Is a fully heparin-bonded cardiopulmonary bypass circuit superior to a standard cardiopulmonary bypass circuit?

Summary

A best-evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was ‘Is a fully heparin bonded cardiopulmonary bypass circuit superior to a standard cardiopulmonary bypass circuit?’ Altogether more than 792 papers were found using the reported search, of which 13 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated (Table 1). The studies analysed show that perfusion with heparin-coated and heparin-polymer-coated bypass does not increase the risk of adverse effects but reduces blood loss, re-operation rates, ventilation time, length of intensive care unit (ICU) and hospital stay and is also associated with improved biocompatibility, as evidenced by platelet preservation, reduced leucocyte and complement activation, and proinflammatory cytokine production. The various coated circuits have comparable biocompatibility as evaluated by a range of inflammatory markers and clinical outcomes. Three studies documented a significant decrease in post-operative blood loss (P = 0.001–0.54) and a meta-analysis found that perfusion with a heparin-bonded circuit resulted in a reduction in blood transfusion requirements (20%), ventilation time (P < 0.01), length of time in the ICU (P < 0.01) and also hospital stay (P = 0.02). Two studies found reduced levels of polymorphonuclear elastase (P < 0.018–0.001) and two trials concluded that the use of heparin-coated circuits in combination with low-dose systemic heparin (activated clotting time >250) resulted in the greatest clinical benefit and improvement in inflammation. One study documented significant platelet preservation with the use of third-generation heparin-polymer-bonded circuits (P ≤ 0.05). We conclude that despite heparin-bonded and newer third-generation heparin-polymer-bonded cardiopulmonary bypass circuits having a greater cost per person, their improved clinical outcomes and biocompatibility in patients undergoing cardiac surgery make them a preferable option to standard non-heparin-bonded circuits.

INTRODUCTION

A best-evidence topic was constructed according to a structured protocol. This is fully described in the ICVTS [1].

THREE-PART QUESTION

In [patients undergoing cardiac surgery] is [a heparin-coated cardiopulmonary bypass circuit] superior [to a standard cardiopulmonary bypass circuit] to improve [survival without morbidity]?

CLINICAL SCENARIO

You are at a national conference hearing about the benefits of a heparin-bonded circuit (HBC) over a conventional cardiopulmonary bypass (CPB) circuit. An eminent speaker from the floor then stands up and contends that there have been no definitively proven benefits for HBC. You have a 67-year old patient, Jehovah's Witness, listed for elective aortic root and arch replacement. With a temptation to use an HBC, you decide to do a literature search.

SEARCH STRATEGY

An English-language literature review from 1948 to July 2011 was performed on MEDLINE using the Ovid interface:

[Heparin.mp. or exp Biocompatible Materials/ or Polymer.mp. or exp Polymers/ or Coated.mp. or Coated Materials, Biocompatible/or Heparin bonded.mp. or Uncoated.mp.]

AND [Cardiopulmonary Bypass/ or Cardiopulmonary bypass.mp or Heart, Artificial/ or Extracorporeal Circulation/ or Extracorporeal circulation.mp.]

AND [Inflammation/ or Inflammatory response.mp. or Oxidative stress.mp. or Oxidative Stress/ or Clinical outcome$.mp. or Platelets.mp. or Blood Platelets/].

SEARCH OUTCOME

The search returned 792 papers. From these, 13 papers provided the best evidence to answer the question. These are tabulated in Table 1.

Table 1:

