Distribution of crystalloid fluid infused during onset of anesthesia-induced hypotension: a retrospective population kinetic analysis

Background Induction of anesthesia causes a drop in arterial pressure that might change the kinetics of infused crystalloid fluid. The aim of this report is to provide a mathematical view of how fluid distributes in this setting. Methods Data were retrieved from three studies where 76 patients (mean age 63 years, mean body weight 66 kg) had received approximately 1.1 L of Ringer’s solution over 60 min by intravenous infusion before and during induction of spinal, epidural, or general anesthesia. A population kinetic model was used to analyze the fluid distribution and its relationship to individual-specific factors. Frequent measurements of blood hemoglobin and the urinary excretion served as dependent variables. Results Before anesthesia induction, distribution to the extravascular space was threefold faster than elimination by urinary excretion. Both distribution and elimination of infused fluid were retarded in an exponential fashion due to the anesthesia-induced decrease in the mean arterial pressure (MAP). A decrease in MAP from 110 to 60 mmHg reduced the rate of distribution by 75% and the rate of elimination by 90%. These adaptations cause most of the infused fluid to remain in the bloodstream. Age, gender, type of anesthesia, and the use of ephedrine had no statistically significant effect on plasma volume expansion, apart from their possible influence on MAP. Conclusion The decrease in MAP that accompanies anesthesia induction depresses the blood hemoglobin concentration by inhibiting both the distribution and elimination of infused crystalloid fluid. The report provides mathematical information about the degree of these changes.

Isotonic saline causes greater volume overload than electrolyte-free irrigating fluids

Objectives Systemic absorption of the irrigating fluid used to flush the operating site is a potentially serious complication in several types of endoscopic operations. To increase safety, many surgeons have changed from a monopolar to a bipolar resection technique because 0.9% saline can then be used instead of electrolyte-free fluid for irrigation. The present study examines whether the tendency for excessive plasma volume expansion is greater with saline than with electrolyte-free fluid. Methods Pooled data were analyzed from four studies in which a mean of 1.25 L of either 0.9% saline or an electrolyte-free irrigating fluid containing glycine, mannitol, and sorbitol was given by intravenous infusion on 80 occasions to male volunteers and patients scheduled for transurethral prostatic surgery. The distribution of the infused fluid was analyzed with a population volume kinetic model based on frequently measured hemodilution and the urinary excretion. Results Electrolyte-free fluid distributed almost twice as fast and was excreted four times faster than 0.9% saline. The distribution half-life was 6.5 and 10.6 min for the electrolyte-free fluid and saline, respectively, and the elimination half-lives (by urinary excretion) from the plasma volume were 21 and 87 min. Simulation showed that the plasma volume expansion was twice as great from 0.9% saline than from electrolyte-free fluid. Conclusions Isotonic (0.9%) saline expands the plasma volume by twice as much as occurs with electrolyte-free irrigating fluids. This difference might explain why signs of cardiovascular overload are the most commonly observed adverse effects when saline is absorbed during endoscopic surgery.

Abstract P160: C1q/TNF-related Protein 1 Induces Obesity-related Hypertension In Mice Via Renal Na+ Retention In The Proximal Tubules

A recently identified adipokine C1q/TNF-related protein 1 (CTRP1) displayed a potent beneficial effect in managing metabolic disorders during type 2 diabetes and obesity. However, little is known about a potential role of CTRP1 in regulation of renal function and blood pressure (BP) in the context of obesity. Therefore, the present study aimed to determine the effect of a recombinant CTRP1 protein (termed CTRP1-His) on blood pressure in mice with diet-induced obesity (DIO). 8-mo-old male C57/B6 mice were fed a high-fat diet (60 Kcal% fat) for eight weeks and were infused with vehicle or CTRP1-His (10 ng/min/kg) via subcutaneously implanted osmotic minipump for the last seven days. BP parameters were recorded using telemetry devices. Consistent with other groups’ studies, mice infused with CTRP1-His exhibited remarkably improved multiple metabolic parameters, including hyperglycemia and hyperinsulinemia. Compared to the vehicle group, BP responses to CTRP1-His treatment developed a modest but significant increase in BP (MAP on day 7 [mmHg]: 122.3 ± 2.2 vs. 109 ± 1.73, n = 3 per each group, p < 0.01) accompanied with decreased hematocrit (Hct [%]: 43.8 ± 1.3 vs. 49 ± 1.2 %, p < 0.05), an index of plasma volume expansion. The DIO mice infused with CTRP1-His demonstrated a reduced urinary sodium excretion (U Na /Creatinine [mmol/mg]: 0.17 ± 0.04 vs. 0.27 ± 0.06, p = 0.07). By immunoblotting CTRP1-His infusion induced significant upregulation of renal abundances of p-NHE3, V2R, and AQP2 but suppressed obesity-induced renal abundances of p-NCC/NCC, p-NKCC2/NKCC2, and cleaved α-ENaC protein. Interestingly, CTRP1-His infusion tends to decrease albuminuria (urine albumin/Creatinine [mg/g]: 78.8 ± 7.7 vs. 120.5 ± 14, p = 0.07) in the DIO mice. Overall, our results indicated that CTRP1-His exerted a pressor effect in DIO mice via stimulating sodium-water retention through activation of NHE3 and AQP2 associated with compensatory attenuation of Na+ transporters in the distal nephron.

