Diuretic response to Ringer's solution is normal shortly after awakening from general anaesthesia: a retrospective kinetic analysis.

Background: The elimination of Ringer's solution is severely depressed during general anaesthesia, but the degree to which this continues postoperatively is poorly established. Methods: An intravenous infusion of Ringer's acetate solution 20 ml kg-1 was administered over 60 min in 12 patients undergoing laparoscopic cholecystectomy. Population kinetic analysis was performed based on repeated measurements of blood haemoglobin concentration and urinary excretion over 240 min regardless of when the operations were finished. The analysis contrasted the periods before and after awakening from general anaesthesia and compared them with data from 18 volunteers who received the same fluid at the same rate. Results: Patients were monitored for approximately 2 h after awakening from general anaesthesia. The rate constant for redistribution of fluid from the extravascular space to the plasma (k21) and the rate constant for urinary excretion (k10) were significantly higher postoperatively than during the surgical period. Computer simulations indicated that urinary excretion after surgery was almost restored to the rate found in the volunteers. In contrast, the redistribution of fluid from the extravascular space to the plasma, which was almost nil during the surgery, showed only limited recovery during the postoperative phase, and was only approximately 10% of the flow rate found in the volunteers. The combination of nearly normalised urinary excretion and lack of adequate return of distributed fluid to the plasma promoted postoperative hypovolaemia. Conclusion: The kinetic analysis indicates that plasma volume support should be given during the first 2 h after laparoscopic cholecystectomy.

Functionalizing Polystyrene with N-Alicyclic Piperidine-Based Cations via Friedel-Crafts Alkylation for Highly Alkali-Stable Anion-Exchange Membranes.

Different anion-exchange membranes (AEMs) based on polystyrene (PS)-carrying benzyltrimethyl ammonium cations are currently being developed for use in alkaline fuel cells and water electrolyzers. However, the stability in relation to these state-of-the-art cations needs to be further improved. Here, we introduce highly alkali-stable mono- and spirocyclic piperidine-based cations onto PS by first performing a superacid-mediated Friedel-Crafts alkylation using 2-(piperidine-4-yl)propane-2-ol. This is followed by quaternization of the piperidine rings either using iodomethane to produce N,N-dimethyl piperidinium cations or by cyclo-quaternizations using 1,5-dibromopentane and 1,4-dibromobutane, respectively, to obtain N-spirocyclic quaternary ammonium cations. Thus, it is possible to functionalize up to 27% of the styrene units with piperidine rings and subsequently achieve complete quaternization. The synthetic approach ensures that all of the sensitive ß-hydrogens of the cations are present in ring structures to provide high stability. AEMs based on these polymers show high alkaline stability and less than 5% ionic loss was observed by 1H NMR spectroscopy after 30 days in 2 M aq NaOH at 90 °C. AEMs functionalized with N,N-dimethyl piperidinium cations show higher stability than the ones carrying N-spirocyclic quaternary ammonium. Careful analysis of the latter revealed that the rings formed in the cyclo-quaternization are more prone to degrade via Hofmann elimination than the rings introduced in the Friedel-Crafts reaction. AEMs with an ion-exchange capacity of 1.5 mequiv g-1 reach a hydroxide conductivity of 106 mS cm-1 at 80 °C under fully hydrated conditions. The AEMs are further tuned and improved by blending with polybenzimidazole (PBI). For example, an AEM containing 2 wt % PBI shows reduced water uptake and much improved robustness during handling and reaches 71 mS cm-1 at 80 °C. The study demonstrates that the critical alkaline stability of PS-containing AEMs can be significantly enhanced by replacing the benchmark benzyltrimethyl ammonium cations with N-alicyclic piperidine-based cations.

N-Spirocyclic Quaternary Ammonium Ionenes for Anion-Exchange Membranes.

The development of cationic polymers for anion-exchange membranes (AEMs) with high alkaline stability and conductivity is a considerable challenge in materials chemistry. In response, we here present the synthesis and properties of N-spirocyclic quaternary ammonium ionenes (spiro-ionenes) containing 5- and 6-membered rings fused by central nitrogen cations. High-molecular weight and film-forming spiro-ionenes are successfully synthesized in cyclo-polycondensations of tetrakis(bromomethyl)benzene and dipiperidines under mild conditions. These polyelectrolytes show excellent thermal and alkaline stability with no degradation detected by NMR spectroscopy after more than 1800 h in 1 M KOD/D2O at 80 °C. Even at 120 °C, the spiro-ionenes display reasonable alkaline stability. Transparent and mechanically robust AEMs based on ionically cross-linked blends of spiro-ionene and polybenzimidazole reach OH- conductivities up to 0.12 S cm-1 at 90 °C. The current findings demonstrate that spiro-ionenes constitute a new class of alkali-stable anion-exchange polymers and membranes.