Best-evidence papers

Author, date, journal and country Study type (level of evidence)	Patient group	Outcomes	Key results	Comments, study weaknesses
McCarthy et al. (1999), Ann Thorac Surg [2] USA Prospective randomized controlled trial (level 1b)	370 patients undergoing cardiac reoperation CABG only (58%) Valve operations (42%) HBC (Duraflo II) (n = 173) Mean age = 64 NHBC (n = 177) Mean age = 64	Adverse events Units of RBC transfused Major bleeding episodes (>2 l chest tube drainage) Reoperation for bleeding Cardiopulmonary bypass time (min) Length of stay in ICU Intubation time	No adverse effects related to the use of heparin-coated circuit Percentage requiring >16 units while in ICU HBC = 1.2% NHBC = 5.4% (P = 0.035) HBC = 0% NHBC = 2.9% (P = 0.06) HBC = 1.2% NHBC = 2.8% CABG subgroup HBC = 0% NHBC = 4.0% (P = 0.058) HBC = 216 ± 87 NHBC = 204 ± 80 (P > 0.05) HBC = 49.5 ± 42.2 NHBC = 50.9 ± 40.4 (P = NS) HBC = 31 ± 62 NHBC = 29 ± 59 (P = NS)	Heparin-coated circuits improve clinical outcome, evidenced by a reduction in major bleeding episodes, need for blood transfusion and reoperation for bleeding, without increasing the risk of adverse events Single-centre trial. Perfusionists not blinded. No mention of power calculation
Jansen et al. (1995), J Thorac Cardiovasc Surg, The Netherlands [3] Randomized controlled trial (level 1b)	30 patients undergoing elective first-time CABG HBC (n = 15) Mean age = 60 NHBC (n = 15) Mean age = 58 Full-dose systemic heparin given to all patients	Differences in patient recovery assessed by a score based on; (1) Fluid balance (l) (2) Post-operative extubation time (h) (3) Difference between rectal and skin temperature (°C) Overall clinical performance score [(1) + (2)/4 + (3)] Post-operative blood loss Blood transfusion TCC concentration PMN elastase concentration	HBC = 2.4 ± 0. 3 NHBC = 3.0 ± 0.4 (P = 0.24) HBC = 17.4 ± 1.2 NHBC = 20.0 ± 2.1 (P = 0.30) HBC = 4.0 ± 0.3 NHBC = 4.6 ± 0.2 (P = 0.12) HBC = 10.7 ± 0.4 NHBC = 12.6 ± 0.8 (P = 0.03) (P = NS) (P = NS) HBC = median 775 μg/l, inter-quartile range 600–996 NHBC = median 1249 μg/l, inter-quartile range 988–1443 (P = 0.004) Lower in the coated group (P = 0.07)	The biocompatibility of CPB, as assessed by complement activation, can be improved by coating the inner surfaces of these circuits with heparin No complications occurred and all patients survived and were discharged from ICU on the first postoperative day Single-centre trial using a small sample, process of randomization and blinding not described
Tayama et al. (2001), Artif Organs, Japan [4] Randomized controlled trial (level 1b)	27 patients undergoing cardiac surgery HBC (Bioline) (n = 15) Mean age = 69 Male:female, 10:2 NHBC (n = 12) Mean age = 66 Male:female, 11:4 Both groups received full systemic heparinization (ACT>480 s)	Peak values of; neutrophil elastase (leucocyte activation) C3a (complement activation) IL-6, and IL-8 (proinflammatory cytokine production) TAT (thrombin generation) D-dimer (fibrin degeneration) β-TG, PF-4 (platelet activation) Haemostasis time (duration between termination of CPB and completion of the operation) Post-operative 12 h blood loss Required amount of autologous blood transfusion Ventilation duration	Significantly reduced in the HBC group compared with the NHBC group (P < 0.05) at the end of and 2 h post-CPBs (P < 0.05) at 2 h post-CPB (P = NS) (P = NS) (P = NS) (P > 0.05)	Bioline heparin-coated circuits partially improve biocompatibility in the areas of leucocyte and complement activation and proinflammatory cytokine production However, it does not affect platelet activation, coagulation or fibrinolysis cascade and overall, clinical impact is minimal Single centre, small sample size, majority of patients male
