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Three Part Question

In [patients undergoing elective Cardiac Surgery] does [prophylactic Haemofiltration] improve [survival or time to discharge or days in CSU]?

Clinical Scenario

You are performing a difficult aortic valve replacement in an 80-year-old patient that also requires three coronary grafts and has an ejection fraction of only 35%. You know that the bypass time is going to be long. The perfusionist informs you that in the last institution he worked at, every patient was prophylactically haemofiltered if bypass was used and that this reduced inflammatory mediators and improved outcome. You decide to use a haemofilter in this high risk case but resolve to look up the evidence for this after the case.

Search Strategy

Medline 1966-07/03 using the OVID interface.
[(exp hemofiltration/ OR hemofiltration.mp OR haemofiltration.mp OR ultrafiltration.mp) AND (exp thoracic surgery/ or thoracic surgery.mp or cardiac surgery.mp or CABG.mp OR exp Cardiopulmonary Bypass/ OR Cardiopulmonary bypass.mp] LIMIT to Human and English

Search Outcome

273 papers were found of which 9 were deemed to be relevant.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Despotis et al, 1997, USA	20 patients undergoing CABG Investigated how haemofiltration effects heparin level variability and whether it filters the low molecular weight fraction Heparin measured indirectly using anti-Xa and anti-II.a assays	Case Series (4)	Levels of heparin activity	Pre haemofiltration anti-Xa heparin activity was 3.9 +/- 1.7 U/ml Post haemofiltration Anti-Xa heparin activity was 5+/-1.8 U/ml P=0.003 Haemofiltration increases heparin concentration and contributes to variability HF does not filter out low molecular weight heparin into ultrafiltrate	Small study. Main finding is that low molecular weight heparin is NOT filtered out They then report their positive secondary finding which seems to have C.I.s that cross
Babka et al, 1997, USA	60 patients undergoing CBP Ultrafiltration group: n=30, ultrafiltration with CPB control group n=30 standard CPB	Prospective case – control trial (3b)	Physiological parameters	No difference in blood loss, blood transfused, length of stay or cost of patient Significant difference in post op weight gain (3.5 Vs 4.8 lbs) and mean ultrafiltrate vol was 2510ml	Ultrafiltration was of little clinical value Controls had a significantly longer Xclamp time (32 vs 38mins) No power studies given for null findings
Tassani et al, 1999, Germany	43 patients having elective CABG Modified ultrafiltration group: n=21- zero fluid balance maintained Control group : n=22	PRCT (1b)	Immune mediator levels	IL-6 and IL-8 significantly lower levels in the Ultrafiltration group immediately post CPB These levels were not significantly different at 2 and 4 hours No difference in IL-10 and IL-1 levels	There was a short difference in inflammatory mediators that disappeared after 2 hours
Van Norman et al, 2000, USA	2 groups of patients randomised to haemofiltration or no haemofiltration during cardiopulmonary bypass	PRCT (1b)	Aprotinin levels	No difference in aprotinin levels in the two groups	Haematocrit improved with haemofiltration
			Haematocrit	Significantly higher haematocrit levels in the haemofiltration group
Grunenfelder et al, 2000, Switzerland	97 patients undergoing CABG with CPB MUF group, n=60, Modified ultrafiltration for 15mins on CPB Control group, n=37, CPB only Stratified study as 2 groups also subdivided into Normo thermic and Hypothermic CPB. Hypothermic patients had temp 26-28 C on CPB	PRCT (2b)	Immune mediators	MUF led to a significantly lower level of cytokines IL-6, IL-8, TNF and IL2R) and adhesion molecules Normothermia also led to a similar reduction	No clinical differences found Roller pump used for CPB Underpowered to make conclusions regarding mortality or morbidity
			Clinical outcome	No difference in time to discharge or mortality/morbidity between the filtered and unfiltered groups
Boga et al, 2000, Turkey	40 CABG adult patients Control, n=20, standard CPB Treatment, n=20, modified haemofiltration for 20 mins on rewarming at the end of CPB	PRCT (1b)	Haemodynamic parameters	Immediately postoperatively CI and SVR both higher in filtered group. These differences quickly became non significant Haematocrit was higher (0.33 vs 0.29 ) and blood transfusion needs also significantly lower 0.83 vs 1.84 in the HF group, P<0.05	Small study but did find significant improvements in post op blood loss and CI post op
Blanchard et al, 2000, France	2 groups of CABG patients, Control, N=13, standard rewarming and CPB Treatment, N=13, Haemofiltration on rewarming on Cardio Pulmonary Bypass. 15ml/kg filtered Haemodynamic and echogardiographic parameters measured on completion of rewarming	Single blind PRCT (1b)	Haemodynamic parameters	Treatment: No change in SVR or CI Control : Significant drop in SVR and rise in HR and CI
			Echocardiographic parameters	Significantly improved kinetic score in treatment group compared to the control group
Onoe et al, 2001, Japan	18 patients undergoing cardiac surgery Treatment: 9 patients had CPB and standard ultrafiltration followed by MUF on rewarming Control: 9 controls had CPB only Serum IL-8 measured immediately after CPB and 3h after CPB (IL-8 is a cytokine which strongly promotes neutrophil degranulation and infiltration)	PRCT (2b)	Serum Levels of IL-8	Treatment group: IL-8 reduced from 69.5=/-33 to 58.9+/-32 after ultrafiltration instituted P=0.0029	IL-8 level is reduced by a little and the haematocrit is increased But all findings have v.wide confidence intervals, all of which seem to cross on the graphical images of their results Trend towards higher BP also reported but NS
			Haematocrit	Treatment group: Haematocrit increased from mean 21 to 24 P=0.0008 Control: No change in haematocrit
Leyh et al 2001 Germany	48 patients undergoing myocardial revascularisation randomised to: Conventional Ultrafiltration CUF (n=16) Modified ultrafiltration MUF (n=16) Control group (n=16)	PRCT (1b)	Post-op transfusion volume	MUF 2.0ml/kg bw CUF 6.9ml/kg bw Control 7.0ml/kg bw P=0.029	This study finds that there is less blood loss and need for transfusion with MUF but not CUF Small study Roller pump CPB used
			Post-op blood loss	MUF 6.4 ml/kg bw in 24hrs CUF 9.2 ml/kg bw in 24hrs Control 8.9 ml/kg bw in 24hrs P=0.008
			Other	No difference in levels of any clotting or fibrinolytic system markers, including ACT, PT, APTT, fibrinogen, platelet count

