DOI: 10.1097/CCM.0b013e3181a5c1c2

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PMID: 19448471

Issn Print: 0090-3493

Publication Date: 2009/06/01


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Regional citrate anticoagulation—Finally on its way to standardization?*

Michael Joannidis

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Regional anticoagulation with citrate for intermittent hemodialysis was first introduced in 1983 (1). It took another 10 years for this method to be instituted in continuous renal replacement therapy (CRRT) by Mehta et al (2), describing its application for continuous arteriovenous hemodialysis in patients with a high risk of bleeding. Application of citrate anticoagulation in CRRT substantially differs from conditions in intermittent forms. Continuous administration of citrate may be accompanied by either overproduction of bicarbonate, resulting in metabolic alkalosis, or in citrate accumulation and metabolic acidosis, if citrate metabolism is impaired as in liver failure. Accumulation of citrate may also be the basis for pronounced hypocalcemia. Furthermore, life-threatening hypocalcemia has been reported as a consequence of several handling errors (e.g., switching citrate and calcium infusion lines) during the application of regional citrate anticoagulation. Hypomagnesemia may occur because citrate also chelates magnesium. Finally, hypernatremia may be associated with the use of trisodium citrate, resulting in the delivery of high amounts of sodium (3).
Because of substantial physicochemical differences between the various modalities available in modern CRRT, a number of protocols depending on local habits and conditions have been published. Several protocols have been reported for continuous venovenous hemodiafiltration (4–6), allowing the concomitant use of unbuffered and buffered substitution or dialysis solutions. Few protocols have been published for continuous venovenous hemofiltration (7, 8) where increased rates of citrate infusion are required by high blood flows, which are necessary to enable weight-adjusted high-dose hemofiltration (usually 35 mL · kg−1 · hr−1 or higher) while keeping filtration fraction low (3). According to current literature, it seems as if every unit should establish its own protocol for citrate anticoagulation to provide a safe treatment routine.
In this issue of Critical Care Medicine, Morgera et al (9) present a protocol for anticoagulation in continuous venovenous hemodialysis using dialysate rates adjusted to body weight, which seems to have the potential for becoming a new standard. The authors could demonstrate excellent efficacy in 161 patients achieving a median circuit survival of 62 hours by aiming at ionized postfilter calcium of 0.25–0.35 mmol/L. Acid–base control was excellent and major adverse events were not observed, with the only exemption of significant citrate accumulation occurring in two patients with impaired liver function, a well-known limitation of continuous citrate anticoagulation (10). Citrate and calcium delivery were kept in a constant relationship to blood flow. By the end of the study period, a machine type with an integrated pump for citrate and calcium delivery coupled to blood pump rate was introduced.
The protocol reported is relevant because it fulfills several criteria of safety required for modern CRRT. The routine is simple to establish because it only requires adjustment of dialysate flow or blood flow, which determines citrate delivery for control of acid–base state. Switching between dialysates with various compositions is not necessary. It allows for dose adjustment according to body weight, without changing the protocol. Finally, this protocol can be incorporated into an integrated machine type, which does not require any external perfusor pumps, avoiding dangerous handling errors like continuing infusion of calcium and/or citrate when blood pump is stopped or when there is confusion between calcium and citrate ports.
The major drawback of this method, however, seems to be the somewhat slow correction of metabolic acidosis, especially in patients with larger body weight, which took up to 48 hours (9). When compared with continuous venovenous hemofiltration, inferior correction of acid–base status has also been described for other modalities using only diffusion-like extended daily dialysis (sustained low efficiency dialysis) (11).

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