Early change of oxygen metabolism after isolated mitral valve replacement or mitral valve replacement and concomitant aortic valve replacement in patients with pulmonary hypertension

Journal of military pharmaco-medicine n03-2018

EARLY CHANGE OF OXYGEN METABOLISM AFTER ISOLATED
MITRAL VALVE REPLACEMENT OR MITRAL VALVE REPLACEMENT
AND CONCOMITANT AORTIC VALVE REPLACEMENT IN PATIENTS
WITH PULMONARY HYPERTENSION
Kieu Van Khuong*; Pham Thi Hong Thi**; Nguyen Quoc Kinh***
SUMMARY
Objectives: To verify oxygen metabolic changes and to assess the corellation between
oxygen consumption (VO2), oxygen delivery (DO2) and oxygen extraction (ERO2). Subjects and
methods: 67 patients with pulmonary hypertension related left heart diseases who underwent
elective (MVR) and/or aortic valve replacement (AVR) enrolled in the study. Calculated
parameters by pulmonary artery catheter inserted at operation theater and monitor system.
Results and conclusion: Cardiac output index (CI), ERO2 and VO2 increased significantly intra
and after operation with respect to baseline levels. DO2 decreased after intubation and
cardiopulmonary bypass stop but increased significantly at intensive care unit admission.
The close corellation between VO2 and DO2, ERO2 was at all postoperative points of time.
* Keywords: Mitral valve replacement; Pulmonary hypertension; Oxygen delivery;
Oxygen metabolism; Aortic valve replacement.

INTRODUCTION
The important problems of postoperative
cardiac care are those of cardiac output,
tissue oxygenation, the ratio of myocardial
oxygen supply and demand. Ideally, one
should strive to obtain a cardiac index
greater than 2.2 L/min/m2 with a normal
mixed venous oxygen saturation while
optimizing the oxygen supply/demand ratio.
Oxygen delivery (DO2) is considered
as principal target for adequate tissue

perfusion [1].

anerobic metabolism occurs. From this
point, the resulting oxygen debt leads
to increased arterial lactate production.
This physiological dependence of oxygen
consumption (VO2) on DO2 should be
avoided, as hyperlactatemia is associated
with increased postoperative mortality,
morbidity and hospital length of stay.
Previous studies have shown that a
drop of DO2 levels under a critical level
during cardiopulmonary bypass (CPB) is
independently associated with acute kidney
injury [2].

When oxygen exceed a threshold value
whereby sufficient DO2 can not be
assured by increasing cardiac output (CO)
or hematocrit levels, a shift from erobic to

The postoperative course after heart
valve surgery with CPB is characterized
by a progressive increase in cellular
oxygen demand. This increase, known as

* 103 Military Hospital
** Vietnam Natinoal Heart Institute
*** Vietduc Hospital
Corresponding author: Kieu Van Khuong ()

Date received: 10/01/2018
Date accepted: 06/03/2018
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Journal of military pharmaco-medicine no3-2018

hypermetabolic status, persists for several
hours [3, 4] or, in some experiences, for a
few days [5] after surgery. Previous reports
have suggested that CPB could be the main
cause of the increased metabolism after
cardiac surgery and of the perioperative
changes between VO2 and DO2 [5, 6].
The aim of this study was to: Evaluate
oxygen metabolism changes after isolated
mitral valve replacement or mitral valve
replacement and concomitant aortic valve
replacement.
SUBJECTS AND METHODS
1. Subjects.
This study was carried out at Heart
Center of Hue Center Hospital from May
to November 2017. We enrolled 67 patients
with pulmonary hypertension associated
with left heart diseases who underwent
isolated MVR or MVR and concomitant
AVR. The study protocol was approved by
Ethics Committee of Hospital and a written
consent was obtained for each patient.

Patients were excluded if they had any
evidence of sepsis (temperature > 37.50C,
WBC > 12 G/L), a history of hyper-orhypothyroidism or claustrophobia or facial
deformities (canopy kit intolerence or ill-fit).
2. Methods.
* Preoperative assessment:
A 4-lumen pulmonary artery catheter
(PAC) (7.5F size) with a thermistor probe
(B.Braund) was inserted via the right internal
jugular vein.
* Anesthesia:
General anesthesia was induced with
fentanyl, 3 - 5 µg/kg and mydazolam
0.2 mg/kg. The therapy for PAH was
134

instituted with a nitroglycerin infusion
(0.5 - 1 µg/kg/min), deliberate hypocarbia
(arterial carbon dioxide tension < 35 mmHg),
fractional inspired oxygen concentration
(FiO2) of 1.0, and elective ventilation for at
least 12h in the postoperative period.
Rocuronium and vecuronium were used
as muscle relaxants.
* Technique of MVR:
All patients were operated on CPB
under moderate hypothermia (28 - 300C)
using standard techniques. Mitral valve
was approached either through the left
atrium or via the interatrial septum