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.

Hypovolaemia after glucose/insulin infusions in volunteers.

High-dose intravenous infusion of 5% glucose promotes rebound hypoglycaemia and hypovolaemia in healthy volunteers. To study whether such effects occur in response to glucose/insulin, 12 healthy firemen (mean age, 39 years) received three infusions over 1-2 h that contained 20 ml of 2.5% glucose/kg of body weight, 5 ml of 10% glucose/kg of body weight with 0.05 unit of rapid-acting insulin/kg of body weight, and 4 ml of 50% glucose/kg of body weight with 1 unit of insulin/kg of body weight. The plasma glucose concentration and plasma dilution were compared at 5-10 min intervals over 4 h. Regardless of the amount of administered fluid and whether insulin was given, the plasma glucose concentration decreased to hypoglycaemic levels within 30 min of the infusion ending. The plasma dilution closely mirrored plasma glucose and became negative by approx. 5%, which indicates a reduction in the plasma volume. These alterations were only partially restored during the follow-up period. A linear relationship between plasma glucose and plasma dilution was most apparent when the infused glucose had been dissolved in only a small amount of fluid. For the strongest glucose/insulin solution, this linear relationship had a correlation coefficient of 0.77 (n=386, P<0.0001). The findings of the present study indicate that a redistribution of water due to the osmotic strength of the glucose is the chief mechanism accounting for the hypovolaemia. It is concluded that infusions of 2.5%, 10% and 50% glucose, with and without insulin, in well-trained men were consistently followed by long-standing hypoglycaemia and also by hypovolaemia, which averaged 5%. These results emphasize the relationship between metabolism and fluid balance.

Population volume kinetics predicts retention of 0.9% saline infused in awake and isoflurane-anesthetized volunteers.

BACKGROUND: In previous work, extravascular expansion was observed to be enhanced by isoflurane anesthesia in sheep when a crystalloid bolus was administered. The aim of the current study was to further elaborate these investigations to humans and to explore the use of population kinetics in the analysis of fluid shifts. METHODS: Eleven healthy volunteers participated in two experiments each, either awake or isoflurane anesthetized, during which they received 25 ml/kg saline, 0.9%, intravenously over 20 min. Plasma dilution data were derived from repeated sampling of hemoglobin concentration, and population pharmacokinetic analysis was conducted using the WinNonMix 2.0.1 software (Pharsight Corporation, Mountain View, CA). Plasma hormones were measured, and hemodynamic values were monitored. RESULTS: Fluid infusion during isoflurane anesthesia was followed by a higher cardiac output, lower arterial pressure, and lower urinary excretion as compared with the awake protocol (P < 0.05). Albumin dilution was greater than hemoglobin concentration-derived plasma dilution, which indicates a transcapillary leak of albumin. A two-compartment model with an isoflurane-depressed, intercompartmental distribution parameter predicted that more than 50% of the infused volume was retained in the peripheral compartment at 180 min in both protocols. Isoflurane markedly increased the plasma levels of renin and aldosterone, whereas vasopressin was mostly unchanged. CONCLUSION: Fluid retention after rapid infusion of 0.9% saline was prominent in both awake and isoflurane-anesthetized subjects. Altered kinetics of infused 0.9% saline during isoflurane anesthesia was expressed as reduced clearance and a slower distribution, resulting in a small but significant increase in fluid accumulation in the body fluid compartments. These changes may be due to the associated decreasing of mean arterial pressure and increased release of renin and aldosterone.

Intravascular fluid administration and hemodynamic performance during open abdominal surgery.

We studied whether central hemodynamics measured by a pulmonary artery catheter can serve as a pharmacodynamic expression of fluid therapy in 10 patients undergoing open abdominal surgery. We examined how closely hemodynamic variables follow plasma dilution, which is an index of plasma volume expansion, during and after an IV infusion of 25 mL/kg of lactated Ringer's solution over 45 min. Pulmonary artery wedge pressure and central venous pressure responded to IV fluid with an increase that correlated with accompanying plasma dilution. Six of 10 patients showed a decrease in cardiac output that was probably secondary to an increase in peripheral vascular resistance (nonresponders), whereas the rest increased cardiac output (responders). Volume kinetic analysis suggested that 54% of the infused fluid resided in the central fluid space at the end of the infusion and 25% at the end of the study in the responders compared with 25% and 3%, respectively, in nonresponders. In conclusion, half of the patients undergoing open abdominal surgery responded to crystalloid fluid with a decrease in cardiac output. Pulmonary artery wedge pressure and central venous pressure responded more consistently to different degrees of plasma dilution, which can be simulated for various fluid regimens using volume kinetics.

Optoacoustic monitoring of blood hemoglobin concentration: a pilot clinical study.

