Is prophylactic haemofiltration during cardiopulmonary bypass of ...

Interactive Cardiovascular and Thoracic Surgery 2 (2003) 420–423 www.icvts.org

Best evidence topic - Cardiopulmonary bypass

Is prophylactic haemofiltration during cardiopulmonary bypass of benefit during cardiac surgery? Satish Das, Joel Dunning* Department of Cardiothoracic Surgery, Wythenshawe Hospital, South Moor Road, Manchester M23 9LT, UK Received 26 August 2003; accepted 28 August 2003

Summary A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether prophylactic haemofiltration during cardiopulmonary bypass is of benefit during cardiac surgery? Altogether 273 papers were found using the reported search, of which nine presented the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of these papers are tabulated. We conclude that haemofiltration will increase the haematocrit, reduce some inflammatory markers and may increase the variability of heparin levels. It may also reduce postoperative blood transfusion and possibly increase BP and cardiac index immediately after haemofiltration, although no differences in morbidity or mortality has ever been shown. q 2003 Elsevier B.V. All rights reserved. Keywords: Haemofiltration; Preoperative care; Evidence-based medicine; Thoracic surgery

1. Clinical scenario

2.1. Search strategy

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.

Medline 1966 –July 2003 using the OVID interface [(exp haemofiltration/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.

2. Three-part question In [Patients undergoing elective Cardiac Surgery] does [prophylactic haemofiltration] improve [survival or time to discharge or days in CSU]. * Corresponding author. Department of Cardiothoracic Surgery, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK. Tel.: þ 44-7801548122. E-mail address: [email protected] (J. Dunning).

2.2. Search outcome Two hundred and seventy-three papers were found of which nine were deemed to be relevant [1 –9]. These are tabulated in Table 1. 2.3. Comment(s) It is noted that modified haemofiltration (MUF) is the technique of performing haemofiltration for 10 –20 min 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

1569-9293/$ - see front matter q 2003 Elsevier B.V. All rights reserved. doi:10.1016/S1569-9293(03)00205-6 Downloaded from https://academic.oup.com/icvts/article-abstract/2/4/420/704787/Is-prophylactic-haemofiltration-during by guest on 06 October 2017

S. Das, J. Dunning / Interactive Cardiovascular and Thoracic Surgery 2 (2003) 420–423

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Table 1 Summary of best evidence papers Author, date and country

Patient group

Study type (level of evidence)

Outcomes

Key results

Study weaknesses

Leyh et al. (2001) Eur J Cardiothorac Surg, Germany [1]

48 patients undergoing myocardial revascularisation randomised to:

PRCT (level 1b)

Post-op transfusion volume

MUF 2.0 ml/kg bw CUF 6.9 ml/kg bw Control 7.0 ml/kg bw P ¼ 0.029

This study finds that there is less blood loss and need for transfusion with MUF but not CUF.

Post-op blood loss

MUF 6.4 ml/kg bw in 24 h CUF 9.2 ml/kg bw in 24 h Control 8.9 ml/kg bw in 24 h P ¼ 0.008

Roller pump CPB used

Other

No difference in levels of any clotting or fibrinolytic system markers, including ACT, PT, APTT, fibrinogen, platelet count

Serum levels of IL-8

Treatment group: IL-8 reduced from 69.5 ¼ /233 to 58.9 ^ 32 after ultrafiltration instituted P ¼ 0.0029

Haematocrit

Treatment group: Haematocrit increased from mean 21 to 24 P ¼ 0.0008

Conventional ultrafiltration CUF (n ¼ 16) Modified ultrafiltration MUF (n ¼ 16) Control group (n ¼ 16)

Onoe et al. (2001) Perfusion, Japan [2]

18 patients undergoing cardiac surgery.

PRCT (level 2b)

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 3 h after CPB

Small study

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

Control No change in haematocrit

(IL-8 is a cytokine which strongly promotes neutrophil degranulation and infiltration) Blanchard et al. (2000) J Cardiothorac Vasc Anaesth, France [3]

2 groups of CABG patients:

Single blind PRCT (level 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

Control, N ¼ 13, standard rewarming and CPB Treatment, N ¼ 13, haemofiltration on rewarming on cardio pulmonary bypass. 15 ml/kg filtered. Haemodynamic and echogardiographic parameters measured on completion of rewarming.

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Table 1 (continued) Author, date and country

Patient group

Study type (level of evidence)

Boga et al. (2000) Perfusion, Turkey [4]

40 CABG adult patients PRCT control, n ¼ 20, (level 1b) standard CPB

Outcomes

Key results

Study weaknesses

Haemodynamic parameters

Immediately postoperatively CI and SVR both higher in filtered group. These differences quickly became non-significant

Small study but did find significant improvements in post op blood loss and CI post op.

Treatment, n ¼ 20, modified haemofiltration for 20 min on rewarming at the end of CPB

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 Immune mediator levels No differences in the serum levels of IL-6 or IL-8, or neopterin, but all detected in filtrate

Grunenfelder et al. (2000) Eur J Cardiothorac Surg, Switzerland [5]

97 patients undergoing CABG with CPB

PRCT (level 2b)

Immune mediators

MUF group, n ¼ 60, Modified ultrafiltration for 15 min on CPB Control group, n ¼ 37, CPB only.

