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Configuration of the CRRT circuit under citrate anticoagulation. Qb, blood flow (L/h); Qc—4% citrate flow (L/h); Qd—dialysis flow (L/h); Qeff,— effluent flow (L/h); UF indicates ultrafiltration, that is, net fluid removal (L/h). doi:10.1371/journal.pone.0158179.g001
Source publication
Background:
The requirements for magnesium (Mg) supplementation increase under regional citrate anticoagulation (RCA) because citrate acts by chelation of bivalent cations within the blood circuit. The level of magnesium in commercially available fluids for continuous renal replacement therapy (CRRT) may not be sufficient to prevent hypomagnesemia...
Contexts in source publication
Context 1
... inhibits coagulation through chelation of ionised calcium (Ca 2+ ) which is the principle of all citrate modes of regional anticoagulation. The postfilter decrease of ionized cal- cium is used to guide the prefilter dosage of citrate and substitution of calcium at venous end of blood tubing is required to maintain systemic level of Ca 2+ (Fig 1). ...
Context 2
... fluxes of magnesium and calcium and possible relationships to citrate dosage and citra- temias were studied during postdilution continuous venovenous hemodiafiltration (CVVHDF) and continuous venovenous haemofiltration (CVVH) performed on Aquarius device (Bax- ter1, Irvine, CA, USA) with 1.9 m 2 polysulfone filter (Aquamax1, Bellco, Mirandola, Italy) (Fig 1). Indications for renal replacement therapy were renal failure with elevated levels of ure- mic toxins and loss of response to diuretics. ...
Context 3
... substitution in CVVHDF modality was given as postdilution and divided equally between predilution and postdilution in CVVH modality (see Fig 1). The blood flow (Qb) was set initially at 100 ml/min in both modalities. ...
Context 4
... T18(Mg1.50) and T27(Mg1.50) were drawn from the arterial blood, the effluent, the prefilter and postfilter ports of the circuit (see Figs 1 and 2). Besides total calcium and magnesium the laboratory analysis consisted of citrate levels (mea- sured by capillary zone electrophoresis, P/ACE 5100, Beckman). ...
Similar publications
Background
It is widespread practice during citrate anticoagulated renal replacement therapy to monitor circuit ionised calcium (iCa²⁺) to evaluate the effectiveness of anticoagulation. Whether the optimal site to sample the blood path is before or after the haemofilter is a common question.
Methods
Using a prospectively collected observational da...
Citations
... Postfilter Mg supplementation is generally limited in convective modalities compared to diffusive modalities because of the higher blood flows used, necessitating higher prefilter volumes of citrate buffer to achieve [28]. More concentrated citrate buffer solution would go some way to alleviate this problem [28], while using a postfilter fluid with a higher Mg concentration (1.5 mmol/L) [40], and increasing systemic Mg supplementation based on more frequent controls also limits negative Mg flux [28,38]. Modalities incorporating diffusive modalities, allowing lower blood flows and a lower net citrate load, such as CVVHD or CVVHDF, may therefore be advantageous when overcoming insufficient replacement of magnesium. ...
... Citrate dose-dependent loss in effluent, in diffusive modalities blood flow is lower [4,12,28,[38][39][40] Negative phosphate balance Early sampling and supplementation, use of substitution fluids with higher phosphate concentration < 12 h (dependent on initial value) ...
The use of citrate, through reversible binding of calcium, has become the preferred choice for anticoagulation in continuous renal replacement therapy in the critically ill patient. Though generally considered as very efficacious in acute kidney injury, this type of anticoagulation can cause acid–base disorders as well as citrate accumulation and overload, phenomena which have been well described. The purpose of this narrative review is to provide an overview of some other, non-anticoagulation effects of citrate chelation during its use as anticoagulant. We highlight the effects seen on the calcium balance and hormonal status, phosphate and magnesium balance, as well as oxidative stress resulting from these unapparent effects. As most of these data on these non-anticoagulation effects have been obtained in small observational studies, new and larger studies documenting both short- and long-term effects should be undertaken. Subsequent future guidelines for citrate-based continuous renal replacement therapy should take not only the metabolic but also these unapparent effects into account.
... Though typically standard of care, data on the benefits of treating or preventing CKRT-induced hypomagnesemia, hypocalcemia, or hypokalemia-beyond normalizing serum levels-are lacking. 80,81 Interestingly, some animal and observational human data suggest harm from calcium supplementation in the setting of sepsis or general critical illness, [82][83][84] but the relevance of these observations to KRT patients is unclear. ...