Fosse et al. (1997), Eur J Cardiothorac Surg, Sweden and Norway [5] European multicentre trial (level lb)	151 patients undergoing CABG HBC = 76 Duraflo II heparin coating Mean age = 64 Male:female, 64:12 NHBC = 75 Mean age = 64 Male:female, 62:9 Both groups received full-dose systemic heparin	Peak values of: C4bc (nM) C3bc (nM) TCC (AU/ml) Myeloperoxidase (mg/l) Lactoferrin (mg/l) Adverse effects Blood loss Blood transfusion	HBC = 320.2 ± 190.5 NHBC = 273.0 ± 277.4 (P = 0.2) HBC = 1019.4 ± 54.9 NHBC = 1176.1 ± 64.7 (P = 0.066) HBC = 5.2 ± 0.24 NHBC = 8.09 ± 0.57 (P = 0.00002) HBC = 717.5 ± 33.3 NHBC = 734.9 ± 28.1 (P = 0.69) HBC = 1588 ± 85.4 NHBC = 1732 ± 98.4 (P = NS) (P = NS) Intra-operative; HBC = 369.3 ± 361.8 NHBC = 404.4 ± 298.0 ml Post-operative; HBC = 893.6 ± 415.0 NHBC = 835.2 ± 439.8 ml (P = NS) HBC = 14.6% NHBC = 13.3% (P = NS)	Duraflo II heparin coating reduces complement activation, particularly TCC formation, during CPB, but not the release of specific neutrophil granule enzymes Heparin coating does not reduce blood loss, ICU stay or ventilation time. No certain correlation was established between complement and granulocyte activation and clinical outcome Majority of patients male (126/151). Only included low-risk patients. Process of randomization not described. Blinding not described
Mangoush et al. (2007), Eur J Cardiothorac Surg, UK [6] Meta-analysis (level 1a)	41 RCTs n = 3434	Primary outcomes: Blood loss (chest tube drainage) Incidence of post-operative blood product transfusion Secondary outcomes All-cause mortality Post-operative incidence of acute myocardial infarction, stroke, re-sternotomy rates, wound infections, AF Duration of ventilation ICU length of stay (LOS) Total hospital LOS	Blood loss did not differ in both groups within the first 24 h post-surgery HBCs reduce the number of patients requiring packed red cell transfusion by 20% (95% CI, 10–40%; number needed to treat (NNT) = 18 No difference in death rates in both groups HBCs reduce re-sternotomy by 40% (P = 0.002) HBCs reduce average duration of ventilation by 78 min (P < 0.001) average ICU-LOS by 9.3 h (P < 0.001) and average hospital LOS by 0.5 day (P = 0.02)	HBCs have benefit over NHBCs in terms of incidence of blood transfusion, re-sternotomy rates, ventilation time, ICU-LOS and total hospital stay, but no significant difference in 24 h chest tube drainage The majority of the included trials excluded emergency, re-do and high-risk patients; the results of this meta-analysis cannot therefore be generalized to these subgroups No comment on how many patients were included in the HBC or NHBC group. Included studies with different patient demographics, inclusion and exclusion criteria, surgical procedures and types of circuit
Mirow et al. (2008), J Cardiovasc Surg, Germany [7] Prospective randomized trial (level 1b)	n = 450 A = NHBC, conventional dose systemic heparin (ACT>480 s) (n = 149) B = HBC, conventional dose systemic heparin (ACT>480 s) (n = 152) C = HBC, low-dose systemic heparin (ACT >240 s) (n = 149)	Blood transfusion Blood loss within first 12 h post-operatively (ml) Pro-coagulant activity markers and immunological parameters Intra-operative platelet counts and maximal intra-operative concentrations of platelet factor 4, β-thromboglobulin, and PMN elastase Concentrations of thrombin–antithrombin complex Adverse events  and 30-day mortality	Group A = 49% Group B = 41% Group C = 31.5% Group A = 457 ± 204 Group B = 431 ± 178 Group C = 382 ± 188 (P < 0.01) No difference pre-operatively and post-operatively between the groups Lowest in Group C (P < 0.018–0.001) Highest in Group C (P < 0.018–0.001) (P = NS)	The combined use of heparin-coated circuits and low-dose systemic heparinization is able to reduce early post-operative blood loss without enhancing the risk of complications Single-centre trial, post-operative blood loss only assessed within the first 12 h
Svenmarker et al. (2002), Scand Cardiovasc J, Sweden [8] Departmental analysis (level 1b)	2 RCTs n = 415 patients undergoing CABG HBC (ACT >250 s) (n = 259) NHBC (ACT >480 s) (n = 156)	Long-term survival (5 years) Chest drain blood volume at 8 h (ml) Need for allogenic blood transfusion Length of hospital stay ICU stay Post-operative ventilator time Heparin requirements Protamine requirements Incidence of adverse events	HBC = 94.5% NHBC = 96.1% (P = 0.703) HBC = 540 ± 245 NHBC = 676 ± 385 (P = 0.001) HBC = 23.9% NHBC = 39.2% (P = 0.001) HBC = 7.3 ± 1.8 NHBC = 7.8 ± 2.5 days (P = 0.040) HBC = 21.8 ± 15.6 NHBC = 21.3 ± 12.2 h (P = 0.710) HBC = 8.2 ± 8.5 h NHBC = 9.7 ± 9.2 (P = 0.018) HBC = 136 ± 38 NHBC = 396 ± 78 (P = 0.000) HBC = 85 ± 55 NHBC = 168 ± 134 (P = 0.000) HBC = 36.7% NHBC = 47.2% (P = 0.035)	Perfusion with a heparin-coated circuit reduces post-operative bleeding and inflammatory response, thereby protecting the patient against post-operative complications Heparin-coated circuits are not associated with any demonstrable adverse effects Over 80% of patients were males. Limited to only two studies
