Redefining the Therapeutic Objective in Decompensated Heart Failure: Hemoconcentration as a Surrogate for Plasma Refill Rate

doi:10.1016/j.cardfail.2006.01.011

Journal of Cardiac Failure

Volume 12, Issue 4, May 2006, Pages 247-249

https://doi.org/10.1016/j.cardfail.2006.01.011 Get rights and content

Abstract

Background

Acute decompensated heart failure is a growing epidemiologic problem about which little consensus exists on guidelines and recommendations for therapy.

Methods and Results

Available databases suggest that a large percentage of patients are being inadequately decongested while hospitalized, resulting in poor clinical outcomes. This is partly from a lack of an appropriate target to define therapeutic success. The demonstration of a prerenal state by blood work does not indicate adequate decongestion but rather means that the rate of fluid removal has exceeded the plasma refill rate. Hemoconcentration, as evidenced by a rising hematocrit is an appropriate surrogate to indicate that the plasma refill rate has been exceeded by the rate of fluid removal. This surrogate of plasma refill rate can be easily and continuously measured by using an in-line hematocrit sensor during ultrafiltration therapy.

Conclusion

We propose that the therapeutic objective in acute decompensated heart failure should be redefined and that the rate of volume extraction should be adjusted to approximate the plasma refill rate and that complete decongestion will have occurred only once hemoconcentration is observed at minimal rates of volume extraction.

Section snippets

Clinical Prognosis Linked to the Adequacy of Decongestion

In the patient with adCHF, clinical prognosis is directly related to the adequacy of decongestion as represented by a reduction in the pulmonary capillary wedge pressure.¹ Yet, 49% of patients hospitalized for adCHF either lose less than 5 pounds or gain weight while hospitalized, suggesting they are being inadequately decongested.² If the success of decongestion therapy is dependent on reaching a desired dry weight, the failure to substantially reduce weight in patients hospitalized for adCHF

Defining the Plasma Refill Rate

In a patient with adCHF, the primary objective is to remove the excessive interstitial fluid in addition to the excessive intravascular fluid. By reducing the intravascular volume through diuresis, capillary hydrostatic pressure declines to the point where interstitial pressure plus serum oncotic pressure exceeds the luminal hydrostatic pressure and fluid is passively reabsorbed from the interstitium into the intravascular space. The rate at which this occurs is termed the PRR and is

Diuretics and the Plasma Refill Rate

Intravenous diuretics are the most commonly used therapeutic agents to decongest patients with adCHF either as boluses or as a continuous infusion.² The diuretic dose is titrated to achieve a “suitable” rate of diuresis until symptom resolution is achieved. Symptom resolution has not been shown to be particularly helpful in determining the adequacy of decongestion nor has it been shown to correlate with improved clinical outcomes. Diuresis is often terminated and dry weight is considered

Hemoconcentration as a Surrogate for PRR

Therefore, a mechanism to continuously measure the PRR is necessary to optimize the management of adCHF without activation of the RAAS and SNS. Unfortunately, the PRR is impossible to measure directly and therefore a surrogate must be used to estimate these compartmental volume shifts. Dynamic changes in PRR can be indirectly monitored with the concentration of agents that remain confined to the intravascular space such as red blood cells. Thus the hematocrit is diluted when vascular volume is

Universality of Concept

The hypothesis of titrating decongestion therapy to reduce interstitial edema without embarrassing intravascular volume is applicable to all forms of decongestion therapy. Using hemoconcentration as a surrogate for PRR is obviously more amenable to therapies in which there is continuous access to blood such as ultrafiltration. However, if the hypothesis is proven, then it becomes incumbent on investigators to find adequate similar surrogates for PRR which are adaptable for other forms of