Acute kidney injury (AKI) and ICU-acquired weakness (ICU-AW) are two frequent complications of critical illness which, until recently, have been considered unrelated processes. The adverse impact of AKI on ICU mortality is clear, but its relationship with muscle weakness – a major source of ICU morbidity – has not been fully elucidated. Furthermore, improving ICU survival rates have refocused the field of intensive care towards improving long-term functional outcomes of ICU survivors. We begin our review with the epidemiology of AKI in the ICU and of ICU-AW, highlighting emerging data suggesting that AKI and AKI-requiring kidney replacement therapy (AKI-KRT) may independently contribute to the development of ICU-AW. We then delve into human and animal data exploring the pathophysiologic mechanisms linking AKI and acute KRT to muscle wasting, including altered amino acid and protein metabolism, inflammatory signaling, and deleterious removal of micronutrients by KRT. We next discuss the currently available interventions that may mitigate the risk of ICU-AW in patients with AKI and AKI-KRT. We conclude that additional studies are needed to better characterize the epidemiologic and pathophysiologic relationship between AKI, AKI-KRT, and ICU-AW and to prospectively test interventions to improve the long-term functional status and quality of life of AKI survivors.
... In particular, hypomagnesemia has been linked with skeletal muscle weakness in small human studies, and some limited data have associated hypomagnesemia in general ICU populations with higher rates of mechanical ventilation, prolonged ICU stay, and mortality (76,77). However, prospective data on the benefits of treating or preventing CKRT-induced hypomagnesemia are lacking (78). ...
AKI is a common complication of critical illness and is associated with substantial morbidity and risk of death. Continuous KRT comprises a spectrum of dialysis modalities preferably used to provide kidney support to patients with AKI who are hemodynamically unstable and critically ill. The various continuous KRT modalities are distinguished by different mechanisms of solute transport and use of dialysate and/or replacement solutions. Considerable variation exists in the application of continuous KRT due to a lack of standardization in how the treatments are prescribed, delivered, and optimized to improve patient outcomes. In this manuscript, we present an overview of the therapy, recent clinical trials, and outcome studies. We review the indications for continuous KRT and the technical aspects of the treatment, including continuous KRT modality, vascular access, dosing of continuous KRT, anticoagulation, volume management, nutrition, and continuous KRT complications. Finally, we highlight the need for close collaboration of a multidisciplinary team and development of quality assurance programs for the provision of high-quality and effective continuous KRT.
... Consequently, higher citrate doses not only imply more Mg chelation and loss, but also lower Mg replacement post filter. As suggested before, a negative Mg balance can be alleviated, by using a post filter fluid with a higher Mg concentration (1.5 mmol/L) [27], by using more concentrated citrate solutions pre-filter, and by increasing systemic Mg supplementation based on more frequent controls, e.g. every 6 h. ...
Background
Regional citrate anticoagulation may cause a negative calcium balance, systemic hypocalcemia and parathormone (PTH) activation but randomzed studies are not available. Aim was to determine the effect of citrate dose on calcium (Ca) and magnesium (Mg) balance, PTH and Vitamin D.
Methods
Single center prospective randomized study. Patients, requiring continuous venovenous hemofiltration (CVVH) with citrate, randomized to low dose citrate (2.5 mmol/L) vs. high dose (4.5 mmol/L) for 24 h, targeting post-filter ionized calcium (pfiCa) of 0.325–0.4 mmol/L vs. 0.2–0.275 mmol/L, using the Prismaflex® algorithm with 100% postfilter calcium replacement. Extra physician-ordered Ca and Mg supplementation was performed aiming at systemic iCa > 1.0 mmol/L. Arterial blood, effluent and post-filter aliquots were taken for balance calculations (area under the curve), intact (i), oxidized (ox) and non-oxidized (nox) PTH, 25-hydroxy-Vitamin D (25D) and 1,25-dihydroxy-Vitamin D (1,25D).
Results
35 patients were analyzed, 17 to high, 18 to low citrate. Mean 24-h Ca balance was - 9.72 mmol/d (standard error 1.70) in the high vs − 1.18 mmol/d (se 1.70)) ( p = 0.002) in the low citrate group and 24-h Mg-balance was − 25.99 (se 2.10) mmol/d vs. -17.63 (se 2.10) mmol/d ( p = 0.008) respectively. Physician-ordered Ca supplementation, higher in the high citrate group, resulted in a positive Ca-balance in both groups. iPTH, oxPTH or noxPTH were not different between groups. Over 24 h, median PTH decreased from 222 (25th–75th percentile 140–384) to 162 (111–265) pg/ml ( p = 0.002); oxPTH from 192 (124–353) to 154 pg/ml (87–231), p = 0.002. NoxPTH did not change significantly. Mean 25 D (standard deviation), decreased from 36.5 (11.8) to 33.3 (11.2) nmol/l ( p = 0.003), 1,25D rose from 40.9 pg/ml (30.7) to 43.2 (30.7) pg/ml ( p = 0.046), without differences between groups.