Lindholm et al. (2004) Ann Thorac Surg, Sweden [9] Prospective randomized control trial (level 1b)	41 patients undergoing CABG or aortic valve replacement HBC (n = 21) NHBC (n = 20) ACT >480 s in both groups	Markers of complement activation (mean concentrations of C3a, sC5b-9, Bb, C4d in the heparin-coated vs. uncoated groups) Cytokine release (mean concentrations of TNF-α, IL-6 and IL-8) Neutrophil activation (PMN concentrations) Patients requiring >1 day on ICU Post-operative inotropic support Blood loss 12 h post-operatively Reoperation for bleeding ICU stay (days) Time on respirator (hours);	Mean concentrations during rewarming; C3a = −39% (P = 0.008) sC5b-9 = −70% (P < 0.001) Bb = −38% (P < 0.001) C4d = (P = NS) IL-8 = −60% (P = 0.009) TNF-α = (P = 0.15) IL-6 = (P = 0.07) During rewarming (P < 0.003) 60 min post-operatively (P < 0.001) HBC = 0% NHBC = 20% (P = 0.031) HBC = 29% NHBC = 55% (P = 0.09) HBC = 746 ± 74 NHBC = 891 ± 128 (P = 0.54) HBC = 1 (5%) NHBC = 2 (10%) (P = 0.52) HBC = 1 ± 0 NHBC = 2.6 ± 1.3 (P = 0.24) HBC = 4.6 ± 0.5 NHBC = 25 ± 20 (P = 0.98)	Included elderly patients with a long expected CPB time (90 min) Improved biocompatibility in comparison to a standard circuit. As shown by decreased complement activation, neutrophil degradation, cytokine release and fibrinolytic activation in elderly patients Single-centre trial using a small sample size and lacks statistical power in clinical endpoints
Thiara et al., (2010), Perfusion, Norway [10] Randomized trial (level 1b)	30 patients undergoing elective cardiac surgery Bioline (n = 15) Phosphorylcholine (Phisio) (n = 15) ACT >480 s in both groups	24 h post-op levels; platelet counts (×109) Leucocyte counts (×109) Syndecan-1 Neutrophil activation (myeloperoxidase) Complement activation (C3a and TCC) Lactate dehydrogenases concentration Cytokine activation	Phisio = 176 (144–203) Bioline = 171 (131–204) (P = 0.66) Phisio = 11.4 (10.1–14.5) Bioline = 11.5 (10.5–14.5) (P = 0.17) Phisio = 23(16–40) Bioline = 21(16–50) (P = 0.28) Higher in the Bioline group (P = 0.001) No significant differences between the groups Higher in the Phisio group (P < 0.01) No significant difference between the groups.	Phisio- and bioline-coated CPB circuits have comparable biocompatibility as evaluated by a broad panel of inflammatory markers and clinical endpoints Small sample size. Process of randomization not described
Sohn et al. (2009), Perfusion, Canada [11] Randomized controlled trial (level 1b)	78 patients undergoing CABG Trillium (n = 16) Bioline (n = 16) Phosphorylcholine (n = 16) Polymethoxyethyl acrylate (PMEA) (n = 16) Uncoated control (n = 14)	TNF-α concentration - Trillium - Bioline - Phosphorylcholine IL-6 IL-10 – Trillium NOx – Phosphorylcholine – PMEA – Bioline – Phosphorylcholine Myeloperoxidase	Increased 6 and 72 h post-CPB (P < 0.05) Increased 72 h post-CPB (P < 0.05) No significant difference in the comparison of the TNF-α value among groups at the same time points All groups increased at 6 and 72 h post-CPB in comparison with baseline (P < 0.01) All groups showed increased levels at 6 h post-CPB compared with baseline (P < 0.01, with P < 0.05 in the PMEA group) Increased compared with the control group at 72 h post-CPB (P < 0.05) All groups showed a decrease at 72 h post-CPB. Decreased 6 h post-CPB compared with baseline (P < 0.05). Increased 6 h post-CPB (P < 0.05) Decreased serum levels compared with other groups 6 h post-CPB (P < 0.05). Significantly elevated at 6 and 72 h post-CPB in all groups (P < 0.05).	Heparin-coated (Trilium and Bioline) and the phosphorylcholine-coated circuits induce less inflammatory responses and oxidative stress compared with other circuits during CABG Small sample size. Variability in specimen preparation
