No benefit found in switching to citrate anticoagulation for ICU kidney injury treatment

New research has found no added benefit of using citrate-based drugs in the treatment of acute kidney disease in intensive care, when compared to the anticoagulation drug heparin, despite their extra cost.

People with acute kidney injury (when the kidneys stop working correctly) may need a machine to take over their kidneys' functions and filter their blood, a process called continuous kidney replacement therapy. Heparin is used during this process to stop the blood from clotting, but in recent years, citrate-based drugs have replaced heparin in many intensive care units (ICUs).

The findings of the study, which was supported by the NIHR Oxford Biomedical Research Centre and involved patients at Oxford University Hospitals, have been published in the Journal of Critical Care.

The study was based on routinely collected data from a national audit of ICUs. It included 69,001 people from 181 ICUs in England and Wales, all of whom had received continuous kidney replacement therapy. The researchers linked this data with information on survival.

They also looked at hospital admissions, extra medical support, long-term kidney problems, and treatment costs.

This large study compared data from ICUs that continued using heparin for the treatment of kidney injury, to those that switched to the newer citrate-based drugs. It found no clear benefit from the switch to citrate-based drugs, which were also more expensive in the short-term.

The study concluded that using citrate anticoagulation was 'associated with significant increases in healthcare resource use, without corresponding clinical benefit, and is highly unlikely to be cost-effective' in the short term.

The results suggest that clinical guidelines should be updated.

The findings are significant because approximately half of all people admitted to intensive care in the UK have acute kidney injury, and about 10 percent of people in intensive care with acute kidney injury need continuous kidney replacement therapy, which includes anticoagulation drugs to prevent clotting.

Today, more than half the intensive care units in England and Wales use citrate-based anticoagulation.

Small studies have suggested that citrate-based drugs may reduce a person's risk of an internal bleed during treatment, but the evidence is inconclusive. Despite this lack of evidence, clinical guidelines suggest that citrate-based drugs are used in kidney replacement therapy for people with acute kidney injury.

The study found that switching to citrate-based anticoagulation was associated with:

• no difference in deaths between the two groups 90 days after treatment 
• people in the citrate group spending slightly more time receiving medical support for their kidneys and heart, compared with the heparin group
• people in the citrate group spending slightly longer in intensive care than the heparin group.

Switching to citrate-based anticoagulation may have been associated with fewer bleeding episodes but the difference was smaller than previously reported.  

After one year, the switch to citrate-based drugs was associated with an extra cost of £2,376 per patient and did not provide value for money. In the long-term, cost-effectiveness is highly uncertain.

The study found that in 2019, there were 17,905 patients meeting the criteria for inclusion and receiving continuous kidney replacement therapy.

If all ICUs had just transitioned from heparin to citrate anticoagulation, this would have equated to an estimated additional 4,297 to 26,678 ICU bed days and cost an extra £18m to £70m.

Picture: Olga Kononenko via Unsplash