Conclusions
A higher citrate dose caused a more negative CVVH Ca balance than a lower dose, due to a higher effluent Calcium loss. Physician-ordered Ca supplementation, targeting a systemic iCa > 1.0 mmol/L, higher in the high citrate group, resulted in a positive Ca-balance in both groups. iPTH and oxPTH declined, suggesting decreased oxidative stress, while noxPTH did not change. 25D decreased while 1,25-D rose. Mg balance was negative in both groups, more so in the high citrate group.
Trial registration
ClinicalTrials.gov : NCT02194569. Registered 18 July 2014.
... In the same way, the onset of hypokalemia in course of CKRT has been successfully minimized by using replacement and/or dialysate solutions with a potassium concentration of 4 mEq/l [265]. Concerning magnesium, despite the majority of the originally KRT solutions were characterized by a low magnesium concentration to correct the KF-related hypermagnesemia, with the diffusion of regional citrate anticoagulation, the use of dialysis and replacement fluids with increased magnesium concentration may be indicated to prevent KRT-related hypomagnesemia [255,263]. ...
Acute kidney disease (AKD) - which includes acute kidney injury (AKI) – and chronic kidney disease (CKD) are highly prevalent among hospitalized patients, including those in nephrology and medicine wards, surgical wards, and intensive care units (ICU), and they have important metabolic and nutritional consequences.
Moreover, in case kidney replacement therapy (KRT) is started, whatever the modality used is, the possible impact on nutritional profiles, substrate balance, and nutritional treatment processes cannot be neglected.
The present guideline is aimed at providing evidence-based recommendations for clinical nutrition in hospitalized patients with AKD and CKD. Due to the significant heterogeneity of this patient population as well as the paucity of high-quality evidence data, the present guideline is to be intended as a basic framework of both evidence and - in most cases - expert opinions, aggregated in a structured consensus process, in order to update the two previous ESPEN Guidelines on Enteral (2006) and Parenteral (2009) Nutrition in Adult Renal Failure. Nutritional care for patients with stable CKD (i.e., controlled protein content diets/low protein diets with or without amino acid/ketoanalogue integration in outpatients up to CKD stages four and five), nutrition in kidney transplantation, and pediatric kidney disease will not be addressed in the present guideline.
... Despite routine magnesium sulfate supplementation at a rate of 0.81 mmol/hour, in our group, hypomagnesaemia was more common (22.3%) than previously reported from the CVVHD RCA study in cancer patients with AKI (2.3%) [19]. It was proposed that the magnesium concentration in substitution uids used in ICU patients should be supra-normal rather than subnormal to compensate for increased losses due to its chelation by citrate [25]. Previously, supra-normal values of magnesium were observed in 54% of samples during haemodia ltration treatment, which might increase the risk of muscle weakness [12]. ...
Background: Patients with known or new-onset acute renal failure after cardiovascular surgery, requiring renal replacement therapy, can benefit from adequate non-heparin circuit anticoagulation. The idea behind not using heparin relates to the post-operative risk of bleeding. Simplified regional citrate anticoagulation (RCA) protocol proposes the use of citric acid dextrose formula A (ACD-A) during post-dilutional continuous veno-venous hemofiltration (CVVH) with standard bicarbonate buffered calcium containing replacement solution. Citrate accumulation diagnosed upon total to ionized calcium ratio (tCa/iCa) and low ionized calcium (iCa) are considered as the biggest risks related to regional citrate accumulation.
Methods: This prospective observational study evaluated electrolyte and acid-base homeostasis in cardiovascular surgery patients with known chronic or new-onset acute renal failure treated with post-dilution continuous veno-venous haemofiltration (CVVH) with a simplified RCA protocol with ACD-A. In total, 50 consecutive cardiovascular surgery patients treated with CVVH with RCA were evaluated. Base excess; pH; bicarbonate, lactate, Na⁺, Cl⁻, Mg⁺⁺, and inorganic phosphate concentrations; the total to ionized calcium ratio (tCa/iCa); and high anion gap metabolic acidosis were assessed during haemofiltration treatment in survivors and non-survivors.