Eynden et al. (2008), J Card Surg, Belgium [12] Randomized controlled trial (level 1b)	78 patients undergoing cardiac surgery A = Avecor oxygenator with Trillium (n = 99) B = Control (n = 101)	Inflammatory markers: IL-8 (pg/ml) – Pre-operative – 5 h post-operative C3a (µg/l) – Pre-operative – 5 h post-operative Fibrinogen – Pre-operative – 5 h post-operative – 24 h post-operative Coagulation: Platelet count – Pre-operative – 5 h post-operative D-dimer (µg/l) – Pre-operative – 5 h post-operative Hospital stay (days) Intubation time (h) Blood loss (ml) – Intra-operative – Post-operative Required blood transfusions (units): – Intra-operative – Post-operative Death (n) Stroke, n (%)	A = 14.5 ± 9.9 B = 13.8 ± 11.8 A = 186.1 ± 318.4 B = 200.1 ± 281.1 (P = 0.727) A = 641.5 ± 622.7 B = 819.3 ± 1115.3 A = 4452.0 ± 2849.6 B = 4109.5 ± 2303.2 (P = 0.17) A = 3.9 ± 1.2 B = 3.9 ± 1.5 A = 3.2 ± 1.1 B = 3.1 ± 1.2 A = 5.5 ± 1.4 B = 5.8 ± 1.7 (P = 0.23) A = 1.2 ± 0.6 B = 1.2 ± 0.8 A = 4.6 ± 2.0 B = 4.5 ± 2.1 (P = 0.74) A = 529.8 ± 347.5 B = 515.4 ± 375.6 A = 755.5 ± 401.7 B = 783.6 ± 466.7 (P = 0.40) A = 8 ± 5 B = 9 ± 9 (P = 0.408) A = 13 ± 12 B = 19 ± 70 (P = 0.391) A = 429.4 ± 258.0 B = 552.7 ± 409.2 (P = 0.001) A = 756.8 ± 817.5 B = 721.7 ± 646.0 (P = 0.12) A = 1.9 ± 1.1 B = 1.9 ± 1.2 (P = NS) A = 2.7 ± 2.9 B = 2.7 ± 2.2 (P = 0.71) A = 0 B = 2 (P = 0.160) A = 5 (5.05%) B = 0 (0%) (P = 0.024)	The surface membrane-coated Avecor decrease intra-operative blood loss during surgery without affecting the overall blood transfusion requirement. Coated extracorporeal circuit offer no significant additional beneficial effects Single-centre trial using small sample size. Quantity of blood coming into contact with pericardium not measured
Hoel et al. (2004), Perfusion, Norway [13] Randomized controlled trial (level 1b)	30 patients undergoing CABG or aortic valve replacement Trilium (n = 15) Duraflo II (n = 15) ACT >480 s in both groups	Complement activation products; (C3bc and TCC) Platelet activation – Platelet count – BTG Leucocyte activation; Coagulation and fibrinolysis – TAT	No significant differences between the groups No significant differences between the groups (P = 0.09) Trillium group demonstrated significantly higher concentrations at 30 min (P = 0.02) and 60 min (P = 0.01) No differences between the two groups at any time No significant differences between the two groups	Apart from an earlier increase in the BTG concentrations, there are no added benefits of using a Trillium CPB circuit over the Duroflo II Small sample, single-centre trial
Gunaydin et al. (2010), Interact Cardiovasc Thorac Surg, Turkey [14] Randomized controlled trial (level 1b)	Ninety patients undergoing CABG A = Hyaluronan-based HBCs (n = 45) B = Uncoated control (n = 45) ACT >480 s in both groups Each group further divided into three subgroups (n = 15) with respect to EuroSCORE; Low risk (0–2) Medium risk (3–5) High risk (6+) Blood samples collected; After induction (T1) After heparinization (T2) 15 min after start of CPB (T3) Before cessation of CPB (T4) 15 min after reversal (T5) First post-operative day (T6)	Mortality Hospital stay Post-operative haemorrhage (ml) Respiratory support time (h) Length of ICU stay (days) Blood transfusion requirements (units) Platelet counts Leucocyte counts Protein desorption (microalbumin) on fibres (mg/mm3)	A = 2/45 B = 5/45 (P > 0.05) A = 7.2 ± 0.23 B = 8.7 ± 0.48 (P = 0.006) A = 493.8 ± 15.4 B = 602.7 ± 31.2 (P = 0.002) A = 9.18 ± 0.31 B = 12.7 ± 0.8 (P = 0.0001) A = 2.57 ± 0.14 B = 3.4 ± 0.19 (P = 0.001) A = 1.2 ± 0.16 B = 1.5 ± 0.2 (P > 0.05) Significant preservation at T4 and T5 in the hyaluronan group (P ≤ 0.05 vs. control) in high-risk cohort Lower at T5 in the hyaluronan group (P ≤ 0.05 vs. control) in high-risk cohort Lower in the hyaluronan vs. control groups (P ≤ 0.05)	Hyaluronan coating reduces platelet adhesion and cell adsorption, modulates inflammatory response and reduces the risks associated with CPB in patients, especially those at high risk Single-centre trial. Small sample size