Comment(s)

It is noted that modified haemofiltration (MUF) is the technique of performing haemofiltration for 10-20mins at the end of bypass, during rewarming and in contrast to conventional haemofiltration, which is performed throughout cardiopulmonary bypass. To perform modified haemofiltration, the patient is first weaned off bypass and then the haemofilter pressure is maintained by the difference in pressure between the arterial inflow and the right atrial outflow. Three studies showed a reduction in inflammatory markers including IL-8 and IL-6 with haemofiltration, although one study found no difference. Two studies showed a reduction in post-operative bleeding, although one study found there to be no difference. Three studies report improved haemodynamics after haemofiltration including improved cardiac index and BP. Five studies report an improved haematocrit or reduced patient weight post haemofiltration. Individual studies also find an increased variability in heparin concentration but no change in aprotinin levels. All studies are small and therefore there is no reliable data on the effect of haemofiltration on mortality or morbidity.

Clinical Bottom Line

Haemofiltration will increase the haematocrit, reduce some inflammatory markers and may increase the variability of heparin levels. It may also reduce post-operative blood transfusion and possibly increase BP and cardiac index immediately after haemofiltration, although no differences in morbidity or mortality have ever been shown.

References

1. Despotis GJ, Levine V, Filos KS, et al. Hemofiltration during cardiopulmonary bypass: the effect on anti-Xa and anti-IIa heparin activity. Anesth Analg 1997;84(3):479-83.
2. Babka RM, Petress J, Briggs R, et al. Conventional haemofiltration during routine coronary bypass surgery [erratum appears in Perfusion Nov;12(6):347]. Perfusion 1997;12(3):187-92.
3. Tassani P, Richter JA, Eising GP, et al. Influence of combined zero-balanced and modified ultrafiltration on the systemic inflammatory response during coronary artery bypass grafting. J Cardiothorac Vasc Anesth 1999;13(3):285-91.
4. Van Norman GA, Patel MA, Chandler W et al. Effects of hemofiltration on serum aprotinin levels in patients undergoing cardiopulmonary bypass. J Cardiothorac Vasc Anesth 2000;14(3):253-6.
5. Grunenfelder J, Zund G, Schoeberlein A, et al. Modified ultrafiltration lowers adhesion molecule and cytokine levels after cardiopulmonary bypass without clinical relevance in adults. Eur J Cardiothorac Surg 2000;17(1):77-83.
6. Boga M, Islamoglu, Badak I, et al. The effects of modified hemofiltration on inflammatory mediators and cardiac performance in coronary artery bypass grafting. Perfusion 2000;15(2):143-50.
7. Blanchard N, Toque Y, Trojette F, et al. Hemodynamic and echocardiographic effects of hemofiltration performed during cardiopulmonary bypass. J Cardiothorac Vasc Anesth 2000;14:393-8.
8. Onoe M, Magara T, Yamamoto Y, et al. Modified ultrafiltration removes serum interleukin-8 in adult cardiac surgery. Perfusion 2001;16(1):37-42.
9. Leyh RG, Bartels C, Joubert-Hubner E, et al. Influence of modified ultrafiltration on coagulation, fibrinolysis and blood loss in adult cardiac surgery. Eur J Cardiothorac Surg 2001;19(2):145-51.