Results: Thirty-three (66%) patients died. In total, 235 haemofiltration sessions with a median circuit survival time of 57 hours (1-117) were evaluated. The therapies were very well balanced with regard to sodium and chloride homeostasis. The lactate concentration and anion gap decreased during CVVH sessions longer than 72 hours, but no inter-group difference was observed. The tCa/iCa ratio exceeded 2.5 in 11 of 246 (4.5%) readings and was significantly higher in non-survivors (p=0.037). No correlation was observed between the lactate concentration before haemofiltration and the tCa/iCa ratio during haemofiltration. Magnesium and phosphate concentrations decreased during CVVH, and additional supplementation with magnesium was necessary. The magnesium concentration was lower in the non-survivors.
Conclusions: The CVVH RCA protocol provides stable sodium and chloride concentrations and a tendency towards higher pH values and bicarbonate concentrations. Supplementation with magnesium and phosphate ions is needed. The incidence of citrate accumulation exceeded 4% and was significantly higher in non-survivors.
Trial registration: retrospectively registered: Clinicaltrials.gov, NCT03836742.
A patient admitted to the ICU with shock and acute kidney injury required continuous renal replacement therapy (CRRT). CRRT was initiated using regional citrate anticoagulation (RCA) with an initial magnesium (Mg) level of 1.7 mg/dL. Over 12 days the patient received 68 g of Mg sulfate. After 58 g the patient’s Mg level was 1.4 mg/dL. On day 13, CRRT was changed to a heparin circuit from concerns of citrate toxicity. Over the next 7 days the patient required no Mg replacement with a mean Mg level of 2.22. This was significantly higher than the final 7 days on RCA (1.99; P = .00069). This case illustrates the challenges in maintaining Mg stores during CRRT. RCA is now the preferred method of circuit anticoagulation, with prolonged filter life and fewer bleeding complication compared to heparin circuits. Citrate inhibits coagulation within the circuit by chelating ionized calcium (Ca2+). Free Ca2+ and Ca-citrate complexes diffuse across the hemofilter with a percentual calcium loss as high as 70%, requiring continuous post-filter infusions of calcium to prevent systemic hypocalcemia. Magnesium loss during CRRT is also significant and may approach 15% to 20% of the total body pool within a week. Citrate chelates Mg with percentual losses comparable to calcium. Twenty-two CRRT patients on RCA had median losses >6 g/day. Doubling the Mg content in the dialyzate of 45 CRRT patients significantly improved Mg balance, but with the potential risk of increased citrate toxicity. A major obstacle to replacing Magnesium loss with the same precision as calcium is few hospitals can measure ionized Mg++ levels and must rely on total magnesium levels to guide replacement, despite a literature showing poor correlation with total body stores. Post-circuit continuous replacement of magnesium, as with calcium, in the absence of ionized magnesium levels would likely be very inexact and arduous. Being aware of the losses that can occur with CRRT, especially with RCA, and adjusting magnesium replacement empirically on rounds may be the only pragmatic action plan for this clinical issue.
Clinical profile and outcomes of patients with severe sepsis: a
prospective analysis from an intensive care unit in India
Nutritional support in mechanically ventilated patients: are we
doing enough?
Background:
Patients after cardiovascular surgery, requiring renal replacement therapy, can benefit from adequate non-heparin circuit anticoagulation. Simplified regional citrate anticoagulation (RCA) protocol proposes the use of citric acid dextrose formula A (ACD-A) during post-dilutional continuous veno-venous hemofiltration (CVVH) with standard bicarbonate buffered calcium containing replacement solution. Citrate accumulation diagnosed upon total to ionized calcium ratio (tCa/iCa) and low ionized calcium (iCa) are considered as the biggest risks related to regional citrate accumulation.
Methods:
This prospective observational case-control study evaluated electrolyte and acid-base homeostasis in cardiovascular surgery patients treated with post-dilution CVVH with a simplified RCA protocol with ACD-A. In total, 50 consecutive cardiovascular surgery patients were evaluated. Base excess, pH, bicarbonate, lactate, Na+, Cl-, Mg++, and inorganic phosphate concentrations, the total to ionized calcium ratio (tCa/iCa), and high anion gap metabolic acidosis were assessed during haemofiltration treatment in survivors and non-survivors.
Results:
Thirty-three (66%) patients died. The therapies were very well balanced in sodium and chloride homeostasis. The lactate concentration and anion gap decreased during CVVH sessions lasting longer than 72 hours, but no inter-group difference was observed. The tCa/iCa ratio exceeded 4.5% and was significantly higher in non-survivors (p=0.037). Initial lactate concentration did not correlate with tCa/iCa ratio during haemofiltration. Magnesium and phosphate concentrations decreased and additional supplementation with magnesium was necessary. The magnesium concentration was lower in the non-survivors.
Conclusions:
The incidence of citrate accumulation exceeded 4% and was significantly higher in non-survivors. Supplementation with magnesium and phosphate ions is needed in CVVH with RCA.
