To MUF or not to MUF, that is the question.
Jordan P. Bloom, MD, MPH
Cardiac Surgery Fellow, Massachusetts General Hospital
Gus J. Vlahakes, MD
Professor of Surgery, Harvard Medical School and Massachusetts General
Hospital
Contact information for correspondence:
Gus J. Vlahakes, MD
Massachusetts General Hospital
55 Fruit Street, COX630
Boston, MA 02114
vlahakes.gus@mgh.harvard.edu
Phone: 617-726-1861
Professor Talwar and colleagues revisit the ultrafiltration debate by
reporting a randomized prospective trial comparing conventional (CUF)
vs. modified (MUF) ultrafiltration in pediatric patients undergoing
operative repair of Tetralogy of Fallot (TOF)1. Of the
79 patients in the study, 40 were randomized to CUF only and 39 to
CUF+MUF. The primary outcome was hematocrit, which was shown to be
significantly higher in patients who received MUF (44.7 vs. 37.2,
p<0.001). The authors report numerous statistically
significant differences in secondary outcomes, however the clinical
significance of many of these is negligible (CVP, peak airway pressures,
and inotrope score). Two of the secondary outcomes were clinically very
different. Time to peripheral rewarming was 6.3 hours in the CUF+MUF
group vs. 13.7 hours in the CUF only group. This finding shows a
remarkable difference; the other significant finding was a difference in
mechanical ventilation time: 14.7 hours vs. 6.3 hours. Finally, cardiac
biomarkers and inflammatory markers were measured in the patients. Of
these, there was a remarkable difference in troponin between groups with
the CUF+MUF group being much lower (231 vs. 5057). The others have
negligible clinical significance.
Modified ultrafiltration involves spending 20-30 minutes running the
circuit and patient blood through a hemofilter after discontinuation of
cardiopulmonary bypass. This technique was originally described by Naik
et al in 19912 and has been shown to reduce the total
body water concentration3,4. As the authors accurately
point out, there have been numerous studies reporting mixed results
about the potential benefits of MUF. We think it is safe to say that
other than additional time in the operating room on bypass, there are no
clear disadvantages to ultrafiltration. The real question to ask about
this study and the technique of MUF is whether it confers any
improvement in outcomes? A metanalysis by Ziyaeifard et al. evaluated 65
papers published between 1987 and 2013 and concluded that there is an
association between MUF and an attenuation in mortality after pediatric
cardiac surgery5. They further conclude that MUF
results in well-known advantages in children with improvements in the
hemodynamic, pulmonary, coagulation and other organs functions and
results in decrease in blood transfusion, reduction of total body water,
and blood loss after surgery. Unfortunately, all the data referenced in
both the metanalysis and this manuscript are older than 10 years. Over
the past decade there have been drastic changes in the way that
perfusionists setup and pump pediatric patients. These include the use
of blood priming, autologous priming and reduction in circuitry volume,
all which result in hemoconcentration of the
perfusate5,6. These advances question the need for MUF
and it is not clear from this manuscript whether these are routine
practices at the authors’ institution. More studies are needed to
compare outcomes in the modern era, and we applaud the authors for a
timely study.
There are several issues with this trial. First, the authors report it
is a double-blinded study. Indeed, there were blinded participants in
the study however the authors were not blinded and thus they are subject
to the typical bias of a non-blinded study. We feel this study should
not be referred to as a double-blinded trial. Clearly the authors have
redemonstrated what is already known, that there is an inverse
relationship between time spent ultrafiltrating and total body water
resulting in higher a hematocrit7. Interestingly,
despite this there was no difference in rate of donor blood transfusion
in either group. So, is more better? There is a dramatic reduction in
time to re-warming and time to extubation in the CUF+MUF group. The
authors state that patients are not considered for
extubation until they have achieved peripheral rewarming . As such,
these two variables are colinear and the difference in mechanical
ventilation time is almost assuredly due to the difference in time to
rewarming. One might postulate that a decrease in the time to achieving
rewarming might result in less post-operative bleeding. Unfortunately,
the patients who bled post-operatively were excluded from the study.
This is curious and we think those patients should have been included in
the analysis, particularly because there were more of them in the CUF
only group. Another very interesting albeit statistically insignificant
finding was the rate of ventilator associated pneumonia (VAP). Three
patients died from VAP in the CUF only group compared to one patient in
the CUF+MUF. Clearly this study was underpowered to detect differences
in mortality after TOF repair in 20 kg children, which should be close
to zero. That said, the authors might be on to something since we
already know that time on the ventilator is predictive of VAP. With
respect to the biomarkers, there are a number of studies that have
looked at the relationship between troponin and hemofiltration. In this
study, MUF must be clearing troponin from the bloodstream, thus
accounting for the dramatic post-operative differences. It is not clear,
nor addressed in this study, whether this finding has any clinical
significance. Finally, the authors conclude that there were no
significant between group differences in mortality, ICU or hospital
length of stay.
As was pointed out accurately in the manuscript, there is mixed evidence
on whether prolonging the ultrafiltration process after discontinuation
of CPB confers any benefit to the patients. To summarize the literature
at this point, it is safe to say that we don’t know the answer to this
question but despite small differences here and there, this trial failed
to demonstrate any long-term benefit and likely will not change anyone’s
opinions about the addition of MUF to CUF.
References:
1.Talwar S, Sujith NS, Rajashekar P, Makhija N, Sreenivas V, Upadhyay
AD, et al. Modified ultrafiltration & postoperative course in patients
undergoing repair of Tetralogy of Fallot. J Card Surg
2. Naik SK, Knight A, and Elliott, MJ. A successful modification of
ultrafiltration for cardiopulmonary bypass in children. Perfusion
1991;6:41–50.
3. Shen J, Wang W, Zhang W, Jiang L, Yang YY. A high-efficiency MUF
method benefits postoperative hemodynamic stability and oxygen delivery
in neonates with transposition of the great arteries. J Card Surg
2019;34:468-473.
4. Koutlas TC, Gaynor JW, Nicolson SC, Steven JM, Wernovsky G, and Spray
TL. Modified ultrafiltration reduces postoperative morbidity
after cavopulmonary connection. Ann Thorac Surg 1997;64:37–42;
discussion p. 43.
5. Ziyaeifard M, Alizadehasl A, and Massoumi G. Modified ultrafiltration
during cardiopulmonary bypass and postoperative course of pediatric
cardiac surgery. Res Cardiovasc Med 2014;3:e17830.
6. Mejak BL, Lawson DS, and Ing RJ. Con: Modified ultrafiltration in
pediatric cardiacsSurgery is no longer necessary. Journal of
Cardiothoracic and Vascular Anesthesia 2019;33:870–872.
7. Harvey B, Shann KG, Fitzgerald D, Mejak B, Likosky DS, Puis L,et al. International pediatric perfusion practice: 2011 survey
results. J Extra Corpor Technol 2012;44:186–193.