(trans-septal approach). Whenever possible,
total chordal preservation was carried out.
The valve used was ATS or St.Jude
Mediacal bileaflet mechanical prosthesis.
* Measurements and formulas:
Measurements were obtained at the
following time points:
- T0: baseline, pre-induction; T1: postintubation; T2: immediate post-CPB; T3:
at ICU admission; T4: first 6 hours at ICU
and Toff (T14): before PAC removing and
the hemodynamics had been stabilized.
- Mixed venous samples were taken
via the distal port of the PAC. Calculate
DO2 = CO x CaO2 (1) while CaO2 = Hb x
1.34 x SaO2 + (0,003 x PaO2). VO2= CO x
(CaO2 - CvO 2 ). ERO2 = (CaO2 CvO 2)/CaO2 [7].
- Cardiac output (CO) was measured
by the thermodilution technique using
10 mL of 0.9% ice-cold saline and a
hemodynamic monitor (Phillip MP70)
having inbuilt capacity to measure CO


Journal of military pharmaco-medicine n03-2018
and calculate hemodynamic parameters.
Three consecutive successful determinations
were averaged and the difference between
any two readings did not exceed 15%.
Mean value of systolic pulmonary artery
pressure, pulmonary capillary wedge

pressure (PAOP), pulmonary vascular
resistance (PVR) and cardiac index (CI)
were calculated. Baseline (control)
hemodynamics, total complete blood
count and arterial blood gas (ABG)

measurements were obtained before the
induction of anesthesia.
* Statistical analysis:
All values are mentioned as mean ±
standard deviation (SD) and range. Unpaired
student’s t-test and Chi-square test were
used for comparison of data of the two
groups, where applicable. For statistical
analysis, the statistical software SPSS
version 19.0 for windows (SPSS Inc.,
Chicago, IL) was used. p value < 0.05
was considered statistically significant.

RESULTS
1. Patients, demographic and intra-operative characteristics.
Table 1: Patient characteristics.
Variables
Age (year)
Gender [m/f, (%)]

Mean ± SD or number

Range

45.5 ± 10.7

20 - 68

15/52 (22.4/77.6)
2

Body surface area (m )

1.44 ± 0.11

1.2 - 1.7

Body mass index (kg/m )

19.8 ± 2.4

15.4 - 25.2

Weight (kg)

48.0 ± 6.5

33 - 67

Height (cm)

155.9 ± 7.0

142 - 170

PAPs (mmHg)

52.7 ± 15.0

35 - 95

Echocardiographic EF (%)

53.5 ± 8.0

Mitral valve replacement [n (%)]

45 (67.2)

Aortic valve replacement [n (%)]

22 (32.8)

2

CPB (min), mean (range)

114.2 ± 57.7

54 - 466

ACC (min), mean (range)

79.8 ± 36.8

31 - 185

Ventilation time (hour)

20.9 ± 31.7

(Abbreviation: ACC: Aortic cross-clamp time; CPB: Cardiopulmonary bypass time)
Among 67 patients, 45 patients underwent isolated mitral valve replacement and 22
patients underwent MVR and concomitant AVR. The study group was mainly female
(77.6%), mean age 45.51 ± 10.74 years. All patients were pulmonary hypertension
related left heart diseases (PAPs ≥ 35 mmHg measured by echo).
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Journal of military pharmaco-medicine no3-2018
2. Oxygen metabolism and hemodynamic changes.
Table 2: Changes in oxygen consumption and delivery.
Time
points

CI (L/min/m )

SvO2 (%)

DO2 (mL.min .m )

ERO2 (%)

VO2

-1
-2
(mL.min .m )

T0

2.43 ± 0.77

71.2 ± 12.2

616.4 ± 194.6

27.9 ± 11.9

159.5 ± 51.8

T1

1.66 ± 0.42

a

72.4 ± 8.2

372.9 ± 111.9

a

27.2 ± 8.6

96.8 ± 26.6

T2

2.58 ± 0.61

a

74.4 ± 9.0

521.1 ± 167.9

25.9 ± 8.8

131.7 ± 58.8

T3

3.02 ± 0.80

a

69.1 ± 10.5

689.7 ± 215.9

a

29.7 ± 9.9

203.8 ± 102.3

T4

2.65 ± 0.55

a

63.2 ± 12.5

a

541.4 ± 159.5

a

36.1 ± 12.4

187.9 ± 72.9

Toff

3.00 ± 0.69

a

58.6 ± 11.3

a

591.6 ± 141.3

39.3 ± 11.3

228.9 ± 75.2

2

-1

-2

a
a
a

a
a

(ap < 0.0001 vs. baseline; bp < 0.05 vs. baseline)
There was a progressive increase in CI, ERO2 and VO2 after operation with respect
to baseline levels, but significantly decrease in SvO2. No significant differences in DO2
level at T4 and Toff time point. CI, SvO2, DO2, ERO2, VO2 was in mean value.
2. Correlation between oxygen consumption and oxygen delivery, oxygen extraction
in MVR at diffirent time points.
Table 3: Relation between oxygen consumption and oxygen delivery, oxygen extraction
in MVR at diffirent time points.