One-year change in plasma volume and mortality in the Japanese general population: An observational cohort study

Background Changes in plasma volume, a marker of plasma volume expansion and contraction, are gaining attention in the field of cardiovascular disease because of its role in the prevention and management of heart failure. However, it remains unknown whether a 1-year change in plasma volume is a risk factor for all-cause, cardiovascular, and non-cardiovascular mortality in the general population. Methods and results We used a nationwide database of 134,291 subjects (age 40–75 years) who participated in the annual “Specific Health Check and Guidance in Japan” check-up for 2 consecutive years between 2008 and 2011. A 1-year change in plasm volume was calculated using the Strauss–Davis-Rosenbaum formula. There were 220 cardiovascular deaths, 1,001 non-cardiovascular deaths including 718 cancer deaths, and 1,221 all-cause deaths during the follow-up period of 3.9 years. All subjects were divided into quintiles based on the 1-year change in plasma volume. Kaplan–Meier analysis demonstrated that the highest 5th quintile had the greatest risk among the five groups. Multivariate Cox proportional hazard regression analysis demonstrated that a 1-year change in plasma volume was an independent risk factor for all-cause, cardiovascular, non-cardiovascular, and cancer deaths. The addition of a 1-year change in plasma volume to cardiovascular risk factors significantly improved the C-statistic, net reclassification, and integrated discrimination indexes. Conclusions Here, we have demonstrated for the first time that a 1-year change in plasma volume could be an additional risk factor for all-cause, cardiovascular, and non-cardiovascular (mainly cancer) mortality in the general population.

Distribution of Crystalloid Fluid Infused During Onset of Anesthesia-Induced Hypotension: A Retrospective Population Kinetic Analysis

Background. Loading with crystalloid fluid before induction of anesthesia is widely practiced but cannot reduce the accompanying drop in arterial pressure. The aim of this report is to provide a mathematical view of how fluid distributes in this setting.Methods. Data were retrieved from three studies where 76 patients (mean age 63 years, mean body weight 66 kg) had received approximately 1.1 L of Ringer’s solution over 60 min by intravenous infusion before and during induction of spinal, epidural, or general anesthesia. A population kinetic model was used to analyze the fluid distribution and its relationship to individual-specific factors. Frequent measurements of blood hemoglobin and the urinary excretion served as dependent variables.Results. Before anesthesia induction, distribution to the extravascular space was 3-fold faster than elimination by urinary excretion. Both distribution and elimination of infused fluid were retarded in an exponential fashion due to the anesthesia-induced decrease in the mean arterial pressure (MAP). A decrease in MAP from 110 to 60 mmHg reduced the rate of distribution by 75% and the rate of elimination by 90%. These adaptations cause most of the infused fluid to remain in the bloodstream. Age, gender, type of anesthesia, and the use of ephedrine had no statistically significant effect on plasma volume expansion, apart from their possible influence on MAP.Conclusion. The decrease in MAP that accompanies anesthesia induction depresses the blood hemoglobin concentration by inhibiting both the distribution and elimination of infused crystalloid fluid. The report provides mathematical information about the degree of these changes.