HBC: heparin-bonded circuit; NHBC: non-heparin-bonded circuit; CABG: coronary artery bypass grafting; RBC: red blood cell; ICU: intensive care unit; TCC: terminal complement complex; PMN elastase: polymorphonuclear elastase; CPB: cardiopulmonary bypass; TAT: thrombin–antithrombin complex; ACT: activated clotting time; β-TG: β-thromboglobulin; PF4: platelet factor-4; NO_x: oxidized nitric oxide; BTG: beta-thromboglobulin.

RESULTS

A number of studies have investigated the benefits of HBCs and all have found an associated improvement in biocompatibility. McCarthy et al. [2] studied the effects of HBCs with full systemic heparinization in patients undergoing cardiac reoperations. No patient in the HBC coronary artery bypass grafting (CABG) subgroup required reoperation for bleeding (P = 0.058) and this group also had lower blood transfusion requirements (P = 0.035). In addition, there were no adverse effects associated with the use of HBCs.

Jansen et al. [3] observed an improvement in the clinical performance score of patients who underwent heparin-coated bypass and concluded that in combination with full systemic heparinization, HBCs improve biocompatibility, as assessed by complement activation.

Tayama et al. [4] demonstrated that heparin coating was associated with a partial improvement in biocompatibility with respect to leucocyte and complement activation and proinflammatory cytokine production. They found no significant differences in platelet activation, fibrinolysis, haemostasis time, 12 h post-operative blood loss, required amount of blood transfusion or the intubation time between groups and overall, the clinical benefit of HBCs seemed minimal.