Time points

VO2 and DO2
(Spearman’s correlation)

VO2 and ERO2
(Spearman’s correlation)

r

p

r

p

T0

0.189

> 0.05

0.686

< 0.001

T1

0.477

< 0.001

0.492

< 0.001

T2

0.553

< 0.001

0.631

< 0.001

T3

0.726

< 0.001

0.658

< 0.001

T4

0.538

< 0.001

0.558

< 0.001

Toff

0.479

< 0.001

0.719

< 0.001

No significant relation between VO2 and DO 2 could be demonstrated before
anesthesia induction (T0 time point). Since that time point a constantly significant linear
relation between VO2 and DO2 was demonstrated up to remove PAC postoperatively.
There was a negative correlation between VO2 and ERO2 at base time point.
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Journal of military pharmaco-medicine n03-2018
DISCUSSION
Some intraoperative and postoperative
results showed in table 1. The mean CPB
(114.18 ± 57.71 mins) and the mean aortic
cross-clamp time (79.76 ± 36.78 mins) was
similar to Xiaochun Song’s study outcome
(CPB 119.9 ± 37.4 mins and ACC: 82.5 ±
31.8 mins) [8]. This result was higher than

that Abu El-Hussein’s (CPB 55 mins; ACC
28 mins) [9]. The reason for this difference
is the patient group of that study was
replaced one valve surgery only.
Our results showed a significant decrease
in DO2 and VO 2 during operation in
comparison of baseline data (table 2). We
consider that it may be due to the effect of
sedation following premedication and
anesthesia drugs. Besides, we can see
the early increase in VO2 and DO2 at ICU
admission (T3 time point), which was
mostly attributed to rewarming (early phase)
and the neurohumeral catabolic response
to major surgery. These findings are
similar to those in the reports of oxygen
metabolism changes in patients with
rheumatic mitral valve disease at different
intervals after MVR. In the study by P.S.
Myles [5], the mean DO2 as well as VO2
decreased significantly at post-induction
(DO2: from 954 to 681 mL/mins, VO2: from
202 to 139 mL/mins) and after CPB (DO2:
709 mL/mins, VO2: 199 mL/mins) in patients
undergoing coronary artery bypass and
valvular surgery. Another study conducted
by Parolary et al [10] showed effects of
time on the changes in DO2 were significant.
There was a significant postoperative DO2
decrease in both groups, starting after

anesthesia induction and lasting up to

9 and up to 18 postoperative hours. Only
time affected the changes of VO 2
significantly: after surgery, starting from
“skin” time point, VO2 significantly
increased in both groups with respect to
baseline levels. ERO2 behavior was
similar to VO2, both of which increased
dramatically. Only time indicated a
remarkable effect and there was a
significant ERO2 increase over time in
both groups. ERO2 value in the study did
not change at T1, T2 and T3 time point
but increased significantly at T4 and T14
time point (table 2). In our opinion, it may
be due to inadequate cardiac output and
increased oxygen extraction in an attempt
to meet oxygen needs. Such an increase
in oxygen extraction frequently is associated
with a prolonged postoperative recovery
period.
The relation between VO2 and DO2,
this study revealed that in the intraoperative
and early postoperative period of cardiac
surgery, oxygen metabolism was substantially
different from normal conditions, where a
biphasic relation can be demonstrated [11].
There was a significant relationship
between DO2 and VO2 during postoperative

period. During physical activities or
experiments, the increase in oxygen
demand is met by an increase in both
cardiac output and oxygen extraction
ratio. This case was not our patient after
cardiopulmonary bypass. As usual, SvO2
and thus oxygen extraction remained
relatively stable during operation and up
to ICU admission, whereas the increase
in VO2 was primarily matched by an
increase in cardiac output and DO2.
Hence, there was a remarkably close
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Journal of military pharmaco-medicine no3-2018
relationship between VO2 and DO2. Similarly,
the recent study by Christina Routsi [11]
identified relationship between VO2 and
DO2 in 36 patients (159 measurements):
VO2 = 28 + 0.27 x DO2, r = 0.79, p < 0.0001,
which was similar to our results at
postoperative various time points (table 3).
There was a highly significant correlation
between VO2 and DO2 intra-and postoperation. The congruent or significant
relationship between VO 2 and DO 2
expressed the stable balance oxygen
between demand and consumption after
valve replacement. Furthermore, dramatic
relationship between ERO2 and VO2

strongly suggests that the increase in
VO2 was primarily accomplished by an
increase in ERO2, and usually not by an
increase CI. Because patients had preexisting heart failure and cardiac damage
due to surgery, their ability to increase
cardiac output was limited.
There was a significant effect of time
and surgery on this relation: the close
relation between VO2 and DO2 increased
over time, peaking after surgery at 6 hour
postoperative time point (T4). These findings
suggest that careful management of the
patients remains an important issue,
especially in the early postoperative
period, when patients are at higher risk for
the occurrence of oxygen debt and,
consequently, of anaerobic metabolism.
CONCLUSION
Our data indicates that the progressive
increase in VO2 after isolated MVR or MVR
and concomitant aortic valve replacement
is accomplished primarily by an increase
138

in cardiac index and DO2. There was a
significant change in the relation between
VO2 and DO2. Both changes do not depend
on CPB use.
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