Changes in Immune Activation during Pregnancy and the Postpartum Period in Treated HIV Infection

Background Pregnant women with HIV (PWWH) have high postpartum morbidity and mortality from infections like tuberculosis. Immunologic changes during pregnancy and postpartum periods may contribute to these risks, particularly the immunoregulatory kynurenine pathway of tryptophan catabolism, which contributes to both HIV and tuberculosis pathogenesis and increases in the early postpartum. Methods Women with HIV initiating ART in the Uganda AIDS Rural Treatment Outcomes (UARTO) cohort who were pregnant at enrollment or became pregnant during observation were studied (N=54). Plasma kynurenine/tryptophan (KT) ratio, sCD14, sCD163, sCD27, IP-10, D-dimer, IL-6, and I-FABP levels were assessed through the first year of ART and at 3-month intervals throughout pregnancy and one year postpartum. Biomarker changes were assessed with linear mixed models adjusted for ART duration. Hemoglobin concentration changes were used to estimate pregnancy-related changes in plasma volume. Results Median baseline CD4 was 134. D-dimer increased through the third trimester before returning to baseline postpartum while most other biomarkers declined significantly during pregnancy, beyond what would be expected from pregnancy-associated plasma volume expansion. IP-10 and sCD14 remained suppressed for at least 12 months postpartum. KT ratio was the only biomarker that increased above pre-pregnancy baseline in the postpartum (mean +30%, P&lt;0.001) and remained higher than baseline for &gt;9 months (P&lt;0.045 for all timepoints). Conclusions Several immune activation markers decline during pregnancy and remain suppressed postpartum, but the kynurenine pathway of tryptophan catabolism increases above baseline for &gt;9 months postpartum. The mechanisms underlying postpartum kynurenine pathway activity are incompletely understood, but may contribute to increased tuberculosis risk in this setting.

Overview of Monogenic Forms of Hypertension Combined With Hypokalemia

Hypertension is an important risk factor in many conditions and creates a heavy burden of disease and mortality globally. Polygenic hypertension is the most common form; however, it is increasingly recognized that monogenic hypertension is not rare, especially in patients with electrolyte disorders. Single genetic alterations are associated with plasma volume expansion and catecholamines/sympathetic excess with simultaneously increased potassium excretion in the urine and potassium intracellular shift. Early-onset refractory hypertension and profound hypokalemia are characteristics of monogenic hypertension. However, accumulated evidence shows the existence of phenotypic heterogeneity in monogenic hypertension meaning that, even for mild symptoms, clinicians cannot easily exclude the possibility of monogenic hypertension. Genetic, epigenetic and non-genetic factors are all possible mechanisms influencing phenotypic diversity. Genetic sequencing is a precise and efficient method that can broaden the mutant gene spectrum of the disease and is very helpful for understanding the pathophysiology of monogenic hypertension. Genetic sequencing, along with biochemical tests and imaging modalities, is essential for the early diagnosis and targeted management of monogenic hypertension to avoid long-term catastrophic complications.

The Hyperhydration Potential of Sodium Bicarbonate and Sodium Citrate

Buffering agents have not been comprehensively profiled in terms of their capacity to influence water retention prior to exercise. The purpose of this investigation was to profile the fluid retention characteristics of sodium bicarbonate (BIC) and sodium citrate (CIT) to determine the efficacy of these buffering mediums as hyperhydrating agents. Nineteen volunteers (13 males and six females; age = 28.3 ± 4.9 years) completed three trials (randomized and cross-over design). For each trial, a baseline measurement of body mass, capillary blood, and urine was collected prior to ingestion of their respective condition (control condition [CON] = 25 ml/kg artificially sweetened water; BIC condition = CON + 7.5 g/L of sodium in the form of BIC; CIT condition = CON + 7.5 g/L of sodium in the form of CIT). The fluid loads were consumed in four equal aliquots (0, 20, 40 and 60 min; fluid intake was 1.972 ± 361 ml [CON]; 1.977 ± 360 ml [BIC]; 1.953 ± 352 ml [CIT]). Samples were recorded at 20 (body mass and urine) and 60 min (blood) intervals for 180 min. Blood buffering capacity (HCO3−) was elevated (p < .001) in both BIC (32.1 ± 2.2 mmol/L) and CIT (28.9 ± 3.8 mmol/L) at 180 min compared with CON (25.1 ± 1.8 mmol/L). Plasma volume expansion was greater (p < .001) in both BIC (8.1 ± 1.3%) and CIT (5.9 ± 1.8%) compared with CON (−1.1 ± 1.4%); whereas, total urine production was lower in BIC and CIT at 180 min (BIC vs. CON, mean difference of 370 ± 85 ml; p < .001; CIT vs. CON, mean difference of 239 ± 102 ml; p = .05). There were no increases observed in body mass (p = .9). Under resting conditions, these data suggest BIC and CIT induce a greater plasma hypervolemic response as compared with water alone.