Fosse et al. [5] executed a European multicentre trial comparing complement and granulocyte activation. They found that heparin coating reduced complement activation, particularly TCC formation, during bypass, but did not affect the release of specific neutrophil granule enzymes. There was no association between complement and granulocyte activation and clinical outcome, and no difference in myeloperoxidase or lactoferrin release between the groups.

Mangoush et al. [6] in 2007 performed a meta-analysis of 41 randomized controlled trials comparing HBCs and non-HBCs (NHBCs). They found that heparin coating improved clinical outcomes, as evidenced by a 40% reduction in re-sternotomy rates (P = 0.002) and a 20% reduction in patients requiring packed red cell transfusion. In addition, heparin coating reduced average ventilation time by 78 min, average ICU stay by 9.3 h (P < 0.001) and average length of hospital stay by 0.5 days (P = 0.02). There was no significant difference in the 24 h blood loss and adverse effects.

Mirow et al. [7] investigated the effects of HBC in combination with a reduced systemic heparin dose. Intrao-perative platelet counts and maximal intra-operative concentrations of platelet factor 4, β-thromboglobulin, and polymorphonuclear (PMN) elastase were lowest in the group with HBC and low-dose systemic heparin (P < 0.018–0.001). Blood loss 12 h post-operatively was also lowest in this group (P < 0.01). However, no difference between adverse events and 30-day mortality was observed.

Svenmarker et al. [8] performed a departmental analysis of patients undergoing CABG surgery using either a heparin-coated or standard circuit. The patients undergoing heparin-coated bypass received a lower dose of systemic heparin. Several improvements in clinical parameters and a reduction in adverse events by 10.5% (P = 0.035) following surgery were documented in the study group.

Lindholm et al. [9] compared the biocompatibility of HBCs and NHBCs. At 60 min after bypass, there was a significant reduction in the mean concentration of PMN elastase (P < 0.001) and sC5b-9 (P = 0.006) in the study group. Heparin coating also reduced post-operative blood loss (P = 0.54) as supported by McCarthy et al. [2] and Mirow et al. [7].

Thiara et al. [10] compared Phisio- and Bioline-coatings and documented comparable biocompatibility. Sohn et al. [11] compared the benefits of different biocompatible-coated circuits and found that heparin-coated (Bioline), heparin and polymer-coated (Trilium) and phosphorylcholine-coated circuits induced less inflammatory responses and oxidative stress compared with other circuits.

Eynden et al. [12] compared outcomes in patients undergoing CPB with either an Avecor oxygenator with Trilium or an uncoated circuit and found that the Avecor circuit decreased intra-operative blood loss during surgery without affecting overall blood transfusion requirements. Hoel et al. [13] compared outcomes in patients undergoing CPB with either the Trillium or Duraflo II (heparin-bonded) circuits. They documented an earlier increase in the β-thromboglobulin concentration in the Trillium group but found no other significant differences in outcomes.

Gunaydin et al. [14] studied different risk cohorts and found that hyaluronan-based-HBCs preserved platelets during CPB in medium- and high-risk groups and provided better peri-operative outcomes as evidenced by a reduction in mechanical ventilation time, haemorrhage in high-risk groups and cell adsorption. Inflammatory and haematological responses were better controlled in the high-risk study group and resulted in a significantly shorter ICU (P = 0.001) and hospital stay (P = 0.006).

CLINICAL BOTTOM LINE

Heparin-coated and newer third-generation heparin-polymer-coated circuits induce fewer inflammatory responses in patients undergoing cardiac surgery compared with other standard circuits and have comparable biocompatibility as evaluated by a range of inflammatory markers and clinical outcomes. Third-generation circuits preserve platelet function and provide better peri-operative outcomes. With reduction in blood loss, re-operation rates, ventilation time, length of hospital stay and their association with improved biocompatibility, the use of heparin-coated circuits in day-to-day practice justifies their extra cost.

Conflict of interest: none declared.