CARDIOVASCULAR JOURNAL OF AFRICA • Vol 24, No 6, July 2013
AFRICA
225
measurement of alveolar–arterial oxygen gradients, and on
postoperative cardiopulmonary functions using clinical
parameters.
Methods
A prospective, randomised study was carried out. The study was
approved by the local ethics committee and written informed
consent was obtained from every patient. The study followed the
Declaration of Helsinki 2008 on medical protocol.
Between October 2011 and February 2012, patients subjected
to elective CABG surgery were studied. Patients undergoing
redo surgery, and those with pre-operative renal failure (serum
creatinine
>
1.3 mg/dl) or hepatic dysfunction (serum aspartate/
alanine amino transferase
>
40 U/l), myocardial infarction within
six weeks prior to surgery, any kind of pulmonary disease,
pre-operative use of steroids and ejection fraction below 30%
were excluded from the study.
A total of 59 patients were prospectively randomised into
two groups as follows: in the operation room, each patient was
numbered chronologically by the same perfusionist. He reviewed
the patient’s file prior to the induction of anaesthesia, based on
a form explaining the inclusion and exclusion criteria, and the
anesthesiologist was informed about the proposed regimen.
Odd-numbered patients (
n
=
30) were ventilated during CPB and
the even-numbered patients (
n
=
29) were not ventilated.
Peri-operative management and anaesthesia
Pre-operative acetylsalicylic acid 100 mg/day was continued
in all patients prior to the day of surgery. All patients were
pre-medicated with 10 mg of oral diazepam. Anaesthesia was
induced with etomidate 2 mg/kg, fentanyl 1
µ
g/kg, vecuronium
1 mg/kg, isofluorane 1 MAC with 50% oxygen and 50% air,
and remifentanyl 1
µ
g/kg bolus, followed by a 0.5-
µ
g/kg/min
infusion. Intra-operative arterial (through the radial artery
catheter) and central venous pressure (through the right internal
jugular vein catheter) monitoring was done.
The CPB circuit was primed with 1 500 ml Isolyte-S
®
(Eczaciba
ş
i-Baxter, Istanbul), which is a balanced electrolyte
solution, and 5 000 units of heparin were added. After
anticoagulation with heparin (300 U/kg), CPB was established
using a roller pump with a membrane oxygenator (Dideco
Compactflo Evo, Sorin group, Mirandola Modena, Italy). The
average flow rate varied from 2.3 to 2.4 l/min/m
2
. Surgery
was performed under mild hypothermia (33°C). Mean arterial
pressure was kept between 45 and 70 mmHg. All patients
were rewarmed to 37°C (nasopharayngeal temperature) before
weaning from CPB. Heparin was neutralised with 1:1 protamine
sulfate.
Cold (4–8°C) blood cardioplegia (1 000 ml, 25 mEq/l
potassium) was administered after aortic cross clamping, and
500-ml repeat doses were given every 15 to 20 minutes
(antegrade and from the venous bypass grafts; retrograde in the
case of left main stenosis). Terminal warm blood cardioplegia
(36–37°C) was given prior to aortic clamp release. The operating
room temperature was kept at 20–21°C.
Following surgery, the patients were taken to the intensive
care unit (ICU), intubated, and intravenous propofol (1–2 mg/
kg/h) and morphine (0.01–0.02 mg/kg/h) were given for the
maintenance of analgesia and sedation.
Atrial fibrillation (AF) was diagnosed based on an
electrocardiogram. All patients were ECG monitored
continuously during the ICU stay and for the first 24 hours in the
ward. An ECG was immediately performed in cases of irregular
pulse, palpitations or symptoms related to possible AF.
Primary outcome variables included mean time to extubation,
length of stay in ICU and postoperative hospital stay, incidence
of renal dysfunction (based on the finding that the peak
creatinine value was
≥
1.5 times the pre-operative value),
postoperative stroke, total amount of blood loss postoperatively,
postoperative exploration for haemorrhage, amount of blood and
blood products used, and in-hospital mortality.
Ventilation strategy
After intubation, before and after CPB, all patients were
ventilated with F
i
O
2
of 0.4 to 0.5, at a tidal volume of 7 ml/kg
and respiratory rate of 12/min. Positive end-expiratory pressure
was not used, and no requirement for F
i
O
2
over 0.5 was required
to maintain adequate oxygen saturation. The variability in
ventilation parameters was to maintain a partial arterial carbon
dioxide pressure between 35 and 40 mmHg.
In the non-ventilated group (NV), following establishment of
CPB, ventilation was stopped (open to atmospheric pressure).
In the ventilated group (V) mechanical ventilation with 0.5 F
i
O
2
at 5 ml/kg tidal volume and 5/min respiratory rate with zero
end-expiratory pressure was maintained. In the ICU, patients had
volume-controlled ventilation and were extubated when their
haemodynamics were stable, and neurological and respiratory
functions were noted.
Blood sampling and measurements
Peripheral arterial blood samples were collected from the
radial artery catheter after the induction of anaesthesia (T
0
),
and immediately after (T
1
), one (T
2
) and six hours (T
3
) after the
discontinuation of CPB. The blood samples were put into citrated
and EDTA anti-coagulated tubes, centrifuged, and the plasma
was separated and stored at –70°C until the assay.
Plasma levels of IL-6, -8 and -10 were measured by
commercially available enzyme-linked immunosorbent assays
(AssayMax Human ELISA Kit, Assaypro, Missouri, USA).
Plasma lactate levels were measured by blood gas analyser (ABL
700 series, Radiometer
®
, Brønshøj, Denmark).
Alveolar–arterial oxygen gradient (
∆
A–aO
2
) was calculated
as follows:
6
∆
A–aO
2
=
P
A
O
2
– P
a
O
2
P
A
O
2
=
P
i
O
2
– (P
A
CO
2
/
R
)
P
i
O
2
=
(P
B
– PH
2
O) – F
i
O
2
where P
A
O
2
=
alveolar oxygen tension; P
a
O
2
=
partial arterial
oxygen pressure; P
i
O
2
=
partial pressure of inspired oxygen;
P
A
CO
2
=
alveolar carbon dioxide tension (assumed to equal
the partial arterial CO
2
pressure due to the ease of exchange of
CO
2
);
R
=
respiratory quotient (assumed at 0.8); P
B
=
barometric
pressure; PH
2
O
=
water pressure (6.2 kPa, as inspired air is
fully saturated at the level of the carina); and F
i
O
2
=
fractional
concentration of inspired oxygen.
Statistical analysis
Statistical analyses were performed using SPSS software for
