradigm shift, inspired by the animation industry, based on a fundamental shift in perspective from explicit to implicit geometry and then illustrate this with a number of applications to turbomachinery.

Rapid biogeographical plankton shifts in the North Atlantic Ocean

Large-scale biogeographical changes in the biodiversity of a key zooplankton group (calanoid copepods) were detected in the north-eastern part of the North Atlantic Ocean and its adjacent seas over the period 1960–1999. These findings provided key empirical evidence for climate change impacts on marine ecosystems at the regional to oceanic scale. Since 1999, global temperatures have continued to rise in the region. Here, we extend the analysis to the period 1958–2005 using all calanoid copepod species assemblages (nine species assemblages based on an analysis including a total of 108 calanoid species or taxa) and show that this phenomenon has been reinforced in all regions. Our study reveals that the biodiversity of calanoid copepods are responding quickly to sea surface temperature (SST) rise by moving geographically northward at a rapid rate up to about 23.16 km yr−1. Our analysis suggests that nearly half of the increase in sea temperature in the northeast Atlantic and adjacent seas is related to global temperature rises (46.35% of the total variance of temperature) while changes in both natural modes of atmospheric and oceanic circulation explain 26.45% of the total variance of temperature. Although some SST isotherms have moved northwards by an average rate of up to 21.75 km yr−1 (e.g. the North Sea), their movement cannot fully quantify all species assemblage shifts. Furthermore, the observed rates of biogeographical movements are far greater than those observed in the terrestrial realm. Here, we discuss the processes that may explain such a discrepancy and suggest that the differences are mainly explained by the fluid nature of the pelagic domain, the life cycle of the zooplankton and the lesser anthropogenic influence (e.g. exploitation, habitat fragmentation) on these organisms. We also hypothesize that despite changes in the path and intensity of the oceanic currents that may modify quickly and greatly pelagic zooplankton species, these organisms may reflect better the current impact of climate warming on ecosystems as terrestrial organisms are likely to significantly lag the current impact of climate change.

The effect of prescribed fluid consumption on physiology and work behavior of wildfire fighters

The purpose of this study was to examine 1) wildfire fighters' ability to consume the prescribed fluid volume (1200 mL h-1), 2) the effect of fluid intake on plasma sodium and hydration, and 3) the effect of fluid intake on firefighters' heart rate, core temperature and activity during emergency suppression shifts. Methods: Thirty-four firefighters were divided into ad libitum (AD, n = 17) and prescribed (PR, n = 17) drinking groups. Results: PR drinkers did not meet the prescribed fluid target, yet consumed over double the volume of AD drinkers. No differences between groups in plasma sodium or hydration were noted. PR drinking resulted in lower core temperature between 2 and 6 h. This did not coincide with reduced cardiovascular strain, greater work activity or larger distances covered when compared to AD drinkers. Conclusion: Extra fluid consumption (above AD) did not improve firefighter activity or physiological function (though PR firefighters core temperature was lower earlier in their shift). Firefighter can self-regulate their fluid consumption behavior and work rate to leave the fireground euhydrated.

Fluid intake, hydration, work physiology of wildfire fighters working in the heat over consecutive days

PURPOSE: (i) To evaluate firefighters' pre- and post-shift hydration status across two shifts of wildfire suppression work in hot weather conditions. (ii) To document firefighters' fluid intake during and between two shifts of wildfire suppression work. (iii) To compare firefighters' heart rate, activity, rating of perceived exertion (RPE), and core temperature across the two consecutive shifts of wildfire suppression work. METHOD: Across two consecutive days, 12 salaried firefighters' hydration status was measured immediately pre- and post-shift. Hydration status was also measured 2h post-shift. RPE was also measured immediately post-shift on each day. Work activity, heart rate, and core temperature were logged continuously during each shift. Ten firefighters also manually recorded their food and fluid intake before, during, and after both fireground shifts. RESULTS: Firefighters were not euhydrated at all measurement points on Day one (292±1 mOsm l(-1)) and euhydrated across these same time points on Day two (289±0.5 mOsm l(-1)). Fluid consumption following firefighters' shift on Day one (1792±1134ml) trended (P = 0.08) higher than Day two (1108±1142ml). Daily total fluid intake was not different (P = 0.27), averaging 6443±1941ml across both days. Core temperature and the time spent ≥ 70%HRmax were both elevated on Day one (when firefighters were not euhydrated). Firefighters' work activity profile was not different between both days of work. CONCLUSION: There was no difference in firefighters' pre- to post-shift hydration within each shift, suggesting ad libitum drinking was at least sufficient to maintain pre-shift hydration status, even in hot conditions. Firefighters' relative hypohydration on Day one (despite a slightly lower ambient temperature) may have been associated with elevations in core temperature, more time in the higher heart rate zones, and 'post-shift' RPE.

Proteome analysis of human plasma and amniotic fluid by Off-Gel isoelectric focusing followed by nano-LC-MS/MS

This paper presents a comparative proteomic analysis of human maternal plasma and amniotic fluid (AF) samples from the same patient at term of pregnancy in order to find specific AF proteins as markers of premature rupture of membranes, a complication frequently observed during pregnancy. Maternal plasma and the corresponding AF were immunodepleted in order to remove the six most abundant proteins before the systematic analysis of their protein composition. The protein samples were then fractionated by IEF Off-Gel electrophoresis (OGE), digested and analyzed with nano-LC-MS/MS separation, revealing a total of 73 and 69 proteins identified in maternal plasma and AF samples, respectively. The proteins identified in AF have been compared to those identified in the mother plasma as well as to the reference human plasma protein list reported by Anderson et al. (Mol. Cell. Proteomics 2004, 3, 311-326). This comparison showed that 26 proteins were exclusively present in AF and not in plasma among which 10 have already been described to be placenta or pregnancy specific. As a further validation of the method, plasma proteins fractionated by OGE and analysed by nano-LC-MS/MS have been compared to the Swiss 2-D PAGE reference map by reconstructing a map that matches 2-D gel and OGE experimental data. This representation shows that 36 of 49 reference proteins could be identified in both data sets, and that isoform shifts in pI are well conserved in the OGE data sets.

Effect of the pulse trajectory on ultrasonic fluid velocity measurement

In a general situation a non-uniform velocity field gives rise to a shift of the otherwise straight acoustic pulse trajectory between the transmitter and receiver transducers of a sonic anemometer. The aim of this paper is to determine the effects of trajectory shifts on the velocity as measured by the sonic anemometer. This determination has been accomplished by developing a mathematical model of the measuring process carried out by sonic anemometers; a model which includes the non-straight trajectory effect. The problem is solved by small perturbation techniques, based on the relevant small parameter of the problem, the Mach number of the reference flow, M. As part of the solution, a general analytical expression for the deviations of the computed measured speed from the nominal speed has been obtained. The correction terms of both the transit time and of the measured speed are of M 2 order in rotational velocity field. The method has been applied to three simple, paradigmatic flows: one-directional horizontal and vertical shear flows, and mixed with a uniform horizontal flow.