Conclusion

In conclusion, the therapeutic objective for patients admitted with adCHF needs to be redefined. Prompt therapy, at a rate not exceeding the PRR, should preserve renal perfusion while optimizing the rate of removal of interstitial salt and water. Ultimately, the total volume removed should be governed by the limits of recovery of excess volume from both the intravascular and interstitial spaces, rather than titrated against activation of the RAAS and SNS or an adverse clinical event, such as a

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Cited by (67)

Relative Blood Volume Profiles Hours After Loop Diuretic Administration: A Systematic Review and Meta-analysis
2023, CJC Open
Plasma refill rates can be estimated by combining measurements of urine output with relative blood volume profiles. Change in plasma refill rates could guide decongestive loop diuretic therapy in acute heart failure. The objective of the study was to assess average relative blood volume profiles generated from 2 or 3 follow-up measurements obtained hours after loop diuretic administration in subjects with vs without baseline congestion.
A systematic review was conducted of articles written in English, French, Spanish, and German, using MEDLINE (1964 to 2019), Cochrane Reviews (1996 to 2019), and Embase (1974 to 2019). Search terms included the following: diuretics, hemoconcentration, plasma volume, and blood volume. We included studies of adults given a loop diuretic with at least one baseline and one follow-up measurement. A single author extracted subject- or group-level blood volume measurements, aggregated them when needed, and converted them to relative changes.
Across all 16 studies that met the prespecified inclusion criteria, relative blood volume maximally decreased 9.2% (6.6% to 12.0%) and returned to baseline after 3 or more hours. Compared to subjects without congestion, those with congestion experienced smaller decreases in relative blood volume across all follow-up periods (P = 0.001) and returned to baseline within the final follow-up period.
Single doses of loop diuretics produce measurable changes in relative blood volume that follow distinct profiles for subjects with vs without congestion. Measured alongside urine output, these profiles may be used to estimate plasma refill rates—potential patient-specific targets for decongestive therapy across serial diuretic doses.
Le taux de remplissage plasmatique peut être estimé en combinant les mesures de la diurèse et les profils volémiques relatifs. Chez les personnes atteintes d’insuffisance cardiaque aiguë, une variation du taux de remplissage plasmatique pourrait guider un traitement décongestif par un diurétique de l’anse. L’étude avait pour objectif d’évaluer les profils volémiques relatifs moyens obtenus dans le cadre de deux ou trois mesures de suivi réalisées quelques heures après l’administration d’un diurétique de l’anse à des sujets présentant ou non une congestion initiale.
Une revue systématique d’articles rédigés en anglais, en français, en espagnol et en allemand a été effectuée au moyen des bases de données MEDLINE (1964 à 2019), Cochrane Reviews (1996 à 2019) et Embase (1974 à 2019). Les termes de recherche comprenaient : diurétiques, hémoconcentration, volume plasmatique et volume sanguin. Nous avons inclus des études portant sur des adultes ayant reçu un diurétique de l’anse chez qui au moins une mesure initiale et une mesure de suivi avaient été effectuées. Un seul auteur a recueilli des mesures du volume sanguin individuelles ou de groupe, les a regroupées, au besoin, et converties en variations relatives.
Parmi les 16 études qui répondaient aux critères d’inclusion prédéfinis, le volume sanguin relatif a diminué de 9,2 % (de 6,6 % à 12,0 %) et est revenu aux valeurs initiales après trois heures ou plus. Les sujets qui présentaient une congestion ont connu des diminutions du volume sanguin relatif inférieures à celles de ceux n’en présentant pas lors de toutes les périodes de suivi (p = 0,001); le volume sanguin relatif est revenu aux valeurs initiales durant la période finale de suivi.