The optoacoustic technique is noninvasive, has high spatial resolution, and potentially can be used to measure the total hemoglobin concentration ([THb]) continuously and accurately. We performed in vitro measurements in blood and in vivo tests in healthy volunteers. Our clinical protocol included rapid infusion of intravenous saline to simulate rapid change in the [THb] during fluid therapy or surgery. Optoacoustic measurements were made from the wrist area overlying the radial artery for more than 1 h. The amplitude of the optoacoustic signal generated in the radial artery closely followed the [THb] measured directly in concurrently collected blood samples.

Sepsis produced by Pseudomonas bacteremia does not alter plasma volume expansion after 0.9% saline infusion in sheep.

Clinicians generally consider sepsis to be a state in which fluid is poorly retained within the vasculature and accumulates within the interstitium. We hypothesized that infusion of 0.9% saline in conscious, chronically instrumented sheep with hyperdynamic bacteremic sepsis would be associated with less plasma volume expansion (PVE) and greater interstitial fluid volume expansion than in conscious, nonseptic sheep. Six conscious adult sheep received an IV infusion of 25 mL/kg of 0.9% saline over 20 min (1.25 mL.kg(-1).min(-1)) in a control nonseptic state and during early and late sepsis (4 and 24 h, respectively, after initiation of a standard infusion of live Pseudomonas aeruginosa). The distribution and elimination of infused fluid were studied by mass balance (after measurement of plasma volume using Evans blue dye) and volume kinetic analysis. Mass balance demonstrated no significant differences in the time-course of PVE between control, early sepsis, and late sepsis. At the end of the infusions, which averaged 1050 +/- 125 mL in sheep weighing an average of 42 +/- 5 kg, calculated PVE was 312 +/- 50 mL, 386 +/- 34 mL, and 400 +/- 51, respectively. Volume kinetic analysis was similar in all three protocols. In both nonseptic and septic sheep, infusion of 0.9% saline resulted in similar peak PVE and resolution of PVE over a 3-h interval and similar kinetic parameters. Contrary to clinical impressions and to our hypothesis, the distribution of 0.9% saline in this animal model was not changed by bacteremia produced by infusion of Pseudomonas aeruginosa.

The volume kinetics of acetated Ringer's solution during laparoscopic cholecystectomy.

We studied the distribution and elimination of an IV infusion of 20 mL/kg of acetated Ringer's solution (approximately 1500 mL) over 60 min in 12 women undergoing laparoscopic cholecystectomy. A plasma dilution of 4.2% developed during the induction of general anesthesia, even though fluid was withheld. The additional plasma dilution induced by the subsequent volume expansion was slightly larger than expected from previous volunteer experiments and averaged 18%. The diuretic response to intravascular fluid administration was small, and only 20% of the infused fluid had been excreted 4 h later. Volume kinetic analysis showed that the IV fluid expanded a central body fluid space by 3.2 L. The clearance constants for distribution and elimination averaged 115 mL/min and 6.8 mL/min, respectively. These data represent a half-life of the fluid in the patients that is 17 times longer (median, 4.5 h) than the half-life of the plasma dilution (16 min), indicating a strong tendency to the formation of peripheral edema. A nomogram based on the kinetic variables suggests that infusion rates should be relatively rapid early on during surgery but slower later. This strategy creates a constant plasma dilution at any desired level without causing undue peripheral accumulation of fluid.

Low melatonin excretion during mechanical ventilation in the intensive care unit.

Biochemical markers for the circadian rhythm were studied in patients treated at the ICU (intensive care unit) of two regional hospitals. A normal rhythm is characterized by a relatively higher melatonin and a lower cortisol excretion at night. Disturbances affect sleep, mood and cognitive performance. All urine excreted between 07:00 and 22:00 hours (day) and between 22:00 and 07:00 hours (night) was collected and sampled throughout the entire ICU period (median, 10 days) in 16 patients for the excretion of 6-SMT (6-sulphatoxymelatonin), which is a metabolite of melatonin, and free cortisol. The overall excretion of 6-SMT was slightly lower and the cortisol excretion higher than reported for healthy reference populations. Mechanical ventilation was associated with a markedly lower 6-SMT excretion (median, 198 ng/h) compared with periods without such help (555 ng/h; P<0.0001), whereas infusion of adrenergic drugs increased the 6-SMT excretion (P<0.01). Five patients (31%) showed a virtually absent melatonin excretion for 24 h or more. The diurnal rhythms were consistently or periodically disturbed in 65% and 75% of the patients. These alterations cannot be explained by excessive exposure to light at night. In conclusion, there was hyposecretion of melatonin during mechanical ventilation, an overall high cortisol excretion and a disturbed diurnal rhythm of both of these hormones in most patients treated in two ICU departments.