Tassani et al. (1999) J Cardiothorac Vasc Anesth, Germany [7]

No clinical differences found

Normothermia also led to a similar reduction

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.

PRCT 2 groups of patients randomised to (level 1b) haemofiltration or no haemofiltration during cardiopulmonary bypass

Aprotinin levels

No difference in aprotinin levels in the two groups

Haematocrit

Significantly higher haematocrit levels in the haemofiltration group

43 patients having elective CABG

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 h

Stratified study as 2 groups also subdivided into normo thermic and hypothermic CPB. Hypothermic patients had temp. 26–28 8C on CPB. Van Norman et al. (2000) J Cardiothorac Vasc Anesth, USA [6]

MUF led to a significantly lower level of cytokines IL-6, IL-8, TNF and IL2R) and adhesion molecules.

PRCT (level 1b)

Modified ultrafiltration group: n ¼ 21- zero fluid balance maintained Control group: n ¼ 22

Roller pump used for CPB.

Haematocrit improved with haemofiltration

There was a short difference in inflammatory mediators that disappeared after 2 h

No difference in IL-10 and IL-1 levels Babka et al. (1997) Perfusion, USA [8]

60 patients undergoing CBP Ultrafiltration group: n ¼ 30, ultrafiltration with CPB Control group n ¼ 30 standard CPB

Prospective case–control trial (level 3b)

Physiological parameters

No difference in blood Ultrafiltration was of loss, blood transfused, little clinical value length of stay or cost of patient Controls had a significantly longer Significant difference in Xclamp time post op weight gain (3.5 (32 vs. 38 min) vs. 4.8 lb) and mean ultrafiltrate vol was No power studies given 2510 ml. for null findings

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Table 1 (continued) Author, date and country

Patient group

Study type (level of evidence)

Outcomes

Key results

Despotis (1997) Anesth Anal, USA [9]

20 patients undergoing CABG

Case series (level 4)

Levels of heparin activity

Pre haemofiltration anti- Small study. Main Xa heparin activity was finding is that low 3.9 ^ 1.7 U/ml molecular weight heparin is NOT filtered Post haemofiltration out. Anti-Xa heparin activity They then report their was 5 ^ 1.8 U/ml positive secondary P ¼ 0.003 finding which seems to have C.I.s that cross. Haemofiltration increases heparin concentration and contributes to variability

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

Study weaknesses

HF does not filter out low molecular weight heparin into ultrafiltrate

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 found an increased variability in heparin concentration but no change in aprotinin levels. All studies were small and therefore there is no reliable data on the effect of haemofiltration on mortality or morbidity. 2.4. 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.

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[3]

[4]

[5]

[6]

[7]

[8]

References [9] [1] Leyh RG, Bartels C, Joubert-Hubner E, Bechtel JF, Sievers HH. Influence of modified ultrafiltration on coagulation, fibrinolysis and

blood loss in adult cardiac surgery. Eur J Cardiothorac Surg 2001;19: 145–51. Onoe M, Magara T, Yamamoto Y, Nojima T. Modified ultrafiltration removes serum interleukin-8 in adult cardiac surgery. Perfusion 2001; 16:37–42. Blanchard N, Toque Y, Trojette F, Quintard JM, Benammar A, Montravers P. Hemodynamic and echocardiographic effects of hemofiltration performed during cardiopulmonary bypass. J Cardiothorac Vasc Anesth 2000;14:393– 8. Boga M, Islamoglu, Badak I, Cikirikcioglu M, Bakalim T, Yagdi T, Buket S, Hamulu A. The effects of modified hemofiltration on inflammatory mediators and cardiac performance in coronary artery bypass grafting. Perfusion 2000;15:143–150. Grunenfelder J, Zund G, Schoeberlein A, Maly FE, Schurr U, Guntli S, Fischer K, Turina M. Modified ultrafiltration lowers adhesion molecule and cytokine levels after cardiopulmonary bypass without clinical relevance in adults. Eur J Cardiothorac Surg 2000;17:77– 83. Van Norman GA, Patel MA, Chandler W, Vocelka C. Effects of hemofiltration on serum aprotinin levels in patients undergoing cardiopulmonary bypass. J Cardiothorac Vasc Anesth 2000;14: 253–6. Tassani P, Richter JA, Eising GP, Barankay A, Braun SL, Haehnel CH, Spaeth P, Schad H, Meisner H. Influence of combined zero-balanced and modified ultrafiltration on the systemic inflammatory response during coronary artery bypass grafting. J Cardiothorac Vasc Anesth 1999;13:285 –91. Babka RM, Petress J, Briggs R, Helsal R, Mack J. Conventional haemofiltration during routine coronary bypass surgery [erratum appears in Perfusion Nov;12(6):347.]. Perfusion 1997; 12:187–92. Despotis GJ, Levine V, Filos KS, Joiner-Maier D, Joist JH. Hemofiltration during cardiopulmonary bypass: the effect on anti-Xa and anti-IIa heparin activity. Anesth Analg 1997;84:479 –83.

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