Des doses uniques de diurétique de l’anse produisent des changements mesurables du volume sanguin relatif selon des profils distincts chez les sujets présentant une congestion, comparativement à ceux n’en présentant pas. Utilisés en association avec les mesures de la diurèse, ces profils peuvent servir à estimer le taux de remplissage plasmatique, qui constitue potentiellement une cible particulière au patient qui reçoit une série de doses d’un diurétique comme traitement décongestif.
Phenotyping congestion in patients with acutely decompensated heart failure with preserved and reduced ejection fraction: The Decongestion duRing therapY for acute decOmpensated heart failure in HFpEF vs HFrEF- DRY-OFF study
2022, European Journal of Internal Medicine
: To evaluate pulmonary and intravascular congestion at admission and repeatedly during hospitalization for acute decompensated heart failure (ADHF) in HFrEF and HFpEF patients using lung (LUS) and inferior vena cava (IVC) ultrasound.
: Three-hundred-fourteen patients (82±9 years; HFpEF =172; HFrEF=142) admitted to Internal Medicine wards for ADHF were enrolled in a multi-center prospective study. At admission HFrEF presented higher indexes of pulmonary and intravascular congestion (LUS-score: 0.9 ± 0.4 vs 0.7 ± 0.4; p<0.01; IVC end-expiratory diameter: 21.6 ± 5.1 mm vs 20±5.5 mm, p<0.01; IVC collapsibility index 24.4 ± 17.4% vs 30.9 ± 21.1% p<0.01) and higher Nt-proBNP values (8010 vs 3900 ng/l; p<0.001). At discharge, HFrEF still presented higher B-scores (0.4 ± 4 vs 0.3 ± 0.4; p = 0.023), while intravascular congestion improved to a greater extent, thus IVC measurements were similar in the two groups. No differences in diuretic doses, urine output, hemoconcentration, worsening renal function were found. At 90-days follow up HF readmission/death did not differ in HFpEF and HFrEF (28% vs 31%, p = 0,48). Residual congestion was associated with HF readmission/death considering the whole population; while intravascular congestion predicted readmission/death in the HFrEF, no association between sonographic indexes and the outcome was found in HFpEF.
: Serial assessment of pulmonary and intravascular congestion revealed a higher burden of fluid overload in HFrEF and, conversely, a greater reduction in intravascular venous congestion with diuretic treatment. Although other factors beyond EF could play a role in congestion/decongestion patterns, our data may be relevant for further phenotyping HF patients, considering the importance of decongestion optimization in the clinical approach.
Estimated plasma volume status (ePVS) could be an easy-to-use clinical tool to determine the risk of sepsis or death in patients with fever
2020, Journal of Critical Care
Capillary permeability can be increased in patients with sepsis. Indirect estimation of plasma volume status (ePVS) could identify more severely ill patients with fever.
1502 patients evaluated for fever at the Emergency Department (ED) of Merano General Hospital (Italy) between June 1, 2018 and May 30, 2019. The ePVS value registered on ED admission and derived from complete blood count was considered. Associations between the ePVS value and the two outcomes of the study (30-day mortality and sepsis diagnosis) were studied.
Fifty-one of 1502 patients (3.4%) died at 30 days and 5.3% (80/1502) had a diagnosis of sepsis. The median ePVS in patients who died was higher than in those who survived (6.01 dL/g vs 4.49 dL/g, p < .001). In the multivariate analysis, ePVS higher than 4.52 dL/g presented an OR of 2.717 (CI95% 1.103–6.692, p = .020) for 30-day mortality and 1.824 (CI95% 1.055–3.154, p = .030) for the diagnosis of sepsis. ePVS presented a significant improvement in reclassification of the usual evaluation of patients with fever (NRI 21.6% for 30-day mortality and NRI 19.7 for sepsis diagnosis, p < .001).
The ePVS value was a useful additional predictive tool to assess the severity of illness in patients with fever.
Effect on Survival of Concurrent Hemoconcentration and Increase in Creatinine During Treatment of Acute Decompensated Heart Failure
2019, American Journal of Cardiology
