A young IV drug user was admitted with septic shock secondary to staphylococcal sepsis with bilateral shadowing on CXR. He rapidly required intubation due to hypoxia, and institution of vasopressor support. He had a significant metabolic acidosis and consequently was commenced on haemofiltration. Transthoracic echocardiography revealed a large tricuspid vegetation. After 48 hours of haemofiltration, his acidosis haf normalised, and pressor requirements had reduced. He had a prolonged respiratory wean before being transferred to a cardiothoracic centre.

What is the role of haemofiltration (or other modes of renal replacement therapy) in severe sepsis and septic shock?

Katherine Francis

Sepsis and septic shock are the primary cause of multiple organ failure, which is the most frequent cause of death in Intensive Care Units (1). A number of patients with sepsis are admitted to Intensive Care Units for inotropic support whilst antibiotic therapy controls the source. Many of these patients suffer a drop in renal perfusion pressure and acute kidney injury, they may require renal replacement therapy. This formed the basis for using renal replacement therapy in severe sepsis, however more recently haemofiltration has been initiated for acidaemia and lactate load in patients suffering from severe sepsis or septic shock.

The surviving sepsis campaign group have produced updated guidelines this year for management of patients with severe sepsis, based on evidence. Whilst early antibiotic therapy (within 1 hour of presentation), early crystalloid fluid resuscitation and identification of antimicrobial source form the initial management plan, it gives guidance on advanced treatment options such as albumin therapy, choice of vasopressors and the use of continuous veno-venous haemofiltration. (2)

Infection sources are sometimes not easy to identify, and this leads to prolonged courses of broad spectrum antibiotics. Otto et al investigated using the haemofiltration filters to identify the bacteria deposited on the artificial membranous surfaces during renal replacement therapy. They incubated the haemofilters with soy broth after use and cultured under sterile conditions. Even after initiation of antibiotics in 14 of the 16 cases, they found a true positive detection rate of 31%, compared with a true positive detection rate from blood cultures of 10.7%. (3) It is suggested therefore that used haemofilters could be used in the future if patients require renal replacement therapy as an additional culture where micro-organisms prove difficult to identify by standard methods.

Many pro- and anti-inflammatory mediators play a strategic role in sepsis, such as interleukin-6 (IL-6). Continuous renal replacement therapy removes both the ‘good’ and the ‘bad’ mediators from the circulation in a non-selective way. Servillo et al measured IL-6 gene expression by PCR analysis in 13 patients suffering from severe sepsis or septic shock with acute renal failure. They found an IL-6 mRNA reduction after 12 hours of haemofiltration, with progressive increases after 24, 48 and 72 hours, suggesting an immunomodulatory effect and increase in transcriptional activity of IL-6. (1)

Zhou et al investigated further, undertaking a systematic review to identify differences between haemofiltration, haemoperfusion and plasma exchange. They found an all cause mortality reduction when blood purification techniques were used in patients with sepsis, but this was largely driven by trials from Japan involving haemoperfusion using polymixin B resin. (4)

A group in China looked at the effect of intermittent high volume haemofiltration (IHVHF) as an aggressive way to control multi-organ failure in septic shock, defined as >70ml/kg/hr. 28 day mortality was reduced in patients who received IHVHF (38% vs 61%) and in those patients who received a longer duration of IHVHF. (5)

Borthwick et al carried out a Cochrane Database System review in January 2013 to look at high volume haemofiltration, which has evolved from renal replacement therapies used to treat acute kidney injury (AKI) in critically ill patients. (6) However a low volume of studies and patient numbers led to insufficient evidence, but didn’t show any adverse effects from high volume haemofiltration. Therefore further large, multicentre, clinically relevant randomised control trials are needed to assess the effect, both clinically and of cost implications, before it becomes widespread.

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Lessons learnt

Haemofiltration is used widely in patients with severe sepsis in critical care units for a variety of indications. The evidence behind it however, is only class 2 evidence, lacking large randomised control trials. New techniques including high volume haemofiltration, resin filters and plasma exchange may be introduced in the future.

However we need to continue to focus on the basics of managing sepsis, including meeting targets for early goal directed crystalloid fluid therapy, broad spectrum antibiotics and identification of the source. A patient with severe sepsis or septic shock requires a team approach to manage all aspects of support and prevent a deterioration in organ function and mortality.

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References

1) Servillo G Vargas M et al Immunomodulatory effect of continuous venovenous haemofiltration during sepsis: preliminary data. Biomed Res Int 2013; 2013: 108951 doi 10.1155/2013/108951
2) Surviving sepsis campaign; International guidelines for management of severe sepsis and septic shock, 2012. Intensive are Med 2013 Feb;39(2):165-228
3) Otto GP, Kropf M, Sossdorf M et al. Screening for bacteraemia in sepsis and renal failure using haemofilters for renal replacement therapy. Infection 2013 Apr;41(2):387-90.
4) Zhou F, Peng Z et al Blood purification and mortality in sepsis: a meta- analysis of randomized trials. rit are Med 2013 Sep;41(9):2209-20
5) Yan T, Li SL, Wang DX et al. Effects of intermittent high-volume haemofiltration in the treatment of patients with severe sepsis and septic shock. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2013 Jan;25(1):19-23
6) Borthwick EM, Hill J, Rabindranath KS et al. High volume haemofiltration for sepsis. ochrane Database Syst Rev 2013 Jan 31;1: D008075.