Hemoconcentration during the treatment of acute decompensated heart failure is a surrogate for plasma volume reduction and is associated with improved survival, but most definitions only allow for hemoconcentration to be determined retrospectively. An increase in serum creatinine can also be a marker of aggressive decongestion, but in isolation is not specific. Our objective was to determine if combined hemoconcentration and worsening creatinine could better identify patients that were aggressively treated and, as such, may have improved postdischarge outcomes. A total of 4,181 patients hospitalized with acute decompensated heart failure were evaluated. Those who experienced both hemoconcentration and worsening creatinine at any point had a profile consistent with aggressive in-hospital treatment and longer length of stay (p <0.01), higher loop diuretic doses (p <0.001), greater weight (p = 0.001), and net fluid loss (p <0.001) compared with the remainder of the cohort. In isolation, neither worsening creatinine (p = 0.11) nor hemoconcentration (p = 0.36) at any time were associated with improved survival. However, patients who experienced both (21%) had significantly better survival (hazard ratio 0.80, 95% confidence interval 0.69 to 0.94, p_interaction = 0.005). In conclusion, this combination of hemoconcentration and worsening creatinine, which can be determined prospectively during patient care, was associated with in-hospital parameters consistent with aggressive diuresis and improved postdischarge survival.
Biochemical Determinants of Changes in Plasma Volume After Decongestion Therapy for Worsening Heart Failure
2019, Journal of Cardiac Failure
Optimal vascular volume is required to avoid organ dysfunction during decongestive therapy for worsening heart failure (HF). This study investigated the relation between changes in serum substance(s) and the vascular volume after diuresis in HF patients.
Data from 47 patients with HF undergoing conventional diuretic therapy were analyzed. Blood tests included measurements of hemoglobin, hematocrit, and serum albumin/solutes. The relative changes in the plasma volume (%PV) from worsening HF to recovery were determined with the use of the Strauss formula. When divided into 2 groups based on the median %PV, the group with preserved volume (%PV ≥ −10%, range −10% to 21%; n = 23) exhibited a smaller decrease in body weight (−2.50 ± 1.98 vs −4.29 ± 2.60 kg; P = .012) and serum sodium (Na) (−1.57 ± 3.29 vs −4.13 ± 4.96 mEq/L; P = .04) and chloride (Cl) (−2.0 ± 4.06 vs −6.79 ± 5.21 mEq/L; P = .001) concentrations and a smaller increase in albumin (0.20 ± 0.28 vs 0.41 ± 0.24g/dL; P = .009) compared with the group with nonpreserved volume (%PV < −11%, range −33% to −11%; n = 24) after decongestive therapy. Changes in %PV were positively correlated with changes in body weight (r = 0.406; P = .0047) and serum Na (r = 0.433; P = .0024) and Cl (r = 0.408; P = .0044) concentrations and negatively correlated with changes in albumin (r = −0.492; P = .0004), blood urea nitrogen (r = −0.306; P = .037), and creatinine (r = −0.306; P = .036). Multivariate logistic regression analysis demonstrated an independent association between preserved %PV and an increased or preserved serum Cl concentration after decongestive therapy (odds ratio 8.71, 95% confidence interval 1.20–63.0; P = .032).
Positive and independent association exists between change in the vascular volume and the serum Cl concentration under decongestive HF therapy.
Ultrafiltration for the Treatment of Acute Heart Failure
2018, Heart Failure Clinics

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PerspectiveRedefining the Therapeutic Objective in Decompensated Heart Failure: Hemoconcentration as a Surrogate for Plasma Refill Rate

Abstract

Background

Methods and Results

Conclusion

Section snippets

Clinical Prognosis Linked to the Adequacy of Decongestion

Defining the Plasma Refill Rate

Diuretics and the Plasma Refill Rate

Hemoconcentration as a Surrogate for PRR

Universality of Concept

Conclusion

Am Heart J

Persistently high left ventricular filling pressures predict mortality despite angiotensin converting enzyme inhibition in advanced heart failure

Circulation

Perspective
Redefining the Therapeutic Objective in Decompensated Heart Failure: Hemoconcentration as a Surrogate for Plasma Refill Rate